Tadalafil For Longevity | How I Use It

#226

Glad the thread is back on topic. I think it’s a wonder drug IMO. Since I last posted here in February, I’ve been taking 2.5mg/day and it definitely makes a difference. My average SBP is down 3-5 mmHg. It definitely helps with pumps in the gym - doing isolation movements like biceps curls can induce painful pumps. Penis is more consistently “alert” - my wife walks in with a nice perfume and he wakes up quickly.

I’ve never had prostate problems, but the urologist on Attia was saying he prescribed 2.5-5mg/day for patients with hypertrophy, and it was massively helpful.

I also don’t believe there is any dependence issue.

And mechanistically, it makes sense. Peripheral vasodilation should be reducing overall burden placed on the heart during rest times. There are a few studies out there that higher doses, particularly of viagra, might have anabolic effects and improve hypertrophy with training, likely driven by the better blood flow to muscles.

4 Likes
#227

Tadalafil from India seemed to lose effectiveness for me and some others after a few years. I know a lot of medicines don’t really expire at their expiration dates but personally and anecdotally wonder if Tadalafil doesn’t lose effectiveness sooner than many

2 Likes
#228

This a no brainer for any USA General Practioner Physician prescription… and it is cheap. Assume same through out the world.

My urologist still writes my prescription every year at my check-up for tadalafil and finasteride.

But, he says my Personal Physician could do it too.

Cheap… why not get it in the USA?

1 Like
#229

It’s so dirt cheap from India that I renew my supply by including some in my other orders from India. To give an idea of how cheap it is from India, one of my suppliers gave me a free bunch of it in another order.

3 Likes
#230

cheap is relative. What does a urologist visit cost a person who hasn’t met their deductible? will every doctor write a year of refills?
in india no script needed.
plus maybe somebody here getting rapamycin from there already
and what’s cheap? in India is about 61 cents a pill.

#231

In the US, from GoodRX, ~$25-$35 for 90-5mg; so ~$0.28-$0.39 / pill.

#232

Is it safe to take Tadalafil and Telmisartan together? Might it not be too effective? Is anyone using both of these drugs? Which one packs the more powerful punch?

Personally, I don’t think I can take both together given my previous issue with low blood pressure.

#233

Kbaba wrote: Tadalafil from India seemed to lose effectiveness for me and some others after a few years.

If they are giving free as @desertshores says. Maybe it isn’t quality.

Get it from your physician… 3 month tadalafil supply (4 refills) 5 mg nightly… or mornings. Doesn’t go stale on you.

Hopefully, you are seeing a urologist yearly for that prostate gland. That’s when I get my annual check… and new prescription.

1 Like
#234

Good price. (minus the need for a script)
My india price was for 20 mg

#235

My Dr. prescribed 5mg Tadalafil (10mg if “needed”) in addition to the 20mg Telmisartan I’ve been on for ten years.
That’s not a high dose of Telmisartan, but the combination must be safe.
I noticed a small decrease in systolic BP.

2 Likes
#236

N=1 FWIW:
I have been taking both telmisartan (20 mg/day) and tadalafil (10 mg/day) for quite sometime with no problems.

3 Likes
#237

The more I’ve looked into this, the more impressive Tadalafil seems to be:

UK biobank data: Tadalafil reduced mortality at all doses. 10 mg/d: HR 0.72, CI 0.58–0.89. That is a massive effect size (https://onlinelibrary.wiley.com/doi/10.1111/acel.14334)

A study of 50 million men: Tadalafil use was associated with significantly reduced risks of all-cause mortality (RR 0.66), myocardial infarction (0.73), stroke (0.66), venous thromboembolism (0.79), and dementia (0.68) in erectile dysfunction patients. (https://www.amjmed.com/article/S0002-9343(24)00705-8/fulltext) Disclaimer that these patients had ED, which perhaps reflects underlying issues.

