Growth Hormone Secretagogue Side Effects: What Studies Report

This page is for educational purposes only and is not medical advice; consult a licensed physician about any health decision. It summarises what published papers reported about adverse events, tolerability and safety signals associated with growth hormone secretagogues (GHS), and it deliberately stops at description. Where the published record is thin or missing, that absence is stated plainly rather than filled in.

What "growth hormone secretagogue" refers to in the literature

Growth hormone secretagogues are compounds that act at the growth hormone secretagogue receptor (GHSR), the receptor for the endogenous peptide ghrelin. The label covers chemically unrelated molecules studied in very different settings: the orally active compound MK-677 (ibutamoren), described in a 2025 BMJ Case Reports paper on hepatotoxicity induced by MK-677 (PMID 40675653); capromorelin, evaluated for daily administration safety in cats in a 2018 veterinary pharmacology study (PMID 29057482); and the experimental secretagogue JMV2894, studied preclinically in the D2-mdx mouse model of Duchenne muscular dystrophy (PMID 41223758). Because these are separate molecules tested in separate species, the reported tolerability of one does not describe the others.

A 2018 review in Sexual Medicine Reviews addressed the safety and efficacy of growth hormone secretagogues as a class (PMID 28400207), and a 2026 review in the American Journal of Sports Medicine surveyed peptide supplements and their therapeutic applications in sports medicine, a category into which secretagogues are frequently placed (PMID 42578445). Reviews of this kind aggregate existing reports; they do not generate new adverse-event rates.

Liver and Hepatic Signals: What Studies Report

The most direct human adverse-event document in this verified set is a case report. Researchers publishing in BMJ Case Reports in 2025 described hepatotoxicity induced by MK-677 (PMID 40675653). A single case report is a narrative account of one patient; the study design cannot establish how often such an event occurs, whether it depends on amount or duration of exposure, or whether co-exposures contributed. What it does establish is that a hepatic adverse event associated with this compound was considered clinically significant enough to publish.

No paper in this verified set reported liver monitoring outcomes across a controlled human cohort taking a growth hormone secretagogue, so the frequency of hepatic signals in humans is not characterised by the literature reviewed here. That is an absence of data, not evidence of safety.

Glucose, Insulin and Metabolic Signals: What Studies Report

Metabolic signalling is one of the most consistently examined areas in GHSR pharmacology. A 2013 study in Nutrition & Diabetes reported that the ghrelin receptor regulated high-fructose corn syrup-induced adipose inflammation and insulin resistance in a rodent model (PMID 24366371). That work concerned receptor biology under a dietary challenge rather than administration of a pharmaceutical secretagogue, but it is the kind of mechanistic finding that motivates attention to glucose handling when GHSR is stimulated.

On the clinical side, a 2009 study in the Journal of Clinical Endocrinology & Metabolism examined the effects of an oral growth hormone secretagogue in older adults (PMID 19174493), and the 2018 class review assessed safety alongside efficacy for secretagogues generally (PMID 28400207). Readers looking for metabolic adverse-event numbers should consult those primary documents directly; this page does not restate figures beyond the scope of the titles and abstracts verified for it.

Appetite, Muscle and Body-Composition Signals: What Studies Report

Ghrelin-pathway activation is closely tied to appetite and to muscle biology, which is why many secretagogue papers sit in the cachexia and sarcopenia literature rather than the performance literature. A 2020 review in the Journal of Aging Science discussed ghrelin as a "thrifty hormone" in the context of maintaining muscle with age (PMID 34368393). A 2026 study in Peptides reported that ghrelin attenuated skeletal-muscle atrophy by regulating muscle protein degradation and lung inflammation in aged male mice with lipopolysaccharide-induced lung injury (PMID 41722618). A 2025 preclinical paper in Biomedicine & Pharmacotherapy examined the growth hormone secretagogue JMV2894 in the D2-mdx mouse model of Duchenne muscular dystrophy (PMID 41223758).

These are efficacy-oriented animal studies in disease models. They describe intended pharmacology, not adverse events in healthy humans, and the species and disease context limit how far the observations travel. Increased appetite, where it appears in this literature, is typically framed as a therapeutic objective in wasting conditions rather than as a side effect.

Cognitive and Neurological Signals: What Studies Report

Neural effects of ghrelin signalling have been examined at the circuit level. A 2022 paper in Neuropharmacology reported that ghrelin signalling in the dorsal CA1 region suppressed neuronal excitability and impaired memory acquisition via PI3K/Akt/GSK-3β cascades in a rodent model (PMID 34742928). The study was mechanistic and region-specific; it does not describe cognitive outcomes in people using a secretagogue, and no human cognitive safety trial appears in this verified set. Ghrelin biology has also been probed from the opposite direction: a 2024 randomized, double-blind, placebo-controlled study in JCI Insight tested a GHSR blocker in people with alcohol use disorder (PMID 39704175), which illustrates that the receptor is being investigated clinically for central nervous system indications in both agonist and antagonist directions.

