Placebo-controlled, randomised clinical trial: high-dose resveratrol treatment for non-alcoholic fatty liver disease

Heebøll, Sara; Kreuzfeldt, Martin; Hamilton-Dutoit, Stephen; Poulsen, Mikael Kjær; Stødkilde-Jørgensen, Hans; Møller, Holger Jon; Jessen, Niels; Thorsen, Kasper; Hellberg, Ylva Kristina; Pedersen, Steen B.; Grønbæk, Henning

doi:10.3109/00365521.2015.1107620

Cited by 124 publications

(161 citation statements)

References 36 publications

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“…In contrast to these encouraging studies, another very recent, randomized, clinical trial from Denmark including 28 patients with overweight found no indication that RES treatment (1.5 g RES/day for 6 months) had any consistent therapeutic effects (63). In line, a recent systematic review and meta-analysis study published during the revision of the current review concluded that the current evidence was insufficient to support the efficacy of resveratrol in the management of NAFLD (64).…”

Section: Res As a Therapeutically Effective Drug In Human Liver Diseasecontrasting

confidence: 43%

Resveratrol: Is It Really Good for Liver Health?

Weiskirchen¹,

Weiskirchen²

2017

Hepat Mon

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Context: Resveratrol is a natural occurring stilbene present in a limited number of dietary food products and beverages. It is assumed that resveratrol has health-promoting effects by lowering low-density lipoprotein (LDL) cholesterol, improving microcirculation, and inhibiting platelet aggregation. Altogether, these beneficial effects lower the risk of cardiovascular disease. The "French paradox" assumes that a diet with moderate consumption of red wine lowers the risk of cancer and cardiovascular disease. Based on its healthful activities, a large number of studies were performed during the last decades investigating potential biological effects of resveratrol on liver homeostasis and its potential application as a hepatoprotective drug. Objectives: The current study aimed at discussing the proposed therapeutic attributes of resveratrol on liver health and its postulated mode of activity. Evidence Acquisition: To conduct the current study, the PubMed full-text archive depository for articles presenting data on resveratrol in liver health and disease was searched. Results: Out of the 9268 published articles on resveratrol, a total of 742 articles focused on liver. Among them, 352 articles investigated potential therapeutic activities. Although some of the reported in vitro and in vivo benefits of resveratrol were highly encouraging, well-designed clinical studies were missing. Conclusions: Presently, it is still premature to advise nutritional supplementation of resveratrol to cure hepatic diseases. Moreover, uncritical recommendation to drink wine as a liver health-promoting beverage should be avoided.

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Section: Res As a Therapeutically Effective Drug In Human Liver Diseasecontrasting

confidence: 43%

Resveratrol: Is It Really Good for Liver Health?

Weiskirchen¹,

Weiskirchen²

2017

Hepat Mon

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“…Two included RCTs showed a beneficial effect of resveratrol in comparison with the lifestyle modification alone [11,19]. In contrast, the other two RCTs reported that resveratrol has no consistent therapeutic benefit in the management of NAFLD [10,18]. We could not perform a further subgroup analysis based on patients' characteristics due to the unavailability of relevant data.…”

Section: Summary Of the Main Resultsmentioning

confidence: 99%

“…Among the four included RCTs, two trials included only overweight or obese patients diagnosed with NAFLD [10,18]. In two trials resveratrol was administrated at a dose of 300mg and 500mg for three months [11,19], in one study at a dose of 1500mg daily for six months [18], and in one study a dose of 3000mg daily was utilized and followed up the patients were followed-up only for two months [10].…”

Section: Characteristics Of Included Studiesmentioning

confidence: 99%

“…In two trials resveratrol was administrated at a dose of 300mg and 500mg for three months [11,19], in one study at a dose of 1500mg daily for six months [18], and in one study a dose of 3000mg daily was utilized and followed up the patients were followed-up only for two months [10]. One trial recommended a healthy diet and regular exercise for its participants [19], while the remaining trials asked their patients to maintain usual lifestyle and habitual dietary intake.…”

Section: Characteristics Of Included Studiesmentioning

confidence: 99%

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Resveratrol Supplementation in Patients with Non-Alcoholic Fatty Liver Disease: Systematic Review and Meta-analysis

