Resveratrol
1. Introduction
Resveratrol (3,5,4′-trihydroxy-trans-stilbene) is a naturally occurring polyphenolic phytoalexin, a type of stilbenoid produced by several plants in response to stress, injury, or fungal infection. It is most famously found in the skin of red grapes, red wine, peanuts, blueberries, and certain Asian plants like Polygonum cuspidatum (Japanese knotweed) [1].
Chemical/Botanical Basics
Resveratrol exists in two main isomeric forms: cis-resveratrol and trans-resveratrol. The trans isomer is the most common and biologically active form and is the subject of most research and commercial supplements. The compound is often found in nature as a glycoside, known as piceid (or polydatin), where a glucose molecule is attached to the resveratrol structure.
Mechanism of Action
Resveratrol’s health-promoting effects are attributed to its potent antioxidant and anti-inflammatory properties. Its mechanism of action is multifaceted and involves modulating various cellular signaling pathways [1]:
- Antioxidant Activity: It acts as a direct free radical scavenger and, more importantly, enhances the body’s endogenous antioxidant defense system. It achieves this by activating the Nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, which is the master regulator of numerous antioxidant and phase II-detoxifying enzymes (e.g., superoxide dismutase (SOD) and catalase (CAT)).
- Sirtuin Activation: Resveratrol is a known activator of Sirtuin 1 (SIRT1), a protein deacetylase that plays a crucial role in cellular metabolism, stress resistance, and aging. Activation of the SIRT1/AMPK pathway is linked to its anti-aging and metabolic benefits.
- Anti-inflammatory Effects: It inhibits pro-inflammatory enzymes like cyclooxygenase (COX) and lipoxygenase (LOX) and suppresses the activation of the Nuclear Factor-kappa B (NF-κB) pathway, a central regulator of inflammatory responses.
2. Chemical Composition/Key Bioactive Roles
The biological activity of Resveratrol is primarily linked to its trans isomer, which is the most stable and bioavailable form.
| Compound | Chemical Class | Key Bioactive Role | Notes |
|---|---|---|---|
| trans-Resveratrol | Stilbenoid (Polyphenol) | Potent Antioxidant, Anti-inflammatory, SIRT1 Activator | Most biologically active and stable form, commonly used in supplements. |
| cis-Resveratrol | Stilbenoid (Polyphenol) | Antioxidant | Less stable and less biologically active than the trans form. |
| Piceid (Polydatin) | Glycoside of Resveratrol | Precursor, Antioxidant | Glycosylated form, often found in natural sources like Japanese knotweed; converted to Resveratrol in the gut. |
3. Health Benefits
Scientific research, including in-vitro, animal, and human clinical trials, suggests that resveratrol may offer a wide range of health benefits, primarily due to its ability to combat oxidative stress and inflammation [1, 2].
| Health Benefit | Scientific Evidence and Mechanism |
|---|---|
| Cardiovascular Protection | Resveratrol has been shown to improve endothelial function, reduce low-density lipoprotein (LDL) oxidation, and inhibit platelet aggregation, which helps prevent the formation of blood clots (antiplatelet effect). It may also help lower blood pressure by promoting vasodilation [1]. |
| Neuroprotection | Its antioxidant and anti-inflammatory effects protect nerve cells from damage. Studies suggest a potential role in mitigating neurodegenerative diseases like Alzheimer’s and Parkinson’s by reducing amyloid plaque formation and protecting mitochondrial function [1]. |
| Anti-Cancer Potential | Resveratrol exhibits chemopreventive and chemotherapeutic effects by inhibiting cancer cell proliferation, inducing apoptosis (programmed cell death), and suppressing angiogenesis (new blood vessel formation in tumors) across various cancer types, including breast, prostate, and colorectal [1]. |
| Metabolic Health & Anti-Diabetic Effects | By activating the AMPK pathway, resveratrol can improve insulin sensitivity, lower fasting blood glucose, and reduce triglycerides. This makes it a potential therapeutic agent for type 2 diabetes and metabolic syndrome [1]. |
| Anti-Aging and Longevity | The activation of SIRT1, often referred to as the “longevity gene,” is a key mechanism. By mimicking caloric restriction, resveratrol may enhance mitochondrial function and cellular repair processes [2]. |
4. Dosage and Usage
Recommended Dosages
Resveratrol dosage in clinical trials varies significantly based on the target health outcome, ranging from very low to very high doses.
