Is supplemental folic acid harmful?

Folate is a member of the B vitamin family and is found naturally in foods, especially green vegetables. Folate is involved with DNA synthesis and DNA methylation, which essentially turns genes on and off.  Because of these crucial functions, folate plays important roles in fetal development and nerve tissue health as well as cancer initiation and progression.

Folic acid is the synthetic form of folate that is added to food or used as an ingredient in vitamin supplements. Folic acid is added to most enriched, refined grain products like bread, rice and pasta in the U.S. and Canada in an attempt to replace the nutrients lost during the processing of the whole grain. Since folic acid is added to so many refined grain products, it is very easy for a typical diet combined with a multivitamin to end up with high levels of folic acid, the synthetic form. Too much folate obtained naturally from food is not a concern.  It comes naturally packaged in balance with other micronutrients and the body regulates its absorption. Folic acid is not found in natural foods.

The protective effects of folate against neural tube defects (NTDs) have received much attention in the past.  Unfortunately, this knowledge and public attention did not result in a campaign by the U.S. government encouraging women to get plenty of natural dietary folate from vegetables.  Instead, because the Standard American Diet (SAD) is so nutritionally inadequate, the U.S. government and most physicians encourage women to take folic acid supplements, assuming that they are folate-deficient.  This actually perpetuates the widespread vegetable deficiency that does exist.

The problem is that folic acid is chemically different from dietary folate, which results in differences in uptake and processing of these two substances by the cells in the intestinal wall. Some folic acid is chemically modified to be more similar to natural folate, but the intestinal cells are limited in how much folic acid they can modify – folic acid often enters the circulation unmodified. Scientists do not yet know the implications of circulating synthetic folic acid. Many Americans, through multivitamin use and consumption of fortified foods, are taking in excessive amounts of folic acid, and thus may have unmodified folic acid circulating in their blood – this could contribute to cancer-promoting effects. 1-3

Folate is abundant in all green vegetables. We do not need synthetic folic acid supplements to meet our daily folate requirements. Here are a few examples of folate-rich foods (as a reference point, the U.S. RDA for folate is 400µg):4

 

Food Source Micrograms
Edamame (1 cup cooked) 482 µg
Broccoli (2 cups cooked) 337 µg
Asparagus (1 cup cooked) 268 µg
Romaine lettuce (3 cups raw) 192 µg
Brussels sprouts (2 cups cooked) 187 µg
Spinach (3 cups raw) 175 µg

 

Recently, there have been some troubling studies connecting folic acid supplementation with breast, prostate, and colorectal cancers:

  • Women who followed the typical recommendations to take folic acid during pregnancy and were followed by researchers for thirty years were twice as likely to die from breast cancer.5
  • Another study following women for ten years concluded that those who took multivitamins containing folic acid increased their breast cancer risk by 20-30%.6
  • Folic acid supplementation by pregnant women has been associated with incidence of childhood asthma, infant respiratory tract infections, and cardiac birth defects.7-9
  • Men who had taken folic acid supplements for more than three years had a 35% increase in colorectal cancer risk, according to a meta-analysis of several randomized controlled trials.10
  • In a 10-year study, folic acid supplementation was associated with more than double the risk of prostate cancer compared to placebo.11
  • In two trials comparing folic acid supplements to placebo, overall cancer incidence and all-cause mortality were increased in the folic acid group over the 9-year study period.12

In contrast, food folate is associated with protection from cancer and other benefits:

  • Women with lower levels of food folate intake are more likely to be diagnosed with breast cancer.13
  • Food folate intake is inversely associated with prostate cancer risk.11
  • The children of women who consumed more food folate during pregnancy were less likely to develop ADHD.14

Getting enough folate from natural foods may keep tumors from starting by repairing errors in DNA, but synthetic folic acid may feed tumor development and promote  carcinogenesis. In light of this research, I do not include folic acid in my multivitamin or prenatal.  I do not recommend that pregnant women take a prenatal that contains folic acid.  I do recommend a blood test for folate sufficiency before even contemplating pregnancy, and I do recommend a high-folate diet rich in green vegetables.  A diet rich in green vegetables is the safest way to achieve protection from cancer, heart disease and all-cause mortality.

  1. Harvard School of Public Health; The Nutrition Source: Keep the Multi, Skip the Heavily Fortified Foods.  August 29, 2008]; Available from: www.hsph.harvard.edu/nutritionsource/what-should-you-eat/folicacid/.
  2. Hirsch, S., et al., Colon cancer in Chile before and after the start of the flour fortification program with folic acid. Eur J Gastroenterol Hepatol, 2009. 21(4): p. 436-9.
  3. Chustecka, Z. Folic-Acid Fortification of Flour and Increased Rates of Colon Cancer . 2009  [cited 2009; Available from: http://www.medscape.com/viewarticle/591111.
  4. NutritionData.com: Nutrient Search Tool.  2009]; Available from: http://www.nutritiondata.com/tools/nutrient-search.
  5. Charles, D., et al., Taking folate in pregnancy and risk of maternal breast cancer. Bmj, 2004. 329(7479): p. 1375-6.
  6. Stolzenberg-Solomon, R.Z., et al., Folate intake, alcohol use, and postmenopausal breast cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Am J Clin Nutr, 2006. 83(4): p. 895-904.
  7. Whitrow, M.J., et al., Effect of supplemental folic acid in pregnancy on childhood asthma: a prospective birth cohort study. Am J Epidemiol, 2009. 170(12): p. 1486-93.
  8. Haberg, S.E., et al., Folic acid supplements in pregnancy and early childhood respiratory health. Arch Dis Child, 2009. 94(3): p. 180-4.
  9. Kallen, B., Congenital malformations in infants whose mothers reported the use of folic acid in early pregnancy in Sweden. A prospective population study. Congenit Anom (Kyoto), 2007. 47(4): p. 119-24.
  10. Fife, J., et al., Folic Acid Supplementation and Colorectal Cancer Risk; A Meta-analysis. Colorectal Dis, 2009.
  11. Figueiredo, J.C., et al., Folic acid and risk of prostate cancer: results from a randomized clinical trial. J Natl Cancer Inst, 2009. 101(6): p. 432-5.
  12. 12. Ebbing, M., et al., Cancer incidence and mortality after treatment with folic acid and vitamin B12. JAMA, 2009. 302 (19): p. 2119-26.
  13. Sellers, T.A., et al., Dietary folate intake, alcohol, and risk of breast cancer in a prospective study of postmenopausal women. Epidemiology, 2001. 12 (4): p. 420-8.
  14. Wiley-Blackwell (2009, October 28). Attention-deficit/hyperactivity Problems Associated With Low Folate Levels In Pregnant Women. ScienceDaily. 2009  February 5, 2010]; Available from: http://www.sciencedaily.com/releases/2009/10/091028134631.htm.

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