Vitamin B-12 Is Associated with Higher Serum Testosterone Concentrations and Improved Androgenic Profiles Among Men with Infertility.

BACKGROUND: Infertility impacts 16% of North American couples, with male factor infertility contributing to ∼30% of cases. Reproductive hormones, especially testosterone, are essential for spermatogenesis. An age-independent population-level decline in testosterone concentrations over the past few decades has been proposed to result from diet and lifestyle changes. Vitamin B-12 is present in the testes and has been suggested as an adjuvant nutritional therapy for male infertility due to its potential to improve sperm parameters. However, evidence examining the relationship between vitamin B-12 and reproductive hormones is limited. OBJECTIVES: The objective was to cross-sectionally examine the relationship between serum vitamin B-12 and male reproductive hormones (luteinizing hormone, follicular stimulating hormone, total testosterone, estradiol, and prolactin). METHODS: Men with infertility (n = 303) were recruited from Mount Sinai Hospital in Toronto, Canada. Serum was analyzed for vitamin B-12 and reproductive hormones. Statistical analyses included nonparametric Spearman's rank correlation coefficient, linear regression, logistic regression, and effect modification by age and BMI linear regressions. RESULTS: An independent monotonic relationship between serum vitamin B-12 and total testosterone (ρ = 0.19, P = 0.001) was observed. Serum vitamin B-12 was linearly associated with total testosterone (unadjusted ß = 0.0007, P = 0.008 and adjusted ß = 0.0005, P = 0.03). Compared with individuals in the lowest tertile of serum vitamin B-12, those in the middle tertile (adjusted odds ratio [OR] = 0.48; 95% confidence interval [CI]: 0.25, 0.93, P = 0.03) and the highest tertile (unadjusted OR = 0.41; 95% CI: 0.22, 0.77, P = 0.005) and (adjusted OR = 0.44; 95% CI: 0.22, 0.87, P = 0.02) had reduced odds of testosterone deficiency. CONCLUSIONS: These findings suggest that among men with infertility, low serum vitamin B-12 is associated with a higher risk of testosterone deficiency and impaired androgenic hormonal profiles that impact spermatogenesis and consequently, fertility.

The Evolution of Science and Regulation of Dietary Supplements: Past, Present, and Future.

Dietary supplement use in the United States is widespread and increasing, especially among certain population groups, such as older Americans. The science surrounding dietary supplements has evolved substantially over the last few decades since their formal regulation in 1994. Much has been learned about the mechanisms of action of many dietary supplement ingredients, but the evidence on their health effects is still building. As is true of much nutrition research, there are many studies that point to health effects, but not all are at the level of scientific evidence (e.g., randomized controlled interventions), rigor, or quality needed for definitive statements of efficacy regarding clinical endpoints. New technologies and approaches are being applied to the science of dietary supplements, including nutrigenomics and microbiome analysis, data science, artificial intelligence, and machine learning - all of which can elevate the science behind dietary supplements. Products can contain an array of bioactive compounds derived from foods as well as from medicinal plants, which creates enormous challenges in data collection and management. Clinical applications, particularly those aimed at providing personalized nutrition options for patients, have become more sophisticated as dietary supplements are incorporated increasingly into clinical practice and self-care. The goals of this paper are to provide historical context for the regulation and science of dietary supplements, identify research resources, and suggest some future directions for science in this field.

Using Mendelian Randomization to Study the Role of Iron in Health and Disease.

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.

Effect of Caffeine on Endurance Performance in Athletes May Depend on HTR2A and CYP1A2 Genotypes.

