Follistatin-344: what the trials show, status and safety
Summary
Follistatin is a protein the human body makes itself, isolated in 1987 at the Salk Institute. It catches activin A, myostatin and related signals before they reach their receptor, and in mice that makes muscles grow. No country has approved it, for any purpose. Every human study delivered it as gene therapy rather than as an injected protein, and of the three published trials one failed outright. Of 17 products sold under the name, only nine contained follistatin.
Key findings at a glance
- No person has ever received follistatin protein in a registered trial. A register search in September 2026 returned 15 entries. Five test follistatin itself, and all five are gene therapy [1].
- The Duchenne trial missed its target. None of the three boys treated walked further in the six-minute walk test, and one of three improved on a separate motor score [2].
- Four of six improved in Becker muscular dystrophy. Walking distance rose by 58, 125, 108 and 29 metres in four men and not at all in two. There was no control group [3].
- The myositis result is contested in print. The authors reported 56.0 metres gained a year against 25.8 metres lost in an untreated comparison group (p = 0.01). A letter in the same journal called the claim unfounded [4], [5].
- The protein is ill suited to injection. A team at Eli Lilly found native follistatin-315 "poorly suited" for use as an injected medicine. Only a rebuilt version reached roughly 100 times the half-life and 1600 times the exposure [6].
- Nine of 17 products sold as follistatin contained it. Two anti-doping laboratories found other growth-promoting peptides instead in some of the rest, named as MGF and GHRP-2. All nine genuine ones carried a foreign tag and many clumps [7].
- Named in law, not merely caught by a clause. Section S4.3 of the 2026 Prohibited List names follistatin. German anti-doping law names it with a criminal threshold of 450 mg, and Australia forbids possession without authority [8], [9], [10], [11].
What it is
Follistatin is a secreted glycoprotein, meaning a protein carrying sugar chains that cells release into their surroundings. The gene that codes for it, FST, sits on chromosome 5q11.2 [12]. The body makes it in the pituitary gland, the ovary and many other tissues [13].
It is not a peptide in the sense that word usually carries here. The mature protein has 315 building blocks, 36 cysteines linked into 18 internal bridges and two points where sugar is attached [13], [14]. At roughly 35 kilodaltons it sits in the same league as growth hormone, and it cannot be made by peptide synthesis, only grown in cell culture.
The numbers in the product names are not strengths. They mark two stages of the same protein. FST-344 and FST-317 are precursors that still carry a 29-part signal tag; cutting that tag off yields the mature proteins FS-315 and FS-288 [13], [15]. Nothing called "follistatin-344" circulates in the body.
What separates the two mature forms is mainly where they end up. FS-288 sticks to cell surfaces and stays in the tissue, while FS-315 travels in the blood [16]. FS-288 also holds on to activin more tightly than FS-315 does. The gene therapy team chose the 344 transcript for that reason, because the resulting FS-315 binds about ten times more weakly and should disturb the hormone axis less [17].
Quick facts
| Other names | FST-344, FS-344, follistatin isoform FST344 precursor [18] |
| Class | Endogenous glycoprotein; blocks several signals of the TGF-beta family [13] |
| Structure | 344 building blocks as a precursor, 315 when mature; 18 internal bridges; two sugar sites [13], [14] |
| Mass | 38 007 Da calculated for the precursor without sugar; about 34 754 Da for mature FS-315 by the same calculation; measured as roughly 35 000 for the natural protein [13], [19] |
| Half-life in people | Never measured [6] |
| Status | Approved nowhere, for any condition [20], [21], [22], [23] |
| Developer | Isolated at the Salk Institute; gene therapy developed at Nationwide Children's Hospital [19], [3] |
| Gene | FST, HGNC:3971, chromosome 5q11.2 [12] |
| UniProt | P19883 [13] |
| PubChem | No compound entry; listed as a protein target instead [24] |
| CAS and ATC | Neither exists [13] |
How it works
Follistatin works outside the cell, by catching signalling molecules before they can dock.
- It traps several signals, not one. Activin A, myostatin, GDF-11 and several bone morphogenetic proteins are all bound [13]. Calling it a myostatin blocker is too narrow.
- Two copies wrap one signal pair. An X-ray structure at 2 Å resolution shows two copies of the smallest blocking fragment enclosing an activin pair and covering the docking site for the type II receptor. Arginine 192 is the decisive contact [25].
- Less activin in the pituitary gland means less FSH. Follicle-stimulating hormone drives egg and sperm maturation. Binding activin lowers its release, an effect shown directly in sheep and in cultured rat cells [26], [19].
- The muscle effect may not run through myostatin at all. In mice a follistatin-288 vector produced muscle growth through Smad3 and the Akt/mTOR/S6K route, and it persisted whether myostatin was absent or overproduced [27]. Mice with only one working copy of the gene had smaller, weaker muscles even without myostatin [28].
- It may also act inside the nucleus, where it has been reported to slow the making of ribosomes. Nothing discussed on this page rests on that [13].
This sets follistatin apart from the peptides it is usually filed beside. Sermorelin, ipamorelin and CJC-1295 prompt the pituitary gland to release a hormone. Follistatin removes a brake instead, and it is a protein dozens of times their size [13].
