Follistatin (FST-344 / FS-344)

Structure: Follistatin is a single-chain glycosylated protein with three follistatin domains (FSD1-3) plus an N-terminal domain. The bodybuilding peptide market sells "Follistatin 344" (FST-344, the unprocessed gene-therapy precursor used in viral vector research) and less commonly "Follistatin 315" (FS-315, the mature circulating isoform). Both bind and inactivate myostatin and activin A.

Dosage (research / grey-market):

• Typical anecdotal: 100mcg/day SubQ for 10 days, repeat in cycles of 4 to 6 weeks
• Aggressive: 100 to 200mcg/day for 10 to 30 days
• No clinically validated dose; injection product purity from research suppliers is highly variable

Administration:

• SubQ injection, abdomen (systemic) or near target muscle (anecdotal localised effect, weak evidence)
• IM injection has been used by some, no clear advantage over SubQ given systemic action
• 27 to 30g insulin syringe
• Reconstitute with bacteriostatic water, store refrigerated, use within 30 days

Key Notes:

• Mechanism: binds and neutralises myostatin (GDF-8) and activin A, removing the brake on muscle growth. Myostatin null mutations in cattle, dogs, mice, and a single documented human child all produce dramatic hypertrophy.
• Strongest evidence is from gene-therapy follistatin trials in muscular dystrophy (sustained AAV-delivered follistatin), not from injected recombinant peptide. Whether short-acting injected FS-344 produces meaningful hypertrophy in healthy adults is poorly supported.
• Activin A blockade has off-target effects on inflammation, reproduction (FSH suppression possible), and possibly cardiac function. Long-term safety in healthy adults is unknown.
• Often stacked with AAS, GH, or IGF-1 LR3, which makes attribution of muscle gain to follistatin alone difficult in user reports.
• Cancer concerns: myostatin and activin A act as tumour suppressors in some tissues. Chronic systemic blockade is theoretically tumourigenic. Avoid in anyone with personal or family history of cancer.
• Not a substitute for adequate training, calories, or recovery. Underwhelming results are common at typical grey-market doses.
• Monitor: creatine kinase, lipid panel, blood pressure, liver enzymes (if stacking), IGF-1 (if stacking with GH or IGF-1 LR3), FSH and LH at baseline and post-cycle.

References:

• Lee, S. J., & McPherron, A. C. (2001). Regulation of myostatin activity and muscle growth. PNAS, 98(16), 9306-9311. DOI: 10.1073/pnas.151270098
• Mosher, D. S., Quignon, P., Bustamante, C. D., Sutter, N. B., Mellersh, C. S., Parker, H. G., & Ostrander, E. A. (2007). A mutation in the myostatin gene increases muscle mass and enhances racing performance in heterozygote dogs. PLoS Genetics, 3(5), e79. DOI: 10.1371/journal.pgen.0030079
• Hansen, J., Brandt, C., Nielsen, A. R., Hojman, P., Whitham, M., Febbraio, M. A., Pedersen, B. K., & Plomgaard, P. (2011). Exercise induces a marked increase in plasma follistatin: evidence that follistatin is a contraction-induced hepatokine. Endocrinology, 152(1), 164-171. DOI: 10.1210/en.2010-0867
• Mendell, J. R., Sahenk, Z., Al-Zaidy, S., Rodino-Klapac, L. R., Lowes, L. P., Alfano, L. N., et al. (2017). Follistatin gene therapy for sporadic inclusion body myositis improves functional outcomes. Molecular Therapy, 25(4), 870-879. DOI: 10.1016/j.ymthe.2017.02.015