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Fst1.8
Follistatin Research
Mostly mechanism / observational
17 peer-reviewed studies
What the evidence says
Mostly mechanism / observational
Most Follistatin studies are mechanism or observational rather than RCTs that measure a clinical effect — keep findings provisional.
Most evidence is from medium-quality randomised trials published 2001–2026.
Based on 17 studies · 5 RCTs
Confidence
Moderate confidence
By outcome
Lean body mass & muscle growthDramatic muscle hypertrophy in animals; no controlled human evidence for the injectable peptide and broad, poorly-characterised hormonal biology. · Not established (no human trials of the peptide)
Too few graded studies8 studies
Therapeutic & clinical
Too few graded studies6 studies
Muscle strength & powerDramatic muscle hypertrophy in animals; no controlled human evidence for the injectable peptide and broad, poorly-characterised hormonal biology. · Not established (no human trials of the peptide)
Too few graded studies2 studies
Safety profile
Too few graded studies1 study
Active research area
10 studies in the last 5 years
200120132026
1RCT2018
Glasser CE, Gartner MR, Wilson D, Miller B, Sherman ML, Attie KM · Muscle Nerve (2018)
No plain-language summary recorded for this citation — open the paper to read its abstract.
Zimber MP, Ziering C, Zeigler F, Hubka M, Mansbridge JN, Baumgartner M · J Drugs Dermatol (2011)
No plain-language summary recorded for this citation — open the paper to read its abstract.
3Review2026
In plain English: The framework is further strengthened by testable predictions concerning adaptive pulsatility, modality-specific signatures, source attribution, recovery quality, disease-specific decoding and the superiority of multi-marker panels over single-molecule readouts.
Mănescu DC et al. · Cells (2026)
The central argument is that myokine biology should be interpreted not as a catalog of isolated mediators, but as a dynamic adaptive code defined by signal amplitude, temporal pattern, molecular composition, delivery route and recipient-tissue sensitivity.
Its novelty is operational rather than nominal: it requires source confidence, temporal kinetics, co-signal context, delivery route and functional decoding to be evaluated together.
This framework may improve biomarker design, disease-specific exercise prescription and therapeutic strategies aimed at restoring adaptive muscle-organ communication.
In plain English: Despite heterogeneity in duration and sample size, findings support this combined approach as a promising and clinically applicable strategy to prevent and treat sarcopenia.
Cruz-Pierard S, Iñiguez-Jiménez S. · Biomolecules (2026)
Interventions combining resistance exercise three times per week at 60-80% of one-repetition maximum with daily protein supplementation of at least 15 g, mainly from dairy sources, showed synergistic effects.
Improvements were observed in inflammatory and anabolic biomarkers, with reductions in myostatin, activin, and IL-6, and increases in IGF-1, follistatin, and IL-10.
Functional outcomes included gains in muscle strength, fat-free mass, and muscle fiber cross-sectional area.
In plain English: This review discusses the latest discoveries concerning the role of the activin-follistatin system in renal development and pathophysiology and explores the potential therapeutic implications of targeting this system in the management of kidney diseases.
Nagayama I, Takei Y, Takahashi S, Okada M, Maeshima A. · Cytokine & growth factor reviews (2025)
Early studies reported that activins are involved in renal organogenesis, but subsequent research demonstrated that activins also play a significant role in kidney regeneration following injury.
The results of more recent studies suggest activins play roles in both inflammatory kidney diseases and renal fibrosis, conditions that often culminate in end-stage renal disease.
Given these findings, the inhibition of activin activity represents a promising therapeutic approach for treating a range of kidney disorders.
In plain English: Mechanistic insights from functional annotation reveal potential pathways for these associations, highlighting the potential utility of these genetic markers for optimizing training program design.
Cao W, Gu Z, Fu R, Chen Y, He Y, Yang R, Yang X, He Z. · Genes (2025)
Results : Baseline: In females only, the rs3797297 T allele was associated with higher muscle mass (β = 1.159, 95% confidence interval (CI): 0.202-2.116, P _adj = 0.034) and BMC (β = 0.127, 95% CI: 0.039-0.215, P _adj = 0.009), with the BMC effect significantly mediated by muscle mass.
Gene-Exercise Interaction: A significant interaction occurred exclusively in women undertaking hill climbing: the rs3797296 G allele was associated with attenuated muscle mass gains (β = -1.126 kg, 95% CI: -1.767 to -0.485, P _adj = 0.034).
