Health Effects of Resveratrol: Results from Human Intervention Trials

Ramírez-Garza, Sonia L.; Laveriano-Santos, Emily P.; Marhuenda-Muñoz, María; Storniolo, Carolina E; Tresserra‐Rimbau, Anna; Vallverdú‐Queralt, Anna; Lamuela-Raventós, Rosa M.

doi:10.3390/nu10121892

Cited by 186 publications

(147 citation statements)

References 65 publications

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“…RE intake has pleiotropic effects in humans [181]. Although it is generally well tolerated, some adverse effects including nephrotoxicity and gastrointestinal problems were reported in human subjects [182,183].…”

Section: Human Trials With Resveratrolmentioning

confidence: 99%

Potential Adverse Effects of Resveratrol: A Literature Review

Shaito

Posadino

Younes

et al. 2020

IJMS

361

293

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Due to its health benefits, resveratrol (RE) is one of the most researched natural polyphenols. Resveratrol's health benefits were first highlighted in the early 1990s in the French paradox study, which opened extensive research activity into this compound. Ever since, several pharmacological activities including antioxidant, anti-aging, anti-inflammatory, anti-cancerous, anti-diabetic, cardioprotective, and neuroprotective properties, were attributed to RE. However, results from the available human clinical trials were controversial concerning the protective effects of RE against diseases and their sequelae. The reason for these conflicting findings is varied but differences in the characteristics of the enrolled patients, RE doses used, and duration of RE supplementation were proposed, at least in part, as possible causes. In particular, the optimal RE dosage capable of maximizing its health benefits without raising toxicity issues remains an area of extensive research. In this context, while there is a consistent body of literature on the protective effects of RE against diseases, there are relatively few reports investigating its possible toxicity. Indeed, toxicity and adverse effects were reported following consumption of RE; therefore, extensive future studies on the long-term effects, as well as the in vivo adverse effects, of RE supplementation in humans are needed. Furthermore, data on the interactions of RE when combined with other therapies are still lacking, as well as results related to its absorption and bioavailability in the human body. In this review, we collect and summarize the available literature about RE toxicity and side effects.In this process, we analyze in vitro and in vivo studies that have addressed this stilbenoid. These studies suggest that RE still has an unexplored side. Finally, we discuss the new delivery methods that are being employed to overcome the low bioavailability of RE.

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Section: Human Trials With Resveratrolmentioning

confidence: 99%

Potential Adverse Effects of Resveratrol: A Literature Review

Shaito

Posadino

Younes

et al. 2020

IJMS

361

293

View full text Add to dashboard Cite

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“…The contrasting results suggest that in order to obtain beneficial effects, the dose and the way of administration have to be carefully analyzed. It was suggested that a moderate (>450 mg) continuous intake is better than a single, higher dose administration [145].…”

Section: Stilbenesmentioning

confidence: 99%

Phenolic Compounds Exerting Lipid-Regulatory, Anti-Inflammatory and Epigenetic Effects as Complementary Treatments in Cardiovascular Diseases

