Cardiovascular Disease
Conditions
Keywords
Cardiovascular disease, Flavonoid, Isoquercetin, Aspirin, Platelet function, Vascular function, Blood pressure
Brief summary
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.
Detailed description
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)).
Interventions
DRUGVehicle control
Described in arm
DRUGIsoquercetin
Described in arm
DRUGAspirin
Described in arm
DRUGIsoquercetin plus Aspirin
Described in arm
Sponsors
Biotechnology and Biological Sciences Research Council
Quercegen Pharmaceuticals
University of Reading
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to 65 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change from baseline in platelet aggregation | Acute Study: measured at -60 (baseline), 120, 240 and 360min |
Secondary
| Measure | Time frame |
|---|---|
| Change from baseline in blood pressure (systolic pressure, diastolic pressure and pulse pressure) | Acute study: measured at -60 (baseline), 0, 30, 60, 90, 120, 180, 240, 300 and 360min |
| Change from baseline in arterial stiffness measured by digital volume pulse - stiffness index | Acute study: measured at -60 (baseline), 0, 30, 60, 90, 120, 180, 240, 300 and 360min |
| Change from baseline in Closure Time (CT), measured with a Platelet Function Analyzer (PFA) | Acute study: measured at -60 (baseline), 120, 240 and 360min |
| Change from baseline in total plasma quercetin concentration (micromolar) | Acute study: measured at -60 (baseline), 0, 30, 60, 90, 120, 180, 240, 300 and 360min |
| Change from baseline in total urine quercetin concentration (micromolar) | Acute study: measured at 0 (baseline),120, 240 and 360min |
| Change from baseline in arterial stiffness measured by digital volume pulse - reflection index | Acute study: measured at -60 (baseline), 0, 30, 60, 90, 120, 180, 240, 300 and 360min |
Countries
United Kingdom
Outcome results
None listed