Is Resveratrol a Longevity Compound? – FoundMyFitness, Hosted by Dr. Rhonda Patrick

Check out the FoundMyFitness Episode Page & Show Notes

Key Takeaways

  • A 5 oz. glass of red wine contains ~1.8 milligrams of resveratrol
    • Therapeutic doses typically range from 100 milligrams to 1 gram
  • Resveratrol exists in two molecular arrangements: trans- and cis-
    • Trans-resveratrol is the predominant form found in most supplements, and also the more stable (but if exposed to light, it can convert to the less-active cis-resveratrol)
    • Trans-resveratrol is more bioavailable if taken both in the morning and with food
  • More data is needed to determine resveratrol’s effect on exercise
  • Resveratrol activates a variety of anti-inflammatory and antioxidant response pathways
  • Resveratrol is a calorie-restriction mimetic

Intro

  • In this solo-episode. Dr. Rhonda Patrick (@foundmyfitness) provides a research overview of resveratrol, one of the most widely-studied plant compounds

What is Resveratrol?

  • Resveratrol is a natural compound located in the stems, leaves, roots, fruits, and seeds of a variety of plants
    • It’s found in its highest concentrations in the skin of red grapes, but can also be found in peanuts, blueberries, and the root of Japanese knotweed

The History

  • In the 1990s, resveratrol first popped up on the radar when nutrition scientists suggested it was responsible for the cardiovascular benefits thought to be associated with drinking red wine

Resveratrol Improves Cardiovascular and Metabolic Health

  • In people with type 2 diabetes, 1 gram/day of supplemental resveratrol has been found to reduce blood pressure, fasting blood glucose, and fasting insulin levels while increasing HDL levels (Study 1Study 2Study 3Study 4)
  • In obese individuals, 150 mg/day of resveratrol supplementation promoted caloric restriction-like effects (Study)
    • Participants also had significant decreases in blood pressure, blood glucose, and triglyceride levels
  • When people with non-alcoholic fatty liver disease took a resveratrol supplement of either 300 or 500 mg/day for 3 months, their serum LDL levels, liver fat concentrations, and inflammatory biomarkers all decreased, while their insulin sensitivity increased (Study 1Study 2)
  • In a study involving 75 people taking a statin, those who also took a 350 mg resveratrol-enriched grape extract daily for 6 months saw a decrease in several cardiovascular risk markers (LDL decreased by 4.5%, oxidized LDL decreased by 20%, and ApoB decreased by 9.8%) (Study)
    • After the 6-month treatment period, participants received double the original dose for another 6 months. This resulted in a decrease in the inflammatory markers TNF-alpha and IL-6, while increasing the anti-inflammatory marker IL-10. (Study)
  • In people who already experienced a heart attack, taking 10 mg/day of supplemental resveratrol for 3 months resulted in decreases in LDL, as well as improved left ventricular diastolic function and endothelial function (Study)

Resveratrol is Anti-Inflammatory

  • In one study, healthy individuals were given a 6-week course of Japanese knotweed extract containing 40 mg of resveratrol. At the conclusion, the participants had lower levels of reactive oxygen species and suppressed expression of the pro-inflammatory cytokines TNF-alpha and IL-6.
  • In monkeys eating an obesogenic diet, resveratrol improved a variety of inflammatory markers (Study)

Resveratrol Improves Neurological Health

  • “Resveratrol counters neuronal inflammation and improves cognitive performance by mitigating reactive oxygen species, inhibiting pro-inflammatory molecules, and inhibiting beta-amyloid plaque formation in aggregation, a hallmark of Alzheimer’s disease”Dr. Rhonda Patrick
  • 200 mg of resveratrol taken daily for 26 weeks improved memory in healthy individuals aged 50-75 (Study)
  • 500-2000 mg/day of resveratrol improved mental examination status scores, spinal fluid amyloid-beta levels, and spinal fluid levels of matrix metalloproteinase 9 (a mediator of neuro-inflammation) in patients with Alzheimer’s disease (Study)

