Growth Hormone & Regenerative Axis

The pituitary's own growth hormone, made by bacteria, approved for children and adults who are genuinely deficient; its use for anti-aging or sport is unapproved and, in the US, illegal to distribute.

Overview

Human growth hormone (somatropin) is a 191-amino-acid protein made by the pituitary gland. Since 1987 it has been made by recombinant DNA technology in bacteria, with a sequence identical to the natural hormone^[1]. FDA labels cover growth failure from growth hormone deficiency, Prader-Willi syndrome, Turner syndrome, children born small for gestational age, idiopathic short stature, and replacement in adults with diagnosed growth hormone deficiency^[1]. Newer once-weekly analogs, such as somapacitan, carry similar indications^[2].

That is the approved picture. A separate world uses growth hormone for anti-aging, body composition, or athletic performance in people without a deficiency. None of those uses is approved, and US federal law makes distributing growth hormone for any purpose other than treating a disease, on a physician's order, a felony^[6]. Trials in healthy older adults show modest fat loss with frequent side effects^[4].

Mechanism of Action

Growth hormone binds a receptor on cells throughout the body, especially in the liver, which responds by making insulin-like growth factor 1 (IGF-1). In growth hormone deficiency, treatment brings IGF-1 back into the normal range, and IGF-1 helps drive skeletal growth in children^[1]. Growth hormone also acts directly: it mobilizes fat, shrinking fat stores and raising blood fatty acids, and it increases protein synthesis and nitrogen retention^[1]. It works against insulin to some degree, and the label warns that treatment can decrease insulin sensitivity, particularly at higher doses^[1].

The natural hormone is released in pulses, mostly during sleep. Injected somatropin is cleared quickly: the label lists a terminal half-life of about 0.4 hours after intravenous injection and about 3 hours after injection under the skin, the longer figure reflecting slow absorption^[1]. Long-acting analogs extend this. Somapacitan carries a single amino acid change with an attached group that binds reversibly to albumin, giving a half-life of roughly 2 to 3 days in adults^[2]. Because outside hormone suppresses the body's own release through feedback, it replaces rather than boosts natural production.

What the Research Shows

• Adult GHD, label summary of 6 RCTs (n=172, 6 months double-blind, open-label to 24 months): compared with placebo, somatropin increased lean body mass and decreased total fat mass and waist circumference, with effects maintained beyond 6 months. Bone density dipped at 6 months and returned to baseline by 12 months^[1].
• Adult GHD, long-acting analog RCT (34 weeks): truncal fat changed by -1.06% with somapacitan vs +0.47% with placebo, a difference of -1.53 percentage points (P=0.009)^[2].
• Endocrine Society guideline, 2011: rated benefits in body composition and exercise capacity as well supported, with weaker evidence for bone, lipids and quality of life. It stated that replacement has not been shown to reduce mortality and that anti-aging use is not FDA-approved^[3].
• Healthy older women, controlled trial, 1994 (n=27, 6 to 12 months): fat mass fell 11% by skinfolds (P<0.005), but side effects forced 50% dose reductions, and blinded follow-up to 12 months shrank to 8 treated women^[4].
• French SAGhE cohort, 2012 (n=6,928 adults treated as children for isolated GHD or short stature): all-cause mortality was higher than the general population (SMR 1.33), especially at the highest doses (SMR 2.94). Circulatory and brain-bleed deaths were raised. Cancer deaths overall were not, though bone tumor deaths were (SMR 5.00, based on few cases). Observational, so causation is unproven^[5].

• Animal work is extensive but largely superseded by decades of human use. The labels and guideline cited here rely on human trial data for their conclusions^[1,3].

Open Questions

• No trial has shown that growth hormone replacement in deficient adults reduces deaths or heart attacks^[3].
• Whether the higher mortality seen in the French childhood cohort reflects the treatment, the underlying conditions, or chance is unresolved^[5].
• Benefits for strength, endurance or function in healthy older adults or athletes are not established.
• Unregulated products sold outside pharmacies may differ in identity, purity and dose from labeled drugs.

Regulatory Status

FDA-approved prescription biologic (Genotropin and other somatropin brands; long-acting analogs such as Sogroya since 2020) for specific pediatric growth disorders and adult growth hormone deficiency^[1,2]. US law (21 U.S.C. 333(e)) makes distributing growth hormone for non-disease uses, including anti-aging, a felony^[6]. Prohibited in sport at all times under WADA class S2^[7].

Related Compounds

A lab-modified version of insulin-like growth factor 1, designed to escape the proteins that normally hold IGF-1 in check. It has rat and cell data but no human studies.

Overview

IGF-1 LR3 (Long R3 IGF-1) is an engineered analog of insulin-like growth factor 1, the hormone that carries out many of growth hormone's effects. It differs from natural IGF-1 in two ways: one amino acid near the start is swapped (glutamic acid to arginine at position 3), and a short extension is added to the front end^[2]. It was built as a laboratory tool, largely by an Australian research group, to study IGF-1 biology in cell culture and in rats^[2,3].

It should not be confused with mecasermin (Increlex), which is chemically identical to the body's own IGF-1 and is FDA-approved for a rare childhood growth disorder^[1]. That approval and its safety data belong to mecasermin, not to LR3. IGF-1 LR3 has never been tested in a published human trial, and samples sold outside medicine have sometimes turned out to be a different molecule than labeled^[6].

Mechanism of Action

Like natural IGF-1, LR3 activates the IGF-1 receptor, which signals cells to take up nutrients, make protein and divide^[1,2]. The key engineering change is that LR3 binds very weakly to the IGF binding proteins (IGFBPs) that normally hold most circulating IGF-1. In bovine embryo work, its affinity for these binding proteins was at least a thousand times lower than natural IGF-1^[5]. In muscle-derived cells, the analogs were more potent than IGF-1, and the difference grew in cells that secrete binding proteins^[2].

A common claim is that these changes give LR3 a much longer half-life. The rat data point the other way. Because it is not protected by binding proteins, LR3 was cleared from rat circulation faster than natural IGF-1. Its extra potency was about 1.5 to 2 fold when infused continuously and much smaller when injected, and for reversing muscle loss it was roughly equal to IGF-1^[4].

What the Research Shows

• None published. No human trial, pharmacokinetic study or safety study of IGF-1 LR3 was found. Human data for the IGF-1 class come from mecasermin, a different molecule, and are listed under safety only for context^[1].