What the trials found
Five interventional register entries test follistatin, and every one of them delivers it as a gene rather than as a protein [1]. Two of them ran at one academic centre between 2012 and 2017, enrolled 18 people between them and produced the three published reports described below [29], [2]. The other three are commercial and run in Honduras: two have treated 57 people and published nothing, and the third is still recruiting [30], [31], [32].
Becker muscular dystrophy
Phase 1/2a Six adults received a gene therapy vector, rAAV1.CMV.FS344, injected into the thigh muscle of both legs in two dose groups [3]. The trial was open, without a control group and without a statistical test on its main measure.
Walking distance in the six-minute walk test rose in four of the six men and not at all in the other two. Muscle samples showed less scarring and larger fibres, more so in the higher dose group. No adverse effects were reported [3].
Change in walking distance for each of the six participants. Open trial, no control group, no statistical test on this measure. Source [3].
Inclusion body myositis
Phase 1/2a Six people with sporadic inclusion body myositis received the vector into both thighs. They were compared with eight untreated people matched for age, sex and starting values, and each treated person also followed an exercise plan [4].
The authors scaled every result to one year, using the middle value of the follow-up times as that year. On that basis the treated group gained 56.0 metres and the comparison group lost 25.8 metres (p = 0.01). Four improved by 58 to 153 metres, two by only 5 to 23 metres [4].
Published dispute The conclusion did not stand unchallenged. A neurologist at Harvard Medical School published a letter in the same journal headed "Unfounded Claims of Improved Functional Outcomes", and the trial's leader replied [5], [33]. The objections follow from the design: six participants, no randomisation, no blinding, an outside comparison group and exercise in one arm only.
Duchenne muscular dystrophy: the target was missed
Phase 1/2 Three boys received the highest vector dose of the programme, spread across muscles of both legs [2]. Six had been planned. The safety measure was met, with no dose-limiting toxicity.
The efficacy measures were not. None of the three walked further in the six-minute walk test, and one of three improved on the North Star Ambulatory Assessment. One serious event was recorded, a head injury after a fall [2].
This is the only one of the three academic trials whose results were filed in the register, and it is the one least often quoted. No further trial of this line appears after 2017 [1].
Why the protein itself is not injected
Animal data A group at Eli Lilly set out to measure what native follistatin-315 does once it is in the body [6]. Their verdict was that its own properties leave it "poorly suited" for use as an injected medicine acting throughout the body.
They then rebuilt the molecule, fusing it to an antibody fragment and removing the part that sticks to tissue. That version reached roughly 100 times the terminal half-life and 1600 times the exposure, and only it produced a dependable, dose-related effect in mice [6].
The finding comes from a company with an interest in a working follistatin medicine, and it still came out negative for the natural protein. It also explains the development history: the clinical route went through gene therapy because the protein cannot do the job alone.
The hormone finding
Animal data Five ewes whose ovaries had been removed received a single infusion of 150 micrograms per kilogram of follistatin-288 into a vein, with blood sampled every ten minutes for 18 hours. FSH fell furthest after 5 to 6 hours in the blood leaving the pituitary gland, by 65 percent, and after 9 to 10 hours in the rest of the circulation, by 48 percent [26]. The release patterns of GnRH and LH did not change. Follistatin bound to activin left the blood more slowly than free follistatin (p < 0.05), which is how the authors read the effect as activin being taken out of circulation.
Animal data In cultured rat pituitary cells the half-maximal effect appeared at 2.5 to 6.0 nanograms per millilitre in one report and 6.2 to 7.3 in another, the latter given as a concentration of 1.8 x 10^-10 moles per litre. That is about a third of the potency of inhibin [19], [34]. At least 18 hours of contact were needed, and no other pituitary hormone moved.
Animal muscle data
Animal data Mice engineered to overproduce follistatin in muscle grew muscles as large as mice lacking myostatin altogether [35]. A single gene dose kept mass and strength raised for more than two years, including in old animals [36].
Animal data In macaque monkeys the same vector lastingly increased muscle size and strength, with no abnormal findings in the organs examined [37]. That study was the basis for the human trials.
All of these are genetic experiments. None of them involves injecting a protein, and none of them can be read as evidence that injecting one would do anything.
What follistatin levels predict in large populations
Observational More follistatin in the blood tracks with worse health, not better. Each standard deviation higher was linked to a 24 percent higher risk of developing type 2 diabetes over 19 years in 4060 people in Sweden (hazard ratio 1.24, 95 percent confidence interval 1.04 to 1.47). In 883 people in Finland the figure was 31 percent over 4 years (1.31, 1.09 to 1.58) [38].
Observational In 4733 adults aged 45 to 68 and followed for 22.64 plus or minus 5.84 years, each standard deviation higher was linked to raised risk of death from any cause (1.05, 1.00 to 1.11, p = 0.036), of any stroke (1.10, 1.00 to 1.20, p = 0.042), of ischaemic stroke in particular (1.13, 1.03 to 1.25, p = 0.014), of heart failure (1.16, 1.03 to 1.30, p = 0.015) and of chronic kidney disease (1.38, 1.12 to 1.70, p = 0.003) [39].
These are associations in people who were not given anything, so they prove no cause. Several authors work for Eli Lilly, and one has filed a patent on follistatin and diabetes risk [38].
