PopSugar

Smarter Eats: Gwyneth Reminds Us to Get a Healthy Dose of D

FitSugar — Wed, 11 Nov 2009 14:30:31 -0800

Gwyneth Paltrow's dishing out some healthy advice on GOOP this week - get your daily dose of vitamin D. The super-fit star points to Dr. Frank Lipman's healthy tips for getting our fair share of the vital D, who reminds us that, especially this time of year -when we head into the colder season and see less sunlight - it's even more important to supplement our diets with the vitamin, and avoid a vitamin D deficiency.

If you're wondering why it's so important, just remember that vitamin D was first recognized for its importance in maintaining healthy calcium levels for our bones. According to Dr. Lipman, it's now becoming increasingly apparent that we've underestimated the value of the vitamin, and a lack of it has been associated with obesity, high blood pressure, heart disease, and breast cancer - to name a few.

Since we rely on the sun to generate the most reliable way of getting vitamin D, it's a good idea to up your intake of foods that can naturally deliver the goods - try fortified milk in your cereal, dried shitake mushrooms with your stir fry or salad, and wild fatty fish, like salmon and halibut. Just be aware that only 10 percent of your vitamin D intake can come from food, so to really eat smarter and healthier, it might just be a good idea to supplement with the active form of the vitamin, D3. Be sure to read all of Dr. Lipman's great tips, and until we see some sunlight this Spring, make sure you're getting your daily dose with fortified foods.

Breast cancer

FitSugar — Wed, 08 Oct 2008 17:34:59 -0700

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Approvals

In September 2007, Evista (raloxifene) was approved for prevention of breast cancer in postmenopausal women with osteoporosis, and postmenopausal women at high risk for invasive breast cancer. Raloxifene and tamoxifen are the only two drugs approved for breast cancer prevention in high-risk women.
In March 2007, lapatinib (Tykerb) was approved in combination with capecitabine (Xeloda) for treatment of advanced HER2-positive breast cancer.
In November 2006, trastuzumab (Herceptin) was approved for treatment of early-stage HER2-positive breast cancer. Trastuzumab is also approved for advanced HER2-positive breast cancer.

Screening

The American College of Physicians’ 2007 guidelines recommend that women with a low risk for breast cancer talk to their doctor before starting to have mammogram screening at age 40. Other associations, including the American Cancer Society, continue to recommend annual mammograms for women age 40 and older.
Women at high risk for breast cancer should have an MRI scan along with their annual mammogram, according to 2007 guidelines from the American Cancer Society.
For women who have been diagnosed with cancer in one breast, an MRI can help detect tumors in the other breast, indicates a 2007 study in the New England Journal of Medicine.

Post-Treatment Guidelines

The American Society of Clinical Oncology (ASCO)’s 2006 post-treatment guidelines recommend regular physical exams, breast self-exam, mammograms, and genetic counseling. Know how to recognize the signs of breast cancer recurrence. ASCO does not recommend blood and imaging tests for routine recurrence screening.

Hormone Replacement Therapy (HRT) and Breast Cancer Risk

Fewer women are using HRT, which may explain why new cases of breast cancer among postmenopausal women have declined, suggests a recent New England Journal of Medicine study.

Aromatase Inhibitors

Drug treatment with aromatase inhibitors is improving survival in women with hormone-sensitive advanced breast cancer, suggest recent studies. Switching from tamoxifen to an aromatase inhibitor may help improve the odds for survival.

Introduction

Breast cancers are potentially life-threatening malignancies that develop in one or both breasts. The structure of the female breast is important in understanding this cancer:

The interior of the female breast consists mostly of fatty and fibrous connective tissues.
It is divided into about 20 sections called lobes.
Each lobe is further subdivided into a collection of lobules, structures that contain small milk-producing glands.
These glands secrete milk into a complex system of tiny ducts. The ducts carry the milk through the breast and converge in a collecting chamber located just below the nipple.
Breast cancer is either noninvasive (referred to as in situ, confined to the site of origin) or invasive (spreading).

The female breast is either of two mammary glands (organs of milk secretion) on the chest.

Noninvasive breast cancers include:

Ductal carcinoma in situ (also called intraductal carcinoma or DCIS). DCIS consist of cancer cells in the lining of the duct. DCIS is a non-invasive, early cancer, but if left untreated, it may sometimes progress to an invasive, infiltrating ductal breast cancer.
Lobular carcinoma in situ, or LCIS. Although noninvasive, lobular carcinoma in situ is a marker for an increased risk of invasive cancer in both breasts. (Some experts prefer to call this condition lobular neoplasia rather than refer to it as a cancer.) According to a 2001 report, for patients with LCIS the risk for developing invasive cancer in the same breast is about 18% -- and 14% in the other breast -- after 20 years. These invasive cancers can be either lobular or ductal.

At the time of diagnosis of these early cancers (DCIS and LCIS), there is no evidence of invasion.

Invasive cancer occurs when cancer cells spread beyond the basement membrane, which covers the underlying connective tissue in the breast. This tissue is rich in blood vessels and lymphatic channels that are capable of carrying cancer cells beyond the breast. Invasive breast cancers include the following:

Infiltrating ductal carcinoma. This is invasive breast cancer that penetrates the wall of a duct. It comprises between 70 - 80% of all breast cancer cases.
Infiltrating lobular carcinoma. This invasive cancer has spread through the wall of a lobule. It accounts for 10 - 15% of all breast cancers. It may sometimes appear in both breasts, sometimes in several separate locations.

Click the icon to see an image of the breast.

There are other less common breast cancers that are not discussed in this report.

Risk Factors

About 12 - 13% of women develop breast cancer in their lifetime. Experts estimate that about 178,480 women will be newly diagnosed with invasive breast cancer in the United States in 2007. Another 2,030 men will be diagnosed with breast cancer during the year. Although breast cancer in men is rare, the incidence has been increasing, and men are diagnosed at a later stage than women. An estimated 40,460 women and 450 men will die from breast cancer in 2007. The earlier breast cancer is diagnosed, the earlier the opportunity for treatment. According to the American Cancer Society, over 2 million women who have been treated for breast cancer are alive today.

Age is a major identifiable risk factor. More than 80% of breast cancer cases occur in women over age 50, and especially in women over age 65. The odds by age are as follows:

From ages 30 - 39, a woman’s chance for being diagnosed with breast cancer is 1 in 233
Ages 40 - 49, the odds are 1 in 69
Ages 50 - 59, the odds are 1 in 38
Ages 60 - 69, the odds are 1 in 27
Ages 70 - 79, the odds are 1 in 11
After age 80, the odds are 1 in 8

Breast cancer is more prevalent among Jewish women of Eastern European (Ashkenazi) descent. Meanwhile, African-American women tend to get breast cancer at an earlier age than Caucasians. Although African-American women have lower overall rates of breast cancer, they represent the highest proportion of women who are diagnosed with the disease before age 45. Comparative studies of breast cancer rates among sub-Saharan Africans suggest a genetic component, as African women are diagnosed most frequently between ages 35 - 45.

The mortality rate in African-Americans is twice that of Caucasians, although it is declining. Social and economic factors make it less likely that African-American women will be screened, so they are more likely to be diagnosed at a later stage. They are also less likely to have access to effective treatments. However, there also appears to be a biological basis for African-American women’s poorer prognosis. According to research presented at the 2007 Breast Cancer Symposium, African-American women are more likely to have estrogen receptor-negative tumors, a type of breast cancer that is more difficult to treat.

An estimated 10% of all women with breast cancer have a very strong family history of the disease. Inherited forms of breast cancer often appear in young women under the age of 50. In such families, some members may also be at higher risk for ovarian cancer. These mutations can be inherited from either a mother or father.

Prior to menopause, a mass on the ovary that is smaller than 2 centimeters is probably a follicle cyst that will go away on its own. However, if the growth is larger and doesn't go away over the course of a few menstrual cycles, then it may need to be removed.

BRCA Genes. Inherited mutations in genes known as BRCA1 or BRCA2 are responsible for 30 - 50% of hereditary breast cancers, ovarian cancers, or both in families with a history of these cancers. According to some studies, the risk each gene carries is:

Between 25 - 35% of BRCA1 carriers develop breast cancer by age 70.
Between 35 - 50% of BRCA2 carriers develop the disease. BRCA2 genes also increase the lifetime risk of breast cancer in men.

These mutations are present in only about 0.5% of the overall population. However, certain ethnic groups -- such as Jewish women of Eastern European (Ashkenazi) descent -- have a higher prevalence (2.5%) of BRCA gene mutations. BRCA gene mutations are also seen in some African-American and Hispanic women.

Screening Guidelines for BRCA Genes. In 2005, the U.S. Preventive Services Task Force (USPSTF) released updated guidelines for BRCA testing. While women at high risk should be tested, the USPSTF does not recommend routine genetic counseling or testing for BRCA genes in low-risk women (no family history of BRCA 1 or 2 genetic mutations).

ESR Genes. Genetic variations in estrogen receptor genes (ESRs) may increase the risk for some women but offer protection to others. Mutations in the ESR1 and ESR2 genes may be associated with breast cancer susceptibility for Ashkenazi women over age 50 years.

Other Genetic Factors. Mutations in the tumor suppressor gene p53 are more common in the breast cancer tumors of African-American women than in Caucasian women. Researchers have also identified other defective genes that contribute to breast cancer, such as NOEY2 (which is inherited from the father), CHEK2, and ATM, a mutant gene for the rare disorder ataxia-telangiectasia. (The disease itself is rare, but 1% of the population carries a single copy -- enough to increase the risk for breast cancer.) Cowden's syndrome is an inherited disorder caused by a defective PTEN gene that is associated with a higher risk of breast cancer.

Not all genetic mutations are inherited. In 2007, scientists announced they had located a genetic mutation found in as many as 30 - 40% of breast cancers. The IKBKE mutation appears to occur during the course of a women’s lifetime. It causes overproduction of a kinase protein (IKK-epsilon) that fuels cell growth and tumor development. By identifying this genetic mutation, scientists hope they can develop drugs that will target and block IKK-epsilon production.

Because growth of breast tissue is highly sensitive to estrogens, the more estrogen a woman is exposed to over her lifetime, the higher her risk for breast cancer.

Duration of Estrogen Exposure. Early age at menarche (first menstrual period) or later age at menopause may slightly increase a women’s risk for breast cancer.

Pregnancy. Women who have never had children or who had their first child after age 30 may have a slightly increased breast cancer risk. Having children at an early age, and having multiple pregnancies, reduces breast cancer risk.

Although a few studies have suggested a slightly increased risk for breast cancer in women who have had abortions, the weight of evidence does not support an association between abortion and breast cancer. A large-scale 2007 study found that neither induced abortions nor spontaneous abortions (miscarriages) increases breast cancer risk. However, interrupting a pregnancy does reduce the protective features of a full-term pregnancy.

Studies have been mixed on whether breast-feeding decreases breast cancer risk. Breast-feeding reduces a woman’s total number of menstrual cycles, and thereby estrogen exposure, which may account for its possible protective effects. Some studies suggest that the longer a woman breast-feeds, the lower her risk.

Oral Contraception. Studies have been conflicting about whether estrogen in oral contraception increases the chances for breast cancer. Some studies have found no evidence that oral contraceptive use increases the risk for breast cancer, even in women who have taken birth control pills for 15 years or more or had taken them at young ages. In contrast, other studies have reported a slightly higher risk in women who are current or recent users and in women who take them for more than 4 years before a first full-term pregnancy.

Hormone Replacement Therapy. Many studies have reported a higher risk for breast cancer in postmenopausal women who take hormone replacement therapy (HRT) that contains both estrogen and progestin. A combination of estrogen and testosterone also increases breast cancer risk. A 2005 study suggested that HRT with no or low progestin is safer than standard estrogen-progestin combination therapy.

Several 2006 studies of women who had a hysterectomy indicated that estrogen alone does not increase overall breast cancer risk when the drug is used for 7 years or less. However, women who take estrogen for 10 - 15 years or more do have an increased risk, especially women who are already at higher risk for breast cancer. In addition, HRT increases breast cancer density, making mammograms more difficult to read. This can cause cancer to be diagnosed at a later stage. Women who take estrogen HRT should be aware that they need frequent mammogram screenings.

As further evidence of the association between HRT and breast cancer, a 2007 New England Journal of Medicine study noted that breast cancer rates have fallen as HRT use has declined. The decline in rates occurred among women over the age of 50 and was particularly associated with cancers that were estrogen receptor-positive. This type of cancer requires estrogen for growth. Experts think that postmenopausal women’s discontinuation of estrogen-containing HRT may explain the decrease in rates of new cases of estrogen receptor-positive cancer.

A 2007 position statement from the North American Menopause Society recommends that women who are at risk for breast cancer should avoid hormone therapy and try other options to manage menopausal symptoms such as hot flashes. At this time, most experts recommend that women use HRT only for short-term relief of menopausal symptoms. [See In-Depth Report #40: Menopause.]

Infertility and Infertility Treatments. There has been concern that infertility treatments using the drug clomiphene may increase the risk for breast cancer. A reassuring 2006 study indicated that ovulation induction with clomiphene does not increase breast cancer risk, and may actually decrease it. (Clomphine is related to tamoxifen, a drug that is used for breast cancer prevention in high-risk women.) The study also suggested that women who are infertile because of ovulatory dysfunction have a 25% lower risk for breast cancer than fertile women.

Abnormalities or Breast Conditions Suggesting a Higher Risk. Certain factors and breast conditions may increase the risk for breast cancer:

Dense breast tissue is associated with a higher risk for breast cancer. Studies suggest that women with highly dense tissue have 2 - 6 times the risk of women with the least dense tissue. Genetic factors play a large role in breast density. Hormone replacement therapy also increases breast density. In addition, dense breasts make mammograms more difficult to read, which increases the likelihood of missing early signs of cancer.
Benign proliferative breast disease, or unusual cell growth known as atypical hyperplasia, is a significant risk factor for breast cancer.

Some common benign breast abnormalities that pose few or no risks include the following:

Cysts. These mostly occur in women in their middle-to-late reproductive years and can be eliminated simply by aspirating fluid from them.

Click the icon to see an image of cysts in the breast.

Fibroadenoma. These are solid benign lumps that occur in women ages 15 - 30.
Breast abscesses during breast-feeding.

Click the icon to see an image of a breast abscess.

Nipple discharge. Discharge from the nipple is worrisome to patients, but is unlikely to be a sign of cancer. Unexplained discharge still warrants evaluation, however.

Click the icon to see an image of nipple discharge.

Mastalgia. This is breast pain that occurs in association with, or independently from, the menstrual cycle. About 8 - 10% of women experience moderate-to-severe breast pain associated with their menstrual cycle. In general, breast pain does not need assessment unless it is severe and prolonged.

The following physical characteristics have been associated with increased risk:

Obesity increases the risk for all types of estrogen receptor-positive breast cancers. Women who gain weight after menopause are most at risk. (On a positive note, losing weight after menopause decreases breast cancer risk.) In postmenopausal women, estrogen is produced in fat tissue. High amounts of fatty tissue increase levels of estrogen in the body, leading to faster growth of estrogen-sensitive cancers.
Estrogen is involved in building bone mass. Therefore, women with heavy, dense bones are likely to have higher estrogen levels and to be at greater risk for breast cancer.
Some studies have found a greater risk for breast cancer in taller women, possibly due to the higher estrogen levels associated with greater bone growth. In one study, regardless of their actual height, women who reached their full height at age 13 or younger had a higher risk than those who attained maximum height at age 18, reflecting higher estrogen levels at an earlier age.

Exposure to Estrogen-like Industrial Chemicals. Chemicals with estrogen-like effects, called xenoestrogens, have been under suspicion for years. There has been particular concern with pesticides containing organochlorines (DDT and its metabolites, such as dieldrin) and pyrethroids (permethrin), but at this time evidence of any causal association is very weak.

Exposure to Diethylstilbestrol. Women who took diethylstilbestrol (DES) to prevent miscarriage have a slightly increased risk for breast cancer. Recent studies also suggest a slightly increased risk for their daughters (commonly called "DES daughters"), who were exposed to the drug when their mothers took it during pregnancy.

Radiation Exposure. Heavy exposure to radiation is a significant risk factor for breast cancer. Girls who received high-dose radiation therapy face an increased risk for breast cancer in adulthood. Low-dose radiation exposure before age 20 may increase the risk for women with BRCA genetic mutations.

Researchers theorize that viruses may be involved in some types of breast cancers. A study of breast cancer samples taken from Tunisian women in North Africa found similarities with a virus known to cause breast cancer in mice. The samples were compared with those taken from women living in other global regions. The researchers suggested that a human breast cancer virus may be more prevalent in specific parts of the world.

Prevention and Lifestyle Factors

Evidence indicates that regular exercise, particularly vigorous exercise, may offer some modest protection against breast cancer. Exercise can help reduce body fat, which in turn lowers levels of cancer-promoting hormones such as estrogen. In fact, a 2006 study suggested that physical activity may help women reduce the risk for developing estrogen receptor-positive tumors.

Exercise can also help women who have been diagnosed with breast cancer. Studies indicate that both aerobic and weight training exercises benefit the body and the mind, and improve quality of life for breast cancer survivors. Even moderate exercise can help improve survival. A 2005 study in the Journal of the American Medical Association reported survival benefits for women diagnosed with breast cancer who walked 3 – 5 hours per week at an average pace. The American Cancer Society recommends engaging in 45 - 60 minutes of physical activity at least 5 days a week. A recent study indicated that diet and exercise can reduce the risk of breast cancer recurrence.

Physical activity contributes to health by reducing the heart rate, decreasing the risk for cardiovascular disease, and reducing the amount of bone loss that is associated with age and osteoporosis. Physical activity also helps the body use calories more efficiently, thereby helping in weight loss and maintenance. It can increase basal metabolic rate, reduces appetite, and helps in the reduction of body fat.

Despite much research on the association between diet and breast cancer, there is still little consensus. The best advice is to eat a well-balanced diet and avoid focusing on one "cancer-fighting" food. The American Cancer Society’s dietary guidelines for cancer prevention recommend that people:

Choose foods and amounts that promote a healthy weight.
Eat 5 or more servings of fruits and vegetables each day.
Choose whole grains instead of refined grain products.
Limit consumption of processed and red meat.
Women should limit alcohol consumption to 1 drink per day (women at high risk for breast cancer should consider not drinking alcohol at all).

For breast cancer survivors, the American Cancer Society recommends diets that include lots of fruits and vegetables, low amounts of saturated fat (from meat and high-fat dairy products), moderation in soy foods, and moderate or no alcohol consumption.

Here are results from recent studies evaluating diet and breast cancer, for preventing both the development of cancer and its recurrence:

Fats. Research is still mixed on the role that fats, and which specific types of fats, play in breast cancer risk and prevention. Several studies have indicated that red meat, which is high in saturated fat, may increase breast cancer risk when eaten in large quantities on a daily basis. (Red meat is also high in iron, which in itself may increase breast cancer risk.) According to results from the 2006 Women’s Health Initiative study of dietary fat and breast cancer, experts cannot yet definitely say that a low-fat diet will help prevent breast cancer. However, the study suggested that women who normally eat a very high-fat diet may benefit by reducing their fat intake. In the study, the low-fat diet reduced blood estrogen levels by 15%. The low-fat diet also appeared to reduce the risk for developing progesterone receptor-negative tumors.

Fruits and Vegetables. Fruits and vegetables are important sources of antioxidants, which may help protect against the tissue damage linked to increased cancer risk. Antioxidants include vitamin C, vitamin E, and carotenoids such as beta-carotene and lycopene. Richly colored fruits and vegetables -- not supplements -- are the best sources for these nutrients. These fiber-rich foods are an essential part of a healthy diet. However, it is not clear whether fruits and vegetables can specifically prevent breast cancer development or recurrence. According to a 2007 study of women with early-stage breast cancer, a low-fat diet very high in vegetables, fruit, and fiber does not work any better in preventing breast cancer recurrence than the standard 5 servings a day of fruits and vegetables. (However, a combination of diet and exercise may help.)

Calcium and Vitamin D. Eating lots of foods rich in calcium and vitamin D (such as yogurt and milk) may modestly reduce the risk of breast cancer for premenopausal -- but not postmenopausal -- women, according to a 2007 study. Low-fat or non-fat dairy products are a healthier choice than high-fat ones.

Click the icon to see an image of vitamin D sources.

Soy. Soy is an excellent low-fat protein alternative to meat. Soy contains phytoestrogens, which are estrogen-like plant chemicals. In particular, soy contains a type of phytoestrogen called isoflavones. Because many soy foods (such as tofu) are eaten in Asian countries where women tend to have a lower incidence of breast cancer, research has focused on whether soy may have a protective effect. To date, the evidence does not indicate that soy foods or supplements can reduce breast cancer risk. In addition, some studies suggest that high intakes of soy may actually increase the risk of estrogen-responsive cancers such as breast cancer. Some animal studies have suggested that the isoflavone compound genistein may reduce the protective properties of tamoxifen, a drug used to prevent breast cancer in high-risk women. The American Cancer Society recommends that women with breast cancer eat only moderate amounts of soy foods and avoid taking dietary supplements that contain high amounts of isoflavones.

Click the icon to see an image of phytochemicals.

Lifestyle Factors. Premenopausal women at higher risk, usually because of family history, should take as many preventive measures as possible, starting at an early age. The following lifestyle choices may be beneficial:

Exercising and eating healthily is the first essential rule.
High-risk premenopausal women may choose alternatives to oral contraceptives and, if feasible, consider having children early in their life.
High-risk postmenopausal women may want to forego hormone replacement therapy.
Any woman at high risk for breast cancer should consider avoiding alcohol or drinking it very sparingly.

In spite of some rumors published in the popular press, antiperspirants or use of deodorants after shaving have not been linked with any higher risk for breast cancer.

Tamoxifen and Raloxifene. Drugs known as selective estrogen-receptor modulators (SERMs) act like estrogen in some tissues but behave like estrogen blockers (anti-estrogens) in others. Two SERMs -- tamoxifen (Nolvadex) and raloxifene (Evista) -- are approved for breast cancer prevention for high-risk women. Tamoxifen and raloxifene are not recommended as prevention for women at low risk for breast cancer or its recurrence. Women at high risk for breast cancer should discuss with their doctors the risks and benefits of SERMs.

Tamoxifen (Nolvadex) is the most studied of these drugs. It is currently used to treat breast cancer and was the first drug approved for prevention. Evidence strongly suggests that it halves the risk for estrogen receptor-positive cancers in high-risk women, including those with BRCA2 mutations (although possibly not BRCA1). It also helps prevent recurrence in women who have been treated for breast cancers. However, it has no protective effects against estrogen receptor-negative (hormone-insensitive) cancers.

Tamoxifen can increase the risk for uterine (endometrial) cancers. It can also increase the risk for blood clots, strokes, and endometriosis. Less serious side effects include hot flashes and vaginal discharge.

Raloxifene (Evista) was approved in 2007 for prevention of breast cancer in postmenopausal women with osteoporosis and postmenopausal women at high risk for invasive breast cancer. Raloxifene was previously approved for prevention and treatment of osteoporosis in postmenopausal women. One of raloxifene’s main benefits is that it has a lower risk than tamoxifen of causing uterine cancer. However, raloxifene also has some serious risks.

According to the prescribing information from the Food and Drug Administration (FDA), raloxifene can increase the risk of blood clots. Women with a history of blood clots in the legs, lungs, or eyes should not take this medicine. Although studies indicate raloxifene does not increase the risk of stroke, it can increase the risk of dying from a stroke. Women with a history of stroke or current risk factors for stroke should discuss with their doctors whether raloxifene is an appropriate choice. Less serious side effects of raloxifene include hot flashes, leg cramps, swelling of the legs and feet, flu-like symptoms, joint pain, and sweating. Raloxifene can cause birth defects and is approved only for postmenopausal women. It should not be taken with the cholesterol-lowering drug cholestyramine (Questran) or with estrogens.

The FDA based its approval of raloxifene on results from several major studies. The comparison trial Study of Tamoxifen and Raloxifene (STAR), published in 2006 in the Journal of the American Medical Association, indicated that raloxifene works as well as tamoxifen in reducing the risk of invasive breast cancer, and has a lower risk of causing blood clots. However, the Raloxifene Use for the Heart (RUTH) trial, published in 2006 in the New England Journal of Medicine, suggested that raloxifene carries its own risks for blood clots and fatal strokes and may not be a safe choice for women at high risk of heart disease.

Investigational Drugs for Breast Cancer Prevention.

Aromatase inhibitors. Aromatase inhibitors such as anastrazole (Armidex), letrozole (Femara), and exemestane (Aromasin) are effective treatments for hormone-receptor positive breast cancer. Like tamoxifen, they are also being investigated for protection in high-risk women. However, these drugs may decrease bone mineral density and cognitive function, and increase the risk for falls.
Retinoids. Analogues of vitamin A called retinoids are being studied for protection against breast cancer. One retinoid, fenretinide, appears to offer some protection against a second breast cancer in previously diagnosed, premenopausal women (but not in postmenopausal women). It can cause birth defects and should not be used during pregnancy.

Symptoms

Breast cancers in their early stages are usually painless. Often the first symptom is the discovery of a hard lump. Fifty percent of such masses are found in the upper outer quarter of the breast. The lump may make the affected breast appear elevated or asymmetric. The nipple may be retracted or scaly. Sometimes the skin of the breast is dimpled like the skin of an orange. In some cases there is a bloody or clear discharge from the nipple. Many cancers, however, produce no symptoms and cannot be felt on examination. They can be detected only with a mammogram.

Monthly breast self-exams should always include: visual inspection (with and without a mirror) to note any changes in contour or texture, and manual inspection in standing and reclining positions to note any unusual lumps or thicknesses.

Diagnosis

Breast Examination by a Health Professional. Early detection of breast cancer significantly reduces the risk of death. Women ages 20 - 49 should have a physical examination by a health professional every 1 - 2 years. Those over age 50 should be examined annually. A breast exam by a health professional can find 10 - 25% of breast cancers that are missed by mammograms. Between 6 - 46% of the lumps detected by examination are malignant. (The yield is lowest in younger women and highest in older women.)

Self-Examinations. Woman have been encouraged to perform a self-examination each month, but well-conducted studies in 2002 reported no difference in mortality rates between women who were intensively instructed in self-examination and those who were not. This does not mean women should stop attempting self-examinations, but they should not replace the annual examination done by a health professional, which evidence suggests is beneficial.

1. Pick a time of the month that is easy to remember and perform self-examination at that time each month. The breast has normal patterns of thickness and lumpiness that change within a monthly period, and a consistently scheduled examination will help differentiate between what is normal from abnormal.

2. Stand in front of a mirror. Breasts should be basically the same size (one may be slightly larger than the other). Check for changes or redness in the nipple area. Look for changes in the appearance of the skin. With hands on the hips, push the pelvis forward and pull the shoulders back and observe the breasts for irregularities. Repeat the observation with hands behind the head. Move each arm and shoulder forward.

3. Lie down on the back with a rolled towel under one shoulder. Apply lotion or bath oil over the breast area.

The finger action should be as follows: Using the 2nd, 3rd, and 4th finger pads (not tips) held together, make dime-sized circles. Press lightly first to feel the breast area, then press harder using a circular motion.

Using this motion, start from the collarbone and move downward to underneath the breast. Shift the fingers slightly over, slightly overlapping the previously checked region, and work upward back to the collarbone. Repeat this up-and-down examination until the entire breast area has been examined. Be sure to cover the entire area from the collarbone to the bottom of the breast area and from the middle of the chest to the armpits. Move the towel under the other shoulder and repeat the procedure.

Examine the nipple area, by gently lifting and squeezing it and checking for discharge.

4. Repeat step 3 in an upright position. (The shower is the best place for this, using plenty of soap.)

Note: A lump can be any size or shape and can move around or remain fixed. Of special concern are specific or unusual lumps that appear to be different from the normal varying thicknesses in the breast.

Click the icon to see an image of a breast self-exam.

Current Recommendations for Screening. Mammograms are very effective low-radiation screening methods for breast cancer. At this time, the U.S. Preventive Services Task Force recommends screening mammograms, with or without breast examination, every 1 - 2 years for all women over age 40.

Guidelines from the American College of Physicians (ACP), however, debate whether women with a low risk for breast cancer should begin mammogram screening at age 40. The 2007 guidelines, instead, recommend that women in their 40s ask their doctor when they should begin having the test. In contrast, the American Cancer Society and the U.S. National Cancer Institute continue to endorse annual screening for women age 40 and older.

The ACP's guidelines have created controversy within the medical community. Supporters of the guidelines believe that these new recommendations reflect some of the risks involved in screening younger women. These risks include radiation exposure and unnecessary biopsies. Mammographies in younger women produce a relatively high rate of false-positive results (when the test falsely indicates breast cancer). Scientists are working on new technologies to improve mammography's accuracy, but more work is needed. For example, a 2007 New England Journal of Medicine study reported that computer-aided detection software, which is used to help radiologists interpret mammograms, may instead make readings less accurate.

Opponents of the ACP guidelines argue that mammograms help catch tumors while they are in their earliest and most treatable stages, and that the most deadly types of breast cancer tend to occur in women in their 40s.

In addition, according to a review in the American Cancer Society's journal, mammography rates have declined since 2000. In fact, while many experts believe that the recent decline in new cases of breast cancer is partially due to reduced use of hormone replacement therapy, other experts are concerned that fewer cases of breast cancer are being detected because fewer mammographies are being performed.

After age 50, all guidelines recommend annual screenings. The older a women gets, the greater her risk for developing breast cancer. (Women over age 65 account for most new cases of breast cancer.) Women with risk factors for breast cancer, including a close family member with the disease, should consider having annual mammograms starting 10 years earlier than the age at which the relative was diagnosed.

Click the icon to see an image of a mammogram.

Magnetic Resonance Imaging and Ultrasound. Magnetic resonance imaging (MRI) and ultrasound techniques can detect very small tumors (less than half an inch). However, they are expensive and time-consuming procedures. Nevertheless, some doctors believe they are important in identifying small tumors missed on mammography in women who are receiving lumpectomy or breast-conserving surgeries. Such findings would allow the surgeons to remove the optimal amount of abnormal tissue. Ultrasound may also be particularly important for women with dense breast tissue who show signs of breast cancer.

In a report published in 2007, the American Cancer Society recommended that high-risk women have an MRI of their breast with their annual mammogram, including those who have:

A BRCA1 or BRCA2 mutation
A first-degree relative (parent, sibling, child) with a BRCA1 or BRCA2 mutation, even if they have yet to be tested themselves
A lifetime risk of breast cancer that has been scored at 20 - 25% or greater
Had radiation to the chest between ages 10 - 30
Li-Fraumeni syndrome, Cowden syndrome, or Bannayan-Riley-Ruvalcaba syndrome, or may have one of these genetic syndromes based on a history in a first-degree relative

For women who have had cancer diagnosed in one breast, MRIs can also be very helpful for detecting hidden tumors in the other breast. A landmark 2007 study in the New England Journal of Medicine reported that MRI scans of women who were diagnosed with cancer in one breast detected over 90% of cancers in the other breast that had been previously missed by mammography or clinical breast exam. Currently, few women who are diagnosed with cancer in one breast are offered an MRI of the other breast. Some experts advocate MRIs for all women newly diagnosed with breast cancer; others oppose this view. MRI scans may be most useful for younger women with breast cancer who have dense breast tissue that may obscure tumors from mammography readings. MRIs are less likely to be helpful for older women with early tumors in one breast and clear mammography readings in the other.

It is very important that women have MRIs at qualified centers that perform many of these procedures each year. MRI is a complicated procedure and requires special equipment and experienced radiologists. MRI facilities should also be able to offer biopsies when suspicious findings are detected.

Scintimammography. In scintimammography, a radioactive chemical is injected into the circulatory system, which is then selectively taken up by the tumor and revealed on mammograms. This method is very accurate in detecting the presence or absence of breast cancer, and some doctors hope that it might eventually reduce the number of unnecessary invasive biopsies. It is used for women who have had abnormal mammograms or for women who have dense breast tissue. It is not used for regular screening or as an alternative to mammography.

A definitive diagnosis of breast cancer can be made only by a biopsy (a microscopic examination of a tissue sample of the suspicious area).

When a lump can be felt and is suspicious for cancer on mammography, an excisional biopsy may be recommended. This biopsy is a surgical procedure for removing the suspicious tissue and typically requires general anesthetic.

Click the icon to see an image of breast biopsy.

A core biopsy involves a small incision and the insertion of a spring-loaded hollow needle that removes several samples. The patient only requires local anesthetic.
A wire localization biopsy may be performed if mammography detects abnormalities but there is no lump. With this procedure, using mammography as a guide, the doctor inserts a small wire hook through a hollow needle and into the suspicious tissue. The needle is withdrawn, and the hook is used by the surgeon to locate and remove the lesion. The patient may receive local or general anesthetic.
A new vacuum-assisted device may be useful for some biopsies. This uses a single probe through which a vacuum is used to draw out tissue. It allows several samples to be taken without having to remove and re-insert the probe.

Final analysis of the breast tissue may take several days.

If breast cancer has been determined, the next diagnostic step is to find out how far it has spread. To do this, the doctor performs a procedure called an axillary lymphadenectomy, which partially or completely removes the lymph nodes in the armpit beside the affected breast (called axillary lymph nodes). It may require a hospital stay of 1 - 2 days.

Click the icon to see an image of the axillary lymph nodes.

Once the lymph nodes are removed, they are analyzed to determine whether subsequent treatment needs to be more or less aggressive:

If no cancer is found in the lymph nodes, the condition is referred to as node negative breast cancer. The chances are good that the cancer has not spread and is still local.
If cancer cells are present in the lymph nodes, the cancer is called node positive. Their presence increases the possibility that the cancer has spread microscopically to other areas of the body. In such cases, however, it is still not known if the cancer has metastasized beyond the lymph nodes or, if so, to what extent. The doctor may perform further tests to see if the cancer has spread to the bone (bone scan), lungs (x-ray or CT scan) or brain (MRI or CT scan).

Side effects of the procedure include increased risk for infection and pain, swelling in the arm from fluid build-up, and impaired sensation and restricted movement in the affected arm. Patients might ask their doctor about the availability of physical therapy or upper-body exercises after treatment. In two studies, such programs resulted in quicker recovery and no fluid build-up in the arm.

A technique known as a sentinel node biopsy is a less invasive alternative to axillary lymph node dissection. This procedure can help determine if cancer has spread beyond the nodes. If the doctor finds no evidence of cancer, the patient may not need to have a complete axillary lymphadenectomy.

Click the icon to see an image of a sentinel node biopsy.

Sentinel node biopsy involves:

The procedure uses an injection of a tiny amount of a tracer, either a radioactively-labeled substance (radioisotope) or a blue dye, into the tumor site.
The tracer or dye then flows through the lymphatic system into the sentinel node. This is the first lymph node to which any cancer would spread.
The sentinel lymph node and possibly one or two others are then removed.
If they do not show any signs of cancer, it is highly likely that the remaining lymph nodes will be cancer free, making further surgery unnecessary.

Patients who have a sentinel node biopsy tend to have better arm function and a shorter hospital stay than those who have an axillary node biopsy. The American Society of Clinical Oncology's 2005 guidelines recommend sentinel node biopsy instead of axillary lymph node dissection for women with early stage breast cancer who do not have nodes that can be felt during a physical exam. It is still not known if the sentinel node biopsy has any survival advantages compared to standard lymph node removal procedures.

Women often have to wait several days for results of sentinel node biopsies to learn whether they will require another surgery to remove additional lymph nodes. In 2007, the Food and Drug Administration approved the GeneSearch BLN Assay to help speed sentinel node biopsy testing. This molecular-based lab test can detect within 40 minutes whether cancer has spread to nearby lymph nodes. Because the test delivers rapid results while the patient is still on the operating table, it may help spare women the discomforts of a second surgical procedure and help them get treatment earlier.

Prognosis

In the U.S., about 40,460 women will die from breast cancer this year, making it the second most lethal cancer in women. (Lung cancer is the leading cancer killer in women.) The good news is that early detection and new treatments have improved survival rates. The 5-year survival rate for women diagnosed with cancer is 80%. About 88% of women diagnosed with breast cancer will survive at least 10 years. Unfortunately, women in lower social and economic groups still have significantly lower survival rates than women in higher groups.

Several factors are used to determine successful treatment and the possibility for a cure. They include:

The location of the tumor and how far it has spread
Whether the tumor is hormone receptor-positive or -negative
Genetic factors
Tumor size and shape
Rate of cell division
Biologic markers

The good news is that women are living longer with breast cancer, and at this time more than 2 million American women are survivors. Due to better treatment options, from 1990 - 2003, breast cancer mortality rates declined by 24%. However, survivors must live with the uncertainties of possible recurrent cancer and some risk for complications from the treatment itself.

Recurrences of cancer usually develop within 5 years of treatment. However, 25% of recurrences and half of new cancers in the opposite breast occur after 5 years. One study suggested that the risk factors for a first breast cancer do not necessarily place a woman at any higher risk for recurrence. (Women with a first cancer, however, do have a higher risk for a new cancer in the opposite breast. The outlook for such new cancers is independent from those of the first one.)

The location of the tumor is a major factor in outlook:

If the cancer is ductal carcinoma in situ (DCIS) or has not spread to the lymph nodes (is node-negative), the 5-year survival rates with treatment are up to 98%. However, cancer recurs in 9 - 30% of women with node-negative cancers. Recurrence is a potentially life-threatening problem, even if the disease relapses locally in the same breast. In one study of DCIS patients with locally invasive recurrence, 8-year mortality rates were only 12%.
If the lymph nodes contain cancer cells (are node positive) then survival rates fall. If the tumor is larger than 5 cm or there is widespread involvement in the lymph nodes, the cancer is sometimes referred to as locally advanced. In such cases, the survival rate drops to about 75% and below.
If the cancer has spread (metastasized) to other sites (most often the lung, liver, and bone), the average survival time is about 2 years (with some patients living for many years). New drug therapies, particularly aromatase inhibitors, have helped prolong survival for women with metastatic cancer.

The location of the tumor within the breast is an important predictor. Tumors that develop toward the outside of the breast tend to be less serious than those that occur more toward the middle of the breast.

Breast cancer cells may contain receptors, or binding sites, for the hormones estrogen and progesterone. Cells containing these binding sites are known as hormone receptor-positive cells. If cells lack these connectors, they are called hormone receptor-negative cells. About 75% of breast cancers are estrogen receptor-positive (ER-positive, or ER+). About 65% of ER-positive breast cancers are also progesterone receptor-positive (PR-positive, or PR+). Cells that have receptors for one of these hormones, or both of them, are considered hormone receptor-positive.

Hormone receptor-positive cancer is also called "hormone sensitive" because it responds to hormone therapy such as tamoxifen or aromatose inhibitors. Hormone receptor-negative tumors are referred to as "hormone insensitive" or "hormone resistant."

Women have a better prognosis if their tumors are hormone receptor-positive because these cells grow more slowly than receptor-negative cells. In addition, women with hormone receptor-positive cancer have more treatment options. (Hormone receptor-negative tumors can be treated only with chemotherapy.) A 2007 study in the Journal of Clinical Oncology indicated that recent declines in breast cancer mortality rates have been most significant among women with estrogen receptor-positive tumors, due in part to the widespread use of post-surgical tamoxifen therapy.

Determining a "genetic signature" for a tumor may prove to be a very powerful predictor of the aggressive nature of a breast cancer. Researchers have focused on 70 genes whose activity patterns may help make such predictions. In 2007, the Food and Drug Administration approved MammaPrint, a DNA microarray diagnostic test that profiles these 70 genes. The molecular test may help predict how likely it is that breast cancer will recur within 5 - 10 years. However, the accuracy of the test depends on a woman’s risk. It is more accurate when predicting a low risk for recurrence than a high risk.

The relevance of the inherited BRCA1 or BRCA2 mutations to survival is controversial. Some studies have suggested that these mutations offer a survival advantage. Others suggest that they make no difference or even worsen prognosis. Women with these genetic mutations do have a greater risk for a new cancer to develop. Patients with BRCA1 mutations tend to develop tumors that are hormone receptor negative, which can behave more aggressively.

Researchers are investigating numerous substances in tumor cells that may indicate whether or not a cancer is likely to spread. Such chemical markers may help doctors determine treatments, and some may even prove to be targets for future drugs. The following are only a few of the more well-researched markers.

HER2. The American Cancer Society recommends that all women newly diagnosed with breast cancer get a biopsy test for a growth-promoting protein called HER2/neu. HER2-positive cancer usually occurs in younger women and is more quickly-growing and aggressive than other types of breast cancer. The HER2 marker is present in about 20% of cases of invasive breast cancer. Two types of tests are used to detect HER2:

Immunohistochemistry (IHC)
Fluorescence in-situ hybridization (FISH)

Some doctors think that FISH is a more accurate test than IHC. According to 2006 HER2 testing guidelines from the American Society of Clinical Oncology and the College of American Pathologists, either test may be used as long as it is performed by an accredited laboratory. Tests that are not clearly positive or negative should be repeated. Treatment with trastuzumab (Herceptin) or lapatinib (Tykerb) may help women who test positive for HER2.

Angiogenesis Factors. Angiogenesis is the growth of new blood vessels. High levels of angiogenesis factors indicate that the tumor is developing its own supply of blood vessels, which enable the tumor to send colonies of cancer cells into the bloodstream and spread to other parts of the body. Specific angiogenesis factors, such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), may turn out to be important markers for determining treatment and prognosis. The monoclonal antibody bevacizumab (Avastin) targets VEGF. The drug is showing promise in clinical trials for prolonging progression-free survival in women with metastatic breast cancer.

Others. Many other markers are being investigated, including p53, cathepsin-D, protein c-erbB-2, bcl-2, Ki-67, telomerase, thymidylate synthase, CA 15-3, and carcinogenic embryonic antigen (CEA). The American Society of Clinical Oncology (ASCO) cautions, however, that the value of many of these factors has not yet been confirmed.

Tumor Size and Shape. Large tumors pose a higher risk than small tumors. Undifferentiated tumors, which have indistinct margins, are more dangerous than those with well-defined margins.

Rate of Cell Division. The more rapidly a tumor grows, the more dangerous it is. Several tests measure aspects of cancer cell division and may eventually prove to predict the disease. For example, the mitotic index (MI) is a measurement of the rate at which cells divide. The higher the MI, the more aggressive the cancer. Another test measures cells at a certain phase of their division.

Recent evidence has not supported early reports of survival benefits for women with metastatic breast cancer who engage in support groups. However, some studies have suggested that psychotherapy, group support, or both may relieve pain and reduce stress, particularly in women who are suffering emotionally.

Stress has been ruled out as a risk factor either for breast cancer itself or for its recurrence.

Treatment

The three major treatments of breast cancer are surgery, radiation, and drug therapy. No one treatment fits every patient, and combination therapy is usually required. The choice is determined by many factors, including the age of the patient, menopausal status, the kind of cancer (ductal vs. lobular), its stage, and whether or not the tumor contains hormone-receptors.

Breast cancer treatments are defined as local or systemic:

Local Treatment. Surgery and radiation are considered local therapies because they directly treat the tumor, breast, lymph nodes, or other specific regions. Surgery is usually the standard initial treatment.
Systemic Treatment. Drug treatment is called systemic therapy, because it affects the whole body.

Any or all of these therapies may be used separately or, most often, in different combinations. For example, radiation alone or with chemotherapy or hormone therapy may be beneficial before surgery, if the tumor is large or not easily removed at prevention. Surgery followed by radiation and hormone therapy is usually recommended for women with early-stage, hormone-sensitive cancer. There are numerous clinical trials investigating new treatments and treatment combinations. Patients, especially those with advanced stages of cancer, may wish to consider enrolling in a clinical trial.

Treatment strategies depend in part on the stage of the cancer.

Stage 0 (Carcinoma in Situ). Stage 0 breast cancer is considered non-invasive (‘in situ"), meaning that the cancer is still confined within breast ducts or lobules and has not yet spread to surrounding tissues. Stage 0 cancer is classified as either:

Ductal carcinoma in situ (DCIS). These are cancer cells in the lining of a duct that have not invaded the surrounding breast tissue.
Lobular carcinoma in situ (LCIS). These are cancer cells in the lobules of the breast. LCIS rarely develops into invasive breast cancer, but having it in one breast increases the risk of developing cancer in the other breast.

