Here is a highlight of Dr. David Sinclair and I discussing how two separate phase 2 placebo-controlled trials showed resveratrol (1,000mg/day) improved cognitive function and lowered biomarkers of neuroinflammation in people with Alzheimer’s disease.
Resveratrol is a naturally occurring compound found in red grapes and other plants and is also referred to as a potent sirtuin-activating compound (STAC). It protects the plants in which it is found from environmental stressors and disease. When ingested by humans, resveratrol binds to sirtuins, altering their affinity for NAD+ and their protein substrates, thereby increasing sirtuins’ activity. Sirtuins are a family of enzymes that regulate longevity through a variety of mechanisms including epigenetic regulation. As such, resveratrol presents a promising therapeutic strategy to ameliorate age-related diseases and extend healthspan. Resveratrol is a “dirty molecule,” however, known for its multiple cellular targets, so teasing out all the ramifications of this plant-based compound’s use has proven problematic.
One of the mechanisms associated with resveratrol’s beneficial actions in the brain is the activation of autophagy, a cellular defense program that targets old, damaged proteins for destruction and recycling. Animal studies have also shown that resveratrol treatment has been shown to reduce neuronal inflammation and improve cognitive performance by mitigating reactive oxygen species, inhibiting pro-inflammatory molecules such as cyclooxygenase-1, or COX1, and inhibiting beta-amyloid plaque formation and aggregation, a hallmark of Alzheimer’s disease.
Although a couple of phase 2 clinical trials have demonstrated that resveratrol treatment may improve parameters associated with Alzheimer’s disease, larger and longer studies are needed to determine whether resveratrol can promote cognitive and functional improvement.