Follistatin

Follistatin is a naturally occurring protein that blocks myostatin, the body's natural brake on muscle growth, plus a related protein called activin, and it's studied for building muscle. Animals genetically lacking myostatin develop far more muscle mass, which is the biology behind the interest in follistatin. It comes in several forms; research suppliers typically sell the FST-344 form. It's not FDA-approved for any use and is sold only as a research peptide. (ACE-031, a related but different compound, was discontinued after vascular side effects in a trial.)

Follistatin has been studied for muscle growth, since it blocks myostatin — and animals lacking myostatin develop much greater muscle mass. The strongest human evidence is a small Phase 1/2a gene-therapy trial in Becker muscular dystrophy, where 4 of 6 patients improved on a walking test with no serious adverse events — but that gene-therapy delivery differs fundamentally from the injected-protein form used by research communities, which has no controlled human trials. A theoretical concern is suppression of FSH and effects on fertility.

Not FDA-approved for any indication. Follistatin has been studied as a therapeutic in muscular dystrophy contexts via gene therapy delivery (Mendell 2015 Phase 1/2a trial in Becker muscular dystrophy demonstrated 4/6 patients with 6-minute walk test improvement after intramuscular AAV1.CMV.FS344 delivery, with no serious adverse events).[³] Recombinant follistatin protein for direct injection is not in any active FDA-recognized clinical-trial program. The closely-related Acceleron Pharma compound ACE-031 (decoy activin receptor IIB) advanced through Phase 2 in Duchenne muscular dystrophy but was discontinued after vascular adverse events (epistaxis, telangiectasia) — these vascular AEs are widely hypothesized to reflect broader inhibition of TGF-β superfamily ligands beyond myostatin (BMP9 in particular is discussed in this context, though the trial report itself does not establish a mechanism).[⁵] Follistatin available exclusively as a research peptide through unregulated research-peptide supply chains (typically as FST-344 lyophilized vials). Not DEA-scheduled. WADA-banned in regulated sport — explicitly named under Section S4.3 (Agents Preventing Activin Receptor IIB Activation) of the 2026 Prohibited List as a myostatin-binding protein.[⁶]

Follistatin is not FDA-approved, and its injected-protein form has not been studied in controlled human trials. It is banned in regulated sport (named on the WADA Prohibited List, S4.3, as a myostatin-binding protein). VialWise is a research and educational reference, not medical advice — consult a licensed professional.

⚠️ For research and educational purposes only. Follistatin is not approved by the FDA for any indication. The Acceleron Pharma compound ACE-031 (a decoy activin receptor; not follistatin itself but a related myostatin-pathway antagonist) was discontinued after vascular adverse events in a Duchenne muscular dystrophy Phase 2 trial, which the ClinicalTrials.gov record lists as TERMINATED (NCT01099761).[⁵] Follistatin is available exclusively as a research peptide through unregulated supply chains. Information in this entry is informational, not medical advice. Always confirm dose calculations with the in-app calculator and consult appropriate professional guidance before any protocol decisions.

⚠️ Precision matters at low doses. Follistatin is dosed in micrograms (mcg), not milligrams. Typical research-community doses ( per dose) at typical reconstitution concentrations ( vial / 1 mL BAC water =) produce small draws in the range on a U-100 syringe. Always verify draws against the in-app calculator. Same precision concern as BPC-157, GHK-cu, mt-II, igf-1 lr3, and the GHRP-class peptides.

⚠️ Three follistatin isoforms — FST-344, FST-315, FST-288 — have substantially different pharmacology. The research-community-supplied compound is FST-344. This is the load-bearing technical detail of follistatin biology: - FST-288 — the shortest isoform (288 amino acids); binds heparan sulfate proteoglycans on cell surfaces; tissue-localized action; highest affinity for activin A; rapid clearance from circulation. Not the research-community-supplied form. - FST-315 — the longest mature serum-circulating isoform (315 amino acids); reduced cell-surface affinity vs FST-288; systemic action; ~10-fold lower affinity for activin A than FST-288 (a desirable property for muscle-growth applications because it reduces FSH-suppression-related fertility concerns).[⁴] The serum-based form. - FST-344 — the precursor isoform (344 amino acids); undergoes post-translational cleavage in vivo to yield mature FST-315. The form supplied by research-peptide vendors and the form delivered in the Mendell gene-therapy clinical trials (AAV1.CMV.FS344).[³][⁴] Researchers obtaining "follistatin" or "FST-344" from research-peptide supply chains are receiving the precursor that becomes FST-315 in vivo. The clinical implication: the research-community-supplied FST-344 is the most-favorable isoform for muscle-growth applications because (a) it cleaves to FST-315 which has reduced activin affinity (lower FSH-suppression / fertility concern); and (b) FST-315 is serum-circulating (systemic action). The Mendell gene-therapy trials delivered AAV1.CMV.FS344 specifically to take advantage of these properties.[³][⁴]

