Follistatin 344: what it is, what the gene therapy trials found and what is unknown about the injected protein

Follistatin was discovered in the 1980s as a protein from ovarian fluid that suppressed the release of follicle-stimulating hormone (FSH) from the pituitary. In 1988 its human gene was sequenced, and it turned out to code for two precursors by alternative splicing: a 344-amino-acid form and a 317-amino-acid form ^[1]. In 1990 the activin-binding protein purified from rat ovary was shown to be identical to follistatin, which explained how it worked: it binds activin, the hormone that stimulates FSH release, and stops it reaching its receptor ^[2].

The number 344 therefore refers to the precursor. After the signal peptide is removed, the FST344 precursor becomes the 315-amino-acid mature protein, FS-315, which is the main form in blood, while the shorter FST317 precursor becomes FS-288, which binds tightly to cell surfaces ^{[3] [4]}. Follistatin 344 vs 315 is therefore mostly a labelling question: products sold as follistatin 344 are recombinant proteins made in cells, and a few are labelled follistatin 315. Which mature form a given vial contains, and whether it is glycosylated like the natural protein, depends entirely on how it was made.

Follistatin’s relevance to muscle came later. Myostatin, or GDF-8, is a member of the same TGF-beta family as activin and is the main natural brake on muscle growth. In 2001 Se-Jin Lee’s laboratory described the follistatin myostatin interaction: follistatin binds myostatin and blocks it from reaching its receptor, and that mice engineered to overexpress follistatin in muscle had dramatic increases in muscle mass, comparable to mice lacking myostatin altogether ^[5]. That finding is the basis for the sale of follistatin as a muscle-building compound, and for its classification alongside GDF-8 and ACE-031 as a myostatin pathway protein. See what research peptides are for how such proteins reach the market.

Follistatin is a binding protein, not a receptor blocker or a hormone. It wraps around activin, myostatin and, with lower affinity, some bone morphogenetic proteins, and prevents them from binding their receptors on the cell surface ^{[3] [5]}. Removing myostatin and activin signalling releases muscle from their restraint: muscle protein synthesis rises through the Akt/mTOR pathway and fibres enlarge. A 2012 study found that follistatin-driven hypertrophy in mice depended on Smad3 and mTOR signalling and occurred even in mice with no myostatin, showing that follistatin acts on more than one ligand ^[6].

The isoforms matter. FS-288 binds cell-surface proteoglycans strongly and stays where it is made, while FS-315 binds them weakly and circulates; in cell tests, the ability of each isoform to neutralise myostatin and activin tracked its surface binding ^[3]. The gene therapy trials in people used FST344 precisely because the circulating FS-315 it produces has about ten-fold lower affinity for activin than FS-288, which the investigators hoped would spare the pituitary and reproductive system ^{[4] [7]}. The recombinant protein sold online is not delivered by a gene and does not stay in muscle; where an injected dose goes and how long it lasts has not been measured in any species.

Follistatin is also essential in development. Mice lacking the gene are growth-retarded, have thin diaphragms and intercostal muscles, skeletal and skin defects, and die within hours of birth, which shows that follistatin modulates several members of the TGF-beta family, not just myostatin ^[8].

The animal evidence for muscle growth comes almost entirely from gene delivery. Mice given a single injection of an adeno-associated virus (AAV) carrying follistatin or other myostatin inhibitors showed increased muscle mass and strength that lasted more than two years, even when treated in old age, in both normal and dystrophic animals ^[9]. When AAV1-FS344 was injected into the quadriceps of cynomolgus macaques, muscle size and strength increased markedly and durably, and long-term expression produced no abnormal changes in the structure or function of key organs ^[10]. Transgenic mice overexpressing follistatin in muscle had muscle mass increases comparable to myostatin knockouts ^[5], and viral delivery of FS-288 in mice increased muscle mass and force with higher protein synthesis ^[6].

These studies delivered the follistatin gene into muscle, where the protein was produced continuously and locally for months or years. They are the source of the follistatin 344 benefits described online, but they are not studies of injected protein, and no published animal study has tested whether injecting recombinant follistatin under the skin builds muscle.

