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Resveratrol

  • Vitamins & Supplements
  • Updated July 7, 2016

Resveratrol is an antioxidant found in very low levels in red wine and foods such as grapes, berries, chocolate, and peanuts. It is also available as a concentrated supplement. Resveratrol may activate sirtuins, which are proteins involved in aging. In clinical trials, resveratrol has shown few benefits for healthy people. It is rapidly metabolized and excreted from the body, which may be a factor. Resveratrol supplements are regarded as safe, although long-term use has not been sufficiently studied.

Evidence

Several small clinical trials have examined the benefit of resveratrol supplements on cognition and Alzheimer's. Our search identified:

• 0 meta-analyses or systematic reviews related to cognition
• 1 randomized controlled trial in Alzheimer's patients and 5 trials (2 unpublished) on cognition in non-demented adults
• 1 observational study on dietary resveratrol and future cognitive impairment
• Numerous preclinical studies, though with some concerns about reliability [3][4]

Potential Benefit

Some preclinical studies suggested that resveratrol may delay age-related cognitive decline and protect against dementia, but this effect was not found in human studies. Based on small clinical trials, it is unlikely that resveratrol can promote cognitive function for most healthy adults [5][6]. It may benefit memory for overweight adults, [7] but the evidence is not conclusive. Several studies have investigated resveratrol supplements for treating cardiometabolic diseases, which may increase the risk of long-term cognitive decline. Unfortunately, the best evidence to date suggests that resveratrol supplements have no meaningful effect on cardiovascular disease risk factors [8][9] although it might have some minor benefits for diabetes patients [10]. In a long-term study, dietary resveratrol from wine and food was not found to meaningfully affect health in elderly people [11]. Clinical trials are underway in patients with mild cognitive impairment [12] and healthy elderly patients [13].

For Dementia Patients

Evidence regarding resveratrol's impacts for dementia patients is mixed. In a randomized controlled trial of Alzheimer's patients [14], one year of treatment with a high dose of resveratrol had a slight positive effect on the ability to complete daily activities but no effect on several other measures of cognition and function. The effects of resveratrol on the brain were mixed with signs of both benefit and harm. Patients treated with resveratrol showed a slower progression of beta-amyloid plaques but accelerated loss of brain volume. This loss of brain volume, measured by brain imaging, may be due to a reduction in inflammation but it is usually indicative of degeneration. Based on this trial, it is unclear whether resveratrol will help or harm patients in the long term.

Safety

Several small clinical trials report no serious side effects for daily doses of resveratrol between 20 mg and 2 g. In a clinical trial of Alzheimer's patients, one year of use starting at 500 mg and going up to 2 g per day was reported to be safe and well-tolerated [14]. However, there is no reliable information on the safety of long-term use of high doses [15].

Other trials did report diarrhea or gastrointestinal discomfort at doses above 1 g per day [15]. One trial reported moderately serious side effects from 1 g per day in postmenopausal women, including liver enzyme changes and severe skin rash [16]. And yet another trial reported serious risk of kidney failure with resveratrol plus standard medical treatment for multiple myeloma (cancer) patients [17], though again most small clinical trials have not reported serious side effects [9]. Resveratrol may interact in dangerous ways with common drugs such as blood thinners, anti-inflammatory drugs, and anti-hypertensive drugs [18].

NOTE: This is not a comprehensive safety evaluation or complete list of potentially harmful drug interactions. It is important to discuss safety issues with your physician before taking any new supplement or medication.

How to Use

The highest concentration of dietary resveratrol is found in the skin of red grapes. One 5-ounce glass of red wine contains around 200 µg of resveratrol. It would take approximately 20 bottles of red wine a day to equal the level of resveratrol used in even the lowest-dose clinical trials.

To achieve any potential benefit, a high dose of resveratrol would likely be necessary, but long-term use of such high doses has not been studied. Daily doses between 20 mg and 2 g have been used in short clinical trials, with gastrointestinal side effects more common above 1 g per day [15][19]. In one high-dose clinical trial, Alzheimer’s patients were first given 500 mg once per day, which then increased to 1 g twice per day [14].

