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Combining B12 and Protein Benefits Methylation in Pregnancy

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  • Combining B12 and Protein Benefits Methylation in Pregnancy

In the first study of its kind, researchers have evaluated the effects of vitamin B12 combined with dietary protein on methionine metabolism, placental gene expression and DNA methylation in pregnant women with low vitamin B12 status.

The study found the vitamin B12-protein combination was critical for optimal functioning of the methionine cycle in the third trimester of pregnancy.

This randomised, open-label intervention study tested the theory that low quality dietary protein and vitamin B12 deficiency could interact to decrease methionine metabolism during pregnancy by affecting transmethylation and remethylation rates, which may then impact upon the genomic profile of the foetus.

From recruitment until delivery, pregnant Indian women with low vitamin B12 plasma levels in early pregnancy were randomised to receive a dietary milk supplement (providing 16.5 grams of protein and 320kCal energy) with 10mcg of vitamin B12, or milk and a placebo tablet, or a placebo alone. Researchers analysed food intakes, vitamin B12 and amino acid status, placental mRNA gene expression and methylation markers.

The results showed that balanced protein-energy and vitamin B12 supplementation increased the homocysteine remethylation rates, regenerating methionine. Transmethylation to methionine was higher, while transsulfuration to cysteine was lower in the vitamin B12 and milk supplemented group, compared to the placebo group. Remethylation rates were lower in the group supplemented with milk and a placebo, compared to the milk and vitamin B12 group, and the placebo group.

This indicated that vitamin B12 supplementation, alongside high-quality protein intake, is critical for the optimal functioning of the methionine cycle in the third trimester of pregnant women with low vitamin B12 status. Supplementation did not affect placental expression of genes in methionine pathways or methylation.

Vitamin B12 influences 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR) to remethylate homocysteine and regenerate methionine. This study showed that a synergistic effect on the methionine cycle was produced by improving vitamin B12 status with supplementation and increasing amino acid availability through increased protein intake.


  1. Devi S, Mukhopadhyay A, Dwarkanath P, et al. 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. J Nut 2017;147(6):1094-1103. [Abstract]


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Melissa Peterson has been a writer and educator in the health and medical science fields for over 15 years. Naturopathically trained, Melissa also has postgraduate qualifications in literature research and reviewing. Her business, Words On Therapy, provides many services to industry including technical articles, white papers, blogs, SEO content, copywriting and research collation.