Effects of the pure flavonoids epicatechin and quercetin on vascular function and cardiometabolic health: a randomized, double-blind, placebo-controlled, crossover trial.
BACKGROUND
Prospective cohort studies showed inverse associations between the intake of flavonoid-rich foods (cocoa and tea) and cardiovascular disease (CVD). Intervention studies showed protective effects on intermediate markers of CVD. This may be due to the protective effects of the flavonoids epicatechin (in cocoa and tea) and quercetin (in tea).


OBJECTIVE
We investigated the effects of supplementation of pure epicatechin and quercetin on vascular function and cardiometabolic health.


METHODS
Thirty-seven apparently healthy men and women aged 40-80 y with a systolic blood pressure (BP) between 125 and 160 mm Hg at screening were enrolled in a randomized, double-blind, placebo-controlled, crossover trial. CVD risk factors were measured before and after 4 wk of daily flavonoid supplementation. Participants received (-)-epicatechin (100 mg/d), quercetin-3-glucoside (160 mg/d), or placebo capsules for 4 wk in random order. The primary outcome was the change in flow-mediated dilation from pre- to postintervention. Secondary outcomes included other markers of CVD risk and vascular function.


RESULTS
Epicatechin supplementation did not change flow-mediated dilation significantly (1.1% absolute; 95% CI: -0.1%, 2.3%; P = 0.07). Epicatechin supplementation improved fasting plasma insulin (Δ insulin: -1.46 mU/L; 95% CI: -2.74, -0.18 mU/L; P = 0.03) and insulin resistance (Δ homeostasis model assessment of insulin resistance: -0.38; 95% CI: -0.74, -0.01; P = 0.04) and had no effect on fasting plasma glucose. Epicatechin did not change BP (office BP and 24-h ambulatory BP), arterial stiffness, nitric oxide, endothelin 1, or blood lipid profile. Quercetin-3-glucoside supplementation had no effect on flow-mediated dilation, insulin resistance, or other CVD risk factors.


CONCLUSIONS
Our results suggest that epicatechin may in part contribute to the cardioprotective effects of cocoa and tea by improving insulin resistance. It is unlikely that quercetin plays an important role in the cardioprotective effects of tea. This study was registered at clinicaltrials.gov as NCT01691404.
From Top Institute Food and Nutrition, Wageningen, The Netherlands (JID, JMG, LG, PLZ, and PCHH); the Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands (JID, JMG, LG, DK, and PCHH); and Nutrition and Health Department, Unilever R&D Vlaardingen, Vlaardingen, The Netherlands (PLZ).
James I
JI
Dower
From Top Institute Food and Nutrition, Wageningen, The Netherlands (JID, JMG, LG, PLZ, and PCHH); the Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands (JID, JMG, LG, DK, and PCHH); and Nutrition and Health Department, Unilever R&D Vlaardingen, Vlaardingen, The Netherlands (PLZ).
Johanna M
JM
Geleijnse
From Top Institute Food and Nutrition, Wageningen, The Netherlands (JID, JMG, LG, PLZ, and PCHH); the Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands (JID, JMG, LG, DK, and PCHH); and Nutrition and Health Department, Unilever R&D Vlaardingen, Vlaardingen, The Netherlands (PLZ).
Lieke
L
Gijsbers
From Top Institute Food and Nutrition, Wageningen, The Netherlands (JID, JMG, LG, PLZ, and PCHH); the Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands (JID, JMG, LG, DK, and PCHH); and Nutrition and Health Department, Unilever R&D Vlaardingen, Vlaardingen, The Netherlands (PLZ).
Peter L
PL
Zock
From Top Institute Food and Nutrition, Wageningen, The Netherlands (JID, JMG, LG, PLZ, and PCHH); the Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands (JID, JMG, LG, DK, and PCHH); and Nutrition and Health Department, Unilever R&D Vlaardingen, Vlaardingen, The Netherlands (PLZ).
Daan
D
Kromhout
From Top Institute Food and Nutrition, Wageningen, The Netherlands (JID, JMG, LG, PLZ, and PCHH); the Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands (JID, JMG, LG, DK, and PCHH); and Nutrition and Health Department, Unilever R&D Vlaardingen, Vlaardingen, The Netherlands (PLZ).
Peter C H
PC
Hollman
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001794:Blood Pressure / Q000187:drug effects; D002099:Cacao / Q000737:chemistry; D002318:Cardiovascular Diseases / Q000517:prevention & control; D002392:Catechin / Q000008:administration & dosage*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D018592:Cross-Over Studies; D004311:Double-Blind Method; D019332:Endothelin-1 / Q000097:blood; D004730:Endothelium, Vascular / Q000187:drug effects*; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000097:blood; D011794:Quercetin / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D013662:Tea / Q000737:chemistry; D014280:Triglycerides / Q000097:blood; D059289:Vascular Stiffness / Q000187:drug effects
D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D019332:Endothelin-1; D007328:Insulin; D013662:Tea; D014280:Triglycerides; C016527:isoquercitrin; D009569:Nitric Oxide; D002392:Catechin; D011794:Quercetin
CVD; clinical trial; cocoa; epicatechin; flavonoids; flow-mediated dilation; insulin resistance; quercetin; tea; vascular function