Viagra may reduce the risk of Alzheimer’s disease — no, not a joke

Now for something completely different — a newly published peer-reviewed article shows that Viagra may reduce the risk of Alzheimer’s disease. Yes, you read that right, sildenafil (brand names of Viagra or Revatio) users have a substantially lower risk of subsequent diagnoses for dementia.

And, as you know, I’m a proponent of biological plausibility — there appear to be physiological and biochemical reasons why Viagra can reduce the risk of Alzheimer’s disease.

So, let’s take a look at how sildenafil works (no, it’s not about sex), the paper itself, and the plausible mechanisms that may allow it to work. And yes, I’m going to try to avoid the jokes, but you are more than welcome to place them in the comments!

All about sidenafil

Sildenafil was developed by Pfizer (yes, the same company that makes one of the mRNA vaccines for COVID-19) in the late 1980s to be used as a drug for hypertension, or high blood pressure.

I attended a cardiology conference in the early 1990s when data from the studies were being presented, and I had a chance to talk to one of the Pfizer representatives about it. He told me the story that during phase 1 clinical trials, which normally just includes healthy volunteers, “excessive” erections were reported, and the researchers were concerned that the adverse events were going to prevent FDA approval.

Most of the researchers involved with the studies were young, so they didn’t put 2 and 2 together. Another researcher saw the results and essentially talked to the management that they should forget about the hypertension indications and press ahead with research on treating erectile dysfunction. In other words, Pfizer went from having another anti-hypertensive drug to a blockbuster, with 20 years of advertising about it.

Nevertheless, sildenafil actually is still prescribed for a particular disease called pulmonary hypertension, a serious condition. Sildenafil is sold as Revatio for this indication. It also has some other off-label uses, including for altitude sickness — climbers preparing to ascend Mt. Everest used to take the drug to help them survive.

Sildenafil acts by blocking phosphodiesterase 5, an enzyme that promotes the breakdown of cGMP, which regulates blood flow in the penis. It requires sexual arousal, however, to work. It also results in dilation of the blood vessels in the lungs, which is why it is effective in treating pulmonary hypertension.

Sildenafil is now a generic drug, so it is no longer a major profit center for Pfizer, although probably still more than they earn for vaccines.

couple elderly man old
Photo by Pixabay on Pexels.com

Viagra and Alzheimer’s disease — the paper

In a paper published in Nature Aging on 6 December 2021, researchers performed retrospective case-control pharmacoepidemiologic analyses of insurance claims data for 7.23 million individuals in a Medicare database.

Across six years of follow-up, sildenafil users were 69% (!!!, I could not resist the irony) less likely to develop Alzheimer’s disease than non-sildenafil users (hazard ratio = 0.31). That is a statistically significant indicator that sildenafil could be repurposed as a medication to prevent or, possibly, treat Alzheimer’s disease.

Moreover, the researchers stated that the phosphodiesterase 5 inhibitor has been shown to increase neurite growth and decreased tau protein expression in neuron models derived from induced pluripotent stem cells. In other words, this may establish the biological plausibility for sildenafil to be able to reduce the risk of Alzheimer’s disease.

Although these results may, on the surface, show a strong correlation between Viagra use and Alzheimer’s disease, the study only shows potential correlation and not causality between the drug and the diseases. And there’s a lot of information that would need to be gathered in a powerful clinical trial — dosage, the safety of long-term use (which we probably already have after 20 years on the market), and whether it actually does have a clinically and statistically significant effect in a controlled study.

And maybe men and women who take Viagra have confounding factors, like lifestyle choices, that lead to a lower risk of Alzheimer’s disease.

As I have written previously, treating or preventing Alzheimer’s disease has been a difficult process. Many drugs that were purposely developed to treat Alzheimer’s disease have failed or have extremely weak evidence of clinical effectiveness.

Pfizer will probably sponsor clinical studies with Viagra to determine if it has any effect on Alzheimer’s disease — they can create new advertisements for their drug in an attempt to revitalize their sales. Because if it really has an effect on Alzheimer’s disease, it will become a blockbuster once again. Of course, as I usually say, “call me when the phase 3 clinical trials are completed and published in a respected journal.” We’ll see.

At a minimum, this article really shows how real medical databases can be mined for useful information about repurposing drugs. However, only more research will tell us if we have a potential tool to prevent Alzheimer’s disease.

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The Original Skeptical Raptor
Chief Executive Officer at SkepticalRaptor
Lifetime lover of science, especially biomedical research. Spent years in academics, business development, research, and traveling the world shilling for Big Pharma. I love sports, mostly college basketball and football, hockey, and baseball. I enjoy great food and intelligent conversation. And a delicious morning coffee!