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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. 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 (%). 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. Caffeine had no effect on anaerobic performance and variations in several genes did not modify any effects of caffeine. This study was registered with clinicaltrials.gov (NCT02109783).

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.

Infertility affects nearly 50 million couples worldwide, with 40−50% of cases having a male factor component. It is well established that nutritional status impacts reproductive development, health and function, although the exact mechanisms have not been fully elucidated. Genetic variation that affects nutrient metabolism may impact fertility through nutrigenetic mechanisms. This review summarizes current knowledge on the role of several dietary components (vitamins A, B(12), C, D, E, folate, betaine, choline, calcium, iron, caffeine, fiber, sugar, dietary fat, and gluten) in male reproductive health. Evidence of gene-nutrient interactions and their potential effect on fertility is also examined. Understanding the relationship between genetic variation, nutrition and male fertility is key to developing personalized, DNA-based dietary recommendations to enhance the fertility of men who have difficulty conceiving.

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 ( p0.0001) 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).

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-1β 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-1β 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-1β genotypes were extracted from the Affymetrix 6.0 SNP chip.Results:CXCL10 levels were not different across different IL-1β genotypes. Among those with the GA genotype, elevated CXCL10 levels were observed with higher than median ascorbic acid (β = 0.004 ± 0.002, P = 0.047) or higher than median vitamin D status (β = 0.003 ± 0.002, P = 0.044). Among participants with the AA genotype, subjects with low α-tocopherol status had elevated levels of CXCL10 (β = −0.016 ± 0.007, P = 0.012).Conclusion:The association between IL-1β 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-1β and CXCL10 may play an etiological role.

ImportanceCaffeine is detoxified by cytochrome P450 1A2 (CYP1A2), and genetic variation in CYP1A2 impacts the rate of caffeine clearance. Factors that may modify the association between coffee intake and kidney disease remain unclear.ObjectiveTo assess whether CYP1A2 genotype modifies the association between coffee intake and kidney dysfunction.Design, Setting, and ParticipantsThe Hypertension and Ambulatory Recording Venetia Study (HARVEST) was a prospective cohort study of individuals with stage 1 hypertension in Italy; HARVEST began on April 1, 1990, and follow-up is ongoing. The current study used data from April 1, 1990, to June 30, 2006, with follow-up of approximately 10 years. Blood pressure and biochemical data were collected monthly during the first 3 months, then every 6 months thereafter. Data were analyzed from January 2019 to March 2019. Participants were screened and recruited from general practice clinics. The present study included 1180 untreated participants aged 18 to 45 years with stage 1 hypertension; those with nephropathy, diabetes, urinary tract infection, and cardiovascular disease were excluded.ExposuresCoffee intake and CYP1A2 genotype rs762551 were exposures analyzed over a median follow-up of 7.5 (IQR, 3.1-10.9) years.Main Outcomes and MeasuresAlbuminuria (defined as an albumin level of ≥30 mg/24 h) and hyperfiltration (defined as an estimated glomerular filtration rate of ≥150 mL/min/1.73 m2) were the primary outcomes as indicators of kidney dysfunction.ResultsAmong 1180 participants, genotyping, lifestyle questionnaires, and urine analysis data were obtained from 604 individuals (438 [72.5%] male) with a mean (SD) age of 33.3 (8.5) years and a mean (SD) body mass index (calculated as weight in kilograms divided by height in meters squared) of 25.4 (3.4). A total of 158 participants (26.2%) consumed less than 1 cup of coffee per day, 379 (62.7%) consumed 1 to 3 cups per day, and 67 (11.1%) consumed more than 3 cups per day. Genotype frequencies for rs762551 (260 participants [43.1%] with genotype AA, 247 participants [40.8%] with genotype AC, and 97 participants [16.1%] with genotype CC) did not differ between coffee intake categories. The level of risk of developing albuminuria, hyperfiltration, and hypertension, assessed by Cox regression and survival analyses, was not associated with coffee intake in the entire group or among fast metabolizers. The risks of albuminuria (adjusted hazard ratio [aHR], 2.74; 95% CI, 1.63-4.62; P P = .01), and hypertension (aHR, 2.81; 95% CI, 1.51-5.23; P = .001) increased significantly among slow metabolizers who consumed more than 3 cups per day.Conclusions and RelevanceIn this study, the risks of albuminuria, hyperfiltration, and hypertension increased with heavy coffee intake only among those with the AC and CC genotypes of CYP1A2 at rs762551 associated with slow caffeine metabolism, suggesting that caffeine may play a role in the development of kidney disease in susceptible individuals.

