Resveratrol

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• 1 randomized controlled trial in Alzheimer's patients and 5 trials (2 unpublished) on cognition in non-demented adults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]

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.

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.

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].

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AlzForum reports on resveratrol research:
"Dietary Resveratrol Makes Little Difference to Health"
"Resveratrol Improves Memory in Overweight Adults"

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