Elgebaly¹,

Radwan²,

AboElnas³

et al. 2017

JGLD

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Background: Resveratrol is a potential treatment option for management of non-alcoholic fatty liver disease (NAFLD) due to its anti-inflammatory, antioxidant properties, and calorie restriction-like effects. We aimed to synthesise evidence from published randomized clinical trials (RCTs) about the efficacy of resveratrol in the management of NAFLD.Methods: A computer literature search of PubMed, Scopus, Web of Science, and Cochrane Central was conducted using relevant keywords. Records were screened for eligible studies and data were extracted and synthesized using Review Manager Version 5.3 for windows. Subgroup analysis and sensitivity analysis were conducted.Results: Four RCTs (n=158 patients) were included in the final analysis. The overall effect estimates did not favor resveratrol group in terms of: serum ALT (MD -2.89, 95%CI [-15.66, 9.88], p=0.66), serum AST (MD -3.59, 95%CI [-13.82, 6.63], p=0.49), weight (MD -0.18, 95%CI [-0.92, 0.55], p=0.63), BMI (MD -0.10, 95 %CI [-0.43, 0.24], p=0.57), blood glucose level (MD -0.27, 95%CI [-0.55, 0.01], p=0.05), insulin level (MD -0.12, 95%CI [-0.69, 0.46], p=0.69), triglyceride level (MD 0.04, 95%CI [-0.45, 0.53], p=0.87), and LDL level (MD 0.21, 95%CI [-0.41, 0.83], p=0.51). Pooled studies were heterogeneous.Conclusion: Current evidence is insufficient to support the efficacy of resveratrol in the management of NAFLD. Resveratrol does not attenuate the degree of liver fibrosis or show a significant decrease in any of its parameters.Abbreviations: ALT: Alanine aminotransferase; AMPK: AMP-activated protein kinase; AST: Aspartate aminotransferase; BMI: Body mass index; CK-18: Cytokeratin-18; CRP: C-reactive protein; HC: Head circumference; HDL: High density lipoprotein; IL-6: Interleukin-6; LDL: Low density lipoprotein; MD: Mean difference; NAFLD: Non-alcoholic fatty liver disease; NASH: Non-alcoholic steatohepatitis; RCT: Randomized Controlled Trial; RR: Relative risk; SIRT1: Silent information regulation 2 homologue 1; TNF-α: Tumor necrosis factor α; WC: Waist circumference; WHR: Waist hip ratio.

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“…Downregulated Sphk1 could ameliorate inflammatory response, glomerular, and interstitial fibrosis in AN, eventually delaying the progress of FSGS. In fact, several clinical trials have already reported that RSV consumption improved neurovascular coupling capacity in adults with type 2 diabetes mellitus [33], decreased oxidized LDL and ApoB in patients undergoing primary prevention of cardiovascular disease [34,] and could ameliorate liver function tests and liver fat accumulation in non-alcoholic fatty liver disease [35]. However, no reports revealed the therapeutic effect of RSV in alleviating clinical or histological FSGS.…”

Section: Discussionmentioning

confidence: 99%

Resveratrol Attenuates Adriamycin-Induced Focal Segmental Glomerulosclerosis through C3aR/C5aR- Sphingosine Kinase 1 Pathway

et al. 2017

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Background/Aim: Focal segmental glomerulosclerosis (FSGS) typically presents with nephrotic range proteinuria, which could eventually develop into end-stage renal disease. Resveratrol (RSV) is a natural polyphenol compound, which has been reported to suppress inflammatory response and renal interstitial fibrosis. This study is aimed at evaluating the renoprotective effect of RSV treatment on adriamycin-induced FSGS. Methods: In Balb/c mice, adriamycin nephropathy was induced by adriamycin (10 mg/kg body weight, diluted in normal saline) via a tail vein on day 0. Then the mice were treated with RSV (40 mg/kg body weight) once daily by oral gavage, again starting on the day of adriamycin injection and continued for 6 weeks. At 6 weeks, the mice were sacrificed; kidneys and blood samples were collected for further analysis. Results: When treated with adriamycin, the expressions of C3aR, C5aR, sphingosine kinase 1 (Sphk1), and soluble urokinase-type plasminogen activator receptor (suPAR) were upregulated, while RSV treatment could inhibit the expressions of C3aR, C5aR, Sphk1, and suPAR, eventually leading to anti-inflammatory and anti-fibrosis conditions. Conclusion: RSV attenuates adriamycin-induced FSGS through C3aR/C5aR-Sphk1 pathway.

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Placebo-controlled, randomised clinical trial: high-dose resveratrol treatment for non-alcoholic fatty liver disease

Abstract: In this placebo-controlled, high-dose and long-term study, resveratrol treatment had no consistent therapeutic effect in alleviating clinical or histological NAFLD, though there may be a small ameliorating effect on liver function tests and liver fat accumulation.

Cited by 124 publications

References 36 publications

Resveratrol: Is It Really Good for Liver Health?

Resveratrol: Is It Really Good for Liver Health?

Resveratrol Supplementation in Patients with Non-Alcoholic Fatty Liver Disease: Systematic Review and Meta-analysis

Resveratrol Attenuates Adriamycin-Induced Focal Segmental Glomerulosclerosis through C3aR/C5aR- Sphingosine Kinase 1 Pathway

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