Potential Adverse Effects of Resveratrol: A Literature Review

Shaito, Abdullah; Posadino, Anna Maria; Younes, Nadin; Hasan, Hiba; Halabi, Sarah; Alhababi, Dalal; Al-Mohannadi, Anjud; Abdel-Rahman, Wael M; Eid, Ali H.; Nasrallah, Gheyath K.; Pintus, Gianfranco

doi:10.3390/ijms21062084

Cited by 716Sirtuins and Resveratrol in MedicinePhytochemicals and Antioxidant ActivitiesAlcohol Consumption and Health Effects

Potential Adverse Effects of Resveratrol: A Literature Review

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Shaito, Abdullah, Posadino, Anna Maria, Younes, Nadin, Hasan, Hiba, Halabi, Sarah, Alhababi, Dalal, Al-Mohannadi, Anjud, Abdel-Rahman, Wael M +3 more·2020·International Journal of Molecular Sciences

DOI 10.3390/ijms21062084PMC PMC7139620

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Abstract

Due to its health benefits, resveratrol (RE) is one of the most researched natural polyphenols. Resveratrol’s health benefits were first highlighted in the early 1990s in the French paradox study, which opened extensive research activity into this compound. Ever since, several pharmacological activities including antioxidant, anti-aging, anti-inflammatory, anti-cancerous, anti-diabetic, cardioprotective, and neuroprotective properties, were attributed to RE. However, results from the available human clinical trials were controversial concerning the protective effects of RE against diseases and their sequelae. The reason for these conflicting findings is varied but differences in the characteristics of the enrolled patients, RE doses used, and duration of RE supplementation were proposed, at least in part, as possible causes. In particular, the optimal RE dosage capable of maximizing its health benefits without raising toxicity issues remains an area of extensive research. In this context, while there is a consistent body of literature on the protective effects of RE against diseases, there are relatively few reports investigating its possible toxicity. Indeed, toxicity and adverse effects were reported following consumption of RE; therefore, extensive future studies on the long-term effects, as well as the in vivo adverse effects, of RE supplementation in humans are needed. Furthermore, data on the interactions of RE when combined with other therapies are still lacking, as well as results related to its absorption and bioavailability in the human body. In this review, we collect and summarize the available literature about RE toxicity and side effects. In this process, we analyze in vitro and in vivo studies that have addressed this stilbenoid. These studies suggest that RE still has an unexplored side. Finally, we discuss the new delivery methods that are being employed to overcome the low bioavailability of RE.

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High-dose administration of resveratrol in animal experiments shows proinflammatory and cytotoxic effects.
“A high-dose administration of resveratrol in animal experiments showed proinflammatory and cytotoxic effects.”
From Mediterranean Diet as an Antioxidant: The Impact on Metabolic Health and Overall Wellbeing (2021) · cites this paper as [129]
Resveratrol has pharmacokinetic interactions mainly due to CYP450 induction, which may affect the pharmacokinetics of other drugs.
“In addition, pharmacokinetic interactions have been described, mainly due to CYP450 induction, which may affect the pharmacokinetics of other drugs [129].”
From Mediterranean Diet as an Antioxidant: The Impact on Metabolic Health and Overall Wellbeing (2021) · cites this paper as [129]

