Title | Abstract | NumCitations | Date | Authors | LinkToPaper |
The therapeutic potential of resveratrol: a review of clinical trials | Resveratrol is a nutraceutical with several therapeutic effects. It has been shown to mimic effects of caloric restriction, exert anti-inflammatory and anti-oxidative effects, and affect the initiation and progression of many diseases through several mechanisms. While there is a wealth of in vitro and in vivo evidence that resveratrol could be a promising therapeutic agent, clinical trials must confirm its potential. In this work, we reviewed the current clinical data available regarding the pharmacological action of resveratrol. Most of the clinical trials of resveratrol have focused on cancer, neurological disorders, cardiovascular diseases, diabetes, non-alcoholic fatty liver disease (NAFLD), and obesity. We found that for neurological disorders, cardiovascular diseases, and diabetes, the current clinical trials show that resveratrol was well tolerated and beneficially influenced disease biomarkers. However resveratrol had ambiguous and sometimes even detrimental effects in certain types of cancers and in NAFLD. In most of the clinical trials, the major obstacle presented was resveratrol’s poor bioavailability. Thus, this work provides useful considerations for the planning and design of future pre-clinical and clinical research on resveratrol. | 326 | 25 September 2017 | Adi Y. Berman, Rachel A. Motechin, Maia Y. Wiesenfeld & Marina K. Holz | https://www.nature.com/articles/s41698-017-0038-6 |
Resveratrol and health - A comprehensive review of human clinical trials | In the past decade, the small polyphenol resveratrol has received widespread attention as either a potential therapy or as a preventive agent for numerous diseases. Studies using purified enzymes, cultured cells, and laboratory animals have suggested that resveratrol has anti-aging, anti-carcinogenic, anti-inflammatory, and anti-oxidant properties that might be relevant to chronic diseases and/or longevity in humans. Although the supporting research in laboratory models is quite substantial, only recently data has emerged to describe the effects of resveratrol supplementation on physiological responses in humans. The limited number of human clinical trials that are available has largely described various aspects of resveratrol's safety and bioavailability, reaching a consensus that it is generally well-tolerated, but have poor bioavailability. Very few published human studies have explored the ability of resveratrol to achieve the physiological benefits that have been observed in laboratory models, although many clinical trials have recently been initiated. This review aims to examine the current state of knowledge on the effects of resveratrol on humans and to utilize this information to develop further guidelines for the implementation of human clinical trials. | 468 | August 2011 | James M Smoliga, Joseph A Baur, Heather A. Hausenblas | https://www.researchgate.net/publication/51233786_Resveratrol_and_health_-_A_comprehensive_review_of_human_clinical_trials |
Health benefits of resveratrol: Evidence from clinical studies | Resveratrol is a polyphenolic nutraceutical that exhibits pleiotropic activities in human subjects. The efficacy, safety, and pharmacokinetics of resveratrol have been documented in over 244 clinical trials, with an additional 27 clinical trials currently ongoing. Resveretrol is reported to potentially improve the therapeutic outcome in patients suffering from diabetes mellitus, obesity, colorectal cancer, breast cancer, multiple myeloma, metabolic syndrome, hypertension, Alzheimer's disease, stroke, cardiovascular diseases, kidney diseases, inflammatory diseases, and rhinopharyngitis. The polyphenol is reported to be safe at doses up to 5 g/d, when used either alone or as a combination therapy. The molecular basis for the pleiotropic activities of resveratrol are based on its ability to modulate multiple cell signaling molecules such as cytokines, caspases, matrix metalloproteinases, Wnt, nuclear factor-κB, Notch, 5′-AMP-activated protein kinase, intercellular adhesion molecule, vascular cell adhesion molecule, sirtuin type 1, peroxisome proliferator-activated receptor-γ coactivator 1α, insulin-like growth factor 1, insulin-like growth factor-binding protein 3, Ras association domain family 1α, pAkt, vascular endothelial growth factor, cyclooxygenase 2, nuclear factor erythroid 2 like 2, and Kelch-like ECH–associated protein 1. Although the clinical utility of resveratrol is well documented, the rapid metabolism and poor bioavailability have limited its therapeutic use. In this regard, the recently produced micronized resveratrol formulation called SRT501, shows promise. This review discusses the currently available clinical data on resveratrol in the prevention, management, and treatment of various diseases and disorders. Based on the current evidence, the potential utility of this molecule in the clinic is discussed. | 123 | 11 February 2019 | Akhand Pratap Singh,Rachna Singh,Sumit Singh Verma,Vipin Rai,Catherine H. Kaschula,Pralay Maiti,Subash Chandra Gupta | https://onlinelibrary.wiley.com/doi/abs/10.1002/med.21565 |