Premenstrual symptoms are experienced by most women of reproductive age, but effective therapies are limited. Carotenoids may have an attenuating effect on premenstrual symptoms, however, studies to date are equivocal. The objective of the present study was to examine the association between plasma concentrations of seven carotenoids and premenstrual symptom severity in 553 women from the Toronto Nutrigenomics and Health study. Participants provided information on fifteen common premenstrual symptoms and severities. Each participant completed a General Health and Lifestyle Questionnaire and provided a fasting blood sample from which plasma carotenoid concentrations were measured. Multinomial logistic regressions were used to determine associations between plasma carotenoid concentrations and premenstrual symptom severity. Beta-cryptoxanthin was associated with moderate/severe increased appetite for women in the highest compared to the lowest tertile (OR: 2.33, 95% CI: 1.39, 3.89). This association remained significant after adjusting for multiple comparisons. There were no observed associations between other plasma carotenoids and any premenstrual symptoms. In summary, higher concentrations of beta-cryptoxanthin were associated with an increased appetite as a premenstrual symptom, but no associations were observed for any other carotenoid and for any other symptom.

BackgroundVitamin D status has been associated with the presence and severity of several premenstrual symptoms (PMSx) in some, but not all studies. Inconsistencies among findings may be explained by unaccounted genetic variation in the vitamin D receptor (VDR).ObjectiveTo determine whether associations between vitamin D status and individual PMSx are influenced byVDRgenotype.MethodsSeven hundred sixteen women aged 20-29 years old from the Toronto Nutrigenomics and Health study provided plasma samples and completed a questionnaire on the presence and severity of 15 common PMSx. Plasma 25-hydroxyvitamin D (25(OH)D) concentration was measured and participants were categorized into sufficient (≥ 50 nmol/L) and insufficient (< 50 nmol/L) vitamin D status groups. DNA was obtained from blood samples to genotype for a commonVDRsingle nucleotide variant, rs796858. Using logistic regression, odds of experiencing PMSx were compared between vitamin D-sufficient and insufficient women, stratified by genotype.ResultsAmong CC homozygotes, insufficient vitamin D status was associated with higher odds of experiencing premenstrual fatigue (OR, 2.53; 95% CI, 1.40, 4.56) and nausea (OR, 2.44; 95% CI, 1.00, 5.95). Among TT homozygotes, insufficient vitamin D status was associated with lower odds of experiencing fatigue (OR, 0.44; 95% CI, 0.20, 0.97) and increased appetite (OR, 0.48; 95% CI, 0.22, 1.04). Insufficient vitamin D status was associated with higher odds of increased appetite in women with the CT genotype (OR, 1.78; 95% CI, 1.03, 3.07).VDRgenotype modified the association between vitamin D status and the following PMSx: increased appetite (interactionp= 0.027), fatigue (interactionp= 0.016), and nausea (interactionp= 0.039).ConclusionWe found evidence thatVDRgenotype may modify the association between 25(OH)D and some PMSx. Insufficient 25(OH)D was associated with a higher risk of premenstrual fatigue in those with the CC genotype, but lower risk in those with the TT genotype.

