Folate intake, <i>MTHFR</i> genotype and premenstrual symptoms

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 <i>MTHFR</i> genotype with premenstrual symptoms. Females (<i>n</i> 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 <i>MTHFR</i> (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 <i>MTHFR</i> genotypes. We found associations between <i>MTHFR</i> genotype and some premenstrual symptoms. Among women with low folate intake, an additive association was observed between the Tallele of <i>MTHFR</i> 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 <i>MTHFR</i> genotype and premenstrual depression among those with higher habitual intakes of folate. Since the <i>MTHFR</i> 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.