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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 (n 70) 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.

The present study aimed to assess the current state of breast-feeding promotion in hospitals and the prevalence of breast-feeding during the first year of life in Germany and to compare the results with a study 20 years earlier. In the studies on 'breast-feeding and infant nutrition in Germany' named 'SuSe', a cross-sectional survey in hospitals was combined with a subsequent prospective survey of breast-feeding and infant nutrition during the first year of life (0·5, 2, 4, 6 and 12 months after birth) in mother-infant pairs who were recruited in the hospitals. Written questionnaires and phone calls were used in SuSe I and web-based questionnaires in SuSe II. Breast-feeding promotion and prevalence were evaluated using recommendations from the WHO and the UNICEF. Two nationwide surveys SuSe I (1997-1998) and SuSe II (2017-2019). In SuSe I, 177 hospitals and 1717 mother-infant pairs and in SuSe II 109 hospitals and 962 mother-infant pairs were included. In SuSe II, hospitals implemented seven of the WHO 'Ten Steps to Successful Breastfeeding' to a greater extent than the hospitals in SuSe I. More mothers exclusively breastfed for 4 months (57 % v. 33 %) and continued breast-feeding until 6 (78 % v. 48 %) and 12 months (41 % v. 13 %). In both studies, exclusive breast-feeding decreased between 4 and 6 months of age due to the introduction of complementary feeding. In Germany, breast-feeding habits have come closer to the recommendations over the last 20 years.

•Alpha-linolenic acid (ALA) on a daily basis improved lipid profiles in healthy, non-obese men and women.•No evidence of a synergistic effect of ALA plus quercetin on cardiovascular disease risk markers.•Regular intake of supranutritional doses of quercetin increased plasma quercetin. Alpha-linolenic acid (ALA) and quercetin are characteristic compounds in plant-based diets. Cardioprotective effects have been described for both substances, although a possible benefit of combining ALA and quercetin has not, to our knowledge, been evaluated yet. The aim of this study was to investigate the potential independent and additive effects of ALA and quercetin on blood pressure (BP) and lipid and glucose metabolism, as well as on biomarkers of inflammation, oxidative stress, and antioxidant status in healthy, non-obese men and women. Another aim was to examine whether chronic supplementation of supranutritional doses of quercetin would result in an accumulation of plasma quercetin concentration over time. In a double-blinded, placebo-controlled crossover trial, healthy volunteers were randomized to receive 3.6 g/d ALA plus 190 mg/d quercetin or placebo for 8 wk. Data from 67 individuals (34 men, 33 women, mean age: 24.6 y) were assessed. Plasma quercetin, tamarixetin, isorhamnetin, and kaempferol increased significantly from baseline to study end with ALA + quercetin but not with ALA + placebo. No significant effect on office systolic BP, mean 24 h ambulatory BP (ABP), or mean daytime ABP was seen in either study group. Both interventions significantly decreased total cholesterol, low-density lipoprotein cholesterol, non–high-density lipoprotein cholesterol, and apolipoprotein B to a similar extent. No effect on high-density lipoprotein cholesterol, apolipoprotein A1, glucose, uric acid, oxidized low-density lipoprotein, C-reactive protein, or lipid-adjusted retinol, α-tocopherol, or β-carotene was seen in either group. Although dietary supplements of 3.6 g/d ALA over an 8-wk period improved lipid profiles in healthy adults, antioxidative and oxidative status, inflammation, and BP remained unchanged. No evidence was seen for an additive or synergistic effect of ALA plus quercetin on markers of cardiovascular disease risk.

Purpose Chronic low-level systemic and adipose tissue inflammation has been identified as a major etiologic factor in many chronic diseases, including hypertension and cardiovascular diseases. Evidence from experimental studies suggests anti-inflammatory effects of dietary flavonols such as quercetin. Methods We investigated the effects of regular intake of quercetin on leptin, adiponectin, biomarkers of inflammation, glucose and insulin in overweight-to-obese patients with pre- and stage 1 hypertension. Another objective was to assess the safety of daily quercetin supplementation measured by parameters of liver and kidney function and of hematology. Subjects ( n  = 70) were randomized to receive a supra-nutritional dose of 162 mg/d quercetin or placebo in a double-blinded, placebo-controlled crossover trial with 6-week treatment periods separated by a 6-week washout period. Two subjects dropped out for personal reasons. Only data from the remaining 68 subjects were included in the analysis. Results Compared to placebo, quercetin did not significantly affect serum concentrations of leptin and adiponectin, HOMA-AD or the ratios of leptin/adiponectin and adiponectin/leptin. Neither quercetin nor placebo significantly changed serum C-reactive protein and plasma tumor necrosis factor alpha. Compared to placebo, quercetin did not significantly affect glucose, insulin, HOMA-IR, blood biomarkers of liver and renal function, hematology and serum electrolytes. Conclusion A supra-nutritional dose of 162 mg/d quercetin from onion skin extract for 6 weeks is safe but without significant effects on parameters of systemic and adipose tissue inflammation as well as glucose and insulin in overweight-to-obese subjects with (pre-)hypertension. This trial was registered at www.germanctr.de/ and http://apps.who.int/trialsearch/ as DRKS00000555.