Treatment options for DCIS include:

Breast-conserving surgery and radiation therapy (followed by hormone therapy for women with hormone-sensitive cancer)
Total mastectomy (followed by hormone therapy for women with hormone-sensitive cancer)
Breast-conserving surgery without radiation therapy

Treatment options for LCIS include:

Regular exams and mammograms to monitor any potential changes (observation treatment)
Hormone therapy to prevent development of breast cancer (for women with hormone-sensitive cancer)
Mastectomy of both breasts was previously used as treatment, but is now rarely recommended

Stage I and II (Early-Stage Invasive). In stage I cancer, cancer cells have not spread beyond the breast, and the tumor is no more than 2 cm (about 3/4 of an inch) across.

Stage II cancer is classified as either stage IIA or stage IIb.

In stage IIA cancer the tumor is either:

No more than 2 centimeters and has spread to the underarm lymph nodes (axillary lymph nodes)
Between 2 - 5 centimeters and has not spread to the underarm lymph nodes

Treatment options for stage I and stage II breast cancer may include:

Breast-conserving surgery (such as lumpectomy) followed by radiation therapy
Modified radical mastectomy with or without breast reconstruction
Post-surgical therapy (adjuvant therapy), including radiation of lymph nodes, chemotherapy, or hormone therapy
Trastuzumab (Herceptin) given along with or following adjuvant chemotherapy for women with HER2-positive cancer

Stage III (Locally Advanced). Stage III breast cancer is classified into several sub-categories: Stage IIIA, stage IIIB, and stage IIIC (operable or inoperable).

In stage IIIA breast cancer, the tumor is usually confined to the underarm lymph nodes. Treatment options for stage IIIA breast cancer are the same as those for stages I and II.

In stage IIIB breast cancer, the tumor has spread to either:

Tissues near the breast (including the skin or chest wall)
Lymph nodes within the breast or under the arm

Stage IIIB treatment options may include:

Chemotherapy, and possibly hormone therapy (sometimes in combination with chemotherapy)
Chemotherapy followed by surgery (breast-conserving surgery or total mastectomy) with lymph node dissection followed by radiation therapy and possibly more chemotherapy or hormone therapy
Clinical trials

Stage IIIC breast cancer is classified as either operable or inoperable.

In operable stage IIIC, the cancer may be found in:

10 or more of the underarm lymph nodes
Lymph nodes beneath the collarbone and near the neck on the same side of the body as the affected breast
Lymph nodes within the breast as well as underarm lymph nodes

Treatment options for operable stage III breast cancer are the same as those for stage I and II breast cancers.

In inoperable stage III breast cancer, the cancer has spread to lymph nodes above the collarbone and near the neck on the same side of the body as the affected breast. Treatment options are the same as those for stage IIIB.

Stage IV (Advanced Cancer). In stage IV, the cancer has spread (metastasized) from the breast to other parts of the body. In about 75% of cases, the cancer has spread to the bone. The cancer at this stage is considered to be chronic and incurable, and the usefulness of treatments is limited. The goals of treatment for stage IV cancer are to stabilize the disease and slow its progression, as well as to reduce pain and discomfort.

Treatment options for stage IV cancer include:

Surgery or radiation for any localized tumors in the breast. A 2006 study indicated that surgical removal of the primary tumor immediately after metastatic cancer diagnosis can dramatically improve survival.
Chemotherapy, hormone therapy, or both. Targeted therapy with trastuzumab (Herceptin) or lapatinib (Tykerb) should be considered for women with HER2-positive cancer.
Cancer that has spread to the brain may require radiation and high-dose steroids.
Cancer that has spread to the bone may be helped by radiation or bisphosphonate drugs. Such treatments can relieve pain and help prevent bone fractures.
Clinical trials of new drugs or drug combinations, or experimental treatments such as high-dose chemotherapy with stem cell transplant.

In 2006, the American Society of Clinical Oncology (ASCO) released updated guidelines on follow-up care for patients who have been treated for breast cancer. ASCO recommends:

Visit your doctor every 3 - 6 months for the first 3 years after your first cancer treatment, every 6 - 12 months during the fourth and fifth year, and once a year thereafter.
Have a mammogram 1 year after the mammogram that diagnosed your cancer (but no earlier than 6 months after radiation therapy), and every 6 - 12 months thereafter.
Perform a breast self-exam every month (however, this is no substitute for a mammogram).
See your gynecologist regularly (women taking tamoxifen should be sure to report any vaginal bleeding).
A year after diagnosis, you can either continue to see your oncologist or transfer your care to your primary care physician.
If you are on hormone therapy, discuss with your oncologist how often to schedule follow-up visits for re-evaluation of your treatment.

ASCO does not recommend the use of laboratory blood tests (complete blood counts, carcinoembryonic antigen) or imaging tests (bone scans, chest x-rays, liver ultrasound, FDG-PET scan, CT scan) for routine breast cancer follow-up.

Genetic counseling may be helpful if you have:

Ashkenazi Jewish heritage
Personal or family history of ovarian cancer
Personal or family history of cancer in both breasts
Any first-degree female relative (mother, sister, daughter) diagnosed with breast cancer before age 50
Two or more first-degree or second-degree (grandparent, aunt, uncle) diagnosed with breast cancer
History of breast cancer in a male relative

Pregnancy after Breast Cancer Treatment. There are no definite recommendations on how long a woman should wait to become pregnant after breast cancer treatment. Because of the connection between estrogen levels and breast cancer cell growth, some experts recommend delaying pregnancy until 2 years after treatment in order to reduce the risk of cancer recurrence and improve odds for survival. However, a 2007 study indicated that conceiving 6 months after treatment does not negatively affect survival. Discuss with your doctor your risk for recurrence, and when it may be safe to attempt pregnancy.

Recurrent breast cancer is considered to be an advanced cancer. In such cases, the disease has come back in spite of the initial treatment. Most recurrences appear within the first 2 - 3 years after treatment, but breast cancer can recur many years later. Treatment options are based on the stage at which the cancer reappears, whether or not the tumor is hormone responsive, and the age of the patient. Between 10 - 20% of recurring cancers are local. Most recurrent cancers are metastatic. All patients with recurring cancer are candidates for clinical trials.

Because most breast cancer recurrences are discovered by patients in between doctor visits, it is important to notify your doctor if you experience any of the following symptoms. These symptoms may be signs of breast cancer recurrence:

New lumps in the breast
Bone pain
Chest pain
Abdominal pain
Shortness of breath or difficulty breathing
Persistent headaches or coughing
Rash on breast
Nipple discharge

Surgery

Surgery forms a part of nearly every patient's treatment for breast cancer. The initial surgical intervention is often a lumpectomy, the removal of the tumor itself. In the past, mastectomy (the removal of the breast) was the standard treatment for nearly all breast cancers. Now, many patients with early-stage cancers can choose breast-conserving treatment, or lumpectomy followed by radiation, with or without chemotherapy.

For invasive breast cancer, studies indicate that lumpectomy or partial mastectomy combined with radiation therapy works as well as a modified radical mastectomy.

Breast-conserving procedures are now appropriate and as successful as mastectomy in most women with early stage breast cancer. All women should discuss these options fully with their doctor. Recurrence rates with conservative surgery are highest in women under age 45. Some women choose mastectomy over breast-conserving treatment even if the latter is appropriate because it gives them a greater sense of security and allows them to avoid radiation therapy.

Lumpectomy. Lumpectomy is the removal of the tumor, often along with lymph nodes in the armpit. It serves as an opportunity for biopsy, a diagnostic tool, and a primary treatment for small local breast tumors. If invasive cancer is found, the doctor will decide to proceed with breast radiation therapy, to remove additional tissue (should the margins of the specimen show signs of cancer), or to perform a mastectomy. Lumpectomy followed by radiation therapy is appropriate and as effective as mastectomy in most women with Stage I or II breast cancers.

Click the icon to see an illustrated series detailing breast lump removal surgery.

Breast-Conserving Surgery (Quadrantectomy). Breast-conserving surgery (sometimes referred to as quadrantectomy) removes the cancer and a large area of breast tissue, occasionally including some of the lining over the chest muscles. It is less invasive than a full mastectomy, but the cosmetic results are less satisfactory than with a lumpectomy. Excellent studies have found that breast-conserving surgeries plus postoperative radiotherapy offer the same survival rates as radical mastectomy in women with early breast cancer. A new technology called partial breast radiation (MammoSite), approved by the Food and Drug Administration in 2002, confines radiation to the tumor site rather than delivering it to the whole breast, and reduces treatment time from 5 weeks to 5 days in women who undergo breast conserving surgery.

Surgery to remove the breast (mastectomy) is important for women with operable breast cancer who are not candidates for breast conserving surgeries. There are different variations on the procedure:

A total mastectomy involves removal of the whole breast and sometimes lymph nodes under the armpit.
A radical mastectomy removes the breast, chest muscles, all of the lymph nodes under the arm, and some additional fat and skin. (A modified radical mastectomy removes the entire breast and armpit lymph nodes, with the underlying chest wall muscle.) A 25-year study supported other research that observed no survival advantages from radical mastectomy compared to the less invasive mastectomies for the great majority of patients. It is rarely used anymore except when cancer is very advanced.

Click the icon to see an illustrated series detailing mastectomy surgery.

Complications and Side Effects of Surgery. Short-term pain and tenderness occur in the area of the procedure, and pain relievers may be necessary.

The most frequent complication of extensive lymph node removal is edema, or swelling, of the arm, which is usually mild and rarely painful but does increase the risk for infection. The likelihood of edema can be lessened by removing only some of the lymph nodes instead of all of them.

Infrequent complications include poor wound healing, bleeding, or a reaction to the anesthesia.

After mastectomy and lymph node removal, women may experience numbness, tingling, and difficulty in extending the arm fully. These effects can last for months or years afterward.

After a mastectomy, some women choose a breast prosthesis or opt for breast reconstruction, which can be performed during the mastectomy itself, if desired. Several studies have indicated that women who take advantage of cosmetic surgery after breast cancer have a better sense of well-being and a higher quality of life than women who do not choose reconstructive surgery. The breast is reshaped using a saline implant or, for a more cosmetic result, a muscle flap is taken from elsewhere in the body. Muscle flap procedures are more complicated, however, and blood transfusions may be required. (It should be noted that implants, including silicone implants, do not appear to put a woman at risk for breast cancer recurrence.) If the nipple is removed, it is rebuilt from other body tissues and color is applied using tattoo techniques. It is nearly impossible to rebuild a breast that is identical to its partner, and additional operations may be necessary to achieve a desirable effect.

Click the icon to see an illustrated series detailing breast reconstruction surgery.

Numerous studies are investigating minimally invasive techniques that use lasers, deep-freezing of cancer cells (cryosurgery), high-intensity ultrasound, and other experimental approaches to kill cancer cells and reduce severe complications of surgery. Radiofrequency ablation, for example, is an approach that uses an electrode inserted into the tumor. It emits radio waves that produce enough heat to destroy cancer cells. Early trials are promising. These procedures, however, are not considered standard at the present time.

Radiation

Radiation therapy uses high-energy x-rays to kill cancer cells or to shrink the size of a tumor in the breast or surrounding tissue. It is used for several weeks following lumpectomy or partial mastectomy, and sometimes after full mastectomy. Radiation therapy can help reduce the chance of breast cancer recurrence in the breast and chest wall. Radiation is also important in advanced stages of cancer for relief of symptoms and to slow progression. Research shows that radiation therapy is helpful for women of all ages, including those over age 65.

Radiation is generally administered in the following ways:

External Beam Radiation. This type of radiation is administered 4 - 6 weeks after surgery and delivered externally by an x-ray machine that targets radiation to the whole breast. It may be delivered to the chest wall in high-risk patients (large tumors, close surgical margins, or lymph node involvement). The treatment is generally given daily (except for weekends) for about 6 weeks. A follow-up boost of radiation therapy in patients with lumpectomies appears to reduce the risk for recurrence.

Brachytherapy. Less commonly, radiation is delivered in implants (called brachytherapy). Implants are most often used as a radiation boost after whole breast radiation. Studies suggest they improve survival in patients at high risk for local recurrence. Some evidence suggests that implants alone can reduce treatment time and may be as effective as external beam radiation in some patients with early stage breast cancer. A new technology for breast brachytherapy (MammoSite) was approved in 2002. The technique provides 5-year local tumor control rates similar to those of whole-breast radiation for selected patients, with much shorter treatment time and good cosmetic results.

Investigators are also testing other approaches to radiation treatment. One uses a combination of neutrons and protons (mixed-beam) or proton beams rather than the standard photon radiation therapy. Intensity-modulated radiation therapy is a promising technique that delivers different doses to multiple target areas using images of specific regions. Such an approach may improve the coverage of breast cancers while reducing the toxic effects to the heart and lungs.

Side effects of radiation include:

Fatigue is very common and increases with subsequent treatments, but most women are able to continue with normal activities. Exercise may be helpful.
Nausea and lack of appetite may develop and worsen as treatment progresses.
Skin changes and burns can occur on the breast skin. Using a cream that contains a corticosteroid, such as mometasone furoate (MMF), may be helpful. After repeated sessions, the skin may become moist and "weepy." Exposing the treated skin to air as much as possible helps healing. (Washing the affected skin with soap and water does not seem to be harmful and in one study was associated with a lower risk for this side effect.)
Uncommonly, the breast may change color, size, or become permanently firm.
Rarely, the nearest arm may swell and develop impaired mobility or even paralysis.

Future complications include:

Radiation to the left breast may increase the long-term risk for developing heart disease and heart attacks.
There is a very small risk (less than 1%) of lung irritation and scarring.
Some studies have reported a higher risk for future cancer in the opposite breast in younger women who have been given radiation to the chest wall.
Radiation therapy can increase the risk of developing other cancers, such as soft tissue malignancies known as sarcomas.

Current advanced imaging techniques use precise radiation that reduces exposure. These newer techniques are likely to reduce the risks for heart disease and other serious complications.

Medications

The most important advances in the cure of breast cancer have come through the use of drug therapy, also called systemic therapy. Surgery and radiation therapy are effective for treating tumors confined to the breast but not for cancer cells that have spread or are at risk of spreading. In such cases, drug therapy is needed.

Drug treatments for breast cancer include:

Chemotherapy. Chemotherapy drugs are "cytotoxic" (cell-killing) drugs. They are given orally or by injection. They work systemically by killing cancer cells throughout the body. (Unfortunately, they also kill normal cells, which accounts for many of their side effects.) Chemotherapy is always used for advanced breast cancer, but may also be used to treat types of early-stage breast cancer.
Hormone Therapy. The goal of hormone therapy is to prevent estrogen from stimulating breast cancer cells. It is recommended for women whose breast cancers are hormone-receptor positive (either estrogen or progesterone), regardless of the size of the tumor and whether or not it has spread to the lymph nodes. Like chemotherapy, hormone therapy works systemically.
Targeted Therapy. Newer biologic drugs target specific proteins involved in cancer. Because they do not work as systemically as chemotherapy or hormone therapy drugs, they tend to cause fewer widespread side effects. Currently, the monoclonal antibody trastuzumab (Herceptin) and the kinase inhibitor lapatinib (Tykerb) are the two targeted therapies approved for breast cancer. These drugs target the HER2/neu protein and are used to treat HER2-positive breast cancers. Bevacizumab (Avastatin) is a monoclonal antibody that targets vascular endothelial growth factor (VEGF), a protein involved in tumor blood vessel formation (angiogenesis). It is being studied in clinical trials for treatment of metastatic breast cancer.

Drug therapy may be used as:

Primary therapy for patients for whom surgery or radiation therapy is not appropriate.
Neoadjuvant therapy (before surgery or radiation) to shrink tumors to a size that can be treated with local therapy.
Adjuvant therapy (following surgery or radiation) to reduce the risk of cancer recurrence.

For metastatic cancer, drugs are used not to cure but to improve quality of life and prolong survival.

Chemotherapy

Chemotherapy needs to be tailored to the type of cancer involved. Women require different treatments depending on whether the tumor is node-negative or -positive, hormone receptor-positive or -negative, or HER2-positive or -negative. Different treatment approaches are also used for early-stage cancer and advanced cancer.

A 2006 study in the Journal of the American Medical Association indicated that women with hormone receptor-negative cancers respond better to chemotherapy than women with hormone receptor-positive cancer. However, some women with hormone receptor-positive cancer do benefit from chemotherapy, as well as from hormone therapy.

Adjuvant chemotherapy is administered following surgery and before radiation therapy. A 2007 study in the Journal of Clinical Oncology suggested that women with early-stage breast cancer can safely wait for up to 12 weeks after surgery before beginning chemotherapy. However, delaying chemotherapy until more than 12 weeks after surgery significantly increases the risk for breast cancer recurrence and can reduce the odds for survival by as much as 60%.

Many different types of chemotherapy drugs are used to treat breast cancer. Common types of chemotherapy drug classes include:

Anthracyclines include doxorubicin (Adriamycin) and epirubicin (Ellence). Anthracycline-based combination regimens are often used to treat early-stage breast cancer, as well as advanced cancer.
Taxanes include paclitaxel (Taxol) and docetaxel (Taxotere). Two 2003 studies suggested that taxane-based therapy is particularly helpful for node-positive breast cancer. A newer formulation of paclitaxel (Abraxane) is used as a secondary treatment for advanced breast cancer.
Platinum-based drugs include oxaliplatin (Eloxatin) and carboplatin (Paraplatin). These drugs may be used in combination regiments for advanced cancer or for cancers associated with BRCA genes.

Some of the abbreviations used for chemotherapy drug combinations (regimens) refer to drug classes rather than drug names. For example, regimens that contain an anthracycline drug (such as doxorubicin) use the letter "A," and regimens that contain a taxane drug (such as docetaxel) use the letter "T." Cyclophosphamide (Cytoxan), fluorouracil (5-FU), and methotrexate (MTX) are standard cancer drugs used in many breast cancer chemotherapy regimens.

Chemotherapy regimens usually consist of 4 - 6 cycles of treatment given over 3 - 6 months. Common chemotherapy regimens for early-stage breast cancer include:

AC (Doxorubicin and cyclophosphamide)
AC followed by T (Doxorubicin and cylophosphamide followed by paclitaxel)
CAF (Cyclophosphamide, doxorubicin, and 5-FU)
CMF (Cyclophosphamide, methotrexate, and 5-FU)
TAC (Docetaxel, doxorubicin, and cyclophosphamide)

Trastuzumab (Herceptin). Trastuzumab is a monoclonal antibody that targets the HER2 protein on cancer cells. HER2-positive cancers account for 15 - 25% of early-stage breast cancer and are associated with more aggressive disease. Younger women tend to be most affected. In November 2006, the Food and Drug Administration approved trastuzumab for treatment of HER2-positive, early-stage breast cancer (cancer confined to the breasts or lymph nodes that has been surgically removed). Trastuzumab is given along with other chemotherapy drugs following lumpectomy or mastectomy. Research indicates that trastuzumab can help prevent cancer recurrence and death among women with early-stage breast cancer, but it increases the risk of heart problems. Trastuzumab can cause heart failure. Women who have heart failure or weak heart muscle (cardiomyopathy) should not use this drug. Women who take trastuzumab need to have regular heart monitoring, especially if they have already have heart problems.

Patients who develop metastatic disease (cancer that spreads throughout the body) are generally not curable. New advances in drug therapies, however, can help shrink tumors, prolong survival, and improve quality of life.

Chemotherapy regimens for advanced cancer may use a single drug or a combination of drugs. Many chemotherapy regimens used for early-stage breast cancer are also used for advanced breast cancer. Some specific combinations for advanced cancer include:

Gemcitabine and paclitaxel. In 2004, the Food and Drug Administration approved the antimetabolite drug gemcitabine (Gemzar) for use in combination with paclitaxel (Taxol) as a first-line treatment option for women with metastatic breast cancer.
Capecitabine (Xeloda) and docetaxel (Taxotere). Capecitabine is an oral drug that is chemically related to 5-FU. It is also being studied in combination with many other drugs.

Numerous chemotherapy drugs and drug combinations are being tested in clinical trials. Patients with advanced breast cancer may also receive other types of drug treatments. Bisphosphonate drugs, such as zoledronic acid (Zometa) and pamidronate (Aredia), are important supportive drugs for preventing fractures and reducing pain in people whose cancer has spread to the bones.

Two targeted therapy drugs are approved for the treatment of HER2-positive advanced breast cancer

Trastuzumab (Herceptin) was approved in 1998 for treatment of metastatic breast cancer. It is used in adjuvant chemotherapy, along with drugs such as paclitaxel.
Lapatinib (Tykerb) was approved in March 2007 for patients who have not been helped by other cancer drugs, including an anthracycline, a taxane, or trastuzumab. Lapatinib is used in combination with capecitabine (Xeloda). Research suggests it may have fewer risks for heart problems than trastuzumab.

Promising new treatments for advanced breast cancer include:

Ixabepilone (BMS-247550). Ixabepilone is the first of a new class of cancer drugs called epothilones. It is showing encouraging results when combined with capecitabine, according to research presented at the 2007 annual meeting of the American Society of Clinical Oncology.
Bevacizumab (Avastin). Bevacizumab is a targeted therapy anti-angiogenesis drug approved for treatment of colorectal and lung cancers. It is being studied in combination with various chemotherapy drugs for treatment of advanced cancer.

Side effects occur with all chemotherapeutic drugs. They are more severe with higher doses and increase over the course of treatment.

Common side effects include:

Nausea and vomiting. Drugs known as serotonin antagonists, especially ondansetron (Zofran), can relieve these side effects. In one study, a combination of dexamethasone (a corticosteroid) with ondansetron taken within 24 hours of chemotherapy achieved either a major or complete reduction in nausea and vomiting. Aprepitant (Emend), a new drug for preventing chemotherapy-caused nausea and vomiting, was approved in 2006.
Diarrhea
Temporary hair loss
Weight loss
Fatigue
Depression

Serious short- and long-term complications can also occur and may vary depending on the specific drugs used. They include the following:

Anemia. The erythropoietins epoetin alfa (Epogen, Procrit) and darbepoetin alfa (Aranesp) stimulate red blood cell production and can help reduce or prevent anemia, resulting in significant improvement in quality of life. Aranesp persists longer in the blood than epoetin alfa and may therefore require fewer injections.
Increased chance for infection from severe reduction in white blood cells (neutropenia). The addition of a drug called granulocyte colony-stimulating factor (filgrastim and lenograstim) is very helpful in reducing the risk for severe infection.
Liver and kidney damage.
Abnormal blood clotting (thrombocytopenia).
Allergic reaction, particularly to platinum-based drugs.
Menstrual abnormalities and infertility. Premature menopause occurs in about 30% of women, particularly in those over 40. A natural hormone medication called a gonadotropin-releasing hormone analogue, which puts women in a temporary pre-pubescent state during chemotherapy, may preserve fertility in some women. Women may also wish to consider embryo cryopreservation -- the harvesting of eggs, followed by in vitro fertilization and freezing of embryos for later use. The American Society of Clinical Oncology recommends that women being treated for cancer see a reproductive specialist to discuss all available fertility preservation options.
Sexual dysfunction.
Rarely, secondary cancers such as leukemia.
A quarter to a third of women report problems in concentration, motor function, and memory, which can be long-term. In one study, women were having these symptoms 2 years after treatment, although by 4 years they had resolved.
Heart problems. Trastuzumab (Herceptin) may increase the risk for heart failure, particularly in women with pre-existing risk factors. Cumulative doses of anthracyclines (doxorubicin, epirubicin) can also damage heart muscles over time and increase the risk for heart failure.
Taxanes can cause a drop in white blood cells and possible problems in the heart and central nervous system. Allergic reactions can occur, more often in taxol than taxotere. Taking a steroid before taxane administration can help prevent such reactions. Taxane therapy may also cause severe joint and muscle pain in some patients, relievable with corticosteroids.

High-dose chemotherapy along with peripheral-blood stem cell rescue or bone marrow transplantation procedures have been used for cancer that has metastasized and, in some cases, for earlier stages of breast cancer in high-risk patients. The objective of this treatment is to be able to give patients very high toxic doses of cell-killing drugs.

Transplantation procedures are based on stem cells, which are produced in the bone marrow. Stem cells are the early forms for all blood cells in the body (including red, white, and immune cells). Cancer treatments can harm these growing cells as well as cancer cells.

Despite the initial enthusiasm over the use of high-dose therapy for treatment of high risk breast cancer, this approach can no longer be generally recommended and should not be used outside of a clinical trial setting. The results of several randomized studies have failed to show a convincing advantage for the use of high-dose therapy. Nevertheless, some experts believe this approach can still be useful in selected patients, and studies continue. In general, however, transplantation has a limited role in breast cancer management, and its use should be restricted to clinical trials.

Hormone Therapy

Hormone therapy works by blocking estrogen that causes cell proliferation. It is used only for patients with hormone receptor-positive tumors. Different types of hormone therapy work in different ways by:

Blocking estrogen receptors in cancer cells (Tamoxifen)
Suppressing estrogen production in the body (Aromatase inhibitors)
Destroying ovaries, which produce estrogen (Ovarian ablation)

Tamoxifen was the first widely used hormonal therapy drug, but it has been replaced by aromatase inhibitors for some women. Aromatase inhibitors are used only to treat postmenopausal women. Tamoxifen is mainly used as adjuvant therapy for premenopausal women with hormone-sensitive breast cancer.

Tamoxifen (Nolvadex) has been the standard hormonal drug used for breast cancer. It belongs to a class of compounds called selective estrogen receptor modulators (SERMs). SERMs chemically resemble estrogen and trick the breast cancer cells into accepting it in place of estrogen. Unlike estrogen, however, they do not stimulate breast cancer cell growth. Because SERMs block estrogen’s effects on cancer cells, they are sometimes referred to as "anti-estrogen" drugs.

Tamoxifen is used for all cancer stages in women of all ages with hormone receptor-positive cancers. In addition, it is used to prevent breast cancer in high-risk women. Another SERM drug, toremifene (Fareston), is an option for women with advanced cancer, but this drug is rarely used in the United States. A third drug, fulvestrant (Faslodex), works in a similar anti-estrogen way to tamoxifen but belongs to a different drug class. Fulvestrant is approved only for postmenopausal women with hormone-sensitive advanced breast cancer in which tamoxifen or aromatase inhibitors no longer work.

To prevent cancer recurrence, women should take tamoxifen for 5 years following surgery and radiation. Tamoxifen is an effective cancer treatment, but it can cause unpleasant side effects and has small (less than 1%) but serious risks for blood clots and uterine (endometrial) cancer. Immediately report any signs of vaginal bleeding to the doctor, as this may be a symptom of uterine cancer.

Less serious, but discomforting, side effects include hot flashes and mood swings. According to a 2007 study, nearly 25% of women stop taking tamoxifen within 1 year because of these symptoms. By 3.5 years, over 33% stop treatment. Taking tamoxifen for fewer than 5 years, however, increases the risk for cancer recurrence and death. Talk with your doctor about antidepressants or other therapies that may help you cope with tamoxifen’s side effects.

Many doctors now recommend that postmenopausal women switch to an aromatase inhibitor after 2 - 3 years of tamoxifen therapy. Several 2007 studies indicated that switching from tamoxifen to an aromatase inhibitor significantly improves survival rates and reduces the risk of death from breast cancer as well as other causes.

Endometrial cancer is a cancerous growth of the endometrium (lining of the uterus). It is the most common uterine cancer.

Aromatase inhibitors block aromatase, an enzyme that is a major source of estrogen in many major body tissues, including the breast, muscle, liver, and fat. Aromatase inhibitors work differently than tamoxifen. Tamoxifen interferes with tumors’ ability to use estrogen by blocking their estrogen receptors. Aromatase inhibitors reduce the overall amount of estrogen in the body.

Because these drugs cannot stop the ovaries of premenopausal women from producing estrogen, they are recommended only for postmenopausal women.

There are currently three aromatase inhibitors approved for treating early-stage, hormone receptor-positive breast cancer in postmenopausal women:

Anastrazole (Armidex) for treatment after surgery
Exemestane (Aromasin) for women who have taken tamoxifen for 2 - 3 years
Letrozole (Femara) for treatment after surgery or for women who have completed 5 years of tamoxifen therapy

All of these drugs are also approved for women with advanced (metastatic) hormone-sensitive breast cancer. Studies indicate that the introduction of aromatase inhibitors has helped greatly in prolonging survival for women with advanced cancer.

Compared to tamoxifen, aromatase inhibitors are less likely to cause blood clots and uterine cancer. However, these drugs are more likely to cause osteoporosis, which can lead to bone loss and fractures. In general, recent studies indicate that aromatase inhibitors are better than tamoxifen in improving survival and reducing the risk of cancer recurrence. Unfortunately, like tamoxifen, they can cause hot flashes, as well as joint pain.

Ovarian ablation literally shuts down estrogen production from the ovaries. Medications can accomplish ovarian ablation. Destroying the ovaries with surgery or radiation can also shut down estrogen production. (Osteoporosis is one serious side effect of this approach, but several therapies are available to help prevent bone loss.)

Chemical Ovarian Ablation. Drug treatment (non-chemotherapy drugs) to block ovarian production of estrogen is called chemical ovarian ablation. It is often reversible. The primary drugs used are luteinizing hormone-releasing hormone (LHRH) agonists, such as goserelin (Zoladex). (They are also sometimes called GnRH agonists). These drugs block the release of the reproductive hormones LH-RH, therefore stopping ovulation and estrogen production.

Studies suggest that women with estrogen-positive early stage cancer who take goserelin have similar survival rates to those who take standard chemotherapy. They also experience fewer serious side effects. A major analysis of four trials using LHRH agonists plus tamoxifen suggested that this combination should be the standard for patients with advanced breast cancers that are hormone-receptor positive, although this is an area of controversy. (Chemotherapy is still more effective in women with estrogen-negative tumors.)

Ovariectomy. Ovariectomy, the removal of the ovaries, has modestly improved breast cancer survival rates in some premenopausal women whose tumors are hormone receptor-positive. In these women, combining this procedure with tamoxifen may improve results beyond those of standard chemotherapies. Ovariectomy does not benefit women after menopause, and its advantages can be blunted in women who have received adjuvant chemotherapy. The procedure causes sterility and can have a major negative emotional impact on younger patients.

Resources

www.cancer.gov -- National Cancer Institute
www.cancer.org -- American Cancer Society
www.asco.org -- American Society of Clinical Oncology
www.oncolink.org -- Oncolink
www.womenshealth.gov -- National Women's Health Information Center
www.nccn.org -- National Comprehensive Cancer Network
www.plwc.org -- People Living With Cancer
www.cancer.gov/clinicaltrials -- Find clinical trials
www.breastcancer.org -- Find clinical trials

References

Bardia A, Hartmann LC, Vachon CM, Vierkant RA, Wang AH, Olson JE, et al. Recreational physical activity and risk of postmenopausal breast cancer based on hormone receptor status. Arch Intern Med. 2006 Dec 11-25;166(22):2478-83.

Barron TI, Connolly R, Bennett K, Feely J, Kennedy MJ. Early discontinuation of tamoxifen: a lesson for oncologists. Cancer. 2007 Mar 1;109(5):832-9.

Boccardo F, Rubagotti A, Aldrighetti D, Buzzi F, Cruciani G, Farris A, et al. Switching to an aromatase inhibitor provides mortality benefit in early breast carcinoma: pooled analysis of 2 consecutive trials. Cancer. 2007 Mar 15;109(6):1060-7.

Boehm JS, Zhao JJ, Yao J, Kim SY, Firestein R, Dunn IF, et al. Integrative genomic approaches identify IKBKE as a breast cancer oncogene. Cell. 2007 Jun 15;129(6):1065-79.

Boyd NF, Guo H, Martin LJ, Sun L, Stone J, Fishell E, et al. Mammographic density and the risk and detection of breast cancer. N Engl J Med. 2007 Jan 18;356(3):227-36.

Breen N, A Cronin K, Meissner HI, Taplin SH, Tangka FK, Tiro JA, et al. Reported drop in mammography : is this cause for concern? Cancer. 2007 Jun 15;109(12):2405-9.

Chia SK, Speers CH, D'Yachkova Y, Kang A, Malfair-Taylor S, Barnett J, et al. The impact of new chemotherapeutic and hormone agents on survival in a population-based cohort of women with metastatic breast cancer. Cancer. 2007 Jul 23;110(5):973-979 [Epub ahead of print]

Cho E, Chen WY, Hunter DJ, Stampfer MJ, Colditz GA, Hankinson SE, et al. Red meat intake and risk of breast cancer among premenopausal women. Arch Intern Med. 2006 Nov 13;166(20):2253-9.

Coombes RC, Kilburn LS, Snowdon CF, Paridaens R, Coleman RE, Jones SE, et al. Survival and safety of exemestane versus tamoxifen after 2-3 years' tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial. Lancet. 2007 Feb 17;369(9561):559-70.

Fenton JJ, Taplin SH, Carney PA, Abraham L, Sickles EA, D'Orsi C, et al. Influence of computer-aided detection on performance of screening mammography. N Engl J Med. 2007 Apr 5;356(14):1399-409.

Geiger AM, Thwin SS, Lash TL, Buist DS, Prout MN, Wei F, et al. Recurrences and second primary breast cancers in older women with initial early-stage disease. Cancer. 2007 Mar 1;109(5):966-74.

Geyer CE, Forster J, Lindquist D, Chan S, Romieu CG, Pienkowski T, et al. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med. 2006 Dec 28;355(26):2733-43.

Ives A, Saunders C, Bulsara M, Semmens J. Pregnancy after breast cancer: population based study. BMJ. 2007 Jan 27;334(7586):194. Epub 2006 Dec 8.

Jatoi I, Chen BE, Anderson WF, Rosenberg PS. Breast cancer mortality trends in the United States according to estrogen receptor status and age at diagnosis. J Clin Oncol. 2007 May 1;25(13):1683-90. Epub 2007 Apr 2.

Kahlenborn C, Modugno F, Potter DM, Severs WB. Oral contraceptive use as a risk factor for premenopausal breast cancer: a meta-analysis. Mayo Clin Proc. 2006 Oct;81(10):1290-302.

Kerlikowske K, Miglioretti DL, Buist DS, Walker R, Carney PA; National Cancer Institute-Sponsored Breast Cancer Surveillance Consortium. Declines in invasive breast cancer and use of postmenopausal hormone therapy in a screening mammography population. J Natl Cancer Inst. 2007 Sep 5;99(17):1335-9. Epub 2007 Aug 14.

Khatcheressian JL, Wolff AC, Smith TJ, Grunfeld E, Muss HB, Vogel VG, et al.American Society of Clinical Oncology 2006 update of the breast cancer follow-up and management guidelines in the adjuvant setting. J Clin Oncol. 2006 Nov 1;24(31):5091-7. Epub 2006 Oct 10.

Lehman CD, Gatsonis C, Kuhl CK, Hendrick RE, Pisano ED, Hanna L, et al. MRI evaluation of the contralateral breast in women with recently diagnosed breast cancer. N Engl J Med. 2007 Mar 29;356(13):1295-303. Epub 2007 Mar 28.

Lin J, Manson JE, Lee IM, Cook NR, Buring JE, Zhang SM. Intakes of calcium and vitamin D and breast cancer risk in women. Arch Intern Med. 2007 May 28;167(10):1050-9.

Lohrisch C, Paltiel C, Gelmon K, Speers C, Taylor S, Barnett J, et al. Impact on survival of time from definitive surgery to initiation of adjuvant chemotherapy for early-stage breast cancer. J Clin Oncol. 2006 Oct 20;24(30):4888-94. Epub 2006 Oct 2.

Michels KB, Xue F, Colditz GA, Willett WC. Induced and spontaneous abortion and incidence of breast cancer among young women: a prospective cohort study. Arch Intern Med. 2007 Apr 23;167(:814-20.

Moss SM, Cuckle H, Evans A, Johns L, Waller M, Bobrow L. Effect of mammographic screening from age 40 years on breast cancer mortality at 10 years' follow-up: a randomised controlled trial. Lancet. 2006 Dec 9;368(9552):2053-60.

North American Menopause Society. Estrogen and progestogen use in peri- and postmenopausal women: March 2007 position statement of The North American Menopause Society. Menopause. 2007 Mar-Apr;14(2):168-82.

Perez EA, Lerzo G, Pivot X, Thomas E, Vahdat L, Bosserman L, et al. Efficacy and safety of ixabepilone (BMS-247550) in a phase II study of patients with advanced breast cancer resistant to an anthracycline, a taxane, and capecitabine. J Clin Oncol. 2007 Aug 10;25(23):3407-14. Epub 2007 Jul 2.

Pierce JP, Natarajan L, Caan BJ, Parker BA, Greenberg ER, Flatt SW, et al. Influence of a diet very high in vegetables, fruit, and fiber and low in fat on prognosis following treatment for breast cancer: the Women's Healthy Eating and Living (WHEL) randomized trial. JAMA. 2007 Jul 18;298(3):289-98.

Qaseem A, Snow V, Sherif K, Aronson M, Weiss KB, Owens DK; Clinical Efficacy Assessment Subcommittee of the American College of Physicians. Screening mammography for women 40 to 49 years of age: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2007 Apr 3;146(7):511-5.

Ravdin PM, Cronin KA, Howlader N, Berg CD, Chlebowski RT, Feuer EJ, et al. The decrease in breast-cancer incidence in 2003 in the United States. N Engl J Med. 2007 Apr 19;356(16):1670-4.

Saslow D, Boetes C, Burke W, Harms S, Leach MO, Lehman CD, et al. American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography. CA Cancer J Clin. 2007 Mar-Apr;57(2):75-89.

Smith I, Procter M, Gelber RD, Guillaume S, Feyereislova A, Dowsett M, et al. 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial. Lancet. 2007 Jan 6;369(9555):29-36.

Terry KL, Willett WC, Rich-Edwards JW, Michels KB. A prospective study of infertility due to ovulatory disorders, ovulation induction, and incidence of breast cancer. Arch Intern Med. 2006 Dec 11-25;166(22):2484-9.

Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol. 2007 Jan 1;25(1):118-45. Epub 2006 Dec 11.

Review Date:
1/26/2008
Reviewed By:
A.D.A.M. Editorial Team: David Zieve, MD, MHA, Greg Juhn, MTPW, David R. Eltz, Kelli A. Stacy, ELS. Previously reviewed by Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital (11/01/07).

A.D.A.M., Inc. is accredited by URAC, also known as the American Accreditation HealthCare Commission (www.urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows rigorous standards of quality and accountability. A.D.A.M. is among the first to achieve this important distinction for online health information and services. Learn more about A.D.A.M.'s editorial policy, editorial process and privacy policy. A.D.A.M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health on the Net Foundation (www.hon.ch).

A.D.A.M. Copyright

The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed medical professional should be consulted for diagnosis and treatment of any and all medical conditions. Call 911 for all medical emergencies. Links to other sites are provided for information only -- they do not constitute endorsements of those other sites. © 1997-2009 A.D.A.M., Inc. Any duplication or distribution of the information contained herein is strictly prohibited.

adam.com

Breast cancer

admin — Wed, 03 Sep 2008 17:52:59 -0700

HEALTH GUIDE REFERENCE FROM A.D.A.M

Definition

Breast cancer is a cancer that starts in the tissues of the breast.

There are two main types of breast cancer:

Ductal carcinoma starts in the tubes (ducts) that move milk from the breast to the nipple. Most breast cancers are of this type.
Lobular carcinoma starts in parts of the breast, called lobules, that produce milk.

In rare cases, breast cancer can start in other areas of the breast.

Many breast cancers are sensitive to the hormone estrogen. This means that estrogen causes the breast cancer tumor to grow. Such cancer is called estrogen receptor positive cancer or ER positive cancer.

Some women have what's called HER2-positive breast cancer. HER2 refers to a gene that helps cells grow, divide, and repair themselves. When cells have too many copies of this gene, cells -- including cancer cells -- grow faster. Experts think that women with HER2-positive breast cancer have a more aggressive disease and a higher risk of recurrence than those who do not have this type.

Alternative Names

Cancer - breast; Carcinoma - ductal; Carcinoma - lobular

Causes, incidence, and risk factors

Over the course of a lifetime, one in eight women will be diagnosed with breast cancer.

Risk factors you cannot change include:

Age and gender -- Your risk of developing breast cancer increases as you get older. The majority of advanced breast cancer cases are found in women over age 50. Women are 100 times more likely to get breast cancer then men.

Family history of breast cancer -- You may also have a higher risk for breast cancer if you have a close relative has had breast, uterine, ovarian, or colon cancer. About 20-30% of women with breast cancer have a family history of the disease.

Genes -- Some people have genes that make them more prone to developing breast cancer. The most common gene defects are found in the BRCA1 and BRCA2 genes. These genes normally produce proteins that protect you from cancer. But if a parent passes you a defective gene, you have an increased risk for breast cancer. Women with one of these defects have up to an 80% chance of getting breast cancer sometime during their life.

Other genetic defects have been linked to breast cancer, including those found in the ATM gene, the CHEK-2 gene, and the p53 tumor suppressor gene, but these are very rare.

Menstrual cycle -- Women who get their periods early (before age 12) or went through menopause late (after age 55) have an increased risk for breast cancer.

Other risk factors include:

Alcohol use -- Drinking more than 1-2 glasses of alcohol a day may increase your risk for breast cancer.

Childbirth -- Women who have never had children or who had them only after age 30 have an increased risk for breast cancer. Being pregnant more than once or becoming pregnant at an early age reduces your risk of breast cancer.

DES -- Women who took diethylstilbestrol (DES) to prevent miscarriage may have an increased risk of breast cancer after age 40. This drug was given to the women in the 1940s-1960s.

Hormone replacement therapy (HRT) -- You have a higher risk for breast cancer if you have received hormone replacement therapy for several years or more. Many women take HRT to reduce the symptoms of menopause.

Obesity -- Obesity has been linked to breast cancer, although this link is controversial. The theory is that obese women produce more estrogen, which can fuel the development of breast cancer.

Radiation -- If you received radiation therapy as a child or young adult to treat cancer of the chest area, you have a significantly higher risk for developing breast cancer. The younger you started such radiation, the higher your risk -- especially if the radiation was given when a female was developing breasts.

Breast implants, using antiperspirants, and wearing underwire bras do not raise your risk for breast cancer. There is no evidence of a direct link between breast cancer and induced abortion or pesticides.

The National Cancer Institute provides an online tool to help you figure out your risk of breast cancer. See: www.cancer.gov/bcrisktool

Symptoms

Early breast cancer usually does not cause symptoms. This is why regular breast exams are important. As the cancer grows, symptoms may include:

Breast lump or lump in the armpit that is hard, has uneven edges, and usually does not hurt
Change in the size, shape, or feel of the breast or nipple -- for example, you may have redness, dimpling, or puckering that looks like the skin of an orange
Fluid coming from the nipple -- may be bloody, clear-to-yellow, or green, and look like pus

Men get breast cancer, too. Symptoms include breast lump and breast pain and tenderness.

Symptoms of advanced breast cancer may include:

Bone pain
Breast pain or discomfort
Skin ulcers
Swelling of one arm (next to breast with cancer)
Weight loss

Signs and tests

The doctor will ask you about your symptoms and risk factors, and then perform a physical exam, which includes both breasts, armpits, and the neck and chest area. Additional tests may include:

Mammography to help identify the breast lump
Breast MRI to help better identify the breast lump
Breast ultrasound to show whether the lump is solid or fluid-filled
Breast biopsy, needle aspiration, or breast lump removal to remove all or part of the breast lump for closer examination by a laboratory specialist

If your doctor learns that you do have breast cancer, additional tests will be done to see if the cancer has spread. This is called staging. Staging helps guide future treatment and follow-up and gives you some idea of what to expect in the future.

Breast cancer stages range from 0 to IV. In general, breast cancer that stays where it has started is called in situ or noninvasive breast cancer. If it spreads, it is called invasive breast cancer. The higher the number, the more advanced the cancer.

Treatment

Treatment is based on many factors, including type and stage of the cancer, whether the cancer is sensitive to certain hormones, and whether or not the cancer overproduces (overexpresses) a gene called HER2/neu.

In general, cancer treatments may include:

Chemotherapy medicines to kill cancer cells
Radiation therapy to destroy cancerous tissue
Surgery to remove cancerous tissue - a lumpectomy removes the breast lump; mastectomy removes all or part of the breast and possible nearby structures

Other treatments:

Hormonal therapy to block certain hormones that fuel cancer growth
Targeted therapy to interfere with cancer cell grow and function

An example of hormonal therapy is the drug tamoxifen. This drug blocks the effects of estrogen, which can help breast cancer cells survive and grow. Most women with estrogen sensitive breast cancer benefit from this drug. A newer class of medicines called aromatase inhibitors, such as exemestane (Aromasin), have been shown to work just as well or even better than tamoxifen in post-menopausal women with breast cancer.

