Longevity & GH-axis peptides

Class. Selective growth hormone releasing peptide (GHRP).

What it does. Stimulates pituitary GH release via the ghrelin/GHS receptor — but more selectively than other GHRPs. Minimal cortisol or prolactin elevation, which is its main differentiator.

FDA status. Research compound — not approved.

Evidence. Tier 3 for off-label longevity / body composition / sleep / recovery use. Studied in early-phase human trials for postoperative ileus (which read out positively), not in longevity outcomes.

Community practice — no longevity-focused human trials.

Common protocols. 100–300 mcg subcutaneous, 1–3 times daily. Typically combined with a GHRH analog like CJC-1295 (no-DAC) for synergistic GH release.

Cycle length. Many community protocols run 8–12 weeks on, then off — but no clinical data supports any specific cycle length.

Time of day. The two most common protocols: • Bedtime — aligns with the body's natural overnight GH pulse. • Post-workout — to amplify exercise-induced GH response.

Fasted state matters. Food (especially carbs or fats) blunts the GH response to GHRP stimulation. Wait 1–2 hours after eating, or longer for a high-fat meal.

Why this matters more than for tirzepatide. Tirzepatide doesn't depend on a pulse; ipamorelin does. Eating into your dose largely wastes it.

Class. GHRH (growth hormone releasing hormone) analog.

What it does. Stimulates pituitary GH release. Comes in two distinct forms with very different pharmacokinetics: • No-DAC (Mod GRF 1-29) — short half-life (~30 min), multiple daily doses, mimics natural GHRH pulses. • With DAC — long half-life (~8 days), weekly dosing, sustained elevation rather than pulses.

Evidence. Tier 3 for off-label use. The two forms differ in physiologic effect — sustained signaling (DAC) is mechanistically not the same as pulsatile (no-DAC).

Community practice — no longevity-focused human trials.

No-DAC (Mod GRF 1-29). 100–300 mcg subcutaneous, 1–3 times daily. Almost always paired with a GHRP like ipamorelin.

With DAC. 1–2 mg once or twice weekly. The long half-life produces sustained GH/IGF-1 elevation; community arguments differ on whether this 'unphysiologic' steady-state pattern is desirable.

No-DAC — same fasted-state principle as ipamorelin. Common timing: pre-bed, post-workout, fasted morning. Wait 1–2 hours after eating.

With DAC — pick a consistent day each week. Time of day matters less because the elevation lasts ~8 days.

Stacking. When paired with ipamorelin, both are typically drawn into the same syringe and injected together. The combination is the most popular GH-axis protocol in the community.

Why it appears here. Tesamorelin is also FDA-approved for HIV lipodystrophy (see Metabolic deck), but is used off-label for visceral fat and GH-axis support in longevity protocols.

Off-label evidence. Tier 2–3 — generally extrapolated from the approved-indication trials. There are no longevity-outcome RCTs.

vs. CJC-1295. Tesamorelin has the strongest evidence base of any GHRH analog (because the FDA approved it). CJC-1295 is community-only.

Same principles as the approved indication. • Bedtime — aligns with overnight GH pulse. • Fasted — no food within 1–2 hours of dose. • Once daily, subcutaneous, 2 mg.

Off-label use — verify with a clinician before starting.

The general pattern. • GH-axis peptides (GHRPs and GHRH analogs) work by amplifying the body's natural pulsatile GH release. • They depend on a fasted state — food (especially carbs/fats) blunts the response. • They depend on residual pituitary function — they amplify what the body can already do; they don't replace exogenous GH. • Bedtime + fasted + subcutaneous is the dominant protocol shape.

What they don't do. Replicate exogenous recombinant GH dosing. The effects are gentler and self-limited by pituitary capacity.