Increased dietary intake and tissue status of the long-chain n-3 PUFA, EPA and DHA, is associated with cardiovascular benefits. Epidemiological and animal studies suggest that concomitant nutritive intake of flavonoids may increase the conversion of α-linolenic acid (ALA) to longer-chain n-3 fatty acids EPA and DHA. We investigated the effects of increased ALA intake on fatty acid composition of serum phospholipids and erythrocytes in metabolically healthy men and women and whether fatty acid profiles and ALA conversion were affected by regular quercetin intake or sex. Subjects (n 74) were randomised to receive at least 3·3 g/d ALA with either 190 mg/d quercetin (ALA+quercetin) or placebo (ALA+placebo) in a double-blinded, placebo-controlled, crossover trial with 8-week intervention periods separated by an 8-week washout period. A total of seven subjects dropped out for personal reasons. Data from the remaining sixty-seven subjects (thirty-four males and thirty-three females) were included in the analysis. Both interventions significantly increased serum phospholipid ALA (ALA+placebo: +69·3 %; ALA+quercetin: +55·8 %) and EPA (ALA+placebo: +37·3 %; ALA+quercetin: +25·5 %). ALA + quercetin slightly decreased DHA concentration by 9·3 %. Erythrocyte ALA and EPA significantly increased with both interventions, whereas DHA decreased. Fatty acid composition did not differ between sexes. We found no effect of quercetin. Intake of 3·6 g/d ALA over an 8-week period resulted in increased ALA and EPA, but not DHA, in serum phospholipids and erythrocytes. Neither quercetin supplementation nor sex affected the increment of ALA and relative proportions of n-3 PUFA in serum phospholipids and erythrocytes.

Purpose To investigate the plasma kinetics of quercetin derived from hard capsules filled with onion skin extract powder or quercetin dihydrate in humans. Methods In a randomized, single-blind, diet-controlled crossover study, 12 healthy subjects (six men and six women) aged 21–33 years were administered a single oral supra-nutritional dose of approximately 163 mg quercetin derived from onion skin extract powder (containing 95.3 % of total flavonoids as quercetin aglycone) or quercetin dihydrate (134 mg quercetin aglycone equivalent). Blood samples were collected before and during a 24-h period after quercetin administration. The concentrations of quercetin and its two monomethylated derivatives, isorhamnetin (3′- O -methyl quercetin), and tamarixetin (4′- O -methyl quercetin), were measured using HPLC with fluorescence detection after plasma enzymatic treatment. Results The systemic availability, determined by comparing the plasma concentration–time curves of quercetin, was 4.8 times higher, and the maximum plasma concentration ( C max ) was 5.4 times higher after ingestion of the onion skin extract than after ingestion of pure quercetin dihydrate. By contrast, t max did not differ significantly between the two formulations. The C max values for isorhamnetin and tamarixetin were 3.8 and 4.4 times higher, respectively, after administration of onion skin extract than after pure quercetin dihydrate. The plasma kinetics of quercetin were not significantly different in men and women. Conclusion Quercetin aglycone derived from onion skin extract powder is significantly more bioavailable than that from quercetin dihydrate powder filled hard capsules.