et al. 2020

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Atherosclerosis is the main process behind cardiovascular diseases (CVD), maladies which continue to be responsible for up to 70% of death worldwide. Despite the ongoing development of new and potent drugs, their incomplete efficacy, partial intolerance and numerous side effects make the search for new alternatives worthwhile. The focus of the scientific world turned to the potential of natural active compounds to prevent and treat CVD. Essential for effective prevention or treatment based on phytochemicals is to know their mechanisms of action according to their bioavailability and dosage. The present review is focused on the latest data about phenolic compounds and aims to collect and correlate the reliable existing knowledge concerning their molecular mechanisms of action to counteract important risk factors that contribute to the initiation and development of atherosclerosis: dyslipidemia, and oxidative and inflammatory-stress. The selection of phenolic compounds was made to prove their multiple benefic effects and endorse them as CVD remedies, complementary to allopathic drugs. The review also highlights some aspects that still need clear scientific explanations and draws up some new molecular approaches to validate phenolic compounds for CVD complementary therapy in the near future.In the last decade the scientific researchers turned their attention to phytochemicals, as effective, safe and low-cost natural bioactive compounds for CVD treatment.Dyslipidemia consists of increased blood concentrations of total cholesterol (TC), low density lipoproteins-cholesterol (LDL-C) and/or triglycerides (TG), and decreased high density lipoproteins-cholesterol (HDL-C) [6]. The lipid metabolism is complex and the candidate mechanisms that could generate dyslipidemia include: (i) excessive dietary lipid absorption in the small intestine; (ii) packing of exogenous lipids with cholesterol and fatty acids produced de novo in the liver and their secretion as very low density lipoproteins (VLDL); (iii) hydrolysis of TG from VLDL by lipases and their conversion into LDL, which are taken up by the peripheral tissues through LDL receptor (LDL-R) and scavenger receptors; (iv) diminished production of HDL by the liver and small intestine, thereby decreasing reverse cholesterol transport (RCT) from the peripheral tissues to the liver; (v) lowered excess cholesterol excretion from the liver into gallbladder or to the intestinal lumen through the ATP-binding cassette G5 and G8 transporters (ABCG5/G8) that facilitate trans-intestinal cholesterol efflux (TICE). Dyslipidemia is associated with the accumulation of LDL in the sub-endothelium of the artery wall. At this site, LDL undergoes oxidative modifications (oxLDL) that trigger inflammatory responses, and is taken up by the monocyte-derived macrophages infiltrated in the sub-endothelium which thus become lipid-loaded foam cells, the hallmark of atheroma development [7]. Until now, the most effective lipid-lowering treatment for hyperlipidemic patients was the statin therapy. But recen...

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“…Although RES can prevent oxidative stress and inflammation, there is a disagreement regarding its beneficial effects on cardiovascular markers and endothelial dysfunction and in type 2 diabetes patients. The contrasting effects of RES reported in different studies could be explained in terms of different factors, including doses, administration medium and form, age, gender, health status of the intestinal microbiota and its pharmacokinetics [38]. The pharmacokinetic properties of RES are less acceptable and limit its success.…”

Section: Introductionmentioning

confidence: 99%

Liposomal Resveratrol and/or Carvedilol Attenuate Doxorubicin-Induced Cardiotoxicity by Modulating Inflammation, Oxidative Stress and S100A1 in Rats

et al. 2020

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Doxorubicin (DOX) is a cytotoxic anthracycline antibiotic and one of the important chemotherapeutic agents for different types of cancers. DOX treatment is associated with adverse effects, particularly cardiac dysfunction. This study examined the cardioprotective effects of carvedilol (CAR) and/or resveratrol (RES) and liposomal RES (LIPO-RES) against DOX-induced cardiomyopathy, pointing to their modulatory effect on oxidative stress, inflammation, S100A1 and sarco/endoplasmic reticulum calcium ATPase2a (SERCA2a). Rats received CAR (30 mg/kg) and/or RES (20 mg/kg) or LIPO-RES (20 mg/kg) for 6 weeks and were challenged with DOX (2 mg/kg) twice per week from week 2 to week 6. DOX-administered rats exhibited a significant increase in serum creatine kinase-MB (CK-MB), troponin-I and lactate dehydrogenase (LDH) along with histological alterations, reflecting cardiac cell injury. Cardiac toll-like receptor 4 (TLR-4), inducible nitric oxide synthase (iNOS), tumor necrosis factor (TNF)-α and interleukin (IL)-6 protein expression were up-regulated, and lipid peroxidation was increased in DOX-administered rats. Treatment with CAR, RES or LIPO-RES as well as their alternative combinations ameliorated all observed biochemical and histological alterations with the most potent effect exerted by CAR/LIPO-RES. All treatments increased cardiac antioxidants, and the expression of S100A1 and SERCA2a. In conclusion, the present study conferred new evidence on the protective effects of CAR and its combination with either RES or LIPO-RES on DOX-induced inflammation, oxidative stress and calcium dysregulation.

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Health Effects of Resveratrol: Results from Human Intervention Trials

Cited by 186 publications

References 65 publications

Potential Adverse Effects of Resveratrol: A Literature Review

Potential Adverse Effects of Resveratrol: A Literature Review

Phenolic Compounds Exerting Lipid-Regulatory, Anti-Inflammatory and Epigenetic Effects as Complementary Treatments in Cardiovascular Diseases

Liposomal Resveratrol and/or Carvedilol Attenuate Doxorubicin-Induced Cardiotoxicity by Modulating Inflammation, Oxidative Stress and S100A1 in Rats

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