Does folic acid raise the risk of cancer?

What the largest analysis found

A 2013 analysis pooled the data of 13 trials with 49,621 people who took folic acid or a placebo for about 5 years. Folic acid made the level of folic acid in the blood about 4 times higher. It did not change the number of cancers: 1,904 in the folic acid groups and 1,809 in the placebo groups (rate ratio 1.06, not significant).^[1] There was also no effect on cancer of the large intestine, prostate, lung or breast. The doses in these trials were about 10 times higher than what fortified flour gives.^[1]

Trials that found more cancers

Some single trials found more cancers with folic acid:^[2]

• In 2 trials in Norway, 3,411 people with heart disease took 800 µg of folic acid with vitamin B12 or no supplement for about 3 years. Cancer was 21% more common, and cancer deaths 38% more common, with the supplement.^[2]
• In a trial in people who had had colorectal polyps, 1,000 µg of folic acid a day raised the risk of having 3 or more polyps and of other cancers. A later analysis found more prostate cancer.^[2]
• A meta-analysis of 6 trials with 25,738 men found 24% more prostate cancer with folic acid than with placebo.^[2]
• In 2,919 people aged 65 or older, 2 years of folic acid with vitamin B12 and vitamin D led to more cancers than vitamin D alone.^[2]

Colorectal polyps

A pooled analysis of 3 large trials included people who had had colorectal polyps. Folic acid for up to 3.5 years did not raise or lower the number of people whose polyps came back.^[2] In a trial in 1,470 older women, 2,500 µg of folic acid a day with vitamins B6 and B12 for 7.3 years did not change the rate of polyps.^[2]

What expert bodies concluded

In 2015, an expert panel of the US National Toxicology Program and NIH ODS met on this question. It concluded that folic acid supplements do not lower the risk of cancer in people who already get enough folate. It also said that the signs of faster cancer growth justify more research.^[2] In 2023, EFSA found the evidence not enough to conclude that folate causes colorectal or prostate cancer.^[3]

Why timing may matter

One idea is that folate may protect healthy tissue in the early stages, but high doses may help cancer grow once precancerous changes exist. This idea comes from mixed trial results and from lab and animal studies.^[2] Folate from a normal diet may lower the risk of some cancers. The effect of folic acid supplements is unclear, most of all in people who have had colorectal polyps or cancer.^[2]

Who should ask first

People who have had colorectal polyps or cancer should ask a doctor before taking folic acid supplements, because the effect in them is unclear.^[2] People who take methotrexate for cancer should ask their oncologist, because folate could interfere with the drug.^[2]