Purpose To determine whether postprandial metabolic and vascular responses induced by a high-fat and high-carbohydrate meal are attenuated by ingestion of the flavonol quercetin. Methods Twenty-two overweight-to-obese hypertensive patients participated in a randomized, double-blind, controlled, crossover meal study. They consumed a test meal (challenge) rich in energy (4754 kJ), fat (61.6 g), saturated fatty acids (53 % of total fatty acids), and carbohydrates (113.3 g) with either placebo or 54 mg quercetin. Blood pressure, reactive hyperemia index (RHI), high-sensitive C-reactive protein (hs-CRP), soluble endothelial-derived adhesion molecules, parameters of lipid and glucose metabolism, and markers of antioxidant status were measured before the meal and at 2 and 4 h postprandially. Results Systolic and diastolic blood pressure increased significantly over time, but were not affected by treatment (placebo or quercetin). During both treatments, serum endothelin-1, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and plasma asymmetric dimethylarginine slightly decreased over time, whereas RHI increased. Serum triglycerides, total cholesterol, and insulin significantly increased, whereas HDL cholesterol and glucose significantly decreased over time, again with no effect of treatment. Plasma α -tocopherol significantly increased, and plasma Trolox equivalent antioxidative capacity decreased over time. Serum hs-CRP, plasma retinol, and β -carotene did not significantly change during the trial. Conclusion In hypertensive patients, a high-energy meal did not lead to postprandial impairment of vascular endothelial function. Postprandial metabolic responses induced by the challenge, such as lipemia and insulinemia, were not attenuated by the concomitant ingestion of quercetin. Clinical trial This trial was registered at www.germanctr.de/ and http://apps.who.int/trialsearch/ as DRKS00000555.

Increased dietary intake and tissue status of the long-chain n-3 PUFA, EPA and DHA, is associated with cardiovascular benefits. Epidemiological and animal studies suggest that concomitant nutritive intake of flavonoids may increase the conversion of [...]-linolenic acid (ALA) to longer-chain n-3 fatty acids EPA and DHA. We investigated the effects of increased ALA intake on fatty acid composition of serum phospholipids and erythrocytes in metabolically healthy men and women and whether fatty acid profiles and ALA conversion were affected by regular quercetin intake or sex. Subjects (n 74) were randomized to receive at least 3·3 g/d ALA with either 190 mg/d quercetin (ALA+quercetin) or placebo (ALA+placebo) in a double-blinded, placebo-controlled, crossover trial with 8-week intervention periods separated by an 8-week washout period. A total of seven subjects dropped out for personal reasons. Data from the remaining sixty-seven subjects (thirty-four males and thirty-three females) were included in the analysis. Both interventions significantly increased serum phospholipid ALA (ALA+placebo: +69·3 %; ALA+quercetin: +55·8 %) and EPA (ALA+placebo: +37·3 %; ALA+quercetin: +25·5 %). ALA + quercetin slightly decreased DHA concentration by 9·3 %. Erythrocyte ALA and EPA significantly increased with both interventions, whereas DHA decreased. Fatty acid composition did not differ between sexes. We found no effect of quercetin. Intake of 3·6 g/d ALA over an 8-week period resulted in increased ALA and EPA, but not DHA, in serum phospholipids and erythrocytes. Neither quercetin supplementation nor sex affected the increment of ALA and relative proportions of n-3 PUFA in serum phospholipids and erythrocytes.

Background Hematoma volume is a major pathophysiological hallmark of acute intracerebral hemorrhage (ICH). We investigated how the variance in functional outcome induced by the ICH volume is explained by neurological deficits at admission using a mediation model. Methods Patients with acute ICH treated in three tertiary stroke centers between January 2010 and April 2019 were retrospectively analyzed. Mediation analysis was performed to investigate the effect of ICH volume (0.8 ml (5% quantile) versus 130.6 ml (95% quantile)) on the risk of unfavorable functional outcome at discharge defined as modified Rankin Score (mRS) ≥ 3 with mediation through National Institutes of Health Stroke Scale (NIHSS) at admission. Multivariable regression was conducted to identify factors related to neurological improvement and deterioration. Results Three hundred thirty-eight patients were analyzed. One hundred twenty-one patients (36%) achieved mRS ≤ 3 at discharge. Mediation analysis showed that NIHSS on admission explained 30% [13%; 58%] of the ICH volume-induced variance in functional outcome at smaller ICH volume levels, and 14% [4%; 46%] at larger ICH volume levels. Higher ICH volume at admission and brainstem or intraventricular location of ICH were associated with neurological deterioration, while younger age, normotension, lower ICH volumes, and lobar location of ICH were predictors for neurological improvement. Conclusion NIHSS at admission reflects 14% of the functional outcome at discharge for larger hematoma volumes and 30% for smaller hematoma volumes. These results underscore the importance of effects not reflected in NIHSS admission for the outcome of ICH patients such as secondary brain injury and early rehabilitation.