#051 Is Resveratrol a Longevity Compound?
Rhonda provides an in-depth analysis of resveratrol, covering its effects on animal and human health, mechanisms of action, and the bottom line on supplementation and safety. The discussion highlights its cardiovascular, metabolic, and neurological benefits, as well as contradictory findings regarding exercise adaptations.
Deep Dive Analysis
14 Topic Outline
Introduction to Resveratrol and its Historical Context
Resveratrol's Beneficial Effects on Cardiovascular Health
Anti-inflammatory Properties of Resveratrol
Impact of Resveratrol on Neurological Health and Cognition
Resveratrol's Potential in Cancer Prevention and Treatment
Mechanisms: Sirtuin Activation and Caloric Restriction Mimicry
Mechanisms: Induction of Autophagy
Mechanisms: Xenohormesis and Activation of Stress Response Genes
Contradictory Effects of Resveratrol on Exercise Adaptations
Factors Affecting Resveratrol Bioavailability
Resveratrol Dosage, Safety, and Side Effects
Potential Interactions with Drug Metabolism
Resveratrol's Effect on Androgen Precursors
Summary and Future Outlook for Resveratrol Supplementation
5 Key Concepts
Xenohormesis
This biological phenomenon describes how humans and animals interpret signals of plant stress, such as the synthesis of phytochemicals like resveratrol, as indications that their environment may require enhanced biological fitness. This 'interspecies communication' activates protective mechanisms and stress response genes in our cells, conferring resilience against environmental stressors.
Caloric Restriction Mimetic
Resveratrol is considered a caloric restriction mimetic because it can induce physiological changes typically seen with caloric restriction, such as reduced IGF-1 and increased AMP kinase activity. Caloric restriction has been widely shown to increase healthspan across various organisms.
Autophagy
Autophagy is an adaptive cellular response mechanism activated during energy stress to remove unnecessary or dysfunctional cellular components and mobilize stored energy reserves. Resveratrol promotes autophagy through its activation of sirtuins and by inhibiting mTOR, a key regulator of this process.
Direct Antioxidants
Direct antioxidants, such as vitamin C and E, function by binding to and sequestering damaging reactive oxygen species. High doses of these can sometimes blunt exercise-induced adaptations because the reactive oxygen species generated during exercise are important signaling molecules for cardiorespiratory improvements.
Indirect Antioxidants
Indirect antioxidants, like high-dose resveratrol, activate the body's own cytoprotective proteins, such as the NRF2 pathway. This activation subsequently triggers a wide array of genetic pathways, including endogenous antioxidant systems like glutathione, providing longer-lasting benefits without necessarily blunting exercise adaptations.
7 Questions Answered
Resveratrol is a natural compound found in the stems, leaves, roots, fruits, and seeds of various plants, primarily in the skin of red grapes, red wine, peanuts, blueberries, and the root of Japanese knotweed, where it protects plants from stressors like fungal attacks or UV radiation.
Resveratrol has been shown to improve cardiovascular biomarkers by reducing blood pressure, fasting blood glucose, and circulating insulin, while increasing HDL levels and decreasing LDL, oxidized LDL, and inflammatory markers in individuals at risk for or with cardiovascular disease.
Yes, studies indicate that resveratrol can improve the ability to complete memory tasks in healthy adults and shows promise in Alzheimer's disease by countering neuronal inflammation and inhibiting beta-amyloid plaque formation and aggregation.
While resveratrol has been shown to extend lifespan in unhealthy animals and improve healthspan in healthy animals, it did not increase lifespan in healthy mice fed a standard diet, and there is insufficient evidence to confirm lifespan extension in humans.
The effects are contradictory; low doses (150-250 mg daily) have blunted positive exercise adaptations in some human studies, possibly due to direct antioxidant effects, while a higher dose (500 mg daily) showed increased mitochondrial density and maximal oxygen consumption when combined with training.
Resveratrol is only about 25% bioavailable due to rapid metabolism and excretion; its bioavailability is higher in the morning and when taken with a moderate fat breakfast, and can be increased by nanocapsule encapsulation or potentially by co-administration with piperine.
Doses up to 5 grams daily are generally well tolerated, but doses above 2.5 grams can cause mild to moderate GI distress. Resveratrol can also inhibit cytochrome P450 enzymes, which metabolize many drugs (e.g., statins, antiarrhythmics), potentially increasing their systemic levels and risk of toxicity.
24 Actionable Insights
1. Consult Doctor with Medications
If you are taking medications, especially statins, antiarrhythmic drugs, or antihistamines, consult your doctor before supplementing with resveratrol, as it may inhibit drug metabolism enzymes (cytochrome P450) and increase drug toxicity.
2. Caution with Long-Term Resveratrol
Exercise caution with resveratrol supplementation for periods longer than one year, as long-term toxicology studies in humans have not yet been performed.
