Ahmed El-Sohemy

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.

Background Objective biomarkers of diet, such as metabolomics, may improve dietary assessment and provide additional insight into how diet influences disease risk. The portfolio diet, a cholesterol-lowering plant-based diet, is recommended for lowering low-density lipoprotein cholesterol (LDL-C). This diet is low in saturated fat and includes nuts, plant protein (legumes), viscous fiber, and phytosterols. Objective We examined metabolomic profiles in response to the portfolio diet in two randomized controlled trials (RCTs), where all foods were provided to the participants, compared to a control vegetarian diet and the same control diet with a statin. Methods The first RCT included 34 adults (age 58.4 ± 8.6 y) and the second RCT included 25 adults (age 61.0 ± 9.6 y), all with high LDL-C (>4.1 mmol/L). Plasma samples were obtained at baseline, week 2, and week 4 in both RCTs for metabolomics analysis using liquid chromatography–tandem mass spectrometry. Linear mixed models were used to examine effects of the interventions on the metabolites in each RCT, applying a Bonferroni correction. Results Of 496 known metabolites, 145 and 63 metabolites significantly changed within the portfolio diet interventions in the first and second RCT, respectively. The majority were glycerophosphocholines (32%), triacylglycerols (20%), glycerophosphoethanolamines (14%), sphingomyelins (8%), and amino acids and peptides (8%) in the first RCT, and glycerophosphocholines (48%), glycerophosphoethanolamines (17%), and amino acids and peptides (8%) in the second RCT. Fifty-two metabolites were consistently changed in the same direction with the portfolio diet intervention across both RCTs, after Bonferroni correction. Conclusions Many of these metabolites likely reflect the plant-based nature, low saturated fat content, and cholesterol-lowering effects of the diet, such as increased N2-acetylornithine, L-pipecolic acid, lenticin, and decreased C18:0 lipids and cholesteryl esters. Further research is needed to validate these metabolites as biomarkers of a plant-based dietary pattern.

Background: Diet is one of the most significant modifiable lifestyle factors influencing human health, contributing to both morbidity and mortality. Genetic variations in the pleiotropic 9p21 risk locus further shape premature aging, disease susceptibility, and have been strongly linked to cardiovascular disease (CVD), metabolic disorders, certain cancers, and neurodegenerative conditions. However, given that this region was discovered based on Genome-Wide Association Studies, the mechanisms by which 9p21 exerts its effects remain poorly understood and its interactions with diet and biomarkers are insufficiently explored. Methods: This study investigated the association between the rs2383206 SNP in 9p21, dietary patterns, and plasma proteomic biomarkers in a multi-ethnic cohort of 1280 young adults from the Toronto Nutrigenomics and Health Study. Participants’ dietary intake was assessed using a validated food frequency questionnaire, and dietary patterns were categorized using principal component analysis. Plasma proteomics analyses quantified 54 abundant proteins involved in the cardiometabolic and inflammatory pathways. Genotyping identified individuals who were homozygous for the 9p21 risk allele (GG), known to confer the highest susceptibility risk to premature aging and multiple chronic diseases. Results: A significant interaction was observed between the 9p21 genotype and adherence to a micronutrient-rich Prudent dietary pattern for eight plasma proteins (α₁ Antichymotrypsin, Complement C4 β chain, Complement C4 γ chain, Complement C9, Fibrinogen α chain, Hemopexin, and Serum amyloid P-component). However, only Complement C4-γ showed a pattern consistent with the risks associated with the 9p21 genotype and adherence to a Prudent diet. Individuals with the high-risk GG genotype had significantly higher concentrations of Complement C4-γ, but only among those with a low adherence to a Prudent diet. Conclusions: These findings suggest that Prudent dietary patterns rich in micronutrients may counteract genetic-mediated proinflammatory susceptibility by modulating key proteomic biomarkers in young adults, highlighting the potential for tailored dietary interventions to mitigate disease risk. This study also introduces a novel framework for post hoc micronutrient resolution within dietary pattern analysis, offering a new lens to interpret nutrient synergies in gene–diet interaction research.