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. JMO would like to thank the US Department of Agriculture, Agriculture Research Service (8050–51000-098-00D). Sí

Past research using hepatic rat microsomes showed that soy protein suppressed delta-6 desaturase activity (D6D) compared to casein (a dairy protein). The effects of soy and dairy on desaturase pathway activity in humans remain poorly investigated. The objective of this analysis was to investigate the association between soy and dairy consumption with plasma fatty acids and estimate the desaturase pathway activity in a multiethnic Canadian population of young adults. We analyzed data from men (n = 319) and women (n = 764) previously collected for the Toronto Nutrigenomics and Health Study. Food frequency questionnaires and plasma fatty acids were assessed. Relationships between soy and dairy beverages and food consumption with estimated desaturase activities were assessed by regression models and by grouping participants according to beverage and food intake data. Weak inverse associations (p ≤ 0.05) were found between soy consumption and the overall desaturation pathway activity, specifically D6D activity. When participants were grouped based on soy and dairy consumption habits, omega-6 LC-PUFAs, as well as various estimates of the desaturase pathway activity, were significantly lower in individuals consuming soy (with or without dairy) compared to individuals consuming only fluid milk and dairy products. In conclusion, soy consumption, not dairy consumption, appears to suppress desaturase pathway activity.

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.

Background It was suggested that low salivary-amylase activity (SAA) and cooling or stir-frying cooked starch decreases its digestibility and glycemic index. Objective We determined the effects of SAA, cooling, and single-nucleotide polymorphisms (SNPs) in the salivary amylase (AMY1), pancreatic amylase (AMY2A, AMY2B), maltase-glucoamylase (MGAM), and sucrase-isomaltase (SI) genes on starch digestibility and glycemic index of cooked polished rice. Methods Healthy subjects [pilot, n = 12; main, n = 20 with low-SAA ( 105 U/mL)] consumed test meals containing 25 g (pilot) or 50 g (main) available carbohydrate at a contract research organization using open-label (pilot) or assessor-blinded (main), randomized, crossover, Latin-square designs (trial registration: NCT03667963). Pilot-trial test meals were dextrose, freshly cooked polished rice, cooked rice cooled overnight, stir-fried hot rice, or stir-fried cold rice. Main-trial test meals were dextrose, dextrose plus 10 g lactulose, plain hot rice, or plain cold rice. In both trials, blood glucose was measured fasting and at intervals over 2 h. In the main trial, breath hydrogen was measured fasting and hourly for 6 h to estimate in vivo starch digestibility. Data were analyzed by repeated-measures ANOVA for the main effects of temperature and stir-frying (pilot trial) or the main effects of SAA and temperature (main trial) and their interactions. Effects of 24 single nucleotide polymorphisms (SNPs) were assessed separately. Means were considered to be equivalent if the 95% CI of the differences were within ±20% of the comparator mean for glucose response/glycemic index or ±7% for digestibility. Results Pilot: neither temperature nor stir-frying significantly affected glucose incremental AUC (primary endpoint, n = 12). Main: mean ± SEM glycemic index (primary endpoint, n = 40) was equivalent for low-SAA compared with high-SAA (73 ± 3 vs. 75 ± 4) and cold rice compared with hot rice (75 ± 3 vs. 70 ± 3). Estimated starch digestibility (n = 39) was equivalent for low-SAA compared with high-SAA (95% ± 1% vs. 92% ± 1%) and hot rice compared with cold rice (94% ± 1% vs. 93% ± 1%). No meaningful associations were observed between genotypes and starch digestibility or glycemic index for any of the SNPs. Conclusions The results do not support the hypotheses that low-SAA, cooling, and common genetic variations in starch-digesting enzymes affect the glycemic index or in vivo carbohydrate digestibility of cooked polished rice. This trial was registered at clinicaltrials.gov as NCT03667963.