Targeted therapy, also called biologic therapy, is a newer type of cancer treatment. This therapy uses special anti-cancer drugs that identify certain changes in a cell that can lead to cancer. One such drug is trastuzumab (Herceptin). For women with stage IV HER2-positive breast cancer, Herceptin plus chemotherapy has been shown to be work better than chemotherapy alone. Studies have also shown that in women with early stage HER2-positive breast cancer, this medicine plus chemotherapy cuts the risk of the cancer coming back by 50%.

Cancer treatment may be local or systemic.

Local treatments involve only the area of disease. Radiation and surgery are forms of local treatment.
Systemic treatments affect the entire body. Chemotherapy is a type of systemic treatment.

Most women receive a combination of treatments. For women with stage I, II, or III breast cancer, the main goal is to treat the cancer and prevent it from returning. For women with stage IV cancer, the goal is to improve symptoms and help them live longer. In most cases, stage IV breast cancer cannot be cured.

Stage 0 -- Lumpectomy plus radiation or mastectomy is the standard treatment. There is some controversy on how best to treat DCIS.

Stage I and II -- Lumpectomy plus radiation or mastectomy with some sort of lymph node removal is standard treatment. Hormone therapy, chemotherapy, and biologic therapy may also be recommended following surgery.

Stage III -- Treatment involves surgery possibly followed by chemotherapy, hormone therapy, and biologic therapy.

Stage IV -- Treatment may involve surgery, radiation, chemotherapy, hormonal therapy, or a combination of such treatments.

Support Groups

Talking about your disease and treatment with others who share common experiences and problems can be helpful. See: Cancer support group

Expectations (prognosis)

How well you do after being treated for breast cancer depends on many things. The more advanced your cancer, the poorer the outcome.

The 5-year survival rate refers to the number of patients who live at least 5 years after their cancer is found. According to the American Cancer Society (ACS), the 5-year survival rates for persons with breast cancer that is appropriately treated are as follows:

100% for stage 0
100% for stage I
92% for stage IIA
81% for stage IIB
67% for stage IIIA
54% for stage IIIB
20% for stage IV

Complications

New, improved treatments are helping persons with breast cancer live longer than ever before. However, even with treatment, breast cancer can spread to other parts of the body. Sometimes, cancer returns even after the entire tumor is removed and nearby lymph nodes are found to be cancer-free.

You may experience side effects or complications from cancer treatment. For example, radiation therapy may cause temporary swelling of the breast, and aches and pains around the area. Ask your doctor about the side effects you may have during treatment.

Calling your health care provider

Contact your health care provider for an appointment if:

You have a breast or armpit lump
You are a woman age 40 or older and have not had a mammogram in the last year
You are a woman age 35 or older and have a mother or sister with breast cancer, or have already had cancer of the breast, uterus, ovary, or colon.
You do not know how or need help learning how to perform a breast self-examination

Prevention

Many risk factors -- such as your genes and family history -- cannot be controlled. However, a healthy diet and a few lifestyle changes may reduce your overall chance of cancer in general.

Breast cancer is more easily treated and often curable if it is found early.

Early detection involves:

Breast self-exams (BSE)
Clinical breast exams by a medical professional
Screening mammography

Most experts recommend that women age 20 and older examine their breasts once a month during the week following the menstrual period.

Women between the ages 20 and 39 should have a doctor examine their breasts at least once every 3 years. After age 40, women should a clinical breast exam every year.

Mammography is the most effective way of detecting breast cancer early.

Screening recommendations:

The American Cancer Society recommends mammogram screening every year for all women age 40 and older. The National Cancer Institute (NCI) recommends mammogram screening every 1-2 years for women age 40 and older.
If you are high risk, experts say you should start getting a mammogram at age 30. Certain women at high risk of breast cancer should also have a breast MRI along with their yearly mammogram. Ask your doctor if you need an MRI.
For those at high risk, including those who have or had a close family member with the disease, annual mammograms should begin 10 years earlier than the age at which the relative was diagnosed.

Questions have been raised about the benefit of screening mammography in women under age 50 and over the age of 69. Annual mammograms in women between 50 and 69 have been show to save lives. But while screening can also detect early breast cancer in younger and older women, it has not been shown to save lives.

This is a topic filled with controversy. A woman needs to have an informed and balanced discussion with her doctor, along with doing additional reading and researching on her own, to determine if mammography is right for her.

Women at very high risk for breast cancer may consider preventive (prophylactic) mastectomy, which is the surgical removal of the breasts. Possible candidates for this procedure may include those who have already had one breast removed due to cancer, women with a strong family history of breast cancer, and persons with genes or genetic mutations that raise their risk of breast cancer.

References

Saslow D, Boetes C, Burke W, et al. American cancer society guidelines for breast screening with MRI as an adjunct to mammography. CA Cancer J Clin. 2007 Mar-Apr;57(2):75-89.

Lehman CD, Gatsonis C, Kuhl CK, et al. MRI evaluation of the contralateral breast in women with recently diagnosed breast cancer. N Engl J Med. 2007 Mar 29;356(13):1295-303. Epub 2007 Mar 28.

Piccart-Gebhart MJ, Procter M, Leyland-Jones B, et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med. 2005 Oct 20;353(16):1659-72.

Romond EH, Perez EA, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005 Oct 20;353(16):1673-84.

Menard S, Pupa SM, Campiglio M, Tagliabue E. Biologic and therapeutic role of HER2 in cancer. Oncogene. 2003 Sep 29;22(42):6570-8.

Review Date: 4/3/2007

Reviewed By: Rita Nanda, M.D., Department of Medicine, Section of Hematology/Oncology, University of Chicago Medical Center, Chicago, IL. Review provided byVeriMed Healthcare Network.

A.D.A.M. Copyright

adam.com

Source Doc: 1_000913

Vitamins

FitSugar — Wed, 08 Oct 2008 17:35:00 -0700

In This Report

Highlights
Introduction
Carotenoids
Phytochemicals
Healthy Foods
Dietary Health Benefits
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Cancer

Growing evidence suggests that vitamins and micronutrients, especially from foods, may play important roles in the prevention or treatment of certain cancers:

One study found that the risk of prostate cancer risk dropped as consumption of vegetables high in vitamin C, such as broccoli and bell peppers, rose.
A diet high in cruciferous vegetables has been found to reduce the risk of kidney cancer; low consumption of cruciferous vegetables increases the risk.

On the other hand, high amounts of folic acid (a B vitamin) may be associated with colorectal cancer, and beta-carotene supplements are associated with increased lung cancer risk in smokers and people exposed to asbestos.

Macular Degeneration

In 2007, the National Eye Institute recommended that people with intermediate or advanced macular degeneration in one eye take a vitamin formula shown to reduce the risk of macular degeneration in the other eye by 25%. The formula contains vitamin C, vitamin E, beta-carotene, and zinc.

Osteoporosis

Vitamin K is widely used in Japan to treat osteoporosis, and studies suggest it also may be effective in treating rheumatoid arthritis.

Heart Disease

Although people with high levels of homocysteine are prone to developing blood clots in their arteries and veins, a 2007 study found that lowering homocysteine with B vitamins and folic acid does not reduce the incidence of deep vein thrombosis (DVT). A 2007 trial in adults with stable coronary artery disease found that lowering homocysteine levels 33% with folic acid and other B vitamins had no effect on arterial inflammation, meaning that lower levels were unlikely to offer protection against heart attack or stroke.

Introduction

Vitamins do not share a common chemistry, but they do share certain characteristics. They are all organic nutrients that are necessary in small amounts for normal metabolism and good health. Your diet or supplements provide most vitamins. The body can manufacture only three vitamins (D, K, and the B vitamin biotin) from nondietary sources. Unlike carbohydrates, fats, and proteins, vitamins are not sources of energy. Instead, vitamins are chemical partners for the enzymes involved in the body's metabolism, cell production, tissue repair, and other vital processes.

Vitamins are either fat soluble or water soluble. The fat-soluble vitamins, which include A, D, E, and K, are absorbed by the body using processes that closely parallel the absorption of fat. They are stored in the liver and used up by the body very slowly. The water-soluble vitamins include C and the B complex vitamins. The body uses these vitamins very quickly. Excess amounts are eliminated in urine.

The Recommended Daily Allowance (RDA) for vitamins, set by the Food and Nutrition Board of the National Academy of Sciences-National Research Council, has been used for years as a guide for determining the amount of vitamins needed for a healthy diet. The RDA refers to an estimate of the average daily requirement. It is not completely adequate, however, for informing people about the amounts of vitamins they may need.

The RDA is gradually being enhanced using a new standard called the Dietary Reference Intake (DRI). The DRI is based on the following ratings, which will eventually appear on labels:

The recommended daily allowance (RDA). This is the current rating on most vitamins.
The estimated average requirement (EAR). This is the amount adequate for 50% of all people, which will be put on labels when it can be calculated.
Adequate intake (AI). This is an amount that will be used if there is insufficient data to calculate the EAR.
Tolerable upper intake level (UL). This is the maximum dose likely to be safe in nearly all individuals. It will be included on labels if this amount is known.

Food and supplement labels now typically list the Daily Value (DV). This is the percentage of the amount of a nutrient that experts believe a person needs in their daily diet. On food labels it is usually based on one serving size for a person who takes in 2,000 calories a day.

Regulation of dietary supplements by the U.S. Food and Drug Administration (FDA) is a complex issue.

Labels on vitamins and other dietary supplements now include nutrient information and list all ingredients, including identifying parts of plants from which ingredients may be taken. Unlike the labels for drugs, however, labels for vitamins and supplements may not claim to prevent or treat any specific disease. Labels for vitamins and supplements include one of the following:

Health claim -- description of how the substance may reduce the risk of a health-related condition
Nutrient claim -- description of the amount of the nutrient in the product or
Structure or function claim -- description of how the product may affect organs or systems of the body, without claiming to prevent or treat specific disease

The quality of dietary supplements depends on the manufacturer and is not ensured by FDA. The U.S. government does not require that supplements be standardized, meaning that the amounts or quality of nutrients may vary depending on the batch. So, more expensive supplements are not necessarily better than the less expensive ones. Government regulations are in the process of catching up to the boom in the supplement industry. In the meantime, some companies voluntarily adhere to rigorous quality controls, while others do not.

The U.S. Pharmacopeia (USP), an independent organization that sets quality standards for drugs, has also implemented standards for vitamins. Consumers may look for the USP label on products of companies that adhere to these standards. USP verification means the following:

What is in the bottle matches what is listed on the label.
There are no harmful levels of contaminants.
The supplement will be absorbed properly into the body.
It has been produced according to good manufacturing standards.

Before selling any supplement introduced after 1994, manufacturers must submit information as to why the product is considered safe for people. The FDA may refuse to allow it on the market if it finds the evidence insufficient. The FDA does not require manufacturers to provide any scientific evidence that dietary supplements are safe and effective before a product is sold (unlike drugs, which must be proven both safe and effective through clinical trials). If a supplement causes side effects in people once it is for sale, the government may place restrictions on the supplement or withdraw it from the market. The FDA may also withdraw products from the market if their labels are misleading or false.

About 30% of Americans take at least one vitamin or mineral supplement daily. In a large study that examined the death rates of 11,000 people, however, there was no difference in mortality rate between those who took vitamin supplements and those who didn't. Most people who have a healthy diet do not need vitamins, but there are some exceptions.

Pregnant and Breast-Feeding Women. Women who are pregnant or who are breast-feeding generally need additional vitamins. Vitamins B6, B12, and folic acid are particularly important. Women who are vegetarians must be sure to avoid deficiencies, which can harm their offspring. Folic acid reduces the risk for neural tube defects and possibly facial abnormalities, such as cleft palate. Studies also show that low folate levels during pregnancy are associated with low birth weight, a risk factor for the development of cardiovascular disease in adulthood. Multivitamins that contain folic acid also appear to be somewhat protective. A woman's best approach is to take extra folic acid plus multivitamin supplements (which have additional benefits), starting them before becomming pregnant.

The human body stores several years' worth of vitamin B12, so nutritional deficiency of this vitamin is extremely rare. Although, people who follow a strict vegetarian diet and do not consume eggs or dairy products may require vitamin B12 supplements.

Pregnant women with healthy diets may have low folate levels and need to take supplements. Requirements are as follows:

The recommended daily allowance (RDA) for folic acid prior to conception and during pregnancy is 400 mcg.
During breast-feeding 260 - 280 mcg is recommended.

The following vitamins may have some value for pregnant women:

Choline, another vitamin B, is also essential for pregnant (450 mg) and nursing women (550 mg). Choline plays a key role in brain development. Not getting enough during pregnancy can lead to memory and cognitive defects in the baby. Choline supplements can also lessen the cognitive defects of prenatal alcohol exposure.
Vitamin B6 may help improve morning sickness.
Vitamin C may reduce the risk of urinary tract infections during pregnancy.
Vitamin D may help prevent preeclampsia.
One study also suggested that if pregnant women took vitamin K supplements, their infants might not need the required injection of this vitamin after birth, but supplements of vitamin K during pregnancy are not currently recommended.

Some women have low vitamin A reserves in their liver. It is important to note, however, that too much vitamin A significantly increases the risk for birth defects. Daily amounts of 10,000 IU (international units) of vitamin A in supplements and food (an amount not far above the RDA level) can pose a danger. Experts recommend that pregnant women take in no more than 8,000 IU per day and avoid eating liver.

Infants and Children. Infants who are breast-fed by healthy mothers receive enough vitamins except, in some cases, vitamins K and D. Human milk has low levels of K, and the newborn's immature intestinal tract may not produce enough of the baby's own supply. Most babies are given an injection of this vitamin at birth. Infants being breast-fed by malnourished women or those who lack sufficient exposure to sunlight may be deficient in vitamin D. In these cases, supplements of 200 - 300 IU are recommended. Formulas are required to contain sufficient vitamins and minerals. One study suggests that vitamin supplements for infants under 1 year of age may help protect them from developing type 1 diabetes later on. Beyond infancy, most American children receive all the vitamins they need from their diet unless they are living in severely deprived circumstances.

Smokers. Smoking interferes with absorption of several vitamins, importantly vitamins C and D. In one study nearly 25% of female smokers and 31% of male smokers were deficient in vitamin C. Smoking can interfere with the metabolims of vitamin D, resulting in poor muscle function. Taking high doses of antioxidant vitamins, however, may actually be harmful in smokers, especially beta carotene. Instead of taking supplements, most smokers should be sure their diets are rich in fresh fruits and vegetables and whole grains. Of course, smoking cessation is the most important intervention of all.

Click the icon to see an image of sources for vitamin C.

Alcoholics. Alcoholics often suffer from multiple vitamin deficiencies. The most dangerous deficiencies are from vitamins B1 (thiamin), folic acid, B6 (pyridoxine), B2 (riboflavin), and vitamin C. Low levels of B6 are associated with increased risk of colorectal cancer in men who drink large amounts of alcohol.

Overweight Adults. Overweight and obesity causes many problems that often result in metabolic syndrome or type 2 diabetes. Evidence suggests that isoflavones can help regulate cholesterol levels and reduce body weight and fat mass. Because some medications used to control blood sugar levels reduce folic acid and vitamin B12, some people may need vitamin supplements.

People Who Have Had Gastric Bypass Surgery. Vitamin deficiency is a recognized complication of gastric bypass surgery. Women, African-Americans of both sexes, and adults who have had laparoscopic Roux-en-Y bypass surgery are at highest risk. The deficiency is treated with water-soluble vitamin supplements.

Strict Vegetarians. Strict vegetarians need supplements of vitamin B12, unless they get enough of it from fortified cereals and other grain products.

Dieters and Vegetarians. People on weight-reduction diets with less than 1,000 calories a day should probably take a multivitamin and should also check regularly with a physician.

Vegetarians may need riboflavin, vitamin B12, and vitamin D supplements. Vegans, who do not eat dairy or eggs as well as meat, may be at further risk for vitamin A deficiencies if they do not also have plenty of dark colored fruits and vegetables. Those who eat eggs and dairy products need only watch their iron levels.

Deficiencies in vegetarian children may be particularly harmful. (One study, for example, reported that adolescents who had been on macrobiotic diets before age 6 and were deficient in vitamin B12 scored lower on psychological tests.) Pregnant and breast-feeding women who are vegetarians must be sure to have sufficient vitamins. Of special note, maternal deficiencies in vitamin B12 may cause delayed growth and neurologic problems in their newborns.

Click the icon to see an image of sources for vitamin D.

Older Adults. Deficiencies of vitamins and important minerals have been observed in almost a third of elderly people. Often their dietary habits slip and they fail to eat balanced meals regularly. Multiple drug regimens may prevent absorption of some vitamins. Elderly people, particularly if they are not exposed to sunlight, may be deficient in vitamin D. They also may have low levels of important B vitamins. (Older adults showing signs of dementia should be checked for B12 deficiencies as well as other disorders causing mental disturbances.) One study reported that the immune systems of elderly people may benefit from higher levels of vitamin E than the daily recommended dosage. It should be noted, however, that metabolism slows down as a person ages, and in elderly people it takes the liver longer to eliminate drugs and vitamins from the body. The effect of some vitamin supplements, therefore, may be intensified. Dosage levels of vitamin A, for instance, which might be harmless in a younger adult, could be toxic in an elderly patient. Nevertheless, experts are increasingly recommending extra vitamin and mineral supplements for older people.

People Who Need to Avoid Sunlight. People who need to avoid sunlight or are housebound, and whose diet is low in foods that contain vitamin D should take supplements. People with darker skin are at higher risk for deficiencies than those with whiter skin. (Note: vitamin D is toxic in high doses, and no one should exceed the recommended daily intake of vitamin D except under the direction of a physician.)


Benefits	Essential for growth, bone development, night vision, reproduction, and healthy skin.
Recommended daily allowance (RDA) or dietary reference intake (DRI) (mcg = micrograms, mg = milligrams, IU = international units)	Vitamin A RDA and Upper Limit (when toxicity is risk) are the following: For children: 1,000 IU ages one to three (upper limit is 2,000 IU); 1,333 IU ages 4 - 8 (upper limit is 3,000 IU); and 2,000 IU for 9 - 13 (upper limit is 5,665 IU). For nonpregnant women: 2,330 IU ages 14 through adulthood. (Upper limit is 9,335 IU for ages 14 - 18 and 10,000 IU for women over 19.) For pregnant women: 2,500 IU for pregnant women under 18; 2,565 IU for pregnant women over 19. (Upper limit is 9,335 IU for ages 14 - 18 and 10,000 IU for women over 19. It should be noted that some experts recommend 8,000 IU as the upper limit during pregnancy.) Warning: Use of the topical acne medication tretinoin, a vitamin A derivative, during pregnancy can cause birth defects. For nursing women: 4,000 IU for nursing mothers under 18; 4,335 IU for nursing mothers over 19. (Upper limit is 9,335 IU for ages 14 - 18 and 10,000 IU for women over 19.) For men: 3,000 IU ages 14 - 18; 3,000 IU for ages 19 and above. (Upper limit is 10,000 IU.) Note: In determining the daily vitamin A allowance, experts also take note of provitamins, such beta carotene, that convert to vitamin A. Some experts recommend 3 - 6 mg of beta-carotene. Vitamin A is also now being measured with a new unit called the Retinol Activity Equivalent (RAE or RE). One RE is equal to 1 mcg. Retinol is the most active form of vitamin A and it is also converted in the liver from carotenoids. One RE is equal to 12 mcg of beta-carotene or 24 mcg of alpha-carotene or beta-cryptoxanthin).
Foods containing the vitamin	Animal products, such as liver, dairy products, eggs, and fish liver oil. Provitamin A carotenoids are also found in dark red, green, and yellow vegetables and fruits. Requires some dietary fat to be absorbed.
Effects of deficiencies	Skin disorders, severe diarrhea, and eye damage. In less developed countries severe deficiencies cause blindness in 250,000 children each year. Diets low in vitamin A may also increase the risk of developing cancer. Low dietary intake of vitamin A has been associated with impaired lung function in children.
People at risk for deficiencies	Preschool children and any child with inadequate intake of protein, calories, and zinc. Iron deficiency may also impair metabolism of vitamin A. People with asthma. People with serious disorders in the intestine, liver or pancreas, such as cystic fibrosis, steatorrhea, biliary obstruction, inflammatory bowel disease, cirrhosis, and others. People who have undergone Roux-en-Y gastric bypass surgery. Vegans (vegetarians who do not eat eggs and dairy). Such individuals should be sure to have plenty of deep-colored fruits and vegetables. People who abuse alcohol. It should be noted, however, that people with alcoholism may be at risk for vitamin A deficiency, but a combination of high-dose vitamin A and alcohol may cause toxic effects in the liver. Healthy adults usually have a year's store of vitamin A in the liver, so temporary nutritional deficiencies or problems with fat absorption are unlikely to cause serious vitamin A deficiency problems.
Toxicities	Very toxic when taken in high-dose supplements for long periods of time. Symptoms of overdose include dizziness, nausea, vomiting, headache, skin damage, mental disturbances, and, in women, infrequent periods. Can affect almost every part of the body, including eyes, bones, blood, skin, central nervous system, liver, and genital and urinary tracts. Severe toxicity can cause blindness and may even be life threatening. In children, chronic overdose can cause fluid on the brain and as well as adult complications. High consumption of vitamin A may also increase the risk of gastric cancer and the risk of osteoporosis and fractures in both men and women. Pregnant women who take amounts not much higher than RDA levels increase the risk for birth defects in their children. Liver damage can occur in children who take RDA-approved adult levels over prolonged periods of time or in adults who take as little as five times the RDA-approved amount for 7 - 10 years.


	B Vitamins: General Information	Vitamin B1 (thiamin)
Benefits	The B vitamins have a wide and varied range of functions in the human body. Most B vitamins are involved in the process of converting blood sugar into energy.	Essential for converting blood sugar into energy and is involved in metabolic activities in nerves, heart, and muscles and in the production of red blood cells.
Recommended daily allowance (RDA) or dietary reference intake (DRI) (mcg = micrograms, mg = milligrams, IU = international units)		RDA is 1.2 mg per day for men and 1.1 mg for women.
Foods containing the vitamin		Best source is pork and good sources are dried fortified cereals, oatmeal, corn, nuts, cauliflower, and sunflower seeds. Supplements for people with normal diets and health are unnecessary.
Effects of deficiencies	Deficiencies are uncommon in the U.S., but when they occur, they usually involve several B vitamins, since many of them come from the same food groups.	Severe vitamin B1 deficiency is known as beriberi. It can cause visual disturbances, paralysis, staggering, loss of sensation in the legs and feet, psychosis, and congestive heart failure.
People at risk for deficiencies	Alcohol interferes with these vitamins, and some of the physical and mental problems that alcoholics experience may be attributed to a deficiency of B vitamins. Elderly people are also at risk for deficiencies because of inadequate diets and potential interference with B-vitamin absorption by medications. Deficiencies can occur in severely malnourished people or in those receiving long-term dialysis or intravenous feeding. Vegetarians may be at risk.	See general vitamin B description.
Toxicities	Because the B vitamins are water-soluble and eliminated in the urine, toxic reactions from oral administration of most of them are extremely rare. (Exceptions are niacin and B6.) It should be noted that substances known as B15 (pangamic acid) and B17 (laetrile) are neither vitamins nor nutrients; both chemicals are highly dangerous and have no proven nutritional or health value.	No toxic effects have been reported from thiamin.


	Vitamin B2 (riboflavin)	Vitamin B3 (niacin) also known as nicotinic acid	Vitamin B5 (Pantothenic Acid)
Benefits	Important in the production of energy.	Helps break down blood sugar for energy. Acts as a vasodilator, widening blood vessels and increasing blood flow. May be prescribed for improving cholesterol levels.	Important for metabolism of fats, carbohydrates, and proteins, as well as production of steroid hormones and other important chemicals.
Recommended daily allowance (RDA) or dietary reference intake (DRI) (mcg = micrograms, mg = milligrams, IU = international units)	DRI is 1.7 mg.	DRI is 20 mg.	Adequate intake (AI) is 4 - 7 mg.
Foods containing the vitamin	Liver, dried fortified cereals, dairy products, fish. Some dark green vegetables. Supplements for people with normal diets and health are unnecessary.	Mackerel, swordfish, chicken, veal, dried fortified cereals, pork, salmon, and beef liver. Supplements are unnecessary in people with normal health and diets.	Whole grains, beans, milk, eggs, and liver. Supplements are unnecessary in people with normal health and diets.
Effects of deficiencies	Deficiencies affect the skin and mucous membranes and can cause cracks on the lips or corners of the mouth, eczema of the face and genitals, a burning sensation on the tongue, eye irritation. May contribute to anemia when iron levels are low and contribute to elevated levels of homocysteine, a heart risk factor.	Deficiency causes pellagra; symptoms can include eczema, intestinal and stomach distress, depression, headache, thinning of the hair, and excess saliva production.	Deficiency is unlikely except in company with other B vitamin deficiencies. Symptoms include abdominal distress, burning sensation in the heels, and sleep problems.
People at risk for deficiencies	See general vitamin B description.	Alcoholics and any malnourished persons.	Alcoholics and any malnourished persons.
Toxicities	Until recently, no toxic effects had been reported even from large doses of riboflavin. However, one study indicated that high consumption of vitamin B2 might increase the risk of stomach cancer. More research is needed. (In the same study, vitamins B1, B3, and B6 were protective.)	Even mildly high doses of niacin can cause hot flushing of the face and shoulders, headache, itchiness, and stomach problems. Some report heart disturbances and temporarily lowered blood pressure. Large doses may produce ulcers, gout, diabetes, and liver damage, which are usually reversed when high doses are discontinued.	Although no toxicity has been reported in humans, high dosages have caused liver damage in rats.


	Vitamin B6 (pyridoxine)	Vitamin B12 (cobalamin)
Benefits	Has an effect on over 60 proteins in the body, importantly, those that play a role in the nervous system, in red and white blood cell production, and in heart disease.	Essential for the production of blood cells, manufacturing genetic material, and for healthy functioning of the nervous system. New evidence suggests that high levels of B12 may protect against colon and rectal cancer.
Recommended daily allowance (RDA) or dietary reference intake (DRI) (mcg = micrograms, mg = milligrams, IU = international units)	RDA is 1.3 mg in adults under 50 and 1.7 mg for older men and 1.5 for older women. (Some experts recommend 3 to 6 mg for people who need heart protection.) Upper limit is 100 mg for adults.	RDA is 2.4 mcg in men and nonpregnant women, 2.6 mcg in pregnant women, and 2.8 mcg in nursing mothers.
Foods containing the vitamin	Meats, oily fish, poultry, whole grains, dried fortified cereals, soybeans, avocados, baked potatoes with skins, watermelon, plantains, bananas, peanuts, and brewer's yeast.	The only natural dietary sources are animal products, including meats, dairy products, eggs, and fish (clams and oily fish are very high in B12). Like other B vitamins, however, B12 is added to commercial dried cereals.
Effects of deficiencies	Increased levels of homocysteine, associated with heart disease and possibly Alzheimer's disease. Skin problems and nervous system disorders, including impaired memory and concentration. Increased risk for kidney stones. One study found a correlation between vitamin B6 deficiency and inability to conceive or carry a child to term. In unborn children, some evidence shows that lack of vitamin B6, in addition to vitamin B12 and folic acid, may be responsible for defects such as cleft lip and palate and spina bifida. Supplementation with these vitamins is advised during pregnancy. Note: People who have been taking more than 50 mg for some time and stop suddenly are at risk for a so-called rebound deficiency. When people stop, they should taper off slowly.	Deficiencies elevate homocysteine, a possible risk factor for heart disease and Alzheimer's disease. Increased risk of bone fractures. Abnormal gaits in the elderly. May cause severe depression, memory loss, instability, disorientation, and decreased reflexes, and possibly hearing loss. Children who are deficient may experience growth failure. Deficiencies in pregnant and breast-feeding women may cause neurologic harm in their offspring. A genetic defect that causes vitamin B12 deficiencies is responsible for pernicious anemia, a serious disorder that causes rapid heart rate, shortness of breath, dizziness, weakness, and fatigue. It must be treated with injections of vitamin B12 or else neurologic damage may occur.
People at risk for deficiencies	Alcoholics and any malnourished person. In rare cases, infants are born unable to metabolize pyridoxine; in such cases, seizures or convulsions can occur and vitamin B6 must be administered.	Alcoholics and any malnourished persons. Evidence suggests deficiencies may be caused by Helicobacter pylori (H. pylori) bacteria (a cause of ulcers). Nearly 30% of patients with inflammatory bowel disease have vitamin B6 deficiency, as well as low levels of iron and vitamin D. People who take the antibiotic isoniazid, high blood pressure medication hydralazine, and the drug penicillimine are at risk for vitamin B6 deficiency. The elderly and people with Crohn’s disease and those who have undergone ileal and ileocolonic resection may have trouble absorbing natural vitamin B12 and require supplements. Some evidence shows that patients with Parkinson’s disease treated with levodopa plus dopa decarboxylase inhibitor (DDC-i) and catechol-O-methyltransferase inhibitor (COMT-i) have low levels of both vitamin B12 and folate. As a result, they need to take supplements of these vitamins. Other studies have found that patients with diabetes treated with metformin, but not roziglitazone, are at risk for low levels of vitamin B12. Vitamin B12 deficiency is also common in patients with polyneuropathy. In up to one-third of patients, vitamin B12 deficiency is the sole or major contributing cause of their neuropathy. Treatment with vitamin B12 has a high success rate in improving the symptoms. Vegetarians are at higher risk for deficiencies.
Toxicities	Very high doses can cause nerve damage with symptoms of instability and numbness in the feet and hands, which may be permanent in some cases. Of specific concern are possible adverse effects on nerve development in the offspring of pregnant women who take large doses, such as for morning sickness.	There is no evidence of toxicity with this vitamin.


	Biotin (a B vitamin)	Choline (a B vitamin)	Folate, or Folic Acid, its synthetic form (a B vitamin)
Benefits	Involved in the production of amino acid proteins and fatty acids.	Essential for fetal brain development and for learning and memory.	Important for many metabolic processes in the body. It is used in the manufacturing of neurotransmitters (chemical messengers in the brain), in protecting the heart, and for synthesizing genetic materials (DNA) in the cells. It may improve blood flow.
Recommended daily allowance (RDA) or dietary reference intake (DRI) (mcg = micrograms, mg = milligrams, IU = international units)	There is no DRI for biotin; some experts suggest 30-100 mcg.	RDA 425 mg for nonpregnant women, 450 mg for pregnant women, and 550 mg for nursing women.	Supplements may be folate (natural) or folic acid (synthetic). Folic acid is nearly twice as potent as folate. DRI is 400 mcg (.4 mg) of folate for the general population, 600 mcg during pregnancy and 500 mcg while nursing. Women who are planning to be pregnant should certainly take 400 mcg of folic acid before conception, during pregnancy, and while nursing.
Foods containing the vitamin	Dietary sources are eggs, milk, liver, mushrooms, bananas, tomatoes, whole grains, nuts, and brewer's yeast. Also produced by bacteria in the intestines.	Peanuts, eggs, cauliflower, and meats, especially liver.	Avocado, bananas, orange juice, cold cereal, asparagus, green leafy vegetables, dried beans and peas, and yeast. Folic acid supplements are now added to commercial breads and cereals.
Effects of deficiencies	Deficiencies are almost unheard of.	Low levels during pregnancy increase risk of birth defects in newborns.	As with vitamins B6 and B12, deficiencies of folate elevate levels of homocysteine, an amino acid in the body that may increase the risk for heart disease, and possibly Alzheimer's disease. Folic acid supplements lower homocysteine levels, but with little or no impact on risk of atherosclerotic disease in the heart or in the peripheral arteries and veins. This suggests that homocysteine may be a marker of cardiovascular disease, rather than a cause. This being said, one 2007 study found that folic acid supplementation in patients with low folic acids levels substantially reduced the risk of a first stroke. Low levels during pregnancy increase risk of birth defects in newborns, and folic acid supplementation plays a key role in preventing birth defects. Folic acid deficiencies Deficiencies can also cause depression and megaloblastic anemia and impair concentration, memory, and hearing.
People at risk for deficiencies			Alcoholics, malnourished persons, people with conditions that disturb the small intestine, people taking certain drugs, particularly methotrexate. Other risk factors for deficiency: high-dose aspirin, smoking, treatment for seizures, taking oral contraceptives.
Toxicities		Excessive doses can cause intestinal problems, and there is also some concern that high doses can be carcinogenic.	Possible connection between high consumption of folate/folic acid and colorectal cancer now under exploration. Some link between high doses and central nervous system disorders, zinc deficiency, and seizures in epileptics. This risk appears to be low, but results indicate that megadoses should be avoided. High amounts in the elderly may mask symptoms of vitamin B12 deficiencies.


Benefits	Vitamin C is a water-soluble vitamin. Acts as an antioxidant (reduces harm from damaging chemical processes in the body). Essential for the production of collagen, the basic protein in bones, cartilage, tendons, and ligaments. A 2007 study found that vitamin C supplements can help prevent the development of complex regional pain syndrome following wrist fracture. Another study found that prostate cancer risk dropped as consumption of vegetables high in vitamin C, such as broccoli and bell peppers, rose. It may also protect against brochoconstriction during exercise in people with asthma. May help boost the immune system.
Recommended daily allowance (RDA) or dietary reference intake (DRI) (mcg = micrograms, mg = milligrams, IU = international units)	DRI is 75 mg (women) and 90 mg (men). (Smokers need an additional 35 mg.)
Foods containing the vitamin	Citrus fruits and juices, papayas, hot chili peppers, bell peppers, broccoli, potatoes, dark leafy greens, kale, red cabbage, cauliflower, cantaloupe, sweet potatoes, and Brussels sprouts. Orange juice is the most important source of vitamin C in the U.S., with frozen juice being the best source of the vitamin.
Effects of deficiencies	Scurvy is the primary deficiency disease. Affects most body tissues, particularly bones, teeth, and blood vessels. Early symptoms include tiredness, weakness, irritability, weight loss, and vague muscle aches. Later symptoms are bleeding gums, wounds that won't heal, rough skin, and wasting away of the muscles. Deficiencies may contribute to periodontal disease and gallstones. Low dietary intake of vitamin C has been associated with impaired lung function in children. Low intake may also increase lead levels in the blood.
People at risk for deficiencies	Deficiency has been uncommon in the U.S., usually occurring in the elderly, alcoholics, cancer patients, and some people on severely limited diets low in fresh fruits and vegetables. Surprisingly, however, studies now suggest that as many as 16% of middle-aged Americans, with the highest risk in smokers and middle aged men, are deficient in vitamin C. High doses of aspirin taken over a long period of time can interfere with vitamin C.
Toxicities	Tolerable upper limit is 2000 mg/day. High doses may cause headaches and diarrhea. Long-term high doses may increase risk for kidney stones. Ascorbic acid increases iron absorption so people with blood disorders, such as hemochromatosis, thalassemia, or sideroblastic anemia, should avoid high doses. Large doses may also thin blood and interfere with anticoagulant medications, blood tests used in diabetes, and stool tests. Rebound scurvy can occur after abrupt withdrawal from long-term large doses. This may affect infants or pregnant women who withdraw suddenly from high doses.


Benefits	Vitamin D is actually a single term for several hormones that are stored mainly in the liver and also in fat and muscle tissue. It is essential for the absorption of calcium into the bone and for normal bone growth.
Recommended daily allowance (RDA) or dietary reference intake (DRI) (mcg = micrograms, mg = milligrams, IU = international units)	RDA is 200 IU (5 mcg) per day for children and most adults to age 50, 400 IU (10 mcg) for people between ages 50 and 60, and 600 IU over age 70. and 1000 IU (15 mcg) for those over 70. People who are housebound, do not have sufficient exposure to sunlight, or are dark-skinned individuals, as well as breast-fed infants, should take need vitamin D supplements. The maximum tolerated dose after the age of 12 months is 2,000 IU/day
How the body gets the vitamin	There are two forms of vitamin D. Vitamin D3 is made in the body from a chemical reaction to the ultraviolet radiation in sunlight. Vitamin D2 is found in a few food sources, including vitamin D fortified milk, fatty fish, egg yolk, and liver.
Effects of deficiencies	Softening of the bones caused by low levels of calcium and phosphorous (called rickets in children and osteomalacia in adults). Also increases the risk for bone-related knee problems, and hip fractures in postmenopausal women. Associated with a higher risk for prostate cancer and breast cancer risk. Evidence suggests that vitamin D deficiency may be responsible for poor muscle strength after bone fracture. The deficiency is associated with high blood pressure and diabetes, but it is unknown whether supplementation with vitamin D impacts these diseases. Studies now suggest vitamin D plays a role in age-related macular degeneration (AMD), and that drinking milk with added vitamin D can help protect against AMD.
People at risk for deficiencies	Older people, particularly if they live in the North, who are underexposed to sunlight. Obesity may also increase risk. There is some concern, in fact, that vitamin D deficiency may be a growing problem in the US among younger adults as sunscreen use becomes widespread. Individuals at highest risk for vitamin D deficiency are those who assiduously avoid the midday sun, wear protective clothing, regularly use sunscreen, and have dark skin. Exposure to sunlight for about 15 - 20 minutes at mid-morning or mid-afternoon three times a week is recommended for most people who live in temperate climates.
Toxicities	Vitamin D is very toxic in high doses. In infants, daily amounts higher than 1,000 IU can cause mental and growth retardation, kidney failure, and death. In children and adults, daily amounts over 50,000 IU can cause weakness, anorexia, vomiting, diarrhea, and mental changes. Prolonged use of megadoses can cause calcification of soft tissue and life-threatening kidney failure. Low-calcium diets and withdrawal from the vitamin can usually reverse the side effects except for kidney failure.


	Vitamin E (Tocopherol or Tocotrienol)	Vitamin K
Benefits	A fat-soluble antioxidant vitamin that helps prevent cell membrane damage and may inhibit oxidation of LDL cholesterol (a process that increases its harmful effects on arteries). Researchers once thought that vitamin E might protect against cardiovascular disease. This theory has been debunked. However, a 2007 study found that vitamin E supplementation reduced the risk of deep vein thrombosis (DVT) in women at risk for, or with a history of, DVT. Vitamin E supplements have also been shown to produce a statistically significant decrease in menopausal hot flashes. There is also early evidence that vitamin E may protect against ovarian cancer.	The most important function of vitamin K is its role in blood clotting and prevention of bleeding. As a result, the vitamin may be able to help treat hepatoma, leukemia, and hepatocellular carcinoma, a form of liver cancer. The vitamin also contributes to maintaining healthy bones and healing fractures. Vitamin K is widely used in Japan to treat osteoporosis, and studies suggest it may be effective in treating rheumatoid arthritis.
Recommended daily allowance (RDA) or dietary reference intake (DRI) (mcg = micrograms, mg = milligrams, IU = international units)	RDA is 15 mg (22 IU) for all adults, including pregnancy women. Nursing mothers need 19 mg (28 IU). (Supplements should be taken along with some oil or fat to be absorbed.) Vitamin E is composed of 8 compounds (four tocopherols and four tocotrienols). Vitamin E is most often available as supplements of dl alpha tocopherol (a synthetic form). Other vitamin E compounds may prove to be more active than the standard synthetic supplement. They include natural vitamin E, called d-alpha- or RRR-alpha-tocopherol succinate (VES). Other vitamin E compounds of interest are tocotrienol and beta and gamma tocopherol. Supplements that contain a combination of some of these forms may be most beneficial.	RDA is 60 - 65 micrograms (women) and 70 - 80 micrograms (men).
Foods containing the vitamin	Vegetable oils (particularly wheat germ oil), sweet potatoes, turnip greens, mangos, avocados, nuts, sunflower seeds, and soybeans. Tocotrienol (a possibly beneficial form) is found in natural tropical oils. Palm oil sold in the US is refined and does not contain tocotrienol.	Best dietary sources are canola oil, cruciferous vegetables, and soybean oil. Good sources are beef liver, bran, and olive oil. Also produced by bacteria in the intestines.
Effects of deficiencies	Deficiencies have not been established.	Easy bruising, bleeding. May increase the risk of hip fractures in women.
People at risk for deficiencies	Low-birth weight infants. People who eat a low-fat diet. People with medical problems that impair fat absorption, such as Crohn's disease, cystic fibrosis, steatorrhea, liver diseases (such as cirrhosis). People with abetalipoproteinemia, a rare genetic disorder that impairs fat metabolism.	Deficiency may occur in patients who have problems absorbing fats, such as those with cirrhosis, people who are on long-term antibiotic therapy, or who are taking other medications, including cholestyramine, Dilantin, and phenobarbital. Some evidence suggests that more young people may be deficient than previously believed.
Toxicities	Upper level recommended is 1,500 IU of alpha tocopherol. Large doses may cause bleeding problems, particularly in people taking anti-clotting medications. Some research now indicates that vitamin E, like other antioxidants, may have pro-oxidant and damaging effects. Although vitamin E is one of the best studied vitamins, research has yielded conflicting results, and definitive conclusions about the benefits and toxicity of vitamin E have not yet been determined. In a major 2005 study, there was no significant difference in cancer rates between people who took 400 IU of vitamin E daily and those who did not, although those who took the supplement had a higher risk of heart failure. Additional studies also link high levels of vitamin E with a slightly increased risk of heart failure and death. On the other hand, studies show that vitamin E may reduce heart problems in high-risk patients such as certain people with diabetes.	Allergic-type responses, including rash and itching, to high doses have been reported. Those who are taking Coumadin, an anticoagulant, should not take vitamin K without consulting a physician. Vitamin K deficiency can cause anorexia, lethargy, growth retardation, bone loss, soft tissue calcification, and death.

Carotenoids

Carotenoids are a group of more than 700 fat soluble nutrients that produce the colors in foods such as carrots, pumpkins, sweet potatoes, tomatoes, and other deep green, yellow, orange, and red fruits and vegetables. Many are proving to be very important for health. Beta carotene is the most widely studied carotenoid, but others are proving to be of great interest. As with some, but not all, carotenoids, beta carotene is known as a provitamin A because it converts to the vitamin in the body.

They are categorized as either xanthophylls or carotenes according to their chemical composition.

Carotenes are hydrocarbons and most are found in yellow, orange, and red vegetables. They include beta and alpha carotene and lycopene.

Beta Carotene and other Provitamin A Carotenoids. Beta carotene, alpha-carotene, and beta-cryptoxanthin are carotenes that are converted into vitamin A or retinol (the active form of vitamin A) in the body. They are found in many yellow fruits and vegetables. Beta carotene is the most widely studied carotenoid. Evidence now strongly suggests that when taken as a separate supplement it can have harmful effects.
Lycopene. Lycopene is responsible for the red color in fruits and vegetables, including tomatoes, red grapes, watermelon, and pink grapefruit. It is also found in papayas and apricots. It does not convert to vitamin A but may have important cancer fighting properties and other health benefits.
The beneficial actions of most carotenes such as those tomatoes, corn, and carrots, appear to be enhanced by cooking them, especially in oil (preferably olive, canola, or another monounsaturated oil). (Note: Cooking can also destroy certain nutrients, such as vitamin C, in these vegetables.)

Xanthophylls contain oxygen and most are found in green vegetables, such as broccoli, cabbage, and kale. They are also in yellow fruits and vegetables. Xanthophylls include lutein and zeaxanthin, which are both stored in the retina of the eye. Neither converts to vitamin A. Both are powerful antioxidants and may be very important for healthy eyes. Unlike carotenes, cooking may reduce the antioxidant activity of some xanthophylls in foods, although probably not to any significant degree.

Phytochemicals

The word phytochemicals means plant chemicals. Hundreds of phytochemicals are being studied. Many are believed to have a major positive impact on human health. Some contribute to the bright and vivid colors found in fruits and vegetables. The results of studies on specific phytochemicals are not necessarily applicable to the vegetables or fruits that harbor small concentrations of these chemicals.

Nevertheless, it is obvious that vegetables and fruits are healthful, which is probably due to some balance of phytochemicals, carotenoids, vitamins, fibers, and minerals rather than any single substance.

The benefits of individual phytochemical supplements are largely unproven. Furthermore, they are not regulated and high concentrations of some may behave like drugs and can be toxic and possibly even contribute to cancer cell growth.

Polyphenols are important phytochemicals, and flavonoids (or catechins) are members of the polyphenol family that may have significant health benefits. Laboratory studies have shown that specific flavonoids suppress tumor growth, interfere with sexual hormones, prevent blood clots, and have anti-inflammatory properties. In general, flavonoids are found in celery, cranberries, onions, kale, dark chocolate, broccoli, apples, cherries, berries, tea, red wine or purple grape juice, parsley, soybeans, tomatoes, eggplant, and thyme. Most common berries contain flavonoids and are particularly rich in potent antioxidants.

