Follistatin 344 (FS344 / FST344)

Follistatin 344 is an endogenous glycoprotein with a molecular weight of approximately 38 kDa (CAS: 80449-31-6). The 344 designation refers to the full-length transcript that includes the 29-amino-acid signal peptide along with the mature 315-amino-acid protein (FS315). FS344 was selected for clinical gene therapy research because it has lower affinity for activins compared to the shorter FS288 isoform, reducing the risk of disrupting FSH signaling and reproductive function. The science behind follistatin is straightforward: myostatin is the body's primary brake on muscle growth. It signals through the ActRIIB receptor to activate the Smad2/3 pathway, which suppresses satellite cell proliferation and protein synthesis. Follistatin binds myostatin (and activin A) with near-irreversible affinity, physically preventing them from reaching their receptor. Remove the brake, and muscle grows. The preclinical evidence is strong. A 2008 PNAS study showed that single AAV-delivered FS344 produced over 20% sustained muscle mass increases in mice that lasted more than 2 years. FS344 outperformed all other myostatin inhibitors tested, including soluble ActRIIB and myostatin propeptide. The most significant human data comes from gene therapy trials. Mendell et al. (Molecular Therapy 2015, PMID: 25322757) conducted a Phase 1/2a trial injecting AAV1.CMV.FS344 directly into muscles of 6 patients with Becker muscular dystrophy. Patients showed 29-125 meter improvements on the 6-minute walk test, with histological evidence of reduced endomysial fibrosis, reduced central nucleation, and muscle fiber hypertrophy. However, there is a critical distinction: most human evidence comes from gene therapy delivery (sustained local expression), not subcutaneous peptide injection. Injectable FS344 peptide has a circulating half-life of only 2-4 hours, meaning daily injections provide pulsatile rather than sustained myostatin inhibition. Whether this pulsatile pattern achieves clinically meaningful muscle growth in humans is not well-established. The community-derived injection protocol uses 100-200 mcg/day for 10-30 day cycles, with 4-8 weeks off between cycles. Side effects are generally mild: injection site reactions, transient joint stiffness, and mild LDL cholesterol elevation in approximately one-third of users. A concerning report documented central serous chorioretinopathy (CSCR) in 11 bodybuilders using high-dose follistatin, with average recovery of 2.3 months. Reproductive effects are a real concern. Research has shown that myostatin-neutralizing antibodies reduced FSH by 75% within one week, which could significantly affect ovulation in women. This is particularly relevant for FS344 users of reproductive age. Follistatin's regulatory status is uncertain. It was placed on the FDA Category 2 restricted list, and while the February 2026 HHS announcement indicated many peptides would return to Category 1, follistatin's specific status has not been explicitly confirmed. It is not available through legal compounding pharmacies and is sold only as a research reagent.