Folate - Folic Acid

Folate, a B vitamin, plays a critical role in many biological processes. It participates in the crucial biological process known as methylation, and plays an important role in cell division: without sufficient amounts of folate, cells cannot divide properly. Adequate folate intake can reduce the risk of heart disease and prevent serious birth defects, and it may lessen the risk of developing certain forms of cancer. Because the chances are good that you dont get enough folate in your diet, this is one vitamin really worth paying attention to.

Folate requirements rise with age. The official U.S. and Canadian recommendations for daily intake are as follows:

• Infants 0–6 months, 65 mcg 7–12 months, 80 mcg
   
• Children 1–3 years, 150 mcg 4–8 years, 200 mcg
   
• Males 9–13 years, 300 mcg 14 years and older, 400 mcg
   
• Females 9–13 years, 300 mcg 14 years and older, 400 mcg
   
• Pregnant women, 600 mcg
   
• Nursing women, 500 mcg

Until recently, folate deficiency was fairly common in the developed world, causing thousands of children to be born with preventable birth defects.1,2,3 However, in 1998, widespread fortification of cereal products began in the U.S. and Canada. As a result, the prevalence of folate deficiency has begun to decrease in these countries.
Various drugs may impair your body's ability to absorb or utilize folate, including antacids, bile acid sequestrants (such as cholestyramine and colestipol), H2 blockers, methotrexate, various antiseizure medications (carbamazepine, phenobarbital, phenytoin, primidone, or valproate), sulfasalazine and possibly other certain NSAID-type drugs, high-dose triamterene, nitrous oxide, and the antibiotic trimethoprim-sulfamethoxazole.In addition, some of these drugs might put pregnant women at higher risk of giving birth to children with various kinds of birth defects; taking folate supplements may help reduce this risk.31Oral contraceptives may also affect folate slightly, but there doesn't appear to be a need for supplementation.
Good sources of folate include dark green leafy vegetables, oranges, other fruits, rice, brewer's yeast, beef liver, beans, asparagus, kelp, soybeans, and soy flour.

For most uses, folate should be taken at nutritional doses, about 400 mcg daily for adults. However, higher dosages—up to 10 mg daily—have been used to treat specific diseases. Before taking more than 400 mcg daily, it is important to make sure that you dont have a vitamin B12 deficiency (see Safety Issues). A particular kind of digestive enzyme, pancreatin, may interfere with the absorption of folate. You can get around this by taking the two supplements at different times of day.

The use of folate supplements by pregnant women dramatically decreases the risk that their children will be born with a serious birth defect called neural tube defect. This congenital problem consists of problems with the brain or spinal cord. Folate supplements may also help prevent other types of birth defects, such as defects of the heart, palate, and urinary tract; conversely, drugs that impair folate action may increase risk of birth defects. (See Requirements/Sources for a list of the drugs involved.) An observational study suggests that folate supplements may reduce this risk in pregnant women taking such drugs. Folate also lowers blood levels of homocysteine, a suspected risk factor in heart disease. According to some experts, increased folate supplementation of foods could reduce heart disease deaths in the United States by as much as 50,000 people annually. Folate has been suggested as a treatment for depression. In addition, according to one double-blind placebo-controlled trial, folate supplements at a dose of 500 mcg daily may help antidepressants work more effectively. Studies suggest that a deficiency in folate might predispose people to develop cancer of the cervix, colon, lung, breast, pancreas, and mouth. Large observational studies suggest that folate supplements may help prevent colon cancer, especially when taken for many years. This is yet another reason to make sure you get enough folate daily. High-dose folate (10 mg daily) might be helpful for normalizing abnormalities in the appearance of the cervix (as seen under a microscope) in women taking oral contraceptives, but it does not appear to reverse actual cervical dysplasia. Folate deficiency may also increase the risk of Alzheimers disease, although this has not yet been proven. Folate supplements may be helpful for individuals taking the drug methotrexate for certain conditions. Folate supplements may also help medications in the nitroglycerin family remain effective. Very high dosages of folate may be helpful for gout, although some authorities suggest that it was actually a contaminant of folate that caused the benefit seen in some studies. Furthermore, other studies have found no benefit at all. Based on intriguing but not yet definitive evidence, folate in various dosages has been suggested as a treatment for bipolar disorder, osteoarthritis (in combination with vitamin B12), osteoporosis, restless legs syndrome, rheumatoid arthritis, seborrheic dermatitis, and vitiligo (splotchy loss of skin pigmentation). Other conditions for which it has been suggested include migraine headaches and periodontal disease.

