A healthier approach to clinical trials evaluating resveratrol for primary prevention of age-related diseases in healthy populations

Abstract

In recent years, the wealth of basic science research supporting resveratrol's potential to treat, delay, and even prevent age-related chronic diseases has led to a number of human clinical trials. While such translational research has yielded promising results in clinical populations, recently published conflicting results from studies evaluating resveratrol's potential for primary prevention of chronic disease in healthy / asymptomatic individuals have generated considerable controversy and do not initially appear consistent with findings from animal models. We argue that trials targeting healthy humans are often fundamentally flawed owing to inappropriate use of paradigms only applicable to populations with overt clinical disease and the consequent misleading (typically negative) results can severely retard advancement of drug development. To appropriately perform translational research centered on resveratrol as a primary prevention agent in non-clinical populations, it is critical to utilize study designs which can provide adequate information on clinically relevant outcome measures, avoid paradigms and assumptions from interventions which are specific to clinical populations, and maintain realistic expectations compared to interventions which provide the theoretical maximal response (e.g., caloric restriction and aerobic exercise training).

Caloric restriction, resveratrol and melatonin: Role of SIRT1 and implications for aging and related-diseases

“…Nevertheless, results obtained from clinical trials in humans evaluating the potential effects of resveratrol have generated considerable controversy, and in some cases the findings of these trials are not consistent with results from animal models (Yoshino et al, 2012;Smoliga et al, 2013). However, disparity in dosing protocols and clinical paradigms may cause conflicting findings.…”

“…However, disparity in dosing protocols and clinical paradigms may cause conflicting findings. Only long-term epidemiological studies and meta-analysis can clarify the use of resveratrol as a therapy to reduce the physiological decline and age-related diseases (Smoliga et al, 2013).…”

Serum from obstructive sleep apnea patients induces inflammatory responses in coronary artery endothelial cells

“…Major inflammatory biomarkers such as CRP are clearly elevated by acute cardiovascular events and have some value in predicting risk or reclassification [41], but common therapies and medications may affect CRP levels and nullify the predictive power [42]. Moreover, elevations of one inflammatory factor my be offset by an anti-inflammatory factor, which motivated the development of the SCIP assay as an unbiased means of addressing how a pathology-relevant cell type, such as endothelial cells, interpret the gestalt balance of circulating pro- and anti-inflammatory factors [43]. This assay has proven valuable for both studies of therapeutic benefit [24] and environmental health outcomes [44], as well as highlighting inflammatory differences between coronary artery disease patients and controls even after months of standard of care pharmacotherapy [23].…”

The effects of resveratrol on aging vessels

“…Yet, there is no clinical justification to treat those subjects or expect such effects. Moreover, it is not clear how positive effects in an already healthy population should be interpreted (Smoliga et al, 2013). On the other hand, enough evidence has been gathered to suggest that compromised populations such as the elderly do benefit from treatment with RV (Smoliga et al, 2013).…”

“…Moreover, it is not clear how positive effects in an already healthy population should be interpreted (Smoliga et al, 2013). On the other hand, enough evidence has been gathered to suggest that compromised populations such as the elderly do benefit from treatment with RV (Smoliga et al, 2013). Even though a recent series of publications in aged humans (Gliemann et al, 2014(Gliemann et al, , 2013Olesen et al, 2014b) reveals no benefit from RV supplementation in a broad range of cardiovascular and metabolic parameters, further research needs to be conducted to definitely validate the claims both in favor and against RV.…”