Mealtime media use and cardiometabolic risk in children.

OBJECTIVES: To examine the association between mealtime media use and non-HDL-cholesterol as well as other markers of cardiometabolic risk (CMR) in children. DESIGN: A repeated measures study design was used to examine the association between mealtime media use and CMR outcomes. Multivariable linear regression with generalised estimating equations was used to examine the association between mealtime media use and CMR outcomes. Analyses were stratified a priori by age groups (1-4 and 5-13 years). SETTING: The TARGet Kids! Practice-based research network in Toronto, Canada. PARTICIPANTS: 2117 children aged 1-13 years were included in the analysis. RESULTS: After adjusting for covariates, there was no evidence that total mealtime media use was associated with non-HDL-cholesterol in 1-4 year olds (P = 0·10) or 5-13 year olds (P = 0·29). Each additional meal with media per week was associated with decreased HDL-cholesterol in 5-13 year olds (-0·006 mmol/l; 95 % CI -0·009, -0·002; P = 0·003) and log-TAG in 1-4 year olds (ß = -0·004; 95 % CI -0·008, -0·00009; P = 0·04). Media use during breakfast was associated with decreased HDL-cholesterol in 5-13 year olds (-0·012 mmol/l; 95 % CI -0·02, -0·004; P = 0·002), while media during lunch was associated with decreased log-TAG (-0·01 mmol/l; 95 % CI -0·03, -0·002; P = 0·03) in children aged 1-4 years. Total mealtime media use was not associated with total cholesterol, glucose or insulin in either age group. CONCLUSIONS: Mealtime media use may be associated with unfavourable lipid profiles through effects on HDL-cholesterol in school-aged children but likely not in pre-schoolers.

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.

FTO genotype, dietary protein intake, and body weight in a multiethnic population of young adults: a cross-sectional study.

BACKGROUND: Variation in the fat mass and obesity-associated gene (FTO) has been associated with susceptibility to obesity, but the association appears to be modified by diet. We investigated whether dietary protein intake modifies the association between FTO variant rs1558902 and body mass index (BMI) and waist circumference in young adults (n = 1491) from the cross-sectional Toronto Nutrigenomics and Health Study. RESULTS: Lifestyle, genetic, anthropometric, and biochemical data were collected and diet was assessed using a Toronto-modified Willett Food Frequency Questionnaire. General linear models stratified by ethnicity and adjusted for age, sex, and total energy intake were used to examine the association between FTO genotypes and measures of body weight, and whether protein intake modified any of the associations. East Asians who were homozygous for the rs1558902 risk allele (A) had a greater BMI (p = 0.004) and waist circumference (p = 0.03) than T allele carriers. This association was not observed in individuals of Caucasian or South Asian ancestry. Among East Asians, a significant FTO-protein interaction was observed for BMI (p = 0.01) and waist circumference (p = 0.007). Those with low protein intake (≤ 18% total energy intake) who were homozygous for the rs1558902 risk allele (A) had significantly higher BMI (p <  0.0001) and waist circumference (p = 0.0006) compared to carriers of the T allele. These associations were absent in the high protein intake group (> 18% total energy intake). Compared to Caucasians and South Asians, East Asians consumed a significantly higher ratio of animal-to-plant protein (p <  0.05). CONCLUSIONS: These findings suggest that high dietary protein intake may protect against the effects of risk variants in the FTO gene on BMI and waist circumference.

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

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

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

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

Retraction: Circulating plant miRNAs can regulate human gene expression in vitro.

This corrects the article DOI: 10.1038/srep32773.

Prevalence of positive coeliac disease serology and HLA risk genotypes in a multiethnic population of adults in Canada: a cross-sectional study.

