25 March 2021 In Phenolic compounds

Resveratrol is a naturally occurring stilbene endowed with multiple health-promoting effects. It is produced by certain plants including several dietary sources such as grapes, apples, raspberries, blueberries, plums, peanuts, and products derived therefrom (e.g., wine). Resveratrol can be isolated and purified from these biological sources or synthesized in a few steps with an overall high yield.

This compound and its glucoside, the trans-polydatin piceid, have received worldwide attention for their beneficial effects on cardiovascular, inflammatory, neurodegenerative, metabolic, and age-related diseases. These health-promoting effects are particularly attractive given the prevalence of resveratrol-based nutraceuticals and the paradoxical epidemiologic observation that wine consumption is inversely correlated to the incidence of coronary heart disease.

However, the notion of resveratrol as a "magic bullet" was recently challenged by clinical trials showing that this polyphenol does not have a substantial influence on health status and mortality risk.

In the present review, we discuss the proposed therapeutic attributes and the mode of molecular actions of resveratrol. We also cover recent pharmacologic efforts to improve the poor bioavailability of resveratrol and influence the transition between body systems in humans.

We conclude with some thoughts about future research directions that might be meaningful for resolving controversies surrounding resveratrol.

24 March 2021 In Phenolic compounds

Ageing and menopause contribute to endothelial dysfunction, causing impaired cerebral perfusion, which is in turn associated with accelerated cognitive decline. In a 14-week pilot study, we showed that supplementation with low-dose resveratrol, a phytoestrogen that can enhance endothelial function, improved cerebrovascular and cognitive functions in postmenopausal women.

We sought to confirm these benefits in a larger, longer-term trial. A 24-month randomized, placebo-controlled crossover trial was undertaken in 125 postmenopausal women, aged 45-85 years, who took 75 mg trans-resveratrol or placebo twice-daily for 12 months and then crossover to the alternative treatment for another 12 months. We evaluated within individual differences between each treatment period in measures of cognition (primary outcome), cerebrovascular function in the middle cerebral artery (cerebral blood flow velocity: CBFV, cerebrovascular responsiveness: CVR) and cardio-metabolic markers as secondary outcomes.

Subgroup analyses examined effects of resveratrol by life stages. Compared to placebo, resveratrol supplementation resulted a significant 33% improvement in overall cognitive performance (Cohen's d = 0.170, P = 0.005). Women >/=65 years of age showed a relative improvement in verbal memory with resveratrol compared to those younger than 65 years. Furthermore, resveratrol improved secondary outcomes including resting mean CBFV (d = 0.275, P = 0.001), CVR to hypercapnia (d = 0.307, P = 0.027), CVR to cognitive stimuli (d = 0.259, P = 0.032), fasting insulin (d = 0.174, P = 0.025) and insulin resistance index (d = 0.102, P = 0.034).

Regular supplementation with low-dose resveratrol can enhance cognition, cerebrovascular function and insulin sensitivity in postmenopausal women. This may translate into a slowing of the accelerated cognitive decline due to ageing and menopause, especially in late-life women. Further studies are warranted to observe whether these cognitive benefits of resveratrol can reduce the risk of dementia.

23 February 2021 In Phenolic compounds

PURPOSE: Red wine polyphenols (RWP) are plant-based molecules that have been extensively studied in relation to their protective effects on vascular health in both animals and humans. The aim of this review was to quantify and compare the efficacy of RWP and pure resveratrol on outcomes measures of vascular health and function in both animals and humans.

METHODS: Comprehensive database searches were carried out through PubMed, Web of Science and OVID for randomised, placebo-controlled studies in both animals and humans. Meta-analyses were carried out on acute and chronic studies of RWP in humans, alongside sub-group analysis where possible. Risk-of-bias assessment was carried out for all included studies based on randomisation, allocation, blinding, outcome data reporting, and other biases.

RESULTS: 48 animal and 37 human studies were included in data extraction following screening. Significant improvements in measures of blood pressure and vascular function following RWP were seen in 84% and 100% of animal studies, respectively. Human studies indicated significant improvements in systolic blood pressure overall (- 2.6 mmHg, 95% CI: [- 4.8, - 0.4]), with a greater improvement in pure-resveratrol studies alone (- 3.7 mmHg, 95% CI: [- 7.3, - 0.0]). No significant effects of RWP were seen in diastolic blood pressure or flow-mediated dilation (FMD) of the brachial artery.

CONCLUSION: RWP have the potential to improve vascular health in at risk human populations, particularly in regard to lowering systolic blood pressure; however, such benefits are not as prevalent as those observed in animal models.

23 November 2020 In Phenolic compounds

The aim of this study was to investigate the effects of dietary supplementation with a nonalcoholic red wine extract (RWE), including resveratrol and polyphenols, on insulin sensitivity and Sirt1 expression in nondiabetic humans. The present study was a single-arm, open-label and prospective study.

Twelve subjects received supplementation with RWE, including 19.2 mg resveratrol and 136 mg polyphenols, daily for 8 weeks. After 8 weeks, metabolic parameters, including glucose/lipid metabolism and inflammatory markers, were evaluated. mRNA expression of Sirt1 was evaluated in isolated peripheral blood mononuclear cells (PBMNCs). Additionally, Sirt1 and phosphorylated AMP-activated kinase (p-AMPK) expression were evaluated in cultured human monocytes (THP-1 cells). Supplementation with RWE for 8 weeks decreased the homeostasis model assessment for insulin resistance (HOMA-IR), which indicates an increase in insulin sensitivity. Serum low-density lipoprotein-cholesterol (LDL-C), triglyceride (TG) and interleukin-6 (IL-6) were significantly decreased by RWE supplementation for 8 weeks. Additionally, Sirt1 mRNA expression in isolated PBMNCs was significantly increased after 8 weeks of RWE supplementation.

Moreover, the rate of increase in Sirt1 expression was positively correlated with the rate of change in HOMA-IR. The administration of RWE increased Sirt1 and p-AMPK expression in cultured THP-1 cells. Supplementation with RWE improved metabolism, such as insulin sensitivity, lipid profile and inflammation, in humans. Additionally, RWE supplementation induced an increase in Sirt1 expression in PBMNCs, which may be associated with an improvement in insulin sensitivity.

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