Effects of acute and short-term grape seed extract supplementation on blood pressure responses to exercise in individuals at cardiometabolic risk: A randomised, double-blind, placebo-controlled exploratory crossover trial

Background & aim Grape seed extract (GSE) has been suggested as a potential non-pharmacological strategy for lowering blood pressure (BP), exerting vascular benefits comparable to those induced by exercise. However, its effects when combined with exercise, the cornerstone intervention for BP management, remain unclear. Therefore, this study aimed to investigate the acute and short-term effects of GSE supplementation on BP and vascular responses to exercise. Methods A randomised, double-blind, placebo-controlled crossover trial was conducted in ten sedentary adults (N=6 males and 4 females; 62±6 yr) with elevated BP (systolic and diastolic BP, 132.7±13.6 and 77.2±11.7 mmHg, respectively) and overweight/obesity (body mass index, 31.4±6.0 kg·m -2 ). Participants performed two exercise bouts in two conditions in a random order: a) placebo or b) GSE. BP response was assessed at rest, during exercise, and following exercise completion (i.e., post-exercise hypotension and ambulatory) after acute and 7 days of PLAC or GSE intake. Endothelial function was also evaluated using flow-mediated dilation (FMD). During the acute intake study visit, plasma nitrite and nitrate concentrations were assessed during exercise and at recovery. Results Acute and short-term GSE intake did not significantly affect post-exercise hypotension (i.e., BP response during the 40 min after exercise; p condition >0.064, p condition x time >0.379). Exploratory analyses showed lower ambulatory systolic BP (acute, -3.1, 95% CI -5.9 to -0.4 mmHg, p =0.028; short-term, -3.5, 95% CI -6.9 to -0.1 mmHg, p =0.047) and mean arterial pressure during exercise (MAP; acute, -4.4, 95% CI -8.8 to -0.1 mmHg, p =0.047; short-term, -5.1, 95% CI -9.3 to -0.8 mmHg, p =0.045) in GSE conditions, together with enhanced FMD (acute; 2.42, 95% CI 0.83 to 4.01 %; p =0.007) and increased plasma nitrite concentrations (0.55, 95% CI 0.02 to 1.08 umol·L -1 ; p =0.044) in response to exercise after acute GSE intake. 7 days of GSE supplementation reduced resting BP (MAP; -6.2, 95% CI -10.5 to -1.8 mmHg, p =0.011). However, GSE intake at the end of this period transiently increased resting BP 90 min after ingestion (MAP; 4.6, 95% CI 0.4 to 8.8 mmHg, p=0.036). Conclusion Although GSE supplementation did not significantly affect post-exercise hypotension, our results suggested favourable effects on daytime ambulatory BP, acute endothelial function, and exercise BP. These findings warrant further investigation into the potential role of GSE as an adjunct to exercise in adults with cardiometabolic risk. Clinical trial registration ClinicalTrials.gov Identifier: NCT06985407 ClinicalTrials.gov Identifier NCT06985407