• Rats treated with dexamethasone (1992): IGF-1 analogs including LR3 increased gut weight by up to 60% and were several times more potent than IGF-1 at countering the steroid's catabolic effects^[3].
• Normal female rats, 14 days (1993): weight gain and food efficiency rose 18 to 26%, with LR3 the most potent analog tested^[7].
• Rat infusion vs injection (1996): LR3 was cleared faster than IGF-1. It was 1.5 to 2 times more potent by continuous infusion, much less by injection, and about equal to IGF-1 for reversing muscle wasting^[4].
• Bovine embryo culture (2001): LR3 modestly increased blastocyst cell numbers (105 vs 91 in controls, P<0.05), consistent with its weak binding-protein affinity^[5].

• Rat L6 myoblasts: the analogs were more potent than IGF-1 at stimulating protein synthesis, with the largest difference in cells that secrete IGF binding proteins^[2].

Open Questions

• Whether any of the rat findings translate to humans has never been tested.
• How fast LR3 is cleared in people, and how that compares with natural IGF-1, is unknown; rat data suggest faster, not slower^[4].
• Whether bypassing the IGF binding proteins changes long-term cancer or metabolic risk is unknown.
• The purity and true identity of material sold outside medicine is uncertain^[6].

Regulatory Status

Not approved for any use; the only approved IGF-1 drug is mecasermin (Increlex), a different molecule approved in 2005 for severe primary IGF-1 deficiency in children^[1]. IGF-1 LR3 does not appear on the FDA's compounding safety-risk lists and was not reviewed at the July 2026 advisory committee. The WADA 2026 Prohibited List names LR3 IGF-1 under S2^[8].

Related Compounds

A lab-made growth hormone-releasing hormone that hitches a ride on blood albumin so it lasts about a week, studied briefly in humans before its developer halted the program.

Overview

CJC-1295 is a modified version of the active 29-amino-acid piece of growth hormone-releasing hormone (GHRH), the brain's signal telling the pituitary to release growth hormone. It was designed by the Canadian company ConjuChem with a small chemical hook that latches onto albumin, the most abundant protein in blood^[3]. That hook is what "with DAC" refers to, and it stretches a signal that normally lasts minutes into one that lasts days. Its estimated half-life in humans was 5.8 to 8.1 days^[1].

In healthy adults, a single injection raised growth hormone 2- to 10-fold for six days or more and IGF-1 1.5- to 3-fold for 9 to 11 days^[1]. A 192-person phase 2 trial in people with HIV-related belly fat was stopped in July 2006 after a participant died; the cause was not publicly confirmed^[5]. No later clinical results have been published.

Mechanism of Action

CJC-1295 binds the GHRH receptor on growth hormone-producing cells of the anterior pituitary, prompting them to release the body's own growth hormone, which in turn drives IGF-1 production, mostly in the liver^[1,3]. Its peptide backbone carries four amino acid swaps (D-alanine at position 2, glutamine at 8, alanine at 15, leucine at 27) that make it resistant to DPP-4, the enzyme that rapidly clips native GHRH. An extra lysine at the end carries a maleimide group that reacts with a specific spot (cysteine 34) on circulating albumin, forming a stable conjugate after injection^[3]. In rats, the albumin-bound form was still detectable beyond 24 hours and the peptide beyond 72 hours^[3].

An open question with any long-acting signal is whether it flattens the body's natural on-off rhythm of growth hormone release. In a small overnight sampling study in healthy young men, one week after a single injection, the size and frequency of growth hormone pulses were unchanged, but the baseline between pulses rose 7.5-fold, mean growth hormone rose 46%, and IGF-1 rose 45%^[2]. The authors suggested that the raised baseline, rather than bigger pulses, drives the IGF-1 increase^[2]. Whether that pattern holds with repeated use over months was never studied.

What the Research Shows

• Two randomized, placebo-controlled, double-blind dose-escalation trials, JCEM 2006 (healthy adults aged 21 to 61, 28 and 49 days): single injections raised mean growth hormone 2- to 10-fold for at least 6 days and IGF-1 1.5- to 3-fold for 9 to 11 days. With repeated injections, IGF-1 stayed above baseline for up to 28 days. No serious adverse reactions were reported. Exact enrollment was not given in the abstract, and the work was sponsored by ConjuChem^[1].
• Pulsatility study, JCEM 2006 (small group of healthy men aged 20 to 40, 12-hour overnight sampling before and 1 week after one injection): trough growth hormone up 7.5-fold (P<0.0001), mean growth hormone up 46% (P<0.01), IGF-1 up 45% (P<0.001); pulse frequency and amplitude unchanged^[2].
• Phase 2 RCT in HIV-associated visceral obesity, 2006 (n=192, weekly injections of low dose, high dose or placebo): dosing stopped in July 2006 after a participant at a site in Argentina died hours after an injection, according to an unconfirmed report. Efficacy results were never published^[5].

• Rats: CJC-1295 produced a 4-fold larger growth hormone response over 2 hours than unmodified GRF(1-29), and the peptide remained in plasma beyond 72 hours^[3].
• GHRH knockout mice, growth model: one injection every 24 hours for 5 weeks normalized body weight, body length and leg bone length in mice genetically lacking GHRH; spacing injections 48 or 72 hours apart improved growth but did not normalize it. Pituitary growth hormone mRNA and somatotroph numbers increased^[4].

• Rat anterior pituitary cells: three albumin-conjugated GRF(1-29) derivatives (the series that produced CJC-1295) kept their ability to trigger growth hormone secretion and were more resistant to DPP-4 breakdown than native GRF(1-29)^[3].

Open Questions

• Whether days-long GHRH stimulation produces any meaningful benefit in people, since no outcome trial was ever completed.
• What caused the 2006 trial death, and whether the drug contributed^[5].
• Whether the preserved growth hormone pulse pattern seen after one injection persists with months of use^[2].
• How often the body makes antibodies against the albumin-bound peptide, a concern FDA has flagged^[6].
• Whether products sold under this name actually contain the albumin-binding molecule, since the name is often applied loosely to a different peptide (see Modified GRF 1-29).

Regulatory Status

Not FDA-approved for any use. FDA's compounding safety list (updated April 2026) lists CJC-1295 among bulk substances whose compounding nominations were withdrawn after FDA flagged safety concerns, and it was not among the seven peptides reviewed at the July 2026 Pharmacy Compounding Advisory Committee^[6,8]. Named explicitly as prohibited at all times under WADA class S2^[7].

Related Compounds

A short-acting, enzyme-resistant copy of the growth hormone-releasing hormone signal, widely sold as "CJC-1295 without DAC," with essentially no published research on the molecule itself.