Among the important flavonoids are resveratrol, quercetin, and catechin. Evidence suggests that resveratrol (found in red wine, grapes, olive oil) may be extremely potent. In laboratory studies, it increases cell survival and has been shown to increase the life span of worms and fruit flies. Catechins are the primary flavonoids in tea and may be responsible for its possible beneficial effects. Flavonoids in dark chocolate may also be health protective.

Isoflavones, commonly known as phytoestrogens, have actions that are similar to the female hormone estrogen. A high consumption of soy, which is primarily composed of isoflavones, may reduce symptoms resulting from estrogen depletion during menopause. In a recent study, supplementation with isoflavones decreased hot flashes by 57% and night sweats by 43%, but other research is less favorable.

Lignan is another phytoestrogen and is found in the fiber layers of whole-grains, berries, some seeds, some vegetables, and a few fruits.

Isothiocyanates and related substances, indoles, are also known as mustard oils and are responsible for the sharp taste in cruciferous (also called brassica) vegetables. Such vegetables include broccoli, cabbage, Brussels sprouts, cauliflower, collards, kale, kohlrabi, mustard greens, rutabaga, turnips, and bok choy. Isothiocyanates also stimulate enzymes that convert estrogen to a more benign form and may block steroid hormones that promote breast and prostate cancers. (Cruciferous vegetables are also high in fiber, vitamin C, and selenium.)

Monoterpenes have two important phytochemicals, perillyl alcohol and limonene. They block proteins that stimulate cell growth and reproduction and are being tested for actions against cancer. Limonene is found in the peels of citrus fruits.

Organosulfurs are part of the allium family of phytochemicals. Compounds, such as allicin, may have benefits on the immune system, assist the liver in rendering carcinogens harmless, and reduce production of cholesterol in the liver. These compounds are found in garlic, leeks, onions, chives, scallions, and shallots.

Capsaicin seems to reduce levels of substance P, a compound that contributes to inflammation and the delivery of pain impulses from the central nervous system. Research suggests that it may inhibit cancer-generating substances. It is found in hot red peppers.

Sterols, which include sitosterol, stigmasterol, campesterol, and squalene, are found in vegetable oils. Sitosterol is the most studied and appears to have cholesterol-lowering effects.

Beta-sitosterols may help improve urine flow and urinary symptoms in men with enlarged prostate glands (benign prostatic hyperplasia, or BPH). A recent review study of five randomized trials (519 men) found that urinary flow and other urinary symptoms improved in men who took the herbal remedy from 4 - 26 weeks. The study’s authors cautioned that while beta-sitosterols show effectiveness in the short term, their long-term effectiveness, ability to prevent complications from BPH, and safety are not known. More research is necessary. Beta-sitosterols come from South African star grass, Hypoxis rooperi, or species of Pinus and Picea.

Healthy Foods

Evidence increasingly suggests that a varied diet, not individual food chemicals, is essential for basic health and a longer life. Such diets are rich in fresh fruits and vegetables and whole grains, and low in saturated fats.


Foods	Phytochemicals and Carotenoids	Vitamins and other valuable food components	Benefits
Apples	Flavonoids		May have activity against certain cancers (lung). Also may help maintain healthy cholesterol. May protect against asthma.
Beans	Flavonoids	Folate, iron, potassium, and zinc	Some experts believe beans are the perfect food.
Berries, all kinds of dark colored	Ellegic Acid	Vitamin C, minerals	The anthocyanins in berries such as bilberries, blueberries, cranberries, elderberries, and others, have numerous healthful properties including anti-cancer and antioxidant effects. Bilberry (Vaccinium myrtillis) is widely used to prevent macular degeneration. Blueberries may protect the aging brain. (In one study blueberries were most effective.)
Broccoli (also kale, Brussels sprouts, cauliflower)	Flavonoids, isothiocyanates, lutein, beta and alpha carotene. Note: Young sprouts of broccoli and cauliflower contain much higher levels of isothiocyanates than their mature forms.	Vitamin C, folate, fiber, and selenium	Anticancer properties. Protective against heart disease and stroke.
Carrots and other bright yellow vegetables	Lutein, beta carotene and other provitamin A carotenoids	Vitamin A (converted from carotenoids), vitamin C	Protects eyes, lungs. (Cooking carrots may increase the potency of food nutrients.)
Chocolate, dark. Note: Milk chocolate does not have benefits.	Flavonoids		Heart protective (may improve lipids and help prevent blood clotting. May have protective properties against lung cancer (not other cancers).
Eggs	Lutein	Many B vitamins, vitamin A, vitamin D	Although egg yolks are high in cholesterol, very little of it has a negative effect on people with normal levels. And the health benefits of eggs are now known to be very high. (People with diabetes or those with high cholesterol should restrict eggs, however.)
Fish, oily (mackerel, salmon, sardines)		Vitamin B3, B12. Essential fatty acids, selenium	Heart and brain protective.
Garlic	Allium (organosulfurs)		Possibly protective against certain cancers, heart diseases, and infection. Heating garlic can reduce benefits. Allowing crushed fresh garlic to stand 10 minutes before heating, however, may preserve beneficial chemicals while cooking.
Ginger	Zingiberaceae		Cancer fighting properties.
Grains (whole)	Lignans (phytoestrogens)	Vitamin B, Selenium (important antioxidant mineral), fiber, folate	May help reduce the ability of cancer cells to invade health tissue.
Grapes, including purple grape juice, and red wine	Flavonoids, (resveratrol, quercetin and catechin)		Fight heart disease and cancer. May help lower the risk for asthma.
Nuts		Vitamin E, vitamin B1, essential fatty acids, folate	Protects the heart and may help prevent stroke.
Onions	Flavonoids, allium (organosulfurs)		May have activity against certain cancers (lung).
Oranges	Monoterpenes	Vitamin C, folate, potassium.	Many health benefits. Increases HDL levels.
Potatoes (Sweet)		Vitamin C, vitamin E, vitamin A	Many health benefits.
Soy. The best products are tofu, soy milk, or whole soy protein.	Isoflavones (phytoestrogens), flavonoids, phytosterol, phytate, saponins.		May have effects similar to estrogen, including maintaining bone and benefiting the heart in women. May also be protective against prostate cancer and possibly other cancers. More studies are needed. Effects on breast cancer are uncertain. (Note: Soy may have different effects in men than in women. Of some concern is one study reporting more mental decline in men who consume greater amounts of tofu.)
Spinach and other dark green leafy vegetables	Zeaxanthin, Beta carotene	Vitamin C, folate, vitamin A (converted from carotenoids)	Protects lungs and brain.
Tea (Both black and green tea are beneficial. Best results associated with green tea.)	Flavonoids (primarily catechins)		Cancer fighting properties, particularly in green tea, which may be especially beneficial for smokers. Both black and green tea may protect against heart disease and stroke, although studies are mixed. Tea drinking also may help with weight control and help prevent osteoporosis.
Tomatoes	Lycopene, Flavonoids	Vitamin C, biotin, minerals	Studies link to reductions in prostate and other cancers. Infection fighters.
Note on Organic versus Inorganic Products. There is some evidence that organic produce has higher levels of antioxidants and that some agricultural chemicals may destroy flavonoids. Nevertheless, organic produce is expensive, and fruits and vegetables, no matter how they are grown, are still filled with healthful nutrients.

Dietary Health Benefits

The benefits of any dietary factors are very difficult to prove, and, to date, there is little evidence that most dietary supplements protect against major diseases in otherwise healthy people with normal eating habits. An exception is lutein, which is known to reduce the risk of macular degeneration. However, a diet naturally high in vitamins and minerals can be the best defense against many diseases. Fresh fruits and vegetables and whole grains are the primary sources of vitamins, carotenoids, and vitamins, as well as of fiber and important minerals.

Description of Oxygen-Free Radicals (Oxidants). Currently, the most important benefit claimed for vitamins A, C, E, and many of the carotenoids and phytochemicals is their role as antioxidants, which are scavengers of particles known as oxygen-free radicals (also sometimes called oxidants). These chemically active particles are by-products of many of the body's normal chemical processes. Their numbers are increased by environmental assaults, such as smoking, chemicals, toxins, and stress. In higher levels, oxidants can be very harmful in the following way:

They can damage cell membranes and interact with genetic material, possibly contributing to the development of a number of disorders including cancer, heart disease, cataracts, and even the aging process itself.
Oxygen-free radicals can also enhance the dangerous properties of low-density lipoprotein (LDL) cholesterol, a major player in the development of atherosclerosis.

Description of Antioxidants and Warnings on High-Dose Supplements. Antioxidant vitamins (A, C, and E), carotenoids, and many phytochemicals can neutralize free radicals. Unfortunately, although it is clear that vitamins are required to prevent deficiency diseases, high doses of vitamin C, vitamin E, and beta carotene supplements may also have pro-oxidant effects, which can be harmful in patients with cancer. In these people, high doses of antioxidant vitamins may actually protect cancer cells just as they do healthy cells.

The strongest evidence on negative effects to date comes from studies reporting an increase in lung cancer and overall mortality rates among smokers who took beta carotene supplements. In determining reasons for this disturbing effect, one animal study suggested that beta carotene increased enzymes in the lungs that actually promote cancerous changes. One study also reported a higher risk for cancer in male smokers who took multivitamins plus A, C, or E.

Some evidence also indicates that high doses of vitamin C may speed up atherosclerosis, or hardening of the arteries. In one study, women with heart disease who took antioxidant vitamins had a higher risk for heart attack or death than those who didn't take one.

Another study also reported a higher incidence and greater severity of respiratory infections in older adults who took 200 mg of vitamin E daily. Some researchers speculate that certain immune factors generate oxidants to fight bacteria. This antioxidant vitamin, then, may block that action. Research published in 2005 suggests that those who take large amounts of vitamin E (1,500 IU/day) may slightly increase their risk for heart failure and death, but this evidence is not considered conclusive. Further study is necessary.

Vitamins and Heart Protection.

Antioxidant Vitamins A, C, and E. Deficiencies in vitamins A, C, E, and beta carotene have been linked to heart disease. All of these nutrients have antioxidant effects and other properties that should benefit the heart. A study in patients with heart failure has shown that vitamin C can work with dobutamine, a powerful intravenous medication, to strengthen the heart’s ability to contract following a heart attack. In fact, a 2005 study has found that taking high doses of vitamin E is associated with an increased risk of heart failure. In 2007, the Women’s Antioxidant Cardiovascular Study failed to find that vitamins C, E, and beta carotene could reduce the risk of heart attack, stroke, need for revascularization, or cardiovascular death in women. According to the U.S. Preventive Service Task Force, evidence is insufficient to confirm or refute the benefits of supplements of any of these vitamins in protecting against heart disease.
Folate and B12 Vitamins. Deficiencies in the B vitamins folate (known also as folic acid) and B12 have been associated with elevated blood levels of homocysteine, an amino acid that has been associated with a higher risk for heart disease, stroke, and heart failure. One study, reported lower failure rates after heart surgery in patients who took folic acid and vitamins B12 and B6. And a major 2002 study suggested that lowering homocysteine levels with folic acid would reduce the risk for heart disease by 16% and stroke by 24%. However, a 2007 trial in adults with stable coronary artery disease found that lowering homocysteine levels 33% with B vitamins and folic acid had no effect on arterial inflammation, meaning that lower levels were unlikely to offer protection against heart attack or stroke. More evidence is needed to determine whether homocysteine plays a causal role in cardiovascular disease and whether the B vitamins are protective. Folate improves blood flow through the arteries, which may be important for the heart, regardless of its effect on homocysteine. Although people with high levels of homocysteine are prone to damaging blood clots in their arteries and veins, a 2007 study found that lowering homocysteine with folic acid and other B vitamins does not reduce the incidence of blood clots in the peripheral veins (deep venous thrombosis).
Niacin. Niacin (vitamin B3) is used for lowering unhealthy cholesterol levels. Although vitamin B3 is available over the counter, it can have significant side effects. A physician should prescribe niacin in order to ensure its safety and effectiveness. [See In-Depth Report #23, Cholesterol.]

Carotenoids and Heart Protection. Studies have reported that a diet high in fruits and vegetables containing beta carotene, lycopene, and other carotenoids may reduce the risk of heart attack. A small Finish study found that a diet high in tomatoes reduced total cholesterol and LDL ("bad") cholesterol. Diets low in lycopene (particularly from tomatoes) were associated with a significantly higher risk of heart disease and stroke.

Atherosclerosis is a disease of the arteries in which fatty material is deposited in the vessel wall, resulting in narrowing and eventual impairment of blood flow. Severely restricted blood flow in the arteries to the heart muscle leads to symptoms such as chest pain. Atherosclerosis shows no symptoms until a complication occurs.

Phytochemicals and Heart Protection. Several phytochemicals are associated with heart protection.

Flavonoids. Certain flavonoids, found in both black and green tea, dark chocolate, onions, red wine or red grape juice, and apples, appear to be strongly heart protective. In one study, people who consumed the most flavonoids in foods had a 20% lower risk for heart disease than those with low consumption. Flavonoids may protect against damage done by cholesterol and help prevent blood clots. A number of studies have now reported heart protection from the flavonoid catechin, which is found in both black and green tea. The flavonoid resveratrol, which is found in grape skin, appears to be responsible for the well-known heart protective effects in red wine and purple grape juice.
Organosulfurs. Organosulfurs found in onions and garlic have been under investigation for possible beneficial effects on cholesterol levels. One study reported an association between taking garlic capsules and significantly lower cholesterol-build up in the arteries of older women but not in older men. In the study, daily garlic supplements dramatically reduced the build-up of newly formed plaque in the arteries, while having much less effect on older, harder plaque deposits. Garlic supplements for cardiovascular disease may be most beneficial when used during earlier years among men and later years among women.
Isoflavones. Soy protein is the most studied source of isoflavones (known as phytoestrogens, or plant estrogens). Not all studies are consistent, but the majority has shown an improvement in at least one of the cholesterol components in people who consumed at least 25 grams of soy protein. A 2007 meta-analysis of all soy protein studies performed from 1990 - 2006 found that soy protein significantly decreased total cholesterol and LDL cholesterol, but had no effect on HDL or triglycerides. The effect was particularly evident in people with hypercholesterolemia. A 2007 study found that 12 weeks of soy supplement lowered total cholesterol and LDL levels in both Caucasian and African-American postmenopausal women. Soy may also reduce other heart risk factors, at least in certain populations. For example, in one 2002 study, soy was beneficial for controlling blood sugar and lowering LDL in postmenopausal women with type 2 diabetes. In a 2007 study of overweight men and postmenopausal women, soy protein reduced blood pressure and arterial stiffness. In another study, soy protein was associated with lower systolic blood pressure in men. The best sources are soy products (tofu, soy milk) or whole soy protein. Powdered soy protein that contains at least 60 mg of isoflavones may provide similar benefits.
Sterols. The plant sterols, including sitosterol, are also proving to be potent cholesterol fighters by blocking the absorption of cholesterol in the intestine. Sitostanol, a derivative of sitosterol, is being used in new margarine products to lower cholesterol levels. Sterols and stanols are now found in breads, cereals, yogurt, and fruit juices.

A healthy diet rich in fruits and vegetables and low in salt and saturated fats may significantly lower the risk for a first stroke, perhaps by helping to protect against high blood pressure -- a major risk factor for stroke.

Vitamins and Stroke Protection. The effects of antioxidant vitamins and carotenoids on stroke, dementia, or both are being studied. Studies are conflicting, however. A 2007 study of 8,171 women with cardiovascular disease reported that vitamins C, E, and beta carotene offered no protection against heart attack and stroke.

The B vitamin folate (usually in the form of folic acid) may protect against stroke. However, exactly which people benefit from this therapy has yet to be determined. Studies have suggested that people who have higher blood levels of folate have a lower than average risk for stroke. Its primary benefit in this case appears to be to reduce levels of homocysteine, an amino acid that has been strongly linked to an increased risk of coronary artery disease, stroke, and Alzheimer's disease. A 2007 meta-analysis of 8 trials found that folate supplements decreased homocysteine 20% and lowered stroke risk 18%. Interestingly, lowering homocysteine with folic acid and B vitamins had no effect on heart attack, strokes, amputations, need for dialysis, or death in patients with chronic or end-stage kidney disease.

Carotenoids and Stroke Protection. Some, but not all, studies have reported a lower risk of stroke from carotenoids, including beta carotene and lycopene.

Many fresh fruits and vegetables contain chemicals that may fight many cancers, including lung, breast, colon, and prostate cancers. Examples of important cancer fighting foods include the following:

Cruciferous vegetables (such as cabbage, Brussels sprouts, and broccoli)
Tomatoes (which contain lycopene)
Carrots (which contain alpha carotene)

Some evidence suggests that antioxidants may enhance the anticancer effects of chemotherapy. In multiple studies, patients who maintained their antioxidant levels were better able to withstand the high stress caused by chemotherapy or radiation therapy compared to those with low antioxidant levels. Antioxidant nutrients that may help reduce the side effects of chemotherapy include vitamins E and C, beta carotene, genistein and daidzein (isoflavones found in soy), and quercetin (found in red wine an purple grape juice).

Any protective effects of vitamins or specific phytochemical against cancer, however, appear to depend on the cooperative effort among them. Individual supplements of any vitamin or food chemical have not as yet shown any benefits.

Additionally, certain supplements may actually encourage tumor growth, particularly when taken in large amounts. Two 2007 studies found a connection between folate supplements and colorectal cancer. In one study, which was designed to evaluate the benefits of folic acid in patients who had previous colorectal adenomas (precancerous polyps), the researchers instead found that folic acid was associated with a higher risk of having 3 or more adenomas and noncolorectal cancers. In another study, it was noted that the downward trend in colorectal cancer diagnoses abruptly started to rise in 1996 when mandatory folate enrichment of grains within the U.S. and Canada began. Rates continue to exceed pre-1996 levels. Additionally, a large 2007 National Cancer Institute/AARP study found an increased risk of advanced and fatal prostate cancer in men who took more than 7 multivitamins a week, but no association between multivitamin use and localized prostate cancer.

High consumption of cruciferous vegetables (at least once per week) was associated with lower risk of kidney cancer, and low consumption (less than once per month) of cruciferous vegetables was associated with higher risk of kidney cancer in a multinational 2007 European study. Cruciferous vegetables also appear to offer protection against head and neck cancer resulting from chemical toxins found in cigarettes and alcohol, for example.

Vitamins and Cancer Protection. Because many cancers are thought to be initiated by the effects of oxygen-free radicals on DNA, the antioxidants A, C, and E and beta carotene have been intensively studied. A major study found that men who took selenium for 6 or 7 years reduced their risk of prostate cancer by 52%. Nevertheless, most individual supplements have not been proven to protect against cancer, and high doses may be dangerous.

A 2007 review of the diets of men exposed to asbestos found a decreased risk of prostate cancer associated with increasing intakes of vitamin C-rich vegetables, but not fruits and vegetables high in vitamin A. The chemopreventive role of silymarin (Silybum marianum), found in milk thistle extract, has been extensively studied and has shown anticancer efficacy against various cancers, especially prostate and skin, by inhibiting UVB radiation.

A review of 13 cancer registries found 416,134 cases of skin cancer and 3,776,501 cases of non-skin cancer as a first cancer. Rates from cancer registries in sunny countries (such as Australia and Spain) and less sunny countries (such as Canada and Iceland) were compared. The researchers concluded that vitamin D production in the skin decreases the risk of several solid cancers, especially stomach, colorectal, liver and gallbladder, pancreas, lung, female breast, prostate, bladder, and kidney cancers. The apparently protective effect of sun exposure against second primary cancer is more pronounced after non-melanoma skin cancers than melanoma.

Consumption of aflatoxins, a common fungus-related toxin infecting cereal grains, oil seeds, spices, tree nuts, and the milk of animals fed contaminated feed, is known to cause hepatocellular carcinoma, a deadly form of liver cancer. Rodent studies have shown that phenolic antioxidants, dithiolethiones, isothiocyanates, and triterpenoids may act as chemopreventive agents, dispersing aflatoxins and protecting against hepatocellular carcinoma. Human trials are planned. A similar study found that several isothiocyanates, diallyl sulfide, and polyphenolic compounds can prevent esophageal dysplasia from progressing to squamous cell carcinoma.

A review of all articles on vitamins and cancer published through February 2007 found that multivitamin/mineral supplement use may prevent cancer in individuals with poor or suboptimal nutritional status. One trial on poorly nourished Chinese showed supplementation with combined Beta-carotene, vitamin E and selenium reduced gastric cancer incidence and mortality, and overall cancer mortality. In a French trial, combined vitamin C, vitamin E, beta-carotene, selenium, and zinc reduced cancer risk in men but not in women. With few exceptions, neither beta-carotene nor vitamin E had benefits for preventing cancer. Beta-carotene supplementation increased lung cancer risk in smokers and persons exposed to asbestos.

A 2007 study of nearly 82,000 men and women in Sweden found that high intake of methionine was associated with reduced risk of pancreatic cancer. The same relationship was not seen with vitamin B6 or folate.

Vitamin A, C, and E. Although some studies have reported an association between low blood levels of these antioxidant vitamins and a higher risk for cancer, supplements of vitamins A, C, and E appear to have few advantages in most cases. And there are some studies finding higher cancer risks with high intakes of antioxidants. For example, a 2003 study reported a higher risk in melanoma in people with vitamin-C rich diets. Another study also reported a higher risk for cancer in male smokers who took multivitamins plus A, C, or E. (Vitamin E may be protective against bladder cancer and ovarian cancer.)
Vitamin D. Some studies have suggested that certain vitamin D compounds may inhibit certain cancer cells, specifically prostate cancer, from proliferating. More research is needed. In 2007, the National Cancer Institute confirmed that ultraviolet (UV) radiation exposure may reduce the risk of developing non-Hodgkin lymphoma (NHL), but only in patients with certain variations in the D vitamin receptor gene. A second 2007 study found that variations in this gene increase the risk of diffuse large B-cell lymphoma. A 2007 prospective analysis of 31,500 women in the Women’s Health Study evaluated calcium and vitamin D intake. The researchers found a moderately lower risk of premenopausal, but not postmenopausal, breast cancer with higher intakes of total calcium and vitamin D. A 2007 review of breast cancer cases reported in Ontario, Canada, found reduced breast cancer risks were associated with increasing sun exposure in women ages 10 - 19, less evidence for associations in women ages 20 - 29, and no evidence for ages 45 - 54. Researchers concluded that sun exposure earlier in life, particularly during breast development, may be key in the connection between vitamin D exposure and breast cancer risk.
Folic acid and B12. These B vitamins convert the amino acid homocysteine to methionine, a substance that helps prevent cells from becoming malignant. Folic acid may provide some protection against cervical and colon cancer. One small study showed a reduction of lung cancer cells in smokers taking folic acid and vitamin B12, but the study was very small, of short duration, and other factors might have biased the results. Still another study reported that folic acid may reduce the risk for breast cancer among women who regularly drink alcohol. (In the study, folic acid had no other effect on breast cancer.)

In 2006, a study for the National Institutes of Health reviewed randomized trials evaluating the effectiveness and safety of multivitamin and mineral supplements in preventing cancer and chronic disease. The studies had mixed results, and some supplements reduced cancer rates in certain populations. However, the reviewers concluded that current evidence is not sufficient to determine whether multivitamin and mineral supplements may prevent cancer and chronic disease.

Carotenoids and Cancer Protection. A number of studies have reported that fruits and vegetables rich in carotenoids are associated with protection against many cancers. Lycopene, found in tomatoes, may have particular value in protection against prostate, colon, lung, and bladder cancer. A 2005 study found that in one out of four men with genetic variations that cause them to be more sensitive to oxidative stress, supplementation with selenium, vitamin E, and lycopene significantly reduces the risk of prostate cancer. Individual supplements, however, do not offer any advantage. In fact, evidence now strongly suggests that beta carotene supplements increase the risk for lung cancer in smokers and people exposed to asbestos

Phytochemicals and Cancer Protection. The following phytochemicals appear to have cancer-protecting properties.

Isothiocyanates. Isothiocyanates and sulforaphane, found in cruciferous vegetables, may block the effects of carcinogens and suppress tumor growth. In one study, for example, women with the highest consumption of cruciferous vegetables had a 24% lower risk of breast cancer than women with the lowest consumption.
Isoflavones. Isoflavones, found in soy beans and flax seed, behave like estrogen in some ways and not in others. Researchers are very interested, then, in their effects on hormone-related cancers, including breast and prostate cancers. Much research has focused on soy. In general, a number of Asian studies have reported an association between a higher intake of soy and a lower incidence of reproductive and breast cancers. The effects of phytoestrogens, however, in all women are far from settled. Some evidence suggests the genistein in soy may have properties that are protective against lung cancer. Nonfermented soy products (tofu, soy milk) also may protect against stomach cancer, while fermented soy products (miso, soy paste) appears to increase the risk.
Organosulfurs. The organosulfur compounds found in the onion and garlic family may have very potent properties in suppressing or blocking carcinogenic substances. A 2007 study found that synthetic organosulfur compounds act as selective inhibitors of growth in breast cancer cells. Studies indicate that people who regularly consume fresh or cooked garlic have about half the risk of developing stomach cancer and two thirds the risk of colorectal cancer as people who eat little or no garlic. One possible explanation for garlic's anti-cancer effect in the stomach is its antibacterial action against H. pylori, which can promote stomach cancer. Taking garlic supplements, however, did not offer these benefits.

It should be noted that studies on the health benefits of vitamins and minerals have some important limitations. Some are held to rigorous standards, while others are not. In most cases, the results of existing research are complex, as they can easily be complicated by factors such as diet, exercise, the presence of healthy or unhealthy lifestyle behaviors, environmental factors, and more.


Disease or Condition	Vitamins	Carotenoids, Phytochemicals, and Healthy Foods
Alzheimer's Disease	Vitamin E. Some reports, including a large 2002 population study, have suggested that vitamin E intake, from food or supplements, may protect against mental decline. (One study suggested that the vitamin protected only those who carried the apoE4 gene. No strong evidence to date has found any protection from antioxidant supplements.) Some studies performed since 2002 challenge this finding, while others agree with it. B Vitamins. Some studies suggest that deficiencies of the B vitamins B6, B12, and folate may be a risk factor for Alzheimer' diseases, possibly because deficiencies elevate homocysteine levels, which some research now associated with a higher risk for Alzheimer's disease. Of these, folates may offer the best protection. In 2007, researchers at Tufts-New England Medical Center reviewed all human studies on folate, vitamin B-6, vitamin B-12, and cognitive function in the elderly conducted between 1966 and November 2006. Six of 10 folate studies reported a significant association between low baseline blood folate concentrations and poor cognitive test performance; 4 of 9 folate studies found associations between low blood folate concentrations and increased prevalence of Alzheimer's disease. No association between vitamin B-6 and vitamin B-12 blood concentrations and cognitive-test performance or Alzheimer's disease was seen, and B-vitamin dietary intake was not associated with cognitive function. Although the majority of studies indicated that low blood folate concentrations predicted poorer cognitive function, data are not solid, due to variations in the way the studies were conducted and lack of agreement on what constitutes a low B-vitamin status.	According to several studies, eating plenty of darkly colored fruits and vegetables may slow brain aging. The estrogen-like properties in isoflavones are of interest in the study of Alzheimer's disease. Animal studies suggest that soy might be protective against AD, particularly in postmenopausal women. Of some concern, however, were one population and a few animal studies suggesting that soy intake may pose a risk for greater mental decline among older men. More research is needed to confirm the effects of soy on the aging brain and to determine if there are gender differences.
Infectious Disease	Studies are mixed whether vitamin supplements protect against upper respiratory infections. Large doses of vitamin C, for example, may help reduce the duration of a cold, but they do not appear to protect against one in the first place, even after exposure to a cold virus. Two studies in 2002 on multivitamins reported opposite results, with one finding fewer infections and one finding no difference. It is possible that vitamin C or multivitamin supplements may be helpful in specific people, such those who are vitamin deficient or have medical problems that impair their immune systems. A review of all studies on vitamin C and pneumonia prevention found only 1 placebo-controlled, randomized trial conducted in an English boarding school during World War II. The trial found a statistically significant (80% or greater) reduction in pneumonia incidence among boys consuming vitamin C. Two less-well-constructed trials arrived at the same conclusion. Therapeutic trials were even scarcer. Only one randomized, double-blind, placebo-controlled study of vitamin C for treatment of pneumonia was found. In this trial, elderly patients given vitamin C had lower mortality and respiratory symptom scores. However, the benefits were restricted to the sickest patients. One other trial of adults in the former Soviet Union found a dose-dependent reduction in the time to recover with two vitamin C doses. One 2007 study on vitamin D found that a single dose by mouth of this vitamin might prevent healthy individuals from activating the bacterium that causes tuberculosis in patients who harbor the infection. Studies on vitamin E specifically have been mixed. A 2002 study, in fact, reported a higher incidence and greater severity of respiratory infections in older adults who took 200 mg of vitamin E daily. However, a 2004 clinical trial conducted among elderly nursing home residents found that daily supplementation with 200 IU of vitamin E did provide protection from upper respiratory infections, especially the common cold. At present, there is not enough evidence to recommend vitamin E for infection prevention. Diarrhea is a worldwide problem, particularly in developing countries and those with poor sanitation. Taking supplements with B-complex vitamins, vitamin C, vitamin E, and selenium may reduce the risk of diarrhea, depending upon the organism that causes the disease. Meanwhile, iron supplements appear to increase the risk of infection from organisms that cause diarrhea. Vitamin A has not been shown to prevent diarrhea. Urinary tract infections (UTIs) may affect as many as 25% of pregnant women. A 2007 study found that women who took vitamin C (100 mg) for 3 months had significantly fewer UTIs than women who did not take vitamin C supplements. Rotavirus is a common cause of acute gastric pain in children under age 5. A 2007 study showed that the high amount of isoflavones found in soy-based infant formula can help prevent rotavirus infection.	Lycopene, found in tomatoes, appears to have properties that protect infection-fighting white blood cells. Saponins extracted from ginseng and allicin (found in garlic) have properties that boost the immune system. Both ginseng and garlic have long been traditionally used for their health benefits.
Asthma	Vitamin C from diet has been associated with lower risk for asthma. In one study, some people with exercise-induced asthma benefited from taking vitamin C one hour before strenuous physical activity. In a 2007 study, taking 1,500 mg supplements of vitamin C for 2 weeks helped prevent exercise-induced airway narrowing in patients with asthma.	Flavonoids found in apples and red wine may help lower the risk for asthma. Some evidence indicates that a low dietary intake of antioxidant nutrients could increase the risk for lung damage. Such nutrients should be obtained from fresh, deep green and yellow-orange fruits and vegetables. A 2007 study found low blood lycopene levels in people with asthma. Increasing lycopene- and vitamin A-rich foods may help raise lycopene levels.
Eye Disorder	Cataracts and Macular Degeneration. Oxygen-free radicals play a role in cataract formation and age related macular degeneration, the most common cause of irreversible blindness in the elderly. Bilberry (Vaccinium myrtillis), which contains powerful anthocyanins, is widely used to prevent macular degeneration. Low levels of vitamin C in the lens of the eye have been particularly strong predictors of cataracts. People with cataracts are frequently deficient in vitamin A, the carotenes, lutein, and zeaxanthin. Studies on protection against cataracts using antioxidant supplements have been mixed, including two identically conducted studies that reported opposite results. Vitamin C currently has the strongest evidence for protection, but even with this antioxidant studies are not consistent. A combination of zinc and antioxidants, including vitamin C and E, may slow the progression of macular degeneration. (Vitamin E alone does not appear to be protective.) Glaucoma. Although no evidence exists that antioxidants will prevent glaucoma, some studies reported an association between vitamin E and improved visual fields in patients with glaucoma.	Several studies report that the consumption of antioxidant-rich foods is associated with a decreased risk for cataracts. Carotenoids, especially lutein, lycopene, and zeaxanthin, are especially eye-protective and may help prevent cataracts and macular degeneration. The National Eye Institute in 2007 suggested that people with intermediate- or advanced macular degeneration in one eye may want to take a vitamin formula shown to reduce the risk of macular degeneration in the other eye by 25%. The formula contains vitamin C, vitamin E, beta-carotene, and zinc. They also suggest that a diet high in lutein and zeaxanthin may help reduce the risk of advanced age-related macular degeneration. Several studies report that the consumption of antioxidant-rich foods is associated with a decreased risk for cataracts. Carotenoids, especially lutein lycopene, and zeaxanthin are especially eye-protective and may help prevent cataracts and macular degeneration.
Skin Disorders and Wrinkles	Topical vitamin A (retinol) has been shown to improve fine wrinkles due to aging, by increasing glycosaminoglycan, which retains water, and increasing collagen production. One small study found that taking a combination of vitamins oral C and E supplements may help reduce sunburn reactions, although the protection is much less than from sunscreens. Taking the vitamins singly did not have any effect. In fact, a 2002 study reported that oral vitamin C had no effect on sunburn reaction. Of concern, in the same study some natural antioxidants in the body were reduced in people who took the vitamin. Also of concern are studies reporting no benefits and possibly harm from topical vitamin C in the form of ascorbyl palmitate, which is soluble in fat. One study reported that older adults had fewer wrinkles if they ate whole grains, fresh fruits and vegetables, and the use of healthy oils (such as olive oil). Diet played a role in improving skin regardless of whether the people in the study smoked or lived in sunny countries.	The following foods and phytochemicals may be especially skin protective: Both green tea and ginger appear to have properties that may provide some protection against skin cancer. Green tea skin care products are now available. The substance silymarin, found in the milk thistle family (which includes artichokes), may inhibit UVB-promoted cancers in animals. In one interesting study, eating garlic protected animals very effectively against UVB damage by interfering with urocanic acid in the skin. Whether these results may apply to humans (and what quantities of garlic might be beneficial) is still unknown.
Osteoporosis	Vitamin D. Vitamin D is the essential companion to calcium in maintaining strong bones. Supplements may be needed for people who have poor exposure to sunlight. It should be noted that diet supplies most people's need and high amounts of vitamin D can be toxic. Of interest: Taking vitamin D supplements does not prevent bone loss in post-menopausal African American women, according to research published in 2005. Further study will be needed to determine whether vitamin D prevents bone loss in women from other ethnic groups. Vitamin K. Studies suggest that vitamin K has properties that protect bone and prevent fracture. Vitamin K2 (menatetrenone), a form of vitamin K, is proving to prevent fractures in people with osteoporosis. Vitamin K affects blood clotting, and supplements are not recommended without specific physician instruction. Vitamin B12. One study reported that in people with osteoporosis and pernicious anemia, taking vitamin B12 (which is used to treat the anemia) also increased bone density. Vitamin C and E. There has been some indication of a positive association between vitamin C and E intake and bone density, although evidence proving actual benefits is weak. Note on Vitamin A. High amounts of dietary vitamin A reduces bone density and may even increase the risk for fracture in both postmenopausal women and men. (A form of vitamin A, retinoic acid, has been found to stimulate bone break down.) Beta carotene does not appear to increase risk. Studies suggest that diets rich in fresh fruits and vegetables (which include those high in potassium and magnesium) reduce elimination of calcium from the body and help preserve bones.	Studies suggest that diets rich in fresh fruits and vegetables (which include those high in potassium and magnesium) reduce elimination of calcium from the body and help preserve bones. Studies are suggesting that isoflavones-rich soy products may actually improve bone density in postmenopausal women. A 2007 study of postmenopausal women in Italy found that 24 months of treatment with genistein plus calcium and vitamin D increased bone density, while women who took calcium and D alone lost bone density. Flavonoids and other compounds in tea may protect the bones.
Menstrual Disorders	Vitamin B6. Limited clinical evidence suggests that vitamin B6 may be beneficial in reducing premenstrual symptoms, including depression. Typically, women take 100 mg per day, although one study suggested that a lower dose (50 mg) may have the same effect. Other preliminary research indicates that women who receive the equivalent of 1,200 mg of calcium and 400 IU of vitamin D per day (through food or supplements) have a significantly lower incidence of premenstrual symptoms than women who did not. Vitamin B1. One study reported relief from menstrual pain using vitamin B1 (thiamin). Vitamin E. Several randomized controlled trials have shown that vitamin E significantly improves both physical and emotional premenstrual symptoms. One study reported that high doses of vitamin E helped reduce menstrual cramps. The doses were much higher than those recommended and could possibly increase the risk for bleeding. Although anecdotal evidence reports that vitamin E helps reduce the frequency of hot flashes for menopausal women, there is no clinical evidence to support this claim.

Resources

http://fnic.nal.usda.gov -- The Food and Nutrition Information Center
http://dietary-supplements.info.nih.gov -- Office of Dietary Supplements, National Institutes of Health
www.ars.usda.gov/ba/bhnrc/ndl -- Nutrient Data Laboratory
www.fda.gov -- Food and Drug Administration
www.eatright.org -- The American Dietetic Association
www.acsh.org -- American Council on Science and Health
www.aicr.org -- American Institute for Cancer Research
www.nutritiondata.com -- Information on vitamins and nutrients in foods
www.consumerlab.com -- Independent testing of nutritional supplements' contents and quality
www.usp.org -- US Pharmacopeia
www.herbs.org -- Herb Research Foundation

References

Age-Related Eye Disease Study Research Group, SanGiovanni JP, Chew EY, Clemons TE, Ferris FL 3rd, Gensler G, Lindblad AS, Milton RC, Seddon JM, Sperduto RD. The relationship of dietary carotenoid and vitamin A, E, and C intake with age-related macular degeneration in a case-control study: AREDS Report No. 22. Arch Ophthalmol. 2007;125(9):1225-1232.

Ambrosini GL, de Klerk NH, Fritschi L, Mackerras D, Musk B. Fruit, vegetable, vitamin A intakes, and prostate cancer risk. Prostate Cancer Prostatic Dis. 2007 May 22; [Epub ahead of print]

Aubertin-Leheudre M, Lord C, Khalil A, Dionne IJ. Six months of isoflavone supplement increases fat-free mass in obese-sarcopenic postmenopausal women: a randomized double-blind controlled trial. Eur J Clin Nutr. 2007 Feb 21; [Epub ahead of print]

Bermudez Y, Ahmadi S, Lowell NE, Kruk PA. Vitamin E suppresses telomerase activity in ovarian cancer cells. Cancer Detect Prev. 2007;31(2):119-28. Epub 2007 Feb 28.

Bodnar LM, Catov JM, Simhan HN, Holick MF, Powers RW, Roberts JM. Maternal vitamin d deficiency increases the risk of preeclampsia. J Clin Endocrinol Metab. 2007 ;92(9):3517-22. Epub 2007 May 29.

Clements RH, Katasani VG, Palepu R, Leeth RR, Leath TD, Roy BP, Vickers SM. Incidence of vitamin deficiency after laparoscopic Roux-en-Y gastric bypass in a university hospital setting. Am Surg. 2006;72(12):1196-202.

Coull DB, Tait RC, Anderson JH, McKee RF, Finlay IG. Vitamin B12 deficiency following restorative proctocolectomy. Colorectal Dis. 2007;9(6):562-566.

Dietary Guidelines for Americans 2005. Dept of Health and Human Services, US Dept of Agriculture. Accessed 10/3/2007.

Fischer Walker CL, Black RE. Micronutrients and diarrheal disease. Clin Infect Dis. 2007;45 Suppl 1:S73-S77.

Glynn RJ, Ridker PM, Goldhaber SZ, Zee RY, Buring JE. Effects of random allocation to vitamin E supplementation on the occurrence of venous thromboembolism: report from the Women's Health Study. Circulation. 2007;116(13):1497-503.

Headstrom PD, Rulyak SJ, Lee SD. Prevalence of and risk factors for vitamin B(12) deficiency in patients with Crohn's disease. Inflamm Bowel Dis. 2007 Sep 20; [Epub ahead of print]

Inderjeeth CA, Glennon D, Petta A, Soderstrom J, Boyatzis I, Tapper J.Vitamin D and muscle strength in patients with previous fractures. N Z Med J. 2007;120(1262):U2730.

Ishihara J, Otani T, Inoue M, Iwasaki M, Sasazuki S, Tsugane S; Japan Public Health Center-based Prospective Study Group. Low intake of vitamin B-6 is associated with increased risk of colorectal cancer in Japanese men. J Nutr. 2007;137(7):1808-1814.

J.G. Ray, C. Kearon, Q. Yi, P. Sheridan, and E. Lonn, for the Heart Outcomes Prevention Evaluation 2 (HOPE-2) Investigators. Randomized Trial of Homocysteine-Lowering Therapy and Risk for Venous Thromboembolism. Ann Intern Med. 2007;146(11):761-767.

Kitchin B, Morgan SL. Not just calcium and vitamin D: other nutritional considerations in osteoporosis. Curr Rheumatol Rep. 2007;9(1):85-92.

Kune G, Watson L. Colorectal cancer protective effects and the dietary micronutrients folate, methionine, vitamins B6, B12, C, E, selenium, and lycopene. Nutr Cancer. 2006;56(1):11-21.

Lim MR, Huang RC, Wu A, Girardi FP, Cammisa FP Jr. Evaluation of the elderly patient with an abnormal gait. J Am Acad Orthop Surg. 2007;15(2):107-117.

Martin H, Lindblad B, Norman M. Endothelial function in newborn infants is related to folate levels and birth weight. Pediatrics. 2007;119(6):1152-1158.

Mason JB, Dickstein A, Jacques PF, Haggarty P, Selhub J, Dallal G, Rosenberg IH. A temporal association between folic acid fortification and an increase in colorectal cancer rates may be illuminating important biological principles: a hypothesis. Cancer Epidemiol Biomarkers Prev. 2007;16(7):1325-1329.

Nardin RA, Amick AN, Raynor EM. Vitamin B(12) and methylmalonic acid levels in patients presenting with polyneuropathy. Muscle Nerve. 2007;36(4):532-535.

Ochoa-Brust GJ, Fernández AR, Villanueva-Ruiz GJ, Velasco R, Trujillo-Hernández B, Vásquez. Daily intake of 100 mg ascorbic acid as urinary tract infection prophylactic agent during pregnancy. Acta Obstet Gynecol Scand. 2007;86(7):783-787.

Parekh N, Chappell RJ, Millen AE, Albert DM, Mares JA. Association between vitamin D and age-related macular degeneration in the Third National Health and Nutrition Examination Survey, 1988 through 1994. Arch Ophthalmol. 2007;125(5):661-669.

Pham DQ, Plakogiannis R. Vitamin E supplementation in Alzheimer’s disease, Parkinson’s disease, tardive dyskinsia, and cataract: Part 2. Ann Pharmacother. 2005;39(12): 2065-2072.

Riccioni G, Bucciarelli T, Mancini B, Di Ilio C, Della Vecchia R, D'Orazio N. Plasma lycopene and antioxidant vitamins in asthma: the PLAVA study. J Asthma. 2007;44(6):429-432.

Ronnenberg AG, Venners SA, Xu X, Chen C, Wang L, Guang W, Huang A, Wang X. Preconception B-vitamin and homocysteine status, conception, and early pregnancy loss. Am J Epidemiol. 2007;166(3):304-12. Epub 2007 May 2.

Sahin M, Tutuncu NB, Ertugrul D, Tanaci N, Guvener ND. Effects of metformin or rosiglitazone on serum concentrations of homocysteine, folate, and vitamin B12 in patients with type 2 diabetes mellitus. J Diabetes Complications. 2007;21(2):118-123.

Tamori A, Habu D, Shiomi S, Kubo S, Nishiguchi S. Potential role of vitamin K(2) as a chemopreventive agent against hepatocellular carcinoma. Hepatol Res. 2007;37 Suppl 2:S303-307.

Tecklenburg SL, Mickleborough TD, Fly AD, Bai Y, Stager JMAscorbic acid supplementation attenuates exercise-induced bronchoconstriction in patients with asthma. Respir Med. 2007;101(:1770-1778.

Triantafyllou NI, Kararizou E, Angelopoulos E, Tsounis S, Boufidou F, Evangelopoulos ME, Nikolaou C, Vassilopoulos D. The influence of levodopa and the COMT inhibitor on serum vitamin B12 and folate levels in Parkinson's disease patients. Eur Neurol. 2007;58(2):96-99.

Vagianos K, Bector S, McConnell J, Bernstein CN. Nutrition assessment of patients with inflammatory bowel disease. J Parenter Enteral Nutr. 2007;31(4):311-319.

Velasquez MT, Bhathena SJ. Role of dietary soy protein in obesity. Int J Med Sci. 2007; 4(2):72-82.

