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.
Reviewed by the amino101 editorial team. , first published .
Quick start
What people commonly do. Not a prescription.- Typical dose
- 200 to 500 mcg
- How often
- once daily
- Where
- Subcutaneous, belly or thigh, rotate sites
- Timing
- Right before bed on an empty stomach, at least 2 hours after the last meal
- Effects timeline
- sleep quality 1 to 2 weeks, IGF-1 rise on bloodwork 4 to 6 weeks, body composition and skin 2 to 3 months if at all
- Storage
- Lyophilized in fridge or freezer away from light; reconstituted in fridge 2 to 8 C, use within 4 weeks
- Cycle length
- 3 to 6 months
- Break between
- reassess with IGF-1; many run it ongoing with periodic breaks of a few weeks
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.
Where the research stands
Pediatric growth hormone deficiencyStrong evidence
- Growth velocity in GHD children. Clinical trials behind the original approval showed increased growth over 6 to 12 months of daily injections, less than recombinant GH.
Diagnostic stimulation testingStrong evidence
- Growth hormone reserve testing. Approved and used clinically as a stimulation test for pituitary GH reserve.
Body composition in older adultsModerate evidence
- Lean mass and IGF-1. A 16 week human RCT in adults aged 55 to 71 found higher IGF-1 and a modest lean mass increase with nightly dosing.
- Fat loss. Changes in fat mass in the same trials were small and inconsistent.
SleepEmerging
- Slow wave sleep. GHRH increased slow wave sleep in small human lab studies; sermorelin itself has not been trialed for sleep.
General anti-agingWeak or mixed
- Energy, skin, and wellbeing. Clinic marketing claims that rest on anecdote; no controlled trial has measured these endpoints with sermorelin.
- 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.
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.
Levels over time
Modeled from the half-life. Illustrative, not measured.A half-life of 15 min against dosing every 24 h means each dose has cleared before the next. Nothing stacks; you start from zero every time, and the tissue effect is what carries over.
It is degraded by DPP-IV within minutes, so each dose gives one small pulse; that is why it is injected nightly at the moment somatostatin is lowest, and why it produces a weaker response than the stabilized analogs.
Sermorelin dosage and protocols
Clinics typically prescribe it continuously for 3 to 6 months before rechecking IGF-1, and many patients stay on it long term with occasional breaks. Some protocols use 5 nights on and 2 off. There is no loading or taper.
| Goal | Dose | Frequency | Route |
|---|---|---|---|
| Clinic standard | 200 to 300 mcg | once daily before bed | Subcutaneous |
| Higher single dose | 500 mcg | once daily before bed | Subcutaneous |
| Stacked with a GHRP | 200 mcg | once daily before bed, with 100 mcg ipamorelin | Subcutaneous, same syringe |
| 5 on 2 off variant | 300 mcg | once daily, weekdays only | Subcutaneous |
Bedtime on an empty stomach is the whole strategy: the natural growth hormone surge in early deep sleep is when a short lived GHRH pulse does the most, and insulin from a recent meal suppresses it. Avoid eating for about 30 minutes after injecting. It combines well in one syringe with a GHRP.
clinics commonly prescribe 200-300 mcg nightly; higher doses give diminishing returns
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.
| 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 |
How to reconstitute Sermorelin
- 1
Wash your hands and wipe the work surface. Swab both vial stoppers with alcohol and let them dry.
- 2
Pick the water volume with the calculator above and write it on the vial. The concentration means nothing without it.
- 3
Draw the bacteriostatic water into a mixing syringe.
- 4
Insert at an angle and let the water run down the inside wall. Never squirt it straight onto the powder.
- 5
Swirl gently or leave it to dissolve. Do not shake.
- 6
Label with the date and water volume. Store in the fridge at 2 to 8 C and use within about 4 weeks.
- 7
Unmixed vials keep for months in the fridge and longer in the freezer, sealed and out of light.
- Full walkthrough with syringe reading and site rotation: reconstitution guide.
- ✓White, fluffy cake
Lyophilized powder should look like a small white puck or fluffy cake at the bottom of the vial. That is a proper freeze-dry.
- ✓Clear after mixing
Once dissolved the solution should be water-clear with nothing floating in it.
- !Slight clumping
Small clumps that dissolve with gentle swirling are fine. Shipping compacts powder.
- ✕Collapsed or melted
Powder stuck to the sides, glassy, or shrunken means it got hot in transit. Contact the vendor.
- ✕Cloudy or particles
Persistent cloudiness or visible particles after mixing means degraded or contaminated product. Do not use it.
- Week 1 to 2
Injection site redness or itching, occasional flushing, and often deeper sleep within the first several nights.
- Week 2 to 6
Sleep benefit settles in, IGF-1 begins to rise, little else noticeable.
- Week 6 to 12
Bloodwork confirms whether IGF-1 moved; some people notice better recovery or skin, many notice nothing beyond sleep.
- Month 3 to 6
Modest lean mass change at best; decide whether to continue based on IGF-1 and how you feel.
Interactions and stacking
Ipamorelinsynergistic
Adds the ghrelin receptor pathway and turns a small sermorelin pulse into a meaningful one.
CJC-1295 (no DAC)caution
Same receptor with a more stable sequence; combining them is redundant, most people simply switch.
Tesamorelincaution
Also a GHRH analog on the same receptor; use one or the other.
HGHcaution
Exogenous growth hormone suppresses pituitary output through feedback, leaving little for sermorelin to release.
Thyroid medicationcaution
Untreated hypothyroidism blunts the growth hormone response; thyroid status should be corrected first.
Corticosteroidscaution
Glucocorticoids raise somatostatin and shrink the pulse.
Insulin and diabetes medicationscaution
Growth hormone opposes insulin; the effect is small with sermorelin but glucose should still be watched.
Food near the doseavoid
Eating before or soon after the injection wastes most of it.
Safety
- ▲Injection site redness, itching, or small lumps
- ▲Flushing or warmth shortly after a dose
- ▲Headache or dizziness
- ▲Mild water retention
- ▲Drowsiness, which is why bedtime dosing is preferred
- ▲Nausea in a small number of people
- ▲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.
- ■Persistent tingling, numbness, or joint swelling
- ■IGF-1 above the reference range for your age
- ■Fasting glucose or HbA1c drifting up
- ■A new lump, growth, or any cancer diagnosis
- ■No measurable IGF-1 change after 3 months, in which case it is not worth continuing
Community poll
Self-reported by visitors. Not clinical evidence.Sermorelin: 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