James PT, Jawla O, Mohammed NI, et al. - Via a randomized controlled trial in nonpregnant women (n = 298) in the rural Gambia, experts examined the efficiency of a novel nutritional supplement designed to improve one-carbon-related nutrient status by decreasing plasma homocysteine and evaluated its potential future use in preconception trials. At the endline (our primary endpoint), the drink powder and United Nations Multiple Micronutrient Preparation (UNIMMAP) decreased mean plasma homocysteine by 23.6% and 15.5%, respectively in comparison with the controls. In contrast with UNIMMAP, the drink powder lessened mean homocysteine by 8.8%. At the midline, the influences were stronger. No impact of either intervention on blood pressure or pulse was noted compared with the control at the endline. In both intervention arms, self-reported adverse events (AEs) were comparable. Two serious AEs were reported over the trial term, both in the drink powder arm, but judged to be independent of the intervention. Hence, this trial validates that dietary supplements can affect metabolic pathways that were exhibited in former studies to prognosticate offspring DNA methylation. Both supplements decreased homocysteine efficiently and remain potential candidates for prospective epigenetic trials in pregnancy in the rural Gambia.