Resveratrol and Cancer

  • “Some rodent studies have shown the potential of resveratrol for the treatment of various types of cancer including pancreatic, prostate, colorectal, liver, and breast cancer, but there simply isn’t enough evidence to suggest that resveratrol is a viable option for cancer therapy in humans” – Dr. Rhonda Patrick
    • That said, resveratrol may help prevent cancer by reducing IGF-1, which is associated with tumor proliferation (at large doses of 1-2.5 g/day)

Resveratrol is a Calorie Restriction Mimetic

  • Resveratrol works mainly through sirtuin activation (sirtuins are a class of proteins that plan an essential role in aging and keeping cells healthy)
    • Sirtuin activation mimics many of the longevity benefits of caloric restriction (and thus, resveratrol is a caloric restriction mimetic) 
      • In mice, resveratrol supplementation resulted in several physiological changes typically seen with caloric restriction, such as reduced IGF-1 and increased AMP-kinase activity (Study)
  • As a caloric restriction mimetic, resveratrol promotes autophagy (Study)
    • Autophagy is the process by which cells (or cellular components) eat themselves under conditions of nutrient deprivation (AKA fasting). The dysfunctional cells (like cancer cells) or dysfunctional cell components tend to be “eaten” first.

Resveratrol Activate Genes That Promote Resilience Against Stress (AKA Stress Response/Longevity Genes)

  • Plants produce phytochemicals (like resveratrol) under stress 
    • These compounds either attract pollinators or in some cases, deter insects
    • In humans, phytochemicals activate a variety of stress response pathways, resulting in many beneficial effects such as:
      • The activation of SIRT1, which is linked to anti-inflammatory activity, metabolic adaptations, and neurological protection
      • The activation AMP-kinase, a fuel-sensing enzyme that inhibits mTOR, leading to the down-regulation of cellular growth pathways

Resveratrol and Exercise

  • 250 mg/day of resveratrol blunted the positive effects of exercise in elderly men (aged 60-72) who exercised by engaging in cycling and CrossFit 3x/week for 8 weeks (Study)
    • Which positive effects? – Reduced blood pressure, improved cholesterol levels, and improved oxygen uptake
  • In another study of 22-year-old men who engaged in high-intensity interval training 3x week, 150 mg/day of supplemental resveratrol limited increases in aerobic/anaerobic capacity and muscle fiber-specific adaptations
  • In a 12-week study among men and women aged 65-80 who practiced resistance training 3x/week, 500 mg/day of resveratrol increased mitochondrial density, muscle fibers, and maximal oxygen consumption (compared to exercise training alone)
  • In summary, the data surround resveratrol and exercise is contradictory 
    • At a low dose, resveratrol acts as s a mild direct antioxidant (which bind to and sequester reactive oxygen species)
      • This isn’t preferable – the reactive oxygen species generated during exercise are essential for cardio-respiratory adaptations
    • At higher doses, resveratrol seems to act as an indirect antioxidant (which activates the body’s own endogenous antioxidant systems, like glutathione)

Resveratrol Bioavailability

  • 🎧 Resveratrol exists in two molecular arrangements: trans- and cis-
    • Trans-resveratrol is the predominant form found in most supplements, and also the more stable (but if exposed to light, it can convert to the less-active cis-resveratrol)
    • Trans-resveratrol is more bioavailable if taken both in the morning and with food

Dose Matters

  • 🎧 A 5 oz. glass of red wine contains a minimal amount of resveratrol (~1.8 mg)
    • Therapeutic doses typically range from 100 mg – 1 g
    • Fun fact: To get the same amount of resveratrol as mice in scientific studies, you’d have to drink roughly a barrel of red wine
  • Doses of resveratrol up to 5 grams/day in humans do not seem to cause any adverse side effects
    • That said, doses > 2.5 grams can bring on mild to moderate gastrointestinal distress

Additional Notes