Oral nutraceutical intervention to improve endothelial function: Evidence from in vitro and pilot clinical studies

Objective: Aortic valve sclerosis affects 30 % of individuals over 65 and is associated with coronary artery disease, with risk of progression to aortic stenosis. Endothelial dysfunction, mediated by oxidative stress, impaired nitric oxide (NO) signaling, inflammation, and lipoprotein deposition, plays a central role in disease initiation and progression. This study investigated whether a combination of bioactive compounds could counteract these mechanisms and support vascular health. Methods: The effects of curcuma longa, coenzyme Q10, black garlic, vitamin B1, and vitamin D3 were tested in vitro on aortic valve endothelial cells. Cell viability, reactive oxygen species (ROS), and NO levels were quantified by commercially available kits, while gene expression was analyzed by RNA sequencing. A 4-week prospective pilot clinical study in 10 healthy volunteers without cardiovascular disease evaluated endothelial function and arterial stiffness. Results: The compounds reduced ROS production (>27 %; p < 0.05), enhanced endothelial viability (>33 %; p < 0.05; except curcuma and black garlic), and increased NO production (>6 %; p < 0.05; except black garlic). Beneficial effects were reflected in upregulation of anti-atherosclerotic (GIPR, +0.058 copies per million, CPM; p < 0.05), antioxidant (GADL1, +0.55 CPM; p < 0.001), and anti-inflammatory (IL12A, +0.17 CPM; p < 0.01) genes. Clinically, daily supplementation improved endothelial function in participants found to have pre-existing endothelial dysfunction (p = 0.0336), with 50 % achieving normal levels after 4 weeks, while all subjects exhibited reduced arterial stiffness (p = 0.0016) without hepatic toxicity. Conclusions: The oral supplementation of the combination of these bioactive compounds improved endothelial function and vascular health, particularly in individuals with endothelial dysfunction, offering potential therapeutic benefits for cardiovascular health.