⚠️ Activin pathway interaction is the load-bearing safety concern — both for fertility (FSH suppression) and for vascular effects (the Acceleron ACE-031 trial-termination story). Follistatin and the broader myostatin-pathway compound class share a fundamental safety challenge: - Activin A regulates pituitary FSH release. Follistatin binds and neutralizes activin A, which suppresses FSH secretion from pituitary gonadotrophs. Sustained follistatin exposure can suppress FSH and impair fertility — particularly in men where FSH is required for spermatogenesis. The FST-315 form (lower activin affinity than FST-288) is the most-favorable isoform for managing this concern. - The Acceleron ACE-031 trial-termination story. ACE-031 was a soluble activin receptor type IIB-Fc fusion protein (decoy receptor) that bound myostatin plus several structurally related TGF-β superfamily ligands (activin A, GDF-11, BMP-2, BMP-7). The Phase 2 trial in Duchenne muscular dystrophy boys was terminated after vascular adverse events emerged in the second dosing cohort: epistaxis (nosebleeds) and telangiectasias (small dilated blood vessels); the trial report names these two as the safety concerns that stopped the study.[⁵] The vascular AEs are commonly hypothesized to reflect broader inhibition of TGF-β superfamily ligands beyond myostatin — BMP9 (bone morphogenetic protein 9), which has a role in vascular homeostasis, is the most-discussed candidate — but the trial publication itself does not establish this mechanism. Acceleron discontinued ACE-031 development. Follistatin's mechanism is partially overlapping with ACE-031 — both compounds inhibit myostatin-pathway signaling, though follistatin's binding spectrum is more selective (myostatin + activins) than ACE-031's broader TGF-β superfamily inhibition. Whether the BMP9-related vascular AE concern applies to follistatin specifically at research-community doses is not characterized in published human data. Researchers should be aware of the class-level vascular safety signal that ended ACE-031 development.

⚠️ WADA-banned — explicitly named under Section S4.3 (Agents Preventing Activin Receptor IIB Activation) as a myostatin-binding protein. The 2026 WADA Prohibited List Section S4.3 names follistatin explicitly under the "Myostatin inhibitors" category, specifically as a "Myostatin-binding protein."[⁶] Verbatim from the canonical PDF, S4.3 lists *"Myostatin inhibitors such as: – Agents reducing or ablating myostatin expression – Myostatin-binding proteins (e.g. follistatin, myostatin propeptide) – Myostatin- or precursor-neutralizing antibodies (e.g. apitegromab, domagrozumab, landogrozumab, stamulumab)"*. The S4.3 section also lists ACE-031 ("decoy activin receptors") and bimagrumab ("anti-activin receptor IIB antibodies"). Per the S4 section header, S4.3 substances are non-Specified Substances — distinct from S4.1 and S4.2 substances which are Specified Substances. Non-Specified Substance status carries a stricter sanction range under WADA's framework than the SERMs (Tamoxifen, Clomiphene/Enclomiphene — S4.2 Specified) and AIs (Anastrozole — S4.1 Specified) that comprise the rest of the S4 cluster in the library. First S4.3 entry in the library — opens the myostatin-pathway WADA cluster.

According to PubMed-indexed research, follistatin is an endogenous secreted glycoprotein that binds and neutralizes members of the TGF-β superfamily — most importantly myostatin (GDF-8) and activin A. The compound was first identified in ovarian follicular fluid as an inhibitor of FSH-stimulated steroidogenesis (hence "follistatin"). Its broader role as a master regulator of TGF-β superfamily signaling — and particularly its role as a myostatin antagonist — is the basis for its therapeutic and research-community interest.

The myostatin pathway — the foundational evidence base. Per PubMed, McPherron, Lawler, and Lee published the foundational discovery paper in *Nature* in 1997 ([DOI](https://doi.org/10.1038/387083a0)) characterizing GDF-8 (later renamed myostatin) as "a new TGF-beta superfamily member" expressed specifically in skeletal muscle. GDF-8 null mice showed a 2–3-fold increase in skeletal muscle mass via a combination of muscle cell hyperplasia and hypertrophy — establishing GDF-8 / myostatin as a negative regulator of skeletal muscle growth.[¹] This finding triggered an entire field of myostatin-pathway pharmaceutical development. The phenotype is shared across species: myostatin null mutations produce massive muscle hypertrophy in cattle (Belgian Blue, Piedmontese), dogs (whippets), and humans (rare cases). The Schuelke 2004 *NEJM* case report ([DOI](https://doi.org/10.1056/NEJMoa040933)) described a German child with a myostatin loss-of-function mutation showing extreme muscle hypertrophy from infancy[²] — the human equivalent of the McPherron mouse phenotype.

