Resveratrol Capsules

Resveratrol is a type of natural stilbene, a class of polyphenolic compounds, found in many plants but most notably in the skin of grapes.^[1] It is a biologically active compound commonly produced by plants during infections or UV irradiation.^[1] Trans-resveratrol and its glucoside have been studied for a prospective impact on human health, proposing potential benefits such as antioxidant effects, anti-cancer properties, and both estrogenic and anti-estrogenic effects.^[1]
Resveratrol is found in over 70 plants, fruits, vegetables, and herbs.^[2] The name “Resveratrol” comes from the plant it was found in, the Veratrum species, and from the chemical from which it was derived.^[2]
As a type of stilbene, it is a natural compound belonging to the larger group of polyphenols.^[3] Specifically, resveratrol is a phytoalexin, a substance that plants produce in response to adverse environments.^[4] Per Shetty et al., resveratrol has been used in traditional Eastern medicine for various dermatologic issues and fungal infections.^[2] Resveratrol has gained attention for potential health benefits and is often associated with the “French paradox,” where despite a diet heavy in saturated fats, some French populations exhibit lower rates of coronary heart disease.^[3]
Resveratrol may influence various factors related to inflammation, cell growth, and cell function, which pose potential for its use in longevity.^[3]

As mentioned, resveratrol is a stilbene and has a chemical structure with two phenol rings connected by an ethylene bridge.^[1] The structure exists in two forms: cis- and trans-resveratrol.^[1] Salehi et al notes: the “trans form is dominant in terms of its prevalence and different biological activities are attributed, namely in inducing cellular responses such as cell cycle arrest, differentiation, apoptosis, and to enhance cancer cells anti-proliferation.”^[1] Per Shetty et al., exposure to light may convert the more stable trans-resveratrol to the cis form.^[2]
Resveratrol may have anti-inflammatory properties due to the potential to suppress the expression of COX-2, an enzyme associated with inflammation.^[3] In vitro studies of resveratrol in certain cancer cells suggest that resveratrol targets multiple signaling pathways, including COX-2, which are involved in cancer cell growth and survival.^[3] This may reduce proliferation of these cells.^[3] In an animal study focused on heart failure, resveratrol’s action at the cellular level suggested the potential to reduce hypertrophy and oxidative stress.^[5]
According to one animal study, resveratrol may decrease serum levels of thyroid hormones (T3, T4) and increase levels of thyroid-stimulating hormone (TSH) in hyperthyroid-induced rats.^[6] Per Hadi et al., the mechanism of this effect on the thyroid may involve the inhibition of sodium-iodide symporter (NIS) and antioxidant effects of resveratrol.^[6]
Per Shaito et al, resveratrol may influence essential factors within cells, specifically in the cytoplasm and nucleus.^[7] According to preliminary research, resveratrol may support the creation of new mitochondria, the cellular powerhouses responsible for energy production.^[7] This process, known as mitochondrial biogenesis, is vital for overall cell function and energy balance.^[7] The pathways through which resveratrol may promote mitochondrial biogenesis are the SIRT1/PGC-1α/NRF-1 and SIRT1/FoxO3a/PGC-1α pathways.^[7] Per Shetty et al., resveratrol’s molecular action relies mainly on its binding to an enzyme named SIRT1.^[2] The interaction between resveratrol and SIRT1 may depend on the dose, with low to moderate doses relying on SIRT1, but higher doses acting independently of SIRT1.^[2]

Per Shaito et al., resveratrol may exhibit dose-dependent effects.^[7] Some research proposes that this may be due to the potential to act as an antioxidant at low doses but turn into a pro-oxidant at high doses.^[7] Shaito et al. suggest that understanding dosage and how resveratrol interacts on a cellular level is crucial.^[7] Differences in patient characteristics, resveratrol doses, and duration of supplementation may contribute to conflicting data, so more comprehensive studies are needed.^[7]
The potential for estrogenic and anti-estrogenic effects may be prohibitive in patients with estrogen sensitive disease states such as breast cancer.^[1]

In a study in healthy volunteers, resveratrol was given orally in the form of an uncoated immediate-release caplet.^[10] Per the researchers, this formulation was mostly well-tolerated at doses of 0.5 g daily for a duration of 29 days.^[10] One patient on this dose experienced raised total blood bilirubin, an adverse event determined possibly associated with resveratrol.^[10] When given higher doses (2.5 g or more per day), a larger number patients experienced side effects determined to be associated with resveratrol, including nausea, vomiting, or diarrhea.^[10] Liver dysfunction is also possible, especially in individuals with non-alcoholic fatty liver disease.^[1] Doses of up to up to 5 g daily have been reported to be well-tolerated, but it is important to note that these studies were conducted in healthy populations and response may vary in individuals with specific health conditions.^[1]
Additionally, orally administrated resveratrol may be metabolized by microorganisms in the GI tract, making it challenging to distinguish effects that are attributable to resveratrol or its metabolites.^[1]
Animal and in vitro studies have proposed other potential adverse events with resveratrol supplementation. An in vitro study suggested resveratrol may inhibit platelet aggregation, which may increase risk of bruising or bleeding in humans.^[1] Concerningly, an animal study suggested that long term use of resveratrol may cause nephrotoxicity.^[11] Further trials are needed to determine how these studies may correlate to potential adverse events in humans.
Some researchers speculate possible drug interactions due to resveratrol’s potential to inhibit P450 cytochromes.^[1] Per Salehi et al., due to this potential effect on cytochrome p450 activity, resveratrol may interact with drugs that use this metabolic pathway.^[1]

