Resveratrol is a polyphenol found in the skin of fruit such as red grapes and berries. You may have noticed that resveratrol is all over the place right now. The hype around it is massive and it is advertised as a “wonder compound” with a myriad of benefits in disease protection, including cardiovascular diseases, cancer, diabetes, neurodegeneration, and rheumatic diseases, just to name a few.

I have briefly mentioned resveratrol when I talked about the benefits of red wine. But, as stated at the time, its naturally occurring form has a relatively low half-life in plasma and the amount of resveratrol present in many foods or beverages may be too low to lead to significant beneficial effects. Nevertheless, it may be only a matter of time until new more stable synthetic analogs of resveratrol are developed.

Is this just another fad or is resveratrol really that wondrous?

Although clinical evidence of its effects is still scarce, experimental studies on the effects of resveratrol are clearly a massive trend: a search on Pubmed reveals that more than half the research on this topic was published in the last five years.

Although there are some controversies around resveratrol (and even cases of scientific misconduct), experimental evidence does suggest that it may have interesting benefits.

Resveratrol’s effects are mostly due to its potent anti-inflammatory and antioxidant properties. Most diseases that benefit from these type of actions are therefore likely candidates for its health benefits. In cardiovascular diseases, for example, resveratrol has shown beneficial effects in animal models of hypertension, atherosclerosis, stroke, ischemic heart disease, arrhythmia, chemotherapy-induced cardiotoxicity, diabetic cardiomyopathy, and heart failure. These actions seem to be mediated by its anti-oxidant, anti-inflammatory, anti-platelet, insulin-sensitizing, and lipid-lowering properties. But clinical studies in the context of cardiovascular diseases are still limited, with conflicting results from trials having been reported.

In cancer research, also using animal models, resveratrol has been found to be effective against a number of human cancers, suggesting that it could be a useful chemotherapeutic agent, with the advantage of being well tolerated and having minimal side effects even at very high doses. Resveratrol has also shown experimental metabolic improvements, namely in glucose metabolism, body composition, liver fat accumulation, and in protection against obesity and obesity-related diseases such as type-2 diabetes. Resveratrol seems to mimic the effects of calorie restriction by regulating cellular energy homeostasis and mitochondrial biogenesis. But, again, clinical trials have had mixed results.

Resveratrol administration has also been studied on many neurological conditions. Beneficial effects on age-related neurological disorders, macular degeneration, stroke, and cognitive deficits with or without dementia have been attributed to resveratrol, most likely due to its neuroprotective action, as seen in many animal models of toxicity. In Alzheimer’s disease, for example, resveratrol has been shown to increase the clearance of amyloid-beta, and to modulate oxidative stress, neuronal energy homeostasis, cell death and longevity.

The neuroprotective actions of resveratrol have also been attributed to an effect against glutamate-induced neurotoxicity. Glutamate is a major neurotransmitter in the central nervous system that, when excessively accumulated extracellularly, can induce a calcium overload and be neurotoxic, leading to neuronal injury or death, and being associated with acute and chronic neurodegenerative diseases. Therefore, research on neuroprotective effects against glutamate-induced neurotoxicity it has been a therapeutic strategy to for treating both acute and chronic forms of neurodegeneration. In that context, resveratrol has been shown to be able to block these toxic glutamate-associated pathways.

Resveratrol has even been shown to extend the lifespan of multiple organisms, namely yeast, worms, and flies. By protecting against age-related diseases in mammals, resveratrol will most likely also have similar life-extending effects. Still, most of these actions remain to be reproduced in clinical trials.

Thanks to all the hype around resveratrol, there are now many nutritional supplements available in the market containing it. Regardless of how wonderful resveratrol may seem, beware of dietary supplements: the doses may not be adequate for an actual beneficial effect and, on the other hand, little is still know about its long-term actions. Until dose-effect clinical trials are successfully carried out and and reproduced, it is unlikely that dietary supplements will get it right.

References

Bhullar KS, & Hubbard BP (2015). Lifespan and healthspan extension by resveratrol. Biochimica et biophysica acta, 1852 (6), 1209-1218 PMID: 25640851

Bitterman JL, & Chung JH (2015). Metabolic effects of resveratrol: addressing the controversies. Cellular and molecular life sciences : CMLS, 72 (8), 1473-88 PMID: 25548801

de Ligt M, Timmers S, & Schrauwen P (2015). Resveratrol and obesity: Can resveratrol relieve metabolic disturbances? Biochimica et biophysica acta, 1852 (6), 1137-1144 PMID: 25446988

Pasinetti GM, Wang J, Ho L, Zhao W, & Dubner L (2015). Roles of resveratrol and other grape-derived polyphenols in Alzheimer’s disease prevention and treatment. Biochimica et biophysica acta, 1852 (6), 1202-1208 PMID: 25315300

Poulsen MM, Fjeldborg K, Ornstrup MJ, Kjær TN, Nøhr MK, & Pedersen SB (2015). Resveratrol and inflammation: Challenges in translating pre-clinical findings to improved patient outcomes. Biochimica et biophysica acta, 1852 (6), 1124-1136 PMID: 25583116

Singh CK, Ndiaye MA, & Ahmad N (2015). Resveratrol and cancer: Challenges for clinical translation. Biochimica et biophysica acta, 1852 (6), 1178-1185 PMID: 25446990

Szkudelski T, & Szkudelska K (2015). Resveratrol and diabetes: from animal to human studies. Biochimica et biophysica acta, 1852 (6), 1145-1154 PMID: 25445538

Zhang LN, Hao L, Wang HY, Su HN, Sun YJ, Yang XY, Che B, Xue J, & Gao ZB (2015). Neuroprotective effect of resveratrol against glutamate-induced excitotoxicity. Advances in clinical and experimental medicine : official organ Wroclaw Medical University, 24 (1), 161-5 PMID: 25923101

Zordoky BN, Robertson IM, & Dyck JR (2015). Preclinical and clinical evidence for the role of resveratrol in the treatment of cardiovascular diseases. Biochimica et biophysica acta, 1852 (6), 1155-1177 PMID: 25451966

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