The importance of folate, vitamins B6 and B12 for the lowering of homocysteine concentrations for patients with recurrent pregnancy loss and MTHFR mutations

Reprod Toxicol. 2017 Sep:72:159-163. doi: 10.1016/j.reprotox.2017.07.001. Epub 2017 Jul 6.


In patients with MTHFR (methylenetetrahydrofolate reductase) mutations and hyperhomocysteinemia, recurrent pregnancy loss is a frequent feature. The aim of the study was to evaluate the impact of folic acid, vitamins B6 and B12 supplementation for the lowering of total homocysteine concentrations and pregnancy. 16 patients who had had 3 or more miscarriages and MTHFR mutations were used in the study. They received methylfolate (5mg/day), vitamin B6 (50mg/day) and vitamin B12 (1mg/week). Supplementation induced a decrease in homocysteine from 19.4±5.3μmol/L to 6.9±2.2μmol/L after folate supplementation (p<0.05). During one year 7 women became pregnant and delivered. Two women delivered from the homozygous C677T mutations group (7 patients) and combined heterozygous C677T/A1298C mutations group (5 patients), while 3 deliveries were in A1298C homozygous mutations group (4 patients). In conclusion, supraphysiologic methylfolate, vitamins B6 and B12 supplementation in woman with MTHFR mutations has a beneficial effect on pregnancy outcome.

Keywords: Folic acid; Homocysteine; Recurrent pregnancy loss; Vitamin B12; Vitamin B6.

MeSH terms

  • Abortion, Habitual / blood
  • Abortion, Habitual / drug therapy*
  • Abortion, Habitual / genetics
  • Adult
  • Female
  • Folic Acid / blood
  • Folic Acid / therapeutic use*
  • Homocysteine / blood
  • Humans
  • Hyperhomocysteinemia / blood
  • Hyperhomocysteinemia / drug therapy*
  • Hyperhomocysteinemia / genetics
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics*
  • Mutation
  • Pregnancy
  • Vitamin B 12 / therapeutic use*
  • Vitamin B 6 / therapeutic use*
  • Vitamin B Complex / therapeutic use*


  • Homocysteine
  • Vitamin B Complex
  • Vitamin B 6
  • Folic Acid
  • MTHFR protein, human
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • Vitamin B 12