- General Supplementation: Typical over-the-counter dosages range from 150 mg to 500 mg per day of trans-resveratrol.
- Therapeutic Doses (Clinical Trials): Doses of 1,000 mg (1 gram) to 2,000 mg (2 grams) per day have been used in human clinical trials for specific conditions, such as improving metabolic markers or cardiovascular function [3].
- Upper Limit: Clinical trials have demonstrated that doses up to 5,000 mg (5 grams) per day are generally well-tolerated for short periods, although doses above 2.5 g/day increase the risk of gastrointestinal side effects [3].
Note: For optimal absorption, it is often recommended to take resveratrol supplements with a meal containing fat.
Food Sources
Resveratrol is found in the skin of various fruits and plants. However, the amount is typically much lower than what is found in supplements.
| Food Source | Compound | Concentration (Approximate) |
|---|---|---|
| Red Wine | trans-Resveratrol | 0.2 to 5.8 mg per liter |
| Red Grapes (skin) | trans-Resveratrol, Piceid | 0.16 to 3.52 mg per 100g |
| Peanuts | trans-Resveratrol, Piceid | 0.01 to 1.92 mg per 100g |
| Japanese Knotweed (Polygonum cuspidatum) | Piceid, trans-Resveratrol | High concentration source, often used for supplement extraction. |
5. Safety and Precautions
Resveratrol is generally considered safe and well-tolerated at typical supplemental doses (up to 1,500 mg/day). However, precautions are necessary, especially at high doses [3].
Side Effects
- Gastrointestinal Distress: The most common side effects, particularly with high doses (above 1,000 mg/day), include mild to moderate gastrointestinal issues such as diarrhea, nausea, and abdominal discomfort [3].
- High Doses: Doses greater than 2.5 g/day may cause more severe GI upset.
Contraindications
- Pregnancy and Breastfeeding: Due to a lack of sufficient safety data, resveratrol supplementation is generally advised against during pregnancy and breastfeeding.
- Hormone-Sensitive Cancers: Resveratrol can exhibit weak estrogenic activity. Individuals with hormone-sensitive conditions (e.g., breast, ovarian, uterine cancer, or endometriosis) should use it with caution and consult a healthcare provider.
Drug Interactions
Resveratrol can interact with several types of medications, primarily by inhibiting certain liver enzymes (Cytochrome P450 enzymes, particularly CYP3A4) responsible for drug metabolism and by possessing antiplatelet activity [3].
- Blood Thinners (Anticoagulants/Antiplatelets): Resveratrol’s antiplatelet effects may increase the risk of bleeding or bruising when taken with medications like warfarin, aspirin, clopidogrel, or NSAIDs (e.g., ibuprofen, naproxen).
- Cytochrome P450 Substrates: Resveratrol may increase the concentration and effect of drugs metabolized by the CYP3A4 enzyme. This includes certain statins, calcium channel blockers, immunosuppressants, and anti-cancer drugs.
- Blood Pressure Medications: Due to its potential to lower blood pressure, combining it with antihypertensive drugs may lead to excessive drops in blood pressure (hypotension).
WARNING: Individuals taking any prescription medications, especially blood thinners or drugs metabolized by the liver, MUST consult a healthcare professional before taking resveratrol supplements.
6. References
[1] Meng, X., Zhou, J., Zhao, C.-N., Gan, R.-Y., & Li, H.-B. (2020). Health Benefits and Molecular Mechanisms of Resveratrol: A Narrative Review. Foods, 9(3), 340. doi:10.3390/foods9030340. URL: https://pmc.ncbi.nlm.nih.gov/articles/PMC7143620/ [2] Salehi, B., Mishra, A. P., Nigam, M., Sener, B., Kilic, M., Sharifi-Rad, M., … & Sharifi-Rad, J. (2018). Resveratrol: A Double-Edged Sword in Health Benefits. Biomolecules, 8(3), 91. doi:10.3390/biom8030091. URL: https://pmc.ncbi.nlm.nih.gov/articles/PMC6164842/ [3] Shaito, A., Aramouni, K., Assi, S., El-Haj, S., & Harajly, H. (2020). Potential Adverse Effects of Resveratrol: A Literature Review. Toxics, 8(1), 13. doi:10.3390/toxics8010013. URL: https://pmc.ncbi.nlm.nih.gov/articles/PMC7139620/Category: Polyphenol
