library.onepin.app/tadalafil Peptide Education Library
Education only, not medical advice 21+ Every dose is an example to finalize with a licensed provider

OnePin Peptide Library · Hormonal

Hormonal Peptide Not FDA-approved · investigational

Tadalafil

Cialis

Tadalafil (brand names Cialis, Adcirca) is a long-acting, selective phosphodiesterase-5 (PDE5) inhibitor approved for erectile dysfunction (ED), benign prostatic hyperplasia (BPH), and pulmonary arterial hypertension (PAH). Compared to other PDE5 inhibitors (sildenafil/Viagra, vardenafil/Levitra), tadalafil's distinguishing feature is its dramatically longer half-life - ~17.5 hours vs 3-5 hours for sildenafil. This makes it suitable for daily low-dose use (2.5-5mg daily) rather than only on-demand higher dosing.,Beyond its FDA-approved indications, daily low-dose tadalafil has gained interest in the longevity, cardiovascular, and athletic communities for its endothelial function support, vasodilatory effects, possible cardiovascular protection, and workout performance benefits (improved blood flow, pumps, recovery). Dr. Peter Attia and others have discussed daily tadalafil as part of cardiovascular optimization protocols.,Daily low-dose tadalafil (2.5-5mg) provides sustained PDE5 inhibition without peak/trough variability of on-demand dosing. This supports continuous endothelial nitric oxide signaling, smooth muscle relaxation in vasculature, and potentially reduced cardiovascular events. It is often prescribed for men dealing with both ED and BPH simultaneously.

Quick Start
Route
Oral
Start low
5mg daily (Cialis daily) OR 10mg on-demand
Frequency
Once daily OR as needed
Timing
Anytime

Daily dose: take same time each day with or without food. On-demand: take 30 min - 2 hours before sexual activity (effect can last 24-36 hours). Avoid taking with high-fat meals on first doses (slightly delays onset, minimally affects efficacy).

Start here. Every protocol below is ordered lowest-first. Begin at the smallest effective dose, hold about a week to assess tolerance, and step up only if needed.

Tiered Protocols · lowest first
Quick Start
Conservative start
5mg daily (Cialis daily) OR 10mg on-demand · Oral · Once daily OR as needed
Lowest starting point. Hold about a week to assess tolerance before stepping up.
5mg daily (Cialis daily) OR 10mg on-demand
Once daily OR as needed
Standard
Daily Endothelial & Prostate Health
5 mg · Oral · Daily
human clinical trial · FDA Cialis label
5 mg
Daily
Standard
On-Demand ED
10-20 mg · Oral · As needed
human clinical trial · FDA Cialis label
10-20 mg
As needed
01

How it works

Tadalafil selectively inhibits PDE5 (phosphodiesterase type 5), the enzyme that breaks down cyclic guanosine monophosphate (cGMP). Inhibiting PDE5 increases cGMP levels in tissues with high PDE5 expression - primarily corpus cavernosum (penile erectile tissue), prostate/bladder smooth muscle, and pulmonary vasculature.,Increased cGMP causes smooth muscle relaxation via protein kinase G activation. In penile tissue, this allows arterial inflow and venous occlusion necessary for erection (in response to sexual stimulation - tadalafil doesn't cause spontaneous erections without arousal).,In prostate and bladder smooth muscle, cGMP increase relaxes lower urinary tract tissue, improving urinary flow in BPH.,In pulmonary vasculature, cGMP-mediated vasodilation reduces pulmonary artery pressure - the basis for PAH treatment.,Off-label endothelial benefits: PDE5 is expressed in systemic vasculature (lower than in target tissues but functionally relevant). Daily PDE5 inhibition improves systemic endothelial function via sustained NO/cGMP signaling. This may explain cardiovascular benefits seen in observational studies.,Workout performance: improved blood flow during exercise enhances oxygen delivery to muscles, supporting endurance and recovery. Anecdotal reports of improved 'pumps' and reduced muscle fatigue.,Long half-life (~17.5 hours) provides sustained effect - on-demand 10-20mg lasts 24-36 hours; daily 2.5-5mg provides continuous baseline.

