Tadalafil (daily, for longevity)
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Prescription only; requires physician management. This record grades tadalafil taken for longevity. It says nothing about tadalafil prescribed for erectile dysfunction, enlarged prostate or pulmonary arterial hypertension.
At a glance
Tadalafil is the erection drug sold as Cialis, now promoted as a daily pill for living longer. Studies of insurance records found that men who filled tadalafil prescriptions had fewer heart problems and deaths than men who did not. Those men were not picked at random, and healthier men are more likely to fill such a prescription. No study has given tadalafil to healthy men to see if they live longer. It must not be combined with nitrate heart medicines.
- What was measured
- Heart attacks, strokes and other major heart events, and deaths, recorded in insurance claims for men with erection problems.
- How big
- No trial: in the claims data, men who filled tadalafil prescriptions had 19% fewer major heart events than men who filled none, and fewer deaths, a difference that can reflect who fills the prescription rather than what the drug does.Read from the summary of PMID PubMed ID: the permanent number the US National Library of Medicine gives a published paper. Each one links to that paper's record on PubMed. 38377018.
- Who it applies to
- Men with erectile dysfunction in a US insurance database, about three years of follow-up. It says nothing about healthy men taking tadalafil for aging, which no trial has tested.
- Safety
- Dangerous with nitrate heart medicines, and in men with heart disease taking both, deaths were higher.
- Compared with
- Men with erection problems who filled no prescription for this drug class, not assigned at random.
- Certainty
- Grade D, resting on: Observational Research that watches what people already do rather than assigning a treatment. It can show that two things travel together, not that one causes the other. claims and cohort studies An observational study that follows a group of people over time and compares what happens to them.; no randomized trial on aging (D Route 1 No human randomized trial has been run, so the record rests on animal or mechanistic evidence only. One of the two routes to the lowest letter on EBL's scale.).
- What would change this grade
- Could rise to C with: Randomized, double-blind Neither the participants nor the people assessing them know who received the real treatment until the trial ends., placebo-controlled trial run independently of companies selling tadalafil for longevity. Who: Men aged 50 and over without cardiovascular disease, not selected for erectile dysfunction. Measured: Major cardiovascular events and death from any cause, as a pre-specified primary outcome. Length: At least 3 years.
- Cost
- No price recorded yet.
- Sources
- 4 studies cited on this record, listed under Sources.
A letter describes the human evidence, not the product, the manufacturer, or the intervention's worth.
Grade D, not yet tested: no human randomized trial has been run. This D records missing trials, not a finding that it does not work. How to read a grade →
See the full evidence record →No human randomized trial has tested this at the dose and form graded, so there is nothing for a higher letter to rest on. A Route 1 Grade D records the absence of trials. It is not a finding against the compound, and it is not a finding that the compound is safe, because neither has been established. It may turn out to work once someone tests it. The grade moves when a qualifying human trial reports.
Tested in humans on the actual molecule, and the result was null or adverse on the endpoint The outcome a trial measures to decide whether the treatment worked, such as heart attacks, blood pressure or a symptom score. that matters.
Why this letter
Why this gradeGrade D, not yet tested. The reasoning, and what the grade does not cover.
Grade D on Route 1: no human randomized trial has tested tadalafil for longevity, cardiovascular events or death in healthy men. The case rests on observational studies of men with erectile dysfunction who filled prescriptions, compared with men who did not: a claims study of 8,156 tadalafil users found 19 percent fewer major cardiovascular events and 44 percent fewer deaths (Kloner et al., 2024; PMID 38377018), and a meta-analysis A study that pools the numbers from several trials into one combined estimate. of 16 cohort studies, with no randomized trials, found similar associations for the drug class (PMID 38777751). Men who fill these prescriptions differ from men who do not in health, activity and income, and a 44 percent drop in death from any cause is larger than any heart drug has produced in a randomized trial, which is the pattern of a healthy-user effect rather than a drug effect. The daily 2.5 mg and 5 mg doses have been tested in randomized trials, but for erections and prostate symptoms, not for aging (PMID 21981682).
WHAT THIS GRADE DOES NOT COVERtadalafil prescribed for erectile dysfunction, enlarged prostate or pulmonary arterial hypertension, which are approved uses with their own trials, and nothing here is a basis for changing a prescribed medication. It also does not cover combination products adding vitamin D3 or other ingredients, which no trial has tested.
