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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 mixed-quality meta-analyses and randomised trials published 1998–2023.
Based on 6 studies · 1 meta-analysis · 2 RCTs
Confidence
ModerateBy outcome
Sildenafil (Viagra) has an evidence score of 3.8/10 — moderate evidence based on 6 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.
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 / observationalLast reviewed June 2026 · evidence from 6 studies · how we score
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.
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.
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.
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.
Tap node to isolate • Pinch to zoom • Tap edge for research
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.
Can be taken without food
| Form | Type |
|---|---|
| 💊Oral tablet (sildenafil citrate) | Recommended |
| 💊Tadalafil (longer-acting PDE5 inhibitor) | Alternative |
Sildenafil's short half-life suits on-demand use; tadalafil suits steady daily dosing.
Compare Sildenafil (Viagra) vs Tadalafil →Minimum: 1 weeks
Optimal: 12 weeks
Cycling: Not required
Note: Short-acting and on-demand for ED (onset ~30-60 min, slowed by high-fat meals); fixed three-times-daily for PAH. Never combine with nitrates.
Dose-response data unavailable. The current published research for Sildenafil (Viagra) does not provide sufficient dose-specific outcome data to generate reliable dose-response curves.
Refer to the Dosage & Timing section above for recommended dose ranges based on available evidence.
Robust RCT and meta-analytic evidence for clinically meaningful improvement in erectile function versus placebo.
SUPER-1 RCT showed improved exercise capacity and hemodynamics; FDA-approved for PAH as Revatio.
Big-data studies associate PDE5-inhibitor/sildenafil use with reduced Alzheimer's incidence — association only, not a prevention trial; confounded by healthy-user effects.
Cohorts of men with ED or coronary disease link PDE5-inhibitor use to fewer cardiovascular and all-cause deaths — observational, not causal.
Common vasodilatory effects — headache, flushing, dyspepsia, nasal congestion, transient blue-tinged vision; rare NAION and sudden hearing loss.
Combined with nitrates it causes severe, potentially fatal hypotension; caution with alpha-blockers and other antihypertensives.
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.
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.
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) is generally safe at recommended doses, with a few precautions worth noting. 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.
A 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.
Raise sildenafil levels (e.g. ritonavir, ketoconazole); dose reduction advised.