Overview

Modified GRF (1-29), often shortened to "Mod GRF," is the 29-amino-acid active fragment of growth hormone-releasing hormone (GHRH) with four amino acids swapped to resist breakdown. The same four swaps form the backbone of CJC-1295, but in the published science the name "CJC-1295" belongs to the version carrying an albumin-binding hook^[1]. Remove that hook and you have this peptide. That makes the common market label "CJC-1295 without DAC" a contradiction in terms: it describes a different, shorter-acting molecule.

The naming matters because the human data people cite for "CJC-1295" (multi-day growth hormone and IGF-1 elevation, a half-life of about a week) come from the albumin-bound version and do not transfer^[2]. The closest well-studied relative is sermorelin, the unmodified 1-29 fragment, which was once FDA-approved^[3,4]. For Mod GRF itself, no clinical trial, pharmacokinetic study or dedicated animal study was found.

Mechanism of Action

Like natural GHRH, Mod GRF is expected to bind the GHRH receptor on somatotrophs in the anterior pituitary and trigger release of the body's own growth hormone, which then raises IGF-1^[1,3]. Its four substitutions are D-alanine at position 2, glutamine at 8, alanine at 15 and leucine at 27^[1]. The position 2 change is the important one for durability: the enzyme DPP-4 normally clips the first two amino acids off GHRH, inactivating it within minutes, and the CJC-1295 series was built specifically to resist that enzyme^[1]. These changes were developed as part of the CJC-1295 program, where they were paired with an extra lysine and albumin-binding linker^[1].

Without the albumin hook, the peptide is cleared through normal routes rather than riding on albumin for days^[1,2]. In practical terms, it should behave as a short burst signal, closer to sermorelin than to CJC-1295 with DAC, but its actual half-life, potency and duration in humans have not been published. Claims about how long it lasts or how strongly it acts trace to vendor material and analogy, not measurement.

What the Research Shows

• No published human studies of Modified GRF (1-29) as a standalone compound were found. The human trials often cited under the CJC-1295 name tested the albumin-binding version, which produced growth hormone elevations lasting 6 days or more^[2]. Sermorelin, the unmodified fragment, has pediatric trial data (n=110, height velocity rising from 4.1 to 7.2 cm per year over 12 months) that also cannot be assumed to apply^[3].

• No dedicated animal studies of the unconjugated peptide were identified. The rat experiments that introduced the CJC-1295 series reported results for albumin-conjugated derivatives, not for this molecule alone^[1].

Open Questions

• Basic human pharmacokinetics: half-life, peak timing and how much growth hormone it releases compared with native GHRH(1-29).
• Whether repeated use dulls the pituitary's response or produces antibodies.
• Any clinical outcome at all, from body composition to sleep, since no trial has been run.
• How consistently products sold under this name match the published four-substitution structure^[1].

Regulatory Status

Not FDA-approved and never studied in a registered clinical program under this name. FDA's compounding safety list does not name Modified GRF (1-29) separately; it lists "CJC-1295" among substances whose nominations were withdrawn after safety concerns were raised^[5]. WADA prohibits GHRH and its analogs at all times under class S2^[6].

Related Compounds

A popular pairing of two growth hormone-releasing peptides that push the pituitary through two different 'on' switches; the logic is well grounded, but this exact combination has never been studied.

Overview

"CJC-1295 No DAC + Ipamorelin" is a market product category. The first component is Modified GRF (1-29), a stabilized copy of the first 29 amino acids of growth hormone-releasing hormone (GHRH); it is often sold as "CJC-1295 without DAC," but it is a different, much shorter-acting molecule than true CJC-1295, which carries an albumin-binding attachment. The second, ipamorelin, is a five-amino-acid peptide that activates the ghrelin receptor and releases growth hormone selectively in animals^[2].

Pairing the two classes has a real scientific basis: in a 1990 study of 18 men, a growth hormone-releasing peptide and GHRH together released growth hormone synergistically^[1]. But that study used different molecules. We found no published study of Modified GRF (1-29) and ipamorelin together, in people or animals.

Mechanism of Action

GHRH analogs bind GHRH receptors on growth hormone-producing cells of the pituitary and trigger release of the body's own growth hormone. Ghrelin-receptor agonists such as ipamorelin act through a separate receptor, the growth hormone secretagogue (ghrelin) receptor. In normal men, an early growth hormone-releasing peptide (GHRP) combined with GHRH released growth hormone synergistically, meaning more than expected from either alone^[1]. This is the rationale for the pairing.

Ipamorelin's selling point is selectivity. In pigs, it released growth hormone without raising ACTH or cortisol, even at amounts more than 200 times its effective level, while the older peptides GHRP-6 and GHRP-2 did raise them; prolactin, LH, FSH and TSH were unaffected^[2]. Modified GRF (1-29) differs from native GHRH by a few amino-acid substitutions meant to slow breakdown, but we found no published human pharmacology for it. Both components act upstream, so the body's feedback loops still limit growth hormone output.

What the Research Shows

• GHRH + GHRP synergy study, 1990 (n=18 healthy men, single intravenous tests): combining lower amounts of the peptide with GHRH released growth hormone synergistically. Neither molecule was Modified GRF (1-29) or ipamorelin^[1].
• Ipamorelin alone, phase 2 RCT, 2014 (n=117 bowel-surgery patients, up to 7 days intravenous): no significant effect on time to first tolerated meal (25.3 vs 32.6 hours, P=0.15). Adverse events occurred in 87.5% vs 94.8% on placebo^[3].
• No published study has tested Modified GRF (1-29) and ipamorelin together.

• Rats and pigs (ipamorelin alone): growth hormone release with potency similar to GHRP-6 and no rise in ACTH or cortisol in pigs, unlike GHRP-6 and GHRP-2^[2].

• Rat pituitary cells (ipamorelin alone): growth hormone release with an EC50 of 1.3 nmol/L, close to GHRP-6, acting through the growth hormone-releasing peptide receptor^[2].

Open Questions

• Whether Modified GRF (1-29) and ipamorelin actually show synergy in people, and how large it is.
• Whether any rise in growth hormone or IGF-1 from the pairing produces meaningful changes in muscle, fat, sleep or recovery.
• Long-term safety, including effects on glucose, cancer risk and pituitary function.
• Basic human pharmacology of Modified GRF (1-29), which has little published data of its own.