References

  1. Hubbard BP, Gomes AP, Dai H et al. (2013) Evidence for a common mechanism of SIRT1 regulation by allosteric activators. Science 339, 1216-1219.
  2. Neves AR, Lucio M, Lima JL et al. (2012) Resveratrol in medicinal chemistry: a critical review of its pharmacokinetics, drug-delivery, and membrane interactions. Current medicinal chemistry 19, 1663-1681.
  3. Visioli F (2014) The resveratrol fiasco. Pharmacological research : the official journal of the Italian Pharmacological Society 90, 87.
  4. Baell J, Walters MA (2014) Chemistry: Chemical con artists foil drug discovery. Nature 513, 481-483.
  5. Wightman EL, Reay JL, Haskell CF et al. (2014) Effects of resveratrol alone or in combination with piperine on cerebral blood flow parameters and cognitive performance in human subjects: a randomised, double-blind, placebo-controlled, cross-over investigation. The British journal of nutrition 112, 203-213.
  6. Kennedy DO, Wightman EL, Reay JL et al. (2010) Effects of resveratrol on cerebral blood flow variables and cognitive performance in humans: a double-blind, placebo-controlled, crossover investigation. The American journal of clinical nutrition 91, 1590-1597.
  7. Witte AV, Kerti L, Margulies DS et al. (2014) Effects of resveratrol on memory performance, hippocampal functional connectivity, and glucose metabolism in healthy older adults. The Journal of neuroscience : the official journal of the Society for Neuroscience 34, 7862-7870.
  8. Tang PC, Ng YF, Ho S et al. (2014) Resveratrol and cardiovascular health--promising therapeutic or hopeless illusion? Pharmacological research : the official journal of the Italian Pharmacological Society 90, 88-115.
  9. Sahebkar A, Serban C, Ursoniu S et al. (2015) Lack of efficacy of resveratrol on C-reactive protein and selected cardiovascular risk factors--Results from a systematic review and meta-analysis of randomized controlled trials. International journal of cardiology 189, 47-55.
  10. Hausenblas HA, Schoulda JA, Smoliga JM (2015) Resveratrol treatment as an adjunct to pharmacological management in type 2 diabetes mellitus--systematic review and meta-analysis. Molecular nutrition & food research 59, 147-159.
  11. Semba RD, Ferrucci L, Bartali B et al. (2014) Resveratrol levels and all-cause mortality in older community-dwelling adults. JAMA Intern Med 174, 1077-1084.
  12. Charite University B, Germany (2010) PROTOCOL: Effects of Dietary Interventions on the Brain in Mild Cognitive Impairment (MCI). In clinicaltrialsgov.
  13. Florida Uo (2014) PROTOCOL: Resveratrol to Enhance Vitality and Vigor in Elders (REVIVE). In clinicaltrialsgov.
  14. Turner RS, Thomas RG, Craft S et al. (2015) A randomized, double-blind, placebo-controlled trial of resveratrol for Alzheimer disease. Neurology 85, 1383-1391.
  15. Vang O, Ahmad N, Baile CA et al. (2011) What is new for an old molecule? Systematic review and recommendations on the use of resveratrol. PloS one 6, e19881.
  16. Chow HH, Garland LL, Heckman-Stoddard BM et al. (2014) A pilot clinical study of resveratrol in postmenopausal women with high body mass index: effects on systemic sex steroid hormones. J Transl Med 12, 223.
  17. Popat R, Plesner T, Davies F et al. (2013) A phase 2 study of SRT501 (resveratrol) with bortezomib for patients with relapsed and or refractory multiple myeloma. Br J Haematol 160, 714-717.
  18. Detampel P, Beck M, Krahenbuhl S et al. (2012) Drug interaction potential of resveratrol. Drug Metab Rev 44, 253-265.
  19. la Porte C, Voduc N, Zhang G et al. (2010) Steady-State pharmacokinetics and tolerability of trans-resveratrol 2000 mg twice daily with food, quercetin and alcohol (ethanol) in healthy human subjects. Clin Pharmacokinet 49, 449-454.

Photo: Yuxuan Wang