A grade describes the human evidence for a named use. It is not advice, and it is not a judgment on any individual prescription. How the letters are decided →
The trial that would change this grade.
A positive trial of this shape would move this entry to C.
Why the current trials fall short
Every human signal comes from men who chose to fill prescriptions, compared with men who did not. A randomized trial is the only design that separates the drug from the kind of man who takes it.
Why people believe itThree human sources; no published case reports of benefit; no reports of harm.
The case for daily tadalafil as a longevity drug is that it relaxes blood vessels and improves the lining of the arteries, and that men taking PDE-5 inhibitors for erectile dysfunction have fewer heart events and deaths in large record studies.
What supporters point to, and what each source actually shows. None of it is enough to move this letter higher; the trial described above under Evidence wanted is what would.
- Population study, not a trialIn US insurance claims, men with erectile dysfunction who filled tadalafil prescriptions had 19% fewer major heart events and 44% fewer deaths than men who filled none. Not randomized, and funded through a Sanofi grant. PMID 38377018
- Population study, not a trialSixteen cohort studies pooled: men using PDE-5 inhibitors had fewer heart events and deaths. Every study compared men who chose the drug with men who did not. PMID 38777751
- Human trial, a different useDaily tadalafil at 2.5 mg or 5 mg improved erections, and 5 mg improved prostate symptoms, over 12 weeks. A trial of the approved uses, not of aging. PMID 21981682
A case report describes what happened to one or a few patients. It cannot show the treatment caused the change, and reports of success are published more often than reports of failure.
A PubMed search in November 2026 found no published case report of benefit for this use.
Searched PubMed, November 2026: case report record(s) returned. No case report describes tadalafil taken for aging or longevity.
ClinicalTrials.gov, the public registry run by the U.S. National Library of Medicine, lists studies that are recruiting volunteers. The link below searches it for Tadalafil among studies recruiting now. EBL has no relationship with any listed study and receives no payment for this link.
Search recruiting studies of Tadalafil on ClinicalTrials.gov
Observational only for longevity. Men with erectile dysfunction who filled tadalafil prescriptions had fewer heart events and deaths than men who did not, but no randomized trial has tested the drug for aging, and the size of the death difference points to who takes it rather than what it does.
Dose, form and timing
No trial has given tadalafil to healthy men for aging. The observational studies recorded men with erectile dysfunction filling ordinary tadalafil prescriptions, at doses chosen for erections, and compared them with men who filled none (Kloner 2024; PMID 38377018). Daily tadalafil at 2.5 mg or 5 mg was tested for 12 weeks in men aged 45 and over with erectile dysfunction and prostate symptoms (Egerdie 2012; PMID 21981682), not for heart events, death or aging.
Safety
Tadalafil is contraindicated with nitrate medicines because the combination can drop blood pressure sharply, and in Swedish registers men with coronary artery disease who took both had higher mortality than men on nitrates alone.
Cautions documented in human studies. Each caution on this record, sorted by what it rests on.
- Taken with nitrate heart medicines, PDE-5 inhibitors went with higher mortality and more heart attacks in men with coronary artery disease. (PMID 38233015)
- Daily 2.5 mg and 5 mg doses were reported as well tolerated over 12 weeks, with no adverse change in standing blood pressure. (PMID 21981682)
None recorded.
None recorded.
None recorded.
Does not apply: human harm data are listed above.
Grade history
How this letter has changedLatest: No. 434 · November 2026 · First graded.
Daily tadalafil is now sold as a longevity drug, often compounded at 2.5 mg with vitamin D3. The human evidence is observational: in US insurance claims, men with erectile dysfunction who filled tadalafil prescriptions had 19 percent fewer major heart events and 44 percent fewer deaths than men who filled none (Kloner et al., Clin Cardiol, 2024; PMID 38377018), and a meta-analysis of 16 cohort studies found the same pattern for the drug class (PMID 38777751). No randomized trial has tested tadalafil for aging, heart events or death in healthy men; a PubMed search in November 2026 found none. Men who fill these prescriptions are healthier on average than men who do not, and a 44 percent fall in death from any cause is the size of a healthy-user effect, not of any heart drug in a randomized trial. Grade D on Route 1. The record also states the nitrate interaction, with Swedish register data showing higher mortality in men with heart disease who took both (PMID 38233015).PMID 38377018 PMID 38777751 PMID 38233015
Every change to a letter on this site is dated and published. The full evidence log →
Sources
- Citations
- Every paper cited on this page is matched to its PubMed record on every build.