Regulatory Status

Neither component is FDA approved. Ipamorelin acetate remains on FDA's Category 2 compounding safety-risk list, while the CJC-1295 nomination was withdrawn; neither was among the peptides reviewed by FDA's advisory committee in July 2026^[4,5]. WADA prohibits GHRH analogs (naming CJC-1295) and growth hormone secretagogues (naming ipamorelin) under S2^[6].

Related Compounds

A small synthetic peptide that triggers growth hormone release through the ghrelin receptor, notably selective in animal studies, but its only patient trial (for post-surgery gut recovery) failed.

Overview

Ipamorelin is a five-amino-acid synthetic peptide first described in 1998. It mimics ghrelin, a gut hormone that, among other jobs, tells the pituitary to release growth hormone^[1]. What set it apart in early animal work was selectivity: unlike older growth hormone-releasing peptides, it did not raise the stress hormones ACTH and cortisol even at doses more than 200 times higher than those needed to release growth hormone^[1].

In humans, the published record is thin. A pharmacology study in healthy men measured a half-life of about 2 hours^[2]. Because ghrelin also speeds up the gut, ipamorelin was later tested for postoperative ileus (the bowel shutting down after surgery). A 117-patient phase 2 trial found no significant benefit over placebo^[3].

Mechanism of Action

Ipamorelin is an agonist of the growth hormone secretagogue receptor (GHS-R1a), the receptor natural ghrelin uses. It was found in a series of compounds derived from the older peptide GHRP-1^[1]. In rat pituitary cells it released growth hormone with potency similar to GHRP-6 (half-maximal effect at 1.3 vs 2.2 nmol/L)^[1]. In pigs it did not change FSH, LH, prolactin or TSH, and unlike GHRP-6 and GHRP-2 it did not significantly raise ACTH or cortisol^[1]. The authors described this selectivity as similar to GHRH itself. Ghrelin-receptor activation works alongside, not through, the GHRH receptor, which is why the two classes are often discussed together.

In healthy men given intravenous infusions, growth hormone peaked about 40 minutes after the start and then declined, with a terminal half-life of about 2 hours^[2]. Ghrelin receptors are also found in the gut and its nerves. In rats after abdominal surgery, ipamorelin sped stomach emptying and reversed suppressed muscle contraction in gastric tissue, apparently through nerves that release acetylcholine^[4]. That gut effect was the rationale for the human ileus trial^[3].

What the Research Shows

• Pharmacokinetic-pharmacodynamic study, 1999 (healthy men, 8 per dose level across 5 levels, single 15-minute IV infusions): terminal half-life about 2 hours, clearance 0.078 L/h/kg, and growth hormone peaking at about 0.67 hours before declining^[2].
• Phase 2 proof-of-concept RCT, 2014 (n=117 randomized, 114 analyzed; bowel resection patients; IV ipamorelin or placebo twice daily for up to 7 days): median time to tolerating a solid meal was 25.3 vs 32.6 hours, not statistically significant (P=0.15). No secondary efficacy measure differed. Funded by Helsinn^[3].

• Rats and pigs, selectivity: in conscious pigs, growth hormone release was similar in potency to GHRP-6 without the ACTH and cortisol rise seen with GHRP-6 and GHRP-2^[1].
• Rats, postoperative ileus: after laparotomy, 78% of a test meal stayed in the stomach with vehicle vs 52% with ipamorelin (P<0.05), compared with 44% in rats without surgery^[4].
• Adult female rats, bone growth (15 days): longitudinal bone growth rose from 42 to as high as 52 micrometers per day (P<0.0001), with no change in total IGF-1^[5].
• Adult female rats, bone mineral (12 weeks): bone mineral content rose, but only in proportion to larger bones and body weight; bone density itself did not change^[6].

• Rat pituitary cells: half-maximal growth hormone release at 1.3 nmol/L with 85% of GHRP-6's maximal effect^[1].

Open Questions

• Whether ipamorelin's stress-hormone selectivity in animals holds in people with repeated use, since human data are limited to single infusions and a 7-day trial^[2,3].
• Whether it has any measurable benefit for body composition or function in adults, which has never been tested in a controlled trial.
• How the pituitary adapts to long-term ghrelin-receptor stimulation^[5].
• The details of the serious adverse events FDA cites, which have not been fully characterized in the literature^[7].

Regulatory Status

Not FDA-approved for any use. As of FDA's April 2026 update, ipamorelin remains in Category 2 (significant safety risks) for 503B outsourcing facilities, and its 503A nomination is listed as withdrawn^[7]; it was not among the seven peptides reviewed at the July 2026 Pharmacy Compounding Advisory Committee^[9]. Named explicitly as prohibited at all times under WADA class S2^[8].

Related Compounds

A lab-made, longer-lasting version of the brain's own growth hormone "go" signal, FDA-approved to shrink deep abdominal fat in people with HIV-associated fat redistribution.

Overview

Tesamorelin is a copy of growth hormone-releasing hormone (GHRH), the signal the hypothalamus sends to tell the pituitary gland to release growth hormone. A small chemical cap on one end protects it from the enzymes that normally break GHRH down within minutes^[1,9]. It is one of the few compounds in this reference with a full regulatory approval behind it.

In two large phase 3 trials of adults with HIV and excess abdominal fat, 26 weeks of tesamorelin reduced visceral fat (the fat packed around the organs) by roughly 15% relative to placebo, while raising IGF-1 and lowering triglycerides^[4,5]. Smaller trials have since reported reduced liver fat^[6,7] and a modest cognitive signal in older adults^[8].

Mechanism of Action

Tesamorelin binds GHRH receptors on the somatotroph cells of the anterior pituitary with potency similar to the body's own hormone, triggering release of the body's own growth hormone. Growth hormone then raises circulating IGF-1 and IGFBP-3, mostly through the liver^[1]. Because it acts upstream at the pituitary, the body's normal feedback controls on growth hormone stay in place. The label reports no clinically significant changes in TSH, LH, ACTH or prolactin, which points to a selective effect on the growth hormone axis^[1].

The key structural change is a trans-3-hexenoyl group on the first amino acid. In non-clinical studies this made the peptide resistant to the enzyme DPP-4 and slowed its breakdown in rat, dog and human plasma compared with native GHRH^[9]. Even so, the peptide itself is short-lived: the label lists an elimination half-life of about 11 minutes^[1]. Its effects come from the growth hormone and IGF-1 response it triggers, not from the peptide lingering in the blood. Exactly how that response translates into less visceral and liver fat was not directly tested in the trials.

