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A Busy B—Maybe Too Busy

The B vitamin folate has gotten lots of publicity in recent years. Abundant in leafy greens and other vegetables, beans, some fruits, and wheat germ, folate is essential to healthy cell growth and thus is especially important during pregnancy. Actually, what has attracted the most attention is folic acid, the synthetic form of folate used in enriched wheat flour, fortified foods, and supplements. Besides preventing birth defects, this vitamin has been linked to heart health and cancer prevention. But lately some studies have linked folic acid to an increased risk of some cancers. Is folic acid a nutritional chameleon, as one scientist put it—protective in some circumstances, dangerous in others?

Folate for healthy mothers and babies . . .

In pregnant women low blood levels of folate can lead to neural tube birth defects, such as spina bifida. These devastating defects occur in the first days or weeks of pregnancy, before a woman may know she is pregnant. So women need to start building folate stores before conception. Adequate folate levels may also reduce the risk of early miscarriages, premature birth, and congenital heart defects.

Since 1992 the U.S. government has urged all women of childbearing age to consume at least 400 micrograms of folate daily, and in 1998 the FDA required small amounts of folic acid to be added to refined wheat flour. As a result, the number of neural tube defects has fallen by more than a third. The story has been similar in Canada.

To be sure they’re getting enough folate, all women who may become pregnant are advised to take a multivitamin containing 400 micrograms of folic acid. The folic acid from supplements and fortified foods is better absorbed than the folate found naturally in foods. This year the U.S. Preventive Services Task Force upped the recommendation to 400 to 800 micrograms of supplemental folic acid daily.

. . . and for healthy hearts and brains?

During the past 20 years there was hope that folic acid supplements could help prevent cardiovascular disease as well as dementia. B vitamins, especially folate, help lower blood levels of homocysteine. Studies found that people with high levels of this amino acid are more likely to have heart disease, strokes, and cognitive decline. But some more recent research has found that lowering homocysteine via vitamin supplements, including folic acid, does not reduce the likelihood of heart disease, and two studies found increased risk. And studies on the effects of lowering homocysteine and/or taking folic acid on brain health have yielded contradictory findings.

. . . and cancer prevention—or promotion?

Since folate is vital for healthy cell growth, it’s theorized that the vitamin may help prevent the abnormal cell growth characteristic of cancer. But there are equally plausible theories as to how folate may increase cancer risk.

• Colon cancer. Many studies have linked a high folate intake from food or supplements with a reduced risk of colon cancer. Diets rich in fruits and vegetables go along with a lower risk of colon cancer, and the folate in these foods may be one reason for this. But some research has found no relationship. Moreover, a widely publicized study from 2007 found that people prone to precancerous colon polyps (adenomas) who were given a high dose of folic acid—1,000 micrograms a day—for three years had more new or advanced polyps than those taking placebo.

• Breast cancer. A few recent studies have suggested that a high intake of folate may reduce the risk of breast cancer. But the benefit was found only in certain groups of postmenopausal women, such as those with very low folate intakes to begin with, or heavy drinkers (alcohol interferes with folate in the body and also increases the risk of breast cancer). And other studies have found no benefit, while one suggested increased risk.

• Prostate cancer. Again, studies have produced mixed results, with some showing an increased risk with high intakes. Notably, a large 10-year study this year in the Journal of the National Cancer Institute found that the risk of prostate cancer more than doubled in men taking folic acid (1,000 micrograms a day). But folate from food seemed to reduce the risk slightly.

Cancer conundrum: Timing may be crucial. Healthy people who increase their folate intake may reduce their risk, but in those who already have precancerous growths or cancer, large amounts of folic acid may fuel the progression. The dose may also be the key: animal studies have shown that inadequate intakes may increase cancer risk, but that high intakes may also do so. That suggests that people who are deficient in folate may get some protection by boosting their intakes, while those who already have enough in their body and take high doses may actually be harmed. No one knows what the optimal folate intake is to reduce the risk of cancer.

Bottom line

The recommended dietary allowance (RDA) for folate is 400 micrograms daily for adults, and 600 micrograms for pregnant women. Many Americans get much more than that, since about 40% of those over 60 take a multi, which typically supplies 400 micrograms (listed as 100% of the "Daily Value" on the label). In addition, many people take a supplement of B vitamins (called the B-complex, which includes folic acid) and eat highly fortified foods. The government has set an upper limit for folic acid from pills and fortified foods at 1,000 micrograms a day, because higher levels may "mask" a vitamin B12 deficiency in older people and thus delay its diagnosis and treatment, and may also worsen the neurological damage of a B12 deficiency.

There are still a lot of unknowns, but here is our best advice:

• Women of childbearing age should take a supplement providing 400 to 800 micrograms of folic acid a day.

• To be on the safe side, men and postmenopausal women should limit their intake of folic acid from supplements and fortified foods to not much more than the Daily Value—especially if they have had colon cancer or polyps. Read the labels on foods, beverages, and supplements. A multi supplies 400 micrograms; one small serving of a highly fortified cereal (such as Total, Special K, or Product 19) adds another 400; a B-complex pill, 400 more; enriched grain products, perhaps another 200; and vitamin-spiked bottled waters, energy drinks, and sports bars add even more. Thus it’s easy to consume more than 1,000 micrograms a day, the amount found to increase cancer risk in some studies.

• Don’t worry about the folate naturally in foods, such as leafy greens and citrus. No research has ever linked such foods to an increased risk of cancer—instead, studies have found them to be protective. And don’t worry about the modest amount of folic acid added to foods made from enriched wheat flour. Still, whole-wheat products, which retain the grain’s natural folate, are healthier choices.

UC Berkeley Wellness Letter, September 2009