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The effects of resveratrol supplementation on cardiovascular risk factors in patients with non-alcoholic fatty liver disease: a randomised, double-blind, placebo-controlled study
Open accessAbstract
Non-alcoholic fatty liver disease (NAFLD) is usually associated with insulin resistance, central obesity, reduced glucose tolerance, type 2 diabetes mellitus and hypertriacylglycerolaemia. The beneficial effects of resveratrol on metabolic disorders have been shown previously. The aim of this study was to evaluate the effects of resveratrol supplementation on cardiovascular risk factors in patients with NAFLD. In this randomised double-blinded placebo-controlled clinical trial, fifty NAFLD patients were supplemented with either a 500-mg resveratrol capsule or a placebo capsule for 12 weeks. Both groups were advised to follow an energy-balanced diet and physical activity recommendations. resveratrol supplementation reduced alanine aminotransferase (ALT) and hepatic steatosis significantly more than placebo (P0·05). There were no significant changes in blood pressure, insulin resistance markers and TAG in either group (P>0·05). Our data have shown that 12-week supplementation of 500 mg resveratrol does not have any beneficial effect on anthropometric measurements, insulin resistance markers, lipid profile and blood pressure; however, it reduced ALT and hepatic steatosis in patients with NAFLD.
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“Given that chronic hyperinsulinemia can stimulate an excessive production of androgens in PCOS women, the antiandrogenic effects of resveratrol are probably indirect and driven by the reduction of IR in these patients [141,142,143,144], in contrast to pharmacologic intervention with metformin [145,146].”
From Mediterranean diet nutrients to turn the tide against insulin resistance and related diseases (2020) · cites this paper as [143]
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“The supplementation of 500mg RSV for 12 weeks significantly decreased the alanine aminotransferase (ALT) concentration and hepatic steatosis in 50 NAFLD patients compared to the placebo (P < 0:05); however, no expected improvements in anthropometric measurements, insulin resistance (IR), lipid profile, and BP were obs…”
BackgroundYari, Z., Rahimlou, M., Eslamparast, T., Ebrahimi-Daryani, N., Poustchi, H., & Hekmatdoost, A. (2016) · International Journal of Food Sciences and Nutrition · doi:10.3109/09637486.2016.1161011 · Cited by 118
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“By contrast, a randomized control trial failed to show the beneficial role of resveratrol in glucose metabolism and lipid profile in higher doses, but not in the steatosis level (48).”
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“, 50 NAFLD patients were divided to receive lifestyle modification and placebo or 500 mg of resveratrol for 12 weeks and after the study period the treatment group had improved inflammatory cytokines, ALT, and hepatic steatosis compared to the placebo group [27,29].”
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“Another study investigated the effects of RSV supplementation (500mg for 12 weeks) on nonalcoholic fatty liver disease subjects [15].”
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“Other studies using the HOMA model have shown both unchanged(5,7,11) and improved(9,12,13) insulin sensitivity in type 2 diabetic individuals(12) and in overweight/obese individuals.(5,7,9,11,13) However,”
ResultDietary Composition and Cardiovascular Risk: A Mediator or a Bystander?
Korakas, E., Dimitriadis, G., Raptis, A. E., & Lambadiari, V. (2018) · Nutrients · doi:10.3390/nu10121912 · Cited by 48
“In studies with diabetic patients [136], healthy obese men [137], and healthy adult smokers [138], resveratrol showed beneficial effects on the lipid profile of the subjects, yet this result was achieved through the supplementation of high doses of resveratrol (250–1000, 150, and 500 mg/day, respectively), which canno…”
BackgroundFrendo‐Cumbo, S., MacPherson, R. E. K., & Wright, D. C. (2016) · Physiological Reports · doi:10.14814/phy2.12877 · Cited by 40
“15 | e12877 Page 9 RSV supplementation, especially in humans, has marginal effects on improving glucose homeostasis in conditions of pre-existing insulin resistance and obesity (Timmers et al. 2011; Yoshino et al. 2012; Faghihzadeh et al. 2015).”