What the Research Shows

• Phase 3 RCT, NEJM 2007 (n=412 adults with HIV and abdominal fat, 26 weeks): visceral fat fell 15.2% with tesamorelin vs a 5.0% rise on placebo (P<0.001). Triglycerides changed by -50 vs +9 mg/dL and IGF-1 rose 81%. Glucose did not differ significantly between groups^[4].
• Pooled analysis of two phase 3 RCTs, JCEM 2010 (n=806, 26 weeks plus a 26-week extension): visceral fat changed by -24 vs +2 cm², a 15.4% treatment effect (P<0.001). Subcutaneous belly fat did not change significantly. Among those who continued to 52 weeks, visceral fat was 17.5% below baseline^[5].
• Liver and visceral fat RCT, JAMA 2014 (n=50, 6 months): liver fat fell 2.9 percentage points net of placebo (P=0.003). Fasting glucose rose briefly at 2 weeks but the difference was gone by 6 months. The authors called the results preliminary^[6].
• HIV with fatty liver disease RCT, Lancet HIV 2019 (n=61, 12 months): liver fat fraction fell 4.1 points more than placebo, a 37% relative reduction (P=0.02). Liver fat dropped below 5% in 35% vs 4% on placebo, and fibrosis progressed in 10.5% vs 37.5% (P=0.04). Existing fibrosis did not improve^[7].
• Cognition RCT, Archives of Neurology 2012 (n=152 adults aged 55 to 87, 66 with mild cognitive impairment, 20 weeks): a favorable effect on a cognitive composite (P=0.03), driven mainly by executive function. IGF-1 rose 117% but stayed within the normal physiological range^[8].

• Rats and dogs, 4-month repeated-dose studies: marked rises in growth hormone and IGF-1 with increased weight gain. Dogs showed reversible liver, kidney and blood changes attributed to sustained supraphysiological GH/IGF-1 exposure^[9].
• No lifetime rodent carcinogenicity studies have been conducted^[1].

Open Questions

• No trial has shown fewer heart attacks, liver failures or deaths. Fat reduction and IGF-1 are surrogate markers.
• Benefits reversed when treatment stopped, so durability depends on continued use^[5].
• The liver studies were small and came from a single research group; most phase 3 data were sponsor-funded^[6,7].
• Persistently high IGF-1 in some patients raises cancer-risk questions that long-term data have not resolved^[1].

Regulatory Status

FDA-approved prescription drug (Egrifta, BLA 022505) since November 2010, with later formulations marketed as Egrifta SV and Egrifta WR. The label limits use to adults with HIV and lipodystrophy and states it is not indicated for weight loss^[1,2]. Prohibited in sport at all times under WADA class S2^[3].

Related Compounds

The active first 29 amino acids of the brain's growth hormone-releasing hormone, once an FDA-approved drug for children with growth hormone deficiency before its maker discontinued it.

Overview

Sermorelin is a synthetic copy of the first 29 amino acids of growth hormone-releasing hormone (GHRH), the shortest piece of the natural hormone that keeps its full activity^[3]. It tells the pituitary to release its own growth hormone. Sold as Geref by Serono, it was FDA-approved in 1990 as a diagnostic test of pituitary function and in 1997 to treat children with idiopathic growth hormone deficiency^[1]. That regulatory history makes it the best-documented compound in the short-acting GHRH family.

EMD Serono, the only U.S. maker, discontinued Geref in 2008, which also removed the standard GHRH-arginine stimulation test from U.S. endocrine practice; FDA withdrew the approvals in 2009^[1,6]. In 2013, FDA formally determined the product was not pulled for safety or effectiveness reasons^[1]. Studies in older adults showed it can restore youthful growth hormone and IGF-1 levels, but they were small, short and did not test hard health outcomes^[4,5].

Mechanism of Action

Sermorelin binds GHRH receptors on the somatotroph cells of the anterior pituitary, stimulating synthesis and release of the body's own growth hormone, which then raises IGF-1 mainly through the liver^[3]. Because it acts upstream, the body's normal brakes stay in place: somatostatin can still suppress release, and rising IGF-1 still feeds back on the system. That is the main conceptual difference from injecting growth hormone itself. It also explains the diagnostic use: a single intravenous injection tests whether the pituitary can respond, though a normal result does not rule out a problem higher up in the hypothalamus^[3].

Sermorelin has no protective chemical modifications, so it is broken down quickly in the blood. Later analogs (tesamorelin, Modified GRF 1-29 and CJC-1295) were designed largely to fix this. Its short action shaped how it was studied: in children, height gains with sermorelin given by continuous infusion or divided daily injections were smaller than with once-daily growth hormone, although the approved regimen was never compared head-to-head^[3]. In older men, two weeks of twice-daily injections restored 24-hour growth hormone and IGF-1 levels to those of young men^[4].

What the Research Shows

• Open-label multicenter trial in children, JCEM 1996 (n=110 prepubertal children with growth hormone deficiency, 86 analyzed, up to 12 months): height velocity rose from 4.1 cm/yr to 8.0 cm/yr at 6 months and 7.2 cm/yr at 12 months; 74% were good responders at 6 months. Bone age did not advance faster than height age. No control group^[2].
• Review of clinical program, BioDrugs 1999: catch-up growth in most treated children, with limited data suggesting gains persisted to 36 months; effects on final adult height were unknown. As a diagnostic, IV sermorelin produced fewer false positives in children without deficiency than other stimulation tests^[3].
• Randomized dose-order study in older men, JCEM 1992 (n=10 men averaging 68 years vs 9 young controls, 14 days at each of two doses): the higher dose increased mean 24-hour growth hormone (P<0.001) and IGF-1 (P<0.005), erasing the age-group differences. Fasting glucose was unchanged^[4].
• Single-blind placebo-run-in study of a close analog, JCEM 1997 (n=19 adults aged 55 to 71, 16 weeks of nightly [Nle27]GHRH(1-29)): IGF-1 rose within 2 weeks; lean body mass and insulin sensitivity improved in men only; skin thickness rose in both sexes. This used a modified 1-29 peptide, not sermorelin itself^[5].

• No recent animal research on sermorelin itself was identified; its preclinical work predates its 1990 approval and is reported mainly in summary form within regulatory and review literature^[3].

Open Questions

• Whether sermorelin produces lasting benefits in adults without diagnosed growth hormone deficiency, since adult trials were small and short^[4,5].
• Effects on final adult height in treated children were never fully reported in the sources reviewed^[3].
• Quality and consistency of currently available non-approved products, since no FDA-approved version is on the market^[1].
• How its effects compare head-to-head with growth hormone or newer GHRH analogs at matched exposure^[3].