Animal and Veterinary Safety Studies: What Studies Report

Two of the more explicitly safety-framed papers in this set come from veterinary and laboratory-animal medicine. Researchers evaluated the safety of daily administration of capromorelin in cats in a 2018 study published in the Journal of Veterinary Pharmacology and Therapeutics (PMID 29057482), and a 2024 paper in JAALAS evaluated the safety and efficacy of capromorelin in rhesus macaques (PMID 38423529). Studies designed around repeated dosing with safety as a primary endpoint are comparatively rare in the secretagogue literature, which is one reason veterinary data are cited so often in discussions of this class.

Where the human safety record is absent

Several things commonly asked about this class are not answered by the papers verified for this page, and it is more useful to say so than to speculate:

• Incidence rates. No paper here reported the frequency of any adverse event in a human population exposed to a growth hormone secretagogue; the hepatic signal comes from a single case report (PMID 40675653).
• Long-term outcomes. No multi-year human follow-up study appears in this set; the longest-running safety-focused designs cited here were in cats (PMID 29057482) and rhesus macaques (PMID 38423529).
• Cancer, cardiac and mortality endpoints. These were not endpoints in any verified paper listed on this page.
• Non-prescription products. Compounds sold outside regulated pharmaceutical channels are not the same material tested in published trials, and no paper here characterised the content of such products.

Ibutamoren (MK-677) has not been approved as a human medicine by the US Food and Drug Administration, and material labelled for research use only is not manufactured to clinical standards. That regulatory framing is factual context, not legal advice.

How the class reviews frame the question

Narrative reviews are where most readers first meet this topic. The 2018 Sexual Medicine Reviews article was written explicitly around the safety and efficacy of growth hormone secretagogues (PMID 28400207), and the 2026 American Journal of Sports Medicine review placed peptide supplements, including secretagogue-type compounds, in a sports medicine context (PMID 42578445). A review's conclusions inherit the limitations of the studies it summarises: when the underlying trials are small, short, or conducted in animals, a favourable summary sentence does not upgrade that evidence.

Reading adverse-event literature on this class

1. Check the species. Much of the mechanistic ghrelin-pathway work cited above was rodent (PMID 41722618, PMID 34742928).
2. Check the molecule. Capromorelin safety findings (PMID 38423529) do not describe MK-677 or JMV2894 (PMID 41223758).
3. Check the direction of the intervention. The 2024 randomized, double-blind, placebo-controlled trial tested a GHSR blocker rather than an agonist (PMID 39704175).
4. Check whether safety was an endpoint at all. Efficacy studies in disease models often report tolerability only incidentally.

For background on what these compounds are and how the receptor pathway was characterised, PeptideU's growth hormone secretagogue course (/learn/growth-hormone-secretagogue/) covers the pharmacology; this page stays on the safety and adverse-event literature. Neither page recommends use of any compound.

References

• Hepatotoxicity induced by MK-677 (BMJ Case Reports, 2025)
• A randomized, double-blind, placebo-controlled study of a GHSR blocker in people with alcohol use disorder (JCI Insight, 2024)
• The Safety and Efficacy of Growth Hormone Secretagogues (Sexual Medicine Reviews, 2018)
• Thrifty Hormone Ghrelin: The Secret of Aging Muscularly (Journal of Aging Science, 2020)
• Ghrelin signaling in dCA1 suppresses neuronal excitability and impairs memory acquisition via PI3K/Akt/GSK-3β cascades (Neuropharmacology, 2022)
• Evaluation of the safety of daily administration of capromorelin in cats (Journal of Veterinary Pharmacology and Therapeutics, 2018)
• Ghrelin attenuates skeletal-muscle atrophy by regulating muscle protein degradation and lung inflammation in aged male mice with lipopolysaccharide-induced lung injury (Peptides, 2026)
• Ghrelin receptor regulates HFCS-induced adipose inflammation and insulin resistance (Nutrition & Diabetes, 2013)
• Peptide Supplements and Their Therapeutic Applications in Sports Medicine (The American Journal of Sports Medicine, 2026)
• Novel insights into the effects of JMV2894, a growth hormone secretagogue, in Duchenne muscular dystrophy: A preclinical study in the D2-mdx mouse model (Biomedicine & Pharmacotherapy, 2025)
• Evaluating the Safety and Efficacy of Capromorelin in Rhesus Macaques (Macaca mulatta) (JAALAS, 2024)
• Effects of an oral growth hormone secretagogue in older adults (The Journal of Clinical Endocrinology & Metabolism, 2009)