Ascorbic acid is associated with favourable hormonal profiles among infertile males.

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.

Ready-to-eat cereal consumption is associated with improved nutrient intakes and diet quality in Canadian adults and children across income levels.

Background: Results from observational studies suggest ready-to-eat cereal (RTEC) consumption is associated with higher diet quality. In the United States, studies have shown that RTEC is an important contributor to nutrient intakes across income levels. However, it is unknown if this association varies by income level in the Canadian population. Given its affordability, RTEC may represent an important source of nutrients for lower-income individuals. Objective: This study evaluated the association of RTEC consumption with nutrient intakes and diet quality across household income levels in Canadian adults and children. Methods: Income and dietary data from 24 h dietary recalls were obtained from the 2015 Canadian Community Health Survey (CCHS)-Nutrition in 6,181 children (2-18 years) and 13,908 adults (19+ years). Diet quality was assessed with a modified Nutrient Rich Food Index (NRF) 9.3. Income levels were stratified into low, middle, and high based on family size, and data were analyzed by RTEC consumption and income level using multivariate linear regression adjusted for energy, age, and sex. Results: Diet quality was greater in adult and child RTEC consumers across all household income levels. Children and adults consuming RTEC also had higher nutrient intakes, including shortfall nutrients such as calcium, dietary fiber, iron, magnesium, and vitamin D. RTEC provided <10% of energy intake, <4% of saturated fat intake, and <9% of total sugar intake across all ages and income levels, while also providing one-third of daily iron intake and at least 10% of daily intake of dietary fiber, thiamin, folate, and vitamin B6. Conclusion: RTEC consumption was associated with improved nutrient intakes and diet quality in adults and children across household income levels. Nutrient dense and affordable food choices, such as RTEC, may be a helpful strategy to improve the diet quality of Canadians, particularly those with a lower household income.

Plasma Carotenoids and Premenstrual Symptoms in a Multi-Ethnic Population of Young Women.

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.

Variation in the vitamin D receptor gene, plasma 25-hydroxyvitamin D, and risk of premenstrual symptoms.

BACKGROUND: Vitamin 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). OBJECTIVE: To determine whether associations between vitamin D status and individual PMSx are influenced by VDR genotype. METHODS: Seven 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 common VDR single nucleotide variant, rs796858. Using logistic regression, odds of experiencing PMSx were compared between vitamin D-sufficient and insufficient women, stratified by genotype. RESULTS: Among 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). VDR genotype modified the association between vitamin D status and the following PMSx: increased appetite (interaction p = 0.027), fatigue (interaction p = 0.016), and nausea (interaction p = 0.039). CONCLUSION: We found evidence that VDR genotype 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.

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.

Nutrition, genetic variation and male fertility.

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, B12, 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.

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.

HFE Genotype and Endurance Performance in Competitive Male Athletes.

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.

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.

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.

ABO genotype, 'blood-type' diet and cardiometabolic risk factors.

BACKGROUND: The 'Blood-Type' diet advises individuals to eat according to their ABO blood group to improve their health and decrease risk of chronic diseases such as cardiovascular disease. However, the association between blood type-based dietary patterns and health outcomes has not been examined. The objective of this study was to determine the association between 'blood-type' diets and biomarkers of cardiometabolic health and whether an individual's ABO genotype modifies any associations. METHODS: Subjects (n = 1,455) were participants of the Toronto Nutrigenomics and Health study. Dietary intake was assessed using a one-month, 196-item food frequency questionnaire and a diet score was calculated to determine relative adherence to each of the four 'Blood-Type' diets. ABO blood group was determined by genotyping rs8176719 and rs8176746 in the ABO gene. ANCOVA, with age, sex, ethnicity, and energy intake as covariates, was used to compare cardiometabolic biomarkers across tertiles of each 'Blood-Type' diet score. RESULTS: Adherence to the Type-A diet was associated with lower BMI, waist circumference, blood pressure, serum cholesterol, triglycerides, insulin, HOMA-IR and HOMA-Beta (P<0.05). Adherence to the Type-AB diet was also associated with lower levels of these biomarkers (P<0.05), except for BMI and waist circumference. Adherence to the Type-O diet was associated with lower triglycerides (P<0.0001). Matching the 'Blood-Type' diets with the corresponding blood group did not change the effect size of any of these associations. No significant association was found for the Type-B diet. CONCLUSIONS: Adherence to certain 'Blood-Type' diets is associated with favorable effects on some cardiometabolic risk factors, but these associations were independent of an individual's ABO genotype, so the findings do not support the 'Blood-Type' diet hypothesis.

Plasma 25-hydroxyvitamin D, hormonal contraceptive use, and cardiometabolic disease risk in an ethnically diverse population of young adults.

