Sildenafil as a candidate drug for Alzheimer’s disease | Hacker News Reader

Sildenafil as a candidate drug for Alzheimer’s disease

nature.com

66 pointsCharlesW36 comments

Unrelated but funny anecdote.

My daughter was on Sildenafil while she was in the NICU on ECMO (look it up if you want to see something very metal for an 11 day old infant to be on). While she was on ECMO, she was medically paralyzed so she didn't pull the cannula out of her jugular vein. She was on sildenafil as a blood thinner so her blood didn't clot in the ECMO circuit.

I was chatting about this on facebook and soon after realized that sildenafil is a common drug used to treat ED in men. I got ED ads in facebook for the better part of 2 years after this one post and found it quite amusing.

She's a healthy and happy 4 year old now. That treatment (and sildenafil) ultimately saved her life.

Glad to hear your daughter is healthy and happy! I'm not sure where you're based out of, but I am thankful that my kids had access to a highly sophisticated NICU's.

And funny enough Sildenafil for a ED treatment came about because that was a sideffect during medical trials for treating blood pressure.

She was treated at Lurie Children’s in Chicago. We learned the difference between a level 4 NICU and not, is part of the literal life and death difference with kids born with what she was. We were very lucky. Thanks!

Did they say it was a blood thinner? vs. lowering the blood pressure in her pulmonary arteries in conjunction w/ heparin as the blood thinner?

It was in fact both. She was born with a diaphragmatic hernia if you’re medically inclined. Her left lung was 23% the size it needed to be so she had severe pulmonary hypertension. Post surgery to fix it, her heart basically gave out and her vitals took a dive. ECMO for eleven days gave her enough time to grow enough to figure it out.

It was a blood thinner to keep the blood from clotting in the ECMO circuit, but also helped with her rather severe pulmonary hypertension. She was intubated approximately ten second after I cut the umbilical chord and stayed that way for three months. A diaphragmatic hernia is no joke man!

Yeah, except this was published in December 2021. A NIH study from October 2022 with actual control and experimental groups shows no reduced risk of Alzheimer's among sildenafil takers: https://www.nih.gov/news-events/news-releases/nih-dream-stud...

And indeed that one links to OP's article as an example of the original results it was investigating.

Confounded stats, of course. Older people who are physically and mentally healthy enough for sex are far less likely to have Alzheimer's.

Agree this is a very possible explanation. Though it is also possible that the use of viagra leads to more sexual activity for the elderly which promotes and maintains their health to begin with. So not directly attributable to the pharmacology of the viagra but still a contributing factor to the result.

Off-label uses that appear to actually be effective include altitude sickness and prevention of SIPE (Swimming Induced Pulmonary Edema). I take it for the latter, and it's remarkable. No Sildenafil = I cough up blood after just a few minutes swimming in cold water (as in a triathlon). Sildeanfil = no ill effects whatsoever. I'm unclear how a vasodilator would impact a neurological disease.

Asking because I am genuinely curious, if you are willing to share: What mindset do you have where you keep doing an activity that normally results in you coughing up blood? I know that sounds like a super disrespectful question, it's just the sort of thing I think about a lot due to having some health related activity restrictions that I've had to negotiate with myself. Always interested in what other people's journeys are in this space.

Ha, fair. I love open water swimming and triathlon, and I can do it in not-cold water or a pool indefinitely, plus the Sildenafil entirely prevents it in cold water. Even without Sildenafil all I have to do is stop swimming and I'm fully better after an hour or so.

Well that's good! I imagine the first time it happened must have been disturbing.

Yes. The first time it happened was in the Hudson River in the NYC triathlon. I thought for sure that I'd just ingested some sludge, and I went on to complete the race, after which I was sent to the hospital (I walked). My pulse ox was 86. Most triathlon deaths occur during the swim portion of the race and are attributed to cardiac events, often SCD, but pulmonary edema may actually be the primary cause. A teeny bit of education (chest congestion? get out of the damn water!) could save lives, but nobody in the business of triathlon wants to scare off new participants, since the amateur fee-paying end of the sport is really the whole game.

Wow, I had no idea. That would not have been on my list of potential dangers from long swims at all!

This off-label use of sildenafil for SIPE was part of a bigger scandal in the US Navy SEALs. Specifically, during the selection course for the SEALs, so many recruits suffered from SIPE it was common for many of them to surreptitiously take Viagra and keep training.

