Reproducibility and validity of the Toronto-modified Harvard food frequency questionnaire in a multi-ethnic sample of young adults.

BACKGROUND/OBJECTIVES: To assess the reproducibility and validity of a Toronto-modified Harvard food frequency questionnaire (FFQ) among a multi-ethnic sample of young adults. SUBJECTS/METHODS: A total of 150 participants recruited from the Toronto Nutrigenomics and Health Study cohort who had existing dietary intakes assessed by FFQ (FFQ1) and reassessment one year later (FFQ2). Of these, 100 participants also completed a three-day food record to evaluate the validity of the FFQ for 38 nutrients (energy, 14 macronutrients, 22 micronutrients, and 1 bioactive). Analyses were also stratified between the two major ethnic groups (Caucasian and East Asian). RESULTS: Among the full sample, mean intakes of most nutrients (27/38) did not differ significantly between estimates derived from FFQ2 compared to the three-day food record. Energy, sex, and ethnicity adjusted deattenuated Pearson correlation coefficients ranged from 0.20 to 0.92 (mean r = 0.52 ± 0.15), and 34/38 validity coefficients were r ≥ 0.32. Gross misclassification of intakes between FFQ2 and the three-day food record was low (<6%), but energy, polyunsaturated fatty acids (PUFA), and sodium were underestimated by FFQ2. Mean intakes between FFQ1 and FFQ2 did not differ significantly for any nutrient. Between the two major ethnic groups, mean validity coefficients were similar, but varied for individual nutrients with saturated fat, PUFA, and omega 3 being among the most discrepant. CONCLUSIONS: Compared to a three-day food record, the Toronto-modified Harvard FFQ is a reproducible and valid tool to estimate dietary intake among a multi-ethnic sample of young adults. However, incorporation of protocols to improve the assessment of culturally diverse diets should be considered.

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.

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.

Association between the plasma proteome and plasma α-tocopherol concentrations in humans.

Vitamin E is a lipophilic antioxidant that has been inversely associated with certain chronic diseases; however, the biological processes regulated by this vitamin have not been fully elucidated. The objective of the present study was to examine the association between the most biologically active and abundant form of vitamin E in the circulation, α-tocopherol, and the plasma proteome. Subjects were from the Toronto Nutrigenomics and Health Study and included men and women (n=1,022) who completed a general health and lifestyle questionnaire and 196-item food frequency questionnaire, and provided a fasting blood sample. Plasma α-tocopherol concentrations were measured by high-performance liquid chromatography and 54 plasma proteins were assayed by a mass spectrometry-based multiple reaction monitoring method. Analysis of covariance was used to compare mean concentrations of plasma proteins across tertiles of α-tocopherol. Plasma concentrations of apolipoprotein C-III, fibrinogen alpha, beta, and gamma chains, fibronectin and fibrinopeptide A were significantly and positively associated with plasma α-tocopherol, while intermediate levels of α-tocopherol were significantly associated with higher levels of alpha-1B-glycoprotein (all P<.0009). These findings show that circulating levels of α-tocopherol are significantly associated with specific plasma proteins and suggest novel physiological effects of vitamin E.

The association between obesity, cardiometabolic disease biomarkers, and innate immunity-related inflammation in Canadian adults.