Resveratrol | Polyphenols are the secondary metabolites of plants and has an important role in human nutrition as the leading antioxidants. According to the carbon number-based classification of polyphenols, resveratrol is a natural polyphenol in the stilbene group with antioxidant and anticarcinogenic effects. Its beneficial effects on cardiovascular diseases have also been reported. It was first identified in 1940 and has recently gained importance especially in medicine and pharmacy. Researchers have carried out various studies on resveratrol and its time-honored use in traditional eastern medicine has also been reported. The study focuses on resveratrol's physical properties, effects on health and use in foods as a functional component. | 35 | 21 September 2019 | Ayla Arslaner, Zehra Türkoğlu | https://www.researchgate.net/publication/338344536_Resveratrol |
Recent Advances in the Study on Resveratrol | Appropriate long-term drinking of red wine is associated with a reduced risk for lifestyle-related diseases such as cardiovascular disease and cancer, making resveratrol, a constituent of grapes and various other plants, an attractive compound to be studied. Historically, resveratrol has been identified as a phytoalexin, antioxidant, cyclooxygenase (COX) inhibitor, peroxisome proliferator-activated receptor (PPAR) activator, endothelial nitric oxide synthase (eNOS) inducer, silent mating type information regulation 2 homolog 1 (SIRT1) activator, and more. Despite scepticism concerning the biological availability of resveratrol, a growing body of in vivo evidence indicates that resveratrol has protective effects in several stress and disease models. Here, we provide a review of the studies on resveratrol, especially with respect to COX, PPAR, and eNOS activities, and discuss its potential for promoting human health. | 143 | March 2012 | Rieko Nakata, Satoru Takahashi, Hiroyasu Inoue | https://www.researchgate.net/publication/221881022_Recent_Advances_in_the_Study_on_Resveratrol |
Resveratrol:A review of plant sources, synthesis, stability, modification and food application | Resveratrol, a stilbene molecule belonging to the polyphenol family, is usually extracted from a great many natural plants. The technologies of preparation and extraction methods are developing rapidly in resveratrol. As resveratrol has many beneficial properties, it has been widely utilized in food and medicine industry. In terms of its structure, resveratrol is susceptible to degradation and can undergo chemical changes during food processing. Therefore, different studies have paid more attention to various aspects of resveratrol, including anti‐aging, anti‐oxidant and anti‐cancer activity. This review not only classifies the study of resveratrol from plant sources, synthesis, stability, and common reaction as well as food application, but also provides references to boost its food and medical utilization. This article is protected by copyright. All rights reserved. | 73 | November 2019 | Bing Ren Tian, Jiayue Liu | https://www.researchgate.net/publication/337454176_ResveratrolA_review_of_plant_sources_synthesis_stability_modification_and_food_application |
Resveratrol: Twenty Years of Growth, Development and Controversy | Resveratrol was first isolated in 1939 by Takaoka from Veratrum grandiflorum O. Loes. Following this discovery, sporadic descriptive reports appeared in the literature. However, spurred by our seminal paper published nearly 60 years later, resveratrol became a household word and the subject of extensive investigation. Now, in addition to appearing in over 20,000 research papers, resveratrol has inspired monographs, conferences, symposia, patents, chemical derivatives, etc. In addition, dietary supplements are marketed under various tradenames. Once resveratrol was brought to the limelight, early research tended to focus on pharmacological activities related to the cardiovascular system, inflammation, and cancer but, over the years, the horizon greatly expanded. Around 130 human clinical trials have been (or are being) conducted with varying results. This may be due to factors such as disparate doses (ca. 5 to 5,000 mg/day) and variable experimental settings. Further, molecular targets are numerous and a dominant mechanism is elusive or nonexistent. In this context, the compound is overtly promiscuous. Nonetheless, since the safety profile is pristine, and use as a dietary supplement is prevalent, these features are not viewed as detrimental. Given the ongoing history of resveratrol, it is reasonable to advocate for additional development and further clinical investigation. Topical preparations seem especially promising, as do conditions that can respond to anti-inflammatory action and/or direct exposure, such as colon cancer prevention. Although the ultimate fate of resveratrol remains an open question, thus far, the compound has inspired innovative scientific concepts and enhanced public awareness of preventative health care. | 56 | October 2018 | John M. Pezzuto | researchgate.net/publication/328358138_Resveratrol_Twenty_Years_of_Growth_Development_and_Controversy |