Mechanism. Follistatin acts as an extracellular scavenger of myostatin (GDF-8) and activin A — binding both ligands directly and preventing their interaction with the activin receptor type IIB (ActRIIB) on muscle cells. By neutralizing myostatin (a negative regulator of muscle growth), follistatin removes the inhibitory signal and permits muscle hypertrophy and hyperplasia. The myostatin-binding affinity defines the muscle-growth effect; the activin-binding affinity defines the FSH-suppression / fertility-related side effect spectrum. The three follistatin isoforms have substantially different activin affinities (FST-288 highest, FST-315 ~10-fold lower, FST-344 cleaves to FST-315 in vivo) — the basis for the research-community preference for FST-344 / FST-315 over FST-288 for muscle-growth applications.

Isoform pharmacology — the load-bearing technical detail. Per PubMed, the three principal follistatin isoforms differ as follows:[⁴] - FST-288: shortest mature isoform (288 amino acids); binds heparan sulfate proteoglycans on cell surfaces; tissue-localized action; rapid clearance from circulation; highest activin affinity. Not the research-community-supplied form. - FST-315: longest mature serum-circulating isoform (315 amino acids); reduced cell-surface affinity; systemic action; ~10-fold lower activin affinity than FST-288. The form that produces the muscle-growth effect with relatively reduced FSH-suppression concern. - FST-344: precursor isoform (344 amino acids); undergoes post-translational cleavage in vivo to yield mature FST-315. The form supplied by research-peptide vendors and delivered in the Mendell gene-therapy clinical trials (AAV1.CMV.FS344).[³][⁴]

Mendell follistatin gene-therapy clinical trial program (the strongest published clinical evidence for follistatin in humans). Per PubMed, Mendell et al. published the Phase 1/2a gene-therapy trial in *Molecular Therapy* in 2015 ([DOI](https://doi.org/10.1038/mt.2014.200)).[³] Six Becker muscular dystrophy patients received AAV1.CMV.FS344 by direct bilateral intramuscular quadriceps injection at 3 × 10¹¹ vg/kg/leg (Cohort 1, n=3) or 6 × 10¹¹ vg/kg/leg (Cohort 2, n=3). 6-minute walk test (6MWT) results: Patient 01 +58m; Patient 02 +125m; Patient 03 no change; Patient 04 no improvement; Patient 05 +108m; Patient 06 +29m. Four of six patients improved; no serious adverse events. Histology showed reduced endomysial fibrosis, reduced central nucleation, and muscle hypertrophy especially at high dose. The Al-Zaidy 2015 follow-up review in *Journal of Neuromuscular Diseases* synthesized the BMD gene-therapy results, reporting a ~11.5% average 6MWT improvement at six months post-gene-therapy.[⁴] This is the only published clinical-trial evidence for follistatin's effects on human muscle function — and the gene-therapy delivery route is fundamentally different from the research-community recombinant-protein direct-injection route.

The Acceleron ACE-031 trial-termination cautionary tale. Per PubMed, Campbell et al. published the ACE-031 Phase 2 DMD trial in *Muscle & Nerve* in 2017 ([DOI](https://doi.org/10.1002/mus.25268)).[⁵] ACE-031 (a soluble activin receptor type IIB-Fc fusion protein; decoy receptor) was administered subcutaneously every 2-4 weeks to ambulatory boys with Duchenne muscular dystrophy in a randomized, double-blind, placebo-controlled, ascending-dose trial. Trends for maintenance of 6MWT distance vs placebo decline; trends for increased lean body mass and bone mineral density; reduced fat mass. However, the study was stopped after the second dosing regimen due to potential safety concerns of epistaxis and telangiectasias. The broader-TGF-β-inhibition explanation for these vascular events (BMP9 in particular) is a hypothesis discussed in the field, not a finding of the trial report itself. Acceleron discontinued ACE-031 development. This story is the most-cited cautionary safety example in the broader myostatin-pathway compound class.