Study of 30,000 insurance records: Tadalafil claims were associated with 19% lower MACE, 55% lower cardiovascular deaths, 44% lower all-cause death compared to closely matched men, over a mean follow-up of 37 months. Preparing to download ...

Study in Swedish men comparing Tadalafil versus alprostadil. This is very important because it goes after one of the major confounders, that guys taking Cialis are likely to be healthy enough to engage in sex.

This study included 16,548 men treated with PDE5i and 1,994 treated with alprostadil. The mean follow-up was 5.8 years, with 2,261 deaths (14%) in the PDE5i group and 521 (26%) in the alprostadil group. PDE5i compared with alprostadil treatment was associated with lower mortality (hazard ratio: 0.88; 95% confidence interval: 0.79 to 0.98) and with similar associations for MI, heart failure, cardiovascular mortality, and revascularization.

And there was some dose-dependent effect:

When quintiles (q) of filled PDE5i prescriptions were compared using q1 as reference, patients in q3, q4, and q5 had lower all-cause mortality. Among alprostadil users, those in q5 had a lower all-cause mortality compared to q1.

In mice, Tadalafil is protective after induced myocardial infarction (Tadalafil Prevents Acute Heart Failure with Reduced Ejection Fraction in Mice - PMC) reducing fibrosis from 21.9% to 8.8% of the left ventricle. It also was protective after stroke in rats (Tadalafil, a long-acting type 5 phosphodiesterase isoenzyme inhibitor, improves neurological functional recovery in a rat model of embolic stroke - PubMed) improving neurological recovery (but without affecting the size of the injury area).

There is a very nice study here: Chronic inhibition of phosphodiesterase 5 with tadalafil affords cardioprotection in a mouse model of metabolic syndrome: role of nitric oxide | Molecular and Cellular Biochemistry | Springer Nature Link They dosed mice with tadalafil for 28 days, then gave them myocardial infarctions. But, what is awesome is that they did an experiment where they removed the hearts and hooked them up to a perfusion system, then induced myocardial infarction (i.e. ex vivo). The hearts from pre-treated mice took less damage and maintained better function - all while outside the body (i.e. independent from vasodilation, neural input, hormones etc). That means the drug actually did something to the cardiac cells to make them more resilient.

And for longevity, this study in C.elegans (Comprehensive evaluation of lifespan‐extending molecules in C. elegans - PMC ) found that Tadalafil was 1 of only 5 compounds identified (out of ~200 screened) that reproducibly extended lifespan. However, this was not found in the Ora C.elegans experiments (Million Molecule Challenge Results and Leaderboard – Ora Biomedical, Inc.) This is interesting because worms don’t have vascular systems (or penises), meaning the effect presumably doesn’t come from vasodilation,

In terms of downsides: common side effects are headaches, flushing, stuffy nose (I get this one at any higher than 5mg/eod) and lower back pain. All resolve after stopping. Serious side effects: ear ringing, hearing loss, and very rarely there are reports of people losing their vision. That sounds scary, but the drug is safe enough that even in the UK it’s now basically available over-the-counter after a very quick pharmacist questionnaire, and it’s advertised openly in normal pharmacies.

All together, this looks like a fairly powerful pro-longevity drug to me, with very few downsides.

10 Likes
#238

I think it has to be top 5. In the elite category with Rapamycin, SGLT2, statins, and Acarbose (and maybe GLP1).

3 Likes
#239

I have been taking tadalafil at 5 mg daily for quite some time. I guess this dose is not optimal.

But maybe 10 mg isn’t either, since I can’t find any info for 15 mg daily. Maybe 15 mg daily is closer to the optimal dose?

The optimal number might be closer to 5 mg. Even at 20 mg, I do not feel any dizziness upon standing.

FWIW: Gemini:

1. The Mathematical “Sweet Spot”

If we apply a quadratic fit (a parabola) to the data points from the Morin paper—5 mg (HR ~0.82), 10 mg (HR 0.72), and 20 mg (HR ~0.95)—the calculated “optimal” dose actually lands at approximately 11 mg, not 10 mg.

