RSSMethylfolate vs. folic acid for pregnancy

Posted on Tue, 7 Aug 18

Methylfolate vs. folic acid for pregnancy

Recent clinical studies suggest that a more active from of folate may be superior for correcting deficiency and improving pregnancy outcomes. 

Traditionally, folic acid has been used to for pregnancy, but a more biologically active form of folate, l-5-methyltetrahydrofolate (5MTHF), has become widely available as an alternative.

Direct comparisons of efficacy between folic acid and 5MTHF are scarce, but recently the results of two clinical studies suggested that 5MTHF has important advantages. 

A clinical trial published in The Journal of Nutrition compared the ability of folic acid (1000 µg) or 5MTHF (1000 µg) to improve blood folate levels in women. After 12-weeks, red blood cell and plasma folate concentrations were higher in the women supplemented with 5MTHF than in the women supplemented with folic acid [1]. 

And in a report published in Journal of Assisted Reproduction and Genetics, thirty couples with fertility problems with genetic variants that limit the metabolism of folic acid (methylene tetra hydrofolate reductase (MTHFR) isoforms C677T and A1298C) and who were previously treated unsuccessfully with high doses of folic acid (5 mg/day) were given 5-MTHF (600 µg/ day) for 4-months [2].

After switching to 5MTHF 13 couples conceived spontaneously, 13 with assisted reproductive treatment, leaving only 3 couples who did not fall pregnant, yet.

These studies are important as they suggest 5MTHF may be more effective than folic acid for correcting deficiency and improving fertility in people with MTHFR-gene variants. Despite some controversy, it is not yet clear if 5MTHF has safety advantages over folic acid [3]. 

Importantly, increasing intake of folate rich foods (300 g/ day of lentils, soybeans, corn, peas, carrots, zucchini, lettuce, chard, beets, broccoli, cauliflower, tomatoes, or cucumbers, which is equivalent to around 200 µg folate/ day) is also an effective way to improve blood folate levels, including those with MTHFR-gene variants [4]. 


  1. Henderson AM, Aleliunas RE, Loh SP, Khor GL, Harvey-Leeson S, Glier MB, Kitts  DD, Green TJ, Devlin AM. l-5-Methyltetrahydrofolate Supplementation Increases Blood Folate Concentrations to a Greater Extent than Folic Acid Supplementation in Malaysian Women. J Nutr. 2018 Jun 1;148(6):885-890
  2. Servy EJ, Jacquesson-Fournols L, Cohen M, Menezo YJR. MTHFR isoform carriers.  5-MTHF (5-methyl tetrahydrofolate) vs folic acid: a key to pregnancy outcome: a case series. J Assist Reprod Genet. 2018 Jun 7. doi: 10.1007/s10815-018-1225-2
  3. Kim YI. Folate and cancer: a tale of Dr. Jekyll and Mr. Hyde? Am J Clin Nutr. 2018 Feb 1;107(2):139-142.
  4. Ribeiro MR, Lima RPA, Lisboa JVC, et al. Influence of the C677T Polymorphism of the MTHFR Gene on Oxidative Stress in Women With Overweight or Obesity: Response to a Dietary Folate Intervention. J Am Coll Nutr. 2018 Apr 27:1-8.

Tags: Folate, Pregnancy

Related Articles

« Back to Latest Blog Entries