What the same axis did in other hands
Phase 2 RCT Bimagrumab is an antibody against the same receptor that follistatin acts on from further upstream. In 16 older adults aged 70 to 85, randomly assigned and compared against a placebo nobody could identify, a single infusion raised thigh muscle volume by 5.3 plus or minus 1.8 percent at the lower dose and 6.1 plus or minus 2.2 percent at the higher one, against 0.5 plus or minus 2.1 percent on placebo (both p at or below 0.02). The paper adds: "with no change in muscle strength" [40].
Phase 2 RCT ACE-031, a decoy version of the same receptor, was tested in boys with Duchenne muscular dystrophy and stopped after the second dosing schedule. The reason was nosebleeds and small dilated vessels in the skin, findings that have nothing to do with muscle [41].
Bimagrumab in older adults at week 4, randomised and placebo-controlled, 24 participants in all. Muscle strength did not change in any group. Source [40].
What is still unknown about Follistatin-344
- No human trial has ever given the protein. There is no human pharmacokinetic data, no data on repeated use and none on injection under the skin [1], [6].
- No human data exist on FSH, LH, testosterone, sperm counts or ovulation after follistatin is given, although hormone suppression is its best documented effect [26].
- No purity, endotoxin or clumping figures exist for traded goods beyond the finding that they are tagged and partly clumped [7].
- No study has looked at whether the human immune system reacts to the tagged recombinant protein [7].
- No cancer studies to regulatory standard exist, and the animal findings point both ways [42], [43].
- No results have appeared from the three trials in Honduras, where 57 people have been treated and 12 more are planned [30], [31], [32].
- No results were filed for the largest academic trial, which enrolled 15 people; the publications cover parts of it [29].
Side effects and safety
The entire published human safety record covers 15 people, reported from three open trials of local gene therapy into muscle; the two register entries behind them enrolled 18 [29], [2]. That says nothing about injected protein.
- Pain affected all three participants in the Duchenne trial, and bruising two of three [2].
- Single events in that trial of three included a sore throat, a runny nose, influenza, anxiety, agitation, disturbed sleep, reflux, constipation, a compression fracture and worsening muscle weakness [2].
- One serious event was recorded, a head injury after a fall [2]. With three participants, nothing can be attributed to the treatment either way.
- "No adverse effects were encountered" is the wording in the Becker publication [3]. Six people in an open trial cannot establish safety.
- Clumps and a foreign tag were present in all nine traded products that did contain follistatin [7]. Clumped protein is the classic trigger of immune reactions, and a histidine tag is a sequence the body has never seen.
Four risks deserve stating plainly.
The hormone and fertility axis. One infusion cut FSH by up to 65 percent in sheep [26]. Mice made to overproduce follistatin for life developed Leydig cell overgrowth, halted sperm production and degenerating tubules in males, blocked follicle growth in females, and infertility in both [43]. This is the reason the gene therapy team picked the isoform that disturbs the axis least [17].
A broad blockade, not a narrow one. Mice born without follistatin die within hours, with defects of the diaphragm, skin, palate, ribs, teeth and whiskers [44]. The damage is wider than in activin-deficient animals. What a lasting pharmacological blockade of that network would do in a person is unknown.
Effects on blood vessels. The ACE-031 programme against the same receptor was halted over nosebleeds and dilated skin vessels [41]. The running trial in Honduras lists new heart failure or arrhythmias as a safety measure of its own [32].
Gene therapy cannot be switched off. Expression lasted more than two years after one dose in mice and long-term in monkeys [36], [37]. Outside a regulated setting that decision cannot be taken back.
Analysis by two accredited anti-doping laboratories. In some of the eight, other growth-promoting peptides were found instead, named as MGF and GHRP-2. Source [7].
Endotoxin was not measured in that work. A comparable study of semaglutide bought online found endotoxin in all three delivered samples, 2.16 to 8.95 units per milligram. Purities ran from 7.7 to 14.4 percent against a label claim of 99 percent [45].
There are no contraindications and no interaction warnings on file, because no authority has ever reviewed a product label for follistatin in any market [20], [21].
Doses used in studies
The doses below are simply what the cited studies gave, listed so that the results can be understood. They are not advice on how to use anything.
Every human line in this table is a gene therapy dose. What it counts is virus particles, written as vector genomes per kilogram of body weight, injected into a muscle on a single occasion. Nothing in it describes an amount of protein, and the lines from sheep and from cells in a dish cannot be carried over to people.
