In a recent editorial in The Annals of Internal Medicine entitled “Enough Is Enough: Stop Wasting Money on Vitamin and Mineral Supplements,” authors make a case that multivitamins are not a good value (Dec 17, 2013 issue).  This editorial was based on new research that demonstrated that there was no association between multivitamin use and rates of mortality, cognitive decline and recurrent cardiovascular events in three different studies.  The assertion that multivitamins are not worth the money was widely reported in the media.

However, there is a major case to be made for the routine use of multivitamins in reproductive aged women.  We have long known that supplemental folic acid is preventative against birth defects, particularly neural tube defects.  Importantly, the timing for the benefits of folic acid appear very early in pregnancy, starting pre-conception, and this is extremely important to note as many pregnancies are unplanned, and some women do not even realize they are pregnant before this window of opportunity to take folic acid has largely passed.

New information makes the periconceptual use (before conception and into the first trimester) of folic acid even more compelling.  A recent major research breakthrough has issued the finding that periconceptual folic acid use has been associated with a decreased risk of autism spectrum disorders (1-3).  Women with genetic variants that make folate metabolism inefficient are more likely to have children with autism spectrum disorders, suggesting a particularly important role for supplemental folic acid in pregnancy (1).  Early pregnancy- and the weeks leading up to conception – appear to be a window for major benefits.  In one study, the use of folic acid between four weeks before conception to 8 weeks after conception was associated with a lower risk of autism (2), and another found the most robust association with prevention of autism spectrum disorders within use of folic acid during the first four weeks of pregnancy (3).

The ability to make general recommendations is complicated, as some individuals do not efficiently metabolize folate.  Genetic studies indicate that a common polymorphism (C677T) of the enzyme methylene tetrahydrofolate reductase (MTHFR) is essential for the conversion of dietary folate to its active metabolite, MTHF or L-methylfolate.  It is believed that women with this variant of MTHFR have lower levels of L-methylfolate available for basic metabolic processes (1).

The implications for public health are tremendous, as some women are more likely to require higher than standard doses of folic acid or supplementation with folate-related compounds, such as l-methylfolate). In addition, a recent article from the Motherisk program notes that there are some women who are clearly at greater risk for folate deficiency during pregnancy.  On this list, they include women with the polymorphism in the MTHFR C677T gene described above, as well as women who:

  • Have diabetes
  • Are obese
  • Smoke
  • Take antiepileptic drugs (e.g., valproic acid, carbamazepine, barbiturates)
  • Take folate antagonists (e.g., methotrexate, sulfonamides)
  • Belong to high-risk ethnic groups (e.g., Sikh, Celtic, Northern Chinese)

More research is needed in this area in order to individualize supplement recommendations for women who are trying to conceive or who are pregnant. The prevention of neurodevelopmental disorders has long-lasting implications for individuals, families, and society.

Recommendations disregarding multivitamin use are potentially dangerous, particularly for women of reproductive age, considering about half of pregnancies are unplanned.  The U. S. Public Health Service and CDC recommend that all women of childbearing age consume 0.4 mg (400 micrograms) of folic acid daily to reduce the risk of serious birth defects and long-term neurodevelopmental disorders.  (Most prenatal vitamins contain 0.8 mg or 800 mcg of folic acid.)

Marlene Freeman, MD


  1. Pu D, Shen Y, Wu J. Association between MTHFR gene polymorphisms and the risk of autism spectrum disorders: a meta-analysis. Autism Res; 2013; 6(5):384-92.
  2. Surén P, Roth C, Bresnahan M, Haugen M, Hornig M, Hirtz D, Lie KK, Lipkin WI, Magnus P, Reichborn-Kjennerud T, Schjølberg S, Davey Smith G, Øyen AS, Susser E, Stoltenberg C. Association between maternal use of folic acid supplements and risk of autism spectrum disorders in children. JAMA. 2013; 309(6):570-7.
  3. Schmidt RJ, Tancredi DJ, Ozonoff S, Hansen RL, Hartiala J, Allayee H, Schmidt LC, Tassone F, Hertz-Picciotto I. Maternal periconceptional folic acid intake and risk of autism spectrum disorders and developmental delay in the CHARGE (CHildhood Autism Risks from Genetics and Environment) case-control study. Am J Clin Nutr. 2012; 96(1):80-9.

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