- Retractions
- None of these papers is retracted or under a journal expression of concern. PubMed is checked again on every build.
- Read against the papers
- November 2026. By a language model (AI-assisted reading), not yet reviewed by a clinician.
- Outside review
- Not yet done. No reviewer outside EBL has checked this record.
What each of these checks can and cannot show: evidence integrity.
- PMID 38377018 →The association of tadalafil exposure with lower rates of major adverse cardiovascular events and mortality in a general population of men with erectile dysfunction.
- PMID 38777751 →Long-term effects of phosphodiesterase-5 inhibitors on cardiovascular outcomes and death: a systematic review A review that searches for every study on a question using a method set in advance, then assesses them together. and meta-analysis.
- PMID 21981682 →Tadalafil 2.5 or 5 mg administered once daily for 12 weeks in men with both erectile dysfunction and signs and symptoms of benign prostatic hyperplasia: results of a randomized, placebo-controlled, double-blind study.
- PMID 38233015 →Risk of Death in Patients With Coronary Artery Disease Taking Nitrates and Phosphodiesterase-5 Inhibitors.
Primary evidenceFour papers, each linked to its PubMed record.
Kloner et al. (Clin Cardiol, 2024; PMID 38377018): retrospective cohort in a US commercial insurance claims database; 8,156 men with erectile dysfunction and at least one tadalafil claim against 21,012 with no claim for any PDE-5 inhibitor, matched for cardiovascular risk factors. Over about three years, adjusted major cardiovascular events were 19 percent lower (hazard ratio How often an event happened in the treated group compared with the control group over the same period. A ratio of 0.80 means 20 percent fewer events. 0.81, 95% CI 0.70 to 0.94) and death from any cause 44 percent lower (hazard ratio 0.56, 0.43 to 0.74). Funded through a grant from Sanofi; the first author is a paid Sanofi consultant. Soulaidopoulos et al. (Eur Heart J Cardiovasc Pharmacother, 2024; PMID 38777751): meta-analysis of 16 cohort studies, 1,257,759 people, 99.4 percent men; PDE-5 inhibitor use went with fewer major cardiovascular events (risk ratio 0.78) and lower all-cause mortality (0.70); the authors call for randomized trials, which have not been run. Egerdie et al. (J Sex Med, 2012; PMID 21981682): randomized phase 3 trial, tadalafil 2.5 mg or 5 mg once daily or placebo An inactive substitute made to look like the real treatment, so participants cannot tell which one they received. for 12 weeks in 606 men aged 45 and over with erectile dysfunction and prostate symptoms; both doses improved erections, only 5 mg improved prostate symptoms. Trolle Lagerros et al. (J Am Coll Cardiol, 2024; PMID 38233015): Swedish registers, 55,777 men with coronary artery disease on nitrates; the 5,710 who also filled PDE-5 inhibitor prescriptions had higher mortality (hazard ratio 1.39) and more heart attacks (1.72). Observational. Grade D on Route 1: the longevity claim has no randomized trial behind it.
Evidence Based Longevity, Inc. is owner-operated and edited by Arnold Sandlow, D.C., a California-licensed chiropractor. Evidence Based Longevity publishes in English only · Machine translations are not produced or reviewed by EBL for accuracy
How EBL searched for the trials (1 search)
The search that was run, what it returned, and what was left out and why, so the absence of evidence can be checked as well as its presence.
(tadalafil[tiab] OR "PDE5 inhibitor*"[tiab] OR "phosphodiesterase-5 inhibitor*"[tiab]) AND "erectile dysfunction"[tiab] AND (mortality[tiab] OR "cardiovascular events"[tiab] OR "major adverse cardiovascular"[tiab])PubMed watch: does a new study change the grade? (nothing new)
No new paper matching the searches behind this grade has been added to PubMed since November 2026.
Last run November 2026. A letter on EBL moves only after a logged review. A new paper never moves a letter by arriving: it is read, the answer is written here, and any change to the letter is published in the evidence log.
For each trial behind a letter on this page, the funding its PubMed record lists. "No funder" means PubMed lists none, not that the trial had no funding.
- “Tadalafil 2.5 or 5 mg administered once daily for 12 weeks in men with both erectile...” (PMID 21981682): PubMed lists no funder for this trial.
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