Ghrelin
Evidence: B/C — Meaningful Human EvidenceGastrointestinal / Gut-Hormone Signaling
Evidence Snapshot
What this grade covers
Applies specifically to acylated (octanoylated) ghrelin, administered intravenously to healthy human volunteers in controlled crossover/randomized studies (Wren 2001, PMID 11739476; Druce 2005, PMID 15917842; Vestergaard 2008, PMID 18776138) -- Evidence Grade B. Des-acyl (unacylated) ghrelin is graded separately at C: two small (n=8, n=17) genuine controlled human IV-infusion studies exist (Benso 2012 PMID 22379116; Tong 2014 PMID 24550190), but both measure metabolic/insulin-secretion endpoints only, neither measures appetite/food intake, and the two studies' own findings are not fully concordant. The C grade must not be merged with, or used to imply equivalence to, the acylated-form B grade. No approved native-ghrelin drug product exists; the receptor-agonist/secretagogue drug class (Ibutamoren, Anamorelin, GHRP family) is firewalled entirely and is not graded on this page at all, not even as a related programme.
Regulatory Context
Native Ghrelin is an endogenous hormone and is not itself an FDA-approved drug product for any indication. Ghrelin-receptor agonists and secretagogues (e.g. Ibutamoren/MK-677, Anamorelin, GHRP-2, GHRP-6, Hexarelin, Ipamorelin) are chemically distinct, separately regulated products; their regulatory status, including any FDA compounding-risk determinations, does not apply to native ghrelin.
Research Takeaway
Ghrelin is an endogenous 28-amino-acid peptide hormone produced predominantly in the stomach; its acylated (octanoylated) form is the active ligand at the growth-hormone secretagogue receptor (GHSR-1a), while des-acyl (unacylated) ghrelin is the predominant circulating form and has distinct, in some respects opposing, biology.
Evidence boundary: This identity statement does not itself establish either form's human efficacy or safety. Do not use to imply Obestatin is a Ghrelin form.
See all 7 evidence claims →Quick Summary
Ghrelin is the body's primary hunger-signaling hormone, produced mainly in the stomach. Human research distinguishes two circulating forms -- acylated ghrelin, which activates its main receptor and has been shown in controlled infusion studies to increase appetite and food intake, and des-acyl ghrelin, the more abundant form, which has its own separate and more limited human evidence base focused on glucose and fat metabolism rather than appetite. Ghrelin-receptor-agonist drugs (e.g. Ibutamoren, Anamorelin, the GHRP family) are chemically distinct from ghrelin itself and are treated separately.
Mechanism & Research Overview
Ghrelin is the body's primary hunger-signaling hormone, produced mainly in the stomach. Human research distinguishes two circulating forms -- acylated ghrelin, which activates its main receptor and has been shown in controlled infusion studies to increase appetite and food intake, and des-acyl ghrelin, the more abundant form, which has its own separate and more limited human evidence base focused on glucose and fat metabolism rather than appetite. Ghrelin-receptor-agonist drugs (e.g. Ibutamoren, Anamorelin, the GHRP family) are chemically distinct from ghrelin itself and are treated separately.
Evidence Claims
Individual scientific statements drawn from the sources cited below, each shown with the specific evidence boundary that statement does not establish.
Supported
Ghrelin is an endogenous 28-amino-acid peptide hormone produced predominantly in the stomach; its acylated (octanoylated) form is the active ligand at the growth-hormone secretagogue receptor (GHSR-1a), while des-acyl (unacylated) ghrelin is the predominant circulating form and has distinct, in some respects opposing, biology.
Does not establish
Evidence boundary: This identity statement does not itself establish either form's human efficacy or safety. Do not use to imply Obestatin is a Ghrelin form.
Sources: Ghrelin Enhances Appetite and Increases Food Intake in Humans; Metabolic Effects of Overnight Continuous Infusion of Unacylated Ghrelin in Humans
Supported
In controlled human intravenous-infusion studies, acylated ghrelin significantly increases ad-libitum food intake and subjective appetite in healthy lean and obese adults.
Does not establish
Evidence boundary: Established only for acylated ghrelin, only via acute IV infusion in short controlled studies (single sessions, small cohorts); does not establish chronic-use safety or efficacy, and does not extend to des-acyl ghrelin or to any receptor-agonist drug.
Sources: Ghrelin Enhances Appetite and Increases Food Intake in Humans; Ghrelin Increases Food Intake in Obese as Well as Lean Subjects
Supported
Acute IV administration of acylated ghrelin has been shown to induce transient peripheral insulin resistance and increased lipolysis in healthy and hypopituitary adults, independent of growth-hormone signaling.