Resveratrol supplementation: Where are we now and where should we go? | Pre-clinical findings have provided mounting evidence that resveratrol, a dietary polyphenol, may con-fer health benefits and protect against a variety of medical conditions and age-related complications.However, there is no consistent evidence of an increased protection against metabolic disorders andother ailments when comparing studies in laboratory animals and humans. A number of extraneous andpotential confounding variables can affect the outcome of clinical research. To date, most of the studiesthat have investigated the effect of resveratrol administration on patient outcomes have been limitedby their sample sizes. In this review, we will survey the latest advances regarding the timing, dosage,formulation, bioavailability, toxicity of resveratrol, and resveratrol–drug interactions in human studies.Moreover, the present report focuses on the actions of resveratrol treatment in combating diseases, suchas cancer, diabetes, neurodegeneration, cardiovascular disease, and other age-related ailments. | 170 | January 2015 | Marta Garrido Novelle, Devin Wahl, Carlos Dieguez, Michel Bernier, Rafael de Cabo | https://www.researchgate.net/publication/271384262_Resveratrol_supplementation_Where_are_we_now_and_where_should_we_go |
Resveratrol: Review on therapeutic potential and recent advances in drug delivery | Introduction: Natural products have seen a wide range of acceptability for the prevention and treatment of diseases throughout history. Resveratrol, a member of the stilbene family, has been found to potentially exhibit anticancer, antiangiogenic, immunomodulatory and cardioprotective activities as well as being an antioxidant. This is in addition to its usefulness in the treatment of neurodegenerative disease, diabetes and cardiac ailments. Currently, various studies have revealed that resveratrol is a potential drug candidate with multi-spectrum therapeutic application. Areas covered: This review aims to describe the various studies supporting the wide range of pharmacological activities of resveratrol. In addition, it includes a section devoted to discussing the challenges associated with the drug and strategies to improve the properties of resveratrol such as solubility, stability and bioavailability. Expert opinion: Resveratrol demonstrated its ability to be a potential drug candidate for the treatment of different ailments due to its potent antioxidant properties. To improve the drug stability, increase the bioavailability and minimize side-effects of resveratrol, novel drug delivery systems have been formulated to bring this potential candidate to the first line of disease treatment. | 193 | May 2014 | Rudra Pangeni, Jasjeet Sahni, Javed Ali, Shrestha Sharma, Sanjula Baboota | https://www.researchgate.net/publication/262385093_Resveratrol_Review_on_therapeutic_potential_and_recent_advances_in_drug_delivery |
Resveratrol bioavailability and toxicity in humans | Numerous data are now available on the beneficial properties of the polyphenolic compound resveratrol including its anti-inflammatory and antitumor effects. However, few studies have been performed with resveratrol in humans, and the results of these studies appear fragmentary and sometimes contradictory due to variations in conditions of administration, protocols and methods of assessment. This review article presents the results of recent studies investigating the pharmacokinetics, bioavailability, and toxicity of resveratrol in humans. Resveratrol is well absorbed, rapidly metabolized, mainly into sulfo and glucuronides conjugates which are eliminated in urine. Resveratrol seems to be well tolerated and no marked toxicity was reported. These data are important in the context of human efficacy studies, and they provide further support for the use of resveratrol as a pharmacological drug in human medicine. | 444 | December 2009 | Charles-Henry Cottart, Valérie Nivet-Antoine, Christelle laguillier-morizot, Jean-Louis Beaudeux | https://www.researchgate.net/publication/40691272_Resveratrol_bioavailability_and_toxicity_in_humans |
Health benefits of resveratrol: Evidence from clinical studies | 137 | February 2019 | Akhand Pratap Singh, Rachna Singh, Sumit Singh Verma, Vipin Rai, Catherine Kaschula, Pralay Maiti, Subash Chandra Gupta | https://www.researchgate.net/publication/331030445_Health_benefits_of_resveratrol_Evidence_from_clinical_studies | |
