Combination of vitamin B12 active forms improved fetal growth in Wistar rats through up-regulation of placental miR-16 and miR-21 levels

Life Sci. 2017 Dec 15;191:97-103. doi: 10.1016/j.lfs.2017.10.017. Epub 2017 Oct 12.


Aim: Epidemiological studies have indicated importance of folate and vitamin (B12) during pregnancy. Also available evidence on efficacy of B12 forms viz. Cyanocobalamin (Cbl), Methylcobalamin (MeCbl), Adenosylcobalamin (AdCbl) and Hydroxycobalamin (HCbl) in preventing or treating cobalamin deficiency is limited. The present study examines the effect of various forms of B12 in combination with folate during pregnancy and their effect on gestational outcomes.

Main method: In the present study, we examined the effect of various vitamin B12 forms in presence of recommended folate (RFol: 400μg/day) and high folate (HFol: 5mg/day) on gestational outcomes in female Wistar rats.

Findings: Dams dosed with excessive folate (HFol group) delivered low birth weight (LBW) offsprings (p<0.01) as compared to RFol dams. Plasma homocysteine levels were found to be significantly higher (p<0.05) in dams of HFol group and were reduced after vitamin B12 supplementation. Excessive folate supplementation and homocysteine levels showed inverse association with placental weight (p<0.01) and placental efficiency (p<0.05). B12 supplementation significantly up-regulated placental miR-16 and miR-21, associated with fetal growth which in turn reflected in improved birthweights. Supplementation with vitamin B12 forms, especially combination of active forms of cobalamins: MeCbl+AdCbl significantly increased birth weights (p<0.05) and modulated gestational outcomes in RFol as well as HFol supplemented dams.

Significance: Our results indicated supplementing vitamin B12 along with folate during pregnancy had positive impact on the gestational outcomes. We have shown for the first time that combination of active forms of vitamin B12: MeCbl+AdCbl has better efficacy as compared to Cbl, MeCbl, AdCbl and HCbl alone.

Keywords: Birth weight; Folate; Homocysteine; Placenta; Vitamin B12; miR-16 and miR-21.

MeSH terms

  • Animals
  • Animals, Newborn
  • Birth Weight / drug effects
  • Dietary Supplements / analysis
  • Female
  • Fetal Development / drug effects*
  • Folic Acid / administration & dosage
  • Folic Acid / pharmacology*
  • MicroRNAs / genetics*
  • Placenta / drug effects
  • Placenta / metabolism
  • Pregnancy
  • Rats, Wistar
  • Up-Regulation / drug effects
  • Vitamin B 12 / administration & dosage
  • Vitamin B 12 / pharmacology*
  • Vitamin B Complex / administration & dosage
  • Vitamin B Complex / pharmacology*


  • MIRN16 microRNA, rat
  • MicroRNAs
  • mirn21 microRNA, rat
  • Vitamin B Complex
  • Folic Acid
  • Vitamin B 12