ABSTRACT: Guest, NS, Corey, P, Tyrrell, PN, and El-Sohemy, A. Effect of caffeine on endurance performance in athletes may depend on HTR2A and CYP1A2 genotypes. J Strength Cond Res 36(9): 2486-2492, 2022-This investigation determined whether variation in the HTR2A (serotonin receptor) gene modifies the ergogenic effects of caffeine on endurance and further modifies performance by the CYP1A2 genotype. Male athletes ( n = 100; 25 ± 4 years) completed 10-km cycling time trials under 3 conditions as follows: 0, 2, or 4 mg of caffeine per kg body mass. Using a randomized, double-blinded, placebo-controlled design, data were analyzed using analysis of covariance to compare changes in cycling time between placebo (0 mg·kg -1 ) and each caffeine dose and adjusted for the placebo trial and order of treatment. A significance of ρ ≤ 0.05 was used. Subjects were genotyped for HTR2A (rs6313) and CYP1A2 (rs762551). A significant caffeine- HTR2A interaction ( p = 0.003) was observed; however, after adjustment for placebo trials, the interaction was no longer significant ( p = 0.37). Because of the strong caffeine- CYP1A2 interaction ( p < 0.0001) previously reported in these subjects, where the 4-mg dose resulted in divergent effects (slower and faster) on the 10-km cycling time, we conducted a simplified model to examine these same factors by the HTR2A genotype. The post hoc analysis excluded HTR2A CT heterozygotes and 2-mg·kg -1 caffeine trials. Among CYP1A2 fast metabolizers alone, a significant difference (1.7 minutes; p = 0.006) was observed when comparing (4- vs. 0-mg·kg -1 caffeine trials) between the HTR2A CC ( n = 16; 2.4 minutes) and TT ( n = 7; 0.7 minutes) genotypes. Our results show that 4-mg·kg -1 caffeine improves performance in individuals with the HTR2A CC genotype but only in those who are also CYP1A2 AA fast metabolizers. This study was registered with clinicaltrials.gov (NCT02109783).

Recent advances and current controversies in genetic testing for personalized nutrition.

PURPOSE OF REVIEW: Considerable interest in personalized nutrition exists among the general public, policymakers, healthcare organizations and the private sector, but there is also skepticism of its utility. The present review aims to provide a summary of current controversies in the field of nutrigenomics, and to highlight recent research on the potential impact of implementing genetic testing for personalized nutrition in practice. RECENT FINDINGS: Numerous companies already offer genetic testing for personalized nutrition based on research developments in nutritional genomics. However, controversy exists over whethexr genetics contributes to interindividual responses to diet; the utility of single genetic variants versus genetic risk scores; the ability of DNA-based nutritional advice to elicit positive behavior change and health effects; and whether genetic information makes a difference on the type of dietary advice provided. Potential factors contributing to the discrepant viewpoints are discussed. SUMMARY: Despite the existing controversies, a solid body of evidence demonstrates that genetic testing for personalized nutrition is a powerful tool to guide dietary recommendations to improve health and performance, and to elicit positive behavior change.

Genetics of Iron Metabolism and Premenstrual Symptoms: A Mendelian Randomization Study.

BACKGROUND: Many women of reproductive age experience adverse psychological and physiological premenstrual symptoms. These symptoms may last for most of the reproductive years and can negatively affect the quality of life of many women. Some studies have examined the role of micronutrients in premenstrual symptoms, but the research on iron has been limited. OBJECTIVES: The objective of this study was to evaluate the effects of genetic predictors of iron overload and low iron status on premenstrual symptoms using Mendelian randomization. METHODS: We examined 254 White females aged 20-29 y from the Toronto Nutrigenomics and Health Study. DNA was isolated from peripheral white blood cells and genotyped for the homeostatic regulatory iron gene (HFE; rs1800562 and rs1799945), transmembrane protease serine 6 (TMPRSS6; rs482026), transferrin receptor 2 (TFR2; rs3811647), and transferrin (TF; rs738584) polymorphisms. Risk of iron overload or low iron status was determined based on combined genotypes. Binomial logistic regressions were carried out to examine the association between genetic risk of iron overload or low iron status and the presence of premenstrual symptoms. RESULTS: Compared with participants with typical risk of iron overload, those with an elevated risk of iron overload were less likely to experience premenstrual symptoms of confusion (OR: 0.13; 95% CI: 0.02, 1.00), headaches (OR: 0.28; 95% CI: 0.08, 0.98), and nausea (OR: 0.13; 95% CI: 0.02, 0.99) after adjusting for BMI, age, and vitamin C and calcium intake. No associations were seen with the other symptoms. There were also no associations between low iron status genotypes and premenstrual symptoms. CONCLUSIONS: This Mendelian randomization study demonstrates that women with an elevated risk of iron overload may have a lower risk of experiencing some premenstrual symptoms (headache, confusion, and nausea), suggesting that iron status could impact the risk of certain premenstrual symptoms.

