Monday, April 20, 2009

Folic Acid: Risks or Myths?

There are theoretical risks for isolated folic acid in high doses. But these supposed risks fly in the face of established science and are controversial, not at all conclusive. There is also confusion over the significance of the supposed risks of high dose isolated folic acid in test tube and animal studies which do not identify a danger for moderate level supplementation - or even higher dose supplementation if combined with multivitamins or vitamin B-12. In other words, if the theoretical risks do not reflect real world human activities and the way that people actually obtain essential vitamins from their diet, including supplementation, aren’t these improbable risks really irrelevant to us? On the other hand, these negative reports may stop people from taking essential vitamins in quite reasonable amounts even though they are known to promote human health. Published human clinical science has determined that folic acid can reduce birth defects and has been proven to do so. Clinical science has also found mechanisms by which folic acid can prevent cancers, as well as the theoretical possibility that very high doses given in isolation can stimulate colorectal cancers including prostate cancer. There is stronger evidence that taking B-12 or a multivitamin along with high folic acid actually reduces rates of prostate and colon cancers. For example, in one human clinical trial where food intake, blood and plasma levels of folic acid were considered, Multivitamin users had about 2/3 the risk of subsequent prostate cancer as Non-Multivitamin users; only the independent use of folic acid was considered a risk factor. The report concluded, “…on the whole, the biological and epidemiological evidence supports the potential for folate supplementation to prevent colorectal neoplasia in humans.” (Cole) This shows that single nutrient studies, especially if unpublished and not peer reviewed or subjected to subsequent comments by experts in the field, should not be given overinflated importance when they are merely preliminary studies that may conflict with more relevant published human clinical studies. In the case of such conflicts, the human clinicals should bear more weight and be seen as more convincing, especially those that mimic the full range of variables (nutrients) in the human diet. Folic acid itself is considered non-toxic. Also, “data from in vitro and in vivo studies indicate that folic acid is not genotoxic [damaging to genetic material]”. (UK Food Standards Agency) There have been reports of levels as high as 50,000 micrograms per day given with no signs of toxicity in humans. There are accepted problems associated with levels exceeding 5,000 micrograms a day, which resulted in a far more conservative Upper Limit of 1,000 micrograms daily being set. This effect has been demonstrated in patients suffering from pernicious anemia taken off of their successful medicine (vitamin B-12), which was replaced by 5,000 mcg/day of folic acid. The substitution of one vitamin for another was unsuccessful in treating pernicious anemia, but did mask some symptoms. This test – and a large safety margin - provided the rationale given for the current Upper Limit. But it does not logically imply danger to those who are not severely anemic and who obtain B-12 in adequate amounts. (Oakley) It is very uncommon for people to take folic acid singly in doses of thousands of micrograms daily, but this is the method which test tube and animal studies often use. Overemphasizing unproven cancer risks requires ignoring valid studies showing reductions of cancers by taking folic acid and multivitamins. Needlessly scaring people from taking their vitamins, which have in human clinical trials shown significant improvements in birth defect and cancer rates, is not helpful to our common goal of protecting public health. Neil E. Levin, CCN, DANLA QUOTES & REFERENCES: Dr. Gideon Koren, director of the Motherisk Program at the Hospital for Sick Children in Toronto , note that rates of birth defects such as spina bifida and cancers such as neuroblastoma have plummeted since folic acid supplementation was begun. He believes that the known benefits outweigh theoretical risks. "I think it is very important to remember that the scares about cancer are mostly from animal studies and laboratory studies, not from human experience," he says. "We are still awaiting to see such human experience." Health Canada recommends all women of childbearing age take 0.4 mg of folic acid a day, but says taking more than 1 mg a day of folic acid without the advice of a doctor is not recommended. "We continue to encourage all women who could become pregnant to take a daily supplement," the agency says on its website. "We caution against taking more than one multivitamin tablet a day, as excess amounts of certain vitamins can be toxic." “All women who could become pregnant should take a multivitamin containing 0.4 mg of Folic Acid every day. To help reduce the risk of NTDs, you should start taking the vitamin supplement at least three months before you get pregnant and continue through the first three months of your pregnancy. Talk to your health professional to find the supplement best for you…If you have had a previous pregnancy affected by an NTD or have a family history of this problem, see your doctor. You may be advised to take a higher dosage of Folic Acid. If you have diabetes, obesity or epilepsy, you may be at higher risk of having a baby with an NTD, and you should see your doctor before planning pregnancy… Do not take more than one daily dose of vitamin supplement as indicated on the product label. Increasing your dose of Folic Acid beyond 1 mg per day without the advice of a doctor is not recommended.” (Public Health Agency of Canada , 2/27/08; The NIH’s Office of Dietary Supplement reports on the prevention of cancer with the use of supplemental folic acid as part of a multivitamin: “Over 88,000 women enrolled in the Nurses' Health Study who were free of cancer in 1980 were followed from 1980 through 1994. Researchers found that women ages 55 to 69 years in this study who took multivitamins containing folic acid for more than 15 years had a markedly lower risk of developing colon cancer.” (Giovannucci E, et al. Multivitamin use, folate, and colon cancer in women in the Nurses' Health Study. Ann Intern Med 1998;129:517-24; Cole BF, et al. Folic acid for the prevention of colorectal adenomas: a randomized clinical trial. Polyp Prevention Study Group. JAMA. 2007 Jun 6;297(21):2351-9. PMID: 17551129 Figueiredo JC, et al. Folic acid and risk of prostate cancer: results from a randomized clinical trial. J Natl Cancer Inst. 2009 Mar 18;101(6):432-5. Epub 2009 Mar 10. PMID: 19276452 Folic Acid, CASRN: 59-30-3. NLM TOXNET Hazardous Substances Database accessed online 28 March, 2009. Lonn E, Yusuf S, Arnold MJ, Sheridan P, Pogue J, Micks M, McQueen MJ, Probstfield J, Fodor G, Held C, Genest J Jr; Heart Outcomes Prevention Evaluation (HOPE) 2 Investigators. N Engl J Med. 2006 Apr 13;354(15):1567-77. Epub 2006 Mar 12. Erratum in: N Engl J Med. 2006 Aug 17;355(7):746. PMID: 16531613 Oakley GP Jr. When will we eliminate folic acid-preventable spina bifida? Epidemiology. 2007 May;18(3):367-8. PMID: 17435446


Stephanie said...

I work for the National Library of Medicine, the producer of the Hazardous Substances Data Bank (HSDB). I noticed that you link to the Folic Acid HSDB record. I am contacting you to let you know about the correct way to link to an HSDB record. HSDB is set up with frames and you can’t copy and paste the URL. Directions for linking are found at

This is the correct link:

Stephanie Publicker, MLS
Technical Information Specialist
Specialized Information Services, National Library of Medicine

Neil E. Levin, CCN, DANLA said...

Thanks, Stephanie!!!

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