No beneficial effects of resveratrol supplementation on atherogenic risk factors in patients with nonalcoholic fatty liver disease
Abstract
Abstract.Introduction: Cardiovascular disease (CVD) accounts as a major cause of mortality among patients with nonalcoholic fatty liver disease (NAFLD). Resveratrol, a natural polyphenol compound, is known for its antioxidant and antiatherogenic properties and is purported to be beneficial in decreasing CVD risk factors in NAFLD patients. Objectives: This study aimed to investigate the effects of resveratrol on atherogenic risk factors in patients with NAFLD.
Methods: This randomized, double-blind, placebo-controlled clinical trial was performed on 50 patients with NAFLD aged 20-60 years. Subjects were randomly assigned to receive a daily dose of 600 mg resveratrol (n = 25) or placebo (n = 25) for 12 wk. Serum liver enzymes, lipid profile and atherogenic indices, blood pressure and anthropometric values were assessed pre and post-treatment.
Results: Resveratrol supplementation reduced body weight (from 88.75 ± 11.41 to 87.54 ± 11.18 kg, P = 0.005) and BMI (from 31.00 ± 3.16 to 30.60 ± 3.26 kg/m², P = 0.01) significantly compared to the placebo group. A significant reduction in waist circumference was observed within resveratrol group (from 102.70 ± 7.68 to 101.39 ± 7.62 cm, P = 0.02). There were no significant changes in lipid profile (ox-LDL, ApoA1 and ApoB), serum atherogenic indices (LDL-C/HDL-C, ApoB/ApoA1, ox-LDL/ApoB, LDL-C/ox-LDL and AIP), liver enzymes (AST, ALT, ALP and GGT), hip circumference, waist-to-hip ratio and blood pressure in either group (P > 0.05 for all).
Conclusion: These findings indicated that resveratrol supplementation in dose and duration used in this study did not affect most of the CVD risk factors in NAFLD patients. Further studies are warranted to explain more effects of resveratrol on CVD complications of NAFLD.
Registration ID in IRCT: IRCT201511233664N16
References
1 (2011) Atherogenic dyslipidemia and cardiovascular risk in children with nonalcoholic fatty liver disease 2. Clin. Lipidol. 6, 305–314.
2 (2011) Meta-analysis: natural history of non-alcoholic fatty liver disease (NAFLD) and diagnostic accuracy of non-invasive tests for liver disease severity. Ann. Med. 43, 617–649.
3 (2016) Evidence that non-alcoholic fatty liver disease and polycystic ovary syndrome are associated by necessity rather than chance: a novel hepato-ovarian axis? Endocrine. 51, 211–221.
4 (2015) Cardiovascular disease risk assessment in diabetes and metabolic syndrome patients with and without non-alcoholic fatty liver disease. Int. J. Clin. Trials. 2, 91–96.
5 (2017) Prevalence of Nonalcoholic Fatty Liver Disease and its Related Metabolic Risk Factors in Isfahan, Iran. Adv. Biomed. Res. 6, 47.
6 (2016) NAFLD and liver transplantation: Current burden and expected challenges. J. Hepatol. 65, 1245–1257.
7 (2013) Non alcoholic fatty liverdisease in southern Iran: a population based study. Hepat. Mon. 13.
8 (2015) The effects of resveratrol supplementation on cardiovascular risk factors in patients with non-alcoholic fatty liver disease: a randomised, double-blind, placebo-controlled study. Br. J. Nutr. 114, 796–803.
9 (2015) NAFLD: a multisystem disease. J. Hepatol. 62, S47–S64.
10 (2013) Cardiovascular and systemic risk in nonalcoholic fatty liver disease-atherosclerosis as a major player in the natural course of NAFLD. Curr. Pharm. Des. 19, 5177–5192.
11 (2016) Non-alcoholic fatty liver disease and risk of cardiovascular disease. Metabolism. 65, 1136–1150.
12 (2010) Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N. Engl. J. Med. 362, 1675–1685.
13 (2012) The effects of long-term melatonin treatment on plasma liver enzymes levels and plasma concentrations of lipids and melatonin in patients with nonalcoholic steatohepatitis: a pilot study. J. Physiol. Pharmacol. 63, 35.