Background: Fructose providing excess calories in the form of sugar sweetened beverages (SSBs) increases markers of non-alcoholic fatty liver disease (NAFLD). Whether this effect holds for other important food sources of fructose-containing sugars is unclear. To investigate the role of food source and energy, we conducted a systematic review and meta-analysis of controlled trials of the effect of fructose-containing sugars by food source at different levels of energy control on non-alcoholic fatty liver disease (NAFLD) markers. Methods and Findings: MEDLINE, Embase, and the Cochrane Library were searched through 7 January 2022 for controlled trials ≥7-days. Four trial designs were prespecified: substitution (energy-matched substitution of sugars for other macronutrients); addition (excess energy from sugars added to diets); subtraction (excess energy from sugars subtracted from diets); and ad libitum (energy from sugars freely replaced by other macronutrients). The primary outcome was intrahepatocellular lipid (IHCL). Secondary outcomes were alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Independent reviewers extracted data and assessed risk of bias. The certainty of evidence was assessed using GRADE. We included 51 trials (75 trial comparisons, n = 2059) of 10 food sources (sugar-sweetened beverages (SSBs); sweetened dairy alternative; 100% fruit juice; fruit; dried fruit; mixed fruit sources; sweets and desserts; added nutritive sweetener; honey; and mixed sources (with SSBs)) in predominantly healthy mixed weight or overweight/obese younger adults. Total fructose-containing sugars increased IHCL (standardized mean difference = 1.72 [95% CI, 1.08 to 2.36], p < 0.001) in addition trials and decreased AST in subtraction trials with no effect on any outcome in substitution or ad libitum trials. There was evidence of influence by food source with SSBs increasing IHCL and ALT in addition trials and mixed sources (with SSBs) decreasing AST in subtraction trials. The certainty of evidence was high for the effect on IHCL and moderate for the effect on ALT for SSBs in addition trials, low for the effect on AST for the removal of energy from mixed sources (with SSBs) in subtraction trials, and generally low to moderate for all other comparisons. Conclusions: Energy control and food source appear to mediate the effect of fructose-containing sugars on NAFLD markers. The evidence provides a good indication that the addition of excess energy from SSBs leads to large increases in liver fat and small important increases in ALT while there is less of an indication that the removal of energy from mixed sources (with SSBs) leads to moderate reductions in AST. Varying uncertainty remains for the lack of effect of other important food sources of fructose-containing sugars at different levels of energy control.

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.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 kgThere 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.Caffeine had no effect on anaerobic performance and variations in several genes did not modify any effects of caffeine.This study was registered with clinicaltrials.gov (NCT02109783).

INTRODUCTION Hereditary hemochromatosis can cause individuals to absorb too much iron from their diet. Higher tissue iron content, below the threshold of toxicity, may enhance oxygen carrying capacity and offer a competitive advantage. Single nucleotide polymorphisms (SNP) in the homeostatic iron regulator (HFE) gene have been shown to modify iron metabolism and can be used to predict an individual's risk of hemochromatosis. Several studies have shown that HFE genotypes are associated with elite endurance athlete status; however, no studies have examined whether HFE genotypes are associated with endurance performance. PURPOSE The objectives of this study were to determine whether there was an association between HFE risk genotypes (rs1800562 and rs1799945) and endurance performance in a 10-km cycling time trial as well as maximal oxygen uptake (V˙O2peak), an indicator of aerobic capacity. METHODS Competitive male athletes (n = 100; age = 25 ± 4 yr) completed a 10-km cycling time trial. DNA was isolated from saliva and genotyped for the rs1800562 (C282Y) and rs1799945 (H63D) SNP in HFE. Athletes were classified as low risk (n = 88) or medium/high risk (n = 11) based on their HFE genotype for both SNP using an algorithm. ANCOVA was conducted to compare outcome variables between both groups. RESULTS Individuals with the medium- or high-risk genotype were ~8% (1.3 min) faster than those with the low-risk genotype (17.0 ± 0.8 vs 18.3 ± 0.3 min, P = 0.05). V˙O2peak was ~17% (7.9 mL·kg-1⋅min-1) higher in individuals with the medium- or high-risk genotype compared with those with the low-risk genotype (54.6 ± 3.2 vs 46.7 ± 1.0 mL·kg-1⋅min-1, P = 0.003). CONCLUSION Our findings show that HFE risk genotypes are associated with improved endurance performance and increased V˙O2peak in male athletes.