Does not establish
Evidence boundary: A single acute-exposure human study; does not establish chronic metabolic risk, and does not describe des-acyl ghrelin's effects.
Supported
Des-acyl (unacylated) ghrelin has been directly administered to healthy humans in controlled intravenous-infusion studies and produces measurable changes in glucose, insulin, and free-fatty-acid metabolism; it has not been shown in controlled human studies to affect appetite or food intake.
Does not establish
Evidence boundary: Two small controlled human studies exist (n=8 and n=17); findings on specific insulin-secretion endpoints are not fully concordant between them. No human appetite/food-intake trial of des-acyl ghrelin was located. Must not be merged with the acylated-form efficacy claim (ghr-c2).
Sources: Metabolic Effects of Overnight Continuous Infusion of Unacylated Ghrelin in Humans; Acute Administration of Unacylated Ghrelin Has No Effect on Basal or Stimulated Insulin Secretion in Healthy Humans
Supported
Ghrelin-receptor agonists and secretagogues (e.g. Ibutamoren/MK-677, Anamorelin, GHRP-2, GHRP-6, Hexarelin, Ipamorelin) are distinct molecules from native Ghrelin. Their own human clinical data, including any FDA regulatory activity, does not establish native Ghrelin's own efficacy, safety, or regulatory status.
Does not establish
Evidence boundary: Firewall/definitional statement. Never cite a GHRP/Ipamorelin/MK-677/Anamorelin trial as Ghrelin efficacy or safety evidence.
Supported
Obestatin is a separate mature peptide co-derived from the same preproghrelin gene as Ghrelin. It is not a form, fragment, or alias of Ghrelin, and its own evidence base must be assessed independently.
Does not establish
Evidence boundary: Do not use Obestatin data as Ghrelin evidence or vice versa; do not describe Obestatin as 'the opposite of Ghrelin' as an established fact.
Sources: Obestatin, a Peptide Encoded by the Ghrelin Gene, Opposes Ghrelin's Effects on Food Intake
Supported
No native-Ghrelin drug product is FDA-approved for any indication. Ghrelin-receptor-agonist drugs and secretagogues are separately regulated, sequence-distinct products; their regulatory status is not native Ghrelin's regulatory status.
Does not establish
Evidence boundary: Do not imply any present or pending FDA approval for native ghrelin.
Safety & Evidence Limitations
Considerations reported in the sources cited on this page — not a complete list of every possible risk, and not medical advice.
Safety Consideration
A controlled human study (PMID 18776138) found acute IV acylated-ghrelin infusion reduces peripheral insulin sensitivity and increases lipolysis, independent of GH signaling -- a genuine metabolic caution, not a pure benefit finding.Safety Consideration
Acylated and des-acyl ghrelin have materially different, sometimes opposing, biology. Human appetite/food-intake evidence exists only for the acylated form; des-acyl human evidence is metabolic-endpoint-only and must never be presented as appetite evidence.Safety Consideration
Ibutamoren/MK-677, Anamorelin, and the GHRP/hexarelin family act at the same receptor but are distinct, separately-regulated molecules with their own (in some cases FDA-flagged) safety considerations; none of that evidence transfers to native ghrelin.Safety Consideration
All verified human ghrelin intervention studies located in this review are single-session, acute infusions in small cohorts (n=8-17). No chronic administration RCT was identified for either form.
Research Areas Being Studied
Research areas discussed on this page reflect the Gastrointestinal / Gut-Hormone Signaling category and the sources cited below.
Findings Reported in Studies
Educational summary only — reported in cited studies, not a claim of proven benefit.
