¶ Sermorelin for Longevity
| 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 (29 AA) |
| Formula | C149H246N44O42S |
| Molar Mass | 3357.88 g/mol |
| Category | GHRH Analog (Secretagogue) |
| Half-life | 10–20 minutes |
| Admin | Subcutaneous (SubQ) |
| FDA Status | Approved Drug Substance (Geref) |
| CAS | 86168-78-7 |
Sermorelin is a synthetic peptide analog of Growth Hormone-Releasing Hormone (GHRH) used to restore endogenous growth hormone (GH) levels to a youthful range. Originally FDA-approved as the drug Geref for diagnosing and treating growth failure in children, it is now widely prescribed off-label in longevity medicine to improve body composition, sleep quality, and recovery in aging adults.
¶ At a glance
Aliases
- GHRH (1-29): It consists of the first 29 amino acids of the endogenous 44-amino acid GHRH peptide.
- GRF 1-29: Growth Hormone Releasing Factor 1-29.
Key points
- Physiological Restoration: Unlike exogenous HGH which suppresses natural production, Sermorelin stimulates the pituitary to produce its own GH in a natural pulsatile manner.
- Safety Profile: Because it relies on the body's natural feedback loops (specifically somatostatin), it has a significantly lower risk of overdose and side effects compared to synthetic HGH.
- Primary Benefits: Best supported evidence is for improving body composition (increasing lean mass, reducing visceral fat) and enhancing deep slow-wave sleep in older adults.
- Short Half-Life: Its very short half-life (~12 mins) means it is typically taken nightly or combined with other peptides (like CJC-1295) to extend activity.
What people use it for
- Main goals: Anti-aging, muscle preservation (sarcopenia), fat loss, sleep optimization, and recovery from injury.
- Evidence quality: Moderate. Well-established mechanism and solid clinical data for body composition; mixed evidence for cognitive benefits.
¶ Legal & regulatory status
⚠️ CRITICAL INFORMATION: 2023-2025 FDA COMPOUNDING UPDATES
Regulatory Classification
- FDA Status: Sermorelin is an FDA-approved drug substance. It was approved under the brand name Geref (NDA 020443). Although the manufacturer discontinued Geref in 2008 for business reasons, the FDA confirmed this was not due to safety or efficacy concerns.
- Compounding: Unlike novel peptides (e.g., BPC-157) which were placed on the FDA's "Category 2" list of bulk substances raising safety concerns, Sermorelin remains legal to compound in the United States under Section 503A and 503B of the FD&C Act. It does not rely on the interim bulk substance nomination process because it is a component of an approved drug.
- Prescription: Requires a valid prescription from a licensed healthcare provider.
Sports and Competition
- WADA Status: Banned. Sermorelin is classified under S2. Peptide Hormones, Growth Factors, Related Substances, and Mimetics on the WADA Prohibited List. It is prohibited at all times (in and out of competition) for professional athletes.
¶ What is Sermorelin?
Sermorelin is a truncated analog of the naturally occurring Growth Hormone-Releasing Hormone (GHRH). The endogenous GHRH produced by the hypothalamus is 44 amino acids long. However, researchers discovered that the biological activity resides entirely in the first 29 amino acids. Sermorelin is simply this functional 1-29 fragment.
It was developed to diagnose and treat growth hormone deficiency (GHD) in children. In the context of longevity, it serves as a "secretagogue"—a substance that causes another substance to be secreted. By binding to GHRH receptors on the pituitary gland, it signals the body to release more of its own growth hormone.
¶ Mechanism of Action
Sermorelin functions through a specific, self-limiting biological pathway that distinguishes it from exogenous HGH therapy.
Figure 1: The pituitary gland, located at the base of the brain, where Sermorelin binds to somatotroph cells to stimulate Growth Hormone release.
¶ 1. Receptor Binding and Signaling
Sermorelin binds to the GHRH receptor (GHRH-R) on somatotroph cells in the anterior pituitary gland. This binding activates the adenylate cyclase-cAMP-PKA signaling pathway, leading to:
- Increased transcription of the GH gene.
- Release of stored GH vesicles into the bloodstream.
¶ 2. Pulsatile vs. Continuous Elevation
This is the most critical distinction. Endogenous GH is released in pulses, primarily during deep slow-wave sleep.
- Exogenous HGH: Creates a constant, non-physiologic elevation of GH levels. This can lead to receptor downregulation ("tachyphylaxis") and side effects like water retention and insulin resistance.
- Sermorelin: Amplifies the natural pulsatile release. It reinforces the body's existing rhythm rather than overriding it.
¶ 3. The Somatostatin Safety Valve
The release of GH induced by Sermorelin is subject to negative feedback by somatostatin, a hormone that inhibits GH release. If GH or IGF-1 levels rise too high, the hypothalamus releases somatostatin to block the effect of Sermorelin.
- Result: It is nearly impossible to overdose on Sermorelin to the point of acromegaly, as the body's natural "brakes" remain functional.
¶ Evidence summary table (human outcomes)
| Outcome / Goal | Effect | Consistency | Evidence Quality | Trials | Notes |
|---|---|---|---|---|---|
| Body Composition (Lean Mass) | High | Moderate | Multiple | Increases lean mass and reduces visceral fat in older adults with GHD or relative insufficiency[1][2]. | |
| Sleep Quality (Slow Wave) | Moderate | Moderate | 2 Key Studies | Specifically increases deep Slow Wave Sleep (SWS) in older men and women[3]. | |
| Cognitive Function | ↔ / ? | Low | Low | Mixed | Some data showing improved fluid intelligence; others showing no change[4]. |
| Immune Function | Moderate | Low | Small RCTs | Improved B-cell function and T-cell proliferation in elderly subjects[5]. | |
| Skin Thickness | Moderate | Low | Limited | Increases in skin thickness and collagen content observed in GH-deficient adults. |
¶ Effects on different systems
¶ Metabolic Health & Body Composition
The decline in GH and IGF-1 (somatopause) correlates with increased abdominal fat and loss of muscle mass.