A different line of human research concerns Fortetropin, a supplement made from fertilised egg yolk that is marketed as a myostatin reducer and often discussed alongside follistatin. In resistance-trained men, 12 weeks of 6.6 or 19.8 g a day increased lean mass by about 1.7 kg against 0.6 kg on placebo, with no difference in strength gains ^[11]; in older adults, 21 days increased the fractional synthesis rate of muscle proteins by about 18% ^[12]; and in young men with a leg immobilised, it prevented the rise in circulating myostatin but did not prevent muscle loss ^[13]. These are oral supplement trials, not follistatin injections, and they say nothing about follistatin 344 vials.

All human studies of follistatin have used gene therapy, injecting an AAV1 vector carrying the FST344 gene directly into muscle, under the direction of Jerry Mendell at Nationwide Children’s Hospital in Ohio. In the first, six men with Becker muscular dystrophy received bilateral injections into the quadriceps at 3 × 10¹¹ or 6 × 10¹¹ vector genomes per kilogram per leg. Over the following year, four of the six walked further on the six-minute walk test, by 58, 125, 108 and 29 metres, and two showed no change; biopsies showed less fibrosis and more normal fibre size, and no adverse effects were reported ^{[7] [4]}. The same programme then treated patients with sporadic inclusion body myositis, an inflammatory muscle disease of later life, with the higher dose, and reported improved functional outcomes ^[14]. Both cohorts are covered by the registry entry NCT01519349, listed as completed with 15 participants in total ^[15]. A further phase 1/2 study injected the vector into three boys with Duchenne muscular dystrophy between 2015 and 2017 and is listed as completed ^[16].

Three points limit what these follistatin gene therapy trials can tell a buyer of follistatin 344 vials. They were small, open-label studies in people with muscle disease, without placebo groups. They delivered a gene that made muscle cells produce their own follistatin for years, not a protein injected once. And they used the FST344 isoform specifically because it produces the circulating, lower-affinity FS-315, chosen to limit effects on the pituitary ^{[4] [7]}. None of this transfers to a recombinant protein of uncertain isoform injected under the skin.

We found no published trial, case series or pharmacokinetic study of injected follistatin protein in humans, and no registered trial of one. A 2026 review of peptides marketed in sports medicine listed FS-344 among unapproved compounds sold direct to patients and found rigorous human safety data scarce across the class ^[17].

Follistatin 344 vs ACE-031 is a comparison between two ways of removing myostatin. ACE-031 is an engineered decoy receptor, the outer part of the activin receptor IIB fused to an antibody Fc region, with a half-life of 10 to 15 days; it was given as an injected drug in trials, increased lean mass after a single dose in healthy women, and was abandoned after boys with Duchenne developed nosebleeds and dilated skin vessels. Follistatin is a natural binding protein, and its human data come from gene therapy rather than injection. Both bind activin as well as myostatin, which is why both are expected to have effects beyond muscle. Our ACE-031 guide covers that compound in detail, and the GDF-8 guide covers myostatin itself.

Compared with growth hormone-axis compounds, follistatin works on an entirely different pathway. HGH and IGF-1 LR3 push muscle growth forward through IGF-1 signalling; follistatin releases a brake. No study has combined them, so the forum idea that they are additive has no evidence behind it.

No dose of injected follistatin protein has been used in any published human study, so there is no follistatin 344 dosage to report. The gene therapy trials used 3 × 10¹¹ and 6 × 10¹¹ vector genomes per kilogram per leg, injected directly into the quadriceps under anaesthesia ^{[7] [14]}; these are doses of a virus, not of protein, and cannot be converted. In animals, follistatin was delivered by gene expression ^{[5] [6] [9] [10]}, and we found no animal study that injected recombinant follistatin protein to measure muscle growth.

The follistatin 344 dosage protocols found online, typically 100 µg a day for 10 days, are not derived from any study. Vials are usually labelled 1 mg. For the arithmetic only, 1 mg dissolved in 1 mL of bacteriostatic water gives 1 mg per mL, so each unit on a U-100 insulin syringe holds 10 µg; the peptide calculator and the follistatin 344 calculator page handle other volumes. These are calculations, not recommendations, and for this product the more important question is whether the vial contains follistatin at all.