| Study | Model | Dose | Route | Frequency | Duration | Ref |
|---|---|---|---|---|---|---|
| Mendell 2015, Becker muscular dystrophy | 6 adults | 3 x 10^11 and 6 x 10^11 vector genomes per kg per leg | Into the thigh muscle, both legs | Once | Followed up to 2 years | [3], [29] |
| Mendell 2017, inclusion body myositis | 6 adults treated, 8 untreated for comparison | 6 x 10^11 vector genomes per kg | Into the thigh muscle, both legs | Once | Annualised over a median year | [4], [29] |
| NCT02354781, target missed | 3 boys with Duchenne muscular dystrophy | 2.4 x 10^12 vector genomes per kg in total, 1.2 x 10^12 per leg | Into muscles of both legs | Once | Followed up to 2 years | [2] |
| NCT07443826, running | 12 healthy adults planned, 35 to 75 years | 5 x 10^10 and 1 x 10^11 vector genomes per kg; a third arm adds a VEGF plasmid, 4.8 mg in total | Into muscle | Once; the plasmid twice | 90 days to the main measure | [32] |
| NCT06411366 and NCT07285629 | 43 and 14 healthy adults | None stated in the register | Injection, not specified | Once | 3 months | [30], [31] |
| Padmanabhan 2002 | 5 ewes without ovaries | 150 µg/kg of follistatin-288 | Into a vein | Once | 18 hours of sampling | [26] |
| Ueno 1987 and Ying 1987 | Rat pituitary cells | 2.5 to 6.0 and 6.2 to 7.3 ng/ml, half-maximal | Added to the culture medium | Once | At least 18 hours | [19], [34] |
| Datta-Mannan 2013 | Mouse models of muscle loss | No usable figure: the natural protein failed, an engineered variant worked | Under the skin | Weekly | Not stated | [6] |
There is no way to convert those virus counts into milligrams of a protein, and no published method for doing so. For follistatin protein no human dose exists anywhere in the world, because it has never been given to a person in a registered trial [1].
The only clearly quantified doses of the protein itself come from sheep and from rat cells, and both used the other mature form, FS-288 [26], [19].
Development and approval status
Follistatin has never been developed as a medicine. The clinical work was gene therapy at one academic centre, it stopped in 2017, and a separate commercial line began in Honduras in 2022 [1], [30].
From a protein in follicular fluid to two named legal entries
- 1987Isolated from pig follicular fluid at the Salk InstituteSingle-chain protein of about 35 000, named to separate it from inhibin, ref [19]
- 1988The human precursor and its two splice forms are described344 and 317 building blocks, ref [15]
- 1995Mice born without follistatin die within hoursDefects of diaphragm, skin, palate and ribs, ref [44]
- 1998Lifelong overproduction causes infertility in miceBoth sexes affected, ref [43]
- 2001Overproduction in muscle matches myostatin knockout miceTransgenic lines, ref [35]
- 2009Muscle size and strength rise in monkeysThe vector that later went into people, ref [37]
- 2012-2017Three gene therapy trials, 18 people enrolled and 15 reportedOne disputed positive, one clear failure, refs [3], [4], [2]
- 2019Two laboratories analyse traded goodsNine of 17 products contained follistatin, ref [7]
- 2022-2026Plasmid and AAV9 gene therapy offered in HondurasThree single-arm studies, no published results, refs [30], [31], [32]
- 2026Named on the anti-doping list, in German law and in the Australian Poisons StandardRefs [8], [9], [10], [11]
- 1987 — the protein is isolated from pig follicular fluid and named [19], [34].
- 1988 — the human precursor and the two splice forms, 344 and 317, are described [15].
- 1995 to 2001 — mouse genetics map what follistatin does, from perinatal death without it to large muscles with too much of it [44], [43], [35].
- 2009 — the vector raises muscle size and strength in macaque monkeys [37].
- 2012 to 2017 — three gene therapy trials run in Becker muscular dystrophy, inclusion body myositis and Duchenne muscular dystrophy [29], [2].
- 2017 — the myositis result is contested in print and the Duchenne trial misses its efficacy measures. The line ends [5], [2].
- 2019 — two anti-doping laboratories analyse traded goods and publish a detection method [7].
- 2022 to 2026 — three single-arm studies in Honduras treat 57 people without publishing anything [30], [31], [32].
| Market | Status | Note | Ref |
|---|---|---|---|
| United States | Not approved | No entry in any drug database | [20], [21] |
| European Union | Not approved | Derived; no authorisation, no ATC code | [46] |
| Germany | Not approved | Named in anti-doping law | [9], [47] |
| United Kingdom | Not approved | Derived; index not machine-readable | [46] |
| Australia | Prescription-only | Possession without authority is an offence | [11] |
| Canada | Not approved | Empty result, control query worked | [22] |
| Switzerland | Not approved | No entry in the official medicines list | [23] |
Every query behind this table was run on 15 September 2026. Two of the seven are derived rather than measured: the European Medicines Agency search returned an authorisation error and the British product index returned no machine-readable results [46].
Australia is the strictest case. The Poisons Standard of June 2026 lists follistatin as prescription-only. It then lists it again as item 16 in clause 5 of Appendix D, the table of poisons that may not be possessed without authority under the law of the state or territory where the possession happens [11]. No product has ever been licensed there, so a prescription could not realistically be written.
The United States picture has one telling gap. Follistatin appears on none of the compounding lists, not even among the substances nominated and rejected, where GHRP-2 and GHRP-6 do appear [48]. Nobody has ever asked, which fits a 35-kilodalton glycoprotein that no pharmacy could prepare.
Registration on a trial register is worth naming for what it is. It is a sponsor's own filing, not an approval and not a result [30].
Anti-doping
Follistatin is banned in sport at all times, in and out of competition, and it counts as a non-specified substance, the stricter of the two categories [8]. Section S4.3 of the 2026 Prohibited List, headed "agents preventing activin receptor IIB activation", names it among "myostatin-binding proteins (e.g. follistatin, myostatin propeptide)" [8].