Wang Y, Hodge AM, Wluka AE, English DR, Giles GG, O'sullivan R, Forbes A, Cicuttini FM. Effect of antioxidants on knee cartilage and bone in healthy, middle-aged subjects: a cross-sectional study. Arthritis Res Ther. 2007;9(4):R66 [Epub ahead of print]

Wang X, Qin X, Demirtas H, Li J, Mao G, Huo Y, Sun N, Liu L, Xu X. Efficacy of folic acid supplementation in stroke prevention: a meta-analysis. Lancet. 2007;369(9576):1876-1882.

Weingärtner J, Lotz K, Fanghänel J, Gedrange T, Bienengräber V, Proff P. Induction and Prevention of Cleft Lip, Alveolus and Palate and Neural Tube Defects with Special Consideration of B Vitamins and the Methylation Cycle. J Orofac Orthop. 2007; 68(4):266-277.

Wierzbicki AS. Homocysteine and cardiovascular disease: a review of the evidence. Diab Vasc Dis Res. 2007;4(2):143-50.

Zeisel SH. The fetal origins of memory: the role of dietary choline in optimal brain development. J Pediatr. 2006;149(5 Suppl):S131-136.

Ziaei S, Kazemnejad A, Zareai M. The Effect of Vitamin E on Hot Flashes in Menopausal Women. Gynecol Obstet Invest. 2007;64(4):204-207 [Epub ahead of print]

Zollinger PE, Tuinebreijer WE, Breederveld RS, Kreis RW. Can vitamin C prevent complex regional pain syndrome in patients with wrist fractures? A randomized, controlled, multicenter dose-response study. J Bone Joint Surg Am. 2007;89(7):1424-1431.

Review Date:
10/29/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Breast milk - The Basics

FitSugar — Wed, 08 Oct 2008 17:34:50 -0700

HEALTH GUIDE REFERENCE FROM A.D.A.M

Breast milk - The Basics

Breast milk is the perfect source of nutrition for infants. Breast milk contains appropriate amounts of carbohydrate, protein, and fat. It also provides digestive enzymes, minerals, vitamins, and hormones that all infants require. Breast milk also contains valuable antibodies from the mother that can help the baby resist infections. Healthy infants have adequate iron stores to last until 8 months of age. Iron-rich foods can be started at this age. Your pediatrician or dietitian may recommend Fluoride supplementation in communities where water is not fluoridated (areas with less than 0.25 p.p.m. Fluoride).

Cow's milk by itself is inappropriate for infants less than 1 year old. The infant can develop an allergy to dairy products if given cow's milk too early in life. Although cow's milk contains most of the same components as breast milk, these components are not in the same amounts. Cow's milk also lacks the immune factors, called antibodies, that help protect infants until their own immune system fully develops.

Commercially prepared formulas may be based on non-fat cow's milk, whey protein, or soy protein. In order to provide a balanced diet for an infant, formulas are fortified with carbohydrates, fats, minerals, and vitamins. The antibodies found in breast milk, however, can never be added to formulas.

Breast Milk Production

Milk is produced in small sac-like glands (alveoli) in the breast. These sacs develop after specific hormonal (estrogen, progesterone, pituitary prolactin, and placental lactogen) stimulation that begins at four to six months (second trimester) of pregnancy.

The human breast does not store a large volume of milk as cow's do. Most of the milk your baby ingests during breastfeeding is produced during nursing. Suckling stimulates the release of a hormone (prolactin), which stimulates milk production. Suckling also causes the release of another hormone (oxytocin). Oxytocin, in turn, stimulates contraction (or the "let-down reflex") of the milk glands. The milk is squeezed out of the milk gland, into the milk ducts, and into the nipple.

At the beginning of the feeding, the milk is bluish and contains lactose and proteins, but little fat; it is called foremilk. The end of the feeding produces hindmilk. The hindmilk contains more fat, the main source of energy for your baby. If breast milk is allowed to sit for half-an-hour after being expressed, the "cream" separates and settles on top of the watery part. This is because human milk isn't homogenized. Homogenization is the process that makes the water and fat portion in milk stay in "one layer."

Milk Ejection Reflex

Some mothers feel a tingling sensation as the milk begins to eject from the breast due to the let-down reflex. The best way to monitor whether this milk-ejection reflex has begun is by watching the sucking and breathing patterns of your baby. At the start of a feeding, you will notice a pattern such as: suck, suck, suck, swallow, suck, suck, suck, swallow. This pattern may last up to 30 seconds but can be longer. As the milk ejection reflex takes over, the pattern may be described as gulping: one swallow, one deep breath, one swallow, one deep breath. This pattern may last for 2 to 4 minutes. Your baby may want to nurse longer (maybe 15 or 20 minutes) on this breast in order to get more fat from the hind milk or to fill a need for sucking. Mothers used to be told to nurse for 10 minutes a side. Now, experts say to watch your baby, not the clock. Let your baby break off the first breast when he’s ready, and then try switching to the other breast. If she’s not interested, it’s ok to nurse on one side per feeding. Just try to start on the other side next time, so you don’t get lopsided.

Establishing, Maintaining, And Increasing Your Milk Supply

Your milk supply will be established during the first few days and weeks after the birth of your baby. Nursing early (within the first half-hour), and frequently (on demand, or 8-12 times per day), allows you to nurse comfortably and efficiently. It usually takes less than one minute for an infant to stimulate the milk ejection reflex.

You should feel little discomfort or pain when breast feeding appropriately.

Within 6 and 8 weeks, your milk supply will adjust to your baby's needs. Before that time, your breasts may feel either too full or too empty. Frequent, comfortable feedings will maintain your milk supply. Your milk supply will increase or decrease based on your baby's hunger and energetic sucking (milk demand or use). Changes in your milk supply will occur within one to three days after changes in milk demand or use. Every few weeks, your baby may seem to want to eat all the time. It’s thought that this happens when she’s getting ready for a growth spurt. A few days of intense nursing are her way of telling your breasts to increase milk production.

Milk Handling And Storage

When storing milk for home use, wash your hands before expressing (or pumping). Use containers that have been washed in hot, soapy water and rinsed well, or run them through the dishwasher. Always date the milk before storing it. For more information, see pumping and expressing breast milk.

Refrigerated milk and frozen milk should be warmed under a stream of warm tap water. Never microwave breast milk; overheating destroys valuable nutrients and "hot spots" can scald your baby.

Review Date:
1/2/2007
Reviewed By:
Douglas A. Levine, MD, Gynecology Service, Memorial Sloan-Kettering Cancer Center, New York, NY. Review provided by VeriMed Healthcare Network.

A.D.A.M. Copyright

adam.com

Pregnancy Center Links

Menopause

FitSugar — Wed, 08 Oct 2008 17:34:57 -0700

In This Report

Highlights
Introduction
Complications
Symptoms
Lifestyle Changes
Medications
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Black Cohosh Doesn’t Help Hot Flashes

The herbal remedy black cohosh is no better than placebo for treating hot flashes and night sweats, according to a 2006 study in the Annals of Internal Medicine.
Most complementary and alternative medicines are ineffective for relieving menopausal symptoms, according to a 2006 review in the Archives of Internal Medicine.

Hormone Replacement Therapy (HRT)

Short-term use of HRT remains an option for recently menopausal women who have a low risk for stroke, according to a 2007 statement from the North American Menopause Society (NAMS). However, NAMS recommends that women who are at risk for heart disease or breast cancer should consider other approaches for managing hot flashes.
For women who want to discontinue HRT, gradually tapering off the medication or stopping it abruptly appears to make little difference in the recurrence of symptoms, suggests a 2006 study. A gradual approach may delay the reappearance of symptoms, but does not prevent them from returning.

HRT and Heart Disease: Timing Counts

Women who begin HRT within 10 years of menopause have a much lower risk for heart disease and heart attack than women who start HRT later on, indicates a 2007 study in the Journal of the American Medical Association. Experts suggest that HRT is relatively safe for younger women (under age 60) but should not be used by older women. HRT should never be used for prevention of heart disease, and HRT increases the risk for stroke regardless of a woman’s age or when she begins taking it.

HRT and Cancer

A dramatic fall in breast cancer rates has accompanied the decline in HRT use, according to a 2007 study in the New England Journal of Medicine.
Women who use HRT for more than 5 years have a 20% greater risk of developing and dying from ovarian cancer than women who have never used HRT, indicates a 2007 Lancet study of nearly 1 million women.

Introduction

The ovaries contain 200,000 - 400,000 follicles, tiny sacks that contain the materials needed to produce mature eggs, or ova. The ovaries produce two major female hormones: estrogen and progesterone.

The uterus is a hollow muscular organ located in the female pelvis between the bladder and rectum. The ovaries produce the eggs that travel through the fallopian tubes. Once the egg has left the ovary it can be fertilized and implant itself in the lining of the uterus. The main function of the uterus is to nourish the developing fetus prior to birth.

Estrogen. Estrogens have an effect on about 300 different tissues throughout a woman's body:

They are essential for the reproductive process and for the development of the female organs.
Estrogens determine the characteristic female distribution of body fat on the hips and thighs, which develops during adolescence.
They also are involved in tissues in the central nervous system (including the brain), the bones, the liver, and the urinary tract.

Estrogen has different forms:

The most potent form is estradiol.
The other important, but less powerful, estrogens are estrone and estriol.

Most of the estrogens in the body are produced by the ovaries, but they can also be formed by other tissues, such as body fat, skin, and muscle.

Progesterone. Progesterone, the other major female hormone, is necessary for thickening and preparing the uterine lining for the fertilized egg.

As a woman ages, her supply of eggs declines. Menopause occurs naturally after the woman's supply of follicles has been depleted and menstruation ends completely. (Menopause may also be induced if the ovaries are surgically removed.)

Perimenopause. Menopause does not occur suddenly. A period called perimenopause usually begins a few years before the last menstrual cycle. Some experts believe there are three stages in the transition:

Early Stage. The beginning of perimenopause can begin in some women in their 30s, but most often it starts between ages 40 - 44. It is marked by changes in menstrual flow and in the length of the cycle. There may be sudden surges in estrogen.
Middle Stage. In the middle cycle, periods become irregular but they are not skipped.
Late Stage. In the late stages, women begin missing the periods until they finally stop. About 6 months before menopause estrogen levels drop significantly. The fall in estrogen triggers the typical symptoms of vaginal dryness and hot flashes (which can last from half a year to more than 5 years after onset of menopause).

Menopause. At the point at which menopause occurs, the following hormonal changes occur:

Ovarian secretion of estrogen and progesterone ends.
Once the ovaries have stopped producing estrogens, however, they still continue to produce small amounts of the male hormone testosterone, which can be converted to estrogen (estradiol) in body fat.
In addition, the adrenal gland continues to produce androstenedione (a male hormone), which is converted to estrone and estradiol in the body fat.

Click the icon to see an image of the adrenal glands.

The total estrogen produced after menopause, however, is far less than that produced during a woman's reproductive years.

The average age of women at menopause today is 51.4 years although it can occur as early as age 40 to as late as the early 60s. Women now have a life expectancy of more than 80 years. Currently, women can expect to live some 30 or 40 years of their life in the postmenopausal state.

Menopause is not a disease. However, many conditions are associated with estrogen depletion, including heart disease, osteoporosis, and other complications. Fortunately, effective treatments are available for these conditions.

In a number of studies, most women have reported menopause as a positive experience and have welcomed it with relief and as a sign of a new stage in life.

Complications

After a woman reaches menopause, her average life expectancy is 30 - 40 years. During those years, however, she faces certain health risks due to lower levels of estrogen that cause accelerated bone loss and an increase in LDL cholesterol (the so-called bad cholesterol). Her risks for serious disorders are estimated at 46% for heart disease, 20% for stroke, and 15% for hip fracture. In addition, about 8% of people over 75 have dementia, with postmenopausal women having 1.4 - 3 times the risk for Alzheimer's disease compared to men.

Heart disease is the number one killer of women. In 2003, more than 480,000 women died from diseases of the heart and circulation (cardiovascular diseases). Although young women have a much lower risk for cardiovascular disease than young men, after menopause women catch up. After age 51, women’s risk of dying from heart disease is very close to that of men. Estrogen loss is believed to play a major role in this increased risk.

Some studies indicate that women who reach menopause at an early age are at increased risk of heart disease. However, recent research suggests that the reverse may also be true. A 2006 study suggested that women who have heart disease risk factors (smoking, high total cholesterol levels, high blood pressure) during premenopause may enter menopause earlier than women with healthier heart profiles. [See In-Depth Report #3: Coronary artery disease.]

Estrogen has the following effects:

Harmful Effects on Cholesterol and Other Lipids (Fats in the Blood). About 2 years before menopause, as estrogen levels begin to decline, the levels of the harmful low-density lipoprotein (LDL) cholesterol begin to rise, and the advantageous high-density lipoprotein (HDL) levels decrease.
Positive Effect on Blood Flow. Estrogen has significant effects on smoothing, relaxing, and opening blood vessels, thereby increasing blood flow and reducing pressure.
Antioxidant Actions. Estrogen is also an antioxidant. That is, it helps clean up particles called oxygen-free radicals that are released by natural chemical processes in the body, which can cause significant damage, including harm to the arteries.
Mixed Effects on Blood Pressure. The effects of estrogen on blood pressure are not clear. Oral contraceptives, for instance, which contain estrogen, appear to increase pressure slightly.

Blood pressure is the force applied against the walls of the arteries as the heart pumps blood through the body. The pressure is determined by the force and amount of blood pumped and the size and flexibility of the arteries.

Mixed Effects on Blood Clotting. Estrogen affects many blood-clotting factors in the liver: It reduces blood viscosity (stickiness) and may enhance fibrinolysis, the natural process for breaking down blood clots. Unfortunately, estrogen also has other actions that increase the risk for blood clots. Women who take hormone replacement therapy are at risk for thromboembolism -- blood clots that block a vessel.

Click the icon to see an image of thromboembolism.

This action may explain the higher rates of adverse heart events now observed in women with heart disease who take HRT.

Osteoporosis is a disease of the skeleton in which bones become brittle and prone to fracture. In other words, the bone loses density. At age 65, about 30% of women have osteoporosis, and nearly all of them are unaware of their condition. After age 80, up to 70% of women develop osteoporosis. Osteoporosis is a major risk factor for fracture in the spine and hip. The lifetime risk of spinal fracture in women is about 1 in 3 and that for hip fracture is 1 in 6. Furthermore, between 10 - 20% of women who experience a hip fracture die within a year and about 25% require nursing home treatment.

Click the icon to see an image of osteoporosis.

Experts are still puzzled by the extreme speed-up of bone breakdown (resorption) after menopause. Estrogen may have an impact on bone density in various ways:

Estrogen's most important effect on osteoporosis appears to be prevention of bone break down (resorption). Some research suggests that estrogen may control the lifespan of osteoclasts, the cells responsible for bone breakdown.
Part of estrogen's beneficial actions may involve maintaining normal levels of vitamin D, an important nutrient in bone protection.

Risk factors for osteoporosis include:

Being tall and thin
Being Caucasian
Smoking
Taking thyroid hormone
Being sedentary
Early menopause or surgical menopause (removal of ovaries)

Women at risk for osteoporosis should have a bone density test to measure their bone mass and then make a decision about treatment after consulting their doctor. [See In-Depth Report #18:Osteoporosis.]

Depression may occur as a woman transitions into menopause (perimenopause), even among women with no history of clinical depression. Hormonal changes and declines in estrogen levels are probably involved in this process. Research suggests that a depressive disorder is 2.5 times more likely to develop during perimenopause than premenopause. Women who transition to menopause at a younger age are at increased risk of a first episode of depression.

Symptoms of clinical depression include:

Loss of interest or pleasure in activities once enjoyed
Persistent (longer than 2 weeks) sad mood
Decreased energy
Sleep problems (insomnia or oversleeping)
Feelings of guilt, worthlessness, and hopelessness
Difficulty concentrating

Some of these symptoms may overlap with other symptoms that typically accompany perimenopause. Women who experience these symptoms should talk to their doctor. Depression is treatable. [See In-Depth Report #8: Depression.] For many women, depression eases once they reach menopause.

Estrogen, the primary female hormone, appears to have properties that protect against the memory loss and lower mental functioning associated with normal aging. Estrogen's effects on the brain include:

Laboratory studies suggested that estrogen may help block production of beta-amyloid, the source of the sticky plaques found in Alzheimer's brains.
Estrogen may trigger the temporary growth of nerve pathways in the memory portion of the brain.
Estrogen may stimulate production of the neurotransmitters acetylcholine and serotonin, which are depleted in Alzheimer's patients.
Estrogen also appears to smooth, relax, and open blood vessels, which may help blood flow in the brain.
Estrogen is an antioxidant. That is, it helps clean up free-oxygen radicals, the unstable particles thought to play a role in Alzheimer's.
Studies have been mixed on the association between natural estrogen levels and mental functioning in older women.

Estrogen therapy has been associated with reduced gum bleeding and with decreased bone loss around the teeth, and women who take estrogen are less likely to lose their teeth. Thus, the same principle that helps prevent bone loss in osteoporosis is also at work in preventing bone loss in the mouth.

Estrogen, progesterone, or both appear to protect against cataracts.

Click the icon to see an image of a cataract.

Studies also indicate that estrogen helps prevent glaucoma and macular degeneration.

Click the icon to see an image of glaucoma.

Click the icon to see an image of macular degeneration.

The drop in body estrogen levels brought on by menopause may contribute to both urinary stress and urge incontinence.

Women are at increased risk for recurrent urinary tract infections after menopause. Research suggests that estrogen may prevent infection by increasing the number of lactobacilli, a microorganism that fights infection by preventing bacteria from adhering to vaginal cells.

Estrogen may help prevent slackness and dryness in the skin and reduce wrinkles.

Menopause is associated with more sleeping problems, including inability to fall asleep and nighttime wakefulness.

Symptoms

The most prominent symptoms of the transition to menopause include:

Hot flashes and night sweats. Women often experience hot flashes as an intense build-up in body heat, followed by sweating and chills. Some women report accompanying anxiety as the sensation builds. In most cases, hot flashes resolve within 2 years of menopause, although in some women they may persist for years. Women who have a hysterectomy (surgical removal of the uterus) are less likely to experience hot flashes than women who have a natural menopause. However, women who have surgical removal of both ovaries, and who do not receive hormone replacement therapy, may have more severe hot flashes than women who enter menopause naturally.
Heart pounding or racing can occur, with or without hot flashes.
Difficulty sleeping. Insomnia is common during perimenopause. It may be caused by the hot flashes or it may be an independent symptom of hormonal changes. A 2006 study indicated that severe hot flashes are frequently associated with chronic insomnia.
Mood changes. Mood changes are most likely to be a combination of sleeplessness, hormonal swings, and psychological factors as a woman undergoes this intense passage in her life. Once a woman has reached a menopausal state, however, depression is no more common than before, and women with a history of premenstrual depression often experience significant mood improvement.
Sexuality. Sexual responsiveness tends to decline in most women after menopause, although other aspects of sexual function, including interest, frequency, and vaginal dryness vary. It is useful to remember that the symptoms of menopause eventually go away.
Forgetfulness. This appears to be one of the few symptoms that are common across most cultural and ethnic groups.
Urine leakage.
Vaginal dryness.
Joint stiffness.

Women from different ethnic and or cultural groups report different menopausal symptoms. For example, in one study hot flashes occurred in about 30% of Caucasians and 45% of African-Americans. Hispanic women tended to complain of urine leakage, vaginal dryness, and heart pounding. Japanese and Chinese women experienced far fewer menopausal symptoms, except for forgetfulness. All groups complained about this symptom.

Lifestyle Changes

Simple changes in lifestyle and diet can help control menopausal symptoms such as hot flashes. Avoid hot flash triggers like spicy foods, hot beverages, caffeine, and alcohol. Dress in layers so that clothes can be removed when a hot flash occurs. For vaginal dryness, moisturizers, and non-estrogen lubricants, such as KY Jelly, Replens, and Astroglide are available.

When women reach menopause, they are at increased risk for heart disease. A heart-healthy diet is an important way to control cholesterol and blood pressure levels. [See In-Depth Report #42: Heart-healthy diet.]

In 2007, the American Heart Association (AHA) issued revised diet and lifestyle recommendations. The current guidelines recommend:

Balancing calorie intake and physical activity to achieve or maintain a healthy body weight. (Controlling weight, quitting smoking, and exercising regularly are essential companions of any diet program. Try to get at least 30 minutes, and preferably 60 – 90 minutes, of daily exercise.)
Consuming a diet rich in a variety of vegetables and fruits. Vegetables and fruits that are deeply colored (spinach, carrots, peaches, berries) are especially recommended as they have the highest micronutrient content.
Choosing whole-grain, high-fiber foods. These include fruits, vegetables, and legumes (beans). Good whole grain choices include whole wheat, oats/oatmeal, rye, barley, brown rice, buckwheat, bulgur, millet, and quinoa.
Eating fish, especially oily fish, at least twice a week (about 8 ounces/week). Oily fish such as salmon, mackerel, and sardines are rich in the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Consumption of these fatty acids is linked to a reduced risk of sudden death and death from coronary artery disease. Women with existing heart disease may also consider taking a daily dietary supplement of 850 – 1,000 mg of EPA and DHA.
Limiting daily intake of saturated fat (found mostly in animal products) to less than 7% of total calories, trans fat (found in hydrogenated fats, commercially baked products, and many fast foods) to less than 1% of total calories, and cholesterol (found in eggs, dairy products, meat, poultry, fish, shellfish) to less than 300 mg per day. Choose lean meats and vegetable alternatives (such as soy). Select fat-free and low-fat dairy products. Grill, bake, or broil fish, meat, and skinless poultry.
Using little or no salt in your foods. Reducing salt can lower blood pressure and decrease the risk of heart disease and heart failure.
Cutting down on beverages and foods that contain added sugars (corn syrups, sucrose, glucose, fructose, maltrose, dextrose, concentrated fruit juice, honey).
If you consume alcohol, do so in moderation. The AHA recommends limiting alcohol to no more than 1 drink per day for women.
The AHA does not recommend antioxidant supplements (such as vitamin E, C, or beta carotene) or folic acid supplements for prevention of heart disease.

Soy is an excellent food. It is rich in both soluble and insoluble fiber, omega-3 fatty acids, and provides all essential proteins. Soy proteins have more vitamins and minerals than meat or dairy proteins. They also contain polyunsaturated fats, which are better than the saturated fat found in meat. The best sources of soy protein are soy products (tofu, soy milk, soybeans).

For many years, soy was promoted as a food that could help lower cholesterol and improve heart disease risk factors. But an important 2006 review of studies found that soy protein and isoflavone supplement pills do not really have any effects on cholesterol or heart disease prevention. The AHA still recommends soy foods, but not supplements, as a healthy food choice. The benefits of soy on menopausal symptoms are mixed, according to research (see below in Alternative Therapies). A 2006 study reported that increased soy intake does not help reduce the frequency or severity of hot flashes and night sweats.

Soy is high in estrogen-like plant chemicals called isoflavones, which may improve bone health in older women. A 2005 review of 15 clinical trials found that, although the results were mixed, isoflavones appeared to decrease bone loss, especially in younger postmenopausal women. Soy food products, such as tofu, that also contain calcium may be particularly beneficial.

A combination of calcium and vitamin D is important for helping to prevent bone loss. [See In-Depth Report #18: Osteoporosis.]

Calcium. Women should be sure they have sufficient calcium and vitamin D in their diet by consuming low-fat dairy products or calcium-enriched orange juice. Calcium supplements may be another option for some women. For calcium supplements, calcium citrate (Citracal) is better absorbed than calcium carbonate (Tums, Os-Cal) and other types of calcium compounds. Calcium citrate was the first calcium supplement reported to preserve bone density after menopause.

Click the icon to see an image of the benefits of calcium.

The standard recommended calcium dose for adults age 50 years and older is 1,000 – 1,500 mg per day, depending on risk factors. High doses (over 2,500 mg per day) of calcium supplements may increase the risk for kidney stones. (Because many commercial foods are now fortified with calcium, this upper limit may be easier to reach than people think.)

Click the icon to see an image of calcium sources.

For years, doctors have recommended that women take supplements of calcium plus vitamin D to help maintain bone density and reduce the risk for fractures. However, a 2006 New England Journal of Medicine study raised some questions about this approach. In the Women’s Health Initiative study, women were randomly assigned to receive either 1,000 mg of calcium carbonate plus 400 IU of vitamin D a day or placebo. The results indicated that daily calcium and vitamin D supplements:

Improve hip bone density slightly (by 1%)
Prevent hip fracture, but only for women who consistently take the supplements. (Another 2006 study supported this finding.)
Do not prevent spine or other types of fractures
Produce a slight increase in the risk of kidney stones

The medical community has differing views on how to interpret these findings. Some doctors recommend that women over age 60 should still consider taking calcium and vitamin D for bone health. Other doctors feel that due to the risks of kidney stones, supplements are beneficial only for women (especially those over age 70) who do not get enough calcium in their diets. Ask your doctor whether you should take calcium supplements.

Vitamin D. Vitamin D is necessary for the absorption of calcium in the stomach and gastrointestinal tract and is the essential companion to calcium in maintaining strong bones. Some studies suggest that vitamin D protects against osteoporosis only in combination with calcium.

Vitamin D is manufactured in the skin using energy from the ultraviolet rays in sunlight. It can also be obtained from dietary supplements. As a person ages, vitamin D levels decline. Levels also fall during winter months and when people have inadequate sunlight. Pollution may also contribute to less sunlight and declining vitamin D levels.

Click the icon to see an image of vitamin D sources.

Daily dosage guidelines vary. General recommendations include:

400 IU for people age 50 - 60
600 IU for those over age 70 who do not have sufficient exposure to sunlight. (Some evidence suggests that higher doses of vitamin D -- up to 800 IU per day -- may help prevent fractures in people with osteoporosis.)
800 – 1,000 IU for adults over age 50 (the amount recommended by the National Osteoporosis Foundation)

Drinking milk fortified with vitamin D and sunlight exposure supply most people's need for vitamin D. (One cup of whole milk provides about 100 IU of vitamin D.) Oily fish (sardines especially, as well as salmon, fresh tuna, and mackerel) are also important dietary sources of vitamin D. Wild salmon has a much higher vitamin D content than farmed salmon.

Effect on the Heart. One drink a day in women who are not at risk for alcohol abuse may be beneficial for the heart. Red wine in particular contains a substance called resveratrol, which is classified as a phytoestrogen and has estrogen-like effects.

Effect on Bones. Alcohol has different effects on bones depending on how much is consumed. A 2004 study found that moderate wine consumption was linked to improved bone mineral density in postmenopausal women. Alcohol, in moderate amounts, may increase estrogen levels. Excessive drinking, however, has been associated with brittle bones.

Effect on Breast Cancer. Women who drink face an increased risk for breast cancer, but the risk associated with mild-to-moderate drinking is small.

Many women need to increase physical activity and reduce caloric intake before and after menopause. Weight gain is common during these years, and it can be sudden and distressing, particularly when habitual exercise and eating patterns are no longer effective in controlling weight. Gaining weight around the abdomen (the so-called apple shape) is a specific risk factor for heart disease and diabetes and many other health problems. A 2007 study suggested that calcium and vitamin D supplements may help prevent weight gain in postmenopausal women. The benefit was greatest for women who had not been getting enough daily calcium in their diets.

Click the icon to see an image of different types of weight gain.

For protection against all aging diseases, women, whether or not they are taking hormone replacement therapy, should pursue a lifestyle that includes a balanced aerobic and weight resistance exercise program appropriate to their age and medical conditions. Brisk walking, stair climbing, hiking, dancing, and tai chi are all helpful. Several studies report that exercise can help control hot flashes. A healthy diet plus regular, consistent exercise can also help ward off the weight gain associated with menopause. Weight-bearing exercises are specifically helpful for protecting against bone loss. Women should strive for at least 30 minutes of exercise each day (for weight loss, 60 – 90 minutes is preferred). While more exercise is better, any exercise is helpful. A 2007 study showed that postmenopausal sedentary women who exercised only 75 minutes a week experienced improvement in fitness levels.

If a woman smokes, she should quit. Smoking is linked to a decline in estrogen levels. Women who smoke experience menopause about 2 years earlier than nonsmokers. Smoking doubles a woman’s odds of developing coronary heart disease and is a major risk factor for osteoporosis.

Aspirin. The American Heart Association recommends daily low-dose aspirin for all women age 65 years and older who can safely take aspirin. High-risk women may require 75 – 325 mg per day; lower-risk women may benefit from 81 mg a day or 100 mg every other day.

There are many unproven methods for relieving menopausal symptoms, some more effective than others. Acupuncture, meditation, and relaxation techniques are all harmless ways to reduce the stress of menopause, and some people report great benefit from these practices.

Acupuncture, hypnosis, and biofeedback are all alternative ways to control pain. Acupuncture involves the insertion of tiny sterile needles, slightly thicker than a human hair, at specific points on the body.

Women often try herbal or so-called natural remedies to treat menopausal symptoms. There have been numerous studies conducted on various herbal products and other complementary and alterative therapies. These studies have not found that these approaches have any benefit. Some can have adverse side effects.

Many studies have researched plant estrogens (phytoestrogens), which are generally categorized as isoflavones (found in soy and red clover) and lignans (found in whole wheat and flaxseed). No evidence to date indicates that phytoestrogen supplements provide any benefit for hot flashes or other menopausal symptoms. Nevertheless, foods containing them may be healthful.

Supplements containing specific isoflavones found in soy -- typically the estrogen-like compounds genistein and daidzein -- do not appear to provide any benefits compared to the whole soy protein. Taking them separately may, in fact, cause harm, including a possible increase in estrogen-related cancers.

The following herbs are sometimes use for menopausal symptoms and carry certain risks:

Black cohosh (Cimicifuga racemosa), also known as squaw root, is the herbal remedy most studied for menopausal symptoms. Although it contains a plant estrogen, this substance does not act like an estrogen in the human body. Studies have shown mixed results in preventing hot flashes. A rigorous 2006 study found that black cohosh worked no better than placebo for treating hot flashes and night sweats. While it may be ineffective, black cohosh appears to be safe. Headaches and gastrointestinal problems are common side effects.
Dong quai (Angelica sinensis) does not appear helpful for hot flashes or other menopausal symptoms. Do not use dong quai with blood-thinning drugs, such as warfarin, because it may cause bleeding complications.
Ginseng (Panax ginseng) may help menopausal symptoms of depression and sleep problems, but it has no effect on hot flashes.
Kava (Piper methysticum) may relieve anxiety but it does not help hot flashes. This herb is generally considered unsafe, due to several reports of liver failure and death, especially in people with liver disease.
Wild yam (Dioscorea villosa) is an herb sometimes used for menstrual problems as well as menopausal symptoms. It contains a plant progesterone. However, like black cohosh, there is no evidence that the human body can convert this substance into a hormone. Patients should be aware that some commercial herbal wild yam products contain prescription progesterones.
Dehydroepiandrosterone (DHEA) is a weak male hormone secreted by the adrenal gland. It is available as a dietary supplement. DHEA has no benefit for hot flashes and may increase the risk of breast cancer.

Generally, manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like with drugs, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been a number of reported cases of serious and even lethal side effects from herbal products. Patients should check with their doctors before using any herbal remedies or dietary supplements.

Medications

Doctors used to believe that HRT could help reduce the risk of heart disease and other health risks in addition to treating menopausal symptoms. The results of an important study, called the Women's Health Initiative (WHI), led doctors to revise their recommendations regarding HRT.

The WHI, started in 1991, enrolled 161,809 women between the ages of 50 - 79 in 40 different medical centers. Part of the study was intended to examine the health benefits and risks of hormone replacement therapy, including the risks of breast cancer, heart attacks, strokes, and blood clots.

In 2002, one component of the WHI, which studied the use of estrogen and progestin in women who had a uterus, was stopped early because the health risks exceeded the health benefits. The main reason for stopping the estrogen-progestin study was a 26% increase in breast cancer. This combination therapy study also showed an increased risk for heart attack, stroke, blood clots, and dementia. There was a reduced risk for colorectal cancer and bone fractures, but these benefits did not outweigh the considerable risks.

In 2004, a second component of the WHI, which studied estrogen-only therapy in women who no longer have a uterus, was stopped early. This was primarily because of an increase in the risk for strokes and blood clots. The study also found the estrogen-only therapy had no effect on heart attack or colorectal cancer risk. An update in 2006 suggested that estrogen-only therapy does not increase breast cancer risk over the short term (average 7 years) but may increase risk when taken for a longer time (15 years or more). Another WHI update, from 2007, indicated that estrogen-only therapy can help reduce calcium deposits in the coronary arteries (a sign of heart disease) for women in their 50s who have had a hysterectomy. However, women who have a uterus cannot take estrogen-only HRT because it increases the risk for uterine cancer. Combination estrogen-progestin HRT does not have the same benefits for cholesterol reduction as estrogen-only HRT.

While the WHI studies indicate that HRT should not be prescribed for prevention of chronic diseases, many doctors still accept its use for short-term treatment of moderate-to-severe hot flashes and other menopausal symptoms, and in women undergoing premature menopause for medical or other reasons. Current guidelines recommend using the lowest possible dose for the shortest duration of time. A 2007 position statement from the North American Menopause Society (NAMS) supports short-term use of HRT for treatment of hot flashes and other vasomotor symptoms in recently menopausal women who have a low risk for stroke. However, NAMS recommends that women who are at risk for heart disease or breast cancer should avoid hormone therapy and try other options to manage symptoms.

When a woman stops taking HRT, perimenopausal symptoms may recur. There is some debate about whether it is better to abruptly stop the medication or to taper it off gradually. A 2006 study suggested that gradual discontinuation of HRT delays -- but does not prevent -- the reappearance of symptoms. However, when a woman reaches full menopause, symptoms will eventually go away.

Hormones Used in HRT. Hormone replacement therapy uses either estrogen alone (known as ET or unopposed estrogen) or in combination with forms of progesterone (known as combined hormone therapy or EPT). Progesterone is referred to by one of several names:

Progesterone is the name for the natural hormone.
Progestin is the term for any hormone, natural or synthetic, that causes progesterone effects.
Progestogen is any hormone that has effects similar to progesterone.

Both ET and EPT are available in many forms, including oral tablets, skin patches, and vaginal and skin applications. A new form approved by the FDA in 2004 is a topical estrogen gel that is applied to the arm.

HRT is mainly recommended for relieving menopausal symptoms, including hot flashes, night sweats, vaginal dryness, sleep problems, and mild depression. HRT does not prevent certain other problems associated with menopausal changes, such as thinning hair.

Oral hormonal medications and skin patches are equally effective in reducing hot flashes, mild depression, and sleep problems. Progestins may sometimes be prescribed alone for hot flashes and other acute menopausal symptoms, though they can cause side effects, such as mood swings, bloating, and breast tenderness. Estrogen creams, rings, or vaginal tablets restore vaginal elasticity and lubrication and improve sexual pleasure.

HRT may be useful for some women at high risk for osteoporosis, although other drugs, such as bisphosphonates, should be considered first. It increases bone density and also appears to improve balance and protects against falling. Studies also report reductions in fractures (especially hip fractures) among women taking HRT, but the benefits may not outweigh the risks of HRT. It appears that the beneficial effects wear off soon after therapy is stopped. Estrogen must be taken life long for maximum protection against osteoporosis, which then increases the risk for adverse health effects.

Heart Disease. HRT does not prevent heart disease and can increase the risk for heart disease and heart attack, especially in older women. An important 2007 Women’s Health Initiative study in the Journal of the American Medical Association indicated that this risk is time and age dependent. The study found that women who began HRT within 10 years of menopause had less risk of heart disease than women who begin HRT later on. This study suggests that HRT may be safest for women younger than age 60, and should be avoided by women older than age 60. Any woman who is considering HRT should be sure to have her blood pressure and cholesterol levels evaluated.

Another 2007 study, published in the New England Journal of Medicine (NEJM), also indicated that timing is important. The NEJM study found that that estrogen-only HRT may help reduce calcium deposits in coronary arteries in younger women (age 50 - 59) who have had a hysterectomy. (Because of the increased risk for uterine cancer, estrogen-only HRT is only appropriate for women who no longer have a uterus. Women who have a uterus need to take estrogen-progestin HRT. And, estrogen can increase the risk for heart attack in women who have advanced heart disease.) Although the NEJM study found some heart benefits for estrogen-only HRT for younger women, experts still advise that HRT should be used for only a few years. Any woman who is considering HRT should be sure to have her blood pressure and cholesterol levels evaluated.

Stroke. HRT increases the risk of stroke, regardless of years since menopause. In addition, HRT appears to worsen the outlook for women who have had a stroke.

Mental Decline. Observational studies had suggested that hormone replacement therapy (HRT) helped prevent mental decline and even Alzheimer's disease after menopause. Other studies have found no differences in mental performance and no protection from Alzheimer's disease in women taking HRT compared to non-users. A 2004 review of the Women’s Health Initiative Memory Study found that combined HRT did not reduce the risk of cognitive impairment, and actually increased the risk of dementia among women ages 65 and over.

Thromboembolism. HRT is associated with a higher risk for thromboembolism, in which blood clots form in deep veins. This places women at risk for pulmonary embolism, in which the blood clot travels to the lungs.

Click the icon to see an image of a pulmonary embolism.

Breast Cancer. Because breast tissue growth is highly sensitive to estrogens, the more a woman is exposed to estrogen over her lifetime, the higher the risk for breast cancer. A number of studies have reported a higher risk for breast cancer in postmenopausal women taking HRT that contains both estrogen and progestin. A combination of estrogen and testosterone also increases breast cancer risk. A 2005 study suggested that HRT with no or low progestin is safer than standard estrogen-progestin combination therapy.

Several 2006 studies of women who had a hysterectomy indicated that estrogen alone does not increase overall breast cancer risk when the drug is used for 7 years or less. However, women who take the drug for 15 years or more do have an increased risk. Women who are at low risk for breast cancer tend to have fewer breast cancers with estrogen alone, while women at higher risk tend to have more breast cancers. In addition, estrogen therapy may cause abnormal mammogram results. Breast tissue density increases with HRT, which makes mammograms more difficult to read and leads to more breast biopsies. Women who take estrogen HRT should be aware that they need frequent mammogram screenings.

As further evidence of the association between HRT and breast cancer, a 2007 New England Journal of Medicine study noted that breast cancer rates have fallen as HRT use has declined.

Endometrial (Uterine) Cancers. Estrogen overstimulates the tissue lining the uterus (the endometrium) and causes uncontrolled cell growth, a condition known as hyperplasia, which is a strong risk factor for cancer. Taking unopposed estrogen replacement therapy (ERT) increases the risk of endometrial cancer at least five-fold. Adding progestin to HRT appears to pose no risk for this cancer. However, a 2007 study indicated that short-term treatment (3 years) with ERT is associated with a relatively low risk of endometrial cancer. Women who take ERT should anticipate uterine bleeding, especially if they are obese, and may need endometrial biopsies and other gynecologic tests.

Ovarian Cancer. HRT appears to increase the risk for ovarian cancer. A 2007 UK study of nearly 1 million women found that women who used HRT for more than 5 years were 20% more likely to develop and die from ovarian cancer than women who had never taken HRT.

Gallstones. HRT is associated with a higher risk for gallstones.

Despite its risks, hormone replacement therapy appears to be the best treatment for hot flashes. Nonhormonal treatments for hot flashes and other menopausal symptoms include:

Antidepressants. The antidepressants known as selective serotonin-reuptake inhibitors (SSRIs) are sometimes used for managing mood changes and hot flashes. They include fluoxetine (Prozac), sertraline (Zoloft), venlafaxine (Effexor), and paroxetine (Paxil, Asimia). A 2006 review of nonhormonal therapies, found that paroxetine in particular may help hot flashes. However, paroxetine, like other antidepressants, can cause headache, anxiety, and sexual problems. A 2007 study suggested that the antidepressant citalopram (Celexa), given alone or with HRT, may help treat hot flashes.

An investigational antidepressant, desvenlafaxine (Pristiq), is also being studied for treatment of hot flashes, night sweats, and perimenopausal sleep problems. Research presented at the 2007 meeting of the American College of Obstetricians and Gynecologists indicated that desvenlaxafine, which is related to venlaxafine, showed promise in improving symptoms.

Gabapentin.Several small studies suggest that gabapentin (Neurontin), a drug used for seizures and nerve pain, may relieve hot flashes. Gabapentin may cause drowsiness, dizziness, fatigue, and swelling of the hands and feet.

Clonidine. Clonidine (Catapres) is a drug used to treat high blood pressure. Studies show it may help manage hot flashes. Side effects include dizziness, drowsiness, dry mouth, and constipation

Testosterone. Some doctors prescribe combinations of estrogen and small amounts of the male hormone testosterone to improve sexual function and increase bone density. Side effects of testosterone include increased body hair, acne, fluid retention, anxiety, and depression. Testosterone also adversely affects cholesterol and lipid levels. A 2006 study indicated that combined estrogen and testosterone can increase the risk of breast cancer.


HRT Form	Brand Name	Active Ingredient	Side Effects
Oral Estrogens	Premarin	Natural conjugated estrogen, which is a mixture of estrogens derived from the urine of pregnant mares	Bleeding after withdrawal. It is a primary reason why many women stop treatment, although usually lighter or shorter compared to before menopause. If it is distressing, patient should consider continuous estrogen and progestin therapy. Irregular bleeding. This should be checked with the doctor for possible problems. Nausea and vomiting. If it occurs, usually does so only during the first 3 months and is minimal. Rarely with low doses. Headaches. Cramps. Risk for blood clots.
	Cenestin	Synthetic conjugated estrogen, which is a mixture of estrogens derived from compounds found in yams and soy
	Estratab, Menest	Plant-derived estrogens, called esterified estrogens. Usually made from modified soy
	Estrace (oral)	Estradiol, the most potent natural estrogen
	Ogen, Ortho-Est	Estropipate, a version of estrone, which is a weaker form of estrogen
	Estrovis	Quinetrol, a synthetic estrogen
	Estinyl	Synthetic form estradiol, the most potent estrogen

Oral Progestins	Provera, Amen, Curretab, Cycrin	Medroxyprogesterone, a synthetic progestin	Breast tenderness. Usually subsides in 3 - 4 months and can be relieved with over-the-counter painkillers and possibly by decreasing caffeine intake and adding vitamin E. Headache. Fluid build-up. Bloating. Fatigue, unusual tiredness, weakness. Depression, irritability, or other mood changes.
	Norlutin, Aygestin, Norlutate	Norethindrone and norethindrone acetate, synthetic progestins
		Norgestrel

Oral Combinations of Estrogen and Progestin	Prempro, Premphase	Conjugated estrogens plus medroxyprogesterone	May have some of the side effects of both estrogen and progestin. Continuous regimens eliminate menstrual bleeding in more than half of women. Investigators are studying the use of higher progestin doses or a lower estrogen doses and comparing combinations for further reduction of bleeding risk.
	Activelle, Femhrt	Estradiol and norethindrone or norethindrone acetate
	Ortho-Prefest	Estradiol and norgestimate
	Angeliq	Estradiol and drospirenone

Skin Patch Administration of HRT	Estraderm, Alora, Climara, Vivelle, FemPatch, Evorel	Estradiol	Skin irritation where the patch is applied most common. Hormonal side effects associated with formulation of patch.
Skin Patch Administration of HRT	CombiPath	Estradiol plus norethindrone (a progestin)

Vaginal Creams for dryness and irritation	Estrace (cream)	Estradiol (potent estrogen)	Hormonal side effects associated with estrogen or progestins, depending on formulation.
	Ogen (cream)	Estropipate (weaker estrogen.)
	Premarin (cream)	Conjugated natural estrogens
	Ortho-dienestrol (cream)	Dienestrol (synthetic estrogen)
	Crinone (cream)	A natural progesterone
Other forms of vaginal administration	Vagifem (vaginal tablet)
	Estring (vagina Ring)	Estradiol
	Other forms: injections, nasal sprays, and as pellets inserted under the skin twice a year.
Topical Gel	EstroGel	Estradiol	Hormonal side effects associated with estrogen.

Resources

www.menopause.org -- North American Menopause Society
www.acog.com -- American College of Obstetricians and Gynecologists
www.nia.nih.gov -- National Institute on Aging
www.nhlbi.nih.gov/whi/recommend.htm -- Women's Health Initiative Study
www.nih.gov/PHTindex.htm -- National Institutes of Health -- Menopausal Hormone Therapy Information
http://nccam.nih.gov/health/menopauseandcam -- National Center for Complementary and Alternative Medicine

References

Beral V; Million Women Study Collaborators; Bull D, Green J, Reeves G. Ovarian cancer and hormone replacement therapy in the Million Women Study. Lancet. 2007 May 19;369(9574):1703-10.