OBJECTIVES: Coeliac disease (CD) is a complex autoimmune disorder with known genetic risk factors. Approximately 1% of individuals of European ancestry have CD, but the prevalence among different ethnicities living in Canada remains unknown. The objective of the present study was to determine the prevalence of positive CD serology in a population of Canadian adults living in Toronto, and to determine whether the prevalence of CD seropositivity and predisposing human leucocyte antigen (HLA)-DQ2/DQ8 risk genotypes differ between major ethnocultural groups. DESIGN: Cross-sectional screening study of participants from the Toronto Nutrigenomics and Health and the Toronto Healthy Diet studies. SETTING: University campus and households across Toronto, Canada. PARTICIPANTS FREE-LIVING: Adults (n=2832) of diverse ethnocultural backgrounds. MAIN OUTCOME MEASURES: Prevalence of positive CD serology was determined by screening for antitissue transglutaminase antibodies in individuals with predisposing HLA-DQ2/DQ8 genotypes. HLA genotypes were determined using six single nucleotide polymorphisms in the HLA gene region. RESULTS: Of the 2832 individuals screened, a total of 25 (0.88%; 95% CI 0.57% to 1.30%) were determined to have positive CD serology. The majority of seropositive CD cases were undiagnosed (87%). Prevalence was highest among Caucasians (1.48%; 95% CI 0.93% to 2.23%), and similar in those of 'Other' (0.74%; 95% CI 0.09% to 2.63%) or 'Unknown' (0.43; 95% CI 0.01% to 2.36%) ethnicity. No cases of positive CD serology were identified among East Asian or South Asian individuals. East Asians had a lower prevalence of HLA risk genotypes than Caucasians and South Asians (p<0.005). CONCLUSIONS: The prevalence of positive CD serology among Canadian adults living in Toronto is likely ~1%, with 87% of cases being undiagnosed. These findings suggest the need for better screening in high genetic risk groups. TRIAL REGISTRATION NUMBER: NCT00516620; Post-results.

Fructose intake and risk of gout and hyperuricemia: a systematic review and meta-analysis of prospective cohort studies.

BACKGROUND: The prevalence of hyperuricemia and gout has increased in recent decades. The role of dietary fructose in the development of these conditions remains unclear. OBJECTIVE: To conduct a systematic review and meta-analysis of prospective cohort studies investigating the association fructose consumption with incident gout and hyperuricemia. DESIGN: MEDLINE, EMBASE and the Cochrane Library were searched (through September 2015). We included prospective cohort studies that assessed fructose consumption and incident gout or hyperuricemia. 2 independent reviewers extracted relevant data and assessed study quality using the Newcastle-Ottawa Scale. We pooled natural-log transformed risk ratios (RRs) using the generic inverse variance method. Interstudy heterogeneity was assessed (Cochran Q statistic) and quantified (I2 statistic). The overall quality of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: 2 studies involving 125 299 participants and 1533 cases of incident gout assessed the association between fructose consumption and incident gout over an average of 17 years of follow-up. No eligible studies assessed incident hyperuricemia as an outcome. Fructose consumption was associated with an increase in the risk of gout (RR=1.62, 95% CI 1.28 to 2.03, p<0.0001) with no evidence of interstudy heterogeneity (I2=0%, p=0.33) when comparing the highest (>11.8% to >11.9% total energy) and lowest (<6.9% to <7.5% total energy) quantiles of consumption. LIMITATIONS: Despite a dose-response gradient, the overall quality of evidence as assessed by GRADE was low, due to indirectness. There were only two prospective cohort studies involving predominantly white health professionals that assessed incident gout, and none assessed hyperuricemia. CONCLUSIONS: Fructose consumption was associated with an increased risk of developing gout in predominantly white health professionals. More prospective studies are necessary to understand better the role of fructose and its food sources in the development of gout and hyperuricemia. PROTOCOL REGISTRATION NUMBER: NCT01608620.

Circulating plant miRNAs can regulate human gene expression in vitro.

While Brassica oleracea vegetables have been linked to cancer prevention, the exact mechanism remains unknown. Regulation of gene expression by cross-species microRNAs has been previously reported; however, its link to cancer suppression remains unexplored. In this study we address both issues. We confirm plant microRNAs in human blood in a large nutrigenomics study cohort and in a randomized dose-controlled trial, finding a significant positive correlation between the daily amount of broccoli consumed and the amount of microRNA in the blood. We also demonstrate that Brassica microRNAs regulate expression of human genes and proteins in vitro, and that microRNAs cooperate with other Brassica-specific compounds in a possible cancer-preventive mechanism. Combined, we provide strong evidence and a possible multimodal mechanism for broccoli in cancer prevention.

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.

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.

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.