The data suggests that the benefit begins to diminish after the 10 mg mark. In the UK Biobank dataset, the 20 mg dose actually performed worse than the 10 mg dose. This could be due to two factors:

  • Selection Bias: Patients prescribed 20 mg often have more severe underlying vascular disease (which necessitates the higher dose), potentially skewing their mortality risk higher regardless of the drug.
  • Dosing Frequency: While 5 mg is almost always a daily dose, 20 mg is frequently used “on-demand.” The longevity benefits of PDE5 inhibitors are thought to come from steady-state endothelial protection, which is better achieved through consistent daily dosing than intermittent high doses.

2. The Accumulation Factor (Steady State)

Tadalafil has an exceptionally long half-life of roughly 17.5 hours. When taken daily, the drug accumulates in your system until it reaches a “steady state” after about 5 days.

  • 5 mg daily: Leads to a steady-state concentration roughly equivalent to a single 8 mg dose.
  • 15 mg daily: Would lead to a steady-state concentration equivalent to roughly 24 mg.

Since 20 mg is the FDA-approved maximum for a single 24-hour period, a 15 mg daily regimen would likely keep you permanently above the recommended safety ceiling. At age 85, this significantly increases the risk of orthostatic hypotension (dizziness when standing), which is a major contributor to falls and related mortality.

3. Other Research on “Optimal” Dosing

While the Morin paper is exciting, most other “biohacking” and clinical research points toward a lower “sweet spot”:

  • The AgelessRx/Longevity Community: Generally favors 2.5 mg to 5 mg daily. The logic is that this dose is sufficient to inhibit PDE5 enough to lower systemic inflammation and improve flow-mediated dilation without taxing the system or causing “tachyphylaxis” (diminishing sensitivity).
  • Kloner et al. (2023): A large study of 70,000 men found that those with the highest cumulative exposure to PDE5 inhibitors had the lowest mortality, but this was more about consistency of use over years rather than the intensity of the daily dose.

Summary Table: Dose vs. Risk

Daily Dose Estimated HR (Morin) Concentration Primary Risk/Benefit
5 mg ~0.82 Moderate Standard “protection” dose; very safe.
10 mg 0.72 High Maximum benefit in UK Biobank data.
15 mg ~0.85 (est.) Very High Likely exceeds safety ceiling; risk of low BP.
20 mg ~0.95 Extreme Diminishing returns; often used “on-demand.”
3 Likes
#240

In this UK Biobank study that sometimes gets right up here, people who took 10mg had slightly lower all cause mortality than 5mg.

“Tadalafil reduced mortality at all doses, and most pronounced at 10 mg (HR 0.72, CI 0.58–0.89). Sildenafil, likewise, reduced mortality at all doses, with a more pronounced effect at 50 mg (HR 0.85, CI 0.75–0.96).”

Personally, any more than 2.5mg and my eyes are red all day so I take that before bed.

5 Likes
#241

I’ve been taking Tadalafil at 5 mg, and will be switching to 10 mg this summer.

#242

I’ve been taking 5mg for some time now also. I feel the effects taper down a bit, like the body becomes used to it. But, I notice if giving it a week off, things seem to bounce back to original level. Maybe just my perception.

4 Likes
#243

Counterpoint on tadalafil (although I hope that I’m wrong and that you’re right): Large Study Finds Viagra Is Linked to Almost 70% Lower Risk of Alzheimer's - #129 by adssx

5 Likes
#244

Yeah, as I said in that thread, I’m staying away from this class of drugs, not having ED, HT, T2DM or CVD. The MR preprint was the nail in the coffin for me, although the relatively high prevalence of eye issues (11%) was also not encouraging. YMMV.

1 Like
#245

Very interesting. A little hard to interpret overall, but the MR study in particular is thought-provoking for sure. Thanks for sharing.

1 Like