Combined Vitamin B-12 and Balanced Protein-Energy Supplementation Affect Homocysteine Remethylation in the Methionine Cycle in Pregnant South Indian Women of Low Vitamin B-12 Status

Abstract

Low-quality dietary protein intake and vitamin B-12 deficiency could interact to decrease methionine transmethylation and remethylation rates during pregnancy and may affect epigenetic modifications of the fetal genome. The objective of this randomized, partially open-labeled intervention trial was to examine the effect of supplemental high-quality protein and vitamin B-12 on third-trimester methionine kinetics in pregnant Indian women with a low vitamin B-12 status. Pregnant women with low serum vitamin B-12 concentrations (<200 pmol/L) were randomly assigned to 1 of 3 groups: the first group received balanced protein-energy supplementation of 500 mL milk/d plus a 10-μg vitamin B-12 tablet/d (M+B-12 group; = 30), the second group received milk (500 mL/d) plus a placebo tablet (M+P group; = 30), and the third group received a placebo tablet alone (P group; = 33). Third-trimester fasting plasma amino acid kinetics were measured by infusing 1-C,methyl-H-methionine, ring-H-phenylalanine, ring-H-tyrosine,1-C-glycine, and 2,3,3-H,N-serine in a subset of participants. Placental mRNA expression of genes involved in methionine pathways, placental long interspersed nuclear elements 1 (LINE-1) methylation, and promoter methylation levels of vascular endothelial growth factor () were analyzed. Remethylation rates in the M+B-12, M+P, and P groups were 5.1 ± 1.7, 4.1 ± 1.0, and, 5.0 ± 1.4 μmol ⋅ kg ⋅ h, respectively ( = 0.057), such that the percentage of transmethylation remethylated to methionine tended to be higher in the M+B-12 group (49.5% ± 10.5%) than in the M+P group (42.3% ± 8.4%; = 0.053) but neither differed from the P group (44.2% ± 8.1%; > 0.1). Placental mRNA expression, LINE-1, and promoter methylation did not differ between groups. Combined vitamin B-12 and balanced protein-energy supplementation increased the homocysteine remethylation rate in late pregnancy. Thus, vitamin B-12 along with balanced protein-energy supplementation is critical for optimal functioning of the methionine cycle in the third trimester of pregnancy in Indian women with low serum vitamin B-12 in early pregnancy. This trial was registered at clinicaltrials.gov as CTRI/2016/01/006578.

Effect of two different sublingual dosages of vitamin B12 on cobalamin nutritional status in vegans and vegetarians with a marginal deficiency: A randomized controlled trial

“…Finally, we observed no significant effect on blood cell count both at the beginning of the study (see Table 1) and after the intervention (data not shown). These results are not surprising, since our subjects were in stage 2e3 of vitamin B 12 deficiency and this condition does not affect the levels of mean corpuscular volume and hemoglobin [42].…”

Low Vitamin B12 and Lipid Metabolism: Evidence from Pre-Clinical and Clinical Studies

“…Evidence of higher percentage of transmethylation to methionine and reduced transculturation to cysteine were observed as a result of supplementation with both B12 and milk protein compared with only milk supplementation in women. Therefore, among Indian women presenting with low B12 in early pregnancy, supplementation with B12 and energy-protein balance plays a crucial role in enhancing the optimum function of the methionine cycle especially at the third trimester of pregnancy [118]. Similarly, B12, folate, choline and betaine-rich methyl donor supplements were used to regress the accumulation of fats in the liver induced by high-fat-sucrose probably by changing the levels of methylation of CpG areas in the promotor regions of SREBF2, estrogen receptor 1 (ESR1) and/or acylglycerol−3-Oacyltransferase−3 (AGPAT3) [96].…”

Vitamin B12 deficiency: metabolic effects, clinical evaluation, and treatment

“…73 A combined supplementation of vitamin B12 (10 μg/day) and proteins in a balanced diet increased the homocysteine remethylation rate at the end of pregnancy. 74 The significant effect of low doses may be related to the high prevalence of vitamin deficiency in the populations studied. 10,75,76 In 100 elderly patients with serum vitamin B12 < 250 pmol/L, supplementation of 10 μg/d, 100 μg/day or 500 μg/day of cyanocobalamin for 8 weeks improved plasma vitamin B12 and MMA, urinary MMA and serum holo-TC.…”