Funding delayed beyond acceptable start date

The purpose of this study is to investigate the effect of acute isoquercetin supplementation, aspirin, and isoquercetin/aspirin combination on platelet aggregation, blood pressure and vasculat stiffness (eg digital volume pulse), as well as investigating the plasma accumulation and urine excretion profiles of quercetin.

Cardiovascular disease (CVD) is the leading cause of death worldwide. In 2012, approximately 17.5 million people worldwide died from CVD, representing 31% of global death. Flavonoids are a class of plant secondary metabolites, functioning in the plant to aid in growth. These compounds are found in diets worldwide, and many cohort studies have demonstrated the protective effect of diets high in flavonoids against CVD events, with some studies showing flavonoid intake inversely associated with CV event risk, CV non-fatal events and all-cause mortality. One consistent issue with quercetin as a dietary flavonoid is the plasma concentrations it is able to reach are not always sufficient to provide a protective effect. Therefore, supplementation or pharmacological intervention with flavonoids may offer a solution. Supplementation with isoquercetin, the 3-O-glucoside of quercetin, offers the potential for much higher plasma concentrations of quercetin and its metabolites than dietary sources can offer, with associated increased inhibitory, anti-platelet effects. It must therefore be addressed whether isoquercetin supplementation can effectively reduce platelet function ex vivo, measured by aggregation and closure time, as well as improve vascular function, measured through blood pressure (BP) and vascular stiffness (eg digital volume pulse (DVP)).

Inclusion Criteria:

• Plasma TAG (triacylglycerol) < 4.0 mmol/l
• Body mass index (BMI) between 18-35 kg/m2
• Total cholesterol (TC): <7 mmol/l
• Systolic blood pressure <160 mmHg and diastolic blood pressure <100 mmHg
• Consume less than 5 portions of fruit/vegetables per day
• Male

Exclusion Criteria:

• Suffered a myocardial infarction/stroke in the past 12 months
• Diabetic (diagnosed as fasting blood glucose >7 mmol/l) or suffer from other endocrine disorders
• Suffering from renal or bowel disease or have a history of cholestatic liver or pancreatitis
• On drug treatment for hyperlipidaemia, hypertension, inflammation or hypercoagulation
• History of alcohol abuse
• Planning or on a weight reducing regime
• Undertake vigorous exercise more than 3 times a week
• Taking nutritional supplements (e.g. fish oil, calcium)
• Taking flavonoid supplements
• Suffering from hayfever
• Taking any, or intolerant to, NSAIDS including aspirin
• On any medication, prescribed or not prescribed (or willing to abstain from these during period of study as well as prior 2 week washout period)
• Using any recreational drugs
• Vegan
• Intolerant/allergic to nuts, wheat, dairy
• Intolerant/allergic to aspirin
• On, or have taken antibiotics in the last 2 months
• Had surgery in the last 3 months
• Smokers, or have smoked in the last month
• Using e-cigarettes
• Anaemic: haemoglobin <12.5 g/dl
• History of gastric ulcers
• Female

Data will be averaged (some will also be normalized) before publishing, IPD (Individual Participant Data) will not be made available