The polyphenol quercetin may prevent CVD due to its antihypertensive and vasorelaxant properties. We investigated the effects of quercetin after regular intake on blood pressure (BP) in overweight-to-obese patients with pre-hypertension and stage I hypertension. In addition, the potential mechanisms responsible for the hypothesised effect of quercetin on BP were explored. Subjects (n70) were randomised to receive 162 mg/d quercetin from onion skin extract powder or placebo in a double-blinded, placebo-controlled cross-over trial with 6-week treatment periods separated by a 6-week washout period. Before and after the intervention, ambulatory blood pressure (ABP) and office BP were measured; urine and blood samples were collected; and endothelial function was measured by EndoPAT technology. In the total group, quercetin did not significantly affect 24 h ABP parameters and office BP. In the subgroup of hypertensives, quercetin decreased 24 h systolic BP by −3·6 mmHg (P=0·022) when compared with placebo (mean treatment difference, −3·9 mmHg;P=0·049). In addition, quercetin significantly decreased day-time and night-time systolic BP in hypertensives, but without a significant effect in inter-group comparison. In the total group and also in the subgroup of hypertensives, vasoactive biomarkers including endothelin-1, soluble endothelial-derived adhesion molecules, asymmetric dimethylarginine, angiotensin-converting enzyme activity, endothelial function, parameters of oxidation, inflammation, lipid and glucose metabolism were not affected by quercetin. In conclusion, supplementation with 162 mg/d quercetin from onion skin extract lowers ABP in patients with hypertension, suggesting a cardioprotective effect of quercetin. The mechanisms responsible for the BP-lowering effect remain unclear.

Evidence is accumulating that vitamin D may have beneficial effects on respiratory tract, autoimmune, neuro-degenerative, and mental diseases. The present umbrella review of systematic reviews (SRs) of cohort studies and randomised controlled trials (RCTs), plus single Mendelian randomisation studies aims to update current knowledge on the potential role of vitamin D in preventing and treating these extraskeletal diseases. Altogether, 73 SRs were identified. Observational data on primary prevention suggest an inverse association between vitamin D status and the risk of acute respiratory tract infections (ARI), dementia and cognitive decline, and depression, whereas studies regarding asthma, multiple sclerosis (MS), and type 1 diabetes mellitus (T1DM) are scarce. SRs of RCTs support observational data only for the risk of ARI. No respective RCTs are available for the prevention of chronic obstructive pulmonary disease (COPD), MS, and T1DM. SRs of RCTs indicate beneficial therapeutic effects in vitamin D-deficient patients with asthma and COPD, while effects on major depression and T1DM need to be further elucidated. Mendelian randomisation studies do not consistently support the results of SRs. Since several limitations of the included SRs and existing RCTs do not permit definitive conclusions regarding vitamin D and the selected diseases, further high-quality RCTs are warranted.

ApoE is a key protein in lipid metabolism with three major isoforms.ApoEallele frequencies show non-random global distribution especially in Europe with highapoEε3frequency in the Mediterranean area, whereas theapoEε4genotype is enriched in Northern Europe. TheapoEε4genotype is one of the most important genetic risk factors for age-dependent chronic diseases, including CVD and Alzheimer's disease (AD). The apoE polymorphism has been shown to impact on blood lipids, biomarkers of oxidative stress and chronic inflammation, which all may contribute to the isoform-dependent disease risk. Studies in mice and human subjects indicate that theapoEε3but not theapoEε4genotype may significantly benefit from dietary flavonoids (e.g. quercetin) andn-3 fatty acids. Metabolism of lipid soluble vitamins E and D is likewise differentially affected by theapoEgenotype. Epidemiological and experimental evidence suggest a better vitamin D status inapoEε4than ε3subjects indicating a certain advantage of ε4over ε3. The present review aims at evaluation of current data available on interactions between apoE polymorphism and dietary responsiveness to flavonoids, fat soluble vitamins andn-3 fatty acids. Likewise, distinct geographic distribution and chronic disease risk of the different apoE isoforms are addressed.

Dysfunction of the endothelium plays an integral role in atherogenesis. This review summarizes recent findings on the effects of marine [eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA)] and plant [alpha-linolenic acids (ALA)] n-3 polyunsaturated fatty acids (PUFAs) on endothelial function in healthy individuals and in patients with cardiovascular disease (CVD) risk factors or manifest CVD. We identified 33 intervention trials investigating the effects of n-3 PUFA on fasting and/or postprandial endothelial function. In healthy individuals regular supplementation of EPA/DHA or ALA shows inconsistent results on endothelial function, whereas markers of endothelial function seem to be improved in overweight dyslipidaemic patients and type 2 diabetics. Conflicting results are observed in CVD patients. Reasons for discrepancies between the study results include the health status and age of participants, duration of supplementation, dose and fatty acid composition of the administered n-3 PUFAs as well as methods used to assess endothelial function. In individuals with CVD risk factors including overweight, dyslipidemia and type 2 diabetes n-3 PUFAs may improve endothelial function. However, the evidence for a clinical efficacy is not strong enough to make final recommendations with respect to a specific dose and the duration of supplementation.