Should I take resveratrol?

Our read is that resveratrol has been identified as a potent Sirt-1 activator, with some experts suggesting it may offer benefits such as reducing oxidative stress, improving memory, and mitigating age-related diseases.

However, other experts strongly question its effectiveness as a longevity agent, citing unconvincing evidence from human trials, potential negative side effects, and concerns about study biases.

The consensus is that while resveratrol has known mechanisms of action relevant to longevity, its practical benefits in humans remain largely unproven and controversial.

Resveratrol requires dissolution in a lipophilic medium to be absorbed effectively. Pure resveratrol is typically grey or white and greater than 98% pure. Polyphenols like resveratrol are not very soluble or stable in light.

• 01Resveratrol was the best molecule found in a screen for Sirt-1 activators, increasing activity 13-fold (Andrew Huberman, Paul Saladino, David Sinclair, 4x).
• 02Resveratrol activates sirtuins, which is thought to be the mechanism for its healthspan benefits (Peter Attia, Andrew Huberman, Rhonda Patrick, 4x).
• 03Chronic resveratrol intake reduces oxidative stress and brain cell loss, and improves memory in old rats (David Sinclair, 2x).
• 04High doses of resveratrol can ameliorate type 2 diabetes or fasting blood sugar levels, particularly in severely obese individuals with high blood sugar (Paul Saladino, David Sinclair, 3x).
• 05Resveratrol has antioxidant and anti-inflammatory properties and may protect neurons by neutralizing free radicals, reducing inflammation, and enhancing neuronal energy metabolism (Rhonda Patrick, 1x).
• 06Resveratrol supplementation in type 2 diabetics is associated with a significant reduction in C-reactive protein (CRP) levels by approximately 0.34 mg/L (David Sinclair, 1x).
• 07Resveratrol (400 mg/kg) lowers cholesterol, triglycerides, and fat deposition in mice by inducing ESR1 (David Sinclair, 1x).
• 08Resveratrol from red wine inhibits bacteria that cause gingivitis and prevents plaque and inflammation (David Sinclair, 1x).
• 09Resveratrol may help mitigate age-related diseases by affecting fat-associated B-cells (David Sinclair, 1x).
• 10Resveratrol supplementation for 22 weeks improved fertility in middle-aged female mice (David Sinclair, 1x).
• 11Bioactive compounds like resveratrol can mimic some effects of calorie restriction or fasting (Rhonda Patrick, 1x).
• 12Flavonoids like resveratrol, quercetin, and genistein have estrogenic activity by mimicking estrogen receptors (Paul Saladino, 1x).
• 13Syringaresinol activates the longevity enzyme SIRT1 (David Sinclair, 1x).

The evidence for resveratrol's health benefits is largely unconvincing due to biased studies and questionable findings (Peter Attia, 2x). Resveratrol has not been shown to affect the biology of aging or act as a longevity drug (Peter Attia, 3x). Resveratrol was heavily hyped as a longevity agent but evidence suggests it does not extend lifespan in mice and its proposed mechanisms of action are questionable (Peter Attia, 5x). A famous study on resveratrol in mice used a diet poisoned with 60% coconut oil, causing liver swelling and respiratory failure, which is not a valid model for aging (Peter Attia, Andrew Huberman, David Sinclair, 9x). Resveratrol has repeatedly failed in human trials, shown negative effects like decreasing androgen precursors, and potentially causing thrombocytopenia and modulating the immune system negatively (Paul Saladino, 1x). Resveratrol treatment did not result in changes to glucose tolerance, insulin sensitivity, weight, blood pressure, or lipid profile in human studies (Paul Saladino, 3x). Resveratrol has failed in human trials for conditions like non-alcoholic fatty liver disease and metabolic syndrome, and in the latter, it worsened dysglycemia (Paul Saladino, 6x). Resveratrol and terrace do not increase the activity of SIRT1 and have no use case for boosting NAD+ (Rhonda Patrick, David Sinclair, 2x). Resveratrol products may contain contaminants like emodin, which can cause diarrhea (David Sinclair, 1x). Resveratrol may possibly induce autoimmunity (Paul Saladino, 1x). Plant-derived molecules like resveratrol and curcumin have side effects that are often not emphasized or disclosed (Paul Saladino, 3x). Compounds like isothiocyanates in broccoli and kale, and resveratrol from grapes, have significant negative side effects in humans despite being promoted for one positive effect (Paul Saladino, 1x). The logic that wine makes you live longer because it contains resveratrol is not true (Peter Attia, 1x). Proponents of resveratrol criticized the ITP study for low bioavailability, suggesting much higher doses are needed, a criticism voiced only after the study's negative results (Peter Attia, 2x). Resveratrol may act as an endocrine disruptor and have negative side effects (Paul Saladino, 1x). Resveratrol's benefits are uncertain, and ketosis may offer similar benefits (Paul Saladino, 1x). Resveratrol may blunt the benefits of exercise (Rhonda Patrick, 1x).

More robust and unbiased human trials demonstrating consistent positive effects on longevity and healthspan, without significant negative side effects, would change the verdict. Additionally, clearer understanding and validation of its mechanisms of action in humans, particularly regarding sirtuin activation and NAD+ boosting, would be influential.