Resveratrol is not recommended for use in pregnant women.^[8] Observations were made in animal studies concerning alteration in fetal pancreatic development when given to pregnant primates.^[8] Avoid resveratrol supplementation during pregnancy due to potential risks to fetal development.^[8]

Per the Drugs and Lactation Database, there is a lack of information regarding the presence of resveratrol in breastmilk or the use of resveratrol in nursing mothers or infants.^[9]

Store this medication at 68°F to 77°F (20°C to 25°C) and away from heat, moisture and light. Keep all medicine out of the reach of children. Throw away any unused medicine after the beyond use date. Do not flush unused medications or pour down a sink or drain.

1. Salehi B, Mishra AP, Nigam M, Sener B, Kilic M, Sharifi-Rad M, Fokou PVT, Martins N, Sharifi-Rad J. Resveratrol: A Double-Edged Sword in Health Benefits. Biomedicines. 2018 Sep 9;6(3):91. doi: 10.3390/biomedicines6030091. PMID: 30205595; PMCID: PMC6164842. https://pubmed.ncbi.nlm.nih.gov/30205595/
2. Shetty R, Joshi PD, Mahendran K, Jayadev C, Das D. Resveratrol for dry eye disease – Hope or Hype? Indian J Ophthalmol. 2023 Apr;71(4):1270-1275. doi: 10.4103/IJO.IJO_3204_22. PMID: 37026258; PMCID: PMC10276748. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10276748/
3. Catalgol B, Batirel S, Taga Y, Ozer NK. Resveratrol: French paradox revisited. Front Pharmacol. 2012 Jul 17;3:141. doi: 10.3389/fphar.2012.00141. PMID: 22822401; PMCID: PMC3398412. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3398412/
4. Tomé-Carneiro J., Gonzálvez M., Larrosa M., Yáñez-Gascón M.J., García-Almagro F.J., Ruiz-Ros J.A., Tomás-Barberán F.A., García-Conesa M.T., Espín J.C. Grape resveratrol increases serum adiponectin and downregulates inflammatory genes in peripheral blood mononuclear cells: A triple-blind, placebo-controlled, one-year clinical trial in patients with stable coronary artery disease. Cardiovasc. Drugs Ther. 2013;27:37–48. doi: 10.1007/s10557-012-6427-8.
5. Riba A., Deres L., Sumegi B., Toth K., Szabados E., Halmosi R. Cardioprotective effect of resveratrol in a postinfarction heart failure model. Oxid. Med. Cell. Longev. 2017;2017:6819281. doi: 10.1155/2017/6819281
6. Hadi Y, Abdulmahdi, R, Razzaq B. Investigating the impact of resveratrol on thyroid function, structure, and metabolic alterations in hyperthyroidism model: in vivo study. (2022). Journal of Pharmaceutical Negative Results, 13(4), 199-209. https://doi.org/10.47750/pnr.2022.13.04.025
7. Shaito A, Al-Mansoob M, Ahmad SMS, Haider MZ, Eid AH, Posadino AM, Pintus G, Giordo R. Resveratrol-Mediated Regulation of Mitochondria Biogenesis-associated Pathways in Neurodegenerative Diseases: Molecular Insights and Potential Therapeutic Applications. Curr Neuropharmacol. 2023;21(5):1184-1201. doi: 10.2174/1570159X20666221012122855. PMID: 36237161; PMCID: PMC10286596. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10286596/
8. Roberts VH, Pound LD, Thorn SR, Gillingham MB, Thornburg KL, Friedman JE, Frias AE, Grove KL. Beneficial and cautionary outcomes of resveratrol supplementation in pregnant nonhuman primates. FASEB J. 2014 Jun;28(6):2466-77. doi: 10.1096/fj.13-245472. Epub 2014 Feb 21. PMID: 24563374; PMCID: PMC4021444. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4021444/
9. Drugs and Lactation Database (LactMed®) [Internet]. Bethesda (MD): National Institute of Child Health and Human Development; 2006-. Resveratrol. [Updated 2021 Sep 20].https://www.ncbi.nlm.nih.gov/books/NBK501879/
10. Brown VA, Patel KR, Viskaduraki M, Crowell JA, Perloff M, Booth TD, Vasilinin G, Sen A, Schinas AM, Piccirilli G, Brown K, Steward WP, Gescher AJ, Brenner DE. Repeat dose study of the cancer chemopreventive agent resveratrol in healthy volunteers: safety, pharmacokinetics, and effect on the insulin-like growth factor axis. Cancer Res. 2010 Nov 15;70(22):9003-11. doi: 10.1158/0008-5472.CAN-10-2364. Epub 2010 Oct 8. PMID: 20935227; PMCID: PMC2982884.
11. Zhou DD, Luo M, Huang SY, Saimaiti A, Shang A, Gan RY, Li HB. Effects and Mechanisms of Resveratrol on Aging and Age-Related Diseases. Oxid Med Cell Longev. 2021 Jul 11;2021:9932218. doi: 10.1155/2021/9932218. PMID: 34336123; PMCID: PMC8289612.