BackgroundHypoglycemic Effect of Resveratrol: A Systematic Review and Meta-Analysis
García-Martínez, B. I., Ruíz-Ramos, M., Pedraza‐Chaverrí, J., Santiago‐Osorio, E., & Mendoza-Núñez, V. M. (2021) · Antioxidants · doi:10.3390/antiox10010069 · Cited by 38
“(2015) [32] RCT double-blind 500 mg/day 12 weeks 50 subjects with NAFLD 45 ± 10 Glucose and insulin levels, HOMA-IR, HOMA-β, QUICKI Non-significant changes after the resveratrol intervention”
BackgroundLiudvytska, O., & Kołodziejczyk-Czepas, J. (2022) · Nutrients · doi:10.3390/nu14102053 · Cited by 41
Therapeutic Potential of Resveratrol in Diabetic Nephropathy According to Molecular Signaling
Salami, M., Salami, R., Mafi, A., Aarabi, M. H., Vakili, O., & Asemi, Z. (2021) · Current Molecular Pharmacology · doi:10.2174/1874467215666211217122523 · Cited by 37
Zhou, Q., Wang, Y., Han, X., Fu, S., Zhu, C., & Chen, Q. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2022.795980 · Cited by 39
“It has been shown that lipid metabolism also influences modulation of inflammation and cytokine secretion (Glass and Olefsky, 2012; Kumar et al., 2014).”
BackgroundThe Effects of Onion Consumption on Prevention of Nonalcoholic Fatty Liver Disease
Emamat, H., Foroughi, F., Eini‐Zinab, H., & Hekmatdoost, A. (2017) · Indian Journal of Clinical Biochemistry · doi:10.1007/s12291-017-0636-7 · Cited by 35
Guo, X., Li, J., Tang, J., & Li, D. (2017) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2017.1349076 · Cited by 36
“…et al., 2011; Bhatt et al., 2012; Konno et al., 2013; Kumar and Joghee, 2013; Movahed et al., 2013; Faghihzadeh et al., 2014; Goh et al., 2014; Chen et al., 2015; Faghihzadeh et al., 2015; Samsami-Kor et al., 2015), 3 in South America (Mendez-del Villar et al., 2014; Macedo et al., 2015; Figure 1.”
BackgroundResultInfluentialEmamat, H., Foroughi, F., Eini‐Zinab, H., Taghizadeh, M., Rismanchi, M., & Hekmatdoost, A. (2015) · Journal of Diabetes & Metabolic Disorders · doi:10.1186/s40200-016-0248-4 · Cited by 34
“Although the beneficial role of diet and some dietary supplements on NAFLD treatment have been shown recently [3–9], no consensus has yet been achieved.”
BackgroundAmin‐Esmaeili, M., Rahimi‐Movaghar, A., Razaghi, E. M., Baghestani, A. R., & Jafari, S. (2012) · Hepatitis Monthly · doi:10.5812/kowsar.1735143x.806 · Cited by 33
Sangouni, A. A., Abdollahi, S., & Mozaffari–Khosravi, H. (2022) · BMC Cardiovascular Disorders · doi:10.1186/s12872-022-02637-2 · Cited by 32
Stadler, J. T., & Marsche, G. (2021) · Frontiers in Nutrition · doi:10.3389/fnut.2021.761170 · Cited by 35
Gartziandia, O., Lasa, A., Pedraz, J. L., Miranda, J., Portillo, M. P., Igartúa, M., & Hernández, R. M. (2018) · Molecules · doi:10.3390/molecules23081886 · Cited by 28
Alanazi, A. Z., Alqinyah, M., Alhamed, A. S., Mohammed, H., Raish, M., Aljerian, K., Alsabhan, J. F., & Alhazzani, K. (2024) · Redox Report · doi:10.1080/13510002.2024.2416835 · Cited by 26
“Resveratrol reduces inflammatory cytokines, inhibits NF-κB activation, and ameliorates diabetic renal, retinal, neural, and vascular injury [16].”