Dietary inorganic nitrate lowers blood pressure (BP) in healthy individuals through improved nitric oxide (NO) bioavailability. However, there is limited evidence examining the long-term effects of dietary nitrate for managing hypertension. We aimed to determine whether the sustained intake of dietary nitrate improved BP and cardiovascular disease (CVD) risk factors in individuals with early-stage hypertension. The Dietary Nitrate (NO₃) on BP and CVD Risk Factors (DINO₃) Trial was a multi-center, double-blinded, parallel, randomized, controlled trial in participants with elevated BP. Participants were supplemented with high-nitrate (HN) (~400 mg nitrate) or low-nitrate (LN) vegetable powder (~50 mg nitrate) on top of their usual diets for 16 weeks. The primary outcome was office systolic BP at 16 weeks. The secondary outcomes were 24 h ambulatory BP, central BP, heart-rate-corrected augmentation index (AIx75), carotid–femoral pulse wave velocity (cf-PWV), lipids, and high-sensitivity C-reactive protein (hs-CRP). Sixty-six participants were randomized at baseline (39M:27F, age: 51.5 ± 10.8 years, BMI:27.9 ± 3.2 kg/m²). In an intention-to-treat analysis, no differences were observed between HN and LN groups in terms of office systolic BP at 16 weeks (3.91 ± 3.52 mmHg, p = 0.27) or secondary outcomes. In this exploratory study, sustained HN vegetable supplementation did not exhibit more favorable vascular effects than LN vegetable supplementation in individuals with elevated BP.

Approximately 16% of North American couples are affected by infertility, with 30% of cases being attributable to male factor infertility. The regulation of reproductive hormones via the hypothalamic–pituitary–gonadal axis is important for spermatogenesis and subsequently male fertility. Maintaining iron homeostasis is critical to normal reproductive physiological function. This cross-sectional study’s objective was to determine the association between serum biomarkers of iron and reproductive hormones. Men experiencing infertility (n = 303) were recruited from Mount Sinai Hospital, Toronto. Serum was analyzed for iron and ferritin as biomarkers of iron status and reproductive hormones (follicle-stimulating hormone, luteinizing hormone, testosterone, estradiol, and prolactin), which were the primary outcome. Associations were determined using non-parametric Spearman’s rank correlation coefficient, linear regressions, and logistic regressions. A significant independent monotonic inverse relationship between serum iron and prolactin (p = 0.0002) was found. In linear regression analyses, iron was inversely associated with luteinizing hormone (unadjusted p = 0.03, adjusted p = 0.03) and prolactin (unadjusted p = 0.001 and adjusted p = 0.003). Serum ferritin was inversely associated with both gonadotropins, follicle-stimulating hormone (adjusted p = 0.03), and luteinizing hormone (adjusted p = 0.02). These findings suggest that biomarkers of iron are associated with pituitary-produced reproductive hormones, which play a role in the hypothalamic–pituitary–gonadal signaling pathway involved in spermatogenesis, testicular testosterone production, and male fertility.

Iron has been shown to play a dual role in health and disease, with either a protective or harmful effect. Some of the contradictory findings from observational studies may be due to reverse causation, residual confounding, or small sample size. One approach that may overcome these limitations without the high cost of randomized control trials is the use of Mendelian randomization to examine the long-term role of iron in a variety of health outcomes. As there is emerging evidence employing Mendelian randomization as a method of assessing the role of micronutrients in health and disease, this narrative review will highlight recent Mendelian randomization findings examining the role of iron in cardiometabolic disorders, inflammation, neurological disorders, different cancers, and a number of other health-related outcomes.

Introduction: Infertility affects about 16% of North American couples, with the male factor contributing to ∼30% of cases. Reproductive hormones play an integral role in regulating the reproductive system and consequently, fertility. Oxidative stress reduces testosterone synthesis, and reduction in oxidative stress can improve hormone profiles. Ascorbic acid is a potent antioxidant that accounts for up to 65% of seminal antioxidant activity; however, its effects on reproductive hormones in humans are unknown.Methods: The objective was to determine the association between serum ascorbic acid concentrations and male reproductive hormones. We conducted a cross-sectional study involving infertile males (n = 302) recruited from Mount Sinai Hospital, Toronto. Serum was analyzed for ascorbic acid, luteinizing hormone (LH), follicular stimulating hormone (FSH), total testosterone (TT), prolactin and estradiol. Statistical analyses included Spearman's rank correlations, linear regressions, logistic regressions, simple slope and Johnson-Neyman procedures.Results: After adjusting for covariates, ascorbic acid was inversely associated with LH (P = 0.01). Ascorbic acid was positively associated with TT only among males over the age of 41.6 years (P = 0.01).Discussion: Our findings show that ascorbic acid is associated with higher testosterone levels and improved androgenic status in infertile males, and some of the effects appear to be age dependent.