Bioavailability of resveratrol: Possibilities for enhancement | Resveratrol is a naturally occurring polyphenol that has been shown to elicit a variety of beneficial effects in vitro. Translating these gains to in vivo and clinical settings has proven to be a major challenge, because of its poor oral bioavailability. This caveat was confirmed after reviewing clinical trials conducted on this investigational product over the past two years. This review provides alternative methods of administration of resveratrol which may enhance its bioavailability. However, these methods remain to be validated. | 39 | September 2017 | Konrad de Vries, Morné A Strydom, Vanessa Steenkamp | https://www.researchgate.net/publication/319658546_Bioavailability_of_resveratrol_Possibilities_for_enhancement |
The Pharmacology of Resveratrol in Animals and Humans. | In addition to thousands of research papers related to resveratrol (RSV), approximated 300 review articles have been published. Earlier research tended to focus on pharmacological activities of RSV related to cardiovascular systems, inflammation, and carcinogenesis/cancer development. More recently, the horizon has been broadened by exploring the potential effect of RSV on the aging process, diabetes, neurological dysfunction, etc. Herein, we primarily focus on the in vivo pharmacological effects of RSV reported over the past 5 years (2009-2014). In addition, recent clinical intervention studies performed with resveratrol are summarized. Some discrepancies exist between in vivo studies with animals and clinical studies, or between clinical studies, which are likely due to disparate doses of RSV, experimental settings, and subject variation. Nevertheless, many positive indications have been reported with mammals, so it is reasonable to advocate for the conduct of more definitive clinical studies. Since the safety profile is pristine, an added advantage is the use of RSV as a dietary supplement. This article is part of a Special Issue entitled: Resveratol: Challenges in translating pre-clincial findigns to iproved patient outcomes. Copyright © 2015. Published by Elsevier B.V. | 197 | January 2015 | Eun-Jung Park, John M Pezzuto | https://www.researchgate.net/publication/272074007_The_Pharmacology_of_Resveratrol_in_Animals_and_Humans |
Administration of resveratrol: What formulation solutions to bioavailability limitations? | Resveratrol (3,5,4'-trihydroxystilbene), a naturally occurring polyphenol, has attracted considerable interest for its beneficial potentials for human health, which include anti-oxidant, anti-inflammatory, cardioprotective and anti-tumor activities. However, the in vivo biological effects of resveratrol appear strongly limited by its low bioavailability, which is a barrier to the development of therapeutic applications. In this context, an increasing number of recent studies have aimed at designing novel resveratrol formulations to overcome its poor solubility, limited stability, high metabolization and weak bioavailability. This review outlines physicochemical and pharmacokinetic limitations to resveratrol bioavailability, describes formulations tested for resveratrol administration, controlled release and targeting, and identifies future opportunities for resveratrol delivery. | 440 | March 2012 | Ahmed Amri, Jean-Claude Chaumeil, Souad Sfar, C Charrueau | https://www.researchgate.net/publication/51705396_Administration_of_resveratrol_What_formulation_solutions_to_bioavailability_limitations |
The effect of resveratrol on longevity across species: A meta-analysis | Resveratrol has shown evidence of decreasing cancer incidence, heart disease, metabolic syndrome and neural degeneration in animal studies. However, the effects on longevity are mixed. We aimed to quantify the current knowledge of life extension from resveratrol. We used meta-analytic techniques to assess the effect resveratrol has on survival, using data from 19 published papers, including six species: yeast, nematodes, mice, fruitflies, Mexican fruitflies and turquoise killifish. Overall, our results indicate that resveratrol acts as a life-extending agent. The effect is most potent in yeast and nematodes, with diminished reliability in most higher-order species. Turquoise killifish were especially sensitive to life-extending effects of resveratrol but showed much variation. Much of the considerable heterogeneity in our analysis was owing to unexplained variation between studies. In summary, we can report that few species conclusively show life extension in response to resveratrol. As such, we question the practice of the substance being marketed as a life-extending health supplement for humans. | 53 | June 2012 | Katie Hector, Malgorzata Lagisz, Shinichi Nakagawa | https://www.researchgate.net/publication/227710963_The_effect_of_resveratrol_on_longevity_across_species_A_meta-analysis |