Caffeine, genetic variation and anaerobic performance in male athletes: a randomized controlled trial.

PURPOSE: The effect of caffeine on anaerobic performance is unclear and may differ depending on an individual's genetics. The goal of this study was to determine whether caffeine influences anaerobic performance in a 30 s Wingate test, and if 14 single nucleotide polymorphisms (SNPs) in nine genes, associated with caffeine metabolism or response, modify caffeine's effects. METHODS: Competitive male athletes (N = 100; 25 ± 4 years) completed the Wingate under three conditions: 0, 2, or 4 mg of caffeine per kg of body mass (mg kg-1), using a double-blinded, placebo-controlled design. Using saliva samples, participants were genotyped for the 14 SNPs. The outcomes were peak power (Watts [W]), average power (Watts [W]), and fatigue index (%). RESULTS: There was no main effect of caffeine on Wingate outcomes. One significant caffeine-gene interaction was observed for CYP1A2 (rs762551, p = 0.004) on average power. However, post hoc analysis showed no difference in caffeine's effects within CYP1A2 genotypes for average power performance. No significant caffeine-gene interactions were observed for the remaining SNPs on peak power, average power and fatigue index. CONCLUSION: Caffeine had no effect on anaerobic performance and variations in several genes did not modify any effects of caffeine. TRIAL REGISTRATION: This study was registered with clinicaltrials.gov (NCT02109783).

CYP1A2 Genotype Modifies the Effects of Caffeine Compared With Placebo on Muscle Strength in Competitive Male Athletes.

Caffeine is commonly used to improve athletic performance across a variety of sports. Previously, the CYP1A2 gene has been shown to modify the effects of caffeine on endurance performance. The effect of caffeine on strength and power activities is unclear and may differ depending on an individual's CYP1A2 genotype. A randomized controlled trial was used to determine whether caffeine impacts strength and power, determined by the handgrip and vertical jump tests, respectively, and whether CYP1A2 genotype modifies any effects. Competitive male athletes (age = 25 ± 4 years) completed vertical jump (n = 97), and handgrip tests (n = 102) under three conditions: 0 (placebo), 2, or 4 mg of caffeine per kilogram of body mass (in milligrams per kilogram). CYP1A2 (rs762551) genotype was determined from saliva samples. No differences between caffeine doses and placebo were observed for strength or power; however, significant Caffeine × Gene interactions were observed for all exercise tests. Individuals with the CC genotype experienced a 12.8% decrease in handgrip strength with 4 mg/kg of caffeine compared with placebo (53 ± 11 kg vs. 61 ± 17 kg, p = .02). No differences were observed in those with the AC or AA genotypes. Despite observing a significant Caffeine × Gene interaction for vertical jump performance, no differences were observed between caffeine doses and placebo for all genotypes. In summary, caffeine (4 mg/kg) worsened handgrip strength performance in those with the CC genotype, but no differences were observed in those with the AC or AA genotypes. Athletes may want to consider their CYP1A2 genotype prior to using caffeine to improve muscle strength.

Toward the Definition of Personalized Nutrition: A Proposal by The American Nutrition Association.