Regulatory Status

Previously FDA-approved (Geref, NDAs 19-863 and 20-443); approvals were withdrawn effective June 2009 at the manufacturer's request, and a 2013 FDA determination that this was not for safety or effectiveness reasons leaves the door open for generic applications^[1]. Sermorelin does not appear on FDA's April 2026 list of bulk substances flagged for significant safety risks in compounding^[7]. Named explicitly as prohibited at all times under WADA class S2^[8].

Related Compounds

One of the first lab-made peptides found to trigger growth hormone release, GHRP-6 mimics the hunger hormone ghrelin and was mainly used as a research and diagnostic tool, never approved as a treatment.

Overview

GHRP-6 is a synthetic six-amino-acid peptide first described in 1984 as a compound that acts on the pituitary to release growth hormone^[1]. It came before anyone knew what receptor it used. That answer arrived in 1999, when researchers discovered ghrelin, a stomach hormone that turned out to be the body's own key for the same lock^[2]. In practical terms, GHRP-6 is a ghrelin mimic, and that explains both its growth hormone effect and its reputation for making people hungry^[2,11].

Most human research on GHRP-6 is from the 1990s and used it as a probe to study how growth hormone is controlled, or as part of a diagnostic test for growth hormone deficiency^[3,4]. A Cuban group later tested it intravenously in healthy volunteers and studied it in animal models of heart and organ injury^[6,8,9]. No trial has shown that it improves muscle, recovery, body composition or any disease outcome in people.

Mechanism of Action

GHRP-6 activates the growth hormone secretagogue receptor, now known as the ghrelin receptor, whose natural ligand is the stomach peptide ghrelin^[2]. It works through a different receptor and pathway than growth hormone-releasing hormone (GHRH), which is why the two together release far more growth hormone than either alone. In obese adults, GHRP-6 roughly doubled the growth hormone response seen with GHRH, and the combination produced a "massive" discharge, with peaks averaging 42 µg/L^[4]. Its action depends heavily on the hypothalamus: in 12 patients whose pituitary was disconnected from the hypothalamus, the response to GHRP-6 was almost completely blocked while the response to GHRH was preserved^[3].

GHRP-6 is not selective for growth hormone. In a placebo-controlled overnight study in healthy men, it raised ACTH by about 27% and roughly doubled cortisol compared with placebo, in addition to nearly tripling growth hormone^[5]. That stress-hormone effect is one of the concerns FDA cited when restricting its use in compounding^[12]. Because it mimics ghrelin, which increased food intake by 28% when infused into healthy volunteers^[11], GHRP-6 is expected to stimulate appetite. Direct, controlled measurements of hunger with GHRP-6 in humans are scarce.

What the Research Shows

• Placebo-controlled sleep and hormone study, 1995 (healthy young men, single night): growth hormone averaged 15.4 vs 5.5 ng/mL on placebo, ACTH 21.0 vs 16.6 pg/mL and cortisol 56.0 vs 25.2 ng/mL (all P<0.02). Light stage 2 sleep rose by about 25 minutes, but deep slow-wave sleep did not change^[5].
• Hypothalamic disconnection study, 1995 (n=12 patients, 11 controls): the growth hormone response to GHRP-6 fell from 1,435 to 97 units (area under the curve), showing that GHRP-6 needs an intact hypothalamus to work well^[3].
• Obesity study, 1993 (obese adults): GHRP-6 produced a growth hormone peak of 15.7 µg/L vs 6.8 µg/L with GHRH. Combined, the two produced peaks of 14 to 86 µg/L, suggesting the blunted growth hormone seen in obesity is functional and reversible^[4].
• Phase 1 dose-escalation safety trial, Cuba, 2014 (n=18 healthy men, single intravenous dose, no placebo group): 12 of 18 had side effects, mostly sweating (50%) and slowed heart rate (44%), more common at higher levels. No serious events or ECG changes were seen^[6]. A companion study in nine of these men characterized its blood levels^[7].

• Pigs, heart attack model: in a one-hour coronary blockage followed by reperfusion, GHRP-6 rescued more than 70% of the at-risk heart muscle from dying, with less oxidative stress^[8,10].
• Rats, doxorubicin heart damage: survival was 84% with GHRP-6 vs 42% with saline over 52 days, with less muscle-fiber damage (42% vs 91%) and preserved pumping function^[9].
• Most of the organ-protection work comes from a single Cuban research group that also developed GHRP-6 as an investigational drug (CIGB-500)^[6,9,10].

Open Questions

• No randomized trial has tested GHRP-6 for any clinical outcome in people.
• Long-term effects of repeated growth hormone, cortisol and prolactin stimulation are unknown.
• The heart and organ-protection findings come largely from one sponsor-linked research group and have not been independently replicated in humans^[9,10].
• Whether the response weakens with continued use, as seen with the related peptide hexarelin, has not been well studied for GHRP-6.

Regulatory Status

Not approved by FDA or any major regulator for any use. In September 2023 FDA placed GHRP-6 in Category 2 of its interim compounding list for outsourcing facilities (503B), meaning substances that may present significant safety risks^[12]. Named explicitly on the WADA 2026 Prohibited List under S2 and banned in and out of competition^[13].

Related Compounds

A potent lab-made growth hormone releaser from the same family as GHRP-6, studied in the 1990s for growth hormone testing and heart function, but never approved or developed into a medicine.

Overview

Hexarelin (also called examorelin) is a synthetic six-amino-acid peptide from the growth hormone-releasing peptide (GHRP) family, the same group as GHRP-6^[1,6]. Like its relatives, it acts on the receptor whose natural key is ghrelin, the stomach's hunger hormone^[7]. In healthy volunteers it released about twice as much growth hormone as the body's own releasing hormone, GHRH, which is why it is often called one of the most potent compounds in its class^[1].

It drew extra attention because rat studies suggested it could protect heart tissue in ways that did not depend on growth hormone^[5], and a few small human studies reported short-term improvements in heart pumping^[6]. It never became an approved medicine. Its effect also weakened with continued use: over 16 weeks, the growth hormone response dropped by nearly half^[4].

Mechanism of Action

Hexarelin activates the growth hormone secretagogue receptor, the receptor later shown to be the natural target of ghrelin^[7]. In 12 healthy volunteers, intravenous hexarelin produced a growth hormone response about twice that of GHRH (P<0.001), and the response was reproducible on retesting^[1]. It also works when absorbed under the skin, with about 77% bioavailability, but very little survives the gut (about 0.3%) or the nasal lining (about 5%)^[1]. Growth hormone peaked around 30 minutes and returned to baseline within four hours^[2].