Caan B, Neuhouser M, Aragaki A, Lewis CB, Jackson R, Leboff MS, et al. Calcium plus vitamin d supplementation and the risk of postmenopausal weight gain. Arch Intern Med. 2007 May 14;167(9):893-902.

Church TS, Earnest CP, Skinner JS, Blair SN. Effects of different doses of physical activity on cardiorespiratory fitness among sedentary, overweight or obese postmenopausal women with elevated blood pressure: a randomized controlled trial. JAMA. 2007 May 16;297(19):2081-91.

Haimov-Kochman R, Barak-Glantz E, Arbel R, Leefsma M, Brzezinski A, Milwidsky A, et al. Gradual discontinuation of hormone therapy does not prevent the reappearance of climacteric symptoms: a randomized prospective study. Menopause. 2006 May-Jun;13(3):370-6.

Jackson RD, LaCroix AZ, Gass M, Wallace RB, Robbins J, Lewis CE, et al. Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med. 2006 Feb 16;354(7):669-83.

Kalay AE, Demir B, Haberal A, Kalay M, Kandemir O. Efficacy of citalopram on climacteric symptoms. Menopause. 2007 Mar-Apr;14(2):223-9.

Manson JE, Allison MA, Rossouw JE, Carr JJ, Langer RD, Hsia J, et al. Estrogen therapy and coronary-artery calcification. N Engl J Med. 2007 Jun 21;356(25):2591-602.

Mosca L, Banka CL, Benjamin EJ, Berra K, Bushnell C, Dolor RJ, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation. 2007 Mar 20;115(11):1481-501.

Nedrow A, Miller J, Walker M, Nygren P, Huffman LH, Nelson HD. Complementary and alternative therapies for the management of menopause-related symptoms: a systematic evidence review. Arch Intern Med. 2006 Jul 24;166(14):1453-65.

Newton KM, Reed SD, LaCroix AZ, Grothaus LC, Ehrlich K, Guiltinan J. Treatment of vasomotor symptoms of menopause with black cohosh, multibotanicals, soy, hormone therapy, or placebo: a randomized trial. Ann Intern Med. 2006 Dec 19;145(12):869-79.

North American Menopause Society. The role of local vaginal estrogen for treatment of vaginal atrophy in postmenopausal women: 2007 position statement of The North American Menopause Society. Menopause. 2007 May-Jun;14(3 Pt 1):355-69.

Ohayon MM. Severe hot flashes are associated with chronic insomnia. Arch Intern Med. 2006 Jun 26;166(12):1262-8.

Ravdin PM, Cronin KA, Howlader N, Berg CD, Chlebowski RT, Feuer EJ, et al. The decrease in breast-cancer incidence in 2003 in the United States. N Engl J Med. 2007 Apr 19;356(16):1670-4.

Rossouw JE, Prentice RL, Manson JE, Wu L, Barad D, Barnabei VM, et al. Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. JAMA. 2007 Apr 4;297(13):1465-77.

Steiner AZ, Xiang M, Mack WJ, Shoupe D, Felix JC, Lobo RA, et al. Unopposed estradiol therapy in postmenopausal women: results from two randomized trials. Obstet Gynecol. 2007 Mar;109(3):581-7.

Tamimi RM, Hankinson SE, Chen WY, Rosner B, Colditz GA. Combined estrogen and testosterone use and risk of breast cancer in postmenopausal women. Arch Intern Med. 2006 Jul 24;166(14):1483-9.

Review Date:
6/25/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Osteoporosis

FitSugar — Wed, 08 Oct 2008 17:34:56 -0700

In This Report

Highlights
Introduction
Causes
Symptoms
Fractures
Risk Factors
Diagnosis
Lifestyle Changes
Medications
Treatment
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Approvals

In 2007, the Food and Drug Administration (FDA) approved zoledronic acid (Reclast) for postmenopausal osteoporosis treatment. Zoledronic acid is given as an injection once a year. A 2007 study in the New England Journal of Medicine indicated that zoledronic acid can significantly reduce the risk of spine, hip, and other fractures.
In 2007, the FDA approved raloxifene (Evista) for prevention of breast cancer in postmenopausal women with osteoporosis and postmenopausal women at high risk for breast cancer. Raloxifene was previously approved for prevention and treatment of osteoporosis.

Calcium and Vitamin D for Osteoporosis Prevention

In 2007, the Food and Drug Administration proposed allowing manufacturers of food and supplements to put a health claim on their products stating that the combination of calcium and vitamin D can reduce the risk of osteoporosis.
In 2007, the National Osteoporosis Foundation updated its daily intake guidelines to recommend 1,200 mg of calcium, and 800 - 1,000 IU of vitamin D3, for adults age 50 and older.
Calcium plus vitamin D is effective in preventing osteoporosis in people age 50 years and older, according to a 2007 review in the Lancet. The researchers found that a minimum of 1,200 mg of calcium and at least 800 IU of vitamin D per day gave the most protection.

Fosamax: Taking a Break (Without Breaking a Bone)

Women at low risk for fracture may be able to temporarily stop taking alendronate (Fosamax) after 5 years, suggests a 2006 study in the Journal of the American Medical Association.

Antidepressants and Osteoporosis Risk

Selective serotonin reuptake inhibitors (SSRIs), the most commonly used class of antidepressants, may increase the risk for bone loss in both older men and women, according to several studies published in 2007 in the Archives of Internal Medicine. SSRIs include fluoxetine (Prozac), sertraline (Zoloft), and paroxetine (Paxil). The researchers did not find that other types of antidepressants are associated with reduced bone mineral density.

Introduction

Osteoporosis is a disease of the skeleton in which bones become brittle and prone to fracture. In other words, the bone loses density. Osteoporosis is diagnosed when bone density has decreased to the point where fractures occur with mild stress.

The skeleton consists of groups of bones which protect and move the body.

Until a healthy person is around age 40, the process of breaking down and building up bone by cells called osteoclasts and osteoblasts is a nearly perfectly coupled system, with one phase stimulating the other. As a person ages, or in the presence of certain conditions, this system breaks down and the two processes become out of sync. The reasons why this occurs during aging are not clear. Some individuals have a very high turnover rate of bone, some have a very gradual turnover, but the breakdown of bone eventually overtakes the build-up.

The Function of Bones. The skeleton has a dual function:

It provides structural support for muscles and organs.
It also serves as a depot for the body’s calcium and other essential minerals, such as phosphorus and magnesium.

The skeleton holds 99% of the body’s calcium. The remaining 1% circulates in the blood and is essential for crucial bodily functions, ranging from muscle contraction to nerve function to blood clotting.

Bone Turnover: the Breakdown and Growth of Bones. Like other organs in the body, bone tissue is constantly being broken down and reformed again. This turnover is necessary for growth, for repair of minor damage that occurs from everyday stress, and for the maintenance of a properly functioning body. Two essential cells are involved in this process:

Osteoblast cells are produced by bone cells and are the bone builders. They rebuild the skeleton, first by filling in the holes with collagen, and then by laying down crystals of calcium and phosphorus.
Osteoclast cells are formed from certain blood cells and are responsible for the breakdown, or resorption, of the skeleton. These cells dig holes into the bone and release the small amounts of calcium into the bloodstream that are necessary for other vital functions.

Each year, about 10 - 30% of the adult skeleton is remodeled in this way. The bone build up (formation)-break down (resorption) balance is controlled by a complex mix of hormones and chemical factors. If bone resorption occurs at a greater rate than bone build up, your bone loses density and puts you at risk for osteoporosis.

In women, estrogen loss after menopause is associated with rapid resorption and loss of bone density. This group, then, is at highest risk for osteoporosis and therefore for fracture.

There are two primary kinds of osteoporosis: type I and type II:

Type I. Type I, or high turnover, osteoporosis occurs in 5 - 20% of women, most often between the ages of 50 and 75. This is because of the sudden postmenopausal decrease in estrogen levels, which results in a rapid depletion of calcium from the skeleton. This is associated with fractures that occur when the vertebrae compress together, causing a collapse of the spine. It is also associated with fractures of the hip, wrist, or forearm caused by falls or minor accidents. Women have a higher risk for type 1 osteoporosis than men.
Type II. Type II, or low turnover, osteoporosis (also known as age-related or senile osteoporosis) results when the process of resorption and formation of bone are no longer coordinated, and bone breakdown overcomes bone building. (This occurs with age in everyone to some degree.) Type II osteoporosis affects both men and women and is primarily associated with leg and spinal fractures. Older women can have both type I and type II osteoporosis.

Click the icon to see an image of a compression fracture.

What determines the existence of osteoporosis, whether type I or type II, is the amount of calcium left in the skeleton and whether it places a person at risk for fracture. Someone who has exceptionally dense bones to begin with will probably never lose enough calcium to reach the point where osteoporosis occurs, whereas a person who has low bone density could easily develop osteoporosis despite losing only a relatively small amount of calcium.

Secondary osteoporosis is caused by other conditions, such as hormonal imbalances, diseases, or medications (such as corticosteroids or anti-seizure drugs).

Click the icon to see an image of osteoporosis.

Causes

Because the patterns of reforming and resorbing bone often vary from patient to patient, experts believe several different factors account for this problem. Important chemicals (such as estrogen, parathyroid hormone, and vitamin D) and blood factors that affect cell growth are involved with this process. Changes in levels of any of these factors could play a role in the development of osteoporosis.

Although ordinarily associated with women, sex hormones play a role in osteoporosis in both genders, most likely by controlling the birth and duration of life of both osteoclasts (bone breakers) and osteoblasts (bone builders).

Women and Estrogen. Experts are still puzzled by the rapid decline in bone density after menopause, when a woman’s ovaries stop producing estrogen. Estrogen comes in several forms:

The most potent form of estrogen is estradiol. Estradiol deficiency appears to be a very strong factor in the development of osteoporosis.
The other important but less powerful estrogens are estrone and estriol.

The ovaries produce most of the estrogen in the body, but it can also be formed in other tissues, such as body fat, skin, and muscle. After menopause, some amounts of estrogen continue to be manufactured in the peripheral body fat. Even though the ovaries have stopped producing estrogens directly, they continue to be a source of the male hormone testosterone, which converts into estradiol.

Estrogen may have an impact on bone density in various ways:

Estrogen’s most important effect on osteoporosis appears to be prevention of bone breakdown (resorption). Some research suggests that estrogen may control the life span of osteoclasts, the cells responsible for bone breakdown.
One study reported that part of estrogen’s beneficial actions may involve maintaining normal levels of vitamin D, an important nutrient in bone protection.

Men and Androgens and Estrogen. In men, the most important androgen (male hormone) is testosterone, which is produced in the testes. Other androgens are produced in the adrenal glands. Androgens are converted to estrogen in various parts of a man’s body, including bone.

Click the icon to see an image of the adrenal glands.

Studies have suggested that the loss of estrogen as well as testosterone may contribute to bone loss in elderly men. In one study, elderly men were first given a drug that blocked their normal hormones and then were given estrogen and testosterone patches. When the estrogen patch was removed, the bone breakdown process accelerated. When both patches were removed, the number of the bone-building cells (the osteoblasts) decreased. In other words, both hormones appeared to be integral to bone function in men.

Low levels of vitamin D and high levels of parathyroid hormone (PTH) are associated with hip fracture in women after menopause:

Vitamin D is a vitamin with hormone-like properties. It is essential for the absorption of calcium into the bone and for normal bone growth. Lower levels result in impaired calcium absorption, which in turn causes an increase in PTH.
Parathyroid hormone (PTH) is produced by the parathyroid glands. These are four small glands located on the surface of the thyroid gland. They are the most important regulators of calcium levels in the blood. When calcium levels are low, the glands secrete more PTH, which then increases blood calcium levels. High persistent levels of PTH stimulate bone resorption (bone loss).

Click the icon to see an image of the benefits of vitamin D.

Click the icon to see an image of the sources of vitamin D.

Click the icon to see an image of the parathyroid glands.

Several studies on family members, including twins, have strongly suggested that genetic factors help determine bone density. Some examples include the following:

Of particular interest are genetic factors that affect vitamin D, a critical nutrient for calcium absorption in the body.
Many studies are looking at abnormalities in genes that may cause deficiencies in estrogen receptors, molecules that help estrogen work on cells. Estrogen is important in maintaining bone density in both men and women.

Corticosteroids. More than 30 million Americans have disorders that are commonly treated using corticosteroid drugs (also called glucocorticoids or steroids). Oral corticosteroids can reduce bone mass in both men and women. It is not clear whether inhaled steroids carry the same risks, but some studies indicate that they may cause bone loss when taken at higher doses for long periods of time. (Children on inhaled steroids may have temporary impaired growth, but they do not appear to be at risk for bone loss.)

Antidepressants. Selective serotonin reuptake inhibitors (SSRIs) -- a class of antidepressants that includes fluoxetine (Prozac), paroxetine (Paxil), and sertraline (Zoloft) -- may be associated with bone loss in both older men and women, according to two 2007 studies in the Archives of Internal Medicine. The researchers did not find an increased risk for bone loss with other types of antidepressants.

Diuretics. Diuretics, which are used to treat high blood pressure, have different effects on osteoporosis, depending on the type. Loop diuretics, such as furosemide (Lasix), increase the kidneys’ excretion of calcium, which can lead to thinning bones. Thiazide diuretics, on the other hand, protect against bone loss, but this protective effect ends after use is discontinued.

Contraceptives. Hormonal contraceptives that use progestin without estrogen (such as Depo-Provera injection or other progestin-based contraceptives), can cause loss of bone density. For this reason, the Food and Drug Administration (FDA) recommends that Depo-Provera injections should not be used for longer than 2 years. Some, but not all, studies suggest that combination estrogen-progestin oral contraceptives increase the risk for osteoporosis later in life. Women who take birth control pills should be sure to get adequate calcium and vitamin D from diet or supplements.

Other Medications. Anti-epileptic (anti-seizure) drugs increase the risk for bone loss (as does epilepsy itself). Other drugs that increase the risk for bone loss include the blood-thinning drug heparin, and hormonal drugs that suppress estrogen (such as gonadotropin-releasing hormone agonists). A 2006 study in the Journal of the American Medical Association suggested that long-term (greater than 1 year) use of proton-pump inhibitors (PPIs) may increase the risk for hip fractures. PPIs are used to treat gastroesophageal reflux disease (heartburn) and include omeprazole (Prilosec), lansoprazole (Prevacid), and esomeprazole (Nexium).

Predisposing Medical Conditions. Osteoporosis can be secondary to several other conditions, including alcoholism, diabetes, hyperthyroidism, epilepsy, chronic liver or kidney disease, celiac disease, scurvy, rheumatoid arthritis, leukemia, cirrhosis, gastrointestinal diseases, vitamin D deficiency, hypogonadism (impaired development of reproductive organs), lymphoma, hyperparathyroidism, and rare genetic disorders such as Marfan and Ehlers-Danlos syndrome.

Symptoms

Many people confuse osteoporosis with arthritis and believe they can wait for symptoms such as swelling and joint pain to occur before seeing a doctor. However, the mechanisms that cause arthritis are entirely different from those in osteoporosis. Osteoporosis usually becomes quite advanced before symptoms appear.

All too often, osteoporosis becomes apparent in dramatic fashion: a fracture of a vertebra (backbone), hip, forearm, or any bony site if sufficient bone mass is lost. These fractures frequently occur after apparently minor trauma, such as bending over, lifting, jumping, or falling from the standing position.

Pain, disfigurement, and debilitation are common in the latter stages of the disease. Early spinal compression fractures may go undetected for a long time, but after a large percentage of calcium has been lost, the vertebrae in the spine start to collapse, gradually causing a stooped posture called kyphosis, or a "dowager’s hump." Although this is usually painless, patients may lose as much as 6 inches in height.

Click the icon to see an image of osteoporosis.

Fractures

Bone density loss from osteoporosis is a major cause of disability and death in the elderly, mostly due to subsequent fractures. The lifetime risk of spinal fracture in women is about one in three, and that for hip fracture is one in six. Women at highest risk for fractures are those with low bone density plus a history of fractures, particularly nonviolent fractures.

Click the icon to see an animation about osteoporosis.

Each year, there are an estimated 500,000 spinal fractures, 300,000 hip fractures, 200,000 broken wrists and 300,000 fractures of other bones. About 80% of these fractures occur after relatively minor falls or accidents.

Between 25 - 60% of women older than age 60 develop spinal compression fractures. Studies on men with osteoporosis report that they have a 6% risk for hip fracture and between 16 - 25% risk for any fractures related to osteoporosis.

Click the icon to see an image of a compression fracture.

Click the icon to see an image of a hip fracture.

Unfortunately, studies continue to report inadequate treatment after a fracture. In a major 2003 study, for example, only 8.4% of women who had sustained fractures were tested for osteoporosis. Worse, less than half of these women received any treatment for osteoporosis. Overall, in the study fewer than 4% of men and half of women who had sustained fractures were evaluated and treated according to recommended guidelines. The older a woman was, the less likely she was to have adequate treatment.

Risk Factors for Fracture and Falling. The risk for fracture itself in people with low bone density is compounded by certain features. Having multiple risk factors for osteoporosis itself poses a higher risk for fractures. However, not all older women with osteoporosis develop fractures. There is some evidence that the body partially compensates after menopause by increasing bone strength, which can help offset the risk for fracture.

Falling, of course, is the primary risk factor for fracture. So, additional risk factors for fracture are those that increase the risk for falling. They include:

Having chronic medical problems (emphysema, heart disease, stroke, arthritis, and depression), with the risk increasing with multiple health problems. Such problems may account for 30% of falls in older women.
Taking multiple medications (especially tranquilizers and antidepressants).
Poor physical function, importantly slow gait and reduced muscle strength. Inactivity that results in weak thigh muscles and poor balance particularly puts any older person at risk for fracture and particularly those with low bone density.
Poor concentration or mental impairment.
Impaired vision.
Hazardous environment (such as the presence of throw rugs in the house).

Between 25 - 36% of women who experience a hip fracture die within a year afterward, and about a quarter of the patients require nursing home treatment. The mortality rates after major fractures may be even higher in older men than in older women. Mortality rates after hip fractures declined from the 1960s through the early 1980s, but they have since leveled off. Whether or not medical advances can improve mortality rates in the future, prevention of osteoporosis is extremely important.

Risk Factors

Gender. An estimated 10 million adults in the United States have osteoporosis and another 34 million have low bone mass that places them at risk for developing osteoporosis. A 2004 report from the Surgeon General's office estimates that by 2020, half of all Americans over age 50 could be at risk for this condition. Eighty percent of people with osteoporosis are women. Men start with higher bone density and lose calcium at a slower rate than women, which is why their risk is far lower. Nevertheless, after age 50, bone loss increases and, according to recent studies, more rapidly than previously thought.

Ethnicity. Although adults from all ethnic groups are susceptible to developing osteoporosis, Caucasian and Asian women and men face a comparatively greater risk. About 20% of non-Hispanic white and Asian women older than age 50 have osteoporosis, and over 50% are at risk due to low bone mass. Osteoporosis affects 10% of Hispanic women (49% at risk) and 5% of non-Hispanic black women (35% at risk). Body type can also be a factor. Osteoporosis is more common in women who have a small, thin body frame and bone structure.

Events associated with estrogen deficiencies are the primary risk factors for osteoporosis in women.

Natural and Surgical Causes of Estrogen Deficiency.

Menopause. Within 5 years after menopause, the risk for fracture increases dramatically. Fractures occurring during this period are more likely to occur in the wrist or spine than the hip, but their occurrence is a strong predictor of later severe osteoporosis and hip fracture.
Surgical removal of ovaries.
Missing periods for 3 months or longer.
Never giving birth.
Pregnancy and nursing do not increase the risk for osteoporosis even though during those times calcium is diverted from the mother to the baby. A factor believed to be associated with reduced bone density is elevated at a constant level during nursing, but as the baby is weaned, levels of the factor decline and bone formation is restored.

Female Athlete Triad. In athletes, excessive exercise plays a major role in many cases of anorexia (and, to a lesser degree, bulimia), which in turn increases the risk for low estrogen levels and bone loss. The term "female athlete triad" in fact, is now a common and serious disorder facing young female athletes and dancers and describes the combined presence of the following problems:

Osteoporosis
Amenorrhea (absence or irregular menstruation)
Eating disorders

Some specific risk factors in men include:

Hormonal deficiencies, including both testosterone and estrogen, which occur in older men (although much more slowly than in women). Estrogen deficiencies may also play a major role in osteoporosis in older men. It is unknown yet what normal estrogen levels are in men.
Medical conditions that can reduce testosterone levels, such as prostate cancer treatments, testicular surgery, and mumps.
Hypogonadism, which is a severe deficiency in the primary hormone that signals the process leading to the release of testosterone and other important reproductive hormones.

Of concern, are studies suggesting that men who have osteoporosis and suffer hip fractures are far less likely to be tested and treated for low bone density than are women. In one study, only 27% of men were treated for osteoporosis compared to 71% of women.

Dietary Factors. Diet plays an important role in preventing and speeding up bone loss in men and women. Calcium and vitamin D deficiencies, of course, are important factors in the risk for osteoporosis. Other dietary factors may also be harmful or protective for certain people.

Calcium requires adequate vitamin D in order to be absorbed by the body. In the United States, many food sources of calcium such as milk are fortified with vitamin D.

Click the icon to see an image of the sources of calcium.

Lack of Exercise. Lack of exercise can put thinner people at risk for osteoporosis.

Being Underweight. Being underweight is a risk factor for osteoporosis in men as well as women. (Shortness, thinness, and narrow hips all increase the risk for fracture in people with low bone density.)

Lack of Sunlight. The photochemical effect of sunlight on the skin is a primary source for vitamin D. Bone formation peaks in the summer and bone breakdown increases in the winter. People who avoid sun exposure to prevent skin cancer may be at risk for vitamin D deficiency, particularly it they are elderly.

Click the icon to see an image of the sources of vitamin D.

Smoking. Women who smoke, particularly after menopause, have a significantly greater chance of spine and hip fractures than those who don’t smoke. Men who smoke also have lower bone density.

Diabetes. Diabetes changes bone quality and density and increases the risk for osteoporosis, but the effects differ depending on type:

Type 1 diabetes is associated with a slightly reduced bone density, putting patients at risk for osteoporosis and possibly fracture.
Type 2 diabetes, on the other hand, is associated with an increased bone density. In such cases, the bone quality itself may be impaired, since people with type 2 diabetes are still at higher risk for fractures.

Older patients with any diabetes type are at high risk for falling, which compounds the risk for fracture.

The maximum density that bones achieved during the growing years is a major factor in whether a person goes on to develop osteoporosis. Persons, usually women, who never develop peak bone mass in early life are at high risk for osteoporosis later on. Children at risk for low peak bone mass include children who are:

Born prematurely
Have anorexia nervosa (more common in girls)
Young, highly competitive athletes
Take oral corticosteroid drugs (inhaled steroids, which are common in asthma treatments, appear to pose a very low risk or none at all)
Have certain medical conditions (cystic fibrosis, epilepsy, inflammatory bowel disease, and celiac disease)
Have delayed puberty

Although to a large extent genetics predict bone health, exercise and good nutrition during the first three decades of life (when peak bone mass is reached) are still excellent safeguards against osteoporosis (and countless other health problems).

Diagnosis

About 20 - 30% of Caucasian women in the U.S. can expect to be affected by osteoporosis, including having a spinal fracture, after age 60. Hispanic, Asian, and Native American women have an even higher risk. Nearly all of them are unaware of the condition and so fail to seek a diagnosis. Even worse, studies continue to report inadequate evaluation for osteoporosis even after a fracture.

Evidence suggests that screening for osteoporosis can help prevent fractures. Expert groups now recommend bone density screening for the following people:

All women over age 65.
Any postmenopausal women under 65 years with risk factors for osteoporosis (being thin, being a smoker, having a family history of osteoporosis, corticosteroids use, or any serious high-risk condition, such as hyperthyroidism or early menopause).
Any older men or women who suffer a fracture. (Unfortunately, studies suggest that only a minority of these patients are evaluated and treated for osteoporosis. Men are especially less likely to be tested.)

Whether perimenopausal women should be screened is unclear. (Perimenopause is the period that extends a few years before and after menopause, usually ages 50 - 59.) Some experts believe that women as young as 21 who have strong risk factors for osteoporosis (such as anorexia or absence of menstruation due to over-exercising) should consider being tested. It is also important that older women continue to get bone density tests. A 2006 study found that only 10% of women over age 75 receive bone density screenings, even though they are the age group most likely to have hip fractures.

Bone Densitometry. The standard technique for determining bone density is a form of bone densitometry called dual-energy x-ray absorptiometry (DEXA). DEXA is simple and painless and takes 2 - 4 minutes. The machine measures bone density by detecting the extent to which bones absorb photons that are generated by very low-level x-rays. (Photons are atomic particles with no charge.) Measurements of bone mineral density are generally given as the average concentrations of calcium in areas that are scanned.

A bone density scan measures the density of bone in a person. The lower the density of a bone the higher the risk of fractures. A bone scan, along with a patient's medical history, is a useful aid in evaluating the probability of a fracture and whether any preventative treatment is needed. A bone density scan has the advantage of being painless and exposing the patient to only a small amount of radiation.

Bone mineral density is usually measured at the hip rather than the spine or wrist, which appears to be the most predictive of hip fracture. (Hip fractures are the most dangerous fractures, particularly in women older than sixty.) The bone density in the spine may also be measured. (Spinal bone density in older people however may be misleading. Bone density in this group may increase because of compression on the spinal bones from arthritic changes in the spine. Therefore, bone density measurements may be normal or even high, but the patient may actually be at risk for fracture.)

Click the icon to see an image of a hip fracture.

Ultrasound. Ultrasound techniques measure bone density in the heels, fingers, and leg bones. In early studies, advanced ultrasound techniques, such as quantitative ultrasound (QUS), are promising for improving accuracy in predicting fractures when used with DEXA. Ultrasound itself is less expensive than DEXA and uses no radiation. Ultrasound bone tests are sometimes given at health fairs or other non-medical settings. It should be noted that these results typically vary widely from measurements of the hipbone and are not reliable when used alone.

Quantitative Computed Tomography. Quantitative computed tomography (QCT) scans, a form of CT scans, can provide highly detailed information about spinal density. Radiation doses from this technique are higher than the others. Whether QCT predicts fracture risk accurately is, however, unknown.

Osteoporosis is diagnosed when bone density has decreased to the point where fractures will happen with mild stress, the so-called fracture threshold. This is determined by measuring bone density and comparing the results with the norm. However, low scores on bone density are not very accurate in determining fracture risk without consideration of other risk factors for fracture.

In general, doctors take the following steps to determine osteoporosis:

Bone mineral density ) is measured, typically in the hipbone, using bone densitometry.
Measurements of bone mineral density are given as mg/cm.² This is the average concentration of bone mineral in the areas that are being scanned. In general, bone is normal if results are greater than 833 mg/cm.² Low bone density (osteopenia) is between 833 and 648 mg/cm.² Osteoporosis is diagnosed with results below 648 mg/cm.²

These measurements still do not always indicate the true risk for fracture. The doctor also assesses risk factors and other considerations. The next step is to compare the patient's bone mineral density to normal bone density, which is defined as the average bone mineral density in the hipbones of premenopausal Caucasian women. (This group is used as the basis for the norm because of their high risk and greater proportion in the American population.)

The health professional then uses this comparison to determine her standard deviation (SD) from this norm. Standard deviation results are given as Z and T scores:

A T score gives the standard deviation of the patient in relationship to the norm in young adults. Doctors often use the T-score and other risk factors to determine the risk for fracture.
A Z score gives the standard deviation of the patient in relationship to the norm in her own age group. Z scores may be used to monitor the effects of treatments in women who have been diagnosed with osteoporosis.

For example, the lifetime risks for a younger woman with a specific T-score would be higher than the same scores in an older woman because the younger woman would have a longer time to lose bone density. In general, the T scores in a 55-year-old woman suggest the following degrees of risk for hip fracture.

One standard deviation or less below the norm indicates normal bone mineral density. (This carries a lifetime chance for a hip fracture of up to about 20%, depending on age and other risk factors.)
Between 1 and 2.5 standard deviation s below normal defines osteopenia, which is low bone density. This carries between a 20 - 50% lifetime risk for fracture.
More than 2.5 standard deviation s predicts osteoporosis and over a 60% chance for hip fracture. Additional risk factors increase the risk. They include low weight, smoking, risks for falling, and especially a history of previous fractures. For example, in women 65 years old with low bone density but no adverse factors, the risk for fracture is 4.3% in 1 year and 28.6% over 5 years. In similar women with a previous fracture, the probability of fracture at 1 year is 11% and at 5 years is 71.8%.

Not all older women with osteoporosis develop fractures. There is some evidence that the body partially compensates after menopause by increasing bone strength, which can help offset the risk for fracture. Techniques to measure bone strength may better identify women at higher or lower risk.

Note: Because the standards are based on Caucasian women, they do not necessarily apply to men, children, or to non-Caucasian women. For example, men have a lower risk for fracture at the same standard deviations as women. Researchers are attempting to establish risk guidelines for these groups as well.

Laboratory blood or urine tests for identifying certain markers of bone loss may prove to be useful in certain cases:

High levels of the chemicals deoxypyridinoline and C-telopeptide in the blood may indicate increased risk for hip fracture. These substances are produced when bone is broken down.
A urine test detecting a substance called N-telopeptide may indicate bone loss (although it is not associated with any risk for fracture).

Lifestyle Changes

Because osteoporosis affects such a considerable portion of the female population, total prevention may not be possible, particularly for high-risk groups. Once a woman goes through menopause and more rapid bone depletion occurs, the line between prevention and treatment blurs. Despite their lower risk for osteoporosis, men should also protect their bones with the same healthy lifestyle habits.

Exercise is very important for slowing the progression of osteoporosis. Although mild exercise does not protect bones, moderate exercise (more than 3 days a week for more than a total of 90 minutes a week) reduces the risk for osteoporosis and fracture in both older men and women. Everyone who is in good health should aim for more. Exercise should be regular and life-long. Before beginning any strenuous exercise program, older patients, those at risk or those who have serious medical conditions, should talk to their doctors.

Specific exercises may be better than others, depending on the age group:

Children should begin exercising before adolescence, since bone mass increases during puberty and reaches its peak between ages 20 and 30. Some evidence suggests that exercise may help develop bone mass in teenagers more effectively than high calcium intake. High-intensity exercises may be particularly bone-strengthening in young people. (Such regimes should not be confused with the athlete-triad -- intense competitive exercise, eating disorders, and menstrual irregularities -- that causes osteoporosis in young athletes.)
Weight-bearing exercise applies tension to muscle and bone and, in young people, encourages the body to compensate for the added stress, increasing bone density by as much as 2 - 8% a year. In premenopausal women these exercises are very protective. (Young men need high-intensity exercises to increase bone mass.) Careful weight training is also very beneficial for elderly people, especially women.
Regular brisk long walks improve bone density and mobility and may relieve osteoarthritic pain. High-impact exercises can be very bone-protective in young and middle-aged adults who have no precluding medical or physical conditions. Most older individuals should avoid high-impact aerobic exercises (step aerobics), which increase the risk for osteoporotic fractures. (Older people, particularly women who engage in jumping exercises should do so under supervision.) Although low-impact aerobic exercises such as swimming and bicycling do not increase bone density, they are excellent for cardiovascular fitness and should be part of a regular regimen.
Exercises specifically targeted to strengthen the back help prevent fractures later on in life and can be beneficial in improving posture and reducing kyphosis (hunchback), even in people with existing severe conditions.
Low-impact exercises that improve concentration, balance, and strength, particularly yoga and tai chi, have been found to decrease the risk of falling. In one study, tai chi reduced the risk of falling by almost half.

Exercise plays an important role in the retention of bone density in the aging person. Studies show that exercises requiring muscles to pull on bones cause the bones to retain and possibly gain density.

Click the icon to see an image of osteoporosis.

In 2007, the Food and Drug Administration (FDA) proposed a new health claim for foods and dietary supplements that contain calcium and vitamin D. The FDA’s recommendation will allow manufacturers of these products to state that the combination of calcium and vitamin D can reduce the risk of osteoporosis. Also in 2007, the National Osteoporosis Foundation (NOF) updated its recommendations for getting enough calcium and vitamin D3. The NOF now recommends 1,200 mg of calcium/day and 800 - 1,200 I.U. of vitamin D3/day for adults age 50 and older. (For strong bones, people need enough of both calcium and vitamin D.)

For years, doctors have recommended that women take supplements of calcium plus vitamin D to help maintain bone density and reduce the risk for fractures. Many studies, including a 2007 review in the Lancet, show that a combination of calcium and vitamin D can help prevent osteoporosis. However, a 2006 New England Journal of Medicine study raised some questions about this approach. In the Women’s Health Initiative study, women were randomly assigned to receive either 1,000 mg of calcium carbonate plus 400 IU of vitamin D a day or placebo. The results indicated that daily calcium and vitamin D supplements:

Improve slightly (by 1%) hip bone density
Prevent hip fracture, but only for women who consistently take the supplements. (Another 2006 study supported this finding.)
Do not prevent spine or other types of fractures
Produce a slight increase in the risk of kidney stones

Appropriate Daily Doses. Recommended daily amounts of calcium depend on age and risk factors:

In young people, children ages 3 - 8 should take 800 mg of calcium per day, while children and adolescents ages 9 - 17 need 1,300 mg per day. Teenage girls who do not have enough calcium in their diets should consider taking supplements, which can help build bone density during these critical years.
The standard recommended dose for people over age 50 is about 1,200 mg per day, but actual dosage may be higher or lower depending on risk factors. Even doses of 1,000 mg may help preserve bone in many postmenopausal women without osteoporosis, including during winter months (when bone loss is greatest). In women who have already experienced osteoporosis-related fractures, however, 1,000 mg daily may not add any protective benefits without bone-building medication.
Some experts suggest that all pregnant women, adolescents, and those on corticosteroids take 1,000 - 1,300 mg of calcium every day.
Breast-feeding women should have 2,000 mg per day.

Forms of Calcium Supplements. There are several different kinds of calcium supplements, such as calcium carbonate (Caltrate, Os-Cal, Tums), calcium citrate (Citracal), calcium gluconate, and calcium lactate. Although each kind provides calcium, they all have different calcium concentrations, absorption capabilities, and other actions. Their value in preserving bones depends on many different factors:

Calcium Concentrations. Forty percent of calcium carbonate is actually calcium, whereas calcium citrate is 24% calcium, and calcium gluconate is only 9% calcium.
Calcium Absorption Capabilities. The calcium must also be absorbed from the stomach into the bloodstream. Calcium citrate is better absorbed than many other calcium compounds. It was reported to be the first calcium supplement to preserve bone density after menopause. (Calcium citrate also increases iron absorption. Milk and other calcium compounds tend to reduce iron absorption.) One simple method for testing the absorbency of a particular brand of calcium tablet is to place it in a glass of white vinegar at full strength and check to be sure that it breaks up within 30 minutes. Taking large amounts of antacids can impair calcium absorption. People should take calcium supplements after meals.

Side Effects. Calcium supplements, even at normal doses of about 1,000 mg a day, can increase the risk for kidney stones. People should be careful not to exceed the upper limit of 2,500 mg per day. (Because many commercial foods are now fortified with calcium, this upper limit may be easier to reach than people think.) Calcium may boost the effects of drugs used to treat osteoporosis.

Click the icon to see an image of kidney stones.

Although not a specific side effect of calcium, there has been much public concern about reports of a small amount of lead in calcium supplements. Although exposure to high levels of lead can cause health problems, the amount in such supplements is very small and may pose little or no hazard.

Vitamin D. Vitamin D helps the stomach and the gastrointestinal tract absorb calcium. It also is the essential companion to calcium in maintaining strong bones. Moreover, vitamin D protects against osteoporosis only in combination with calcium.

Click the icon to see an image of the benefits of vitamin D.

Vitamin D is made in the skin using energy from the ultraviolet rays in sunlight. People also can get it from dietary supplements.

As a person ages, vitamin D levels decline. They also fall during winter months and when people have inadequate sunlight. Pollution may also contribute to less sunlight and declining vitamin D levels.

Click the icon to see an image of the sources of vitamin D.

Most current adult guidelines recommend:

400 IU (10 mcg) for people aged 50 - 60.
600 IU (15 mcg) for those over age 70 who do not have sufficient exposure to sunlight. (Evidence suggests that higher doses of vitamin D -- up to 1,000 IU per day -- may help prevent fractures in people with osteoporosis.)

There are various recommendations for daily vitamin D intake. In 2007, the National Osteoporosis Foundation updated its guidelines to recommend 400 - 800 IU of vitamin D3 for adults younger than age 50, and 800 - 1,000 IU of vitamin D3 for adults age 50 and older. Vitamin D3, also called cholecalciferol, is the form of vitamin D that is best for bone health. In addition to supplements, food sources for vitamin D3 include fortified milk, egg yolks, saltwater fish, and liver.

In 2007, the U.S. National Institute of Health’s Office of Dietary Supplements released a report regarding vitamin D and bone health. Researchers were not able to definitely separate the effect of vitamin D from that of calcium, as most clinical trials evaluate the combination of these supplements. The report did indicate that a combination of daily vitamin D3 (700 - 800 IU) and calcium (500 - 1,200 mg) decreases the risks of falls, fractures, and bone loss in elderly people (ages 62 - 85 years).

Sufficient sunlight exposure and drinking milk fortified with vitamin D supply most people’s normal needs for vitamin D. One cup of whole milk provides about 100 IU of vitamin D.

Vitamin D is toxic in doses above 2,000 IU a day. No one should exceed the recommended daily intake of vitamin D except under the direction of a doctor.

Many people could become deficient in vitamin D as they avoid sunlight to prevent skin cancers and instead increase their intake of milk products, such as yogurt and skim milk, which may have little vitamin D. Such individuals may need to take supplements. People with darker skin have a higher risk for vitamin D deficiency than those with lighter skin.

Vitamin D derivatives are being investigated for treating osteoporosis. Calcitriol (Calcijex, Rocaltrol), for example, is a prescription-form of vitamin D that can increase bone mass and decrease the rate of spinal fractures. However, calcitriol increases the risk for high blood calcium levels (hypercalcemia) and requires frequent monitoring.

Vitamin K. Vitamin K has properties that protect bone and prevent fracture. Because intestinal bacteria produce vitamin K, and the vitamin is found in leafy vegetables, deficiencies are rare. Some evidence suggests, however, that people may not be consuming enough of this nutrient. Vitamin K affects blood clotting, and taking supplements is not recommended without first talking to a doctor. Vitamin K2 (menatetrenone), a form of vitamin K, may help prevent fractures in people with osteoporosis.

Click the icon to see an image of the benefits of vitamin K.

Click the icon to see an image of the sources of vitamin K.

Vitamin B12. Studies suggest that people need the right amounts of vitamin B12 and folic acid to maintain their bone mineral density.

Vitamin A. High amounts of dietary vitamin A reduce bone density and may even increase the risk for fracture in postmenopausal women. (A form of vitamin A, retinoic acid, has been found to stimulate bone breakdown.)

The DASH Diet and Low Sodium. Perhaps a good general approach for people at risk for osteoporosis (or almost any adult) is the DASH diet plus sodium (salt) restriction. The DASH (Dietary Approaches to Stop Hypertension) diet is used to help people with hypertension maintain healthy blood pressures. A 2003 study also reported that it might help protect bones and improve cholesterol levels. This diet not only is rich in important nutrients and fiber but also includes foods that contain far more potassium, calcium, and magnesium, than are found in the average American diet. All of these minerals are important for bone protection. The dietary recommendations are as follows:

Avoid saturated fat (although include calcium-rich dairy products that are no- or low-fat). When choosing fats, select monounsaturated oils, such as olive or canola oils. These fats are also found in some fish. Although no one wants to be overweight, even a slight excess of fat helps protect bones. In one study, women who ate more fat in their diet were, on average, better able to absorb calcium than were women who had been put on a low-fat, high-fiber diet.
Choose whole grains over white flour or pasta products. Include nuts, seeds, or legumes (dried beans or peas) daily.
Choose fresh fruits and vegetables every day. Many of these foods are rich in potassium, magnesium, and other minerals that are important for bone (as well as heart) protection.
Choose protein preferably from fish, poultry, or soy products. Soy in combination with fiber-rich foods or supplements may have specific benefits. Oily fish may also be particularly beneficial. They contain omega-3 fatty acids, which have been associated with heart and nerve protection.

Salt Restriction. Reducing salt may protect both the heart and the bones. High sodium intake interferes with calcium retention. Note: Fast foods and commercial snacks are usually high in sodium and have been linked with weak bones.

Dairy Products and Calcium-Rich Foods. Although some studies have reported that dairy products benefit the bones, it is not entirely clear if high-calcium diets reduce the risk for fractures compared to adequate intake of vitamin D. Until more is known, people should be sure their diets have sufficient calcium. Dietary calcium is available from many good sources.

Milk and Dairy Products. The best source of calcium in the diet is from milk fortified with vitamin D. Four glasses of milk provide about 1,200 mg of calcium. (Skim milk and yogurt products, unfortunately, are often low in vitamin D, which is important for calcium absorption.) According to a 2003 study, girls who have low milk intake increase their risk for fracture in adulthood. One report even suggests that milk proteins actually slow bone break down. It is not clear, however, if drinking milk after menopause offers any significant bone protection.
Other Calcium-Rich Foods. Other calcium-rich foods include shrimp, canned salmon or sardines, black strap molasses, calcium-fortified tofu, and almonds. A number of commercial foods, including orange juice and some cereals, are now calcium fortified. Dark green vegetables (broccoli, kale, turnip greens) are rich in calcium but little of it is absorbed (kale is best).

Click the icon to see an image of milk and the facial bones.

Mineral-Rich Fruits and Vegetables.

Potassium. Potassium may be very important for strong bones and may help counteract negative effects of high-protein diets. Potassium-rich fruits include bananas, oranges, prunes, and cantaloupes, and vegetables that contain potassium include carrots, spinach, celery, alfalfa, mushrooms, lima beans, potatoes, avocados, and broccoli.
Magnesium. Some studies have observed that low levels of magnesium may contribute to thinning bones. Some studies suggest that magnesium supplements help suppress the cycle that leads to bone loss. Experts recommend 350 mg a day for supplements. However, excessive magnesium may be harmful in people with diabetes or kidney disease. Foods rich in magnesium include dairy products, spinach, potatoes, beets, nuts, sole, and halibut.
Other Minerals. Phosphorous, boron, and zinc have also been associated with bone protection.

Protein. Protein may be important for frail older people for improving muscle strength. Researchers, meanwhile, have associated both low and high protein intake with bone loss. Protein deficiencies appear to trigger hormonal changes that increase bone breakdown. On the other hand, high protein intake increases urinary calcium loss, which can impair bone density in people with low-calcium diets. High-protein diets, however, do not appear to cause bone loss if calcium intake is also high. The bottom line is to eat enough protein but to balance it with plenty of calcium-rich, and other mineral-rich, foods.

The protein source (meat, soy, or fish) may have some effect on bone density, although the effects are not clear. Studies are mixed on whether protein from meat has a positive or negative effect on bone loss. In any case, the best sources of protein for bone protection may be from oily fish or soy.

Choosing protein from fish (especially oily fish such as sardines, salmon, mackerel, fresh tuna, and herring) is a good option. Oily fish are high in vitamin D, which is bone protective. Such fish are also heart protective. Wild salmon has a much higher vitamin D content than farmed salmon. American brands of canned tuna, meanwhile, generally do not contain significant amounts of vitamin D.
Soy may have some modest protection against bone loss. Soy is high in estrogen-like plant chemicals called isoflavones, which may improve bone health in older women. In particular, the isoflavone genistein is being studied for its effects on bone health. A small 2007 study indicated that genistein supplements, when taken with vitamin D and calcium, may help improve bone density in postmenopausal women with thinning bones. (However, other studies indicate that soy has no effect on bone density in healthy premenopausal women.) Soy food products that also contain calcium, such as tofu, may be particularly beneficial. In such cases, 3 ounces of tofu supply 60% of daily calcium requirements.

Alcohol. Alcohol has different effects on bones depending on how much is consumed. One study found that women older than age 65 who drank one to two drinks (1 - 2 oz) of alcohol weekly had higher bone density than non-drinkers. Alcohol in moderate amounts may reduce parathyroid hormone and increase estrogen levels. Excessive drinking, however, has been associated with brittle bones.

