Systematic review data published in Advances in Medical Sciences provide mixed support for the benefits of resveratrol (RSV) in patients with neurodegenerative disorders. While RSV demonstrated neuroprotective effects in chemical and animal studies, few trials have assessed its use in patients at risk for Alzheimer disease.

Investigators at the Medical University of Warsaw in Poland conducted a systematic review of PubMed for experimental and clinical studies of RSV published within the last 10 years. Articles describing the pathology of Alzheimer disease and its relationship to RSV were selected. Investigators provided a summary of the literature data and commentary on RSV’s role in neurodegenerative disease prevention.

RSV is a natural phenol produced by over 70 plant species, including grapes, blueberries, cranberries, and peanuts. It has been widely studied for its antioxidant and anti-inflammatory effects. While the exact mechanism of Alzheimer disease is unclear, research suggests that oxidative stress is closely related to its development. RSV has been shown to inhibit cyclooxygenase-2 (COX-2), thus preventing oxidative damage from free radicals. RSV can also decrease the activity of tumor necrosis factor (TNF)-alpha and interleukin-1 (IL-1), leading to substantial anti-inflammatory properties. Antioxidative and anti-inflammatory effects may have implications for Alzheimer disease treatment, though further research is necessary to interpret changes in these biomarkers during treatment with RSV.

In in vitro studies, RSV was found to destabilize amyloid aggregates and inhibit the production of amyloid ß protein (Aß). Increased Aß levels correlate with cognitive decline in patients with Alzheimer disease, and Aß aggregation and accumulation are considered key risk factors for dementia. Demonstrated in 3 studies, RSV inhibits the formation of Aß-aggregates by activating the deacetylase sirtuin 1 (SIRT1) gene. RSV also promotes the tau protein demethylation and dephosphorylation. Tau proteins, like Aß, are associated with cognitive decline. By promoting effective degradation of tau proteins, RSV may prevent the formation of aggregates associated with Alzheimer disease.


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While in vitro and in vivo studies support RSV’s protective effects, its low solubility and bioavailability limit its efficacy in humans. Efforts to increase its bioavailability include nanoencapsulation in other structure and methoxylation or hydroxylation of the RSV aromatic rings. Further study is necessary to assess the impact of these methods on RSV’s uptake. Additionally, placebo-controlled clinical trials are necessary to better elucidate the neuroprotective effect of RSV in humans. Appropriate RSV recipients may include patients with a family history of Alzheimer disease, or patients with Alzheimer disease in its early stages.

“RSV mechanisms of action indicate that it could be used in [Alzheimer disease] prevention, especially in reference to some familial forms of AD,” the investigators wrote. “The main limitations referring to such presumption include: limited [bioavailability]…and scarcity of clinical studies on RSV pertaining to large groups of humans.”

Reference

Komorowska J, Wątroba M, Szukiewicz D. Review of beneficial effects of resveratrol in neurodegenerative diseases such as Alzheimer’s disease. Adv Med Sci. 2020;65(2):415-423.