The gene therapy form is caught twice over, since section M3.1 covers the transfer of nucleic acids by any mechanism [8]. German law goes further than the sporting rules. The annex to the Anti-Doping Act names "follistatin and its derivatives". The accompanying regulation sets the threshold for a criminal quantity at 450 mg [9], [10].
Detection works on both routes. For the protein, two laboratories built a method from immunomagnetic clean-up, gel separation and an antibody against the histidine tag. It reaches about 0.1 nanograms per millilitre in urine from a 10 millilitre sample, and 5 nanograms per millilitre in serum from 100 microlitres [7]. Because traded goods carry that tag, they can be told apart from the body's own protein. For the gene, PCR methods detect five copies of the transgene against a 25 000-fold excess of the natural gene [49]. The wider picture for this family is at peptides banned in sport.
Compared with related peptides
| Substance | What it is | Approval | Anti-doping | Distinguishing finding |
|---|---|---|---|---|
| Follistatin-344 | The body's own activin and myostatin trap | None, anywhere [20], [23] | Named, S4.3 [8] | No human has received the protein in a registered trial [1] |
| Myostatin propeptide | The natural offcut that keeps myostatin inactive | None [8] | Named in the same line, S4.3 [8] | Produced muscle growth in the same transgenic comparison [35] |
| ACE-031 | Decoy copy of the receptor | None; development halted [41] | Named as a decoy receptor, S4.3 [8] | Stopped over nosebleeds and dilated skin vessels [41] |
| Bimagrumab | Antibody against the receptor | None [8] | Named, S4.3 [8] | Muscle volume up 5.3 to 6.1 percent with no change in strength [40] |
| Stamulumab | Antibody against myostatin | None [9] | Named, S4.3 [8] | Same 450 mg threshold in German law [10] |
Three things follow from this table. Everything aimed at this axis is banned by name, so the sporting question is settled for the whole family rather than for one molecule [8].
The class has a consistent result and it is not the hoped-for one. Bimagrumab produced more muscle volume without more strength, and ACE-031 produced effects on blood vessels serious enough to end a programme [40], [41].
Follistatin differs from all of them in one respect that matters more than any comparison of potency. The others were built as medicines and tested as medicines. Follistatin was never taken down that road, because the protein does not survive the trip [6].
Readers looking at muscle and metabolism substances often arrive here from MOTS-c, SLU-PP-332 or 5-Amino-1MQ. Those act inside the cell on energy handling and belong to a different family entirely.
Common misconceptions
- "Follistatin-344 is the strong version and 315 is the weak one." The numbers mark stages of processing, not strengths. FST-344 is the precursor of mature FS-315, and FS-288 is the form that binds activin more tightly [13], [16]. The 344 transcript was chosen for gene therapy because its product binds about ten times more weakly [17].
- "The trials showed that follistatin works, so injecting it works too." Those trials injected a virus carrying the gene, not the protein, and the doses are counts of virus particles [3], [2]. The one study that measured the protein itself concluded it is unsuited to injection [6].
- "The gene therapy was a success." One trial of six was open and uncontrolled, one was contested in print, and the third missed every efficacy measure in three boys [3], [5], [2]. Nothing followed after 2017 [1].
- "It is a selective myostatin blocker." It binds activin A, GDF-11 and several bone morphogenetic proteins as well, and in mice the muscle effect survived the removal of myostatin [27], [28]. The label hides the side that matters, which is the hormone axis.
- "Follistatin and follistatin-like 1 are the same thing." They are separate genes and separate proteins sharing one domain. Two of the 15 register hits for follistatin concern FSTL1, and much of the literature on follistatin and cancer does too [1], [42].
- "Buying follistatin gets you follistatin." Nine of 17 traded products contained it. Others held MGF or GHRP-2 instead, and all nine genuine ones were tagged and partly clumped [7].
- "More follistatin in the blood is a good sign." In population cohorts each standard deviation higher tracked with more diabetes, stroke, heart failure and kidney disease [38], [39]. That is an association, and it points the wrong way for the anti-ageing story.
- "It causes cancer because it blocks activin." The only solid animal test found fewer metastases, not more, in a lung cancer model [42]. Lifelong overproduction did cause Leydig cell overgrowth [43]. The honest answer is that the question is open and no cancer study to regulatory standard exists.
Frequently asked questions
Is Follistatin-344 approved anywhere?
No. No country has licensed it as a medicine, for any condition, as a protein or as gene therapy. Database queries in the United States, Canada, Switzerland, Germany and Australia were run on 15 September 2026 and came back empty, each with a control query that worked. Australia classes it as prescription-only anyway and forbids possession without authority.
What is Follistatin-344?
It is a form of a human protein the body makes itself. The number counts the building blocks of the precursor, which still carries a 29-part signal tag. Once that tag is cut off, the mature protein has 315 parts and weighs about 35 kilodaltons, roughly the size of growth hormone.
Did the Follistatin-344 trials work?
Only partly, and only as gene therapy. Four of six men with Becker muscular dystrophy walked further, in an open trial without a control group. A myositis result was contested in a letter in the same journal. In Duchenne muscular dystrophy none of the three boys treated walked further.
Has anyone ever been given Follistatin-344 as a protein in a trial?
