L-methylfolate is Superior to Folic Acid for Decreasing Estimated Risk of NTD1

  • The risk of giving birth to a child with a birth defect increases with age. Women over the age of 35 have increased risk for fetal chromosomal abnormalities, and low birth weight of newborn. A clear association has been shown between folate status of mothers and NTDs, other congenital malformations and low birth-weight.
  • The risk of giving birth to a child with birth defect, especially spina bifida, increases with maternal weight. The heaviest obese women (BMI > 35) have the highest risk (OR:2.1) followed by moderately obese women (BMI 30-34.9, OR:1.6) and overweight women (BMI 25-29.9, OR:1.7)5, 6
  • Pre-conception folate supplementation has been shown to reduce the incidence of NTD by 72-100%. In case-controlled studies, the surrogate endpoint of red blood cell folate concentration has been used to determine the risk of having a child born with NTD.4
  • In a study, L-methylfolate was shown to be more effective in increasing RBC folate concentrations and reducing estimated NTD risk1 compared to folic acid.
Intervention Total n Baseline Week 4 Week 8 Week 12 Week 16 Week 20 Week 24 Estimated decrease in NTD risk at week 24
Participants with baseline red cell folate concentrations < 906nmol/L (n=111)
Placebo 26 2.0 1.9 2.3 2.4 2.1 2.2 2.0 0
400µg/d folic acid 27 2.0 1.5 1.3 1.1 0.9 1.0 0.8 58%
416µg/d (6S)-5-MTHF 29 2.3 1.6 1.2 1.1 0.8 0.8 0.8 67%
208µg/d (6S)-5-MTHF 29 2.2 1.6 1.5 1.4 1.2 1.0 1.0 53%

L-methylfolate is Superior to Folic Acid for Increasing Red Blood Cell Folate Concentrations2

  • A long-term double-blinded, randomized, placebo-controlled intervention trial with 144 women showed greater efficacy of biologically active folate 6(S)-5-MTHF compared to equimolar amount of folic acid with respect to increase in RBC folate status.2
  • L-methylfolate has been shown to be more effective than folic acid in increasing red blood cell folate concentrations in women of childbearing ages and during lactation.3
  1. Lamers Y, Prinz-Langenohl R, Bramswig S, Pietrzik K. Natural folate form for prevention of neural tube defects: Effect of supplementation with [6S]-5-methyltetrahydorfolate versus folic acid on red cell folate concentration. CUVILLIER VERLAG, Gottingen 2006 pp 43-59: ISBN 3-86537-756-4
  2. Lamers Yvonne, Prinz-Langenohl Reinhild, Bramswig Susanne, and Pietrzik Klaus: Red blood cell folate concentrations increase more after supplementation with [6S]-5-methyltetrahydrofolate than with folic acid in women of childbearing age. Am J Clin Nutr 2006;84:156-61
  3. Houghton Lisa A, Sherwood Kelly L, Pawlosky Robert, Ito Shinya, and O'Connor Deborah L: [6S]-5-methyltetrahydrofolate is at least as effective as folic acid in preventing a decline in blood folate concentrations during lactation. Am J Clin Nutr 2006;83:842-50.
  4. Lumley J, et al. Periconceptional supplementation with folate and/or multivitamins for preventing neural tube defects. Cochrane Database Syt Rev 2001; CD001056.
  5. Watkins ML, et al. Maternal obesity and risk of birth defects. Pediatrics 2003; 111:1152-8.
  6. March of Dimes, Maternal Obesity and Pregnancy: Weight Matters. 2005.

Néevo® caplets are a prescription medical food for the dietary management of those women under a physician's treatment for vitamin deficiency throughout pregnancy, postnatal and the lactating periods. Néevo® is specifically indicated for: patients with high risk pregnancies, older OB patients, and patients unable to fully metabolize folic acid.