Could Viagra be used to treat Alzheimer's disease?

For a quarter of a century, Viagra (sildenafil) and its younger cousins like Cialis (tadalafil) have been improving the sexual health of men worldwide. These drugs have become the gold standard for treating erectile dysfunction. They work by inhibiting the level of a compound called PDE5, thereby increasing blood flow to the penis. Now, it appears they may also have other positive health effects.

A statistical study published in 2021 found that “sildenafil usage is significantly associated with reduced likelihood of Alzheimer's disease in a longitudinal patient database with 7.23 million subjects.” This work, led by Jiansong Fang of the Cleveland Clinic's Genomics Medicine Institute, demonstrates an emerging and very promising approach called pharmacoepidemiologic analysis. Essentially, they took millions of patient records obtained from insurance companies and looked for drugs that were being taken for other reasons that might be correlated with reduced risk of Alzheimer's.

These researchers weren't just throwing digital darts at the epidemiological data. They also considered genetic factors and the mechanism of action of various drugs. Since sildenafil improves blood flow in the penis, perhaps it may also get more blood to brain tissue. The drug also increases the level of a compound called CGMP, which may benefit brain cells.

The proposed Viagra-alzheimer's link got another huge boost recently with a study from University College, London (UCL). Writing in the Feb. 27, 2024, issue of the journal Neurology, researcher Matthew Adesuyan and colleagues reported that U.K. men taking sildenafil and similar drugs were 18 per cent less likely to develop Alzheimer's in later years. The effect was even more pronounced in men who were more frequent users of the medication. Researchers found a 44 per cent lower risk in men who had 21 to 50 prescriptions during the study period.

Researchers point out that these studies do not prove cause and effect. Perhaps older men who are healthier and less likely to get Alzheimer's are more avid users of PDE5 inhibitor drugs. The UCL researchers did adjust their findings for factors like age, body mass index, underlying health conditions and smoking.

Part of the reason for the enthusiasm around this work is that it involves a drug that is already approved for other uses and that has a long track record of safety. Viagra was initially developed to treat high blood pressure and a heart condition called angina pectoris. In one of those wonderful cases of medical serendipity, researchers discovered the drug's erection-enhancing ability, and the rest is history.

The drug reportedly earned pharmaceutical company Pfizer $400 million in its first three months on the market and reliably produced annual sales of almost $2 billion. Pfizer's patents on the drug expired in 2020, and we now see generic Viagra being sold via TV commercials and on the internet. It still requires a prescription in Canada, the U.S., and many other countries.

One side effect of the success of these drugs is the popularizing of telehealth. Few men are eager to talk about erectile dysfunction face-to-face with their physician. However, if the whole transaction can be done online, perhaps with a short video interview, it seems much less invasive. Of course, you should deal with a reputable company with licensed medical personnel to ensure you get the real thing safely.

Some interesting side effects have been reported by men taking sildenafil. These include vision abnormalities such as cyanopsia, in which everything appears to have a blue tint. This is because the drug also inhibits PDE6, which is involved in colour vision. A few very rare cases of total vision loss have been reported, but most experts agree you will probably not go blind from taking it.

My friends who give out the tongue-in-cheek Nobel prizes for the wackiest published research chose as their 2007 winner “Sildenafil accelerates re-entrainment of circadian rhythms after advancing light schedules.” This paper says that the drug reduced the effect of jet lag on hamsters by 25 to 50 per cent, but only when travelling in an eastbound direction. While this research hasn't really caught fire for human jet lag, it does illustrate the ingenuity of some scientists.

PDE5 inhibitors may have many uses beyond erectile dysfunction. Some believe this class of drugs may be useful for men with benign prostatic hyperplasia, who have difficulty urinating. Other drugs like Flomax treat this condition, but perhaps there's virtue in getting two benefits from one medication.

This brings to mind the elderly man who asks his doctor for a quarter of a Viagra pill. That won't get you a full erection, he was told. No, he replied, I just want to stop peeing on my shoes.