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Low dose resveratrol improves cerebrovascular function in type 2 diabetes mellitus
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Resveratrol Mobilizes Endogenous Copper in Human Peripheral Lymphocytes Leading to Oxidative DNA Breakage: A Putative Mechanism for Chemoprevention of Cancer
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Natural Stilbenoids Have Anti-Inflammatory Properties in Vivo and Down-Regulate the Production of Inflammatory Mediators NO, IL6, and MCP1 Possibly in a PI3K/Akt-Dependent Manner
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Resveratrol Binding to Human Serum Albumin
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Resveratrol exhibits a strong cytotoxic activity in cultured cells and has an antiviral action against polyomavirus: potential clinical use
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Protein kinase CK2 modulates apoptosis induced by resveratrol and epigallocatechin-3-gallate in prostate cancer cells
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Piceatannol induces heme oxygenase-1 expression in human mammary epithelial cells through activation of ARE-driven Nrf2 signaling
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P-gp, MRP2 and OAT1/OAT3 mediate the drug-drug interaction between resveratrol and methotrexate
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Resveratrol promotes oxidative stress to drive DLC1 mediated cellular senescence in cancer cells
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Resveratrol has anti-thyroid effects both in vitro and in vivo
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Characteristics of Patients with Cystic Fibrosis: Experience in a Large Referral Children's Hospital in Tehran, Iran.
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Resveratrol and Quercetin Administration Improves Antioxidant DEFENSES and reduces Fatty Liver in Metabolic Syndrome Rats
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Higher dose of resveratrol elevated cardiovascular disease risk biomarker levels in overweight older adults – A pilot study
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Resveratrol promotes neuroprotection and attenuates oxidative and nitrosative stress in the small intestine in diabetic rats
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Pro‐ulcer effects of resveratrol in mice with indomethacin‐induced gastric ulcers are reversed by l ‐arginine
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Piceatannol attenuates hydrogen-peroxide- and peroxynitrite-induced apoptosis of PC12 cells by blocking down-regulation of Bcl-XL and activation of JNK
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Combination of glucan, resveratrol and vitamin C demonstrates strong anti-tumor potential.
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Unique synergistic formulation of curcumin, epicatechin gallate and resveratrol, tricurin, suppresses HPV E6, eliminates HPV+ cancer cells, and inhibits tumor progression
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Resveratrol, a naturally occurring polyphenol, induces sister chromatid exchanges in a Chinese hamster lung (CHL) cell line
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Resveratrol Inhibits Sodium/Iodide Symporter Gene Expression and Function in Rat Thyroid Cells
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Chai, R., Chen, Y., Yuan, H., Wang, X., Guo, S., Qi, J., Zhang, H., Zhan, Y., & An, H. (2017) · The Journal of Membrane Biology · doi:10.1007/s00232-017-9975-9 · Cited by 31 · see citing works

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[144]Sotoudehmanesh R. Anvari B. Akhlaghi M. Shahraeeni S. Kolahdoozan S. Methotrexate hepatotoxicity in patients with rheumatoid arthritis Middle East J. Dig. Dis. 2010 2 104 109 25197521 PMC4154822

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Authors: Shaito, A., Posadino, A. M., Younes, N., Hasan, H., Halabi, S., Alhababi, D., Al-Mohannadi, A., Abdel-Rahman, W. M., Eid, A. H., Nasrallah, G. K., & Pintus, G.
Affiliations: Lebanese International University (LB)
University of Sassari (IT)
Qatar University (QA)
Justus-Liebig-Universität Gießen (DE)
American University of Beirut (LB)
Department of Medical Laboratory Sciences, College of Health Sciences and Sharjah Institute for Medical Research, University of Sharjah, Sharjah P.O Box: 27272, United Arab Emirates
Corresponding author: Eid, Ali H.
Nasrallah, Gheyath K.
Pintus, Gianfranco
ORCID: Shaito, Abdullah
Posadino, Anna Maria
Younes, Nadin
Hasan, Hiba
Al-Mohannadi, Anjud
Abdel-Rahman, Wael M
Eid, Ali H.
Nasrallah, Gheyath K.
Pintus, Gianfranco
Venue: International Journal of Molecular Sciences
Publisher: MDPI AG
Published: 2020-03-18
Volume: 21
Issue: 6
Pages: 2084
ISSN: 1422-0067 (ISSN-L)
DOI: 10.3390/ijms21062084
PMC: PMC7139620
OpenAlex: W3011177534
Cited by: 716
References: 226
Citations by year: 2026: 104 · 2025: 147 · 2024: 125 · 2023: 116 · 2022: 107 · 2021: 83 · 2020: 31 · 2019: 1
FWCI: 10.47
Type: journal article
Language: en
Open access: gold
dx.doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
Locations: International Journal of Molecular Sciences (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
UnissResearch (Università degli Studi di Sassari) (submittedVersion, cc-by)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Figshare (submittedVersion, cc-by)
Qatar University QSpace (Qatar University) (submittedVersion)
Funders: Qatar University (IRCC#181)
Topics: Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
Health Sciences › Medicine › Biochemistry › Phytochemicals and Antioxidant Activities
Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
Keywords: resveratrol, toxicity, adverse effects, stilbenoids, natural polyphenols, bioavailability, drug interactions, dosage, French paradox, cardioprotection, neuroprotection, anti-inflammatory activity, antioxidant activity, anticancer effects, anti-diabetic effects, anti-aging effects, delivery methods
MeSH terms: Resveratrol, Humans

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Potential Adverse Effects of Resveratrol: A Literature Review

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