Current follistatin gene-therapy landscape (ClinicalTrials.gov, checked 2026-07-18). Follistatin gene-therapy research is ongoing, and it is worth separating from the recombinant-protein injection route this entry mostly describes. The Mendell BMD program is registered as [NCT01519349](https://clinicaltrials.gov/study/NCT01519349) (rAAV1.CMV.huFollistatin344 in Becker MD and sporadic inclusion-body myositis, Phase 1, COMPLETED), with a companion Duchenne study [NCT02354781](https://clinicaltrials.gov/study/NCT02354781) (Phase 1/2, COMPLETED, n=3). Separately, a 43-subject healthy-volunteer FST344 plasmid study run by Minicircle, [NCT06411366](https://clinicaltrials.gov/study/NCT06411366) (Phase 1, COMPLETED, primary completion 2023), has no posted results; a follistatin-plus-klotho plasmid study [NCT07285629](https://clinicaltrials.gov/study/NCT07285629) (Early Phase 1) and an AAV9-follistatin trial for age-related muscle decline [NCT07443826](https://clinicaltrials.gov/study/NCT07443826) (Phase 1/2, start 2026-06-01) are listed as recruiting. All of these deliver a follistatin-expressing gene vector — a fundamentally different intervention from the recombinant-protein subcutaneous injection used in research-community contexts, which still has no controlled human trials. None of the newer registrations has posted efficacy results.

Regulatory status (US — current). Follistatin is not FDA-approved for any indication. Mendell's gene-therapy trial program advanced to Phase 1/2a in BMD but has not progressed to Phase 3 or NDA submission. Recombinant follistatin protein for direct injection is not in any active FDA-recognized clinical-trial program. Follistatin is available exclusively as a research peptide through unregulated research-peptide supply chains — typically supplied as FST-344 lyophilized vials. Not legally compoundable through US 503A pharmacies. Not DEA-scheduled.

Regulatory status (sport — WADA). Follistatin is explicitly named under Section S4.3 (Agents Preventing Activin Receptor IIB Activation) of the 2026 WADA Prohibited List as a myostatin-binding protein.[⁶] Note the important S4.3 framework distinction: per the S4 section header, S4.3 substances are NON-Specified Substances (distinct from S4.1 and S4.2 substances which are Specified). Non-Specified Substance status carries a stricter sanction range under WADA's framework — meaning a positive test for follistatin triggers a more substantial penalty than a positive test for tamoxifen or anastrozole. First S4.3 entry in the library — opens the myostatin-pathway WADA cluster (which also includes ACE-031, bimagrumab, and the various myostatin-neutralizing antibodies apitegromab, domagrozumab, landogrozumab, stamulumab).

Common research interests. Despite the regulatory status and the activin-pathway / vascular-AE concerns, follistatin (typically supplied as FST-344) is used in research-community contexts for: - Muscle hypertrophy / body composition — the dominant research-community use case. Direct subcutaneous protein injection per dose, daily for 10–30 day cycles, 1–3 times per year with extended off-periods. - Athletic recovery — sometimes used during post-injury recovery cycles for accelerated muscle-mass restoration; mechanistically plausible but not validated in published human trials at the recombinant-protein direct-injection route. - Adjunct in research-community AAS / GH-axis cycles — sometimes added to multi-compound stacks for additive muscle-growth effect; no published evidence of synergistic or contraindicated effects with these other compound classes.

Commonly reported

• No serious adverse events in the 6-patient cohort across both dosing arms
• Histological changes consistent with intended effect: reduced endomysial fibrosis, reduced central nucleation, normal fiber size distribution with muscle hypertrophy
• Direct comparison to recombinant-protein direct-injection in research-community use is not possible
• Injection site reactions (typical of subcutaneous protein injection)
• Subjective muscle hypertrophy and recovery acceleration (the intended effect)
• No consistent serious adverse event pattern reported in research-community materials at typical dosing
• Activin-pathway interaction → FSH suppression → fertility impairment — the most-cited theoretical concern. The FST-344 / FST-315 isoform's reduced activin affinity (vs FST-288) partially mitigates this concern but does not eliminate it. FSH monitoring during cycles is appropriate; researchers planning conception should pause follistatin use well in advance of conception attempts.
• Vascular adverse events (the ACE-031 trial-termination story)[⁵] — the ACE-031 vascular AEs (epistaxis, telangiectasias) are hypothesized to reflect broader TGF-β superfamily inhibition than myostatin alone (BMP9 is the most-discussed candidate; the trial report does not establish it). Follistatin's binding spectrum is more selective than ACE-031's, but the class-level vascular safety signal remains a theoretical concern. Researchers should monitor for unusual bleeding (nosebleeds, gum bleeding) and discontinue if symptoms develop.
• Long-term safety in adults using follistatin off-label is not characterized in published literature. No multi-year human safety dataset exists for the recombinant-protein direct-injection route.
• Tumor-growth concerns — myostatin-pathway inhibition theoretically supports tissue growth across all cell types; theoretical concern in any context with active or undiagnosed malignancy.