Like GHRP-6, hexarelin is not perfectly selective. It raised prolactin by up to 180% and cortisol by about 40% in a dose-response study in healthy men^[3], and it caused slight rises in ACTH as well^[2]. Separately, a rat study found that hexarelin protected hearts from ischemia-reperfusion damage even in animals without a pituitary gland, while growth hormone-releasing peptides that do not bind heart tissue did nothing. The authors concluded hexarelin acts through specific cardiac binding sites, not through growth hormone^[5].

What the Research Shows

• Route comparison study, 1994 (n=12 healthy volunteers): growth hormone response roughly double that of GHRH (area under the curve 3,175 vs 1,544, P<0.001); bioavailability 77% under the skin, 4.8% nasal, 0.3% oral^[1].
• Double-blind, placebo-controlled rising-dose study, 1994 (n=12 healthy men): dose-dependent growth hormone release, peaking near 52 to 55 ng/mL vs 3.9 on placebo. Slight rises in prolactin, ACTH and cortisol; no change in glucose, IGF-1, LH, FSH or TSH; well tolerated^[2].
• Dose-response study, 1996 (healthy men): growth hormone, prolactin and cortisol all rose with dose. Pairing a low amount with GHRH gave strong growth hormone release without a cortisol rise^[3].
• 16-week tolerance study, 1998 (adults, no placebo group): the growth hormone response fell from 19.1 to 10.5 units by week 16 (P=0.0003), then recovered four weeks after stopping. IGF-1, body fat, lean mass and bone density did not change significantly^[4].
• Small cardiac studies, 1999 to 2002 (e.g., 7 growth hormone-deficient adults with heart failure; patients after bypass surgery): reported short-term increases in heart pumping (ejection fraction) and cardiac performance that appeared independent of growth hormone. Group sizes were small and outcomes were short-term measurements^[6].

• Rats, ischemia-reperfusion injury after pituitary removal: hexarelin prevented worsened heart damage, reduced creatine kinase leakage and improved recovery of contraction, matching growth hormone's effect, while a non-heart-binding GHRP had no effect^[5].
• Rodent heart failure and cardiomyopathy models: growth hormone-releasing peptides as a class have reduced heart cell death and improved heart function in several studies, reviewed in^[6].

Open Questions

• Whether the reported heart effects in humans translate into any clinical benefit has never been tested in an adequate trial^[6].
• The identity and role of the cardiac binding site in humans remain incompletely characterized^[5].
• Long-term effects of repeated prolactin and cortisol stimulation are unknown^[3].
• Most data are 25 or more years old, from small groups, and some studies involved the drug's developer^[1,2].

Regulatory Status

Not approved by FDA, EMA or any other major regulator for any use. It does not appear on FDA's compounding Category 2 safety-risk list, which reflects a lack of FDA review rather than any finding of safety^[9]. Named on the WADA 2026 Prohibited List under S2 as examorelin (hexarelin) and banned at all times^[8].

Related Compounds

A chemically stabilized fragment based on an IGF-1 gene variant linked to muscle loading. The biology behind it is debated and the product itself has never been studied.

Overview

When muscle is stretched or loaded, the IGF-1 gene can be spliced in different ways, and one variant was named mechano growth factor (MGF). PEG-MGF is a synthetic peptide modeled on the tail end (the "E domain") of that variant, with polyethylene glycol (PEG) chains attached to slow its breakdown. The idea is that this tail fragment carries its own repair signal, separate from IGF-1 itself^[2].

That idea is contested. Researchers have not found a free MGF peptide circulating in the body, in muscle or in cell fluids^[2], and later work suggests the E-peptide effects depend on IGF-1 and its receptor rather than acting alone^[3,4]. An industry team that tried to reproduce MGF peptide effects on muscle cells found none^[5]. No published study has tested PEG-MGF itself.

Mechanism of Action

The IGF-1 gene produces several precursor forms that share the same mature IGF-1 but carry different E-domain tails. In rodents, the version called IGF-IEb (MGF) rises in muscle after loading or damage, and its expression in heart cells has been linked to beating activity^[2,6]. The hypothesis behind MGF peptides is that the cleaved tail acts as an independent signal that activates muscle stem cells before mature IGF-1 takes over^[2].

Mechanistic work has weakened that model. Knocking down the IGF-1 precursors reduced muscle protein production by 70 to 80%, and mature IGF-1 restored it while synthetic E peptides did not^[3]. Other work found that E-peptide effects required both IGF-1 and its receptor, and that the peptides did not activate the receptor directly^[4]. PEGylation is a standard way to extend a peptide's lifespan in the blood, but no study has measured what it does to an MGF peptide.

What the Research Shows

• None published for PEG-MGF. The FDA states it has not identified any human exposure data for drug products containing PEG-MGF^[1].
• Exercise biology (2003): MGF messenger RNA in muscle rose after resistance exercise in young men (n=8) but not in older men (n=7). This measured the body's own gene activity, not a peptide given as a treatment^[7].

• None for PEG-MGF. Animal and expression studies describe the natural splice variant, not the synthetic PEGylated peptide^[2,6].

• Myoblasts and cardiomyocytes, industry replication (2014): MGF peptide at up to 500 ng/mL had no effect on proliferation or differentiation of mouse or human muscle precursor cells, while IGF-1 worked^[5].
• Mouse muscle cells (2011): mature IGF-1, but not synthetic E peptides, restored muscle protein production after precursor knockdown^[3].

Open Questions

• Whether a free MGF peptide exists or acts in the body at all is unresolved^[2].
• Whether E-peptide effects can occur without IGF-1 and its receptor; current evidence suggests not^[3,4].
• What PEGylation does to the peptide's activity, half-life or safety has never been measured.
• Why some early studies reported effects that an independent team could not reproduce^[5].

Regulatory Status

Not approved for any use. A nomination of PEG-MGF for compounding was withdrawn, and the FDA lists it among substances that may pose significant safety risks, citing immunogenicity and an absence of human exposure data^[1]. Mechano growth factors are prohibited under WADA class S2^[8].

Related Compounds

An engineered decoy receptor that soaks up myostatin and related muscle-limiting signals; it built muscle in early trials but was stopped after boys developed nosebleeds and small dilated blood vessels.

