September 23, 2014
Folate: Nutritional Chameleon?

Folate: Nutritional Chameleon?

by Berkeley Wellness  |  

What folate/folic acid is: Abundant in leafy greens and other vegetables, beans, some fruits and wheat germ, the B vitamin folate is essential to healthy cell growth and thus is especially important during pregnancy. Much recent research has focused on folic acid, the synthetic form of folate used in dietary supplements, enriched wheat flour and fortified foods.

Besides preventing birth defects, this vitamin has been linked to heart health and cancer prevention. 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, and lately some studies have linked folic acid to a higher risk of some cancers.

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 percent of those over 60 take a multivitamin, which typically supplies 400 micrograms (listed as 100 percent of the “Daily Value” on the label). In addition, many people take a supplement of B vitamins 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.

Claims, purported benefits: Prevents birth defects; reduces the risk of cancer, heart disease, dementia.

Folic acid: the latest research

Recent research suggests that folic acid may be a nutritional chameleon—protective in some circumstances, dangerous in others.

Cardiovascular disease. B vitamins, especially folate, help lower blood levels of homocysteine. Studies have found that people with high levels of this amino acid are more likely to have heart disease, strokes and cognitive decline. But in recent years 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.

A 2009 review from the Cochrane Collaboration concluded that there’s no evidence to support the use of B vitamins as a preventive for heart disease. And in 2010, in the Archives of Internal Medicine, a well-designed British study looked at 6,000 heart attack survivors who took folic acid and vitamin B12 for almost seven years. Though their homocysteine levels dropped, they were no less likely to have another heart attack or a stroke than their counterparts who took a placebo.

A 2011 Dutch clinical trial whose results were published in the American Journal of Clinical Nutrition found that folic acid supplements (800 micrograms a day) taken for three years did not slow atherosclerotic progression or arterial stiffening, which are markers for cardiovascular risk.

Brain health. Studies on the effects of taking folic acid and/or lowering homocysteine on brain health have yielded contradictory findings. A 2010 English study published in the online journal PLOS ONE found that people with mild cognitive impairment who took large doses of B12, B6 and folic acid had much less brain shrinkage over a two-year period, suggesting a reduced risk of dementia. A study in Stroke in 2013, however, found that high doses of these B vitamins taken for three years had no effect on cognitive decline in people who had previously had a stroke or TIA.

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. In addition, 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 a placebo.

A study from Harvard researchers in 2009, however, found that this same high dose neither prevented nor promoted the growth of adenomas in people prone to them. In fact, people with initially low blood levels of folate seemed to benefit. The large British study mentioned earlier, which focused on cardiovascular disease, also found that folic acid supplements (2,000 micrograms a day) had no effect on cancer risk.

In 2011, a large observational study in the journal Gastro­­enterology linked both folate and folic acid to a reduced risk of colon cancer, though relatively few men took doses of 1,000 micrograms or more. And a meta-analysis published in the International Journal of Cancer combined data from the three largest clinical trials of folic acid supplementation for the prevention of colorectal adenomas. It found that after up to 3.5 years of folic acid use, “there is no clear decrease or increase in the occurrence of new adenomas in patients with a history of adenoma.”

A 2012 study in the Journal of the National Cancer Institute concluded that B vitamins do not affect the risk of colorectal adenomas. It compared high doses of folic acid, B12 and B6 to a placebo in 5,400 women at high cardiovascular risk and found no effect on adenoma risk. And in 2013, an analysis of 13 clinical trials, published in the Lancet, concluded that folic acid supplements, even in high doses, do not increase or decrease the risk of cancer, including colon cancer.

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 two have 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 in the Journal of the National Cancer Institute in 2009 found that the risk of prostate cancer more than doubled in men taking folic acid supplements (1,000 micrograms a day). But folate from food seemed to reduce the risk slightly.

Lung cancer. Published in the Journal of the American Medical Association in 2010, a Norwegian study of people with heart disease (many of whom were smokers) found that those taking 800 micrograms of folic acid daily, plus vitamin B12, had a higher rate of cancer, especially lung cancer, than those taking a placebo.

Cancer conundrum. Timing may be crucial. Healthy people who increase their folate or folic acid 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. This 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.

Autism. To prevent neural tube birth defects, women who may become pregnant have long been advised to consume folic acid. However, women who take folic acid supplements before and after becoming pregnant have a reduced risk of having a child with autism, according to a large observational study from Norway in the Journal of the American Medical Association in 2013. The researchers found that women who took the supplements (any dose) during the crucial window from four weeks before to eight weeks after conception were 40 percent less likely to have children with autism than nontakers. A study of women in California, published in the American Journal of Clinical Nutrition in 2012, also suggested a reduction in autism risk from folic acid. These findings need to be confirmed by further research.

Folate for Depression?

Many observational studies have found that people with low dietary intakes or blood levels of folate have higher rates of depression. Can supplements of this vitamin help boost mood?

Bottom line: Women of childbearing age should take a supplement providing at least 400 micrograms of folic acid (the amount in most multivitamins) a day, and if they become pregnant, 600 to 800 micrograms (the amount in prenatal vitamins) a day. If you have chronic or recurrent depression, talk with your doctor about having your folate level measured.

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 multivitamin 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 more. Thus it’s easy to consume more than 1,000 micrograms a day, the amount found to increase cancer risk in some studies.

Originally published September 2009. Updated December 2013.