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Survey study, 2025

Does folate intake and genes affect premenstrual depression?

Among women eating low folate, those with certain gene types were more likely to have premenstrual depression. Getting enough folate appeared to reduce this risk.

Early or limited evidence 678 Canadian women aged 20-29 from Toronto

What they did

Cross-sectional study of 678 women aged 20-29 in Toronto. Researchers measured what women ate using a food questionnaire, focusing on folate. They tested a specific gene (MTHFR) from each woman's DNA. They asked about 15 different PMS symptoms including depression. They compared depression rates between women with low versus high folate intake and different gene types.

What they found

Gene type was related to some PMS symptoms. Among women with low folate intake, those with a specific gene type variant were more likely to have premenstrual depression. Women who had higher folate intake did not show this link between gene type and depression.

What it means for you

Getting enough folate from food may help prevent premenstrual depression, especially for women with certain genes. This is a cross-sectional study so we cannot know if low folate causes depression or the reverse. Also, these women were from Toronto, so the findings may not apply to women in other countries.

678

women studied

647 mcg/d

median folate intake

20-29

age range

About the study

Original title
Folate intake, <i>MTHFR</i> genotype and premenstrual symptoms
Authors
Zeitoun T, El-Sohemy A
Journal
The British journal of nutrition
Year
2025
Study design
Survey study
Open access
Yes
Original abstract

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.

Reproduced under CC-BY.

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