Resveratrol Tested for Alzheimer’s, Arthritis, and Osteoporosis

Does resveratrol help with inflammation? In humans, the evidence of an anti-inflammatory effect is sparse and conflicting. About half of the studies show a modest anti-inflammatory effect, but the other half failed to find any. The proof, however, is in the pudding. What about clinical effects on inflammatory disease?

In rats and mice, resveratrol can help ameliorate the effects of experimentally-induced periodontitis, the inflammatory gum disease. However, it appears to have no effect on the progression of chronic periodontitis in human sufferers. Resveratrol may help with the inflammatory bowel disease ulcerative colitis, though. A pilot study of 500 mg a day of resveratrol for six weeks resulted in significantly decreased disease activity and elevated quality of life compared to placebo.

What about inflammatory joint diseases? One pilot study of 500 mg a day of resveratrol for knee osteoarthritis found a decrease in pain within a month, but there was no control group; so, the change can’t really be attributed to starting the supplements. However, a second pilot study, a randomized, double-blind, placebo-controlled trial, found that the same dose taken as an “add on” to an anti-inflammatory drug significantly improved pain and function within a month in mild-to-moderate knee osteoarthritis sufferers, more than adding a placebo. The one clinical study of rheumatoid arthritis had a control group, but no placebo, though there were objective signs of improvement in disease activity after taking 1000 mg a day for three months.

Resveratrol may also be beneficial to combat menopausal symptoms. Resveratrol has some estrogenic activity. Although it doesn’t appear to help with hormonal migraines, it does appear to help with a couple symptoms of PCOS, polycystic ovary syndrome. RESHAW—Resveratrol for Healthy Ageing in Women—is the longest study of effects of resveratrol supplementation in postmenopausal women. Those randomized to 75 mg of resveratrol twice a day suffered significantly fewer physical menopausal symptoms, including aches and pains, and a general improvement in overall well-being compared to placebo.

The RESHAW study also looked at bone loss prevention. Unfortunately, though animal studies show protective effects on bone tissue, a meta-analysis of human studies on resveratrol supplementation to improve bone quality found no significant effect on bone health markers or bone mineral density of the spine, hip, or overall skeleton. A similar story was found for cognitive effects.

Most studies on resveratrol for brain function in animal models show positive outcomes, but meta-analyses of human studies show no significant effect on memory, processing speed, executive function, or global cognitive performance, which led reviewers to suggest that resveratrol may be a “cognitive enhancer for mice only.” Most human cognition studies found no effect or mixed results—higher performance on some tasks, but lower performance on others, compared to placebo, resulting in a “lack of interpretable cognitive effects.”

Some have suggested the discrepancy between the animal models and the clinical data is that the rodents were massively dosed, up to a gram per kilogram of body weight a day, which would be like giving people an entire bottle of high-dose resveratrol supplements at once. Or, ironically, it could be the opposite, where the doses researchers gave people were too large. A dose-response study found that human cerebral blood flow was maximally boosted by the lowest dose of resveratrol tested, 75 mg a day. So, when the RESHAW study was developed, that was the dose they used, given twice a day.

RESHAW was primarily designed to test the effects of resveratrol on cognitive performance. Interim analyses at 14 weeks and a year looked promising, leading the researchers to conclude that their findings “support the adoption of resveratrol as a low-cost, effective intervention to help counteract the age- and menopause-related accelerated cognitive decline in our ageing population.” However, by the end of the two-year study, it’s not clear if the apparent benefit in overall cognition survives adjustment for multiple comparisons, meaning there were so many cognitive outcomes tested that the few treatment differences may well have arisen through chance.

What about cognitive benefit for those who really need it? Observational studies find wine drinkers tend to get less dementia, but it’s hard to disentangle the social, cognitive, and personality factors that accompany a wine drinking habit. So, researchers decided to put resveratrol to the test for Alzheimer’s disease.

A randomized double-blind, placebo-controlled pilot out of Cornell in 2006 kicked things off with a bang. Patients with mild-to-moderate Alzheimer’s disease who were randomized to a 5 mg resveratrol concoction twice a day ended up with significantly better cognition after three months compared to placebo. There was a greater than expected deterioration in the placebo group, though, suggesting this may have just been a fluke, especially since an attempt to replicate the study with the same dose for a year failed to find any effects of statistical significance. Maybe the researchers just didn’t use a high enough dose?

More than a hundred patients with mild to moderate Alzheimer’s were randomized to placebo or an escalating dose of resveratrol starting at a hundred times the dose of the previous study—500 mg once a day and ending at a 1000 mg twice a day. After a year, there were no significant improvements in cognition or the performance of activities of daily living compared to placebo. Instead, there was a significant acceleration of brain volume. At the end of the study, there was triple the brain volume loss (3 percent versus 1 percent) in the resveratrol group. And the only other randomized, double-blind, placebo-controlled trial to date found the same thing: no significant cognitive benefits and the same tripling of age-related brain shrinkage. The authors tried to somehow spin this as a positive, like hey—maybe that’s just decreased brain swelling, but as a team of researchers wrote in an understatement of the year, “It is difficult to reconcile these effects as potentially beneficial.”