No. A search of the trial register in September 2026 found 15 entries, five of which test follistatin itself, and all five deliver it as a gene. There is no registered human study in which the protein was injected, and therefore no human pharmacokinetic data at all.
Why is Follistatin-344 delivered as gene therapy rather than injected?
Because the protein does not last. A team at Eli Lilly measured the natural form and called it poorly suited for use as an injected medicine acting throughout the body. Only after fusing it to an antibody fragment and removing its tissue-sticking part did it reach useful exposure in mice.
What are the safety concerns with Follistatin-344?
The clearest is the hormone axis. One infusion cut FSH by up to 65 percent in sheep, and lifelong overproduction in mice caused infertility in both sexes. Blocking the same receptor with other molecules produced nosebleeds and dilated skin vessels, and more muscle volume without more strength.
Is Follistatin-344 banned in sport?
Yes, at all times, in and out of competition, as a non-specified substance. Section S4.3 of the 2026 Prohibited List names follistatin among myostatin-binding proteins, and the gene transfer route is separately covered. Laboratories detect the tagged traded protein down to about 0.1 nanograms per millilitre in urine.
Is Follistatin-344 legal to possess?
That depends on the country and the answer is not reassuring. German law names "follistatin and its derivatives" in the annex to its Anti-Doping Act, with a criminal threshold of 450 mg. Australia lists it in an appendix under which possession without authority is illegal under state law.
How much of what is sold as Follistatin-344 is real?
In the only independent analysis, nine of 17 products contained follistatin at all. Some of the others held different growth-promoting peptides, named as MGF and GHRP-2. All nine genuine ones carried a histidine tag, a foreign sequence, and a high share of clumped protein.
Is Follistatin-344 the same as follistatin-like 1 or FSTL3?
No. Those are separate genes and separate proteins that merely share one structural domain with follistatin. The mix-up has practical consequences for anyone reading the literature, since several trial register entries and many cancer papers labelled "follistatin" are in fact about FSTL1 or FSTL3.
Sources
- ClinicalTrials.gov API v2, intervention searches for "follistatin" (15 records), "FS-344" and "FST-344" (none), retrieved 15 September 2026. Five of the 15 records test follistatin itself and all five are gene therapy; no registered human study has given follistatin protein. https://clinicaltrials.gov
- ClinicalTrials.gov. NCT02354781, phase 1/2 intramuscular gene transfer of rAAV1.CMV.huFollistatin344 in Duchenne muscular dystrophy; sponsor Jerry R. Mendell, Nationwide Children's Hospital; 3 participants of 6 planned; January 2015 to November 2017; results posted, including the six-minute walk test and the adverse event tables. Retrieved 15 September 2026. https://clinicaltrials.gov/study/NCT02354781
- Mendell JR, Sahenk Z, Malik V, et al. (2015). A phase 1/2a follistatin gene therapy trial for becker muscular dystrophy. Molecular Therapy 23(1):192-201. PMID 25322757. DOI 10.1038/mt.2014.200
- Mendell JR, Sahenk Z, Al-Zaidy S, et al. (2017). Follistatin gene therapy for sporadic inclusion body myositis improves functional outcomes. Molecular Therapy 25(4):870-879. PMID 28279643. DOI 10.1016/j.ymthe.2017.02.015
- Greenberg SA (2017). Unfounded claims of improved functional outcomes attributed to follistatin gene therapy in inclusion body myositis letter to the editor. Molecular Therapy 25(10):2235-2237. PMID 28927986
- Datta-Mannan A, Yaden B, Krishnan V, Jones BE, Croy JE (2013). An engineered human follistatin variant: insights into the pharmacokinetic and pharmacodynamic relationships of a novel molecule with broad therapeutic potential. Journal of Pharmacology and Experimental Therapeutics 344(3):616-623. PMID 23249626
- Reichel C, Gmeiner G, Thevis M (2019). Detection of black market follistatin 344. Drug Testing and Analysis 11(11-12):1675-1697. PMID 31758732. Erratum Drug Testing and Analysis 2020;12(10):1522-1533, PMID 33460286. Seventeen traded products analysed by the Seibersdorf doping control laboratory and the Cologne monitoring centre for new doping substances
- World Anti-Doping Agency. The 2026 Prohibited List, in force from 1 January 2026. Section S4.3 "agents preventing activin receptor IIB activation", the note that substances in S4.3 are non-specified, and section M3.1 on the transfer of nucleic acids. Full text checked 15 September 2026
- Annex (to section 2 subsection 3) of the German Anti-Doping Act, BGBl. 2023 I No. 67, pages 1-5, part III item 3 on substances altering myostatin function, wording "Follistatin und seine Derivate". gesetze-im-internet.de, checked 15 September 2026
- Annex to the German regulation setting non-minor quantities of doping agents, BGBl. 2023 I No. 67, pages 5-10, part III item 3: 450 mg for follistatin and its derivatives, the same for stamulumab. Retrieved 15 September 2026
