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.
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