Personalized nutrition holds tremendous potential to improve human health. Despite exponential growth, the field has yet to be clearly delineated and a consensus definition of the term "personalized nutrition" (PN) has not been developed. Defining and delineating the field will foster standardization and scalability in research, data, training, products, services, and clinical practice; and assist in driving favorable policy. Building on the seminal work of pioneering thought leaders across disciplines, we propose that personalized nutrition be defined as: a field that leverages human individuality to drive nutrition strategies that prevent, manage, and treat disease and optimize health, and be delineated by three synergistic elements: PN science and data, PN professional education and training, and PN guidance and therapeutics. Herein we describe the application of PN in these areas and discuss challenges and solutions that the field faces as it evolves. This and future work will contribute to the continued refinement and growth of the field of PN.Teaching pointsPN approaches can be most effective when there is consensus regarding its definition and applications.PN can be delineated into three main areas of application: PN science and data, PN education and training, PN guidance and therapeutics.PN science and data foster understanding about the impact of genetic, phenotypic, biochemical and nutritional inputs on an individual's health.PN education and training equip a variety of healthcare professionals to apply PN strategies in many healthcare settings.PN professionals have greater ability to tailor interventions via PN guidance and therapeutics.Favorable policy allows PN to be more fully integrated into the healthcare system.

The modifying effect of nutritional factors on the association between IL1-ß single nucleotide polymorphism and serum CXCL10 levels in young Canadian adults.

BACKGROUND: Genetic and nutritional factors play an important role in inflammatory response and diseases. CXCL10 is a critical biomarker that is involved in multiple inflammatory diseases, and elevated levels of CXCL10 have been associated with the development of several chronic and infectious diseases. In contrast, micronutrients can attenuate inflammatory responses. Single nucleotide polymorphisms in the pro-inflammatory cytokine genes such as IL-1ß at rs16944 contributed to a number of inflammatory disorders and may substantiate the convergance between chronic and infectious diseases. AIM: This study aims to identify the modifying effect of nutritional factors on the association between IL-1ß genotypes and CXCL10 levels. METHODS: Participants (N = 386) were healthy males and females from the Toronto Nutrigenomics and Health study recruited from the University of Toronto. Levels of micronutrients and inflammatory markers were measured in plasma. IL-1ß genotypes were extracted from the Affymetrix 6.0 SNP chip. RESULTS: CXCL10 levels were not different across different IL-1ß genotypes. Among those with the GA genotype, elevated CXCL10 levels were observed with higher than median ascorbic acid (ß = 0.004 ± 0.002, P = 0.047) or higher than median vitamin D status (ß = 0.003 ± 0.002, P = 0.044). Among participants with the AA genotype, subjects with low α-tocopherol status had elevated levels of CXCL10 (ß = -0.016 ± 0.007, P = 0.012). CONCLUSION: The association between IL-1ß rs16944 genotype and CXCL10 levels was modified by the levels of ascorbic acid, α-tocopherol and vitamin D. These findings may aid in understanding the combined effect of genetic and dietary factors in the development of various infectious and chronic diseases in which IL-1ß and CXCL10 may play an etiological role.

Genetic Variation in 9p21 and the Plasma Proteome.

Single nucleotide polymorphisms (SNPs) in the noncoding region of 9p21 have been associated with cardiovascular disease (CVD), but the mechanisms by which these genetic variants contribute to the pathogenesis of CVD remain unknown since no annotated proteins are present in this region of DNA. The objective of the current study was to determine if 9p21 genotypes are associated with distinct plasma proteins in young adults. Subjects were 1611 young adults aged 20-29 years from the Toronto Nutrigenomics and Health Study (1098 females and 513 males). DNA was isolated from fasting blood to analyze four SNPs in 9p21 (rs2383206, rs10757274, rs10757278, and rs1333049). Abundant plasma proteins ( n = 54) were measured using liquid chromatography multiple reaction monitoring mass spectrometry. Analysis of covariance was used to determine differences in plasma proteins between genotypes. In Caucasians ( n = 524), four SNPs were associated with apolipoprotein E and two with haptoglobin-ß-chain concentration. In East Asians ( n = 388), three SNPs were associated with α-1b-Glycoprotein, two with apolipoprotein B-100, one with apolipoprotein E and one with haptoglobin-ß-chain concentration. In South Asians ( n = 117), one SNP was associated with apolipoprotein B-100 concentration. Our findings suggest that 9p21 genotypes may play a role in various pathophysiological pathways that contribute to risk of CVD in early adulthood that might be distinct among different ethnocultural groups.