14 (2012) The diagnosis and management of non‐alcoholic fatty liver disease: Practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology. 55, 2005–2023.
15 (2014) Nonalcoholic fatty liver disease: a comprehensive review of a growing epidemic. World J. Gastroenterol. 20, 12082–12101.
16 (2011) Current therapies for nonalcoholic fatty liver disease. Drugs. Today (Barc). 47, 915–922.
17 (2014) Non-alcoholic fatty liver disease: what has changed in the treatment since the beginning? World J. Gastroenterol. 20, 14219–14229.
18 (2010) Resveratrol, sirtuins, and the promise of a DR mimetic. Mech. Ageing Dev. 131, 261–269.
19 (2011) Distinct effects of calorie restriction and resveratrol on diet-induced obesity and fatty liver formation. J. Nutr. Metab. 2011.
20 (2011) Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans. Cell Metab. 14, 612–622.
21 (2014) Weight loss in nonalcoholic Fatty liver disease patients in an ambulatory care setting is largely unsuccessful but correlates with frequency of clinic visits. PloS One. 9, e111808.
22 (2015) A systematic review of the efficacy of bioactive compounds in cardiovascular disease: carbohydrates, active lipids and nitrogen compounds. Ann. Nutr. Metab. 66, 168–181.
23 (2013) Resveratrol and clinical trials: the crossroad from in vitro studies to human evidence. Curr. Pharm. Des. 19, 6064–6093.
24 (2012) Resveratrol: French paradox revisited. Front Pharmacol. 3
25 (2013) Resveratrol: botanical origin, pharmacological activity and applications. C. J. N. M. 11, 1–15.
26 (2012) Consumption of a grape extract supplement containing resveratrol decreases oxidized LDL and ApoB in patients undergoing primary prevention of cardiovascular disease: A triple‐blind, 6‐month follow‐up, placebo‐controlled, randomized trial. Mol. Nutr. Food Res. 56, 810–821.
27 (2011) Resveratrol improves insulin sensitivity, reduces oxidative stress and activates the Akt pathway in type 2 diabetic patients. Br. J. Nutr. 106, 383–389.
28 (2012) Resveratrol attenuates steatosis in obese Zucker rats by decreasing fatty acid availability and reducing oxidative stress. Br. J. Nutr. 107, 202–210.
29 (2011) Resveratrol exerts anti-obesity effects via mechanisms involving down-regulation of adipogenic and inflammatory processes in mice. Biochem. Pharmacol. 81, 1343–1351.
30 (2014) Effects of resveratrol and other polyphenols in hepatic steatosis. World J. Gastroenterol. 20, 7366–7380.
31 (2014) Resveratrol attenuates hepatic steatosis in high-fat fed mice by decreasing lipogenesis and inflammation. Nutrition. 30, 915–919.
32 (2014) Resveratrol use in metabolic syndrome. Metab. Syndr. Relat. Disord. 12, 493–496.
33 (2014) Resveratrol and pharmacological potentiation in ischemic stroke. Neurosurgery. 74, N17–N18.
34 (2014) Potential of resveratrol in the treatment of heart failure. Life Sci. 95, 63–71.
35 (2014) Characterization of a novel multifunctional resveratrol derivative for the treatment of atrial fibrillation. Br. J. Pharmacol. 171, 92–106.
36 (2015) Resveratrol supplementation: where are we now and where should we go? Ageing Res. Rev. 21, 1–15.
37 (2015) Resveratrol improves insulin resistance, glucose and lipid metabolism in patients with non-alcoholic fatty liver disease: a randomized controlled trial. Dig. Liver Dis. 47, 226–232.
38 (2014) Resveratrol does not benefit patients with nonalcoholic fatty liver disease. Clin. Gastroenterol. Hepatol. 12, 2092–2103.
39 (2016) Placebo-controlled, randomised clinical trial: high-dose resveratrol treatment for non-alcoholic fatty liver disease. Scand. J. Gastroenterol. 51, 456–464.
40 (2014) The use of guideline images to improve histological estimation of hepatic steatosis. Liver Int. 34, 1414–1427.