An athlete's dietary and supplement strategies can provide a valuable contribution to overall sport performance. Personalized nutrition for athletes and fitness enthusiasts aims to optimize nutrition status, body composition, and exercise performance by tailoring dietary recommendations to an individual's genetic profile. Sport dietitians and nutritionists have long been modifying the one-size-fits-all general population dietary guidelines in order to accommodate the needs of athletes. In general, high-performance sport requires the addition of carbohydrates to fuel training and higher protein intakes to repair muscle. However, generic recommendations still remain with regard to micronutrients, food intolerances, bone health, risk of muscle damage, and various other performance-related nutritional factors that deserve consideration. Genetic variation is known to affect absorption, metabolism, uptake, utilization, and excretion of nutrients and food bioactives, which can alter the activity of metabolic pathways. Nutrigenomics and nutrigenetics are experimental approaches that use genomic information and genetic testing technologies to examine the role of individual genetic differences in modifying an athlete's response to nutrients or substances in foods and supplements. With the exception of caffeine, there have been few randomized, controlled trials examining the effects of genetic variation on performance in response to dietary interventions or ergogenic aids. However, there is a growing foundation of research linking gene–diet interactions on biomarkers of health and nutritional status. This means that reaching specific targets for an athlete's nutritional status to optimize health and body composition will in turn beneficially affect exercise and sport performance. These concepts and their actions form the basis from which the field of sport nutrigenomics continues to develop. Here we review the current science that associates genetic modifiers with foods, nutrients and ergogenic aids, and their impact on athletic performance.

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.

Zinc is an essential trace mineral that serves as a cofactor for the delta-5 and delta-6 desaturases (D5D, D6D) that are critical for long-chain polyunsaturated fatty acid (LC-PUFA) synthesis. While plasma zinc levels are generally reported to be associated with D5D and D6D indices in humans, it remains unclear if dietary zinc intake can be similarly associated with desaturase indices. Therefore, the present investigation examined if zinc intake determined by food frequency questionnaire (FFQ) is associated with desaturase indices in young Canadian adults. Additionally, we explored whether desaturase indices were modified by an interaction between dietary zinc intake and a common variant in the FADS1 gene.Dietary zinc intake (FFQ), plasma fatty acids (gas chromatography) and the FADS1 rs174547 polymorphism were analyzed in young men and women (n = 803) from the cross-sectional Toronto Nutrigenomics and Health Study. Product-to-precursor fatty acid ratios were used to determine desaturase enzyme indices (D5D = 20:4n-6/20:3n-6; D6D = 18:3n-6/18:2n-6). Individuals were grouped according to dietary zinc intake, as well as by their rs174547 genotype (TT vs. TC+CC). Data were analyzed by 1-way and 2-way ANCOVA.Plasma fatty acids and D5D/D6D indices did not differ between individuals grouped according to dietary zinc intake. Further, the recently proposed biomarker of zinc intake, 20:3n-6/18:2n-6, was not associated with dietary zinc intake. Although the FADS1 rs174547 SNP was significantly associated with D5D and D6D indices in both men and women (p 0.0001), we did not find evidence of a dietary zinc intake - FADS1 SNP interaction on D5D or D6D indices.Dietary zinc intake, as determined using FFQs, does not predict differences in desaturase indices, irrespective of FADS1 genotype.

NEW FINDINGS What is the central question of this study? Does a common genetic variant in the β2 -adrenergic receptor (β2 -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 β2 -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, β2 -AR (rs1042713) genotype might influence the responsiveness of skeletal muscle to clinical or exercise-based interventions or β-AR agonist treatment. ABSTRACT This study explored whether the β2 -adrenergic receptor (β2 -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 β2 -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 β2 -AR Arg16Gly genotype has a significant effect on fat-free mass, muscle strength and motor unit behaviour in humans.

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.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.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, β-carotene, β-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.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).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.

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 (

There were 3 presentations at the symposium, one by Ahmed El-Sohemy of the Department of Nutritional Sciences of the University of Toronto; one by George J. Brewer, Emeritus Professor, Department o...