One soldier drowned as a result and another collapsed on land after a punishing swim and died.

https://www.nytimes.com/2022/08/30/us/navy-seal-training-dea...

I participated in the clinical trial at Duke that's linked to from that story, which honestly was a blast. That the medics let this guy keep training is astonishing to me. If they measured his pulse ox and sent him back in anyways, that's criminal. Also, as I understand it, Sildenafil during dives is a bad idea (something about seizures) which might be why it's "banned" in SEAL training.

But who funded the Duke study that surfaced Sildenafil as a candidate drug? The Navy SEALs, of course.

The biggest thing you can do for Alzheimer's is be physically fit at mid life. I don't suppose that's correlated with sex and Viagra usage... Oh wait.

I realize anecdotes aren't data etc. etc. but my grandpa was very fit up through retirement (and stayed spry after retirement) since he repaired dishwashers, washing machines, and dryers for his whole career. Still got an absolutely terrible case of Alzheimer's that led to his death (and made me much more worried about my potential of getting it when I get older). Won't even try to think about if he and my grandma were sexually active though, too gross.

So being physically fit definitely doesn't guarantee you won't get Alzheimer's.

Yeah, it's not a guarantee. Sorry about your grandpa. However, it is the strongest preventative measure we know about currently.

Just like we know exercise is one of them best things you can do for cardiovascular health as well, but it doesn't mean fit people don't get heart attacks.

There is also a confound in the other direction too, people who need sildenafil for erections are probably less healthy than ones who don't

Maybe, maybe not? One reason for a sildenafil prescription could be prostrate surgery for cancer. If that works, and it's a one-and-done, then no further health problems from that should surface. OTOH, if one is taking sildenafil because of side effects of blood pressure medicine, then yeah, there's a point to be made there. OTOOH, some folks take it for side effects of some traumatic event, which did not necessarily have any effect on overall health.

So I'm not so sure that a sildenafil prescription is a reliable health indicator.

My argument isn't "obviously all the confounds run in this direction". Just we don't know if people who use sildenafil or healthier or less healthy than the general population. I suspect it's a function of age, younger people prescribed sildenafil are probably less healthy than age matched controls, and older people are more healthy than age matched controls.(because they have to be with with it and fit enough to convince someone to have sex with them, and be healthy enough to have sex)

If you are getting prostate surgery, they are likely taking the whole thing and the patient’s sex life is effectively over.

The win is not having to wear diapers or use a catheter, which is more and more the outcome.

Sex someday perhaps.

that is the weakness of the study design...."retrospective case–control pharmacoepidemiologic analyses" cannot really control for confounders as well as RCT

That's a roller coaster for this drug; Started off as high blood pressure candidate, ends up at Alzheimer's candidate (with a detour in the middle of course).

Don’t forget about it’s longer acting cousin (tadalafil) working for prostate problems.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4054509/

Sildenafil is used for pulmonary hypertension, oddly after it’s approval for erectile dysfunction. I guess that’s a home run?

And let’s not forget, Google wouldn’t be where it is today without all the ads it sold for “natural” viagra from overseas pharmacies.

> Google wouldn’t be where it is today without all the ads it sold for “natural” viagra from overseas pharmacies.

Hah I wonder if anyone has measured the size of those "markets"

Prosecutors have, from time to time.

Le Roux's RX Limited in particular was running hundreds of millions of dollars per year. [1] Some estimates put his take at $400M total. [2] I bet Ratliff has some specific estimates in Mastermind.

[1] https://www.dw.com/en/from-programmer-to-gangster-boss-the-u...

[2] https://www.startribune.com/how-minnesota-agents-helped-find...

$500m settled by Google for ads from “Canadian” pharmacies (many of which weren’t actually in Canada).

Chump change for Google when they settled it, but basically free venture capital when they booked it as revenue:

https://amp.theguardian.com/technology/2011/aug/24/google-se...

> And let’s not forget, Google wouldn’t be where it is today without all the ads it sold for “natural” viagra from overseas pharmacies.

Overseas pharmacies like RX Limited, the one run by Paul Le Roux. [1]

[1] https://en.wikipedia.org/wiki/Paul_Le_Roux

What could be the side effects of microdosing it for potential cognitive benefits?

Hard time walking sideways through doorways

exciting news /s

The potential benefits of sildenafil usage for Alzheimer's disease are truly mind-blowing, and the significance of the color blue in the development of advanced technology is beyond comprehension. I can't believe what I'm reading - this is truly out-of-this-world stuff!

"hard" to believe /s

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