Reversal of Insulin Resistance in Overweight and Obese Subjects by trans-Resveratrol and Hesperetin Combination—Link to Dysglycemia, Blood Pressure, Dyslipidemia, and Low-Grade Inflammation
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The dietary supplement, trans-resveratrol and hesperetin combination (tRES-HESP), induces expression of glyoxalase 1, countering the accumulation of reactive dicarbonyl glycating agent, methylglyoxal (MG), in overweight and obese subjects. tRES-HESP produced reversal of insulin resistance, improving dysglycemia and low-grade inflammation in a randomized, double-blind, placebo-controlled crossover study. Herein, we report further analysis of study variables. MG metabolism-related variables correlated with BMI, dysglycemia, vascular inflammation, blood pressure, and dyslipidemia. With tRES-HESP treatment, plasma MG correlated negatively with endothelial independent arterial dilatation (r = −0.48, p < 0.05) and negatively with peripheral blood mononuclear cell (PBMC) quinone reductase activity (r = −0.68, p < 0.05)—a marker of the activation status of transcription factor Nrf2. For change from baseline of PBMC gene expression with tRES-HESP treatment, Glo1 expression correlated negatively with change in the oral glucose tolerance test area-under-the-curve plasma glucose (ΔAUGg) (r = −0.56, p < 0.05) and thioredoxin interacting protein (TXNIP) correlated positively with ΔAUGg (r = 0.59, p < 0.05). Tumor necrosis factor-α (TNFα) correlated positively with change in fasting plasma glucose (r = 0.70, p < 0.001) and negatively with change in insulin sensitivity (r = −0.68, p < 0.01). These correlations were not present with placebo. tRES-HESP decreased low-grade inflammation, characterized by decreased expression of CCL2, COX-2, IL-8, and RAGE. Changes in CCL2, IL-8, and RAGE were intercorrelated and all correlated positively with changes in MLXIP, MAFF, MAFG, NCF1, and FTH1, and negatively with changes in HMOX1 and TKT; changes in IL-8 also correlated positively with change in COX-2. Total urinary excretion of tRES and HESP metabolites were strongly correlated. These findings suggest tRES-HESP counters MG accumulation and protein glycation, decreasing activation of the unfolded protein response and expression of TXNIP and TNFα, producing reversal of insulin resistance. tRES-HESP is suitable for further evaluation for treatment of insulin resistance and related disorders.
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Numerous studies have shown that dietary modification, or treatment with probiotics or synbiotics, has the potential to restore normal insulin function.
“Numerous studies have shown that dietary modification [168,169,170], or treatment with probiotics or synbiotics, has the potential to restore normal insulin function [57,171].”
From Polycystic Ovary Syndrome: An Evolutionary Adaptation to Lifestyle and the Environment (2022) · cites this paper as [169]
The citation is attached to the claim about probiotics or synbiotics. The Introduction reports reversal of insulin resistance with a trans-resveratrol–hesperetin supplement in overweight and obese subjects, but the passages found when searching for probiotics, synbiotics, and microbiota do not address treatment with either probiotics or synbiotics. Page numbers are unavailable in our copy. (LLM, conf=0.76)
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- Authors
- Rabbani, N., Xue, M., Weickert, M. O., & Thornalley, P. J.
- Affiliations
- Qatar University (QA)
- Hamad bin Khalifa University (QA)
- University Hospital Coventry (GB)
- Corresponding author
- Thornalley, Paul J.
- Venue
- Nutrients
- Publisher
- MDPI AG
- Published
- 2021-07-11
- Volume
- 13
- Issue
- 7
- Pages
- 2374
- ISSN
- 2072-6643 (ISSN-L)
- PMC
- PMC8308792
- OpenAlex
- W3178181224
- Cited by
- 74
- References
- 73
- Citations by year
- 2026: 15 · 2025: 12 · 2024: 12 · 2023: 18 · 2022: 16 · 2021: 1
- FWCI
- 6.48
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nutrients (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Qatar University QSpace (Qatar University) (submittedVersion)
- Funders
- Innovate UK (Project no 101129)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Natural Antidiabetic Agents Studies
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- trans-resveratrol, hesperetin, insulin resistance, obesity, overweight, methylglyoxal, glyoxalase I, Nrf2, quinone reductase, TXNIP, TNF-α, low-grade inflammation, dyslipidemia, blood pressure, arterial dilatation, RAGE, MCP-1, interleukin-8
- MeSH terms
- Resveratrol, Correlation of Data, Adult, Blood Pressure, Carrier Proteins, Double-Blind Method, Drug Therapy, Combination, Female, Glycosylation, Hesperidin, Humans, Inflammation, Insulin Resistance, Leukocytes, Mononuclear, Male, Obesity, Pyruvaldehyde, Tumor Necrosis Factor-alpha, Body Mass Index, Cross-Over Studies, Inflammation Mediators, Dietary Supplements, Glucose Metabolism Disorders, Dyslipidemias, Overweight
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