What Is New for an Old Molecule? Systematic Review and Recommendations on the Use of Resveratrol

Vang, Ole; Ahmad, Nihal; Baile, Clifton A.; Baur, Joseph A.; Brown, Karen; Csiszár, Anna; Das, Dipak K.; Delmas, Dominique; Gottfried, Carmem; Lin, Hung-Yun; Ma, Qingyong; Mukhopadhyay, Partha; Nalini, Namasivayam; Pezzuto, John M.; Richard, Tristan; Shukla, Yogeshwer; Surh, Young‐Joon; Szekeres, Thomas; Szkudelski, Tomasz; Walle, Thomas; Wu, Joseph M.

doi:10.1371/journal.pone.0019881

Cited by 398 publications

(355 citation statements)

References 142 publications

(143 reference statements)

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“…This suggests that marked benefits may accrue from use of tRES-HESP coformulation. Safety assessments of tRES and HESP indicate that they are highly tolerated (19,20). Studies of human BJ fibroblasts in primary culture showed no toxicity of tRES and HESP individually or with 5 mmol/L combination with primary bioactive compound at concentrations #20 mmol/L.…”

Section: Diabetesdiabetesjournalsorgmentioning

confidence: 99%

“…We limited the small-molecule inducer screen to nontoxic dietary bioactive compounds of known or suspected Nrf2 activation activity to provide an option for use of Glo1 inducers as functional food supplements as well as pharmaceuticals. tRES and HESP also have a .50-fold safety margin at doses used in the HATFF study (19,20). Activation of Nrf2 by dietary bioactive compounds is mostly studied through ARE-linked induction of NQO1 or HMOX1 expression.…”

Section: (232%) [-]mentioning

confidence: 99%

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Improved Glycemic Control and Vascular Function in Overweight and Obese Subjects by Glyoxalase 1 Inducer Formulation

et al. 2016

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Risk of insulin resistance, impaired glycemic control, and cardiovascular disease is excessive in overweight and obese populations. We hypothesized that increasing expression of glyoxalase 1 (Glo1)-an enzyme that catalyzes the metabolism of reactive metabolite and glycating agent methylglyoxal-may improve metabolic and vascular health. Dietary bioactive compounds were screened for Glo1 inducer activity in a functional reporter assay, hits were confirmed in cell culture, and an optimized Glo1 inducer formulation was evaluated in a randomized, placebo-controlled crossover clinical trial in 29 overweight and obese subjects. We found trans-resveratrol (tRES) and hesperetin (HESP), at concentrations achieved clinically, synergized to increase Glo1 expression. In highly overweight subjects (BMI >27.5 kg/m 2 ), tRES-HESP coformulation increased expression and activity of Glo1 (27%, P < 0.05) and decreased plasma methylglyoxal (237%, P < 0.05) and total body methylglyoxal-protein glycation (214%, P < 0.01). It decreased fasting and postprandial plasma glucose (25%, P < 0.01, and 28%, P < 0.03, respectively), increased oral glucose insulin sensitivity index (42 mL $ min 21 $ m 22, P < 0.02), and improved arterial dilatation Dbrachial artery flowmediated dilatation/Ddilation response to glyceryl nitrate (95% CI 0.13-2.11). In all subjects, it decreased vascular inflammation marker soluble intercellular adhesion molecule-1 (210%, P < 0.01). In previous clinical evaluations, tRES and HESP individually were ineffective. tRES-HESP coformulation could be a suitable treatment for improved metabolic and vascular health in overweight and obese populations.

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Section: Diabetesdiabetesjournalsorgmentioning

confidence: 99%

Section: (232%) [-]mentioning

confidence: 99%

Improved Glycemic Control and Vascular Function in Overweight and Obese Subjects by Glyoxalase 1 Inducer Formulation

et al. 2016

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“…A full discussion of these issues is beyond the scope of this review, and has been attempted elsewhere (e.g. [21][22][23]). The complexity of resveratrol's effects in cells and in animals presents a major challenge in moving forward with human studies.…”

Section: Introductionmentioning

confidence: 99%

Resveratrol and health – A comprehensive review of human clinical trials

Smoliga

Baur

Hausenblas

2011

Molecular Nutrition Food Res

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502

308

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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.

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“…Resveratrol has shown evidence of decreasing cancer incidence, heart disease, metabolic syndrome and neural degeneration in animal studies [7]. As human clinical trials of resveratrol are now underway [7], it is high time to review the current state of knowledge regarding the life-extending properties of resveratrol. To our knowledge, this is the first quantitative review of resveratrol using rigorous meta-analytic methods.…”

Section: Introductionmentioning

confidence: 99%

The effect of resveratrol on longevity across species: a meta-analysis

2012

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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.

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What Is New for an Old Molecule? Systematic Review and Recommendations on the Use of Resveratrol

Cited by 398 publications

References 142 publications

Improved Glycemic Control and Vascular Function in Overweight and Obese Subjects by Glyoxalase 1 Inducer Formulation

Improved Glycemic Control and Vascular Function in Overweight and Obese Subjects by Glyoxalase 1 Inducer Formulation

Resveratrol and health – A comprehensive review of human clinical trials

The effect of resveratrol on longevity across species: a meta-analysis

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