Ghrelin
Benefits
About Ghrelin
Ghrelin is a 28-amino-acid peptide hormone discovered in 1999 as the endogenous ligand of the growth hormone secretagogue receptor (GHS-R1a). Uniquely among mammalian peptides, it carries an octanoyl (C8 fatty acid) modification on its third serine residue, which is essential for receptor binding and biological activity. Produced primarily by enteroendocrine cells in the stomach fundus, ghrelin is the only known circulating orexigenic (appetite-stimulating) hormone. It plays a central role in energy homeostasis by stimulating appetite, promoting growth hormone release from the anterior pituitary, regulating gastric motility, and modulating glucose metabolism. Ghrelin levels rise before meals and fall after eating, earning it the designation as the "hunger hormone."
Who Should Consider Ghrelin
- Adults with cancer-related cachexia or anorexia seeking appetite restoration
- Patients with functional dyspepsia or gastroparesis requiring prokinetic support
- Elderly individuals with sarcopenia or age-related appetite decline
- Adults with growth hormone deficiency being evaluated with GH stimulation testing
- Researchers studying energy homeostasis, reward signaling, or GH secretion
How Ghrelin Works
Ghrelin binds to the growth hormone secretagogue receptor type 1a (GHS-R1a), a G-protein-coupled receptor expressed in the hypothalamus, pituitary, and throughout the gastrointestinal tract. At the pituitary, GHS-R1a activation triggers Gq/11-mediated signaling, raising intracellular calcium and stimulating growth hormone release independently of GHRH. In the arcuate nucleus of the hypothalamus, ghrelin activates NPY/AgRP neurons while inhibiting POMC/CART neurons, producing a strong orexigenic drive. The octanoyl modification at Ser3 — catalyzed by the enzyme ghrelin O-acyltransferase (GOAT) — is required for GHS-R1a binding. Ghrelin also activates vagal afferents in the gut to enhance gastric motility and acid secretion, and engages AMPK in peripheral tissues to promote fatty acid oxidation and glucose sparing.
What to Expect
Rapid increase in circulating GH levels within 15-30 minutes. Noticeable hunger and appetite stimulation within 30-60 minutes. Possible mild flushing. Effects wane within 2-3 hours due to short half-life.
Consistent appetite increase when dosed pre-meal. GH pulses become more predictable. Some users report improved sleep quality. Possible mild water retention and increased food intake.
Measurable increase in caloric intake and body weight in cachectic populations. Improved gastric emptying rates. IGF-1 levels may begin to rise. Fat-free mass may start improving in catabolic patients.
Clinical studies show meaningful weight gain in cachexia patients (1-3 kg). Sustained GH elevation with continued dosing. Body composition shifts toward lean mass preservation. Some GHS-R1a tachyphylaxis may begin to appear.
Receptor desensitization may reduce GH-releasing efficacy. Cycling off for 4 weeks is recommended to restore sensitivity. Appetite effects may partially persist. Long-term safety data beyond 12 weeks is limited.
Dosing Protocol
| Level | Dose / Injection | Frequency |
|---|---|---|
| Beginner | 50mcg | Daily |
| Moderate | 100mcg | 2x Daily |
| Aggressive | 200mcg | 2x Daily |
Note: Endogenous 28-amino-acid orexigenic hormone with octanoyl modification at Ser3. Natural ligand of GHS-R1a. Primarily secreted by gastric oxyntic cells. Rapid degradation by esterases — acylated form is the bioactive species. Not widely available as a research peptide; MK-677, GHRP-2, and GHRP-6 are more commonly used synthetic GHS-R agonists.
How to Inject Ghrelin
Inject subcutaneously into the abdominal area or thigh. For appetite stimulation, administer 30-60 minutes before meals. For GH release, administer on an empty stomach, ideally in the morning or before sleep. Rotate injection sites. Due to the short half-life, multiple daily doses may be needed to sustain effects. Reconstitute lyophilized powder with bacteriostatic water along the vial wall; swirl gently, do not shake.
Cycling Protocol
Due to potential GHS-R1a desensitization with chronic exposure, cycling is recommended. Clinical research protocols typically use acute or short-term dosing. Monitor appetite, weight, and fasting glucose during on periods.
Pharmacokinetics
Source: IV half-life ~30 min; SC half-life estimated at 60-90 min based on acyl-ghrelin clearance kinetics (PMID 15191344)
Loading the interactive decay curve.
Side Effects
Increased appetite and potential weight gain are the most common effects. Transient flushing, mild nausea, and diarrhea may occur. Elevated blood glucose due to GH-mediated insulin resistance has been observed at higher doses. Increased gastric acid secretion possible. Water retention and mild edema reported in some clinical studies. Injection site reactions (redness, swelling) are possible with subcutaneous administration.
Contraindications
- Active malignancy — ghrelin may promote tumor growth through GHS-R1a expressed on some cancer cell lines
- Uncontrolled diabetes mellitus — ghrelin raises blood glucose via GH-mediated insulin resistance and direct hepatic effects
- Pregnancy or breastfeeding — no safety data available in these populations
- Prader-Willi syndrome — already characterized by elevated ghrelin and hyperphagia
- Active eating disorders (binge eating disorder, bulimia) — appetite stimulation is contraindicated
- Known hypersensitivity to ghrelin or any excipients
Drug Interactions
- Insulin and oral hypoglycemics — ghrelin increases blood glucose; may require dose adjustment of diabetes medications
- Exogenous growth hormone — additive GH elevation; increased risk of IGF-1-related side effects
- Somatostatin analogs (octreotide, lanreotide) — directly oppose ghrelin-mediated GH release; reduced efficacy
- GLP-1 receptor agonists (semaglutide, liraglutide) — opposing appetite effects may negate ghrelin's orexigenic action
- Corticosteroids — both ghrelin and glucocorticoids raise blood glucose; additive hyperglycemia risk
- Atropine and anticholinergics — may blunt ghrelin's gastroprokinetic effects
Storage & Stability
Molecular Profile
Related Peptides
References
- Ghrelin is a growth-hormone-releasing acylated peptide from stomach (Nature 1999)PubMed 10604470
- Ghrelin, a novel growth hormone-releasing acylated peptide, is synthesized in a distinct endocrine cell type in the gastrointestinal tracts of rats and humans (Endocrinology 2000)PubMed 11089560
- Ghrelin treatment of cancer cachexia: a randomized, double-blind, placebo-controlled trial (J Clin Endocrinol Metab 2010)PubMed 20392870
- Ghrelin O-acyltransferase (GOAT) is essential for growth hormone-mediated survival of calorie-restricted mice (Proc Natl Acad Sci 2010)PubMed 20534566
- Pharmacokinetics and pharmacodynamics of ghrelin in humans — a review (Eur J Endocrinol 2004)Review
- Ghrelin: structure and function (Physiol Rev 2005)Review