The role of genetic variation in influencing an individual’s response to diet and nutritional interventions is being increasingly recognized in nutrition research and practice. Discoveries in the field of nutrigenomics and nutrigenetics have paved the way for personalized nutrition by enabling us to tailor dietary recommendations to an individual’s genotype. This level of personalization is expected to hold great benefit by better aligning dietary recommendations with an individual’s requirements and potentially motivating favorable dietary changes that impact chronic disease risk. In this review, we discuss key findings in the field of nutritional genomics, issues surrounding genetic testing for personalized nutrition, and the role health care providers will play in delivering the science to individuals.

BACKGROUND Trans fatty acids (TFAs) produced from industrial partial hydrogenation of vegetable oils have been the subject of much research regarding their negative effect on the development of chronic diseases, and recommendations to label foods with partially hydrogenated vegetable oils and limit their levels were introduced in Canada in 2003 and 2007, respectively. Our aim was to determine temporal changes in circulating plasma TFAs in a population of young healthy Canadian adults after the introduction of the guidelines. METHODS In this study, circulating plasma concentrations and relative percent composition of individual TFAs over time (2004-2010) were determined in a cross-sectional cohort of young healthy Canadian adults as part of the Toronto Nutrigenomics study. RESULTS A total of 1294 participants were included in the cohort. Relative to 2004, total TFA levels were significantly lower in 2005-2009 (p < 0.05), but not in 2010. Although levels of 16:1t9 and 18:1t11 declined after 2004, levels of 18:1t9 and 18:1t10 were significantly lower in 2005-2009 (p < 0.05), but not in 2010. INTERPRETATION Trans fatty acids were lower in 2009 relative to 2004, but not different in 2010, suggesting that young Canadians may remain vulnerable to partially hydrogenated vegetable oil exposure and that there is a need for further monitoring of specific food categories and vulnerable populations.

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.

Evidence for a relationship between omega-6/omega-3 (n-6/n-3) polyunsaturated fatty acid (PUFA) ratio and obesity in humans is inconsistent, perhaps due to differences in dietary intake or metabolism of PUFAs between different subsets of the population. Since chronic inflammation is central to obesity and inflammatory pathways are regulated by PUFAs, the objective of this study was to examine whether variants in the NFKB1 gene, an upstream regulator of the inflammatory response, modify the association between the n-6/n-3 ratio (from diet and plasma) and anthropometric traits in a multiethnic/multiracial population of young adults. Participants&rsquo, (n = 898) dietary PUFA intake was assessed using a food frequency questionnaire and plasma PUFA concentrations by gas chromatography. Nine tag single nucleotide polymorphisms (SNP) in NFKB1 were genotyped. Significant interactions were found between racial/ethnic groups and plasma n-6/n-3 ratio for body mass index (BMI) (p = 0.02) and waist circumference (WC) (p = 0.007). Significant interactions were also observed between racial/ethnic groups and three NFKB1 genotypes (rs11722146, rs1609798, and rs230511) for BMI and WC (all p &le, 0.04). Significant interactions were found between two NFKB1 genotypes and plasma n-6/n-3 ratio for BMI and WC (rs4648090 p = 0.02 and 0.03, rs4648022 p = 0.06 and 0.04, respectively). Our findings suggest that anthropometric traits may be influenced by a unique combination of n-6/n-3 ratio, racial/ethnic background, and NFKB1 genotypes.