ABO Genotype Does Not Modify the Association between the "Blood-Type" Diet and Biomarkers of Cardiometabolic Disease in Overweight Adults.

Background: Although 7 million copies of Eat Right 4 Your Type have been sold in >60 languages, there has been a lack of evidence supporting the "blood-type" diet hypothesis. Objective: The present study aimed to examine the validity of this diet in overweight adults. Methods: A total of 973 adults [mean ± SEM age: 44.6 ± 0.4 y; mean ± SEM body mass index (BMI; kg/m2): 32.5 ± 0.2; 758 women, 215 men] were participants of the Toronto Healthy Diet Study. A 1-mo, 196-item food-frequency questionnaire was used to determine dietary intakes before and after a 6-mo dietary intervention. Diet scores were calculated to determine relative adherence to each of the 4 blood-type diets as a secondary analysis. ABO blood group was determined by genotyping rs8176719 and rs8176746. ANCOVA was used to compare cardiometabolic risk factors across tertiles of diet scores. Results: At baseline, individuals with a higher adherence score to the type A diet had lower diastolic blood pressure (tertile 3 compared with tertile 1: 70.9 ± 1.1 compared with 73.3 ± 1.1 mm Hg; P < 0.01). Lower waist circumference was observed in individuals with higher adherence to the type B (tertile 3 compared with tertile 1: 100.8 ± 1.8 compared with 105.4 ± 1.7 cm; P < 0.01) and type AB (tertile 3 compared with tertile 1: 101.2 ± 1.8 compared with 104.8 ± 1.7 cm; P < 0.01) diets. After a 6-mo dietary intervention, individuals with increased adherence to the type A and type B diets had greater reductions in BMI and waist circumference, respectively (P < 0.01). Individuals with an increase in type O diet adherence showed decreases in both BMI and waist circumference (P < 0.01). However, matching the diets with the corresponding ABO genotype of each individual did not change the effect size of any of these associations either at baseline or at 6 mo. Conclusions: ABO genotype does not modify any association between blood-type diets and biomarkers of cardiometabolic disease in overweight adults, suggesting that the theory behind this diet is not valid This study was based on the data of a trial that was registered at www.clinicaltrials.gov as NCT00516620.

Genetic variant in the ß2 -adrenergic receptor (Arg16Gly) influences fat-free mass, muscle strength and motor unit behaviour in young men.

NEW FINDINGS: What is the central question of this study? Does a common genetic variant in the ß2 -adrenergic receptor (ß2 -AR) have effects on skeletal muscle function in young, healthy men? What is the main finding and its importance? This study provides preliminary evidence that ß2 -AR Arg16Gly genotype has a significant effect on fat-free mass, muscle strength and motor unit behaviour in recreationally trained men. These data might have important clinical and exercise-related implications. For example, ß2 -AR (rs1042713) genotype might influence the responsiveness of skeletal muscle to clinical or exercise-based interventions or ß-AR agonist treatment. ABSTRACT: This study explored whether the ß2 -adrenergic receptor (ß2 -AR) single nucleotide polymorphism at amino acid 16 (Arg16Gly) has functional effects on skeletal muscle mass, torque production and motor unit behaviour in young, healthy men. Twenty-eight recreationally active men (mean ± SD 23.1 ± 1.3 years of age) were genotyped for Arg16Gly polymorphisms of ß2 -AR as arginine homozygous (ArgArg; n = 5), glycine homozygous (GlyGly; n = 11) or arginine-glycine heterozygous (ArgGly; n = 12). The participants then completed body composition testing, assessments of leg extensor size and echo intensity, and evoked and voluntary isometric leg-extension muscle actions. During the evoked muscle actions, peak twitch torque, peak rate of torque development and peak relaxation rate were assessed. During the voluntary muscle actions, maximal voluntary isometric (MVIC) strength was assessed, and surface EMG signals were obtained during submaximal isometric muscle actions and later decomposed to examine motor unit firing behaviour. Fat-free mass and MVIC strength were greater (P = 0.004, d = 1.74 and P = 0.026, d = 1.10, respectively) in those expressing the GlyGly versus ArgArg allele. The slope of the mean firing rate versus recruitment threshold relationship was more negative in the GlyGly than the ArgArg allele carriers (P = 0.012, d = 1.68) at 50% MVIC, but was less negative in GlyGly and ArgGly versus ArgArg allele carriers (P = 0.013 and 0.016, respectively; d = 1.34 and 1.20, respectively) at 70% MVIC. These data provide preliminary evidence that ß2 -AR Arg16Gly genotype has a significant effect on fat-free mass, muscle strength and motor unit behaviour in humans.