Tadalafil selectively inhibits PDE5 (phosphodiesterase type 5), the enzyme that breaks down cyclic guanosine monophosphate (cGMP). Inhibiting PDE5 increases cGMP levels in tissues with high PDE5 expression - primarily corpus cavernosum (penile erectile tissue), prostate/bladder smooth muscle, and pulmonary vasculature.,Increased cGMP causes smooth muscle relaxation via protein kinase G activation. In penile tissue, this allows arterial inflow and venous occlusion necessary for erection (in response to sexual stimulation - tadalafil doesn't cause spontaneous erections without arousal).,In prostate and bladder smooth muscle, cGMP increase relaxes lower urinary tract tissue, improving urinary flow in BPH.,In pulmonary vasculature, cGMP-mediated vasodilation reduces pulmonary artery pressure - the basis for PAH treatment.,Off-label endothelial benefits: PDE5 is expressed in systemic vasculature (lower than in target tissues but functionally relevant). Daily PDE5 inhibition improves systemic endothelial function via sustained NO/cGMP signaling. This may explain cardiovascular benefits seen in observational studies.,Workout performance: improved blood flow during exercise enhances oxygen delivery to muscles, supporting endurance and recovery. Anecdotal reports of improved 'pumps' and reduced muscle fatigue.,Long half-life (~17.5 hours) provides sustained effect - on-demand 10-20mg lasts 24-36 hours; daily 2.5-5mg provides continuous baseline.

02

What to expect

Early
Days 1–7

Days 1-5: Building to steady state (daily) or acute effect (on-demand).

03

Evidence

HumanPresent
AnimalPresent
In-vitroPresent
2003Efficacy of tadalafil for the treatment of erectile dysfunction at 24 and 36 hours after dosing: a randomized controlled trial · Porst H et al, Urology ↗peer reviewed
2007Tadalafil dosed once a day in men with erectile dysfunction: a randomized, double-blind, placebo-controlled study in the US · Rajfer J et al, International Journal of Impotence Research ↗peer reviewed
2005Chronic treatment with tadalafil improves endothelial function in men with increased cardiovascular risk · Rosano GM et al, European Urology ↗peer reviewed
2017Administration of daily 5 mg tadalafil improves endothelial function in patients with benign prostatic hyperplasia · Yamanaka H et al, The Aging Male ↗peer reviewed
04

Interactions & stacking

What's safe to combine, and what belongs in a separate pin.

Safe & synergistic

Most cardiovascular medicationsGenerally compatible with statins, most antihypertensives (with BP monitoring), antiplatelets.
L-Citrulline / L-ArginineL-citrulline boosts arginine → NO substrate. PDE5 inhibitors prolong cGMP signaling. Combined provides upstream substrate + downstream signaling support.
PycnogenolStudies show pycnogenol + L-arginine combination has ED benefit. Combined with low-dose PDE5 inhibitor may be additive.
Beet Root / Nitrates (dietary)Dietary nitrate (beets) supports NO pathway - synergistic with PDE5 inhibition. NOT same as prescription nitrates (which are dangerous combo).

Keep separate

Nitrates (nitroglycerin, isosorbide)ABSOLUTE CONTRAINDICATION. Combined cGMP elevation causes severe, potentially fatal hypotension. Must wait at least 48 hours after tadalafil dose before nitrates can be given (even in emergency).
Alpha-Blockers (doxazosin, terazosin)Both lower BP - additive hypotension risk, especially orthostatic. Start tadalafil at lowest dose with titration. Specific timing protocols needed.
Strong CYP3A4 Inhibitors (ketoconazole, ritonavir, clarithromycin)Significantly increase tadalafil levels - reduce dose to 2.5-5mg. Can lead to excessive effect and side effects.
Strong CYP3A4 Inducers (rifampin, carbamazepine, phenytoin)Reduce tadalafil levels - may need higher doses for effect.
05

Pharmacokinetics

Illustrative plasma concentration · 24 h
Half-life
~17.5 hours (terminal). Long half-life is the key distinguishing feature vs other PDE5 inhibitors.
Peak · Tmax
~2 hours fasted (slightly delayed with food but bioavailability unchanged).
Elimination
On-demand effect lasts 24-36 hours per dose. Daily dosing reaches steady state in ~5 days.
Activity
Acute: 24-36 hours per dose. Chronic daily: continuous baseline effect at steady state. Wash-out for nitrate compatibility: 48+ hours after last tadalafil dose.

Storage. Store at room temperature (15-30C) in a cool, dry place. Protect from light. Tablets shelf-stable 2-3 years.

06

Regulatory status

PRESCRIPTION REQUIRED in the US. Generic tadalafil widely available since 2018 (significant cost reduction). FDA-approved for ED (Cialis), BPH (Cialis), and PAH (Adcirca 40mg daily). Off-label use for cardiovascular optimization is common but requires physician oversight.

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