3. Beware High-Dose GI Distress
While resveratrol doses up to 5 grams daily are generally not toxic, be aware that doses above 2.5 grams may cause mild to moderate gastrointestinal distress like nausea, gas, abdominal discomfort, and diarrhea.
4. Avoid Direct Antioxidants with Exercise
Avoid high-dose supplemental direct antioxidants like vitamin C and E when exercising, as they have been shown to blunt beneficial exercise-induced cardiorespiratory adaptations.
5. Resveratrol as Preventative Supplement
Consider resveratrol as a preventative supplement due to its potential to activate cellular protective mechanisms and act as a calorie restriction mimetic.
6. Protect Trans-Resveratrol from Light
To maintain its efficacy, protect trans-resveratrol supplements from light, as exposure converts it to the less active cis form.
7. Take Resveratrol in Morning
To maximize bioavailability, consider taking resveratrol in the morning, as its metabolism varies in a circadian fashion with higher bioavailability occurring then.
8. Resveratrol with Moderate Fat Breakfast
Increase resveratrol’s bioavailability by taking it with food, specifically a moderate fat breakfast, rather than a very high fat breakfast.
9. Combine Resveratrol with Piperine
Consider taking resveratrol with piperine (found in black pepper) to potentially enhance its efficacy, as a study showed it improved cerebral blood flow despite not improving bioavailability in humans.
10. Avoid Red Wine for Resveratrol
Do not rely on red wine for therapeutic doses of resveratrol, as a typical glass contains only 1.8 milligrams, far below the 100 milligrams to 1 gram range found in studies.
11. Adjust Resveratrol Dose with Exercise
If using resveratrol with exercise, be aware that low doses (150-250 mg/day) may blunt exercise adaptations, while higher doses (500 mg/day) have shown positive effects on mitochondrial density, muscle fibers, and maximal oxygen consumption.
12. Resveratrol for Type 2 Diabetes
If you have type 2 diabetes, consider a resveratrol treatment of one gram per day, as studies showed it significantly reduces blood pressure, fasting blood glucose, and circulating insulin, while increasing HDL levels.
13. Resveratrol for Fatty Liver
If you have non-alcoholic fatty liver disease, taking a resveratrol supplement of 300 or 500 milligrams per day for 3 months may decrease LDL, liver fat, and inflammatory markers, while increasing insulin sensitivity.
14. Resveratrol for Obesity Markers
For obese individuals, 150 milligrams of resveratrol daily for 30 days may promote caloric restriction-like effects, leading to reduced blood pressure and improved blood glucose, insulin, and triglyceride levels.
15. Resveratrol for Older Adult Memory
Healthy adults aged 50 to 75 years old may improve their ability to complete memory tasks by taking 200 milligrams of resveratrol daily for 26 weeks.
16. Resveratrol for Alzheimer’s Disease
For patients diagnosed with Alzheimer’s, resveratrol treatment starting at 500 milligrams once daily and escalating to 1000 milligrams twice daily showed improvements in mental examination status, amyloid beta levels, and neuroinflammation markers; this should be done under medical supervision.
17. Resveratrol for Cancer Prevention
Healthy individuals may consider resveratrol at doses of one gram or 2.5 grams to potentially prevent cancer by reducing IGF-1 and increasing carcinogen detoxifying enzymes.
18. Resveratrol with Statins for Heart
If taking statins, supplementing with a 350 milligram resveratrol-enriched grape extract daily for 6 months may decrease cardiovascular risk markers like LDL, oxidized LDL, and apolipoprotein B.
19. Low-Dose Resveratrol Post-Heart Attack
For individuals who have experienced a heart attack, a very low dose of 10 milligrams of resveratrol every day for three months may decrease LDL and improve left ventricle diastolic and endothelial function.
20. Resveratrol for Anti-Inflammation
Healthy individuals may consider a six-week course of Japanese knotweed extract containing 40 milligrams of resveratrol to lower reactive oxygen species and suppress pro-inflammatory cytokines.
21. Resveratrol and Prostate Cancer
Men with prostate cancer should be aware that one gram of resveratrol per day for four months was found to lower serum levels of androgen precursors like DHEA, though its clinical relevance is difficult to ascertain.
22. Join FoundMyFitness Premium
Sign up for FoundMyFitness Premium at foundmyfitness.com/premium for $15 a month to gain benefits like early access to content, exclusive content, free genetic report updates, presentation materials, a t-shirt, Q&A access, and a bi-monthly Science Digest.
23. Try Science Digest Trial
Sign up for the bi-monthly Science Digest trial at foundmyfitness.com/trial to receive three free issues, offering a low-effort way to preview the content before committing to a premium membership.
24. Use FoundMyFitness Topic Pages
To learn more about topics like resveratrol, sirtuins, caloric restriction, and autophagy, utilize the free, illustrated, and cited topic pages available on foundmyfitness.com.
1 Key Quotes
To get the same as our mice, you'd have to drink a barrel a day, which I definitely don't recommend, however tempting.
Dr. David Sinclair