Tadalafil – better known by its brand name Cialis – is one of the most commonly prescribed drugs for erectile dysfunction.
But in some biohacking and wellness circles, it's increasingly being repurposed for an entirely different reason.
Online clinics and influential figures are promoting it as a kind of all-purpose longevity drug – delivering benefits for the cardiovascular system, brain and even athletic performance.
The drugs aren't approved for preventing heart attack and stroke, let alone for extending life.
However, the enthusiasm does reflect growing interest among some experts in the field of cardiology and men's health that tadalafil and other drugs in its class could have a legitimate role in preventive health.
"It's a serious area of discussion," says Dr. Robert Kloner, chief science officer at the Huntington Medical Research Institute and a professor at the University of Southern California.
"Cardiovascular disease remains the number one killer – and we have these drugs that may have a potential benefit, but we have to learn a lot more."
The buzz of longevity
Tadalafil belongs to the same class of drugs as sildenafil, i.e., Viagra – with the primary difference being that its effect lasts considerably longer.
While both have been on the market for decades, a handful of large studies, many of them published in recent years, have shown that men taking the drug fare better: They have lower rates of cardiovascular disease and death, and are less likely to develop dementia.
The major studies in this area are observational – and retrospective – meaning they can only show associations, not that tadalafil was the definitive cause.
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But the findings are remarkably "consistent" across the literature, says Kloner, whose lab has studied these medications extensively. "It's a very interesting signal."
The findings have surfaced in the online longevity conversation, and prominent voices – from Stanford neuroscientist and podcaster Andrew Huberman to the immortality-seeking tech mogul Bryan Johnson – have talked up the idea of taking tadalafil for more than sex.
Even some women are getting on board.
"It seemed very harmless," says Kristi Sawicki, who holds a doctorate in molecular oncology and has built a following on social media around longevity.
"If anything it's going to help blood flow and that can be beneficial to our brain and our heart," she told NPR.
Sawicki started taking tadalafil about a year ago.
It was one of the offerings in the online telehealth clinic she used for her GLP-1 prescription. That prompted her to dig into the research herself.
"It's a very well-understood mechanism," she says.
As someone with a family history of heart disease, she saw taking tadalafil as "low-hanging fruit" for cardiovascular health – and has also noticed other benefits, like a better pump in the gym.
The studies
While mostly used for erectile dysfunction, both tadalafil and sildenafil are also approved for treating a rare form of high blood pressure affecting the lungs, as well as symptoms of an enlarged prostate in men.
In essence, these medications – known as PDE-5 inhibitors – work by preventing the breakdown of a signaling molecule, which in turn helps relax smooth muscle cells and dilate blood vessels.
This not only improves blow flow in one particular region but also relaxes and widens blood vessels throughout the body, Kloner says.
Sildenafil – approved in the late '90s – was famously developed as a drug to treat chest pain caused by poor blood flow to the heart, until its "side effects" were recognized and drug makers changed course.
There's evidence – mostly from small trials in humans – that PDE-5 inhibitors like tadalafil may benefit blood-vessels. Plus, lab and animal research have suggested these drugs can also have anti-inflammatory effects.
The studies drawing on medical records of men who were prescribed these drugs, primarily for erectile dysfunction, have shown sizable effects.
For example, an analysis by Kloner of more than 8,000 men taking tadalafil found they had a 55% lower rate of dying from cardiovascular causes and a 44% lower rate of overall mortality during the study period.
Another study – this based on more than half a million patients – showed a 32% lower risk of dementia among those taking tadalafil, along with improved mortality.
"We were particularly fascinated by the dementia piece," says Dr. Dietrich Jehle, chair of emergency medicine at UTMB and lead author of the analysis, noting that data from the U.K. has also indicated a lower risk of Alzheimer's disease.
Researchers like Kloner and Jehle emphasize that without prospective studies – ideally randomized trials – these findings need to be read with caution. There could be unknown factors that influence why men who seek out medications for erectile dysfunction are less likely to die and develop certain diseases. Kloner also acknowledges the drugs are not as well studied in women.
The problem, he says, is that pharmaceutical companies aren't incentivized to run these costly studies because generic versions of the drugs are already available.
"It's not something that cardiologists are routinely recommending, I'll tell you that," Kloner says. "But these drugs in general are very safe."
The online marketplace
Much of the current marketing around tadalafil comes from direct-to-consumer online clinics, where it's often advertised alongside other trendy wellness and longevity therapies.
For example, AgelessRx – a company that Sawicki promotes in her online content – sells a monthly $70 prescription of low dose tadalafil for longevity purposes.
In an interview with NPR, the company's medical director, Dr. Jenell Decker said she felt the data were strong enough to warrant offering it to both men and women over 40.
"In longevity, that's what you have to do with a lot of things, you have to infer," she says, "because if you wait until a person is already showing symptoms, you're already behind."
But some experts are troubled by this off-label use of the medication, without better data in humans.
"Absence of evidence of harms doesn't mean there isn't harm," says Dr. Steve Nissen, chief academic officer of the Cleveland Clinic Heart, Vascular & Thoracic Institute. "In the absence of randomized controlled trial data, it's pretty hard to justify."
Expert panel evaluating the merits
There are signs tadalafil could be gaining wider acceptance outside of the online wellness and optimization world.
The topic came up recently during the latest meeting of an influential medical group, known as the Princeton Consensus Panel, which focuses on men's sexual function and cardiovascular health.
The group of medical experts – which included Kloner and other preventive cardiologists – arrived at consensus language that low dose tadalafil is "appropriate" for a subset of men who are at elevated risk of developing cardiovascular disease due to the build up of plaque in their arteries, according to Dr. Martin Miner, who co-chaired the June conference. (Their formal recommendations are not yet published.)
In an email to NPR, Miner acknowledged some were "hesitant" to endorse this broader use of tadalafil because there were no randomized controlled trials, but ultimately decided to do so, based on the existing observational research.
"This is not for all men," says Miner, who directs the Men's Health Center at Brown University in Providence, R.I., though he does prescribe it for many of his patients who're at higher risk of cardiovascular disease.
"I believe men need all the help we can give them due to the longevity gap in this country," he added.