Therapeutic effect of resveratrol supplementation on oxidative stress: a systematic review and meta-analysis of randomised controlled trials | Background Resveratrol is a naturally occurring polyphenol compound mainly found in grapes and red wine. The evidence has suggested that resveratrol has an antioxidant effect. However, the results are inconsistent and inconclusive. Thus, we conducted a systematic review and meta-analysis to evaluate the effect of resveratrol supplementation on markers of oxidative stress. Methods We searched PubMed, ISI Web of Science, EMBASE, Scopus and the Cochrane library up to December 2018 to identify randomised controlled trials (RCTs) assessing resveratrol supplementation effects on oxidative markers. Heterogeneity, publication bias, risk of bias and subgroup analysis were analysed. This meta-analysis was conducted in accordance with the guidelines of the Preferred ReportingItems for Systematic Reviews and Meta-Analysis (PRISMA). Results Meta-analysis of data from 12 RCTs did not support significant effect of resveratrol supplementation on circulating levels of superoxide dismutase (SOD) (standardized mean difference (SMD) (1.12), (95% CI −0.91 to 3.1), p=0.28), catalase (CAT) (SMD (−0.07), (95% CI −1.4 to 1.3), p=0.92) and glutathione peroxidase (GPx) (SMD (−0.76), (95% CI −2.56 to 1.04), p=0.40). Although, resveratrol supplementation increased significantly circulating total antioxidant capacity (TAC) concentrations (SMD (0.52), (95% CI −0.02 to 1.07), p=0.05). Severe heterogeneity was observed between studies, and no obvious publication bias was observed in included RCTs. Conclusion Collectively, our findings of available RCTs did no show any benefit of resveratrol supplementation on SOD, CAT and GPx except for TAC. Well-designed RCTs are necessary to confirm these results. | 7 | October 2019 | Mehdi Koushki, Mostafa Lakzaei, Hadi Khodabandehloo, Hossein Hosseini, Reza Meshkani, Ghodratollah Panahi | https://www.researchgate.net/publication/336655759_Therapeutic_effect_of_resveratrol_supplementation_on_oxidative_stress_a_systematic_review_and_meta-analysis_of_randomised_controlled_trials |
A Systematic Review on Natural Antioxidant Properties of Resveratrol | Polyphenols, including anthocyanins, flavonoids and stilbenes, which constitute one of the most abundant and ubiquitous groups of plant metabolites, are an integral part of the human diet. Resveratrol (3,5,4’-trihydroxystilbene), a naturally occurring polyphenol produced by some plants as a self-defence agent, has an antifungal activity. Resveratrol has been found in some plants (such as grapevine, pine and peanuts) and is considered to have beneficial effects also on human health. The number of studies on resveratrol greatly increased in PubMed database since 1997, after the anticancer effect of this molecule was first reported. The interest in resveratrol in grape was originally sparked by epidemiological studies indicating an inverse relationship between long-standing moderate consumption of red wine and the risk of coronary heart disease; this effect has been ascribed to resveratrol, which possesses diverse biochemical and physiological properties, including antiplatelet and anti-inflammatory proprieties, and provides a wide range of health benefits ranging from chemoprevention to cardioprotection. Recently, resveratrol has been described as an anti-aging compound. The consumption of resveratrol (red wine) together with a Mediterranean diet or a fast-food meal (“McDonald’sMeal”) had a positive impact on oxidized (ox-) LDL and on the expression of oxidative and inflammatory genes. Therefore, this review summarized the most important scientific data about healing and preventive potential of resveratrol, acting as cardioprotective, neuroprotective, chemopreventive and antioxidant agent. | 24 | September 2018 | Carmela Colica, Maja Milanović, Natasa Milic, Vincenzo Aiello, Antonino De Lorenzo, Ludovico Abenavoli | https://www.researchgate.net/publication/327800506_A_Systematic_Review_on_Natural_Antioxidant_Properties_of_Resveratrol |
Advances in resveratrol studies | Resveratrol is a naturally occurring stilbene, a kind of polyphenolic compounds, found in a limited number of plant species such as grape, peanut, and pine. It has been considered as a phytoalexin in plants, and many studies have also shown its health benefits such as antioxidant activities, cancer prevention, blood thinning, and life span extension. This paper reviews the characteristics of resveratrol in aspects of synthesis, extraction, purification, and determination. In particular, the new outcomes of physiology function and the transgenic approaches have been presented. The challenges and chances for genetic engineering and health-related industries were also discussed. | 6 | December 2008 | Jingjing Han, Wei Liu, Yuping Bi | https://www.researchgate.net/publication/24172679_Advances_in_resveratrol_studies |
Resveratrol: A Double-Edged Sword in Health Benefits | 300 | September 2018 | Bahare Salehi, Abhay Mishra, Manisha Nigam, Bilge Sener, Mehtap Kılıç, Mehdi Sharifi-Rad, Patrick Valere Tsouh Fokou, Natália Cruz-Martins, Javad Sharifi-Rad | https://www.researchgate.net/publication/327513592_Resveratrol_A_Double-Edged_Sword_in_Health_Benefitss |