OBJECTIVES: The relationship between vitamin D and cardiometabolic disease risk across ethnic groups is unclear, and it is not known whether the use of hormonal contraceptives (HCs), which affect vitamin D metabolism and are also associated with cardiometabolic disease risk, modifies this relationship. Our objectives were to determine the prevalence of vitamin D deficiency (plasma 25-hydroxyvitamin D [25(OH)D] < 30 nmol/L) to assess seasonal variation in concentrations of 25(OH)D, and to examine whether 25(OH)D is associated with cardiometabolic biomarkers across ethnic groups and across men, female HC nonusers, and female HC users in an ethnically diverse population of young adults living in Canada. METHODS: The study population consisted of Caucasian, East Asian, and South Asian individuals (n = 1384, 69% female) aged 20-29 years. Participants provided overnight fasting blood samples, from which plasma 25(OH)D and cardiometabolic biomarkers were measured. Vitamin D status distributions were compared using χ(2) tests, and analysis of covariance (ANCOVA) was used to examine seasonal variations in 25(OH)D, as well as the association between 25(OH)D and cardiometabolic biomarkers, across groups. RESULTS: Plasma 25(OH)D concentrations fluctuated seasonally among Caucasians and East Asians and across men, female HC nonusers, and female HC users, but they remained low year-round in South Asians, half of whom were vitamin D deficient. Vitamin D deficiency was associated with higher insulin, homeostasis model assessment-estimated insulin resistance (HOMA-IR), and homeostasis model assessment (HOMA)-beta among Caucasians and East Asians and among men and female HC nonusers and with higher triglycerides among men only. No biomarkers were associated with 25(OH)D among South Asians and female HC users, although nonsignificant trends were observed for higher markers of glycemic dysregulation in those who were vitamin D deficient in both groups. CONCLUSIONS: Vitamin D deficiency varies between ethnic groups and is particularly high among South Asians, and it is associated with biomarkers of glycemic dysregulation; however, HC use among women may attenuate this association. Given the widespread use of HCs by women throughout the world, a better understanding of the extent to which these medications may modify the relationship between vitamin D and processes related to disease is warranted.

Genetic variation in the vitamin D receptor, plasma 25-hydroxyvitamin D, and biomarkers of cardiometabolic disease in Caucasian young adults.

BACKGROUND/AIMS: Vitamin D regulates gene transcription by binding to the vitamin D receptor (VDR), potentially affecting cardiometabolic disease risk. However, studies of 25-hydroxyvitamin D [25(OH)D] and cardiometabolic disease are inconsistent. Inconsistencies may result from unaccounted for interactions between VDR genetic variants and 25(OH)D. We examined the effect of 25(OH)D on the association between VDR variants and cardiometabolic disease biomarkers. METHODS: The relationship between 25(OH)D, 24 VDR variants, and 10 cardiometabolic biomarkers was examined in 488 Caucasians aged 20-29 years. Covariate-adjusted general linear models were used to examine the interaction effect of 25(OH)D × VDR on each biomarker. When interactions were significant (p < 0.05), relationships were further examined with analysis of covariance, stratified by tertiles of 25(OH)D and adjusted for multiple comparisons. RESULTS: In the lowest tertile of 25(OH)D, major allele homozygotes for rs3819545 had higher insulin and HOMA-IR than minor allele carriers (p ≤ 0.002). Fasting insulin and HOMA-IR were lower in the highest than the lowest tertile of 25(OH)D among major allele homozygotes (p < 0.0001), but minor allele carriers had similar levels regardless of vitamin D status. CONCLUSIONS: We identified 25(OH)D-dependent associations between rs3819545 and glycemic dysregulation biomarkers. Major allele homozygotes with low vitamin D status may be at increased risk of insulin resistance.

Plasma vitamin D and biomarkers of cardiometabolic disease risk in adult Canadians, 2007-2009.

INTRODUCTION: Vitamin D may modulate cardiometabolic disease risk, although the relationship has not been investigated in the general Canadian population. Understanding this relationship may inform public health strategies to curb the incidence of cardiometabolic disease in Canada and elsewhere. The objectives of this study were to examine the association between vitamin D and traditional and novel biomarkers of cardiometabolic disease and to describe the extent of the month-to-month fluctuations of vitamin D in the Canadian population. METHODS: We examined the association between plasma 25-hydroxyvitamin D and a range of cardiometabolic risk biomarkers in participants (n = 1,928; age range, 16-79 years) from the Canadian Health Measures Survey. We conducted linear regressions analyses (adjusted for sex, waist circumference, physical activity, hormone use, and season) to assess the relationship between 25-hydroxyvitamin D and biomarkers of dysglycemia, dyslipidemia, and inflammation in the study population. We repeated analyses stratified by sex, and we evaluated monthly fluctuations in 25-hydroxyvitamin D in men and women. RESULTS: We observed wide month-to-month variations in 25-hydroxyvitamin D; fluctuations were more pronounced in men. Plasma 25-hydroxyvitamin D was inversely associated with insulin, insulin resistance, triglycerides, total cholesterol, low-density lipoprotein cholesterol, and the ratio of total to high-density lipoprotein cholesterol but not with fasting glucose, apolipoprotein A1, apolipoprotein B, C-reactive protein, fibrinogen, or homocysteine. This pattern varied between men and women. CONCLUSION: Vitamin D may modulate various metabolic processes and may influence cardiometabolic disease risk in Canadians. These findings may have public health implications when recommending vitamin D for the prevention of cardiometabolic disease and related conditions.