Biomarkers of cardiometabolic health and nutritional status in individuals with positive celiac disease serology.

BACKGROUND: Celiac disease (CD) is an autoimmune disorder characterized by damage to the intestinal mucosa and nutrient malabsorption in severe cases. However, it remains unclear whether nutrient deficiencies and other adverse health effects are prevalent in individuals with positive CD serology identified through screening studies. OBJECTIVE: The objective was to determine whether biomarkers of cardiometabolic health and nutritional status differ between those with positive and negative CD serology identified in a screening study of Canadian adults. METHODS: Participants ( n=2832) were from the Toronto Nutrigenomics and Health Study and the Toronto Healthy Diet Study. Individuals were screened for CD-specific anti-tissue transglutaminase autoantibodies. Lipid profiles as well as concentrations of six carotenoids (α-carotene, ß-carotene, ß-cryptoxanthin, lutein, lycopene, and zeaxanthin), three tocopherols (α-tocopherol, δ-tocopherol, and γ-tocopherol), retinol, ascorbic acid, and 25-hydroxyvitamin D were cross-sectionally compared between those with positive and negative CD serology using general linear mixed models. RESULTS: Individuals with positive CD serology ( n=23) had significantly lower levels of HDL-cholesterol ( p=0.008) and apolipoprotein-AI ( p=0.02), a higher ratio of total cholesterol to HDL-cholesterol ( p=0.006), and a higher apolipoprotein-B/AI ratio ( p=0.03) than those with negative CD serology. Positive CD serology was also associated with significantly lower concentrations of retinol ( p=0.006) in fully adjusted models. Those with positive CD serology had lower serum 25-hydroxyvitamin D in unadjusted models ( p=0.01), but not in fully adjusted models ( p=0.08). CONCLUSIONS: Individuals with undiagnosed CD may have unfavorable lipid profiles and be at elevated risk for inadequacy of certain fat-soluble vitamins, but not widespread nutrient deficiencies.

Lactose Intolerance (LCT-13910C>T) Genotype Is Associated with Plasma 25-Hydroxyvitamin D Concentrations in Caucasians: A Mendelian Randomization Study.

Background: The LCT-13910C>T gene variant is associated with lactose intolerance (LI) in different ethnic groups. Individuals with LI often limit or avoid dairy consumption, a major dietary source of vitamin D in North America, which may lead to inadequate vitamin D intake.Objective: The objective was to determine the prevalence of genotypes predictive of LI in different ethnic groups living in Canada and to determine whether the LCT genotype is associated with plasma 25(OH)D concentrations.Methods: Blood samples were drawn from a total of 1495 men and women aged 20-29 y from the Toronto Nutrigenomics and Health Study for genotyping and plasma 25(OH)D analysis. Intakes of dairy were assessed by using a 196-item food frequency questionnaire. The prevalence of LCT-13910C>T genotypes was compared by using χ2 analysis. Using a Mendelian randomization approach, we examined the association between LCT genotypes and 25(OH)D concentrations.Results: Approximately 32% of Caucasians, 99% of East Asians, 74% of South Asians, and 59% of those with other or mixed ethnicities had the CC genotype associated with LI. Compared with those with the TT genotype, those with the CC genotype had a lower mean ± SE total dairy intake (2.15 ± 0.09 compared with 2.67 ± 0.12 servings/d, P = 0.003), a lower skim-milk intake (0.20 ± 0.03 compared with 0.46 ± 0.06 servings/d, P = 0.0004), and a lower plasma 25(OH)D concentration (63 ± 1.9 compared with 75.8 ± 2.4 nmol/L, P < 0.0001). The CT and CC genotypes were associated with a 50% and a 2-fold increased risk, respectively, of a suboptimal plasma 25(OH)D concentration (<75 nmol/L).Conclusions: In Caucasians, the CC genotype that predicts LI is associated with a lower plasma 25(OH)D concentration, which is attributable at least in part to a lower intake of dairy, particularly skim milk. Increased risk of suboptimal concentrations of vitamin D was also observed among those with the CT genotype, suggesting an intermediate effect of the heterozygous genotype.

