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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
Most Sildenafil (Viagra) studies are mechanism or observational rather than RCTs that measure a clinical effect — keep findings provisional.
Most evidence is from high-quality meta-analyses and randomised trials published 1998–2026.
Based on 178 studies · 22 meta-analyses · 142 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.
180 rigorous studies
147 randomized trials · 23 meta-analyses · 22 systematic reviews
Our evidence rating for Sildenafil (Viagra) is accountable to this entire body of rigorous research indexed in PubMed — not a hand-picked subset.
PubMed · as of Jul 2026
45 trials ongoing or recruiting · 289 completed on ClinicalTrials.gov
82 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for Sildenafil (Viagra), not proof of effect — a registration is a plan, and posted results are sponsor-reported, not peer-reviewed.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 Aug 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 is a medical emergency.
Sildenafil (Viagra) has an evidence score of 3.8/10 — emerging evidence based on 171 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.
The commonly studied dose of Sildenafil (Viagra) is 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 — start at the lower end of the range and adjust based on how you respond.
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. The most commonly reported side effects are headache / flushing, dyspepsia / nasal congestion / blue-tinged or blurred vision, priapism / NAION (sudden vision loss) / sudden hearing loss / symptomatic hypotension. Use caution if any of these apply to you: Concurrent nitrates (any form); Recent cardiovascular event / unstable angina; Severe hypotension.
Testosterone (TRT)
Mostly mechanism / observationalThe primary male androgen and an FDA-approved prescription drug for diagnosed male hypogonadism — and a Schedule III CONTROLLED SUBSTANCE. 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; non-medical, supraphysiologic, and 'anti-aging' use is illegal 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
Mostly mechanism / observationalA 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
Mostly mechanism / observationalA 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
Mostly mechanism / observationalThe 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 notoriously mislabeled supplement potency.
Explore: Best supplements for Men's Health
Reviewed by Dr. Baher Al Hakim · Last reviewed June 2026 · evidence from 182 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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