Follistatin 344 is sold as a freeze-dried recombinant protein in 1 mg vials for subcutaneous injection. As a glycoprotein of about 315 amino acids in its mature form, it cannot be made by peptide synthesis and must be expressed in cells, and it would not survive oral use. The natural protein circulates as FS-315 at concentrations below 5 ng/mL in healthy adults ^[18].

What is actually in the vials has been examined. In 2019, anti-doping researchers in Austria tested 17 black-market products labelled follistatin 344 or 315. Only nine contained follistatin. All nine contained a His-tagged version, carrying a purification label used for laboratory reagents that the natural protein lacks, together with a high proportion of oligomers, and some of the other eight contained different growth-promoting peptides, including MGF and GHRP-2 ^[19]. The His-tag makes black-market follistatin easy to distinguish from the body’s own protein in a doping test ^[19].

There are no human safety data for injected follistatin protein. The gene therapy trials reported no adverse effects in Becker muscular dystrophy ^[7] and were designed with the FST344 isoform to reduce the risk that circulating follistatin would suppress FSH and disturb reproductive hormones ^{[4] [7]}. That risk is inherent to the protein: follistatin was discovered as an FSH-suppressing protein ^{[1] [2]}, and a recombinant product of unknown isoform injected systemically would be expected to reach the pituitary. No study has measured FSH, testosterone or fertility after follistatin injection in people.

Follistatin also neutralises activin and some bone morphogenetic proteins, which have roles in blood vessels, red blood cells, bone, skin and the reproductive system ^{[3] [8]}. The related decoy receptor ACE-031, which likewise removes activin signalling, caused nosebleeds and telangiectasias in a paediatric trial. Whether injected follistatin would do the same is unknown. The macaque gene therapy study found no organ abnormalities over long-term local expression ^[10], but that involved locally produced FS-315 rather than a systemic dose.

For products bought online the composition is the concrete risk. His-tagged, oligomerised recombinant protein from an unregulated source carries risks of immune reactions and contamination that are independent of follistatin’s pharmacology, and eight of 17 products contained no follistatin at all ^[19]. So whether follistatin 344 is safe has no evidence-based answer, and whether a given vial is even follistatin cannot be assumed.

Follistatin is not approved as a medicine anywhere, and the gene therapy remains experimental. In sport, WADA prohibits agents modifying myostatin function under section S4 of the Prohibited List, and anti-doping laboratories treat follistatin and follistatin-based proteins as prohibited at all times ^{[18] [19] [20]}. Detection methods exist for both the His-tagged black-market protein, by immunoprecipitation and Western blotting with a detection limit of about 0.1 ng/mL in urine ^[19], and for follistatin-Fc fusion proteins in serum ^[18]. Gene doping with follistatin is separately prohibited under section M3, and detection methods for a follistatin transgene have been developed in animals ^[21]. UK Anti-Doping applies the same list ^[22].

In the UK, follistatin has no marketing authorisation, and regulation 46 of the Human Medicines Regulations 2012 makes it an offence to sell or supply an unauthorised medicinal product ^[23]. It is not a controlled drug under the Misuse of Drugs Act 1971 ^[24]. See our UK legal status page, the US page and the legal status overview for other countries.

Follistatin is a glycoprotein and more fragile than a short synthetic peptide. Keep the freeze-dried vial cold, dry and dark, reconstitute gently without shaking, refrigerate after mixing and avoid repeated freezing and thawing, which encourages the aggregation and oligomer formation already seen in black-market products ^[19]. See how to store peptides.

PepFinder does not sell follistatin 344. You can compare follistatin 344 prices, including UK listings and US listings, and filter for third-party tested suppliers and published COAs.

For this product, the published finding is that fewer than half of black-market vials contained follistatin, and those that did contained a His-tagged laboratory version ^[19]. A useful certificate of analysis would show a protein of the right size on a gel, identify the isoform, state whether a His-tag is present, and report endotoxin and host-cell protein results; an HPLC purity figure alone cannot do any of this. Read how to read a COA, third-party peptide testing and how to spot a fake peptide supplier. If muscle growth is the aim, our peptides for muscle growth page compares follistatin with compounds that have at least been injected into people.