Evidence for a relationship between omega-6/omega-3 (n-6/n-3) polyunsaturated fatty acid (PUFA) ratio and obesity in humans is inconsistent, perhaps due to differences in dietary intake or metabolism of PUFAs between different subsets of the population. Since chronic inflammation is central to obesity and inflammatory pathways are regulated by PUFAs, the objective of this study was to examine whether variants in the NFKB1 gene, an upstream regulator of the inflammatory response, modify the association between the n-6/n-3 ratio (from diet and plasma) and anthropometric traits in a multiethnic/multiracial population of young adults. Participants’ (n = 898) dietary PUFA intake was assessed using a food frequency questionnaire and plasma PUFA concentrations by gas chromatography. Nine tag single nucleotide polymorphisms (SNP) in NFKB1 were genotyped. Significant interactions were found between racial/ethnic groups and plasma n-6/n-3 ratio for body mass index (BMI) (p = 0.02) and waist circumference (WC) (p = 0.007). Significant interactions were also observed between racial/ethnic groups and three NFKB1 genotypes (rs11722146, rs1609798, and rs230511) for BMI and WC (all p ≤ 0.04). Significant interactions were found between two NFKB1 genotypes and plasma n-6/n-3 ratio for BMI and WC (rs4648090 p = 0.02 and 0.03; rs4648022 p = 0.06 and 0.04, respectively). Our findings suggest that anthropometric traits may be influenced by a unique combination of n-6/n-3 ratio, racial/ethnic background, and NFKB1 genotypes.

Personalized sport supplementation in athletic populations aims to optimize health, body composition, and exercise performance by targeting ergogenic aid recommendations, both nutritional and pharmacological, to an individual's genetic profile. Nutrigenomics and nutrigenetics are experimental approaches that use genomic information and genetic testing technologies to examine the role of individual genetic differences in modifying an athlete's response to nutrients and ergogenic aids. To date, there have been few randomized, controlled trials examining the effects of genetic variation on performance in response to ergogenic aids. However, there is a growing body of evidence linking caffeine-gene interactions, and variability in response to caffeine, which in turn impact exercise and sport performance. This foundation, in the caffeine-exercise body of literature, forms the basis from which the field of nutrigenomics and ergogenic aids continues to develop. Here we review the current science that associates genetic modifiers to ergogenic aids, and the impacts to athletic performance. In addition, we identify several plausible pathways where genetic polymorphisms may play a role in variability in response to ergogenic aids and the potential for personalized sport supplement research and development.

BACKGROUND: Coffee consumption has been linked to lower risk of various health outcomes. However, the biological pathways mediating the associations remain poorly understood. OBJECTIVES: The aim of this study was to assess the association between coffee consumption and concentrations of plasma biomarkers in key metabolic and inflammatory pathways underlying common chronic diseases. METHODS: We investigated the associations of total, caffeinated, and decaffeinated coffee consumption with 14 plasma biomarkers, including C-peptide, insulin-like growth factor 1 (IGF-1), IGF binding protein (IGFBP) 1, IGFBP-3, estrone, total and free estradiol, total and free testosterone, sex hormone–binding globulin (SHBG), total adiponectin, high-molecular-weight (HMW) adiponectin, leptin, C-reactive protein (CRP), interleukin 6 (IL-6), and soluble tumor necrosis factor receptor 2 (sTNFR-2). Data were derived from 2 cohorts of 15,551 women (Nurses’ Health Study) and 7397 men (Health Professionals Follow-Up Study), who provided detailed dietary data before blood draw and were free of diabetes, cardiovascular disease, or cancer at the time of blood draw. Multivariable linear regression was used to calculate the percentage difference of biomarker concentrations comparing coffee drinkers with nondrinkers, after adjusting for a variety of demographic, clinical, and lifestyle factors. RESULTS: Compared with nondrinkers, participants who drank ≥4 cups of total coffee/d had lower concentrations of C-peptide (−8.7%), IGFBP-3 (−2.2%), estrone (−6.4%), total estradiol (−5.7%), free estradiol (−8.1%), leptin (−6.4%), CRP (−16.6%), IL-6 (−8.1%), and sTNFR-2 (−5.8%) and higher concentrations of SHBG (5.0%), total testosterone (7.3% in women and 5.3% in men), total adiponectin (9.3%), and HMW adiponectin (17.2%). The results were largely similar for caffeinated and decaffeinated coffee. CONCLUSION: Our data indicate that coffee consumption is associated with favorable profiles of numerous biomarkers in key metabolic and inflammatory pathways. This trial was registered at clinicaltrials.gov as NCT03419455.