Resveratrol
Specifically for Mitochondrial Dysfunction
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Why it works for Mitochondrial Dysfunction:
SIRT1/AMPK → PGC-1α → mitochondrial biogenesis & oxidative metabolism. RSV activates nutrient-sensing pathways (SIRT1 and AMPK), which can up-regulate PGC-1α, NRF1/2 and TFAM—key drivers of mitochondrial biogenesis and respiratory chain gene expression. Mechanistic and review papers outline these links across tissues. Cell
Antioxidant/anti-inflammatory effects and mitophagy. RSV reduces inflammatory signaling and supports mitochondrial quality control in preclinical models, which matters because many mitochondrial disorders feature oxidative stress and damaged organelles. ScienceDirect
Human metabolic studies show “CR-mimetic” signatures. In a crossover RCT in obese men (150 mg/day for 30 days), RSV increased muscle SIRT1 and PGC-1α proteins and markers consistent with a more oxidative phenotype—consistent with mitochondrial effects. Cell
But mechanisms aren’t uncontested. Some work has argued SIRT1 may inhibit PGC-1α activity in certain contexts, and that RSV feeding didn’t raise muscle mitochondrial biogenesis in rodents—illustrating ongoing debate. PLOS
How to use for Mitochondrial Dysfunction:
Form: look for trans-resveratrol from a reputable brand with third-party testing (e.g., USP/NSF). (General safety and supplement-quality guidance in consumer-health overviews.) Verywell Health
Typical research doses: Human trials commonly use 150–500 mg/day, sometimes up to 1,000 mg/day, for 4–12 weeks. The 150 mg/day dose produced the most cited human “CR-mimetic” effects. Higher doses (≥1–2 g/day) are used in some oncology/metabolism studies but bring more GI side-effects. Cell
Dosing schedule: Because RSV is rapidly metabolized, many clinicians split daily intake (e.g., 150–250 mg twice daily) to smooth exposure; this is a pragmatic extrapolation from pharmacokinetics showing fast glucuronidation/sulfation and low parent-compound availability. NyaSPubs
With food? PK findings are mixed; RSV’s bioavailability is poor regardless, and the strongest peer-reviewed point is extensive first-pass metabolism rather than a consistent meal effect. Avoid drawing hard rules from marketing pages. NyaSPubs
Special formulations: Micronized RSV (e.g., SRT501) achieved higher plasma levels in trials, but the program was abandoned over safety/benefit concerns—so it’s not an option. AACR Journals
Scientific Evidence for Mitochondrial Dysfunction:
Human studies (not primary mitochondrial disease):
- Obese men, RCT, 30 days, 150 mg/day: muscle SIRT1↑, PGC-1α↑, AMPK activation, citrate synthase↑; metabolic shifts consistent with improved mitochondrial function. Cell
- Older adults / exercise & skeletal muscle literature: chapters/reviews note variable effects on mitochondrial capacity and muscle performance; heterogeneity in models/doses limits firm conclusions. ScienceDirect
- Meta-analyses in metabolic conditions (T2D, MetSyn, NAFLD): signal for improvements in inflammatory/oxidative stress markers and some metabolic parameters; these aren’t direct proof of disease-modifying mitochondrial benefits. Frontiers
Primary mitochondrial diseases (e.g., MELAS, mtDNA disorders):
I could not find robust RCTs showing RSV improves clinical endpoints in primary mitochondrial disease. Most “mitochondrial” evidence is mechanistic or from non-mitochondrial populations. Systematic reviews of purified-RSV trials emphasize knowledge gaps and inconsistent clinical benefit overall. MDPI
Mechanistic & translational touchstones:
- Foundational cell/animal data linking RSV → SIRT1/AMPK → PGC-1α/TFAM/NRF1/2 and mitochondrial biogenesis/function. ScienceDirect
- Contradictory mechanistic findings arguing SIRT1 can reduce PGC-1α coactivator activity in certain settings; highlights that pathway effects are context-dependent. PLOS
Specific Warnings for Mitochondrial Dysfunction:
Bleeding risk & drug interactions: RSV has antiplatelet activity; combined use with anticoagulants/antiplatelets (e.g., warfarin, DOACs, clopidogrel, aspirin/NSAIDs) may increase bleeding risk. OUP Academic
CYP-mediated interactions: RSV can inhibit CYP3A4 (and sometimes 2C9/2C19) in vitro/in vivo, potentially raising levels of drugs that depend on these pathways (e.g., midazolam as a probe substrate). If you take narrow-therapeutic-index meds, speak with your clinician/pharmacist. Nature
GI side-effects at higher doses: Nausea, abdominal discomfort, diarrhea are common at gram-level dosing. AACR Journals
Formulation safety: The high-bioavailability SRT501 program was stopped after weak efficacy signals and safety concerns in oncology settings; this underscores that “more exposure” isn’t automatically safer or better. Fierce Biotech
Pregnancy/lactation: Human safety data are insufficient—avoid supplemental RSV (beyond food amounts) unless a clinician recommends it for a specific reason. e-lactancia.org
Bioavailability caveat: Oral RSV has high absorption but very low parent-compound bioavailability due to rapid glucuronidation/sulfation; this limits systemic exposure and may explain inconsistent clinical effects. DMD
General Information (All Ailments)
What It Is
Resveratrol is a naturally occurring polyphenolic compound—a type of antioxidant—found in certain plants, fruits, and beverages. It is most abundant in the skin of red grapes, blueberries, cranberries, peanuts, and particularly in red wine. Resveratrol belongs to a class of compounds known as stilbenes, which plants produce as a defense mechanism against environmental stressors such as UV radiation, injury, or fungal infection.
