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Updated: Sep 19, 2025

Author Spotlight: Studying the Impact of Maternal Dietary Deficiencies on Long-Term Offspring Health Outcomes
Published on: June 28, 2024
Folate intake, MTHFR genotype and premenstrual symptoms
Tara Zeitoun1, Ahmed El-Sohemy1
1Department of Nutritional Sciences, Temerty Faculty of Medicine, University of Toronto, Toronto, ONM5S 3H2, Canada.
None:
Premenstrual symptoms are a cyclic set of symptoms that affect women's psychological and physical well-being. Growing evidence suggests that micronutrients may contribute to the risk and severity of premenstrual symptoms such as depression. Yet the relationship between folate and premenstrual symptoms remains inconclusive. The objective of this study was to determine the association between folate intake and MTHFR genotype with premenstrual symptoms. Females (n 678) aged 20-29 years from the Toronto Nutrigenomics and Health Study self-reported fifteen premenstrual symptoms. Dietary intake was measured using a validated 196-item Toronto-modified Harvard food frequency questionnaire. DNA was isolated from peripheral white blood cells and genotyped for the C677T MTHFR (rs1801133) polymorphism. Using logistic regression, the odds of experiencing premenstrual symptoms were compared between total folate intake below and above the median (647 mcg/d) and between MTHFR genotypes. We found associations between MTHFR genotype and some premenstrual symptoms. Among women with low folate intake, an additive association was observed between the Tallele of MTHFR and premenstrual depression. Compared with those with the CC genotype, the OR (95 % CI) for depression was 1·66 (0·98, 2·87) for those with the CT genotype and 2·41 (1·08, 5·38) for those with the TT genotype. No associations were observed between MTHFR genotype and premenstrual depression among those with higher habitual intakes of folate. Since the MTHFR genotype is involved in the folate metabolic pathway, these findings suggest that folate or its metabolites may be related to the risk of premenstrual depression.
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