DNA methylation potential: dietary intake and blood concentrations of one-carbon metabolites and cofactors in rural African women

Abstract

Background: Animal models show that periconceptional supplementation with folic acid, vitamin B-12, choline, and betaine can induce differences in offspring phenotype mediated by epigenetic changes in DNA. In humans, altered DNA methylation patterns have been observed in offspring whose mothers were exposed to famine or who conceived in the Gambian rainy season.Objective: The objective was to understand the seasonality of DNA methylation patterns in rural Gambian women. We studied natural variations in dietary intake of nutrients involved in methyl-donor pathways and their effect on the respective metabolic biomarkers.Design: In 30 women of reproductive age (18–45 y), we monitored diets monthly for 1 y by using 48-h weighed records to measure intakes of choline, betaine, folate, methionine, riboflavin, and vitamins B-6 and B-12. Blood biomarkers of these nutrients, S-adenosylhomocysteine (SAH), S-adenosylmethionine (SAM), homocysteine, cysteine, and dimethylglycine were also assessed monthly.Results: Dietary intakes of riboflavin, folate, choline, and betaine varied significantly by season; the most dramatic variation was seen for betaine. All metabolic biomarkers showed significant seasonality, and vitamin B-6 and folate had the highest fluctuations. Correlations between dietary intakes and blood biomarkers were found for riboflavin, vitamin B-6, active vitamin B-12 (holotranscobalamin), and betaine. We observed a seasonal switch between the betaine and folate pathways and a probable limiting role of riboflavin in these processes and a higher SAM/SAH ratio during the rainy season.Conclusions: Naturally occurring seasonal variations in food-consumption patterns have a profound effect on methyl-donor biomarker status. The direction of these changes was consistent with previously reported differences in methylation of metastable epialleles. This trial was registered at www.clinicaltrials.gov as NCT01811641.

Nutrigenomics, the Microbiome, and Gene-Environment Interactions: New Directions in Cardiovascular Disease Research, Prevention, and Treatment

“…162 Investigators cleverly took advantage of seasonal nutritional changes among pregnant women in The Gambia to demonstrate an association between naturally occurring maternal nutrient metabolite levels and DNA methylation patterns. 163 Postnatal diet may compensate for some effects occurring in utero. For example, post-weaning supplementation with folate and selenium after a maternal high-fat diet leads to alterations in hepatic methylation.…”

Essential nutrient supplementation prevents heritable metabolic disease in multigenerational intrauterine growth‐restricted rats

“…It was discovered that methylation of our DNA is sufficiently sensitive to essential dietary methyl sources and cofactors to cause human disease over a decade ago (46). For example, methyl sources related to seasonal food consumption in Gambia affect DNA methylation patterns (47). This sensitivity is likely caused by methyl group substrates and cofactors that constitute the one-carbon metabolism pathway, many components of which are essential, and therefore can only be derived from dietary sources (48).…”

Endocrine responses, weight change, and energy sparing mechanisms during Ramadan among Gambian adolescent women

“…They claim that Ramadan meals have higher lipid and carbohydrate content than meals at other times of the year. Higher levels of the methyl donor betaine and B-vitamin choline from bread, potatoes, and eggs were reported in a dietary survey of the study population during Ramadan in 2009, suggesting that dietary content changed during Ramadan (Dominguez-Salas et al, 2013). Elevated levels of leptin and Cpeptide during Ramadan may therefore be the result of later meals, contributing to a shorter overnight fast, and higher glycemic index foods consumed during evening and night meals.…”

“…The timing of Ramadan is determined by a lunar calendar and therefore participants observe the fast during different seasons in different years. Ramadan impacts on dietary composition (Dominguez-Salas et al, 2013;Norouzy et al, 2013), adult weight (Prentice et al, 1981;Ziaee et al, 2006), placental size (Alwasel et al, 2010), breast milk composition (Prentice et al, 1984;Rakicioglu et al, 2006), and birth weight (Alwasel et al, 2011;Yamauchi, 2011), although it does not appear to affect growth in breastfeeding infants (Khoshdel et al, 2007;Rakicioglu et al, 2006). The overlap of Ramadan with gestation also has intergenerational effects on size at birth (Alwasel et al, 2013).…”