How does folic acid affect my risk for cancer?

Dariush Mozaffarian, MD
Internal Medicine
The relationship between B vitamins -- folic acid, in particular -- and cancer has proved complex. There's evidence that people with low blood levels of folate are more prone to cancer, and several large, long-term studies suggest that people who consume more folic acid are less likely to develop colon cancer. Other research suggests that greater consumption of folic acid can lower breast cancer risk, at least among women who drink alcohol and have low folic acid levels. Alcohol consumption is believed to increase the risk of some cancers, including breast and colon cancers. But folic acid seems to counteract, in part, such adverse effects of alcohol.

But while adequate amounts of folic acid appear to stifle the birth and spread of early tumors, it's possible that too much may speed up the growth of existing tumors. In fact, one randomized trial found that folic acid supplements increased the recurrence of adenomatous polyps, which can turn into colon cancer. Several studies suggest that excess folic acid may raise the risk of cancer of the colon, breast, and prostate. A study that reviewed cancer registries in the United States and Canada (which also began folic acid fortification in 1998) revealed a slight uptick in colon cancer rates in the early fortification years, when average blood levels of folate doubled. The findings were published in Cancer Epidemiology Biomarkers and Prevention. However, the steady decline in deaths from colon cancer before and after folic acid fortification suggests that improved screening from colonoscopies is a more likely explanation for the upward blip.

A study in The Journal of the American Medical Association documented an increased risk of cancer in people who took folic acid and vitamin B12 supplements. Done in Norway (where there is no folic acid fortification), the study pooled data from two trials originally designed to see if B vitamins could lower heart disease risk in people who already had the disease. But it's worth noting that the participants were taking 800 micrograms (mcg) of folic acid, which is double the Recommended Dietary Allowance (RDA) in the United States. In fact, the tolerable upper limit -- the maximum safe amount -- for folic acid is 1,000 mcg per day.
Folic acid has been shown to protect against certain cancers. This B vitamin is required to make DNA and RNA, which are involved in protein sysntesis. Folic acid also helps to prevent changes to DNA. Low blood levels of folic acid are associated with cancer risks. This includes breast and colon cancers. Folic acid is often used with a drug called methotrexate to treat cancer. Cancer cells divide very quickly. Methotrexate actually reduces the activity of enzymes that use folate. An enzyme is a protein that causes changes in other substances. This combination may reduce cancer risks.
High exposure to folic acid, which is legally required to be added to flour and flour products in the United States to prevent fetal developmental defects, has been linked to unanticipated risks such as childhood allergy and asthma and elevated cancer risk. In a study in Norway, where folic acid is not added to food, treatment with folic acid plus vitamin B12 was associated with higher cancer rates and all-cause mortality in people with ischemic heart disease. 

In Australia, a study found that consuming synthetic folic acid was statistically associated with colon polyps in older men. Another study in the U.S. found an increased risk of breast cancer among European-American women who ingested the most synthetic folate from fortified foods. In contrast, eating foods naturally high in folate was associated with lower breast cancer risk. In animal studies, folic acid has accelerated progression of mammary tumors.

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