Birth Defects Very strong evidence tells us that regular use of folate by pregnant women can reduce the risk of neural tube defect by 50 to 80%. Less direct evidence suggests that folate can help prevent other kinds of birth defects, especially among women using medications that interfere with folate. Heart Disease Prevention According to a recent study that examined data on 80,000 women, a high intake of folate may cut the risk of heart disease in half. Folate is thought to work by reducing blood levels of a substance called homocysteine. Individuals with high homocysteine levels appear to have more than twice the risk of developing heart disease than those with low homocysteine levels, and folate supplements, alone or in combination with vitamin B6 and vitamin B12, effectively reduce the level of homocysteine in the blood. However, the dose of folate required to achieve maximum homocysteine reduction is 800 mcg daily, higher than the usual recommendations. Depression A 10-week double-blind placebo-controlled trial of 127 individuals with severe major depression found that folate supplements at a dose of 500 mcg daily significantly improved the effectiveness of fluoxetine (Prozac) in female participants. Improvement in male participants was not significant, but blood tests suggest that higher intake of folate might be necessary for men. Methotrexate Side Effects Methotrexate is used in cancer chemotherapy as well as for treating inflammatory diseases such as rheumatoid arthritis and psoriasis. While often highly effective, it can produce a number of severe side effects. These include liver toxicity as well as gastrointestinal distress. Supplementation with folate may help. Methotrexate is called a folate antagonist because it prevents the body from converting folate to its active form. In fact, this inactivation of folate plays a role in methotrexates therapeutic effects. This leads to an interesting Catch-22: methotrexate use can lead to folate deficiency, but taking extra folate might prevent methotrexate from working properly. However, evidence suggests that individuals who take methotrexate for rheumatoid arthritis, juvenile rheumatoid arthritis, or psoriasis can use folate supplements to good effect. Not only does the methotrexate continue to work properly, but its usual side effects may decrease as well. For example, in a 48-week double-blind placebo-controlled trial of 434 individuals with active rheumatoid arthritis, use of folate helped prevent liver inflammation caused by methotrexate. This effect allowed more participants to continue methotrexate therapy; the development of liver inflammation often requires people to stop using the drug. A slightly higher dose of methotrexate was needed to reach the same level of benefit as taking methotrexate alone, but researchers felt this was worth it. Benefits have been seen in other studies of rheumatoid arthritis as well as in juvenile rheumatoid arthritis. In addition, another study found that folate eliminated the gastrointestinal side effects associated with oral methotrexate therapy for psoriasis, without interfering with the drugs therapeutic benefits.

Folate at nutritional doses is extremely safe. The only serious potential problem is that folate supplementation can mask the early symptoms of vitamin B12 deficiency (a special type of anemia), potentially allowing more irreversible symptoms of nerve damage to develop. For this reason, when taking more than 400 mcg daily, it is important to get your B12 level checked. See the article on vitamin B12 for more information. Very high dosages of folate, greater than 5 mg (5,000 mcg) daily, can cause digestive upset. The maximum recommended dosage of folate for pregnant or nursing women is 1,000 mcg daily (800 mcg if under 19 years old). As mentioned previously, the antiseizure drug phenytoin may interfere with folate absorption. However, folate may reduce the effectiveness of phenytoin. If you are taking phenytoin, you should consult with a physician about the proper dosage of folate for you. As noted above, individuals who are taking the drug methotrexate for rheumatoid arthritis, juvenile rheumatoid arthritis, or psoriasis can safely take folate supplements at the same time. However, if you are taking methotrexate for any other purpose, do not take folate except on the advice of a physician.

If you are taking

• Aspirin, other anti-inflammatory medications, drugs that reduce stomach acid (such as antacids, and H2 blockers), sulfa antibiotics, oral contraceptives, estrogen-replacement therapy, valproic acid, carbamazepine, phenobarbital, primidone, triamterene, nitrous oxide, or bile acid sequestrants(such as cholestyramine and colestipol): You may need to take extra folate.
• Phenytoin: You may need more folate. However, too much folate can interfere with this medication and cause seizures! Physician supervision is essential.
• Drugs in thenitroglycerinfamily: Folate may help them remain effective.
• Pancreatin (a proteolytic enzyme): It may be advisable to separate your dose of pancreatin from your dose of folate by at least 2 hours in order to avoid absorption problems.
• Methotrexate for rheumatoid arthritis, juvenile rheumatoid arthritis, or psoriasis: evidence suggests that folate supplements may reduce side-effects of the drug without decreasing its benefits. Nonetheless, physician supervision is highly recommended.

NOTE: if you are taking methotrexate for other conditions, folate might decrease the drug's effectiveness.