Viagra for Brain Health?

A new study adds to the growing body of evidence suggesting that sildenafil (Viagra), commonly used for treating erectile dysfunction (ED), may also offer protection against Alzheimer’s disease (AD).

A comprehensive real-world analysis of patient data from two databases revealed a 30%-54% reduced prevalence of AD among patients who took sildenafil compared to those who did not, after adjusting for various potential confounders.

This finding was reinforced by mechanistic studies showing a decrease in neurotoxic protein levels in brain cells exposed to the phosphodiesterase type 5 inhibitor (PDE5i).

“Our results further support the repurposing of this existing FDA-approved drug as a novel treatment for Alzheimer’s, which urgently needs new therapies,” stated Feixiong Cheng, PhD, director of the Cleveland Clinic Genome Center and the lead researcher, in a news release.

“We utilized artificial intelligence to integrate data across multiple domains, all indicating sildenafil’s potential against this devastating neurological disease,” Cheng added. The study was published online on March 1, 2024, in the Journal of Alzheimer’s Disease.

Neuroprotective Potential

Using real-world patient data from the MarketScan Medicare Supplemental database (2012-2017) and the Clinformatics database (2007-2020), researchers conducted propensity score-stratified analyses, adjusting for gender, age, race, and comorbidities.

They examined individuals with pharmacy claims for sildenafil and four commonly used drugs—bumetanide, furosemide, spironolactone, and nifedipine. Results indicated that sildenafil use was associated with a reduced likelihood of AD compared to the control drugs.

For instance, sildenafil use was linked to a 54% reduced incidence of AD in MarketScan (hazard ratio [HR], 0.46; 95% CI, 0.32-0.66) and a 30% reduced prevalence of AD in Clinformatics (HR, 0.70; 95% CI, 0.49-1.00) compared with spironolactone.

Mechanistically, we know that drugs loke Viagra increase nitric oxide. Nitric oxide improves both cellular metabolism as well as blood flow. Interestingly, elevation of uric acid, associated with increased dementia risk, inhibits nitric oxide as I described in my book, Drop Acid.

Getting back to the study, the authors also revealed that RNA-sequencing data analysis showed that sildenafil specifically targets AD-related genes and pathobiological pathways, further supporting its beneficial effect in AD.

“We believe our findings provide the evidence needed for clinical trials to further examine sildenafil’s potential effectiveness in Alzheimer’s disease patients,” Cheng concluded.

To be clear, this isn’t a recommendation that we should all jump in and start taking Viagra. Rather, in embracing the mechanisms as to how the drug actually provides benefits, it makes sense to keep our nitric oxide levels in the health supportive range by consuming nitrate rich foods like beets, spinach, garlic, and celery. Also, nitric oxide is enhanced by physical exercise. And, as I recently reported, avoiding antibacterial mouthwash is important for maintaining healthy nitric oxide levels.