Hormonal contraceptive use and prevalence of premenstrual symptoms in a multiethnic Canadian population.

BACKGROUND: Hormonal contraceptive use may be associated with a reduction in some premenstrual symptoms, however, the evidence remains equivocal. The objectives of the present study were to investigate the associations between ethnicity and hormonal contraceptive use with premenstrual symptoms. METHODS: One thousand one hundred two women participating in the Toronto Nutrigenomics and Health Study provided data on their premenstrual symptoms and hormonal contraceptive use. Severity of symptoms was classified as none, mild, moderate, or severe. Prevalence of premenstrual symptoms was determined in the total population and among major ethnic groups. Logistic regressions were used to determine the association between ethnicity and prevalence of premenstrual symptoms. Logistic regressions were used to determine the associations between hormonal contraceptive use, and premenstrual symptoms, adjusting for ethnicity and other covariates. RESULTS: Prevalence of individual symptoms varied, and the most commonly reported were cramps (75%), bloating (75%), mood swings (73%), increased appetite (64%), and acne (62%). Prevalence of cramps differed between ethnic groups with East Asians reporting a lower prevalence than Caucasians and South Asians (p < 0.05). Use of hormonal contraceptives was associated with a lower RR (95% CI) of experiencing moderate/severe: cramps (0.82, 0.72-0.93), clumsiness (0.22, 0.07-0.73), confusion (0.22, 0.09-0.54) and desire to be alone (0.45, 0.28-0.73). Hormonal contraceptive use was not associated with the risk of premenstrual symptoms at mild severity. Hormonal contraceptive use was not associated with symptoms of anxiety, bloating, mood swings, increased appetite, acne, fatigue, sexual desire, depression, nausea, headache and insomnia. CONCLUSION: This study demonstrates that East Asians may be at a lower risk of experiencing premenstrual cramps and that hormonal contraceptive use is associated with a lower risk of experiencing many, but not all, premenstrual symptoms at moderate/severe severity.

Recalled taste intensity, liking and habitual intake of commonly consumed foods.

Taste intensity and quality affect the liking of foods, and determine food choice and consumption. We aimed to 1) classify commonly consumed foods based on recalled taste intensity for bitter, sweet, salty, sour, and fatty taste, and 2) examine the associations among recalled taste intensity, liking, and habitual consumption of foods. In Stage 1, 62 Canadian adults recalled the taste intensity of 120 common foods. Their responses were used to identify sets of 20-25 foods classified as strongly bitter, sweet, salty, sour or fatty-tasting. In Stage 2, 287 U.S. adults validated these selections, and let us reduce them to sets of 11-13 foods. Ratings of recalled taste intensity were consistent across age, sex and overweight status, with the exceptions that sweet, bitter and fatty-tasting foods were rated as more intense by women than by men. The recalled intensity ratings of the most bitter, salty and fatty foods (but not sour or sweet foods) were inversely correlated with liking and intake. The negative correlation between fatty taste intensity and fatty food liking was stronger among normal weight than among overweight participants. Our results suggest that the recalled taste intensity of foods is associated with food liking and habitual consumption, but the strength of these relationships varies by taste. The food lists based on taste intensity ratings provide a resource to efficiently calculate indices of exposure to the different tastes in future studies.

Gluten Intake Is Positively Associated with Plasma α2-Macroglobulin in Young Adults.