Active fertility goals or planned conception — activin-pathway → FSH-suppression concern; pause use well in advance

Active malignancy or known myostatin-pathway-sensitive tumors — theoretical contraindication

History of unusual bleeding or vascular fragility — theoretical concern based on ACE-031 trial-termination story

Pregnancy and lactation — no human data; default to contraindicated

Pediatric use — no off-label data; gene-therapy clinical trials only

Concurrent other myostatin-pathway inhibitors — additive risk concerns

Regulatory note (US): Follistatin is not FDA-approved for any indication and is not legally compoundable through US 503A pharmacies.

Regulatory note (sport): WADA-banned under Section S4.3 of the 2026 Prohibited List; non-Specified Substance status carries a stricter sanction range than the SERMs (S4.2) and AIs (S4.1) elsewhere in the library.[⁶]

Not DEA-scheduled.

Protein

A larger molecule made of one or more long amino-acid chains; bigger than a peptide.

Myostatin

A natural protein that acts as a brake on muscle growth; blocking it can increase muscle mass.

Activin

A signaling protein in the TGF-β family; activin A also helps regulate the pituitary hormone FSH, which is why drugs that block it can affect fertility.

Subcutaneous

An injection into the fatty layer just under the skin, rather than into a muscle or vein.

WADA Prohibited List

The list of substances banned in regulated sport by the World Anti-Doping Agency.

1. McPherron AC, Lawler AM, Lee SJ. (1997). Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member. Nature, 387(6628):83–90 (May 1, 1997).(PMID 9139826)
2. Schuelke M, Wagner KR, Stolz LE, Hübner C, Riebel T, Kömen W, Braun T, Tobin JF, Lee SJ. (2004). Myostatin mutation associated with gross muscle hypertrophy in a child. New England Journal of Medicine, 350(26):2682–2688 (June 24, 2004).(PMID 15215484)
3. Mendell JR, Sahenk Z, Malik V, Gomez AM, Flanigan KM, Lowes LP, Alfano LN, Berry K, Meadows E, Lewis S, Braun L, Shontz K, Rouhana M, Clark KR, Rosales XQ, Al-Zaidy S, Govoni A, Rodino-Klapac LR, Hogan MJ, Kaspar BK. (2015). A phase 1/2a follistatin gene therapy trial for becker muscular dystrophy. Molecular Therapy, 23(1):192–201 (October 17, 2014 epub; January 2015 print).(PMID 25322757 · NCT01519349)
4. 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 (September 2, 2015).(PMID 27858738)
5. Campbell C, McMillan HJ, Mah JK, Tarnopolsky M, Selby K, McClure T, Wilson DM, Sherman ML, Escolar D, Attie KM. (2017). Myostatin inhibitor ACE-031 treatment of ambulatory boys with Duchenne muscular dystrophy: Results of a randomized, placebo-controlled clinical trial. Muscle & Nerve, 55(4):458–464 (April 2017).(PMID 27462804)
6. World Anti-Doping Agency. The 2026 Prohibited List, International Standard (effective 1 January 2026). Canonical PDF: wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf (linked from the WADA landing page; local archival copy in `docs/legal/wada-2026-prohibited-list.pdf`). Follistatin is named explicitly under Section S4.3 (Agents Preventing Activin Receptor IIB Activation) — page 8 of the canonical PDF — as a myostatin-binding protein. Verbatim from the canonical PDF, S4.3 lists "Myostatin inhibitors such as: – Agents reducing or ablating myostatin expression – Myostatin-binding proteins (e.g. follistatin, myostatin propeptide) – Myostatin- or precursor-neutralizing antibodies (e.g. apitegromab, domagrozumab, landogrozumab, stamulumab)". The S4.3 section also lists "Activin A-neutralizing antibodies", "Activin receptor IIB competitors such as: – Decoy activin receptors (e.g. ACE-031)", and "Anti-activin receptor IIB antibodies (e.g. bimagrumab)". Per the S4 section header, S4.3 substances are NON-Specified Substances — distinct from S4.1 and S4.2 substances which are Specified. Prohibited at all times.

• BPC-157 / TB-500 Blend — discussed together in this entry's stacks section
• Adipotide — same mechanism class
• FOXO4-DRI — same mechanism class
• PNC-27 — same mechanism class
• Tesofensine — same mechanism class
• ACE-031 — shared research area