Sermorelin + Ipamorelin Blend
Also known as: Serm/Ipa, Anti-Aging GH Blend, Natural GH Stack
Evidence: Preclinical
Overview
Vial blend of sermorelin (GHRH 1-29) and ipamorelin, 5 mg each; sermorelin raised GH and IGF-1 in older men, ipamorelin's only RCT was negative, and no study has tested the pair.
Sermorelin was approved by FDA in 1997 as Geref for pediatric GH deficiency, and its US products were discontinued in 2008 for commercial reasons; this research blend is not that product. It mixes sermorelin and ipamorelin 5 mg each. Sermorelin at 1 mg twice daily restored GH and IGF-1 to young-adult levels in 10 older men (Corpas 1992), while 2 mg nightly raised nocturnal GH without changing body composition (Vittone 1997). Ipamorelin has one human PK study and one negative phase 2 trial in postoperative ileus (Beck 2014). GHRH(1-44) given with GHRP-6 was synergistic in men (Bowers 1990), the rationale for the pairing, but no study has tested sermorelin with ipamorelin. FDA lists ipamorelin in category 2 for 503B outsourcing on its compounding safety-risk page.
Benefits
GH and IGF-1 rise (human, sermorelin, small trials in older men); GH pulse after IV ipamorelin (human PK study); larger combined GH pulse expected from GHRH plus GHRP synergy (human, other analogs). No data for the blend
Dosing reference
- Research dose
- 200 to 800 mcg of blend at bedtime (100 to 400 mcg of each at the 5 mg/5 mg ratio): vendor/community range, no published human dose of the blend. Adult sermorelin trials used 0.5 to 2 mg per injection
- Range
- 200 to 800 mcg, 1x daily before bed
- Reconstitution
- 2 mL bacteriostatic water
- Common vial sizes
- 10 mg
Subcutaneous at bedtime in community use, continuously or 5 days on, 2 days off; neither pattern has been studied for the blend. Adult sermorelin trials used 0.5 to 1 mg twice daily (Corpas 1992) or 2 mg nightly (Vittone 1997), above the 100 to 400 mcg of sermorelin in this range; the pediatric label dose was 30 mcg/kg nightly. Human ipamorelin doses were IV (0.03 mg/kg twice daily in the ileus trial).
Mechanism
Proposed, from component and class studies. Sermorelin is GHRH(1-29) amide, the shortest fully active fragment of GHRH, acting on the pituitary GHRH receptor; it is cleared within minutes in men. Ipamorelin is a ghrelin-receptor agonist that released GH without raising ACTH or cortisol in swine (Raun 1998). GHRH-receptor and ghrelin-receptor agonists given together raise GH more than either alone in men (Bowers 1990), shown with GHRH(1-44) and GHRP-6 rather than this pair. Claims that the blend restores a more natural GH pattern, or suits long-term use better than other combinations, have no published source.
Evidence
Preclinical: animal or in vitro data only
- Sermorelin 1 mg SC twice daily for 14 days restored 24 h GH and IGF-1 in healthy older men to young-adult levels (Corpas et al., 1992)
- Sermorelin 2 mg nightly for 6 weeks raised nocturnal GH and some strength measures, with no change in IGF-1 or body composition (Vittone et al., 1997)
- IV ipamorelin in 40 healthy men gave a single GH peak at 40 min with a 2 h terminal half-life (Gobburu et al., 1999)
- Phase 2 RCT of IV ipamorelin in postoperative ileus (n=114): well tolerated, no efficacy difference from placebo (Beck et al., 2014)
- Human-trial status: no study has tested the blend as sold. Sermorelin was approved in 1997 (Geref) for pediatric GH deficiency and discontinued in 2008; GHRH plus GHRP synergy in men was shown with GHRH(1-44) and GHRP-6, not this pair (Bowers et al., 1990)
References
- Growth hormone (GH)-releasing hormone-(1-29) twice daily reverses the decreased GH and insulin-like growth factor-I levels in old men. Corpas E, Harman SM, Pineyro MA, Roberson R, Blackman MR, Journal of Clinical Endocrinology & Metabolism, 1992
- Effects of single nightly injections of growth hormone-releasing hormone (GHRH 1-29) in healthy elderly men. Vittone J, Blackman MR, Busby-Whitehead J, et al., Metabolism, 1997
- Sermorelin: a review of its use in the diagnosis and treatment of children with idiopathic growth hormone deficiency. Prakash A, Goa KL, BioDrugs, 1999
- Incorporation of D-Ala2 in growth hormone-releasing hormone-(1-29)-NH2 increases the half-life and decreases metabolic clearance in normal men. Soule S, King JA, Millar RP, Journal of Clinical Endocrinology & Metabolism, 1994
- Ipamorelin, the first selective growth hormone secretagogue. Raun K, Hansen BS, Johansen NL, et al., European Journal of Endocrinology, 1998
- Pharmacokinetic-pharmacodynamic modeling of ipamorelin, a growth hormone releasing peptide, in human volunteers. Gobburu JV, Agerso H, Jusko WJ, Ynddal L, Pharmaceutical Research, 1999
- Prospective, randomized, controlled, proof-of-concept study of the Ghrelin mimetic ipamorelin for the management of postoperative ileus in bowel resection patients. Beck DE, Sweeney WB, McCarter MD; Ipamorelin 201 Study Group, International Journal of Colorectal Disease, 2014
- Growth hormone (GH)-releasing peptide stimulates GH release in normal men and acts synergistically with GH-releasing hormone. Bowers CY, Reynolds GA, Durham D, Barrera CM, Pezzoli SS, Thorner MO, Journal of Clinical Endocrinology & Metabolism, 1990
Side effects
No human safety study of the blend has been published. In sermorelin trials, transient facial flushing and injection-site pain were the most common adverse events (Prakash 1999); IV ipamorelin was well tolerated in a phase 2 trial (Beck 2014). Commonly reported by users (anecdotal): injection-site reactions, flushing, head rush, water retention and joint aches; reduced insulin sensitivity and carpal tunnel symptoms are reported with sustained GH elevation. Ipamorelin is in category 2 of FDA's 503B interim policy (added 2023-09-29) and in the withdrawn-nomination table for 503A, as of 2026-04-22: https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks.
Storage
- Storage
- Refrigerate 2-8°C (36-46°F)
- Lyophilized
- 2+ years at room temp, 3+ years refrigerated
- Reconstituted
- 28-30 days refrigerated
Pharmacology
- Half-life
- Sermorelin ~4 min (human, IV infusion). Ipamorelin ~2 h terminal (human, IV)
- Bioavailability
- Not reported for subcutaneous dosing of either component in the sources reviewed; human ipamorelin data are IV. No data for the blend