Positive association between 25-hydroxyvitamin D and C-reactive protein is confounded by hormonal contraceptive use.

BACKGROUND: Studies of the relationship between vitamin D and inflammation are equivocal. This may be due to unaccounted confounding. Hormonal contraceptive (HC) use is associated with elevated circulating 25-hydroxyvitamin D [25(OH)D] in Caucasians and African-Americans, but its effects on 25(OH)D in other ethnicities are unclear. HC use is associated with elevated C-reactive protein (CRP), an inflammatory biomarker. Our objectives were to assess the effect of HC use on 25(OH)D across ethnic groups, and to examine the association between HC, 25(OH)D and CRP in an ethnically diverse population of young adults. METHODS: We recruited Caucasian, East Asian, and South Asian individuals (n=1,403) from Toronto, Canada. Fasting blood measures of 25(OH)D and CRP were obtained. RESULTS: Across ethnic groups, women HC users (n=280) had higher 25(OH)D and CRP than women HC non-users (n=695) and men (n=428) (p<0.008 and p<0.0001, respectively). Circulating 25(OH)D was positively associated with CRP in the entire population in models not accounting for HC use (ß=0.010±0.003; p<0.0001). There was no association when men and women HC non-users were examined separately. Among women HC users, there was no association after accounting for hormone dose. A positive association between 25(OH)D and CRP among individuals above the median 25(OH)D (≥51.9 nmol/L) was not significant after adjustment for HC use. No association was observed among individuals below the median. CONCLUSIONS: HC use and 25(OH)D were positively associated across ethnic groups. We found no association between 25(OH)D and CRP when HC use was accounted for. HC use confounds the association between 25(OH)D and CRP.

Plasma 25-hydroxyvitamin D, hormonal contraceptive use, and the plasma proteome in Caucasian, East Asian, and South Asian young adults.

Vitamin D affects gene expression, but its downstream effects on the proteome are unclear. Hormonal contraceptives (HC), which affect vitamin D metabolism and have widespread effects on the plasma proteome, may confound the association between vitamin D and the proteome. We determined whether HC use modified the association between 25-hydroxyvitamin D (25D) and a panel of 54 high-abundance plasma proteins. Cross-sectional analyses were conducted in healthy, nonsmoking female HC users (n = 216), female HC nonusers (n = 502), and men (n = 301) from Toronto, Canada. Plasma 25D was measured by HPLC-MS/MS, and proteins were measured by LC-multiple-reaction-monitoring (MRM)-MS. The 54 proteins clustered into four distinct proteomic profiles. A positive association was observed between Profile 1, containing positive acute phase proteins, and 25D. In female HC users, a J-shaped association existed between Profile 1 and 25D, but no associations existed in female HC nonusers and men. Twelve proteins were individually associated with 25D in female HC users, but only two were associated with 25D in female HC nonusers and no associations were observed in men. After accounting for hormone dose, only three proteins were associated with 25D. In summary, HC use is an important confounder of the association between circulating 25D and numerous plasma proteins.

Association between the plasma proteome and serum ascorbic acid concentrations in humans.

Vitamin C has been associated with a reduced risk of chronic diseases, but the biological pathways regulated by vitamin C are not all known. The objective was to use a proteomics approach to identify plasma proteins associated with circulating levels of ascorbic acid. Men and women (n=1022) 20-29 years of age from the Toronto Nutrigenomics and Health Study completed a general health and lifestyle questionnaire and a 196-item food frequency questionnaire and provided a fasting blood sample. Circulating ascorbic acid was analyzed by high-performance liquid chromatography, and a mass-spectrometry-based multiple reaction monitoring method was used to measure 54 proteins abundant in plasma that are involved in numerous physiologic pathways. Mean protein concentrations were compared across tertiles of serum ascorbic acid using analysis of covariance adjusted for sex, ethnocultural group, season of blood draw, hormonal contraceptive use among women, waist circumference and tertiles of plasma α-tocopherol. A Bonferroni significance level of P<.0009 was applied, and analyses were adjusted for multiple comparisons using the Tukey-Kramer procedure. Levels of complement C9, ceruloplasmin, alpha-1-anti-trypsin, angiotensinogen, complement C3, vitamin D binding protein and plasminogen were inversely associated with levels of ascorbic acid. The inverse association between ascorbic acid and vitamin D binding protein was highest in those with higher levels of serum 25-hydroxyvitamin D. In conclusion, several plasma proteins from various physiologic pathways are significantly associated with circulating levels of ascorbic acid. These findings suggest that vitamin C may have novel physiological effects.