- Therapeutic Goods (Poisons Standard—June 2026) Instrument 2026, F2026L00633, registered 28 May 2026. Schedule 4 entry "# FOLLISTATIN.", Appendix D clause 5 item 16, and section 64(4) on possession without authority. https://www.legislation.gov.au/F2026L00633/asmade
- HUGO Gene Nomenclature Committee, entry FST: HGNC:3971, locus 5q11.2, Entrez GeneID 10468, Ensembl ENSG00000134363. Retrieved 15 September 2026. https://rest.genenames.org/fetch/symbol/FST
- UniProt Knowledgebase entry P19883 (FST_HUMAN). Precursor of 344 residues, calculated mass 38 007 Da, signal peptide 1-29, chain 30-344, 18 disulfide bonds, glycosylation at Asn124 and Asn288, isoform 2 as FS288, plus the function, tissue specificity and subcellular location sections. Retrieved 15 September 2026. https://rest.uniprot.org/uniprotkb/P19883.json
- Esch FS, Shimasaki S, Mercado M, et al. (1987). Structural characterization of follistatin: a novel follicle-stimulating hormone release-inhibiting polypeptide from the gonad. Molecular Endocrinology 1(11):849-855. PMID 3153465
- Shimasaki S, Koga M, Esch F, et al. (1988). Primary structure of the human follistatin precursor and its genomic organization. Proceedings of the National Academy of Sciences USA 85(12):4218-4222. PMID 3380788
- Schneyer AL, Hall HA, Lambert-Messerlian G, Wang QF, Sluss P, Crowley WF Jr (1996). Follistatin-activin complexes in human serum and follicular fluid differ immunologically and biochemically. Endocrinology 137(1):240-247. PMID 8536619
- Al-Zaidy SA, Sahenk Z, Rodino-Klapac LR, Kaspar B, Mendell JR (2015). Follistatin gene therapy improves ambulation in Becker muscular dystrophy. Journal of Neuromuscular Diseases 2(3):185-192. PMID 27858738. States why the FS-344 transcript was chosen
- NCBI RefSeq entries NP_037541.1 with transcript NM_013409.3 (isoform FST344 precursor, 344 residues, MANE Select) and NP_006341.1 with NM_006350.5 (isoform FST317 precursor). Retrieved 15 September 2026
- Ueno N, Ling N, Ying SY, Esch F, Shimasaki S, Guillemin R (1987). Isolation and partial characterization of follistatin: a single-chain Mr 35,000 monomeric protein that inhibits the release of follicle-stimulating hormone. Proceedings of the National Academy of Sciences USA 84(23):8282-8286. PMID 3120188
- openFDA drugsfda, ndc and label endpoints queried for follistatin on 15 September 2026; all NOT_FOUND, with the control query for somatropin returning results. https://api.fda.gov
- DailyMed API v2, drug names query for follistatin on 15 September 2026: 0 records at database status 14 September 2026, with the control query for somatropin returning results
- Health Canada Drug Product Database, active ingredient query for follistatin on 15 September 2026: empty result, with the control query for somatropin returning several records
- Swissmedic, extended list of authorised medicines, downloaded 15 September 2026 and searched in full: no hit for follistatin, follistatinum or myostatin, against 15, 17 and 61 hits for the control terms somatropinum, semaglutidum and epoetinum
- PubChem PUG-REST queries, 15 September 2026: /compound/name/follistatin returns PUGREST.NotFound while the control query for ipamorelin returns CID 9831659, and /protein/accession/P19883/summary returns follistatin as a protein target
- Harrington AE, Morris-Triggs SA, Ruotolo BT, Robinson CV, Ohnuma S, Hyvönen M (2006). Structural basis for the inhibition of activin signalling by follistatin. EMBO Journal 25(5):1035-1045. PMID 16482217. Structure PDB 2B0U at 2 Å
- Padmanabhan V, Battaglia D, Brown MB, et al. (2002). Neuroendocrine control of follicle-stimulating hormone secretion: II. Biology of Reproduction 66(5):1395-1402. PMID 11967203. Five ovariectomised ewes, recombinant human follistatin-288 at 150 µg/kg into a vein
- Winbanks CE, Weeks KL, Thomson RE, et al. (2012). Follistatin-mediated skeletal muscle hypertrophy is regulated by Smad3 and mTOR independently of myostatin. Journal of Cell Biology 197(7):997-1008. PMID 22711699. Used follistatin-288 in an AAV6 vector, not FS-344
- Lee SJ, Lee YS, Zimmers TA, et al. (2010). Regulation of muscle mass by follistatin and activins. Molecular Endocrinology 24(10):1998-2008. PMID 20810712
- ClinicalTrials.gov. NCT01519349, phase 1 intramuscular gene transfer of rAAV1.CMV.huFollistatin344 in Becker muscular dystrophy and sporadic inclusion body myositis; sponsor Nationwide Children's Hospital; 15 participants in three dose cohorts; completed October 2017; no results posted. Retrieved 15 September 2026
- ClinicalTrials.gov. NCT06411366, single-dose open-label study of an injectable follistatin plasmid gene therapy in healthy subjects; sponsor Minicircle; 43 participants; August 2022 to August 2023; completed with no results posted and no publication traceable. Retrieved 15 September 2026
- ClinicalTrials.gov. NCT07285629, combination klotho and follistatin plasmid gene therapy, single-arm and without placebo; sponsor Minicircle; 14 participants aged 50 to 80; December 2025 to April 2026; no results posted. Retrieved 15 September 2026
