Sermorelin
Also known as GRF 1-29, Geref, Sermorelin acetate, GHRH 1-29
Sermorelin is the first 29 amino acids of natural growth hormone releasing hormone, the shortest fragment that still fully activates the receptor. It was once an approved diagnostic and pediatric drug and is now the most common growth hormone secretagogue prescribed by anti-aging and wellness clinics.
Overview
Sermorelin is GRF 1-29, the biologically active N-terminal fragment of the 44 amino acid growth hormone releasing hormone produced in the hypothalamus. Unlike Mod GRF 1-29, it carries no stabilizing substitutions, so it is cleared quickly by DPP-IV and other enzymes. It was approved by the FDA in the 1990s as Geref, used to diagnose growth hormone deficiency and to treat children with short stature. The manufacturer discontinued it in 2008 for commercial reasons rather than safety concerns, and the compound has since lived on almost entirely through compounding pharmacies.
Human data on sermorelin is older but real. Pediatric trials showed it increased growth velocity in children with growth hormone deficiency, though less than recombinant growth hormone. Studies in healthy older adults in the 1990s found that nightly injections raised growth hormone and IGF-1, improved lean mass modestly, and were well tolerated over several months. Because it works through the pituitary, the body's own feedback keeps IGF-1 from climbing into supraphysiologic territory, which is the main argument clinics make for it over direct growth hormone.
The honest assessment is that sermorelin is safe and works, but it is the weakest of the GHRH analogs. Its short half-life and vulnerability to enzymes mean each dose produces a smaller and less reliable pulse than tesamorelin or Mod GRF 1-29. Clinics prescribe it because it has a regulatory history and is easy to compound, not because it outperforms the alternatives. Most self-directed users who compare them move to Mod GRF 1-29 or tesamorelin.
How it works
Sermorelin binds the GHRH receptor on anterior pituitary somatotrophs, activating adenylate cyclase and raising intracellular cAMP, which stimulates both transcription of the growth hormone gene and exocytosis of stored growth hormone. The pulse is short lived because the peptide is degraded within minutes, and its size is heavily gated by somatostatin, so it is far more effective when injected during the natural nighttime window of low somatostatin tone. The downstream effects, higher IGF-1 and increased lipolysis, follow from the growth hormone pulse rather than from sermorelin acting on peripheral tissues directly.
What the research shows
- clinical (approved drug)Sermorelin increased growth velocity in children with idiopathic growth hormone deficiency over 6-12 months of daily injections.
- human RCTNightly sermorelin in healthy men and women aged 55-71 raised IGF-1 and modestly increased lean body mass over 16 weeks.
- clinical (approved drug)Sermorelin remained effective as a diagnostic stimulation test for growth hormone reserve in adults.
- human pilotGRF 1-29 is rapidly degraded by DPP-IV, with a plasma half-life of roughly 10-20 minutes in humans.
Evidence labels: rodent and in vitro mean no human data for that finding. Human pilot means small, often uncontrolled. Human RCT means randomized and controlled. Clinical means an approved drug with regulatory data.
Dose calculator
U-100 insulin syringeUnits are a volume on the syringe, not an amount of peptide. Concentration changes every time you change the water volume. The standalone calculator explains the math.
Dosing and protocol
clinics commonly prescribe 200-300 mcg nightly; higher doses give diminishing returns
3-6 months, then reassess with IGF-1; many people run it ongoing with periodic breaks
Right before bed on an empty stomach, at least 2 hours after the last meal.
| Vial | Suggested water | Concentration | Low dose draw |
|---|---|---|---|
| 5 mg | 2 mL | 2.5 mg/mL | 8 units |
| 10 mg | 3 mL | 3.333 mg/mL | 6 units |
Lyophilized: fridge or freezer, away from light. Reconstituted: fridge 2-8C, use within 4 weeks.
Cautions
- ▲Injection site redness, itching, and small lumps are the most common complaints.
- ▲Flushing, headache, and dizziness can occur shortly after a dose.
- ▲Eating before or soon after the injection significantly reduces the growth hormone response.
- ▲People with active cancer or untreated hypothyroidism should not use growth hormone secretagogues.
- ▲Expect modest effects; sermorelin is the gentlest of the GHRH analogs, not the strongest.
Commonly stacked with
Frequently asked
Is sermorelin better than growth hormone?
It is safer in the sense that your pituitary stays in control and IGF-1 cannot be pushed as high. It is not stronger. Recombinant growth hormone produces larger and more predictable changes in body composition, at the cost of shutting down your own production while you use it.
Why do clinics prescribe sermorelin instead of tesamorelin or CJC-1295?
Mostly history and logistics. Sermorelin was once an approved drug, so compounding pharmacies can make it with fewer regulatory headaches, and it is cheap. Tesamorelin is stronger but expensive, and Mod GRF 1-29 has never been through the drug approval process.
How long until I notice anything?
Sleep quality often improves within the first couple of weeks. Changes in body composition, skin, and recovery are slower and typically take 2-3 months, if they appear at all. IGF-1 bloodwork at 4-6 weeks tells you whether it is doing anything measurable.
Can I take it with food?
You can, but you will waste most of it. Insulin and free fatty acids from a meal suppress growth hormone release, so the standard advice is to inject on an empty stomach at bedtime and not eat afterward.
References
- Growth hormone-releasing hormone 1-29 (sermorelin) in the treatment of growth hormone deficient children. Journal of Clinical Endocrinology and Metabolism, 1992
- Effects of nightly GHRH 1-29 administration in healthy older men and women. Journal of Clinical Endocrinology and Metabolism, 1997
- Geref (sermorelin acetate for injection) prescribing information. US Food and Drug Administration, 1997