- Findings: Clinical studies show that GHRH analogs can reverse these age-related changes. By stimulating lipolysis (fat breakdown) and protein synthesis, Sermorelin shifts the body composition profile toward a more youthful phenotype.
- Reality Check: While effective, the results are generally subtler and take longer (3-6 months) to manifest compared to high-dose HGH.
¶ Sleep Architecture
One of the most immediate benefits reported by users is improved sleep.
- Mechanism: The GHRH system is bidirectionally linked with sleep. GHRH promotes Non-REM (NREM) deep sleep, and deep sleep triggers GH release.
- Evidence: Vitiello et al. (2000) demonstrated that GHRH administration in healthy older adults significantly increased the time spent in slow-wave sleep and improved sleep efficiency, countering the typical age-related fragmentation of sleep[3:1].
Figure 2: A hypnogram showing healthy sleep architecture. Sermorelin helps restore the deep Slow Wave Sleep (SWS) phases often lost with aging.
¶ Cognitive Function
Because IGF-1 is neuroprotective and promotes neurogenesis, there is a theoretical basis for cognitive enhancement.
- Data: Results are conflicting. One study suggested improvements in fluid intelligence (processing speed/problem solving) in older adults, while others found no significant cognitive benefit compared to placebo[4:1]. It is possible that cognitive gains are secondary to improved sleep quality.
¶ Dosage and Protocols
Standard Anti-Aging Dosage
- Dose: 200 mcg – 500 mcg (0.2 – 0.5 mg) daily.
- Timing: Strictly at bedtime (HS). This timing is crucial to mimic and amplify the natural nocturnal GH spike that occurs shortly after falling asleep.
- Administration: Subcutaneous injection (abdomen or thigh).
The "Stacking" Protocol (Sermorelin + Peptides)
Sermorelin is rarely used alone in modern protocols due to its short half-life (~12 mins). It is frequently stacked to enhance efficacy.
-
Sermorelin + Ipamorelin: The most common "gentle" stack.
- Rationale: Sermorelin increases the amount of GH per pulse. Ipamorelin (a GHRP) increases the number of pulses and suppresses somatostatin. Together, they create a synergistic release 3-5x greater than either alone.
- Protocol: 300 mcg Sermorelin + 300 mcg Ipamorelin daily at bedtime.
-
Sermorelin + GHRP-2: A stronger stack.
- Rationale: GHRP-2 is more potent than Ipamorelin but carries a slight risk of increasing prolactin/cortisol (though less than GHRP-6).
- Protocol: 300 mcg Sermorelin + 150 mcg GHRP-2.
Cycling
To prevent receptor desensitization (tachyphylaxis), cycling is recommended:
- Option A: 5 days on / 2 days off (e.g., Mon-Fri, weekends off).
- Option B: 3 months on / 1 month off.
Reconstitution
- Diluent: Bacteriostatic Water.
- Example: To a 2 mg (2000 mcg) vial of Sermorelin, add 2 mL water.
- Concentration = 1000 mcg/mL.
- Dose (300 mcg) = 0.3 mL (30 units on an insulin syringe).
¶ Safety and Side Effects
Sermorelin is widely regarded as one of the safest peptides due to its inability to bypass the body's negative feedback loops.
Common Side Effects
- Injection Site Reactions: Pain, redness, or swelling (occurring in ~16% of patients).
- Flushing: A warm sensation or flushing of the face immediately after injection (vasodilatory effect).
- Headache/Dizziness: Usually transient.
- Hyperactivity: If taken too close to sleep without winding down, some users report "racing thoughts."
Contraindications
- Active Malignancy: Patients with active cancer should avoid all growth factors (GH/IGF-1) as they drive cell proliferation.
- Benign Intracranial Hypertension: Rare, but possible with increased fluid retention.
¶ References
Walker RF. Sermorelin: a better approach to management of adult-onset growth hormone insufficiency? Clin Interv Aging. 2006;1(4):307-8. https://doi.org/10.2147/ciia.2006.1.4.307 ↩︎
Corpas E, Harman SM, Blackman MR. Human growth hormone and human aging. Endocr Rev. 1993;14(1):20-39. https://doi.org/10.1210/edrv-14-1-20 ↩︎
Vitiello MV, Moe KE, Prinz PN. Growth hormone releasing hormone improves the sleep of older men. Am J Physiol Endocrinol Metab. 2000;279(2):E447-53. https://doi.org/10.1152/ajpendo.2000.279.2.E447 ↩︎ ↩︎
Vitiello MV, et al. GHRH treatment improves sleep and cognition in healthy older adults. Dialogues Clin Neurosci. 2001;3(3):229-36. https://doi.org/10.31887/DCNS.2001.3.3/mvvitiello ↩︎ ↩︎
Khorram O, Yeung M, Vu L, Yen SS. Effects of [norleucine27]growth hormone-releasing hormone (GHRH) (1-29)-NH2 administration on the immune system of aging men and women. J Clin Endocrinol Metab. 1997;82(11):3590-6. https://doi.org/10.1210/jcem.82.11.4365 ↩︎