Cola, Coffee, Tea and Caffeine. One study suggested that drinking tea regularly may help protect bones. Nevertheless, there has been some concern that caffeine consumption, particularly from coffee, may increase calcium levels in urine and reduce levels in the body. In one trial, consumption of lots of coffee (9 or more cups per day) was associated with an increased risk of hip fractures in women, but not in men. However, not all studies support a risk. Some evidence suggests that caffeine may pose a danger for bone loss only in elderly thin women -- but not in those who have normal or high weight. Drinking carbonated beverages, particularly cola, may increase the risk for bone fractures in people with low bone density.

Everyone who smokes should quit. The risk for osteoporosis from smoking appears to diminish after quitting.

An important component in reducing the risk for fractures is preventing falls. Risk factors for falling include:

Slow walking
Inability to walk in a straight line
Certain medications (such as tranquilizers and sleeping pills)
Low blood pressure when rising in the morning
Poor vision

Recommendations for preventing falls or fractures from falls in elderly people include:

Exercise to maintain strength and balance if there are no conflicting medical conditions. In one study of older people, this was the single best intervention for preventing falls.
Do not use loose rugs on the floors.
Move any obstructions to walking, such as loose cords or very low pieces of furniture, away from traveled areas.
Rooms should be well lit.
Have regular eye checkups.
Try wearing hip pads. Hip pads are specially designed to protect hipbones against falls and are worn under clothing. Evidence on their protection against fractures is weak, however, particularly since compliance is poor. Nevertheless, newer hip pads that are thinner and made with newer materials may be helpful and more appealing.
Wear thinner, hard-soled shoes. Studies indicate these shoes are just as comfortable as the popular resilient-soled footwear, but they may be difficult to find. Soft-soled high-resilient so-called athletic footwear may contribute to impaired balance and dangerous falls, in part, because these cushioned shoes offer less stability.

Medications

Many drugs are available to treat osteoporosis. Unfortunately, studies continue to report that doctors fail to evaluate and adequately treat both men and women for this condition, even after a fracture. According to one study of women over age 60, fewer than 2% were evaluated for osteoporosis or spinal fracture by their doctors. Among those who were diagnosed, only 36% received appropriate medication. Among adults who had sustained fractures, less than 5% of men and fewer than half of women were evaluated and treated according to recommended guidelines, indicated two other studies. In one of the studies, only 24% of women received treatment for osteoporosis after a fracture. In both studies, the older a woman was, the less likely she was to have adequate evaluation or treatment.

Drugs Used to Treat Osteoporosis. Two types of drugs are used to treat osteoporosis:

Antiresorptive Drugs. Antiresorptives include bisphosphonates, hormone replacement therapy, selective estrogen-receptor modulators (SERMs), and calcitonin. Bisphosphonates are the standard drugs used for osteoporosis. These drugs block resorption (preventing bone break down), which slows the rate of bone remodeling, but they cannot rebuild bone. Because resorption and reformation occur naturally as a continuous process, blocking resorption may eventually also reduce bone formation.
Anabolic, or Bone-Forming, Drugs. Drugs that rebuild bone are known as anabolics. The primary anabolic drug is low-dose parathyroid hormone (PTH), which is administered through injections. This medicine is proving to be very effective in restoring bone and preventing fractions. PTH is still relatively new, and long-term effects are still unknown. Fluoride is another bone-building drug, but it has limitations and is not commonly used.

Both types of drugs are effective in preventing bone loss and fractures, although they vary in their effectiveness and safety.

Bisphosphonates are antiresorptive drugs. They are the primary drugs for preventing and treating osteoporosis. They can help reduce the risk of both spinal and hip fractures, including among patients with prior bone breaks.

Studies indicate that these drugs are effective and safe for at least 10 years. Eventually, however, bone loss continues with bisphosphonates. This may be due to the fact that bone breakdown is one of two phases in a continuous process of rebuilding bone. Over time, just blocking resorption will interrupt this process and impair the second half of the process -- bone formation. Some researchers think that this problem may be overcome by building bone for a couple of years with parathyroid hormone (PTH), then following this treatment with bisphosphonates to prevent the breakdown of bone. (Administering the two drugs simultaneously is not effective because bisphosphonates interfere with the way PTH works.)

A 2006 study of the bisphosphonate alendronate (Fosamax), the most widely used osteoporosis drug, indicated that women at low risk for fracture may be able to stop using the drug after 5 years without increasing their fracture risk for another 5 years. However, the Journal of the American Medical Association study also suggested that it is safer for women at high risk for spine fractures to keep taking alendronate on a continuous basis.

Candidates. National Osteoporosis Foundation guidelines recommend that the following people should take or consider bisphosphonates:

Women with a below-normal bone density of 2.5 standard deviation or greater and no history of fractures
Women with below-normal bone density 1 standard deviation or more and a history of fractures

Brands. Bisphosphonates are available in different forms:

Oral bisphosphonates. These pills include alendronate (Fosamax), risedronate (Actonel), and ibandronate (Boniva). Alendronate and risedronate are taken once a week. In 2005, ibandronate was approved as the first once-monthly pill. Risedronate is also available in a pill that contains calcium. Risedronate and alendronate are approved for both men and women.
Injectable bisphosphonates. In 2007, zoledronic acid (Reclast) was approved as the first once-yearly injection treatment for osteoporosis. The injectable form of ibandronate (Boniva), approved in 2006, requires injections 4 times a year. Injectable bisphosphonates are an alternative for patients who may have difficulty swallowing pills or sitting upright after oral bisphosphonate treatment.

Side Effects. The most distressing side effects of bisphosphonates are gastrointestinal problems, particularly stomach cramps and heartburn. These symptoms are very common and occur in nearly half of all patients. Other side effects may include irritation of the esophagus (the tube that connects the mouth to the stomach) and ulcers in the esophagus or stomach. Some patients may experience muscle and joint pain. To avoid stomach problems, doctors recommend:

Take the pill on an empty stomach in the morning with 6 - 8 ounces of water (not juice or carbonated or mineral water).
After taking the pill, remain in an upright position. Do not eat or drink for at least 30 - 60 minutes. (Check your drug’s dosing instructions for exact time.)
If you develop chest pain, heartburn, or difficulty swallowing, stop taking the drug and see your doctor.

Osteonecrosis (bone death) of the jaw is a rare side effect that has occurred mainly in patients who received intravenous bisphosphonates for cancer treatment (not osteoporosis). Many of these patients had major dental procedures before developing osteonecrosis. However, this bone decay condition has also been reported in some patients who have taken bisphosphonates by mouth (mainly alendronate). Symptoms may include jaw pain or swelling, gum infections, and poor healing of the gums. Talk to your doctor or dentist if you experience any jaw or gum discomfort while taking a bisphosphonate drug.

Raloxifene (Evista) belongs to a class of drugs called selective estrogen-receptor modulators (SERMs). These drugs are similar, but not identical, to estrogen. Raloxifene provides the bone benefits of estrogen without increasing the risks for estrogen-related breast and uterine cancers. Raloxifene was approved in 1997 to prevent osteoporosis in postmenopausal women, and in 1999 for the treatment of osteoporosis in postmenopausal women. In 2007, the Food and Drug Administration approved raloxifene for prevention of breast cancer in postmenopausal women with osteoporosis, as well as postmenopausal women at high risk for invasive breast cancer.

While there are many SERM drugs, raloxifene is the only one approved for both treatment and prevention of osteoporosis. Only postmenopausal women who have or are at risk for osteoporosis should take this drug. Studies indicate that raloxifene can stop the thinning of bone and help build better quality and stronger bone.

A thrombus is a blood clot that forms in a vessel and remains there. An embolism is a clot that travels from the site where it formed to another location in the body. Thrombi or emboli can lodge in a blood vessel and block the flow of blood in that location, depriving tissues of normal blood flow and oxygen. This can result in damage, destruction (infarction), or even death of the tissues (necrosis) in that area.

Side Effects. Raloxifene increases the risk for blood clots in the veins. Because of this side effect, raloxifene also increases the risk for stroke (but not other types of heart disease). These side effects, though rare, are very serious. Women should not take this drug if they have a history of blood clots, or if they have certain risk factors for stroke and heart disease. More common mild side effects include hot flashes and leg cramps.

Produced by the thyroid gland, natural calcitonin regulates calcium levels by inhibiting the osteoclastic activity, the breakdown of bone. The drug version is derived from salmon and is available as a nasal spray (Miacalcin) and an injected form (Calcimar). Calcitonin is not used to prevent osteoporosis. It treats osteoporosis. It may be effective for spinal protection (but not hip) in both men and women. Calcitonin may be an alternative for patients who cannot take a bisphosphonate or SERM. It also appears to help relieve bone pain associated with established osteoporosis and fracture.

Side Effects. Side effects include headache, dizziness, anorexia, diarrhea, skin rashes, and edema (swelling). The most common adverse effect experienced with the injection is nausea, with or without vomiting. This occurs less often with the nasal spray. The nasal spray may cause nosebleeds, sinusitis, and inflammation of the membranes in the nose. Also, many people who take calcitonin develop resistance or allergic reactions after long-term use.

Although high persistent levels of parathyroid hormone (PTH) can cause osteoporosis, daily injections of low and intermittent doses of this hormone actually stimulate bone production and increase bone mineral density. In clinical studies, teriparatide (Forteo), a drug made from selected amino acids found in parathyroid hormone, reduced the risk for spinal and non-spinal fractures by 50 - 65%. It may prove to be a very useful drug for men with osteoporosis. Unlike most treatments for osteoporosis, including bisphosphonates, the benefits may persist even after the injections have been stopped.

Although the treatment requires injections, researchers are investigating a nasal spray version of PTH. In addition to easing patient discomfort, there is some preliminary evidence that nasal-administered PTH may be better absorbed than injections. Side effects of PTH are generally mild and include nausea, dizziness, and leg cramps. No significant complications have been reported to date.

Early animal studies did report bone tumors in mice that were given parathyroid long-term. Such effects have not been observed in humans to date. However, people with Paget disease, (a disorder in which bone thickens but also, oddly, weakens), should not take parathyroid hormone, since they are at higher than normal risk for bone tumors.

Hormone replacement therapy (HRT) is sometimes used to prevent osteoporosis. A Women’s Health Initiative (WHI) study found that women who received estrogen, or estrogen plus progestin, therapy had fewer fractures than women who received placebo.

However, WHI studies have also shown that estrogen increases the risk for breast cancer, blood clots, strokes, and heart attacks. For this reason, women need to balance the benefits that HRT has on bone-loss protection, with the risks it carries for other serious health conditions. The Food and Drug Administration recommends that women first try other medications for prevention of osteoporosis.

HRT is available in many different forms, including pills and skin patches. [See In-Depth Report #40: Menopause.]

New SERMs. Bazedoxifene (Viviant) is a new selective estrogen receptor modulator (SERM) that is in phase III clinical trials. In research presented at the 2007 annual meeting of the American Society for Bone and Mineral Research (ASBMR), bazedoxifene reduced new cases of non-spine fracture by 52% compared to placebo.
Biologic Drugs. Denosumab is a humanized monoclonal antibody injectable drug currently in phase III studies. It targets the RANK ligand, a protein involved with cells that break down bone (osteoclasts). Results presented at the 2007 ASBMR meeting indicated that denosumab may help increase bone mineral density by as much as 10.6%. Odanacatib is another biologic drug showing promise in phase IIB trials. Odanacatib inhibits cathepsin K, a protein that also plays a role in osteoclast activity.
Strontium. Strontium, a chemical element found in bone, may help increase bone formation and decrease bone resorption. NB S101 is a strontium drug currently in phase II trials.

Treatment

Nonsurgical treatments for fractures include braces, plaster cases, and manipulation of the fracture. Such approaches have not been well studied to determine an optimal method, and patients should discuss all options with their doctors.

Reconstructive surgery is usually used for hip fractures and should be performed within 48 hours, assuming the patient has no other complicating medical conditions. After surgery, the patient should be mobilized within the first day. In one study, protein supplements helped people with hip fractures recover more quickly and reduced bone loss.

Percutaneous vertebroplasty and kyphoplasty are surgical procedures used to lessen pain. Research to date suggests that they are safe and provide pain relief for many patients. In some cases they may increase height. There have been few controlled trials, however, and more research is needed to determine long-term effects.

Percutaneous Vertebroplasty. Percutaneous vertebroplasty involves the injection of a cement-like bone substitute into damaged vertebrae. It is proving useful for stabilizing the spine and relieving pain in patients with spinal compression fractures due to osteoporosis or cancer. Success rates of over 90% have been reported. Serious complications occur in fewer than 1% of cases.

Kyphoplasty. Kyphoplasty is a variant of percutaneous vertebroplasty that may help prevent kyphosis (hunchback) in patients whose spines have collapsed. The procedure inserts a balloon into the fractured vertebrae. As the balloon inflates, the spine is moved upward, to its original location. The balloon is then removed, and the bone and the core of the newly-erect vertebrae are filled with cement. In one 2003 study, short-term symptom relief improved by 70% and was immediate. Long-term effectiveness is not yet known.

Resources

www.nof.org -- National Osteoporosis Foundation
www.niams.nih.gov/Health_Info/Bone -- National Institutes of Health, Osteoporosis and Related Bone Diseases
www.menopause.org -- North American Menopause Society
www.asbmr.org -- American Society for Bone and Mineral Research
www.niams.nih.gov -- National Institute of Arthritis and Musculoskeletal and Skin Diseases

References

Agency for Healthcare Research and Quality. Effectiveness and Safety of Vitamin D in Relation to Bone Health, Structured Abstract. August 2007. Rockville, MD.

Bilezikian JP. Osteonecrosis of the jaw -- do bisphosphonates pose a risk? N Engl J Med. 2006 Nov 30;355(22):2278-81.

Black DM, Delmas PD, Eastell R, Reid IR, Boonen S, Cauley JA, et al. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med. 2007 May 3;356(18):1809-22.

Black DM, Schwartz AV, Ensrud KE, Cauley JA, Levis S, Quandt SA, et al. Effects of continuing or stopping alendronate after 5 years of treatment: the Fracture Intervention Trial Long-term Extension (FLEX): a randomized trial. JAMA. 2006 Dec 27;296(24):2927-38.

Diem SJ, Blackwell TL, Stone KL, Yaffe K, Haney EM, Bliziotes MM, et al. Use of antidepressants and rates of hip bone loss in older women: the study of osteoporotic fractures. Arch Intern Med. 2007 Jun 25;167(12):1240-5.

Haney EM, Chan BK, Diem SJ, Ensrud KE, Cauley JA, Barrett-Connor E, et al. Association of low bone mineral density with selective serotonin reuptake inhibitor use by older men. Arch Intern Med. 2007 Jun 25;167(12):1246-51.

Marini H, Minutoli L, Polito F, Bitto A, Altavilla D, Atteritano M, et al. Effects of the phytoestrogen genistein on bone metabolism in osteopenic postmenopausal women: a randomized trial. Ann Intern Med. 2007 Jun 19;146(12):839-47.

Tang BM, Eslick GD, Nowson C, Smith C, Bensoussan A. Use of calcium or calcium in combination with vitamin D supplementation to prevent fractures and bone loss in people aged 50 years and older: a meta-analysis. Lancet. 2007 Aug 25;370(9588):657-66.

Yang YX, Lewis JD, Epstein S, Metz DC. Long-term proton pump inhibitor therapy and risk of hip fracture. JAMA. 2006 Dec 27;296(24):2947-53.

Review Date:
11/1/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Anemia

FitSugar — Wed, 08 Oct 2008 17:34:56 -0700

In This Report

Highlights
Introduction
Causes
Risk Factors
Complications
Symptoms
Diagnosis
Dietary Factors
Treatment
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

FDA Issues Labeling Changes for Drugs That Boost Red Blood Cells

In November 2007, the U.S. Food and Drug Administration (FDA) made several changes to the prescribing labels for erythropoiesis-stimulating drugs. These drugs -- epoietin alfa (Epogen, Procrit) and darbepoetin alfa (Aranesp) -- increase the production of red blood cells. They are used to treat anemia associated with chronic kidney failure, cancer chemotherapy, and antiretroviral HIV therapy.

The new labels have stronger warnings and updated dosing-related safety information. The FDA advises:

For cancer, erythropoiesis-stimulating drugs are used only to treat anemia associated with chemotherapy. Dosing should increase hemoglobin levels to no more than 12 g/dL. These drugs can shorten survival time and increase tumor growth when hemoglobin levels are raised beyond this point. Treatment should stop as soon as chemotherapy is completed. Erythropoiesis-stimulating drugs are not safe or appropriate for all patients undergoing chemotherapy. Patients should discuss the risks and benefits with their oncologists.
For chronic kidney failure, erythropoiesis-stimulating drugs should be used to maintain a hemoglobin level between 10 - 12 g/dL. Higher hemoglobin levels increase the risk for stroke, heart attack, heart failure, or death.
Erythropoiesis-stimulating drugs are used to increase red blood cell numbers and reduce the need for blood transfusions. They do not help improve anemia symptoms, fatigue, or quality of life for patients with cancer or HIV.
Patients who take these drugs should contact their doctors if they experience symptoms such as leg pain or swelling, increased shortness of breath, increased blood pressure, dizziness, or extreme fatigue.

Introduction

Anemia is an abnormal reduction in red blood cells.

This photmicrograph shows normal red blood cells (RBCs) as seen in the microscope after staining.

Anemia is a global problem, at its worst in developing countries. But it is by no means absent in industrialized nations. An estimated 3.4 million Americans suffer from anemia. Anemia is not a single disease but a condition, like fever, with many possible causes and many forms. Causes of anemia include nutritional deficiencies, inherited genetic defects, medication-related side effects, and chronic disease. It can also occur because of blood loss from injury or internal bleeding, the destruction of red blood cells, or insufficient red blood cell production. The condition may be temporary or long-term, and can manifest in mild or severe forms.

As it is impossible to discuss all types of anemia, this report focuses on three of the most common forms:

Iron deficiency anemia
Anemia of chronic disease (ACD)
Megaloblastic anemia (caused by deficiencies in the B vitamins folate, vitamin B12, or both)

Some less common causes and types of anemia are included in a table in this report.

Blood has two major components:

Plasma is a clear yellow liquid that contains proteins, nutrients, hormones, electrolytes, and other substances. It constitutes about 55% of blood.
White and red blood cells and platelets make up the balance of blood. The white cells are the infection fighters for the body, and platelets are necessary for blood clotting. The important factors in anemia, however, are red blood cells.

Red blood cells (RBCs), also known as erythrocytes, carry oxygen throughout the body to nourish tissues and sustain life. Red blood cells are the most abundant cells in our bodies. Men have about 5.2 million red blood cells per cubic millimeter of blood, and women have about 4.7 million per cubic millimeter of blood.

Hemoglobin and Iron

Each red blood cell contains 200 - 300 hemoglobin molecules. Hemoglobin is a complex molecule, and it is the most important component of red blood cells. It is composed of protein (globulin) and a molecule (heme), which binds to iron.

In the lungs, the heme component binds to oxygen in exchange for carbon dioxide. The oxygenated red blood cells are then transported to the body's tissues, where the hemoglobin releases the oxygen in exchange for carbon dioxide, and the cycle repeats. The oxygen is used in the mitochondria, the power source within all cells.

Red blood cells typically circulate for about 120 days before they are broken down in the spleen. Most of the iron used in hemoglobin can be recycled from there and reused.

Structure and Shape of Red Blood Cells

Red blood cells -- the erythrocytes -- are extremely small and look something like tiny, flexible inner tubes. This unique shape offers many advantages:

It provides a large surface area to absorb oxygen and carbon dioxide.
Its flexibility allows it to squeeze through capillaries, the tiny blood vessels that join the arteries and veins.

Abnormally shaped or sized erythrocytes are typically destroyed and eliminated.

Blood Cell Production (Erythropoiesis)

The actual process of making red blood cells is called erythropoiesis. (In Greek, erythro means "red," and poiesis means "the making of things.") The process of manufacturing, recycling, and regulating the number of red blood cells is complex and involves many parts of the body:

The body carefully regulates its production of red blood cells so that enough are manufactured to carry oxygen but not so many that the blood becomes thick or sticky (viscous).
Most of the work of erythropoiesis occurs in the bone marrow. In children younger than 5 years old, the marrow in all the bones of the body is enlisted for producing red blood cells. As a person ages, red blood cells are eventually produced only in the marrow of the spine, ribs, and pelvis.
If the body needs more oxygen (at high altitudes, for instance), the kidney triggers the release of the hormone erythropoietin (EPO), a hormone that acts in the bone marrow to increase the production of red blood cells.
The lifespan of a red blood cell is 90 - 120 days. The liver and the spleen remove old red blood cells are removed from the blood by the liver and spleen.
When old red blood cells are broken down for removal, iron is returned to the bone marrow to make new cells.

Click the icon to see an image of the formed elements of blood.

Click the icon to see an image of hemoglobin.

Causes

Iron deficiency anemia occurs when the body lacks mineral iron to produce the hemoglobin it needs to make red blood cells. In general, there are three stages leading from iron deficiency to anemia:

First, there is an insufficient supply of iron, which causes iron stores in the bone marrow to be depleted. This stage generally has no symptoms.
Second, iron deficiencies develop and begin to affect hemoglobin production. (Tests will show low hemoglobin and hematocrit levels.)
Hemoglobin production declines to the point where anemia develops.

Most of the iron used in the body can be recycled from blood and reused. Nevertheless, iron deficiency can occur from a number of conditions.

Inadequate Iron Intake. A healthy diet easily provides enough iron. In general, most people need just 1 mg, and menstruating women need 2 mg of extra iron each day. This means that lack of iron in the diet is not a common cause of iron deficiency anemia, except in infants. In fact, most American adults may be consuming too much iron in their diet. Most of the iron in red blood cells is recycled and reused. Iron-poor diets are a cause of anemia only in people with existing risks for iron deficiency. Children who have not yet eaten iron-fortified formulas or iron-enriched cereal may also become anemic.

Blood Loss. Iron deficiencies most commonly occur from internal blood loss due to other conditions that range in severity. These conditions include:

Peptic ulcers, which may be caused by H. pylori infections, or aspirin and drugs or nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen and naproxen. About 70% of long-term users of these medications have some sign of gastrointestinal bleeding, although it is rarely significant enough to cause anemia.
Duodenal ulcers
Hemorrhoids
Colon polyps
Colon, stomach, and esophageal cancer
Very heavy periods (menorrhagia) are the most common causes of anemia in premenopausal women.
Bleeding from esophageal varices, often present in alcoholics

Impaired Absorption of Iron. Impaired absorption of iron is caused by:

Certain intestinal diseases (inflammatory bowel disease, celiac disease)
Surgical procedures, particularly those involving removal of parts of the stomach and small intestine, can impair the ability of the stomach or intestine to absorb iron. (Such conditions also often impair folic acid absorption as well.)
Pica, the craving for non-food substances such as ice, starch, or clay, is a possible cause of iron deficiency. To complicate matters, pica (particularly ice cravings) may also be a symptom, rather than a cause, of anemia.
Certain intestinal infections, such as hookworm and other parasites.

Click the icon to see an image of inflammatory bowel disease.

Genetic Causes. Some people are born with iron deficiency. Certain cases may be due to a mutation of the Nramp2 gene, which regulates a protein responsible for delivering iron to the cells.

Anemia of chronic disease (ACD), also called anemia of chronic inflammation (ACI), is a common condition associated with a wide variety of persistent inflammatory diseases. It can be very severe and require transfusions.

The Inflammatory Process and ACD. ACD is not completely understood. In ACD, iron is not efficiently recycled from blood cells, and red blood cell survival is reduced. In addition, there is impaired response to erythropoietin, the hormone that acts in the bone marrow to increase the production of red blood cells. (Abnormal function and low levels of erythropoietin, in fact, may be the most important factor in ACD, with iron insufficiencies being a consequence.)

The process leading to ACD may occur in the following way:

The immune system activates white blood cells and releases various compounds during times of infection that are intended to fight invaders and heal wounds. Such an event causes an inflammatory state in the areas of the attack.
White blood cells called macrophages release small but powerful proteins known as cytokines, which are critical in the development of ACD. Cytokines are indispensable for healing. However, cytokines are overproduced often in chronic and inflammatory diseases, causing serious tissue injury and, in some cases, even organ damage. In the case of ACD, they prevent production of erythropoietin, the hormone that acts in the bone marrow to increase the production of red blood cells. Specific cytokines implicated in anemia are interleukin 1 (IL-1), tumor necrosis factor (TNF), and interferons.
As part of this process, mechanisms prevent the release of recycled iron needed in the bone marrow for the manufacturing of red blood cells. Iron absorption in the intestines is also blocked. Theoretically, this is a protective measure, since iron may help infectious organisms proliferate. In such cases, iron stores are high, but the usable iron in circulation is low.
Researchers have identified a peptide called hepcidin, which prevents iron absorption in the intestine and blocks the release of iron by immune factors for red blood cell production. Some experts believe high levels of the peptide may play a central role in preventing the release of iron during infection and inflammatory states, and is critical in ACD.

Diseases Associated with ACD and Inflammation. The chronic diseases that are associated with this process include:

Certain cancers. Examples include lymphomas and Hodgkin's disease.
Autoimmune diseases. Examples include rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, and polymyalgia rheumatica.
Long-term infections. Examples include chronic or recurrent urinary tract infections and osteomyelitis.
Hepatitis C. The liver cirrhosis associated with hepatitis C can reduce the production of red blood cells. Gastrointestinal bleeding may also contribute to blood loss.
Heart failure. Experts estimate that 25 - 60% of patients with heart failure also have anemia. However, it is unclear whether anemia actually causes or worsens heart failure. Recent research suggests it may actually be a sign (marker) of heart failure. Iron deficiency in heart failure can be due to a number of factors. It may be caused by a lack of nutrients in a person’s diet or by the body’s inability to absorb nutrients from food. Heart failure can also cause a back up of fluid (edema). This edema produces a higher volume of blood plasma (the liquid part of blood), which can dilute red blood cells and cause anemia.
Chronic kidney disease. The hormone erythropoietin (EPO) is produced in the kidneys and stimulates the bone marrow production of red blood cells. Diseased kidneys do not release sufficient amounts of EPO; anemia can result and is universal in end-stage renal disease. Chronic kidney disease is a common complication of diabetes.
HIV/AIDS. The inflammatory process associated with AIDS can adversely affect EPO levels and red blood cell production.
Anemia in critically ill patients. Evidence suggests similarities between ACD and severe anemia in patients who are in intensive care. Some experts believe that the cause of anemia in such critically ill patients may also be due to inflammatory responses that promote impaired responsiveness to erythropoietin.

Not all chronic diseases involve the inflammatory process and anemia. For example, high blood pressure is a chronic disease, but it does not affect red blood cells.

Treatment-Related Anemia. Anemia can also result from the therapies used to treat conditions. For example, anemia is a common side effect of cancer treatments. Chemotherapy and radiation can impair the bone marrow's production of red blood cells and contribute to the extreme fatigue that many patients experience during cancer therapy. Patients with hepatitis C frequently receive combination therapy of ribavirin and interferon; ribavirin can induce anemia. Hepatitis C also affects many patients with HIV or AIDS. In addition to ribavirin, patients with HIV or AIDS can develop anemia as a result of highly active anti-retroviral therapy (HAART) and, in particular, from the drug AZT.

Other medications that increase the risk for anemia are certain antibiotics, some antiseizure medications (phenytoin), immunosuppressive drugs (methotrexate, azathioprine), antiarrhythmic drugs (procainamide, quinidine), and anti-clotting drugs (aspirin, warfarin, heparin).

Megaloblastic anemia is the end-product of deficiencies in the B vitamins folate or vitamin B12 (also called cobalamin), or both. Such deficiencies produce abnormally large red blood cells (megaloblastic ) that have a shortened lifespan. Neurologic problems are also associated with these deficiencies. Several conditions can cause these deficiencies.

Click the icon to see an image of red blood cells seen in megaloblastic anemia.

Causes of Vitamin B12 Deficiency. Conditions that cause vitamin B12 deficiencies include:

Vitamin B12 deficiency from diet is very rare, since the liver stores over a 3-year supply. It usually does not occur even in alcoholism, vegetarianism, or in malnourished people with kidney failure or cancer. Since animal products are the chief source, however, true vegan vegetarians may need a supplement, fortified food, or appropriate food selection known to contain adequate amounts of this vitamin
Pernicious anemia. Pernicious anemia is an autoimmune disease in which antibodies are tricked into attacking stomach cells. This results in impaired production of intrinsic factor (IF), a compound that is critical for absorption of vitamin B12. Pernicious anemia is diagnosed in about 1% of people over age 60, with women having a higher risk than men.
Complications of gastrointestinal surgery. Surgeries such as stomach bypass or stapling, which remove part or all of the stomach, pose a 15 - 30% chance of causing vitamin B12 deficiencies.
Overgrowth of intestinal bacteria
Tropical sprue (an acquired malabsorption disease occurring in tropical climates)

Click the icon to see an image of the benefits of vitamin B12.

Causes of Folate Deficiency. The body stores only about 100 times its daily requirements for folate and can exhaust this supply within about 3 months if the diet is deficient in folate.

Poor diet coupled with alcoholism is the most common cause of folate deficiency. Alcohol abuse not only contributes to malnutrition but also causes chemical changes that can result in lower folate levels.
Any condition that disturbs the small intestine and impairs its absorption ability can cause a deficiency. Such disorders include inflammatory bowel disease or celiac sprue (a sensitivity reaction to gluten)

Click the icon to see an image of foods that contain gluten.

Parasitic diseases such as giardiasis
Short bowel syndrome
Deficiencies can also arise due to high demand for folic acid caused by conditions such as cancer, pregnancy, severe psoriasis, severe hyperthyroidism, and hemolytic anemia.
Some drugs, including phenytoin, methotrexate, trimethoprim, and triamterene, may also hinder folate absorption.


Form of Anemia	Description and Diagnosis	Causes and Risk Factors	Treatments
Aplastic Anemia	Bone marrow fails to produce all types of blood cells. Symptoms, in addition to standard anemia, are bleeding in mucous membranes and skin, gingivitis, higher risk for infection, and shortness of breath.	Cause is unknown in half the cases. Known causes include hereditary conditions (Fanconi's anemia), viruses (HIV, hepatitis, Epstein-Barr), autoimmune diseases (lupus, rheumatoid arthritis), medications (valproic acid, tacrolimus, azathioprine) or chemicals (benzene, pesticides).	Transfusions, antibiotics, bone marrow or stem cell transplantation, immunosuppressant drugs. (This anemia used to be nearly always fatal, but survival rates now can reach 92% with successful transplants and up to 87% with immunosuppressants.)
Thalassemia	Genetic blood disease caused by a defect in the rate of production of hemoglobin. The two major forms are thalassemia minor and thalassemia major (Cooley's anemia, beta thalassemia). Thalassemia minor is the more common and milder form, in which lifespan is normal. Thalassemia major can be serious, but it is fortunately very rare.	Affects males and females equally. Most common in people of Mediterranean descent, especially Italians and Greeks. Both types of thalassemia are found in an area that extends from northern Africa and southern Europe to Thailand, including Iran, Iraq, Indonesia, and southern China. Thalassemia major is more common in families who intermarry.	Transfusions to supply enough red blood cells to achieve moderate anemia and avoid iron overload are standard approaches for thalassemia major. Investigations are ongoing to find alternatives to transfusions. Hydroxyurea, 5-azacytidine, erythropoietin, or butyrate analogues may help some patients. Bone marrow transplantation may be needed for some types of thalassemia.
Hemolytic Anemias: Acquired	Anemia caused by hemolysis (premature destruction of red blood cells). Diagnosis considered when there is marked increase in RBC production by bone marrow.	Autoimmune hemolytic anemia is the primary type, in which antibodies produced by the immune system damage RBCs. Cause unknown or associated with disorders such as systemic lupus erythematosus, lymphoma, and paroxysmal nocturnal hemoglobinuria. Other causes are high exposure to certain metals or chemicals (lead, copper, benzene, naphthalene), snake and insect bites, malaria, transfusions, post-surgical complications, and drugs such as methyldopa. In infants, blood group incompatibility between mother and child or infections in the womb.	Corticosteroids for autoimmune hemolytic anemia. Transfusions beneficial in many cases. Various immunosuppressive drugs may be tried, as well as splenectomy. Eculizumab (Soliris) is approved for treatment of paroxysmal nocturnal hemoglobinuria.
Hemolytic Anemias: Inherited	Hemolysis (premature destruction of RBCs) caused by sphere-shaped RBCs, which have difficulties circulating through the spleen.	Inherited defects include membrane defects, hemoglobin abnormalities, and enzyme deficiencies. Fava beans may trigger symptoms. More likely and more serious in males than females.	Blood transfusions may be necessary for some types of hemolytic anemia. Experimental trials use immune globulin. Removal of the spleen (splenectomy) or bone marrow transplantation may help some patients.
Sideroblastic Anemias	Group of anemias caused by impaired ability of bone marrow to produce normal RBCs. Normal-to-high iron levels, but iron cannot be used to make hemoglobin. In addition to the standard symptoms of anemia are jaundice, enlarged liver and spleen, fever, headache, loss of appetite, vomiting, and leg sores. Symptoms can be mild. Usually appears in childhood. Infections, trauma, and pregnancy may trigger symptoms.	Inherited or acquired after excessive alcohol use, certain medications, including chloramphenicol, or other disorders, including some cancers and rheumatoid arthritis. More common in the elderly.	Deferoxamine (Desferal) is used to remove iron. Effectiveness is increased when ascorbate is added to the regimen. Folate and pyridoxine are used, but their effectiveness is under question.
Sickle Cell Anemia	Serious, life-threatening, inherited disease. The sickle-shaped, inflexible RBC has impaired ability to squeeze through vessels. Short lifespan of RBC (10-20 days) causes anemia. In addition to anemia symptoms, joint and bone pain, infections, and heart failure can occur.	Disease occurs in 0.6% and the trait is found in the genetic makeup of 9% of African-Americans. Also occurs in people from India and Spanish-speaking and Mediterranean regions.	Measures to avoid cycling and control pain. Including hydration, hydroxyurea, NSAIDs and narcotic analgesics. Bone marrow transplantation. [For information, see In-Depth Report #58: Sickle-cell disease.]

Click the icon to see an image of red blood cells found in sickle cell anemia.

Risk Factors

Although nutritional iron-deficiency anemia has declined in industrialized nations, it affects an estimated 2 billion people worldwide. Even in the U.S., iron deficiency is the most prevalent nutritional deficiency. It is highly associated with poverty. People in lower socioeconomic groups have double the risk of those who are middle or upper class.

Among Americans with iron deficiency anemia, young children have the highest risk followed by premenopausal women. Adolescent and adult men and postmenopausal women have the lowest risk. Men, in fact, are at risk for iron overload, probably because of their higher meat intake.

General Risk Factors for Anemia in Infants and Children. Up to 20% of American children and 80% of children in developing countries become anemic at some point during their childhood and adolescence. Iron deficiency is the most common cause in children, but other forms of anemia, including hereditary blood disorders, can also cause anemia in this population. Hispanic American children have double the rates of iron deficiency as African-American and Caucasian children.

Iron deficiency affects about 9% of children younger than 2 years. About 3% of children in this age group are anemic as a result. Children in lower-income homes are at higher risk than those in higher income homes. In a study of low-income children, ages 6 months to 5 years, the prevalence of anemia was over 10%, and was nearly 18% in children younger than 2 years. However, children in any income group can develop iron deficiency.

Young children 9 - 18 months have the highest risk for iron deficiency anemia in the U.S. Such children also are at great risk for problems in mental development from anemia. Infant boys may have 10 times more risk than baby girls. In general, full-term, breast-fed infants have enough iron stores for their first 6 months of life. After that, they must rely on other sources for iron.

Iron-deficiency anemia in infants and small children can be due to one or more of the following factors:

Stopping breast-feeding too early or using formula that isn't iron-fortified.
Bottle-feeding too long. Studies indicate that the longer children are bottle-fed, the greater the risk for iron-deficiency and anemia. Toddlers 12 months and older should not drink more than 2 cups of milk a day. Cow’s milk is good for children, but it does not contain enough iron. Too much milk can decrease children’s appetite and prevent them from eating the iron-rich food they need. When babies who are bottle-fed are 7 - 9 months old, they should be weaned from bottles and given sippy cups. By the age of 12 months, all children should be using a cup instead of a bottle.
Toddlers’ preferences for iron-poor food. Parents should make sure that their children eat iron-rich foods, such as beans, meat, fortified cereals, eggs, and green leafy vegetables

Better social services and more accurate ways of diagnosing and monitoring anemia are needed in these high-risk groups. There is still considerable debate on how to define iron deficiency and anemia in infants. New research suggests that a reticulocyte hemoglobin content (CHr) test may be better than a standard hemoglobin test for detecting iron deficiency in babies. Reticulocytes are immature red blood cells. The CHr test measures the amount of hemoglobin in these cells.

Up to 10% or more of adolescent and adult women under 49 years are iron deficient. Hispanic American and African-American women have double the prevalence for anemia compared to Caucasian women. The risk for anemia in adolescent girls is about 3%. Anemia is generally mild in young women, however, and is more likely to occur with one or more of the following conditions:

Heavy menstruation for longer than 5 days
Abnormal uterine bleeding, such as from fibroids
Pregnancy. About 20% of women in industrialized countries have iron deficiency during pregnancy. Multiple pregnancies and births significantly increase the risk.

Although studies have reported various estimates on the prevalence of anemia in older adults, one survey suggested that anemia affects about 10% of adults aged 65 years and older, and more than 20% aged 85 years and older. The causes of anemia in older adults were equally distributed among nutritional deficiencies, chronic inflammatory disease, chronic renal disease, and unexplained anemia. Most cases were mild.

People with alcoholism are at risk for anemia both from internal bleeding as well as folate- and vitamin B deficiency-related anemias.

Although most Americans probably consume too much iron in their diets, some people may be at risk for diet-related iron deficiencies, including:

People whose diets are high in processed foods and lack any meat.
Strict vegetarians. Vegetarians who avoid all animal products may have a slightly higher risk for deficiencies in iron and some B vitamins. Although dried beans and green vegetables often contain iron, it is less easily absorbed from plants than from meat. Fortunately, most commercial cereals are fortified with vitamin B12 and folic acid (the synthetic form of folate).

Anyone with a chronic disease that causes inflammation or bleeding is at risk for anemia. Critical illness in the intensive care unit is also highly associated with anemia.

Working out regularly may cause some iron loss, which is comparable to that from menstruation and rarely worrisome. Dietary choices may account for most cases of sports anemia. Intense, sustained exercise, such as that performed by marathon runners, may cause a condition called sports anemia, which may be due to slight gastrointestinal bleeding, damaged red blood cells, low iron intake, or poor intestinal absorption of iron.

Iron deficiency occurs in 20% of pregnant women in developed countries. Even worse, 50% or more of women in nonindustrialized nations become iron deficient, and 30 - 50% are deficient in folic acid. Severe anemia is associated with a higher mortality rate among pregnant women. Mild-to-moderate anemia, however, does not pose any elevated risk.

Pregnancy increases the risk for anemia in different ways:

It increases the body's demand for folic acid and, therefore, poses a risk for deficiencies and an increased risk for megaloblastic anemia. Low levels of folate during pregnancy increase the risk of neural tube defects in newborns.
It increases the body's demand for iron, thus posing a risk for iron deficiency anemia. Pregnant or nursing women need 30 mg of iron per day. Maternal iron deficiency anemia is associated with increased weight or size of the placenta, a condition that may later pose a risk for high blood pressure in the offspring. Pregnant women with low hemoglobin levels (the iron-bearing component in the blood) have an elevated risk for pre-term or low birth weight infants.
Pregnancy is also associated with fluid retention, which in turn may produce high volumes of plasma (the fluid component of blood). This can dilute red blood cells, which may lead to anemia.
After delivery, heavy bleeding, which occurs in 5 - 10% of women who have given birth, can cause symptoms of anemia.

Diagnosing of Iron Deficiency During Pregnancy. A diagnosis of iron deficiency is problematic in pregnant women. The standard test is a measurement of ferritin levels, which are low in most people with iron deficiency. Pregnant women, however, may have high ferritin blood levels into their third trimester but still be iron deficient. A newer test that measures a factor called serum transferrin receptor may prove to be a useful way of diagnosing iron deficiency in women. Researchers are also investigating Doppler ultrasonography as an imaging technique for detecting anemia in the fetus. Traditionally, fetal anemia is diagnosed through amniocentesis. Doppler ultrasonography is a non-invasive method that does not risk causing a miscarriage or a worsening of fetal anemia.

Preventing Anemia in Pregnant Women.

Iron Supplements. For the past 40 years, iron supplements have been recommended for all pregnant women. This practice has been challenged recently, however. There is no clear-cut evidence that the mild iron deficiency most pregnant women experience is harmful. In addition, iron supplements cause gastrointestinal side effects and may not be completely harmless. Some experts suggest iron supplements for all pregnant women whose hemoglobin levels are less than 11 g/dl, and pregnant women whose serum ferritin levels are low, beginning in their 20th - 24th weeks of pregnancy.
Vitamin Supplements. Women who are trying to conceive, who are pregnant, and who are breast-feeding should take 400 mcg of folic acid a day. They should be sure this is folic acid and not folate. Folate is the natural form of folic acid, but 400 mcg supplements of folate are half as potent as the same dose of folic acid. Pregnant and nursing women who are vegetarians should be sure to have supplements of folic acid and other B vitamins as well, since many of these nutrients are found primarily in animal products. Vitamin B12 deficiencies during pregnancy can also produce anemia in both mother and child.
Diets Rich in Vitamin C. Eating foods rich in vitamin C can help absorb iron.

Treating Anemia During Pregnancy. Pregnant women who become anemic and need treatment may be given oral iron supplements, or blood transfusions in severe cases. Intravenous or intramuscular administration of iron helps improve blood levels better than oral iron supplements, but may cause more serious side effects.

Complications

Most cases of anemia are mild, including those that occur as a result of chronic disease. Nevertheless, even mild anemia can reduce oxygen transport in the blood, causing fatigue and a diminished physical capacity. Moderate-to-severe iron-deficiency anemia is known to reduce endurance. Some studies indicate that even iron deficiency without anemia can produce a subtle but still lower capacity for exercise.

Because a reduction in red blood cells decreases the ability to absorb oxygen from the lungs, serious problems can occur in prolonged and severe anemia that is not treated. Anemia can lead to secondary organ dysfunction or damage, including heart arrhythmia and heart failure.

Certain inherited forms of anemia, including thalassemia major, pernicious anemia, and sickle-cell anemia, can be life threatening. Thalassemia major and sickle-cell anemia affect children and are particularly devastating.

Pregnant women with significant anemia may have an increased risk for poor pregnancy outcomes, particularly if they are anemic in the first trimester.

In children, severe anemia can impair growth and motor and mental development. Children may exhibit a shortened attention span and decreased alertness. Children with severe iron-deficiency anemia may also have an increased risk for stroke.

Anemia is common in older people and can have significantly more severe complications than anemia in younger adults. Some studies have reported higher mortality rates in anemic individuals 85 and older compared to their non-anemic peers. (The rates were higher in anemic men than in women.) The following are examples of its effects from different studies:

Anemia may have adverse effects on the heart and increase the severity of cardiac conditions, including reducing survival rates from heart failure and heart attacks.
Elderly people with lower levels of hemoglobin are at an increased risk of death.
Anemia may be associated with an increased incidence of falls.
Even mild anemia may possibly lead to cognitive impairment. A 2006 study of elderly women found that mild anemia worsened problem-solving abilities and other cognitive functions. Anemia may worsen an already existing dementia.

In addition to anemia, vitamin B12 deficiency can cause neurologic damage, which can be irreversible if it continues for long periods without treatment.

Anemia is particularly serious in cancer patients. In people with many common cancers, the presence of anemia is associated with a shorter survival time.

Anemia is associated with higher mortality rates and possibly heart disease in patients with kidney disease.

The combination of anemia and heart failure can increase the risk of hospitalization or death by 30 - 60%. Patients with heart failure whose hemoglobin levels decline do worse than patients with stable levels.

Blood transfusions. Patients with certain types of anemia require frequent blood transfusions. These transfusions can cause iron overload. Patients are treated with iron chelation therapy, which uses a drug that binds to iron. Excess iron is then eliminated by the kidneys. The standard drug for iron chelation therapy, deferoxamine (Desferal), is injected intravenously through an infusion pump. The treatment can be difficult for many patients. In 2005, the FDA approved a new drug, deferasirox (Exjade), to treat iron overload due to blood transfusions. Patients dilute the pills in liquid once a day and drink the mixture.

