Supplementation with Hydroxytyrosol and Punicalagin Improves Early Atherosclerosis Markers Involved in the Asymptomatic Phase of Atherosclerosis in the Adult Population: A Randomized, Placebo-Controlled, Crossover Trial

Abstract

Hydroxytyrosol (HT) and Punicalagin (PC) exert cardioprotective and anti-atherosclerotic effects. This study evaluates the effect of oral supplementation with HT and PC (SAx) on early atherosclerosis markers in middle-aged, seemingly healthy adults. A randomized, double-blinded, placebo-controlled, crossover trial was performed for 20 weeks. There were two treatment sequences (Placebo/SAx, n = 41; SAx/Placebo, n = 43) for which the intervention periods (Placebo and SAx) were 8 weeks long, followed by a 4-week wash out period. The supplement was composed of 9.9 mg of HT and 195 mg of PC, and the placebo was composed of maltodextrin. SAx increased endothelial function (Flow-mediated dilatation [FMD]: 2.36%; p < 0.001) in the endothelial dysfunction subgroup compared to the placebo (2.36 ± 3.9 vs. 0.76 ± 3.5%, p < 0.05). SAx also reduced oxLDL by −28.74 ng/mL (p < 0.05) in subjects with higher levels of oxLDL, which was an improvement compared with the placebo (−28.74 ± 40.2 vs. 25.64 ± 93.8 ng/mL, p < 0.001). The prehypertension and hypertension subgroups exhibited decreased systolic (−15.75 ± 9.9 mmHg; p < 0.001) and diastolic (−6.36 ± 8.7 mmHg; p < 0.001) blood pressure after SAx consumption. Moreover, the systolic prehypertension and hypertension subgroups presented significant differences in systolic blood pressure compared to the placebo (−15.75 ± 9.9 vs. −2.67 ± 12.0 mmHg, p < 0.05). In conclusion, the supplement exerted anti-atherosclerotic effects by improving endothelial function, blood pressure, and levels of circulating oxLDL, especially for persons in whom these parameters were altered.

Betanin as a multipath oxidative stress and inflammation modulator: a beetroot pigment with protective effects on cardiovascular disease pathogenesis

“…Betanin as a putative activator of the anti-oxidative Nrf2-ARE pathway and supressor of the antiinflammatory NFk-B pathway in CVD As mentioned previously, oxidative stress, inflammation and endothelial dysfunction are common conditions in the pathophysiology of several cardiovascular outcomes, such as atherosclerosis (Quir os-Fern andez et al 2019;F€ orstermann, Xia and Li, 2019), heart failure (Ramirez-Sanchez et al 2013;Koning et al 2016;Lubrano and Balzan 2020), myocardial hypertrophy (Wu et al 2012, Wilder et al 2015) and ischemia and reperfusion injury (Tian et al 2015;Granger and Kvietys 2015).…”

The Fluid Aspect of the Mediterranean Diet in the Prevention and Management of Cardiovascular Disease and Diabetes: The Role of Polyphenol Content in Moderate Consumption of Wine and Olive Oil

“…A recent study evaluated the effects of oral supplementation with hydroxityrosol on early atherosclerosis markers in middle-aged healthy adults [143]. Hydroxityrosol showed anti-atherosclerotic properties by improving endothelial function, BP and circulating oxidized LDL levels [144].…”

“…As previously mentioned, a recent study showed that oral supplementation with hydroxityrosol in middle-aged healthy adults exerted anti-atherosclerotic effects by improving endothelial function [144]. In particular, hydroxityrosol may exert its vasculoprotective effects via the activation of a nuclear factor-E (2)-related factor-2 (Nrf2) pathway that increases the expression of other antioxidants, like NAD(P)H: quinone oxidoreductase 1 [193,194].…”

Punicalagin Regulates Key Processes Associated with Atherosclerosis in THP-1 Cellular Model

“…Moreover, the increased prevalence of CVD poses considerable burdens for healthcare systems due to the high costs involved in treating and managing the condition [1,2]. Atherosclerosis remains the primary cause of deadly heart diseases [3] and occurs when long-lasting inflammation affects the vascular system.…”

“…Punicalagin is a phytochemical polyphenolic compound extracted from pomegranate (Punica granatum) and is the most abundant polyphenol in pomegranate juice (80% w/w) [10]. Punicalagin is known to have strong antioxidant characteristics in comparison to other nutraceuticals [3,11]. Studies on patients undergoing hemodialysis demonstrated that pomegranate juice did not affect or alter inflammatory markers expression after six months of about 1000 mg per day uptake [12].…”