41 (2012) The Iranian Version of International Physical Activity Questionnaire (IPAQ) in Iran: content and construct validity, factor structure, internal consistency and stability. World. Appl. Sci. J. 18, 1073–1080.
42 (1972) Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin. Chem. 18, 499–502.
43 (2014) Nonalcoholic fatty liver disease and cardiovascular disease. World J. Gastroenterol. 20, 8407–8415.
44 (2013) Use of atherogenic index of plasma in evaluating the potential cardioprotective effects of red wine consumption: Studies in Nigerian young adult volunteers. Biokemistri. 25, 118–123.
45 (2016) The associations between apolipoprotein B, A1, and the B/A1 ratio and nonalcoholic fatty liver disease in both normal-weight and overweight Korean population. J. Clin. Lipidol. 10, 289–298.
46 (2014) Resveratrol and cardiovascular health–promising therapeutic or hopeless illusion? Pharmacol. Res. 90, 88–115.
47 (2014) Resveratrol suppresses oxidised low-density lipoprotein-induced macrophage apoptosis through inhibition of intracellular reactive oxygen species generation, LOX-1, and the p38 MAPK pathway. Cell. Physiol. Biochem. 34, 603–616.
48 (2010) Resveratrol and cardiovascular health. Mol. Aspects Med. 31, 503–512.
49 (2013) Antioxidant effects of resveratrol in cardiovascular, cerebral and metabolic diseases. Food Chem. Toxicol. 61, 215–226.
50 (2015) Oxidative stress: New insights on the association of non-alcoholic fatty liver disease and atherosclerosis. World J. Hepatol. 7, 1325–1336.
51 (2014) Antioxidant properties of resveratrol and its protective effects in neurodegenerative diseases. Adv. Cell. Biol. 4, 97–117.
52 (2016) Appropriate LDL-C-to-HDL-C ratio cutoffs for categorization of cardiovascular disease risk factors among Uygur adults in Xinjiang, China. Int. J. Environ. Res. Public Health. 13, 235.
53 (2012) Atherogenic risk quantification by using the atherogenic index of plasma (AIP) and cardiovascular risk calculator on hypertensive patients. Med Con. 8, 29–36.
54 (2015) Inverse linear associations between liver aminotransferases and incident cardiovascular disease risk: the PREVEND study. Atherosclerosis. 243, 138–147.
55 (2014) Liver enzymes and risk of cardiovascular disease in the general population: a meta-analysis of prospective cohort studies. Atherosclerosis. 236, 7–17.
56 (2008) Aminotransferase levels and 20-year risk of metabolic syndrome, diabetes, and cardiovascular disease. Gastroenterology. 135, 1935–1944.
57 (2008) Liver enzymes and risk of diabetes and cardiovascular disease: results of the Firenze Bagno a Ripoli (FIBAR) study. Metabolism. 57, 387–392.
58 (2012) Serum alkaline phosphatase is a predictor of mortality, myocardial infarction, or stent thrombosis after implantation of coronary drug-eluting stent. Eur. Heart J. 34, 920–931.
59 (2012) Effect of age and gender on the relationship between alcohol consumption and serum GGT: time to recalibrate goals for normal ranges. Alcohol Alcohol. 47, 558–562.
60 (2016) Six months of resveratrol supplementation has no measurable effect in type 2 diabetic patients. A randomized, double blind, placebo-controlled trial. Pharmacol. Res. 1, 896–905.
61 (2016) The efficacy of resveratrol in controlling hypertension: study protocol for a randomized, crossover, double-blinded, placebo-controlled trial. Trials. 17, 296.
62 (2017) Serum concentrations and gene expression of sirtuin 1 in healthy and slightly overweight subjects after caloric restriction or resveratrol supplementation: A randomized trial. Int. J. Cardiol. 227, 788–794.
63 (2013) Non-alcoholic fatty liver disease (NAFLD); Study from western region of Tamil Nadu. J.C.E.H. 3, S25–S26.
64 (2014) Effect of resveratrol administration on metabolic syndrome, insulin sensitivity, and insulin secretion. Metab. Syndr. Relat. Disord. 12, 497–502.
65 (2013) In vivo and in vitro metabolism of trans-resveratrol by human gut microbiota. Am. J. Clin. Nutr. 97, 295–309.