Symptoms

Symptoms of anemia vary depending on the severity of the condition. Anemia may occur without symptoms and be detected only during a medical examination that includes a blood test. When they occur, symptoms may include:

Weakness and fatigue are the most common symptoms of even mild anemia. Even iron deficiency without anemia can reduce working capacity in some people.
Shortness of breath on exertion
Rapid heartbeat
Lightheadedness or dizziness
Headache
Ringing in the ears (tinnitus)
Irritability and other mood disturbances
Pale skin (however, healthy-looking skin color does not rule out anemia if a patient has risk factors and other symptoms of anemia)
Mental confusion
Loss of sexual drive

Pica. One odd symptom, in some cases a cause of iron deficiency, is pica. This is the habit of eating unusual substances, such as ice (called pagophagia), clay, cardboard, foods that crunch, or raw starch. For example, in one study, half of people whose pica took the form of pagophagia (eating at least one tray of ice every day for 2 months) or eating foods that crunch (such as raw potatoes, carrots, or celery) were iron deficient. The pica often stops, particularly in children, when iron supplements are given. Pica is difficult to detect because patients are often ashamed to admit to such cravings.

Frequent Breath Holding. Studies have also indicated that children who hold their breath frequently when angry or upset, even to the point of fainting, may be iron-deficient. In one study, taking iron supplements reduced this phenomenon in 88% of treated children.

Symptoms of Megaloblastic Anemia. The symptoms of megaloblastic anemia from vitamin B12 or folic acid deficiencies include not only standard anemic symptoms but also:

Inflammation of the mouth (stomatitis)
Inflammation of the tongue (glossitis), which involves shrinkage at the surface and edges of the tongue

Over time, psychiatric and neurologic problems develop. Vitamin B12 deficiencies cause neurologic symptoms (numbness and tingling, depression, memory loss, and irritability), and folate deficiency may result in depression and dementia (in severe cases).

Symptoms of Pernicious Anemia. Early neurologic symptoms of pernicious anemia are due to B12 deficiency. They include numbness and tingling, depression, memory loss, and irritability. Advanced nerve damage can cause loss of balance and staggering, confusion, dementia, spasticity, loss of bladder control, and erectile dysfunction. Folic acid deficiency does not cause neurologic damage, although people with this deficiency can be irritable, forgetful, and experience personality changes. Of concern for patients with pernicious anemia and B12 deficiency anemia is that folic acid supplements can mask the presence of this disease in its early stages but not cure it. The only cure is vitamin B12 supplementation.

Diagnosis

The first step in any diagnosis is a physical examination to determine if the patient has symptoms of anemia and any complications. Because anemia may be the first symptom of a serious illness, determining its cause is very important. This may be difficult, particularly in the elderly, malnourished, or people with chronic diseases, whose anemia may be caused by one or more factors. A detailed medical, personal, and dietary history should report:

Any family or personal history of anemia
A history of gallbladder disease, jaundice, or enlarged spleen
Heavy menstrual bleeding in women
Any occurrence of blood in the stool or other signs of internal bleeding. (Even if the patient has not observed any bleeding, nonvisible blood may be present, so a rectal exam and stool test are essential.)
Any dietary history, particularly in people who are elderly, poor, or both

The doctor should examine the patient carefully, especially checking for swollen lymph nodes, an enlarged spleen, and pale skin and nail color.

Specific blood tests are given to determine anemia from any cause.

Blood and Hemoglobin Counts. A complete blood count (CBC) test is performed to determine the presence of anemia. The red blood cells, or erythrocytes, and their iron-bearing component, hemoglobin, are measured.

For example, severe anemia in adults is defined by the World Health Organization as:

Hemoglobin concentrations below 12 g/dL (7.5 mmol/L) in women. (Some evidence suggests that in older women anemia should be diagnosed at 13 g/dL and below.)
Below 13 g/dL (8.1 mmol/L) in men.

A low red blood cell (RBC) count could indicate a number of problems, including bleeding or a failure by bone marrow to manufacture red blood cells.

Hematocrit. Calculating the percentage of red blood cells in blood plasma (a measurement called the hematocrit) is also important. Plasma is the liquid portion of blood. People with a high volume of plasma may be anemic even if their blood count is normal because the blood cells have become diluted.

Normal percentages are highest in the very youngest individuals and decline as people age. They also vary by gender. The following are some examples of normal range:

Newborns: 42 - 60%
Children: 35 - 45%
Adult males: 41 - 53%
Adult women: 36 - 46%

Normal value ranges may vary slightly among different laboratories.

Smokers, people at high altitudes, and those who are dehydrated tend to have higher than normal hematocrit levels. Those at greater risk for low hematocrit levels include pregnant women and patients with cirrhosis, heart failure, and splenomegaly.

Reticulocyte Count. Reticulocytes are immature red blood cells, and their count reflects the rate of red blood cell production. The upper normal limit is about 100,000/mL. A low count, when bleeding isn't the cause, suggests problems in production in the bone marrow. An abnormally high count indicates that the red blood cells are being destroyed in high numbers and indicates hemolytic anemia. New research suggests that the reticulocyte hemoglobin content (CHr) test may be more accurate than a standard hemoglobin test for detecting iron deficiency in infants. This test may help identify babies who are at risk for becoming anemic and help them get treated earlier.

Blood Morphology. A blood smear viewed under a microscope allows an expert to classify the blood by its color, size, and shape ( morphology ). Generally red blood cells are categorized as:

Pale-colored (hypochromic) and abnormally small (microcytic)
Normal colored and normal sized (normochromic, normocytic)
Abnormally large (macrocytic)

The shape of the red blood cells, which can be distorted in many blood disorders, is also important in determining a diagnosis.

There are two steps in making a diagnosis in patients with symptoms of iron deficiency anemia:

The first step is to determine if a person is actually deficient in iron.
If iron stores are low, the second step is to diagnose the cause of the iron deficiencies, which will help determine treatment.

Determining if Iron Stores are Low. The following findings are important in determining that a person is iron deficient:

Blood cells viewed under the microscope are pale (hypochromic) and abnormally small (microcytic). They are also mostly uneven in shape. (These findings suggest iron deficiency, but they can also appear in cases of anemia due to chronic disease and thalassemia.)
Hemoglobin and iron levels are low. (These findings further suggest iron deficiency, but they can also occur in cases of anemia due to chronic disease.)
Ferritin levels are low. Ferritin is a protein that binds to iron. Low levels typically mean reduced iron stores. High ferritin levels in the blood do not always mean sufficient iron stores. For example, pregnant women may have high ferritin levels into their third trimester but still be iron deficient. Ferritin levels may also be normal or even elevated in patients with inflammation from anemia due to chronic disease, even if they also have low iron stores.
In children with iron deficiencies, reticulocytehemoglobin levels are low. Reticulocytes are immature red blood cells, and this test may be the most effective approach for diagnosing iron deficiency in children.
A test that measures a factor called serum transferrin receptor (TfR) is proving to be very sensitive in identifying iron deficiency in problematic patients, including the elderly with chronic diseases and possibly pregnant women. (It is often very difficult to identify iron deficiencies in patients who also have anemia due to chronic diseases because their ferritin levels are often normal or even high.) For example, levels of TfR are high in patients with ACD and iron deficiency anemia, but they are normal or only slightly raised in ACD alone. The test is expensive, however, and some experts recommend it should be used only when there is a high suspicion of iron deficiency in the elderly.
Measuring erythrocyte zinc protoporphyrin (ZPP), a product of abnormal heme synthesis, is under investigation and may prove to be a simple and precise measure of iron deficiencies, particularly in children.

If internal bleeding is suspected as the cause, the gastrointestinal tract is usually the first suspect as the source. A diagnosis in these cases can often be made if the patient has noticed blood in the stools, which can be black and tarry or red-streaked. Often, however, bleeding may be present but not visible. If so, stool tests for this hidden (occult ) blood are required. Additional tests may then be needed to diagnose the precipitating condition. Endoscopy, in which a fiber optic tube is used to view into the gastrointestinal tract, is helpful in many patients, particularly when the source of bleeding is unclear. A colonoscopy may also be recommended to rule out colorectal cancer.

If the patient's diet suggests low iron intake and other causes cannot be established using inexpensive or noninvasive techniques, then the patient may simply be given a monthly trial of iron supplements. If the patient fails to respond, further evaluation is needed.

Usually anemia of chronic disease is recognized during the management of the primary disease and, if the anemia is mild, additional diagnostic tests are rarely needed. The following are typical findings in ACD:

The blood cells are normal looking.
Blood tests may typically show low levels of iron in the blood, but ferritin levels are normal or even high. (Low levels of ferritin, a protein that binds to iron, indicate iron deficiency.)

Doctors need a multi-step diagnostic procedure for determining vitamin B deficiencies and the anemias that cause or are caused by them. Doctors may arrive at a diagnosis of vitamin B12 or folic acid deficiencies from different routes:

They may diagnose deficiencies after detecting megaloblastic anemia from abnormal blood tests.
They may suspect vitamin deficiencies first from symptoms and history and then look for anemia.

Diagnosing Megaloblastic Anemia. Very large oval red blood cells indicate megaloblastic anemia. Abnormally shaped neutrophils (certain white blood cells) may also be present. Bone marrow aspiration may need to be performed if the disease is strongly suspected but the diagnosis is not clear.

Determining Vitamin Deficiency. Once megaloblastic anemia has been diagnosed, the doctor will need to determine which vitamin deficiency is causing it. This is extremely important, because if a vitamin B12-deficient patient receives folate replacement only, then irreversible nerve injuries may develop. Even if blood tests for megaloblastic anemia are normal, patients with neurologic and psychiatric abnormalities that have no detectable cause should still be tested for vitamin B12 deficiency.

Often, vitamin B deficiencies cannot be determined by a history or symptoms alone. Blood tests are the primary indicators of both vitamin B12 and folic acid deficiencies, but even blood tests for these vitamins are not always straightforward:

Folic acid and vitamin B12 levels must always be measured at the same time because each vitamin may affect the other.
Folate levels may be temporarily low in some people who are not truly deficient.
Folate levels may temporarily rise in deficient people if they have just eaten foods containing the vitamin.
Antibiotics can interfere with B12 levels.

Measuring methylmalonic acid and homocysteine, substances in the blood that increase when levels of one or both vitamins are low, improves accuracy.

Tests for Pernicious Anemia. Once a vitamin B12 deficiency has been established and the doctor has not found any intestinal abnormalities or other factors to account for the deficiency, the doctor presumes a diagnosis of pernicious anemia. Pernicious anemia may also be diagnosed through various blood (such as complete blood count) or urine tests.

Pernicious anemia is treated with vitamin replacement, but the condition is easily missed, particularly in patients whose diets are rich in folic acid. Folic acid can mask the early symptoms of pernicious anemia but not cure it. Consequently the disease may persist until serious neurologic symptoms occur. With folic acid now a required additive in many commercial foods, some experts are concerned about an increased incidence in pernicious anemia.

Dietary Factors

Iron found in foods is either in the form of heme or non-heme iron:

Heme Iron. Foods containing heme iron are the best sources for increasing or maintaining healthy iron levels. Such foods include (in decreasing order of iron-richness) clams, oysters, organ meats, beef, pork, poultry, and fish.
Non-Heme Iron. Non-heme iron is less well-absorbed. About 60% of the iron in meat is non-heme (although meat itself helps absorb non-heme iron). Eggs, dairy products, and iron-containing vegetables have only the non-heme form. Such vegetable products include dried beans and peas, iron-fortified cereals, bread, and pasta products, dark green leafy vegetables (chard, spinach, mustard greens, kale), dried fruits, nuts, and seeds.

The absorption of non-heme iron often depends on the food balances in meals. The following foods and cooking methods can enhance absorption of iron:

Meat and fish not only contain heme iron -- the best form for maintaining stores -- but they also help absorb non-heme iron.
Increasing intake of vitamin-C rich foods, such as orange juice, may enhance absorption of non-heme iron, although it is not clear if it improves iron stores in iron-deficient people. In any case, vitamin-C rich foods are healthy and include broccoli, cabbage, citrus fruits, melon, tomatoes, and strawberries.
Riboflavin (vitamin B2) may help enhance the response of hemoglobin to iron. Food sources include dairy products, liver, and dried fortified cereals.
Cooking methods can enhance iron stores. Cooking in cast iron pans and skillets is well-known to increase the iron content of food. According to one study, boiling, steaming, or stir-frying in utensils composed of any material significantly increased the release of non-heme iron stored in vegetables.
Vitamins B12 and folate are important for prevention of megaloblastic anemia and for good health in general. The only natural dietary sources of B12 are animal products, such as meats, dairy products, eggs, and fish (clams and oily fish are very high in B12). As is the case with other B vitamins, however, B12 is added to commercial dried cereals. The recommended daily allowance (RDA) is 2.4 mcg a day. Deficiencies are rare in young people, although the elderly may have trouble absorbing natural vitamin B12 and require synthetic forms from supplements and fortified foods.

Click the icon to see an image of sources of vitamin B12.

Folate is best found in avocado, bananas, orange juice, cold cereal, asparagus, fruits, green, leafy vegetables, dried beans and peas, and yeast. The synthetic form, folic acid, is now added to commercial grain products. Vitamins are usually made from folic acid, which is about twice as potent as folate. Many experts now recommend that adults have 400 mcg of folic acid daily -- considerably higher than standard recommendations of 400 mcg of folate. Women who are trying to conceive, who are pregnant, and who are breast-feeding should take 400 mcg of folic acid.

Click the icon to see an image of sources of folate.

The Recommended Daily Allowance (RDA) of iron for people who are not iron deficient varies by age group and other risk factors. (Iron supplements are rarely recommended in people without evidence of iron deficiency or anemia.) The RDA recommends these daily amounts of iron:

Children 1 - 3 years old: 10 mg
Teenage boys: 12 mg
Teenage girls and premenopausal women: 15 mg
Pregnant or nursing women: 30 mg
Adult men (up to age 50): 10 mg
Older men and women (over age 50): 10 mg

The main source of iron for an infant from birth to 1 year of age is in milk, from breast milk, iron-fortified infant formula, or cereal. The best methods for preventing iron deficiency during infancy are:

Breast-feeding and Iron-Supplemented Formulas. Mothers should be encouraged to breast-feed their babies for their first year. Up to half of the iron in breast milk is absorbed by the baby and is sufficient to prevent anemia for the first 4 - 6 months, assuming that the mother had adequate iron stores during pregnancy. Breast milk itself is low in iron, but if the mother's diet is healthy, vitamin C and lactose in the breast milk may enhance iron absorption. Breast-fed babies should have iron supplements after 4 - 6 weeks, even if they are still nursing.

Infants who are not breast-fed should start with iron-fortified formulas (7-12 mg/L). Most experts strongly discourage the use of low-iron formulas (less than 4.0 mg/L). Parents should discuss the best formula with their doctor. Children given iron supplements may have a slightly higher risk for diarrhea. Experts advise against cow's milk for the first year of life. When cereals are begun, they should be iron fortified.

Recommendations for Toddlers. Toddlers who did not have iron supplements during infancy should be checked for iron deficiency. After the first year, children should be given a varied diet that is rich in sources of iron, B vitamins, and vitamin C. Milk does not contain enough iron and can decrease children's appetite for iron-rich foods. Toddlers older than 1 year should not drink more than 2 cups of milk a day. A preference for apple juice over vitamin-C rich orange juice does not reduce iron absorption in children with any otherwise healthy diet.

Treatment

Oral iron supplements are the best way to restore iron levels for people who are iron deficient, but they should be used only when dietary measures have failed. However, iron supplements cannot correct anemias that are not due to iron deficiency.

One study reported that doctors prescribed iron pills for 64% of patients with anemia, without performing tests to confirm whether iron deficiency was actually the cause. The study suggested that iron replacement was appropriate in less than half of these patients. Iron replacement therapy can cause gastrointestinal problems, sometimes severe ones. Excess iron may also contribute to heart disease, diabetes, and certain cancers. Experts generally advise against iron supplements in anyone with a healthy diet and no indications of iron deficiency anemia. However, one study suggested that supplements help reduce fatigue in women with low iron stores but no signs of anemia.

Treatment of Anemia of Chronic Disease. In general, the best treatment for anemia of chronic diseases is treating the disease itself. In some cases, iron deficiency accompanies the condition and requires iron replacement. Erythropoietin, most often administered with intravenous iron, is used for some patients.

Treatment of Megaloblastic Anemia. The standard treatments for megaloblastic anemia are vitamin B12 injections and folic acid replacement.

Supplement Forms. To replace iron, the preferred forms of iron tablets are ferrous salts, usually ferrous sulfate (Feosol, Fer-In-Sol, Mol-Iron). Other forms include ferrous fumarate (Femiron, FerroSequels, Feostat, Fumerin, Hemocyte, Ircon), ferrous gluconate (Fergon, Ferralet, Simron), polysaccharide-iron complex (Niferex, Nu-Iron), and carbonyl iron (Elemental Iron, Feosol Caplet, Ferra-Cap). Specific brands and forms may have certain advantages. The following are some examples:

Prolonged-release ferrous sulfate (Slow Fe) may enhance iron absorption with fewer side effects than standard ferrous sulfate pills.
FerroSequels contains a stool softener, which helps prevent constipation.
Polysaccharide-iron complex has fewer side effects and equal absorption rates compared to ferrous salts. It is very expensive, however.
Carbonyl iron is composed of very fine tiny uniform spheres of iron powder and may prove to be less toxic than ferrous iron.
Coated or combination pills do not appear to offer any additional advantages and may hinder absorption of the iron.

Regimen. The general guidelines for iron replacement are as follows:

For adults, doctors usually advise one ferrous sulfate tablet (300 mg) three times a day.
Iron replacement doses for children with deficiencies are significantly lower. In general, they are given as drops or syrup administered three times a day. A single-dose daily regimen is showing promise. IMPORTANT: As few as three adult iron tablets can poison children, even fatally. This includes any form of iron pill.
No one, even adults, should take a double dose of iron if one is missed.

Other tips for taking iron are as follows:

For best absorption, iron should be taken between meals. (Iron may cause stomach and intestinal disturbances, however, and some experts believe that low doses of ferrous sulfate can be taken with food and are still absorbed but with fewer side effects.)
Always drink a full 8 ounces of fluid with an iron pill. Taking orange juice with an iron pill may help increase iron absorption. (Some doctors also recommend taking a vitamin C supplement with the iron pill.)
Tablets should be kept in a cool place. (Bathroom medicine cabinets may be too warm and humid, which may cause the pills to disintegrate.)

Full recovery takes 6 - 8 weeks. Recovery will take longer in people with internal bleeding that is not under control. Iron replacement therapy must continue for about 6 months, even if anemia has been reversed. Treatment must be continued indefinitely for people with chronic bleeding; in such cases, iron levels should be closely monitored.

Side Effects. Common side effects of iron supplements include the following:

Constipation and diarrhea are very common. They are rarely severe, although iron tablets can aggravate existing gastrointestinal problems such as ulcers and ulcerative colitis.
Nausea and vomiting may occur with high doses, but can be controlled by taking smaller amounts. Switching to ferrous gluconate may help some people with severe gastrointestinal problems.
Black stools are normal when taking iron tablets. In fact, if they do not turn black, the tablets may not be working effectively. This tends to be a more common problem with coated or long-acting iron tablets.
If the stools are tarry looking as well as black, if they have red streaks, or if cramps, sharp pains, or soreness in the stomach occur, gastrointestinal bleeding may be causing the iron deficiency and the patient should call the doctor promptly.
Acute iron poisoning is rare in adults but can be fatal in children who take adult-strength tablets.

Interactions with Other Drugs. Certain medications, including antacids, can reduce iron absorption. Iron tablets may also reduce the effectiveness of other drugs, including the antibiotics tetracycline, penicillamine, and ciprofloxacin and the Parkinson's disease drugs methyldopa, levodopa, and carbidopa. At least 2 hours should elapse between doses of these drugs and iron supplements.

Supplements. The following vitamin and mineral supplements may improve iron absorption:

Adding either ascorbic acid (vitamin C) or succinic acid to ferrous sulfate therapy will improve absorption of iron stores.
Some studies have found that the addition of zinc to iron supplements increases hemoglobin levels more than iron alone. Some evidence for this suggests that zinc affects a hormone called insulin-like growth factor-I (IGF-I), which plays a role in the regulation of red blood cell production.

In some cases, iron is administered through muscular injections or intravenously. Intravenous iron has the advantage of causing less gastrointestinal discomfort and inconvenience. It may be in the form of iron dextran (Dexferrum, InFed), sodium ferric gluconate complex in sucrose (Ferrlecit), or iron sucrose (Venofer). Ferrlecit or Venofer are proving to be at least equally effective and safer than iron dextran.

Candidates. The injected or intravenous forms should be limited to the following patients with iron deficiency:

People with iron deficiency anemia in whom oral therapy has clearly failed.
Patients with bleeding disorders in which blood loss continues to exceed the rate at which oral iron is absorbed.
In emergencies, when people need red blood cells but transfusion is not appropriate or available.
In people with serious gastrointestinal disorders, such as inflammatory bowel disease, who cannot take iron therapy by mouth.
People undergoing hemodialysis who receive supplemental erythropoietin therapy. Sodium ferric gluconate complex in sucrose (Ferrlecit) or iron sucrose (Venofer) is specifically approved as first-line therapy for these patients.

Certain patients, even if they meet these qualifications, may not be appropriate candidates or should be monitored closely for complications. They include:

Patients with any underlying autoimmune disease.
Malnourished patients who also have an underlying infection.
Patients who are at risk for iron overload.

Side Effects. Some side effects differ depending on how the iron is administered and include the following:

Muscular injections include pain at the site.
Intravenous administration can cause pain in the vein, flushing, and metallic taste, all of which are brief.

For both methods, side effects and serious complications can include:

Blood clots
Fever
Joint aches
Headache
Rashes
A delayed reaction of joint and muscle aches, headache, and malaise occurs 1 - 2 days after the infusion (most commonly with iron dextran) in about 10% of patients. These symptoms respond quickly to NSAIDs, such as ibuprofen or naproxen, in most people.
Iron toxicity. Symptoms include nausea, dizziness, and a sudden drop in blood pressure. Sodium ferric gluconate in sucrose (Ferrlecit) or iron sucrose (Venofer) may pose a lower risk for toxicity than iron dextran.
Allergic reactions. Allergic reactions that occur with intravenous iron can be very serious and, in rare cases, even fatal. Iron dextran appears to pose a much higher risk than sodium ferric gluconate complex in sucrose or iron sucrose, although allergic reactions can also occur with the latter forms.

Oral and injected iron should never be given at the same time. Intravenous iron therapy may be appropriate for some pregnant women who meet these requirements, depending on the pregnancy term and other factors.

Transfusions are used to replace blood loss due to injuries and during certain surgeries. They are also commonly used to treat severely anemic patients who have thalassemia, sickle cell disease, myelodysplastic syndromes, or other types of anemia. Some patients require frequent blood transfusions. Iron overload can be a side effect of these frequent blood transfusions. If left untreated, iron overload can lead to liver and heart damage.

Iron chelation therapy is used to remove the excess iron caused by blood transfusions. Patients take a drug that binds to the iron in the blood. The excess iron is then removed from the body by the kidneys. For many years, deferoxamine (Desferal) was the only drug used in chelation therapy. This drug is usually injected intravenously, using an infusion pump. The infusion can last 8 - 12 hours and may be needed 5 - 7 days a week until iron levels are normal. A new drug, deferasirox (Exjade), was approved in 2005 for children and adults as a once-daily treatment for iron overload due to blood transfusions. It does not require injections. Patients mix the deferasirox tablets in liquid and drink the medicine. Doctors hope that this new drug may make it easier for patients to tolerate chelation therapy. Studies have shown that deferasirox works as well as deferoxamine in ridding the body of excess iron.

Bloodless Medicine. Bloodless medicine and surgery is a new field designed to reduce or minimize blood loss and transfusions. It also attempts to address the problems in treating certain religious groups, such as Jehovah's Witnesses, who refuse transfusions. Some techniques involved in this field include new surgical procedures or drugs that minimize blood loss, the use of erythropoietin, volume expanders (administration of fluids to dilute blood), using tiny blood samples for testing, and methods (Cell Saver) for recovering and recycling blood during surgery.

Erythropoietin is the hormone that acts in the bone marrow to increase the production of red blood cells. It has been genetically engineered as recombinant human erythropoietin (rHuEPO) and is available as epoetin alfa (Epogen, Procrit, and Eprex). Novel erythropoiesis stimulating protein (NESP), also called darbepoetin alfa (Aranesp), lasts longer in the blood than epoetin alfa and requires fewer injections. These medications are also called “erythropoiesis-stimulating drugs.”

Levels of erythropoietin are reduced in anemia of chronic disease. Injections of synthetic erythropoietin can help increase the number of red blood cells in order to avoid receiving blood transfusions. Erythropoietin is used to treat anemia. It does not help improve anemia symptoms, fatigue, or quality of life for patients with cancer or HIV. This drug can cause serious side effects, including blood clots, and is approved only for treating patients with anemia related to the following conditions:

Cancer. For select patients, erythropoietin is used to treat the anemia associated with chemotherapy.
Chronic kidney failure. Erythropoietin is an important anemia treatment for patients with chronic kidney failure, including those on dialysis.
HIV/AIDS. Erythropoietin helps treat the anemia caused by zidovudine (AZT) therapy.

In November 2007, the Food and Drug Administration (FDA) made major changes to the prescribing information for erythropoiesis-stimulating drugs. The new labels describe in detail the risks that Aranesp, Epogen, and Procrit can pose to patients with cancer and chronic kidney disease. The FDA has also established separate dosing recommendations for each of these conditions.

Erythropoiesis-Stimulating Drugs and Cancer. Erythropoietin should be used only to treat anemia caused by chemotherapy -- not anemia due to other causes in patients with cancer. Erythropoietin treatment does not help prolong survival. In fact, these drugs can shorten survival time and cause tumors to grow faster. Discuss with your doctor whether an erythropoiesis-stimulating drug is appropriate for you.

Survival and tumor growth risks are especially pronounced for patients with advanced breast, head and neck, lymphoid, or non-small cell lung cancer when dosing attempts to achieve a hemoglobin level of 12 g/dL or greater. However, there may be similar risks for patients dosed to less than 12 g/dL. (The American Society of Clinical Oncology and the American Society of Hematology recommend starting erythropoietin when a patient’s hemoglobin level falls to less than 10 g/dL.) The doctor should use the lowest effective dose and erythropoietin treatment should be stopped as soon as the chemotherapy course is completed.

Erythropoiesis-Stimulating Drugs and Chronic Kidney Failure. For patients with chronic kidney failure, the FDA recommends that erythropoiesis-stimulating drugs be used to maintain hemoglobin levels between 10 - 12 g/dL. (The exact level within this range varies by individual.) There is a greater risk of death and serious cardiovascular events, such as heart attack, stroke, and heart failure when these drugs are used to achieve higher hemoglobin levels (13.5 - 14g/dL) compared to lower hemoglobin levels (10- 11.3 g/dL).

Warning Symptoms. Contact your doctor if you experience any of the following symptoms while being treated with an erythropoiesis-stimulating drug:

Pain or swelling in the legs
Worsening in shortness of breath
Increases in blood pressure (be sure to regularly monitor your blood pressure)
Dizziness or loss of consciousness
Extreme fatigue
Blood clots in hemodialysis vascular access ports

H. pylori, the bacteria that cause peptic ulcers, is associated with anemias from vitamin B12 deficiency and iron deficiency. People whose anemia is associated with H. pylori infection, however, do not respond to iron therapy. Studies indicate that the eradication of H. pylori infection with antibiotics can reverse anemia in such patients and may lead to long-lasting recovery.

Vitamin B12 Therapy. Injections of vitamin B12 (usually formulations called cyanocobalamin or hydroxocobalamin), oral folic acid therapy, or both, rapidly reverse the production of abnormally large red blood cells. (Treatments still may not reverse neurologic symptoms if they are extensive or have continued for too long.)

A typical regimen for vitamin B12 replacement is as follows:

If diagnostic tests indicate pernicious anemia and neurologic symptoms are present, vitamin B12 therapy should begin immediately. (Usually vitamin therapy is not an emergency, however.)
Cyanocobalamin or hydroxocobalamin injections are given every day for up to 2 weeks. Only small doses are needed.
This is followed by injections twice a week for another month. (Hemoglobin levels rise in the first week of therapy and reach normal levels in 8 weeks.)
After that, injections are usually given monthly.
During recovery, there is a risk of potassium deficiency as the new red cells take up the existing supply, so potassium supplements may be needed.

Other forms of vitamin B12 are also available and can be used to treat B12 deficiency. Vitamin B12 nasal spray offers the same advantage of avoiding the need for absorbing the vitamin in the GI tract without the inconvenience of the injections. Some experts feel that even oral B12 in high doses (2,000 mcg/day) can maintain B12 levels once the deficiency is treated.

The injections are safe and have no adverse side effects, but they may mask an underlying medical or psychological condition.

Some doctors give vitamin B12 injections for fatigue and other vague symptoms of general mild discomfort. In one study, 10% of patients in a rural clinic were given regular B12 shots, with 6% of patients having no medical need for them.

Folic Acid Treatment. Folate deficiency is easily remedied in 4 - 5 weeks with daily oral doses of 1 - 2 milligrams of folic acid. Many doctors give vitamin B12 along with folic acid unless B12 deficiency is definitely ruled out.

Resources

www.anemia.org -- National Anemia Action Council
www.nhlbi.nih.gov -- National Heart, Lung and Blood Institute
www.irondisorders.org -- Iron Disorders Institute
www.thalassemia.org -- Cooley's Anemia Foundation
www.aamds.org -- Aplastic Anemia & MDS International Foundation
http://kidney.niddk.nih.gov/kudiseases/pubs/anemia -- National Kidney and Urologic Diseases Clearinghouse (Anemia in kidney disease and dialysis)

References

Brotanek JM, Gosz J, Weitzman M, Flores G. Iron deficiency in early childhood in the United States: risk factors and racial/ethnic disparities. Pediatrics. 2007 Sep;120(3):568-75.

Killip S, Bennett JM, Chambers MD. Iron deficiency anemia. Am Fam Physician. 2007 Mar 1;75(5):671-8.

Komajda M, Anker SD, Charlesworth A, et al. The impact of new onset anaemia on morbidity and mortality in chronic heart failure: results from COMET. Eur Heart J. 2006 Jun;27(12):1440-6. Epub 2006 May 22.

KDOQI. KDOQI Clinical Practice Guideline and Clinical Practice Recommendations for anemia in chronic kidney disease: 2007 update of hemoglobin target. Am J Kidney Dis. 2007 Sep;50(3):471-530.

Maguire JL, deVeber G, Parkin PC. Association between iron-deficiency anemia and stroke in young children. Pediatrics. 2007 Nov;120(5):1053-7.

Martí-Carvajal AJ, Solà I. Treatment for anemia in people with AIDS. Cochrane Database Syst Rev. 2007 Jan 24;(1):CD004776.

Notebaert E, Chauny JM, Albert M. Short-term benefits and risks of intravenous iron: a systematic review and meta-analysis. Transfusion. 2007 Oct;47(10):1905-18.

Reveiz L, Gyte GM, Cuervo LG. Treatments for iron-deficiency anaemia in pregnancy. Cochrane Database Syst Rev. 2007 Apr 18;(2):CD003094.

Rizzo JD, Somerfield MR, Hagerty KL, et al. Use of epoetin and darbepoetin in patients with cancer: 2007 American Society of Clinical Oncology/American Society of Hematology Clinical Practice Guideline Update. J Clin Oncol. 2007 Dec 21 [Epub ahead of print]

Review Date:
1/1/2008
Reviewed By:
Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.

A.D.A.M. Copyright

adam.com

Breast milk

admin — Thu, 04 Sep 2008 18:56:41 -0700

Overview

Alternative Names
Function
Recommendations

HEALTH GUIDE REFERENCE FROM A.D.A.M

Alternative Names

Milk - human; Human milk; Milk - breast

Function

Breast milk is the perfect source of nutrition for infants. Breast milk contains appropriate amounts of carbohydrate, protein, and fat. It also provides the digestive proteins, minerals, vitamins, and hormones that infants need. Breast milk contains valuable antibodies from the mother that may help the baby resist infections.

Healthy infants have adequate iron stores to last until 8 months of age. Iron-rich foods can be started at this age. Your pediatrician or dietitian may recommend fluoride supplementation if you live in a community where water is not fluoridated.

Cow's milk by itself is inappropriate for infants less than 1 year old. The infant may develop an allergy to dairy products if given cow's milk too early in life. Although cow's milk contains most of the same components as breast milk, these components are not in the same amounts. Cow's milk also lacks the immune factors (antibodies) that help protect infants until their own immune system fully develops.

Commercially prepared formulas may be based on non-fat cow's milk, whey protein, or soy protein. In order to provide a balanced diet for an infant, formulas must be fortified with carbohydrates, fats, minerals, and vitamins. The antibodies found in breast milk, however, can never be added to formulas.

BREAST MILK PRODUCTION

Milk is produced in small sac-like glands in the breast. These sacs develop after specific hormones (such as estrogen, progesterone, pituitary prolactin, and placental lactogen) stimulate them, beginning during the second trimester of pregnancy.

The human breast does not store a large volume of milk, as cows do. Suckling stimulates the release of a hormone called prolactin, which stimulates milk production and the release of another hormone called oxytocin. Oxytocin stimulates contraction (or the "let-down reflex") of the milk glands. The milk is squeezed out of the milk gland, into the milk ducts, and into the nipple.

At the beginning of the feeding, the milk is bluish and contains lactose and proteins, but little fat. Such milk is called foremilk. The end of the feeding produces hindmilk. The hindmilk contains more fat, the main source of energy for your baby. If breast milk is allowed to sit for half-an-hour after being expressed, the "cream" separates and settles on top of the watery part. This is because human milk isn't homogenized, the process that makes the water and fat portion in milk stay blended.

MILK EJECTION REFLEX

At the start of a feeding, you will notice a pattern: suck, suck, suck, swallow, suck, suck, suck, swallow. This pattern may last up to 30 seconds, but could be longer. As the milk ejection reflex takes over, the pattern may be described as gulping: one swallow, one deep breath, one swallow, one deep breath. This pattern may last for 2 - 4 minutes.

Your baby may want to nurse longer (maybe 15 or 20 minutes) on this breast in order to get more fat from the hindmilk or because your baby needs to fill a need for sucking. Rather than watching the clock to let him nurse 10 minutes on each side, you may want to allow your baby to pull away from the first breast naturally before switching to the other breast.

Recommendations

Your milk supply will be established during the first few days and weeks after the birth of your baby. Nursing early (within the first half-hour), and frequently (on demand, or 8 - 12 times per day), allows you to nurse comfortably and efficiently. It usually takes less than 1 minute for an infant to stimulate the milk ejection reflex. You should feel little discomfort or pain when breast feeding appropriately.

Within 6 - 8 weeks, your milk supply will adjust to your baby's needs. Before that time, your breasts may feel either too full or empty. Frequent, comfortable feedings will maintain your milk supply. Your milk supply will increase or decrease based on your baby's hunger and energetic sucking (milk demand or use). Changes in your milk supply will occur within 1 - 3 days after changes in milk demand or use.

MILK HANDLING AND STORAGE

When storing milk for home use, wash your hands before expressing (pumping). Use containers that have been washed in hot, soapy water and rinsed well. Always date the milk before storing it.

Fresh breast milk can be kept at room temperature up to 8 hours, and refrigerated for 5 to 7 days. Frozen milk can be kept in a freezer compartment inside the refrigerator for 2 weeks; in a separate door refrigerator/freezer up to 3 or 4 months; or in a deep freezer at constant 0 degrees for 6 months. Frozen and thawed milk can be refrigerated for up to 9 hours, but it should not be refrozen.

Plastic containers are the best for storing breast milk. For freezing, use small (2 or 3 ounce) containers to avoid the waste of unused portions at the end of the day. Refrigerated milk and frozen milk should be warmed under a stream of warm tap water. Never microwave breast milk -- overheating destroys valuable nutrients and "hot spots" can scald your baby.

Breast-feeding tips

admin — Thu, 04 Sep 2008 18:56:44 -0700

Overview

Function
Recommendations
References

Illustrations

Breast feeding

HEALTH GUIDE REFERENCE FROM A.D.A.M

Function

Proper nipple care, positioning, appropriate nursing frequency, and other measures can prevent many common breast-feeding problems.

Recommendations

Most women's breasts have nipples that protrude slightly at rest and become erect when stimulated, as with cold. During pregnancy, the nipple and the pigmented area around it (areola) thicken in preparation for breast-feeding. Little glands (Montgomery glands) on the areola become more noticeable. They contain a lubricant to keep the nipple and areola from drying, cracking, or becoming infected.

Soaps and harsh washing or drying of the breasts and nipples can cause extreme dryness and cracking and should be avoided. Some experts recommend leaving milk on the nipple after feeding and allowing it to dry and protect the nipple. Keeping the nipples dry is important to prevent cracking and infection. For cracked nipples, apply 100% lanolin after feedings.

ENGORGEMENT

Many times the breasts will become swollen and painful 2-3 days after birth. The best treatment for this is to nurse the baby more frequently. Also, it may be helpful to pump your breasts should you have to miss a feeding, or if a feeding does not relieve the pain. See your health care provider if there is no improvement after 1 day.

BABY'S POSITION

Comfortable nursing requires correct positioning of the baby at the breast. Some guidelines are given to help you develop your own technique. Observing someone else breastfeed or practicing with an experienced nursing mother or a lactation consultant may also help.

Cradle Hold:

Sit in a comfortable chair, with arm rests if possible. Place your baby on your abdomen, tummy-to-tummy. The baby's head is cradled in the crook of your arm and the face to your breast. The baby's knees are underneath your other breast. The infant's head, back, and legs should all be in a straight line. This position can be held for the entire duration of the feeding. If you feel your nipple starting to hurt half-way into the feeding, check to see if your baby has slipped down and if the knees are starting to face the ceiling instead of being tucked in next to your side.

Football hold:

Cradle the back of your baby's head in your hand, with the body under your breast and toward the elbow. Place a pillow under your elbow to help you support your baby's bottom. Use your other hand to support your breast. This position allows you to control the baby's head and assures good positioning to latch on.

Side lying:

Lie on your side with one arm supporting your head. Your baby can lie beside you with the head facing your breast. Pull the baby in snugly and place a pillow behind to support the infant.

Rarely, a baby may have a sucking disorder which will need to be observed by a health care provider. A certified lactation consultant can be of tremendous help in teaching a baby to breast-feed. If your physician or local hospital cannot refer you to a lactation consultant, call ILCA at (708) 260-8874.

NURSING FREQUENCY

Most babies normally breastfeed every 1 1/2 to 2 1/2 hours during the first month. Breast milk is digested more quickly than formula so breast-feeding is needed more frequently. Even if you cannot measure the amount of milk your baby drinks, you can tell that the baby has had enough if: baby nurses every 2 to 3 hours, has 6 to 8 really wet diapers per day, and is gaining weight appropriately (1 pound each month). The frequency of feeding does decrease with age as the baby can eat more at each feeding. So, don't get discouraged; you will eventually be able to do more than sleep and nurse!

NIGHTTIME FEEDING

While you were pregnant, your baby was continuously fed and didn't know hunger. After birth, babies need to be fed frequently. During the first few weeks, your baby will want to breastfeed around the clock. This is perfectly normal. Some mothers find that bringing the baby in bed at night or placing a bassinet within reach, allows them to meet the child's needs while losing minimal rest. Other mothers prefer to keep the baby in a separate bedroom, and have a comfortable chair there. "Horror stories" are told about parents rolling over babies and smothering them during sleep. The American Academy of Pediatrics recommends you should not sleep with your infant. While nursing an infant in bed is acceptable, you should return the infant to their crib or bassinet when the feeding is done. Avoid bringing an infant into bed if you are very tired or taking medications that cause drowsiness.

If you return to work, don't be surprised if your baby wants to nurse more frequently at night. If you do not sleep well with your baby in your bed, you may find that keeping them in the same room or a room close enough to hear them is just fine.

You may have heard that night nursing can lead to what used to be called baby bottle tooth decay. Breast milk by itself is the healthiest food for babies’ teeth, day or night. It tends to slow bacterial growth and acid production. However, when breast milk is alternated with sugary foods or drinks, the rate of tooth decay can be faster than with sugar alone. Night nursing can be wonderful, but avoid sugary snacks and drinks for your baby or toddler throughout the day – and especially close to sleep time.

MILK SUPPLY

Some mothers stop nursing during the first few days or weeks because they feel they aren't producing enough milk. It may seem like your baby is always hungry. You can't measure the amount of milk your baby is drinking so you may worry that you aren't producing enough milk. In reality, your baby's increased need to nurse signals your body to produce more milk. This is a natural way your body determines the amount of milk needed and provides an adequate milk supply.

The first weeks may be difficult and frustrating for you but don't give up. If you can resist supplementing your baby's diet with formula feedings for the first four to six weeks, your body will respond appropriately and produce an adequate supply of milk. Supplementing your baby's diet with formula feeding will only trick your body into believing the current supply of breast milk is adequate.

GROWTH SPURT

Around the 2nd week, and the 2nd, 4th, and 6th months, it may seem that your baby wants to nurse "all the time." Your baby may want to nurse every 30 or 60 minutes, and stay at the breast for longer periods. It may seem that the only thing you are doing all day is nursing. This increase in nursing is normal and signals your body to produce more milk as your baby enters a growth spurt. Within a few days, your milk supply will have increased to provide enough milk at each feeding and the baby will start eating less frequently and for shorter periods of time.

Many nursing mothers have trouble finding the time to devote to their baby's increased feeding needs during this adjustment period. Often, understanding how and why this happens and that it is only temporary can help. Slow down and enjoy the job of feeding your baby; a job that only you can do. Ask for and accept help with other responsibilities to free your time for feeding.

THE 6 O'CLOCK SYNDROME

Babies frequently seem fussy and want to nurse more frequently late in the afternoon and into the evening, when everyone else (especially you) is tired. You may feel too tired to nurse again or assume that you just don't have any more milk to give. It may be tempting to give your baby a bottle of formula while you attend to other responsibilities.

But remember, bottle feeding your baby formula when you are tired or your milk supply seems low will signal your body to produce less milk which will result in more fatigue and frustration for you and your baby. breast-feeding a baby on demand is full-time and exhausting work. Your body needs energy to produce enough milk. Be sure you get adequate nutrition, rest, and sleep. Taking good care of yourself is necessary if you're going to take good care of your baby.

BABY'S STOOLS

Your baby's bowel movements (stools) during the first two days will be black and tar-like (sticky and soft). Early and frequent breast-feeding during the first 48 hours will flush this sticky stool (meconium) from the infant's bowels. The stools will become yellow-colored and seedy. This is the normal stool consistency for a breastfed baby and should not be confused with diarrhea.

During the first month, your baby may have a bowel movement after each breast-feeding. This frequency decreases with age. Don't worry if bowel movements occur after every feeding or every three days, as long as the pattern of bowel movements is regular and your baby is growing well (gaining weight).

NIPPLE CONFUSION

The human breast and nipple are very different from a bottle and nipple. A baby has to learn to adapt to the type of nipple used. Exposure to a rubber nipple can create nipple confusion for your baby and make breast-feeding more difficult, especially during the first two weeks. After that, your milk supply will be well established, you both will be comfortable with the technique and routine of breast-feeding, and occasional use of a rubber nipple will cause less nipple confusion.

References

American Academy of Pediatrics Task Force on Sudden Infant Death Syndrome. The changing concept of sudden infant death syndrome: diagnostic coding shifts, controversies regarding the sleep environment, and new variables to consider in reducing risk. Pediatrics. 2005;116:1245-1255.

American Dental Association. ADA statement on early childhood caries. Chicago, IL. Position Statement 2000:454.

Azevedo TD. Feeding habits and severe early childhood caries in Brazilian preschool children. Pediatr Dent. 2005;27(1): 28-33.

Ribeiro NM, Ribeiro MA. Breastfeeding and early childhood caries: a critical review. J Pediatr (Rio J). 2004 Nov;80(5 Suppl):S199-210.

Rosenblatt A, Zarzar P. Breast-feeding and early childhood caries: an assessment among Brazilian infants. Int J Paediatr Dent. 2004 Nov;14(6):439-45.

Review Date: 1/14/2008

Reviewed By: David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc. Previously reviewed by Daniel Rauch, MD, FAAP., Director, Pediatric Hospitalist Program, New York University School of Medicine, New York, NY (Review provided by VeriMed Healthcare Network); and Alan Greene, MD, FAAP, Department of Pediatrics, Stanford University School of Medicine, Lucile Packard Children’s Hospital; Chief Medical Officer; A.D.A.M., Inc. (7/26/2007)

A.D.A.M. Copyright

adam.com

Source Doc: 1_002453