Vitamin D deficiency in childhood obesity is associated with high levels of circulating inflammatory mediators, and low insulin sensitivity.

HYPOTHESIS: Childhood obesity is accompanied by low-grade systemic inflammation, which contributes to the development of insulin resistance and cardiovascular complications later in life. As vitamin D exhibits profound immunomodulatory functions and vitamin D deficiency is highly prevalent in childhood obesity, we hypothesized that vitamin D deficiency in childhood obesity coincides with enhanced systemic inflammation and reduced insulin sensitivity. METHODS: In a cross-sectional study of 64 obese and 32 healthy children aged 6-16 years, comprehensive profiling of 32 circulating inflammatory mediators was performed, together with assessment of 25-hydroxyvitamin D (25(OH)D) levels and measures for insulin sensitivity. RESULTS: Severe vitamin D insufficiency, which is further referred to as vitamin D deficiency, was defined as a 25(OH)D level ≤37.5 nmol l(-1), and was highly prevalent in obese (56%) versus healthy control children (16%). Throughout the study, 25(OH)D-deficient children were compared with the other children, including 25(OH)D insufficient (37.5-50 nmol l(-1)) and 25(OH)D sufficient children (≥50 nmol l(-1)). First, 25(OH)D-deficient obese children showed a lower insulin sensitivity than other obese children, as measured by a lower quantitative insulin sensitivity check index. Second, the association between 25(OH)D deficiency and insulin resistance in childhood obesity was confirmed with multiple regression analysis. Third, 25(OH)D-deficient obese children showed higher levels of the inflammatory mediators cathepsin S, chemerin and soluble vascular adhesion molecule (sVCAM), compared with the other obese children. Finally, hierarchical cluster analysis revealed an over-representation of 25(OH)D deficiency in obese children expressing inflammatory mediator clusters with high levels of cathepsin S, sVCAM and chemerin. CONCLUSION: 25(OH)D deficiency in childhood obesity was associated with enhanced systemic inflammation and reduced insulin sensitivity. The high cathepsin S and sVCAM levels may reflect activation of a pro-inflammatory, pro-diabetic and atherogenic pathway, which could be inhibited by vitamin D supplementation.

High maternal vitamin E intake by diet or supplements is associated with congenital heart defects in the offspring.

OBJECTIVE: To study associations between maternal dietary and supplement intake of antioxidants vitamin E, retinol and congenital heart defects (CHDs). DESIGN: Case-control study. SETTING: Erasmus MC, University Medical Center Rotterdam, the Netherlands. POPULATION: Participants were 276 case mothers of a child with CHD and 324 control mothers with their children. METHODS: Food frequency questionnaires covering the intake of the previous 4 weeks were filled out at 16 months after the index pregnancy. Data were compared between cases and controls using the Mann-Whitney U test. Risk estimates for the association between CHD and dietary intake of vitamin E and retinol were estimated in a multivariable logistic regression model. MAIN OUTCOME MEASURES: Medians (5-95th percentile) and odds ratios with 95% CI. RESULTS: Dietary vitamin E intake was higher in case mothers than in controls, 13.3 (8.1-20.4) and 12.6 (8.5-19.8) mg/day (P= 0.05). CHD risk increased with rising dietary vitamin E intakes (P-trend = 0.01). Periconception use of vitamin E supplements in addition to a high dietary vitamin E intake above 14.9 mg/day up to nine-fold increased CHD risk. Retinol intakes were not significantly different between the groups and not associated with CHD risk. CONCLUSIONS: High maternal vitamin E by diet and supplements is associated with an increased risk of CHD offspring.