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Sildenafil (PDE5 inhibitor)
A short-acting PDE5 inhibitor (Viagra; Revatio for pulmonary hypertension) with a very large RCT base for erectile dysfunction and a real role in pulmonary arterial hypertension. It also draws geroscience interest from big-data analyses linking PDE5-inhibitor use to lower Alzheimer's incidence and fewer cardiovascular deaths — but that is association, not causation, with no longevity RCT. A prescription drug, not a supplement.
Prescription medication — not a dietary supplement
Sildenafil (Viagra) is a prescription (or investigational) drug, not a supplement. It is included here for reference because people research and discuss it (often used off-label) — not as a recommendation. Take it only under a qualified clinician's supervision and only as prescribed; do not source it from grey-market vendors, where identity, purity, and dosing are unverified. The evidence below reflects its clinical trials.
What the evidence says
Sildenafil (Viagra) doesn't have enough studies with structured effect-size data yet to pool a verdict. Browse the studies below for individual findings.
Most evidence is from high-quality meta-analyses and randomised trials published 1998–2026.
Based on 192 studies · 25 meta-analyses · 147 RCTs
Confidence
High confidenceBy outcome
Sildenafil has a strong, well-replicated RCT and meta-analytic base for erectile dysfunction and a landmark RCT (SUPER-1) for pulmonary arterial hypertension — for those approved uses the evidence is strong. The longevity-relevant signal (lower Alzheimer's incidence, lower cardiovascular/all-cause mortality) is consistent but entirely observational with strong healthy-user confounding and no longevity RCT, which holds the overall score below the top tier.
141 randomised trials
80% were about Sildenafil (Viagra) in an audit of 50 of them
Every randomised or controlled trial of Sildenafil (Viagra) indexed in PubMed, not a hand-picked subset. Meta-analyses and systematic reviews are deliberately excluded from this count: most of them cover many compounds at once, so counting them would inflate it.
PubMed · as of Sep 2026
42 trials ongoing or recruiting · 294 completed on ClinicalTrials.gov
83 of the completed trials have posted results
Registered trials show research momentum for Sildenafil (Viagra), not proof of effect — a registration is a plan, and posted results are sponsor-reported, not peer-reviewed. They are never counted toward the evidence rating above.
Browse these trials on ClinicalTrials.govClinicalTrials.gov · as of Nov 2026
Sildenafil is an oral phosphodiesterase-5 (PDE5) inhibitor — the original of its class, marketed as Viagra for erectile dysfunction and as Revatio for pulmonary arterial hypertension. By blocking PDE5 it raises cyclic GMP, prolonging nitric-oxide-mediated smooth-muscle relaxation and vasodilation.
For erectile dysfunction the evidence is robust: large double-blind randomized controlled trials and meta-analyses show clinically meaningful improvement on the International Index of Erectile Function versus placebo.
For pulmonary arterial hypertension the SUPER-1 trial established that sildenafil improves exercise capacity and hemodynamics, which is why the FDA approved it (as Revatio) for that indication.
Its key practical difference from tadalafil is duration: sildenafil is short-acting (~3-5 h half-life, onset roughly 30-60 minutes, blunted by a high-fat meal), versus tadalafil's long action.
Beyond the approved uses, sildenafil sits at the center of the same geroscience hypothesis as the rest of its class: large observational and insurance-claims analyses associate PDE5-inhibitor use with reduced incidence of Alzheimer's disease, and cohort data in men with erectile dysfunction or coronary disease associate PDE5-inhibitor use with lower cardiovascular and all-cause mortality.
The honest caveat is that this is associational. Men who are prescribed and fill PDE5 inhibitors differ systematically from those who are not (healthier, more active, better healthcare access — classic healthy-user confounding), and no randomized trial has shown that sildenafil extends lifespan or prevents dementia.
Sildenafil is generally well tolerated (headache, flushing, dyspepsia, nasal congestion, transient blue-tinged vision), but it is dangerous combined with nitrates (severe, potentially fatal hypotension), needs caution with alpha-blockers and other antihypertensives, and carries rare risks of priapism, sudden hearing loss, and non-arteritic anterior ischemic optic neuropathy (NAION).
The score reflects strong, well-replicated efficacy for its approved indications against a longevity/neuroprotection signal that is suggestive but observational and unproven.
Sildenafil blocks PDE5, raising cyclic GMP and prolonging nitric-oxide-mediated vasodilation — the basis for its erectile and pulmonary-vascular effects.
Enhanced NO/cGMP signaling improves endothelial function and blood flow, including the pulmonary vasculature in PAH and, by hypothesis, cerebral perfusion.
cGMP signaling has additional effects on mitochondrial function and inflammation that are proposed to underlie the vascular-aging and neuroprotection associations.