INTRODUCTION: Obesity is associated with a state of chronic inflammation, and increased cardiometabolic disease risk. The present study examined the relationship between body mass index (BMI) and cardiometabolic and inflammatory biomarkers among normal weight, overweight, and obese Canadian adults. METHODS: Subjects (n = 1805, aged 18 to 79 years) from the Canadian Health Measures Survey (CHMS) were examined for associations between BMI, cardiometabolic markers (apolipoprotein [Apo] A1, ApoB, low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], total cholesterol, total cholesterol/HDL ratio [total:HDL-C ratio], triglycerides, and glycosylated hemoglobin [HbA(1c)]), inflammatory factors (C-reactive protein [CRP], fibrinogen, and homocysteine), and 25-hydroxyvitamin D [25(OH)D]. Bootstrap weights for variance and sampling weights for point estimates were applied to account for the complex survey design. Linear regression models adjusted for age, sex, physical activity, smoking status, and ethnicity (in addition to season of clinic visit, for vitamin D analyses only) were used to examine the association between cardiometabolic markers, inflammatory factors, and BMI in Canadian adults. RESULTS: All biomarkers were significantly associated with BMI (P ≤ 0.001). ApoA1 (ß = -0.31, P < 0.0001), HDL-C (ß = -0.61, P < 0.0001), and 25(OH)D (ß = -0.25, P < 0.0001) were inversely associated with BMI, while all other biomarkers showed positive linear associations. Distinct patterns of association were noted among normal weight, overweight, and obese groups, excluding CRP which showed a significant positive association with BMI in the overall population (ß = 2.80, P < 0.0001) and in the normal weight (ß = 3.20, P = 0.02), overweight (ß = 3.53, P = 0.002), and obese (ß = 2.22, P = 0.0002) groups. CONCLUSIONS: There is an apparent profile of cardiometabolic and inflammatory biomarkers that emerges as BMI increases from normal weight to obesity. Understanding these profiles may permit developing an effective approach for early risk prediction for cardiometabolic disease.

Glutathione S-transferase (GST) M1, but not GSTT1, genotype influences plasma proteomic profiles in Caucasian and East Asian young adults.

Glutathione S-transferase (GST) M1 and T1 are major detoxifying enzymes that have been associated with a number of chronic diseases, but their effect on various physiological pathways remains unclear. We investigated the association between the common GSTM1 and GSTT1 genotypes and multiple disease-related high-abundance proteins of the plasma proteome in young Caucasian (n = 476) and East Asian (n = 352) adults. Overnight fasting blood samples were collected, and 54 high-abundance plasma proteins from several physiological pathways were quantified by mass spectrometry-based multiple reaction monitoring (LC-MRM/MS). Subjects were genotyped for GSTM1 and GSTT1 deletion polymorphisms. Principal component analysis was used to identify proteomic profiles, and differences in individual protein concentrations between genotypes were assessed by ANCOVA. Among Caucasians, 19 proteins differed between GSTM1 genotypes (P < 0.05), with all protein concentrations being higher among the null genotypes. However, only complement C3 reached the Bonferroni-corrected significance threshold for multiple testing (P < 0.0009). Among East Asians, three proteins differed between GSTM1 genotypes (P < 0.05) with higher concentrations among the null genotypes, but none reached the Bonferroni level of significance. Protein concentrations did not differ between GSTT1 genotypes in either ethnicity. These findings suggest that GSTM1 may have novel physiological effects related to immunity and cardiometabolic disease.

Associations between polymorphisms in the AHR and CYP1A1-CYP1A2 gene regions and habitual caffeine consumption.

BACKGROUND: Recent genome-wide association studies (GWASs) from populations of European descent identified single nucleotide polymorphisms (SNPs) in aryl-hydrocarbon receptor (AHR) and cytochrome P450 1A1 and 1A2 (CYP1A1-CYP1A2) genes that are associated with habitual caffeine and coffee consumption. OBJECTIVE: We examined whether these SNPs (AHR: rs6968865 and rs4410790; CYP1A1-CYP1A2: rs2472297 and rs2470893) and 6 additional tag SNPs in the AHR gene were associated with habitual caffeine consumption in a Costa Rican population. DESIGN: Subjects were from a case-control study of gene-diet interactions and myocardial infarction. Subjects with hypertension or missing information on smoking, caffeine intake, or genotype were excluded. Subjects were genotyped by using polymerase chain reaction with mass spectrometry-based detection, and caffeine intake was assessed by using a validated food-frequency questionnaire. RESULTS: Compared with subjects who consumed <100 mg caffeine/d, subjects who consumed >400 mg caffeine/d were more likely to be carriers of the T, C, or T allele for rs6968865, rs4410790, and rs2472297, respectively. The corresponding ORs and 95% CIs were 1.41 (1.03, 1.93), 1.41 (1.04, 1.92), and 1.55 (1.01, 2.36). Multivariate-adjusted ORs (95% CIs) for rs6968865 were 1.44 (1.03, 2.00) for all subjects, 1.75 (1.16, 2.65) for nonsmokers, 1.15 (0.58, 2.30) for current smokers, 2.42 (1.45, 4.04) for subjects >57 y old, and 1.00 (0.65, 1.56) for subjects ≤57 y old. A similar effect modification was observed for rs4410790 but not for rs2472297. CONCLUSION: Our findings show that previous associations between SNPs in AHR and CYP1A1-CYP1A2 and caffeine and coffee consumption from GWASs in European populations are also observed in an ethnically distinct Costa Rican population, but age and smoking are important effect modifiers.

