Tara Zeitoun, HBSc: No relevant financial relationship(s) with ineligible companies to disclose.
Objectives: To determine the association between folate intake and MTHFR genotype with premenstrual symptoms (PMSx).
Methods: Females (n=678) aged 20-29 years from the Toronto Nutrigenomics and Health Study completed a General Health and Lifestyle Questionnaire, capturing fifteen PMSx. 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 MTHFR (rs1801133) polymorphism. Using logistic regression, odds of experiencing PMSx were compared between total folate intake below and above the median (647 mcg/d), and between MTHFR genotypes. Mendelian randomization was used to examine the effect of MTHFR genotype as a proxy measure of folate status. Multivariate analysis adjusted for BMI, age, ethnicity, vitamin B12 intake and physical activity level.
Results: Folate intake was not associated with any PMSx, and MTHFR did not modify the association between folate intake and PMSx. In our Mendelian randomization analyses, we found associations between MTHFR genotype and PMSx in women with folate intake above the median (≥ 647 mcg/day). Among women with higher folate intake, those with the TC genotype, had increased odds of reporting premenstrual bloating/swelling/breast tenderness, compared to those with the CC genotype (OR: 1.93; 95% CI: 1.09, 3.21). We observed other associations between MTHFR genotype and PMSx in those with folate intakes below the median ( < 647 mcg/day). Among women with lower folate intake, those with the TC genotype had increased odds of reporting premenstrual confusion/difficulty concentrating/forgetfulness (OR: 2.19; 95% CI: 1.16, 3.80) and depression (OR: 1.66; 95% CI: 0.98, 2.87), compared to those with the CC genotype. Those with the TT genotype also had a higher risk of reporting premenstrual depression (OR: 2.41; 95% CI: 1.08, 5.38).
Conclusions: We found associations between MTHFR genotype and premenstrual bloating/swelling, depression, and confusion/difficulty concentrating. 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 symptoms.
Funding Sources: Peterborough KM Foundation and the Allen Foundation
