Joseph Jamnik

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.

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 (β=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.

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.

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.

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, 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. 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.

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

We are retracting this Article as we no longer have confidence in the data to support our central conclusion – the detection of Brassica oleracea microRNAs in the bloodstream of humans who consumed broccoli.

Genetic variation related to caffeine metabolism or response during exercise

Methods We examined whether a panel of 25 SNPs in 19 genes that might be related to caffeine metabolism or response modified exercise performance, or were associated with any physiologic outcomes during exercise. Subjects were trained male cyclists (n = 33) who underwent a doubleblind placebo-controlled crossover trial to test the effects of caffeine (6 mg/kg) on various performance parameters during a computer-simulated 40 km time trial. The 25 SNPs were genotyped using the Sequenom MassARRAY system, and caffeine-genotype interactions on time trial time, VO2 max, heart rate, respiratory exchange ratio and rate of perceived exertion were assessed using repeated measures analysis of variance.