Genetic determinants of dietary antioxidant status.

Oxidative stress refers to a physiological state in which an imbalance between pro-oxidants and antioxidants results in oxidative damage. Oxidative stress has been associated with the development of numerous chronic diseases such as type 2 diabetes, cardiovascular disease (CVD), osteoporosis, and cancer. Endogenous production of free radicals occurs during normal physiological processes, such as aerobic metabolism, oxidation of biological molecules, and enzymatic activity. Environmental factors such as ultraviolet radiation, air pollution, and cigarette smoking can also contribute to the accumulation of free radicals in the body. Excess free radicals can damage tissues and promote the upregulation of disease-related pathways such as inflammation. Modulating oxidative stress by dietary supplementation with antioxidant micronutrients such as vitamins C and E or phytochemicals such as different carotenoids may help prevent or delay the development of certain diseases. However, research on antioxidant supplementation and disease has yielded inconsistent findings, which may be due, in part, to interindividual genetic variation. Polymorphisms in genes coding for endogenous antioxidant enzymes or proteins responsible for the absorption, transport, distribution, or metabolism of dietary antioxidants have been shown to affect antioxidant status and response to supplementation. These genetic variants may also interact with environmental factors, such as diet, to determine an individual's overall antioxidant status. This chapter examines current knowledge of the relationship between genetic variation and dietary antioxidant status.

Nutrigenetics and modulation of oxidative stress.

Oxidative stress develops as a result of an imbalance between the production and accumulation of reactive species and the body's ability to manage them using exogenous and endogenous antioxidants. Exogenous antioxidants obtained from the diet, including vitamin C, vitamin E, and carotenoids, have important roles in preventing and reducing oxidative stress. Individual genetic variation affecting proteins involved in the uptake, utilization and metabolism of these antioxidants may alter their serum levels, exposure to target cells and subsequent contribution to the extent of oxidative stress. Endogenous antioxidants include the antioxidant enzymes superoxide dismutase, catalase, glutathione peroxidase, paraoxanase, and glutathione S-transferase. These enzymes metabolize reactive species and their by-products, reducing oxidative stress. Variation in the genes coding these enzymes may impact their enzymatic antioxidant activity and, thus, the levels of reactive species, oxidative stress, and risk of disease development. Oxidative stress may contribute to the development of chronic disease, including osteoporosis, type 2 diabetes, neurodegenerative diseases, cardiovascular disease, and cancer. Indeed, polymorphisms in most of the genes that code for antioxidant enzymes have been associated with several types of cancer, although inconsistent findings between studies have been reported. These inconsistencies may, in part, be explained by interactions with the environment, such as modification by diet. In this review, we highlight some of the recent studies in the field of nutrigenetics, which have examined interactions between diet, genetic variation in antioxidant enzymes, and oxidative stress.

Fifty years of memory of college grades: accuracy and distortions.

One to 54 years after graduating, 276 alumni correctly recalled 3,025 of 3,967 college grades. Omission errors increased with the retention interval, and better students made fewer errors. Accuracy of recall increased with confidence in recall. Eighty-one percent of commission errors inflated the actual grade. Distortions occur soon after graduation, remain constant during the retention interval, and are greater for better students and for courses students enjoyed most. Confidence in recall is unrelated to distortion. Courses that were not freely recalled, but had to be cued, were recalled less accurately and with less distortion. The data support a supplementary theory of memory distortion. The theory assumes that forgetting and distorting memory content are relatively independent processes, that relevant generic memories are used to fill in gaps after episodic memory fails, that systematic distortions affect autobiographical content that is emotionally and motivationally valenced, and that most individuals supplement with content that is emotionally more gratifying than the veridical content. The data conflict with dynamic displacement theories according to which screen memories actively block access to unpleasant veridical content.