Resveratrol (trans-3,5,4′-trihydroxystilbene) is a polyphenolic phytoalexin produced by several plants in response to biotic and abiotic stress and acts as a defence against microbes. Although resveratrol is naturally present in grapes, peanuts, almonds, blueberries and dark chocolate, the highest concentration of resveratrol is found in wine (4–20 mg/L)1. Although there are various reported health benefits of resveratrol, its stereoisomeric forms are often overlooked. This article will explore the stereoisomeric forms of resveratrol – cis and trans.
What are stereoisomers?
Stereoisomers are molecules that have same chemical formula but different arrangements of functional group atoms in space. Stereoisomers exist in cis-trans configurations. In cis-resveratrol (c-RESV), the stilbene functional group is on the same side of the plane, while in trans-resveratrol (t-RESV), this functional group lies on the opposite side.
Adapted from https://pubchem.ncbi.nlm.nih.gov/
Which form is more effective biologically?
A comparative study on the antioxidant activity of diastereomers of resveratrol showed that t-RESV is more efficient in protecting keratinocytes from cumene hydroperoxide mediated oxidative damage than c-RESV 2. However, more research is needed to compare the other benefits of the two forms of resveratrol.
Trans-resveratrol: Beyond the boundary of antioxidant molecule
Besides having excellent antioxidant properties, researchers suggest it possesses excellent anti-inflammatory, anti-diabetic, neuroprotective and cardioprotective activities 3–5.
In a 14-week double-blind, placebo-controlled trial, the effect of resveratrol on postmenopausal women’s mood and Cognitive health was assessed. Resveratrol supplementation (75 mg of 99% t-RESV twice daily) was observed to improve mood and cognitive health in postmenopausal women5.
Another 24-week clinical trial investigated the hypoglycaemic effects of resveratrol in a cohort of 110 participants. Resveratrol supplementation (200 mg, once daily) significantly reduced plasma glucose and inflammatory markers (CRP, TNF-α, IL-6)4.
In conclusion, trans-resveratrol is more prominent than cis-resveratrol found naturally in plants and has more pronounced biological activity.
References
(1) Tian, B.; Liu, J. Resveratrol: A Review of Plant Sources, Synthesis, Stability, Modification and Food Application. Journal of the Science of Food and Agriculture. John Wiley and Sons Ltd March 15, 2020, pp 1392–1404. https://doi.org/10.1002/jsfa.10152.
(2) Bononi, I.; Tedeschi, P.; Mantovani, V.; Maietti, A.; Mazzoni, E.; Pancaldi, C.; Brandolini, V.; Tognon, M. Antioxidant Activity of Resveratrol Diastereomeric Forms Assayed in Fluorescent-Engineered Human Keratinocytes. Antioxidants 2022, 11 (2). https://doi.org/10.3390/antiox11020196.
(3) Kazemirad, H.; Kazerani, H. R. Cardioprotective Effects of Resveratrol Following Myocardial Ischemia and Reperfusion. Mol Biol Rep 2020, 47 (8), 5843–5850. https://doi.org/10.1007/s11033-020-05653-7.
(4) Mahjabeen, W.; Khan, D. A.; Mirza, S. A. Role of Resveratrol Supplementation in Regulation of Glucose Hemostasis, Inflammation and Oxidative Stress in Patients with Diabetes Mellitus Type 2: A Randomized, Placebo-Controlled Trial. Complement Ther Med 2022, 66. https://doi.org/10.1016/j.ctim.2022.102819.
(5) Evans, H. M.; Howe, P. R. C.; Wong, R. H. X. Clinical Evaluation of Effects of Chronic Resveratrol Supplementation on Cerebrovascular Function, Cognition, Mood, Physical Function and General Well-Being in Postmenopausal Women—Rationale and Study Design. Nutrients 2016, 8 (3). https://doi.org/10.3390/nu8030150.