Location: Children's Nutrition Research CenterTitle: 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
|DEVY, SARITA - St John'S National Academy Of Health Sciences|
|MUKHOPADHYAY, ARPITA - St John'S National Academy Of Health Sciences|
|DWARKANATH, PRATIBHA - St John'S National Academy Of Health Sciences|
|THOMAS, TINKU - St John'S National Academy Of Health Sciences|
|CRASTA, JULIAN - St John'S National Academy Of Health Sciences|
|THOMAS, ANNAMMA - St John'S National Academy Of Health Sciences|
|SHEELA, CN - St John'S National Academy Of Health Sciences|
|HSU, JEAN - Children'S Nutrition Research Center (CNRC)|
|TANG, GRACE - Children'S Nutrition Research Center (CNRC)|
|JAHOOR, FAROOK - Children'S Nutrition Research Center (CNRC)|
|KURPAD, ANURA - St John'S National Academy Of Health Sciences|
Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/27/2017
Publication Date: 4/26/2017
Citation: Devy, S., Mukhopadhyay, A., Dwarkanath, P., Thomas, T., Crasta, J., Thomas, A., Sheela, C., Hsu, J.W., Tang, G.J., Jahoor, F., Kurpad, A.V. 2017. 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. Journal of Nutrition. 147(6):1094-1103.
Interpretive Summary: In India, underweight pregnant women give birth to a high number of low birth weight babies suggesting that underweight women are not able to provide sufficient energy and protein for their baby to grow normally in the womb. As pregnancy progresses there is increased need to also provide a compound called methyl, which the growing fetus needs to make new DNA and proteins, and, unlike normal weight American women, underweight Indian women are unable to make more methyl as pregnancy progresses. The reason for this could be due to the fact that these women eat mostly vegetables, which have protein that is low in a compound called methionine, and vegetables also lack vitamin B-12. Both methionine and vitamin B-12 are needed to make methyl in the body so the vegetable based diet of these Indian women could be the reason for this methyl shortage during pregnancy. Of course this will also slow down the growth of the baby in their womb and they will give birth to a small, underweight baby. In this study we wanted to determine the effect of supplementing the diet of pregnant women who had low vitamin B-12 in their blood with extra vitamin B-12 and high quality protein from milk, which has a lot of methionine. One group of women also got additional calories while a third group did not get any extra food. All three groups of women were given the extra foods (or no extra food) from week 11 of pregnancy to time of delivery. We found that women who received more vitamin B-12 plus more protein and energy during pregnancy were making more methyl and also remaking more methionine from a compound called homocysteine in late pregnancy. Therefore pregnant women need a diet that has sufficient amounts of protein, energy and vitamin B-12 in order to make sufficient amounts of methyl during pregnancy.
Technical 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-g vitamin B-12 tablet/d (M+B-12 group; n = 30), the second group received milk (500 mL/d) plus a placebo tablet (M+P group; n = 30), and the third group received a placebo tablet alone (P group; n = 33). Third-trimester fasting plasma amino acid kinetics were measured by infusing 1-13C,methyl-2H3-methionine, ring-2H5-phenylalanine, ring-2H4-tyrosine,1-13C-glycine, and 2,3,3-2H3,15N-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 (VEGF) 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 mol/ kg-1/ h-1, respectively (P = 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%; P = 0.053) but neither differed from the P group (44.2% +/- 8.1%; P > 0.1). Placental mRNA expression, LINE-1, and VEGF 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.