- Acute Administration of Unacylated Ghrelin Has No Effect on Basal or Stimulated Insulin Secretion in Healthy Humans (2014):
- Metabolic Effects of Overnight Continuous Infusion of Unacylated Ghrelin in Humans (2012):
- Ghrelin Infusion in Humans Induces Acute Insulin Resistance and Lipolysis Independent of Growth Hormone Signaling (2008):
- Ghrelin Increases Food Intake in Obese as Well as Lean Subjects (2005):
- Ghrelin Enhances Appetite and Increases Food Intake in Humans (2001):
Study Tables by Evidence Type
Human Studies & Clinical Data
| Title | Year | Population / Model | Dose / Duration / Finding | Safety Notes | Source |
|---|---|---|---|---|---|
| Acute Administration of Unacylated Ghrelin Has No Effect on Basal or Stimulated Insulin Secretion in Healthy Humans | 2014 | 17 healthy subjects (9M/8F), randomized crossover | IV unacylated ghrelin (4 microg/kg/h) alone or combined with acylated ghrelin had no effect on basal or glucose-stimulated insulin secretion during a 3-hour IV glucose tolerance test. | Genuine negative/null finding for a proposed unacylated-ghrelin insulin-secretion benefit. Acute, single-dose. | |
| Metabolic Effects of Overnight Continuous Infusion of Unacylated Ghrelin in Humans | 2012 | 8 healthy normal-weight subjects | Overnight (16h) IV unacylated (des-acyl) ghrelin infusion (1.0 microg/kg/h) produced significant changes in glucose, insulin, and free-fatty-acid profiles vs. saline, via a mechanism independent of the classical acylated-ghrelin receptor. | Metabolic-endpoint study only, NOT an appetite/food-intake study -- must not be used to support any des-acyl-ghrelin appetite claim. Very small (n=8), single-center. | |
| Ghrelin Infusion in Humans Induces Acute Insulin Resistance and Lipolysis Independent of Growth Hormone Signaling | 2008 | Acute IV acylated ghrelin infusion (5 pmol/kg/min), double-blind crossover in healthy men and hypopituitary adults, produced acute peripheral (not hepatic) insulin resistance and stimulated lipolysis, independent of GH signaling. | A negative/limiting metabolic-safety finding, not a benefit result -- must not be framed as a pure benefit. | ||
| Ghrelin Increases Food Intake in Obese as Well as Lean Subjects | 2005 | Dose-dependent IV acylated ghrelin infusion (1 and 5 pmol/kg/min) increased energy intake in both lean (+20.1%) and obese (+70.1%) subjects. | Small cohort, acute exposure only. Acylated-form-scoped; not evidence for des-acyl ghrelin. | ||
| Ghrelin Enhances Appetite and Increases Food Intake in Humans | 2001 | 9 healthy volunteers | IV acylated ghrelin infusion (5.0 pmol/kg/min) significantly increased mean energy consumed from a free-choice buffet by 28% vs. saline (p<0.001), with no effect on gastric emptying (paracetamol absorption test). | Small (n=9), single-dose, acute, healthy-volunteer-only study. Findings apply specifically to acylated ghrelin and must not be generalized to des-acyl ghrelin. |
Animal / Cell / Preclinical Data
| Title | Year | Population / Model | Dose / Duration / Finding | Safety Notes | Source |
|---|---|---|---|---|---|
| Obestatin, a Peptide Encoded by the Ghrelin Gene, Opposes Ghrelin's Effects on Food Intake | 2005 | rat, not human | Original description of obestatin: rat administration suppressed food intake, inhibited jejunal contraction, and decreased body-weight gain; proposed GPR39 as the obestatin receptor. This original anorexigenic/GPR39 claim was directly contradicted by multiple independent later studies (see Obestatin page). | Rodent-only, never independently replicated in humans. Must not be cited as human efficacy evidence for either Ghrelin or Obestatin. On the Ghrelin page this is identity/precursor-context only (obestatin is a separate peptide co-derived from the same gene, not a Ghrelin form); on the Obestatin page it is the original primary source, superseded by the replication record. |
Regulatory Documents & Official Trial Registries
No Regulatory Documents & Official Trial Registries Listed Yet
This section will be updated as sources are added.
Anecdotal Reported Patterns — Not Medical Advice
Anecdotal Reported Patterns — Not Medical Advice
Reported dosing patterns are included for educational context only. They are self-reported, unverified, not medical advice, and not instructions for human use. Community-submitted patterns are not yet available in this Phase 1 prototype; this section is a placeholder reserved for moderated, aggregated community data.
Lab Markers to Discuss With a Clinician
Educational topics only — not self-monitoring instructions.
FAQ
Disclaimer
Educational information only. This page summarizes published research on endogenous ghrelin and does not constitute medical advice, a treatment recommendation, or dosing guidance for any ghrelin-related substance.
Educational use only. This content is provided for informational and research-summary purposes only. It is not medical advice, not a treatment recommendation, not a dosing guide, and not a substitute for care from a licensed medical professional. Nothing here is intended to diagnose, treat, cure, prevent, or mitigate disease. Reported dosing patterns, when shown elsewhere on the site, must be labeled either as Study / Trial Dosing or Anecdotal Reported Patterns — Not Medical Advice. Community reports are self-reported, unverified, and not scientific proof.
Community-reported experiences, once enabled, must be displayed only as moderated, anonymized, or aggregated data. They are anecdotal, self-reported, unverified, and should never be presented as proof of safety, efficacy, or expected results.
Content status: Published. Last updated 2026-08-26.
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