How Sildenafil (Viagra) works — from molecular targets to health outcomes. Click an edge to see supporting research.This visualization is in beta — pathways are being refined and expanded.
Absolute contraindication — dangerous hypotension.
Avoid until cleared by a clinician.
Use low starting doses and monitor blood pressure.
Discuss the rare risk of optic-nerve injury with a clinician before use.
Combined PDE5 inhibitor + nitrate causes severe, potentially fatal hypotension — an absolute contraindication.
Additive blood-pressure lowering — use caution and lower starting doses.
Raise sildenafil levels (e.g. ritonavir, ketoconazole); dose reduction advised.
Tip: Vasodilatory; usually mild and transient.
Tip: Class/dose-related; visual changes are usually transient.
Tip: Seek urgent care; avoid nitrates; An erection lasting 4 hours or longer is an emergency whether or not it hurts: go to an emergency department now. One approaching 3 to 4 hours, or a painful erection unrelated to arousal, needs urgent medical assessment now. Do not wait.
Sildenafil (Viagra) has an evidence score of 3.8/10 — emerging evidence based on 192 indexed studies, including 1 meta-analysis. A short-acting PDE5 inhibitor (Viagra; Revatio for pulmonary hypertension) with a very large RCT base for erectile dysfunction and a real role in pulmonary arterial hypertension. It also draws geroscience interest from big-data analyses linking PDE5-inhibitor use to lower Alzheimer's incidence and fewer cardiovascular deaths — but that is association, not causation, with no longevity RCT. A prescription drug, not a supplement. Representative study: PMID 16239897.
Dosing for Sildenafil (Viagra): Approved on-demand ED dosing is 25-100 mg taken ~30-60 minutes before activity (50 mg typical start). PAH dosing (Revatio) is 20 mg three times daily. Any off-label use is clinician-directed; this is not an approved longevity regimen. Individual needs vary, so check the right dose for you with a healthcare provider.
Timing is flexible for Sildenafil (Viagra) — consistent daily use matters more than the time of day. Short-acting; onset ~30-60 minutes and a high-fat meal slows/blunts absorption, so it is often taken on a relatively empty stomach.
Sildenafil (Viagra) should be used with caution — talk to a healthcare provider before taking it. Reported side effects include priapism / NAION (sudden vision loss) / sudden hearing loss / symptomatic hypotension, headache / flushing, dyspepsia / nasal congestion / blue-tinged or blurred vision. How often they occur is not established for all of them. Use caution if any of these apply to you: Concurrent nitrates (any form); Recent cardiovascular event / unstable angina; Severe hypotension.
Testosterone (TRT)
Too few graded studiesThe primary male androgen and a prescription medicine with US FDA-approved products for specified causes of male hypogonadism, and a Schedule III controlled substance in the US. For men with genuinely low testosterone, randomized trials show real benefits: the Testosterone Trials (TTrials) improved sexual function, mood, anemia and bone density in older hypogonadal men, and the large TRAVERSE trial found TRT non-inferior to placebo for major cardiac events. But those benefits were modest and indication-specific, NOT a longevity or anti-aging result. It is prescription-only in Germany and Austria. Non-medical, supraphysiologic and 'anti-aging' use is not established as safe or effective for longevity and carries serious harms — erythrocytosis, suppressed sperm production/fertility, cardiovascular and psychiatric risk. This is a harm-reduction reference, not a recommendation, and testosterone is NOT a dietary supplement.
Nicotinamide Riboside
Too few graded studiesA vitamin B3 precursor that reliably raises cellular NAD+ levels and is well tolerated — but human trials have so far shown mostly null or mixed results on the functional outcomes (muscle, metabolism, blood pressure, cognition) that elevation is meant to drive.
MitoQ
Too few graded studiesA mitochondria-targeted antioxidant — CoQ10 conjugated to a triphenylphosphonium (TPP+) cation so it accumulates several-hundred-fold inside mitochondria. Sold OTC as a supplement. Its best human signal is improved endothelial/vascular function in older adults (one small RCT); several trials are null (Parkinson's, exercise adaptation), and almost all outcomes are surrogate/biomarker, not hard clinical endpoints.
Yohimbine
Too few graded studiesThe purified alkaloid (not crude yohimbe bark) — an alpha-2 adrenoceptor antagonist with modest evidence for erectile dysfunction and fasted fat loss, but real anxiety and cardiovascular risks and supplement potency that may differ from the label.
Explore: Best supplements for Men's Health
Reviewed by Dr. Baher Al Hakim · Last reviewed June 2026 · evidence from 198 studies · how we score · editorial policy
This information is for educational purposes only. It is not a substitute for professional medical advice. Always consult a qualified healthcare provider before starting, stopping, or changing any supplement or medication.
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