Sermorelin

Growth Hormone Secretagogue (GHRH Analog)formerly FDA-approved

Also known as: GRF 1-29, Geref, Sermorelin Acetate, GHRH(1-29)NH2

The first 29 amino acids of natural GHRH, previously FDA-approved for pediatric GH deficiency. Now widely used off-label for anti-aging GH optimization as a safer alternative to direct HGH therapy.

Overview

Sermorelin is a synthetic peptide consisting of the first 29 amino acids of the 44-amino acid human growth hormone-releasing hormone (GHRH). These 29 amino acids represent the bioactive portion responsible for GHRH receptor binding and GH stimulation. Sermorelin was previously FDA-approved (as Geref) for the diagnosis and treatment of growth hormone deficiency in children, though the branded product was discontinued in 2008 due to manufacturing issues (not safety concerns). It remains available through compounding pharmacies and is one of the most commonly prescribed peptides by anti-aging and functional medicine physicians. Sermorelin is considered a safer approach to GH optimization compared to direct HGH administration because it stimulates endogenous GH production while preserving the body's natural feedback mechanisms, preventing supraphysiological GH levels.

Mechanism of Action

Sermorelin works by: (1) Binding to GHRH receptors (GHRH-R) on pituitary somatotroph cells, stimulating synthesis and secretion of growth hormone; (2) Preserving natural GH pulsatility โ€” the pituitary responds to sermorelin but is still regulated by somatostatin feedback; (3) Cannot produce supraphysiological GH levels because the pituitary has a finite capacity for GH release (unlike exogenous HGH which bypasses this); (4) Stimulates GH gene transcription, potentially supporting long-term pituitary health; (5) Enhanced effects during sleep when somatostatin tone is naturally low; (6) Downstream effects include increased IGF-1, improved protein synthesis, enhanced lipolysis, and better sleep architecture.

Molecular Formula

C149H246N44O42S

Molecular Weight

3357.88 g/mol

Sequence

Tyr-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Met-Ser-Arg-NH2

Dosage Protocols

Dose Range

200mcg โ€“ 500mcg

Frequency

Once daily (before bed)

Route

subcutaneous

Cycle Length

3-6 months, then reassess

Inject before bed on an empty stomach to enhance natural nocturnal GH surge. Effects are gradual; most patients notice improvements in sleep, energy, and body composition over 3-6 months.

Source: Clinical prescribing protocols

Side Effects

EffectSeverity
Injection site reactionsmild
Flushingmild
Headachemild
Dizzinessmild
Hyperactivity in childrenmild

Pros & Cons

โœ“

Previously FDA-approved with established clinical safety data โ€” one of the most thoroughly vetted GH peptides

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Cannot produce supraphysiological GH levels โ€” much safer than direct HGH injection

โœ“

Available through licensed compounding pharmacies with a prescription, ensuring quality and legality

โœ“

Preserves natural GH pulsatility and pituitary feedback mechanisms

โœ“

Very mild side effect profile with decades of clinical use data

โœ—

Less potent than newer GHRH analogs (Mod GRF 1-29) due to rapid enzymatic degradation (half-life ~10-20 min)

โœ—

Effectiveness decreases with age as pituitary capacity to produce GH declines

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Requires daily injection, typically before bed

โœ—

Results are subtle and gradual โ€” takes months to see full benefits

โœ—

Branded product (Geref) discontinued; now only available through compounding pharmacies

Research Studies

Legal Status

Previously FDA-approved (Geref, discontinued 2008). Available through compounding pharmacies with a prescription. Legal for off-label use when prescribed. Banned by WADA.

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