BackgroundBeneficial Effects of Plant-Derived Natural Products on Non-alcoholic Fatty Liver Disease
Simental‐Mendía, L. E., Gamboa‐Gómez, C. I., Guerrero‐Romero, F., Simental-Mendía, M. A., Sánchez‐García, A., & Rodríguez-Ramírez, M. (2021) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-64872-5_18 · Cited by 26
Resveratrol Metabolites Are Able to Reduce Steatosis in Cultured Hepatocytes
Trepiana, J., Krisa, S., Renouf, E., & Portillo, M. P. (2020) · Pharmaceuticals · doi:10.3390/ph13100285 · Cited by 27
Ferro, Y., Pujia, R., Mazza, E., Lascala, L., Lodari, O., Maurotti, S., Pujia, A., & Montalcini, T. (2022) · Journal of Translational Medicine · doi:10.1186/s12967-022-03579-1 · Cited by 25
“As shown in several clinical and preclinical studies, some nutraceuticals in NAFLD exert their beneficial effects in the early stage (due to the antiinflammatory, antioxidant therapeutic properties) while others acts in the late stage of the disease (due to the antifibrotic properties, especially in individuals with s…”
Backgroundxu, X., Liu, Q., Li, J., Xiao, M., Gao, T., Zhang, X., Lu, G., Wang, J., Guo, Y., Wen, P., et al. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.940406 · Cited by 25
Arbizu, S., Mertens‐Talcott, S. U., Talcott, S. T., & Noratto, G. D. (2023) · Nutrients · doi:10.3390/nu15030681 · Cited by 26
“Another clinical study reported significant reductions of ALT in NAFLD patients after a 12-week consumption of resveratrol (500 mg/day) [61].”
BackgroundCurrent strategies for nonalcoholic fatty liver disease treatment (Review)
Sun, J., Jin, X., & Li, Y. (2024) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2024.5412 · Cited by 27
“The blood fat, hepatic steatosis, hepatic apoptosis, liver function, insulin sensitivity and insulin metabolism of patients with NAFLd were ameliorated after supplementa‑ tion of resveratrol (98,100).”
BackgroundAskari, G., Aghajani, M., Salehi, M., Najafgholizadeh, A., Keshavarzpour, Z., Fadel, A., Venkatakrishnan, K., Salehi‐Sahlabadi, A., Hadi, A., & Pourmasoumi, M. (2020) · Journal of Herbal Medicine · doi:10.1016/j.hermed.2020.100364 · Cited by 26
Murugan, D. D., Balan, D., & Wong, P. (2021) · Phytotherapy Research · doi:10.1002/ptr.7205 · Cited by 24
Sergi, C. M., Chiu, B., Feulefack, J., Shen, F., & Chiu, B. (2020) · Archives of Medical Science - Atherosclerotic Diseases · doi:10.5114/amsad.2020.95884 · Cited by 23
“Faghihzadeh [71] (2015), Iran P 84 500 50 NAFLD 44.”
Effect of resveratrol supplementation on biomarkers associated with atherosclerosis in humans
Santana, T. M., Ogawa, L. Y., Rogero, M. M., Barroso, L. P., & de Castro, I. A. (2021) · Complementary Therapies in Clinical Practice · doi:10.1016/j.ctcp.2021.101491 · Cited by 20
Hesarooeyeh, Z. G., Basham, A., Sheybani‐Arani, M., Abbaszadeh, M., Asl, A. S., Moghbeli, M., & Saburi, E. (2023) · Phytotherapy Research · doi:10.1002/ptr.8023 · Cited by 22
“…pressure alteration in some of the human studies may be attributed to several causes; the short duration of the therapy, as we see in the study of Faghihzadeh et al. with a 12-week trial, or for administering non-formulated RES that provides low bioavailability (Faghihzadeh et al., 2015) and…”
Current understanding and controversies on the clinical implications of fibroblast growth factor 21
Badakhshi, Y., & Jin, T. (2020) · Critical Reviews in Clinical Laboratory Sciences · doi:10.1080/10408363.2020.1864278 · Cited by 20
Yang, M., Shen, Y., Zhao, S., Zhang, R., Dong, W., & Lei, X. (2023) · BMC Neuroscience · doi:10.1186/s12868-023-00797-1 · Cited by 19
Plant-Derived Nutraceuticals Involved in Body Weight Control by Modulating Gene Expression
Vrânceanu, M., Hegheş, S. C., Cozma-Petruț, A. P., Banc, R., Stroia, C. M., Raischi, V., Miere, D., Popa, D., & Filip, L. A. (2023) · Plants · doi:10.3390/plants12122273 · Cited by 22
“In several clinical trials, oral curcumin intake decreased the plasma lipid levels induced by HFD, an aspect correlated with AMPK and PPARα activation (both of which inhibit acetyl-CoA carboxylase (ACC)), followed by a decrease in lipid accumulation and FA synthesis [93,94].”