In supplemental form, resveratrol is often derived from Japanese knotweed (Polygonum cuspidatum) or grape extracts. It is commonly marketed as a nutraceutical for its potential anti-aging, cardiovascular, and neuroprotective benefits.
How It Works
Resveratrol’s effects stem from its ability to influence several key biological pathways related to aging, inflammation, and metabolism. Some of the main mechanisms include:
- Antioxidant Activity: It neutralizes harmful free radicals—unstable molecules that can damage cells and DNA—thereby reducing oxidative stress, a major contributor to aging and chronic diseases.
- Activation of Sirtuins (SIRT1): Resveratrol is known to activate sirtuin 1 (SIRT1), an enzyme involved in cellular regulation and longevity. Activation of SIRT1 enhances DNA repair, improves mitochondrial function, and promotes cellular resilience under stress. This is one reason resveratrol is sometimes linked to the concept of “mimicking calorie restriction.”
- Anti-Inflammatory Effects: It inhibits inflammatory signaling pathways, such as NF-κB and COX enzymes, helping to reduce chronic low-grade inflammation that contributes to diseases like arthritis, diabetes, and atherosclerosis.
- Cardioprotective Actions: Resveratrol helps increase nitric oxide (NO) production, which relaxes blood vessels, improving circulation and reducing blood pressure. It also prevents oxidation of LDL cholesterol, reducing plaque formation in arteries.
- Neuroprotective and Anti-Cancer Pathways: In laboratory studies, resveratrol modulates signaling cascades involved in neuronal survival, apoptosis, and tumor suppression, though the effects in humans are still being investigated.
Why It’s Important
Resveratrol has gained attention because it may support multiple systems in the body simultaneously, offering potential protection against age-related decline. Its importance lies in the following health areas:
- Heart Health: Associated with reduced risk of coronary artery disease and improved endothelial function (this is part of the so-called “French Paradox”, where moderate red wine intake correlates with lower heart disease rates).
- Brain Health: May protect against neurodegenerative disorders like Alzheimer’s and Parkinson’s disease by limiting oxidative stress and inflammation in neurons.
- Metabolic Health: Studies suggest it may improve insulin sensitivity and glucose metabolism, potentially aiding in type 2 diabetes prevention.
- Longevity Research: Through SIRT1 activation and mitochondrial enhancement, resveratrol is studied for its role in slowing biological aging and extending lifespan in animal models (though human evidence is limited).
In essence, resveratrol represents a compound at the intersection of nutrition, pharmacology, and geroscience—bridging natural dietary sources with potential therapeutic benefits.
Considerations
While resveratrol shows promise, several important points should be considered:
Bioavailability Issues
- Resveratrol is poorly absorbed and rapidly metabolized in the human body, which limits how much actually reaches tissues in its active form. Efforts are ongoing to improve its bioavailability through new formulations (e.g., liposomal, micronized, or combined with other compounds).
Dosage and Safety
- Typical dietary intake from food or wine is very low compared to doses used in studies.
- Supplement doses vary (50–500 mg/day are common), but higher doses may cause gastrointestinal upset or interact with medications.
- Long-term human data on safety are still limited.
Medication Interactions
- Resveratrol can inhibit platelet aggregation, potentially increasing bleeding risk when combined with anticoagulants (e.g., warfarin, aspirin). It may also affect the metabolism of certain drugs processed by cytochrome P450 enzymes.
Not a Substitute for a Healthy Lifestyle
- While it may offer supplementary benefits, resveratrol is not a replacement for balanced nutrition, regular exercise, or medical treatment for chronic diseases.
Research Limitations
- Much of the evidence for resveratrol’s benefits comes from animal or cell studies. Human trials are fewer and often produce mixed results, especially regarding longevity and disease prevention.
Helps with these conditions
Resveratrol is most effective for general wellness support with emerging research . The effectiveness varies by condition based on clinical evidence and user experiences.
Detailed Information by Condition
Menopause
Phytoestrogen & vascular effects: Resveratrol is a plant polyphenol that can act on estrogen receptors and up-regulate endothelial nitric-oxide sy...
Fatty Liver
Metabolic re-programming (SIRT1 → AMPK): Resveratrol activates SIRT1 and downstream AMPK signaling, pathways that reduce hepatic lipogenesis and impro...
Oxidative Stress
Amplifies your own antioxidant defenses (not just “scavenging ROS”). Resveratrol can activate the Nrf2–ARE pathway, increasing enzymes like HO-1 and N...
Cellular Aging
Sirtuin/AMPK/PGC-1α axis: Resveratrol can activate SIRT1 and AMPK, increasing mitochondrial biogenesis and shifting metabolism toward a calorie-restri...
Mitochondrial Dysfunction
SIRT1/AMPK → PGC-1α → mitochondrial biogenesis & oxidative metabolism. RSV activates nutrient-sensing pathways (SIRT1 and AMPK), which can up-regu...
Multiple Chemical Sensitivity
Resveratrol has well-documented anti-inflammatory, antioxidant, mitochondrial-protective and signaling (SIRT1/Nrf2/NF-κB) effects that make it biologi...
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Helps With These Conditions
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