Overview

ACE-031 is a lab-made fusion protein: the outer, signal-catching part of the activin type IIB receptor (ActRIIB) joined to the Fc tail of a human antibody. It circulates as a decoy that binds myostatin and related growth factors before they can reach muscle^[1]. It is a large biologic drug, not a short peptide, and its development by Acceleron targeted Duchenne muscular dystrophy (DMD)^[1,3].

A single injection increased lean mass and thigh muscle volume in healthy postmenopausal women^[2]. In boys with DMD, a randomized trial was stopped early after nosebleeds and telangiectasias (small dilated blood vessels in the skin) appeared, and ClinicalTrials.gov lists it as terminated based on preliminary safety data^[1,3]. No later human trials of ACE-031 have been reported.

Mechanism of Action

Myostatin and several related members of the TGF-beta family slow muscle growth by binding the activin type IIB receptor on muscle cells. ACE-031 contains the extracellular ligand-binding domain of ActRIIB fused to an IgG1 Fc fragment, so it binds myostatin and related ligands in the circulation and blocks their inhibitory signal^[1]. In mice, a soluble ActRIIB decoy produced more muscle growth than inhibitors aimed at myostatin alone and still increased muscle in mice lacking myostatin, showing that it blocks more than one brake^[4].

The Fc portion slows clearance. In healthy volunteers, drug exposure rose in proportion to the amount given, with a mean half-life of 10 to 15 days^[2]. Biomarker changes in that study also suggested effects on bone and fat metabolism, consistent with a drug that acts on several signaling pathways rather than muscle alone^[2]. Which captured ligands explain the vascular side effects seen in the Duchenne trial was not established in the published report^[1].

What the Research Shows

• Single ascending-dose RCT, healthy postmenopausal women, 2013 (n=48, randomized 3:1 to drug or placebo, one injection): at day 29 in the highest dose group, total lean mass rose 3.3% (P=0.03, DXA) and thigh muscle volume 5.1% (P=0.03, MRI). The main adverse event was injection-site redness^[2].
• Multiple ascending-dose RCT, boys with DMD, 2017 (n=24 enrolled per registry, double-blind, placebo-controlled): stopped after the second dosing regimen because of nosebleeds and telangiectasias. No serious adverse events were attributed to the drug. The treated groups showed non-significant trends toward maintaining 6-minute walk distance, more lean mass and bone density, and less fat^[1,3].

• Mice, soluble ActRIIB decoy: produced more muscle growth than myostatin-specific inhibitors and increased muscle even in myostatin-knockout mice, indicating that ligands other than myostatin also restrain muscle^[4].

Open Questions

• Whether the muscle gains would translate into better strength or function was never shown; the walking data were non-significant trends^[1].
• Which of the captured growth factors caused the vascular side effects, and whether they would reverse fully with longer exposure, is not established.
• Effects on fertility, bone and blood vessels over months or years are unknown.
• Products sold outside clinical trials under this name have no verified identity or purity.

Regulatory Status

Not approved by the FDA or any major regulator; the sponsor's phase 2 Duchenne trial was terminated in 2011 based on preliminary safety data^[3]. Activin receptor IIB decoys such as ACE-031 are prohibited at all times under WADA class S4^[5].

Related Compounds

Follistatin is a natural protein that blocks myostatin and related muscle-limiting signals. Its human evidence comes from small gene-therapy trials in muscle disease, not from injected protein.

Overview

Follistatin is a protein the body makes to regulate members of the TGF-beta family, including myostatin and activin, which act as brakes on muscle growth. FST344 refers to the longest precursor form of the human protein (344 amino acids, including its signal sequence)^[3,5]. The same name appears in a clinical trial registry for a gene-therapy program^[3].

Mouse genetics made follistatin famous: animals engineered to overproduce it grew roughly four times the normal muscle mass^[6]. Human evidence is limited to two small trials at one US children's hospital that delivered the follistatin gene directly into thigh muscles of adults with muscular dystrophy or inclusion body myositis^[1,2]. No trial has tested injected follistatin protein.

Mechanism of Action

Follistatin binds and neutralizes several TGF-beta family proteins, most importantly activin and myostatin, preventing them from reaching their receptors on muscle cells^[5,6]. Different follistatin forms vary in how strongly they stick to cell surfaces, which affects whether they act locally or circulate; myostatin competes for binding more potently than related bone proteins^[5]. In mice, follistatin overexpression still increased muscle when myostatin was already absent, showing it blocks more than myostatin alone^[6].

Follistatin-driven muscle growth in mice depended on the IGF-1 receptor, Akt and mTOR growth pathway: blocking the IGF-1 receptor blunted it by 63% and blocking Akt by 65%^[7]. That means follistatin works partly by unlocking the same growth machinery that IGF-1 uses, which is relevant to both its potential and its theoretical risks.

What the Research Shows

• Becker muscular dystrophy gene-transfer trial, 2015 (n=6, uncontrolled, one-time injection into both thigh muscles): 6-minute walk distance improved in 4 of 6 patients (by 29 to 125 m) and did not improve in 2, who had extensive muscle scarring. Biopsies showed less fibrosis. No adverse effects were reported^[1].
• Inclusion body myositis gene-transfer trial, 2017 (n=6 treated vs 8 untreated comparison patients): median yearly change in walk distance was +56 m vs -25.8 m (P=0.01), and 4 of 6 treated patients improved^[2].
• Registry record (NCT01519349): phase 1, completed, 15 participants total, primary outcome safety over 2 years^[3].

• Transgenic mice (2001, 2007): follistatin overexpression produced about four times normal muscle mass, more than myostatin deletion alone^[6,8].
• Mice, pathway blocking (2012): follistatin-induced muscle growth required IGF-1 receptor and Akt signaling and was partly mTOR dependent^[7].

• Cell binding studies (2006): follistatin forms differ in cell-surface binding and in how strongly they neutralize myostatin versus related proteins^[5].

Open Questions

• Whether injected follistatin protein reaches muscle in useful amounts, or lasts long enough to matter, has never been tested in people.
• Whether the gene-transfer results hold up in larger, controlled trials.
• Long-term effects of blocking activin and myostatin on reproductive, bone and cardiovascular health.
• What exactly is in products sold as FST344, and whether they are correctly folded and active.

Regulatory Status

Not approved for any use. Follistatin does not appear on the FDA's compounding safety-risk lists and was not reviewed at the July 2026 advisory committee. The WADA 2026 Prohibited List names follistatin under S4 (myostatin-binding proteins)^[10].

Related Compounds