BackgroundNon-alcoholic fatty liver disease: Dietary and nutraceutical approaches
Cogorno, L., Formisano, E., Vignati, A., Prigione, A., Tramacere, A., Borgarelli, C., Sukkar, S. G., & Pisciotta, L. (2023) · Liver Research · doi:10.1016/j.livres.2023.08.005 · Cited by 19
“98 Resveratrol supplementation has already been shown to exert improvements in systolic blood pressure, insulin sensitivity, and glycated hemoglobin in T2DM patients.”
Venkatesan, T., Jeong, M.-J., Choi, Y.-W., Park, E. J., El‐Desouky, S. K., & Kim, Y. (2016) · Integrative Cancer Therapies · doi:10.1177/1534735416636958 · Cited by 19
Jin, T. (2018) · Obesity Medicine · doi:10.1016/j.obmed.2018.11.002 · Cited by 19
Zhou, T., Jin, Z., Jiang, R., & Li, W. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1600439 · Cited by 19
Charytoniuk, T., Harasim‐Symbor, E., Polak, A., Drygalski, K., Berk, K., Chabowski, A., & Konstantynowicz-Nowicka, K. (2018) · Anti-Cancer Agents in Medicinal Chemistry · doi:10.2174/1871520619666181224161255 · Cited by 17
The Clock‐NAD+‐Sirtuin connection in nonalcoholic fatty liver disease
Aggarwal, S., Trehanpati, N., Nagarajan, P., & Ramakrishna, G. (2022) · Journal of Cellular Physiology · doi:10.1002/jcp.30772 · Cited by 17
“While one report suggests resveratrol can reduce hepatic steatosis in patients with NAFLD, the other report found no beneficial effects (Chachay et al., 2014; Faghihzadeh et al., 2015).”
Metadata
- Authors
- Faghihzadeh, F., Adibi, P., & Hekmatdoost, A.
- Affiliations
- National Nutrition and Food Technology Research Institute (IR)
- Corresponding author
- Hekmatdoost, Azita
- ORCID
- Hekmatdoost, Azita
- Venue
- British Journal Of Nutrition
- Publisher
- Cambridge University Press (CUP)
- Published
- 2015-08-03
- Volume
- 114
- Issue
- 5
- Pages
- 796-803
- ISSN
- 0007-1145 (ISSN-L)
- 1475-2662
- OpenAlex
- W2246929884
- Cited by
- 188
- References
- 35
- Citations by year
- 2026: 9 · 2025: 9 · 2024: 17 · 2023: 13 · 2022: 28 · 2021: 18 · 2020: 17 · 2019: 15 · 2018: 20 · 2017: 12 · 2016: 25 · 2015: 2
- FWCI
- 9.94
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- British Journal Of Nutrition (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation
- Iran National Science Foundation
- National Nutrition and Food Technology Research Institute
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Keywords
- resveratrol, non-alcoholic fatty liver disease, cardiovascular risk factors, insulin resistance, alanine aminotransferase, hepatic steatosis, lipid profile, blood pressure, hypertriglyceridemia, dietary supplementation
- MeSH terms
- Resveratrol, Adult, Alanine Transaminase, Anti-Inflammatory Agents, Antioxidants, Blood Pressure, Cardiovascular Diseases, Double-Blind Method, Fatty Liver, Female, Humans, Insulin Resistance, Liver, Male, Phytotherapy, Middle Aged, Plant Extracts, Risk Factors, Stilbenes, Triglycerides, Biomarkers, Dietary Supplements, Lipid Metabolism, Non-alcoholic Fatty Liver Disease
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