- ClinicalTrials.gov. NCT07443826, AAV-follistatin combined with an angiogenesis-inducing VEGF plasmid; sponsor Unlimited Biotechnology LLC; 12 participants planned, aged 35 to 75; recruiting from June 2026; the safety measures name new-onset symptomatic heart failure or arrhythmias. Retrieved 15 September 2026
- Mendell JR (2017). Reply to letter to the editor. Molecular Therapy 25(10):2238-2240. PMID 28939086
- Ying SY, Becker A, Swanson G, et al. (1987). Follistatin specifically inhibits pituitary follicle stimulating hormone release in vitro. Biochemical and Biophysical Research Communications 149(1):133-139. PMID 3120723
- Lee SJ, McPherron AC (2001). Regulation of myostatin activity and muscle growth. Proceedings of the National Academy of Sciences USA 98(16):9306-9311. PMID 11459935
- Haidet AM, Rizo L, Handy C, et al. (2008). Long-term enhancement of skeletal muscle mass and strength by single gene administration of myostatin inhibitors. Proceedings of the National Academy of Sciences USA 105(11):4318-4322. PMID 18334646
- Kota J, Handy CR, Haidet AM, et al. (2009). Follistatin gene delivery enhances muscle growth and strength in nonhuman primates. Science Translational Medicine 1(6):6ra15. PMID 20368179
- Wu C, Borné Y, Gao R, et al. (2021). Elevated circulating follistatin associates with an increased risk of type 2 diabetes. Nature Communications 12(1):6486. PMID 34759311. Several authors are employed by Eli Lilly and one has filed a patent on follistatin and diabetes risk
- Pan J, Nilsson J, Engström G, De Marinis Y (2024). Elevated circulating follistatin associates with increased risk of mortality and cardiometabolic disorders. Nutrition, Metabolism and Cardiovascular Diseases 34(2):418-425. PMID 38000997
- Rooks D, Petricoul O, Praestgaard J, Bartlett M, Laurent D, Roubenoff R (2020). Safety and pharmacokinetics of bimagrumab in healthy older and obese adults with body composition changes in the older cohort. Journal of Cachexia, Sarcopenia and Muscle 11(6):1525-1534. PMID 33264516
- Campbell C, McMillan HJ, Mah JK, et al. (2017). Myostatin inhibitor ACE-031 treatment of ambulatory boys with Duchenne muscular dystrophy: results of a randomized, placebo-controlled clinical trial. Muscle and Nerve 55(4):458-464. PMID 27462804
- Ogino H, Yano S, Kakiuchi S, et al. (2008). Follistatin suppresses the production of experimental multiple-organ metastasis by small cell lung cancer cells. Clinical Cancer Research 14(3):660-667. PMID 18245525
- Guo Q, Kumar TR, Woodruff T, Hadsell LA, DeMayo FJ, Matzuk MM (1998). Overexpression of mouse follistatin causes reproductive defects in transgenic mice. Molecular Endocrinology 12(1):96-106. PMID 9440814
- Matzuk MM, Lu N, Vogel H, Sellheyer K, Roop DR, Bradley A (1995). Multiple defects and perinatal death in mice deficient in follistatin. Nature 374(6520):360-363. PMID 7885475
- Ashraf AR, Mackey TK, Vida RG, et al. (2024). Multifactor quality and safety analysis of semaglutide products sold by online sellers without a prescription. Journal of Medical Internet Research 26:e65440. PMID 39509151. Used here only as a methodological comparison for unregulated injectable goods
- European Medicines Agency full-text search and the British MHRA product index, queried 15 September 2026. The EMA search returned HTTP 401 and its bulk data files HTTP 404; the MHRA index returned no machine-readable result and its search path HTTP 404. Both null findings are therefore derived from the absence of any authorisation elsewhere and of an ATC code
- Annex 1 of the German regulation on prescription-only medicines, retrieved and searched in full on 15 September 2026: no entry for follistatin, myostatin or activin, with the control term somatropin present. https://www.gesetze-im-internet.de/amvv/anlage_1.html
- U.S. Food and Drug Administration compounding lists, checked 15 September 2026: 21 CFR 216.23 with its six substances, the list of bulk drug substances nominated under section 503A as of 14 May 2026 where GHRP-2 and GHRP-6 appear in category 3, the significant-safety-risks page and the 503B list. Follistatin appears on none of them
- Baoutina A, Bhat S, Li DK, Emslie KR (2023). Towards a robust test to detect gene doping for anabolic enhancement in human athletes. Drug Testing and Analysis 15(3):314-323. PMID 36445200. Four PCR assays including follistatin; five transgene copies detected against a 25 000-fold excess of the natural gene
Cite this page
The facts on this page were checked on 15 September 2026, and every database query behind the status table was run on that date. The parts most likely to change are the running trial in Honduras and the legal entries.
myPeptides Research & Editing. (2026). Follistatin-344: what the trials show, status and safety. Version 1.0, 15 September 2026. myPeptides Peptide Register. Retrieved from https://mypep.app/peptides/follistatin-344
How pages in this register are compiled and graded is described under methodology; the full register is at peptides.
| Version | Date | Change |
|---|---|---|
| 1.0 | 2026-09-15 | Initial publication |
Last verified: 15 September 2026. Next review: on any result from the running gene therapy trial, on any publication from the three studies in Honduras, or on any change to the anti-doping or Poisons Standard entries.