BACKGROUND: Gluten-free foods have increased in popularity over the past decade and are now being consumed by individuals without celiac disease. However, the physiologic effects of gluten intake in individuals without celiac disease remain unknown. High-abundance plasma proteins involved in inflammation, endothelial function, and other physiologic pathways may represent potential biomarkers of biological effects of gluten intake. OBJECTIVE: The objective was to examine the association between gluten intake and plasma proteomic biomarkers in a population of adults without clinically diagnosed celiac disease. METHODS: Subjects (n = 1095) were participants of the Toronto Nutrigenomics and Health Study, a cross-sectional examination of young adults aged 20-29 y. Dietary gluten intake was estimated by using a 1-mo, 196-item semiquantitative food-frequency questionnaire. The concentrations of 54 plasma proteins were measured simultaneously by liquid chromatography/multiple-reaction monitoring mass spectrometry. The association between gluten intake and each proteomic biomarker was examined by using general linear models. Analyses were then conducted in individuals who do not have the human leukocyte antigen (HLA)-DQ2 or DQ8 risk variants required for the development of celiac disease to determine whether any associations observed could have been due to undiagnosed cases of celiac disease. RESULTS: Increased gluten intake was associated with increased concentrations of plasma α2-macroglobulin (P = 0.01), a marker of inflammation and cytokine release. The association remained after adjusting for age, sex, BMI, ethnicity, physical activity, energy intake, fiber intake, and hormonal contraceptive use among women. This relation was not modified by HLA risk variants. CONCLUSION: Gluten consumption is associated with increased plasma α2-macroglobulin in young adults, which appears to be independent of celiac disease, suggesting possible effects of gluten on inflammation.

Maternal Choline Status, but Not Fetal Genotype, Influences Cord Plasma Choline Metabolite Concentrations.

BACKGROUND: Choline deficiency during pregnancy can lead to adverse birth outcomes, including impaired neurodevelopment and birth defects. Genetic variants of choline and one-carbon metabolism may also influence birth outcomes by altering plasma choline concentrations. The effects of maternal ad libitum choline intake during pregnancy and fetal genetic variants on maternal and cord concentrations of choline and its metabolites are unknown. OBJECTIVES: This prospective study sought to assess the effect of 1) maternal dietary choline intake on maternal and cord plasma concentrations of choline and its metabolites, and 2) fetal genetic polymorphisms on cord plasma concentrations. METHODS: The dietary choline intake of 368 pregnant Canadian women was assessed in early (0-16 wk) and late (23-37 wk) pregnancy with the use of a food frequency questionnaire. Plasma concentrations of free choline and its metabolites were measured in maternal samples at recruitment and delivery, and in the cord blood. Ten fetal genetic variants in choline and one-carbon metabolism were assessed for their association with cord plasma concentrations of free choline and its metabolites. RESULTS: Mean maternal plasma free choline, dimethylglycine, and trimethylamine N-oxide (TMAO) concentrations increased during pregnancy by 49%, 17%, and 13%, respectively (P < 0.005), whereas betaine concentrations decreased by 21% (P < 0.005). Cord plasma concentrations of free choline, betaine, dimethylglycine, and TMAO were 3.2, 2.0, 1.3, and 0.88 times corresponding maternal concentrations at delivery, respectively (all P < 0.005). Maternal plasma concentrations of betaine, dimethylglycine, and TMAO (r(2) = 0.19-0.51; P < 0.0001) at delivery were moderately strong, whereas maternal concentrations of free choline were not significant (r(2) = 0.12; P = 0.06), predictors of cord plasma concentrations of these metabolites. Neither maternal dietary intake nor fetal genetic variants predicted maternal or cord plasma concentrations of choline and its metabolites. CONCLUSION: These data collectively indicate that maternal choline status, but not fetal genotype, influences cord plasma concentrations of choline metabolites. This trial was registered at clinicaltrials.gov as NCT02244684.

Biomarkers of Iron Are Associated with Anterior-Pituitary-Produced Reproductive Hormones in Men with Infertility.

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.