Baseline follistatin correlated with body composition (stronger in males) and increased post-exercise (primarily in males, Hill/Running groups) but did not mediate SNP effects on exercise adaptation.
In plain English: Short-term liraglutide treatment reduces total and regional mass without altering relative body composition.
Gutierrez de Piñeres V, Ramirez-Cisneros A, Tamayo-Torres CS, Angelidi AM, Kavelidou M, Stefanakis K, Mantzoros CS. · Diabetes research and clinical practice (2026)
Absolute lean mass in the trunk and extremities decreased, whereas relative lean mass and fat-free mass percentages remained stable at treatment completion.
Absolute fat-free mass was slightly but significantly lower.
Conclusions Short-term liraglutide treatment reduces total and regional mass without altering relative body composition.
In plain English: In conclusion, activins B and AB, as well as the ratios of all activins to follistatin and of activin AB to FSTL3 increased with teriparatide treatment, possibly in a compensatory manner.
Anastasilakis AD, Polyzos SA, Makras P, Savvidis M, Mantzoros CS. · Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research (2024)
In conclusion, activins B and AB, as well as the ratios of all activins to follistatin and of activin AB to FSTL3 increased with teriparatide treatment, possibly in a compensatory manner.
Future studies are needed to study the potentially important role activins may play in bone biology and any associations with the effect of teriparatide on BMD.
In plain English: We appraise 15-PGDH inhibition, now in early clinical development, together with its counter-case, and propose a mass-matched trial design capable of separating the three.
Oh JH, Ku CR, Oh CM. · Ageing research reviews (2026)
Mapping every therapeutic class onto these axes shows that anabolic agents engage none of them, that classes engaging a quality axis engage exactly one, and that no sarcopenia programme has been designed around innervation or intramuscular lipid.
Two experiments make the innervation gap concrete: soluble activin receptor IIB failed to protect denervated muscle, and follistatin overexpression, added to voluntary exercise, rescued neither motor-unit loss nor neuromuscular junction transmission beyond exercise alone.
We appraise 15-PGDH inhibition, now in early clinical development, together with its counter-case, and propose a mass-matched trial design capable of separating the three.
In plain English: It was found that spexin, which provides metabolic homeostasis, and follistatin, which expresses the increase in muscle mass, increased with the implementation of a 12-week aerobic and resistance exercise program in elderly individuals, and these increases were found to be associated with each other.
Ayaz EY, Dincer B, Cinbaz G, Karacan E, Benli RK, Mete E, Bilgiç H, Mesci B. · Journal of cachexia, sarcopenia and muscle (2025)
Results The mean age of the 62 participants who completed the study (E n = 31, C n = 31) was 73.25 ± 6.44 years, and 62.9% were female.
A correlation was observed between the change in follistatin level and the change in spexin level (r = 0.438, p = 0.001).
A negative correlation was found between the amount of decrease in body fat mass and the decrease in spexin level (r = -0.380, p = 0.005).
In plain English: Further studies are needed to confirm this rhythm and clarify its clinical relevance.
Zilstorff DB, Sennels HP, Jørgensen HL, Wewer Albrechtsen NJ, Richter MM. · The Journal of clinical endocrinology and metabolism (2026)
Results Plasma follistatin showed a significant 24-hour rhythm (P < .001) with a relative amplitude of 18% around a rhythm adjusted average (mesor ± SD) of 873 ± 25 pg/mL, peaking at 11:50 Am.
ANOVA confirmed a significant effect of time, with morning and evening levels differing significantly.
Conclusion Plasma follistatin displayed a significant 24-hour rhythm in our cohort of 22 healthy young men.
In plain English: AAV-mediated FST delivery exhibited decreased obesity-induced inflammatory adipokines and cytokines systemically and in the joint synovial fluid.
In plain English: Binding of myostatin to Act RIIB could be inhibited by the activin-binding protein follistatin... Independent transgenic mouse lines for each construct exhibited dramatic increases in muscle mass comparable to those seen in myostatin knockout mice.
Lee SJ, McPherron AC. · Proc Natl Acad Sci U S A (2001)
Foundational mechanism: follistatin binds and blocks myostatin's interaction with the activin type IIB receptor
Transgenic mice expressing follistatin in muscle developed dramatic hypertrophy comparable to myostatin-knockout mice
Establishes follistatin as one of the most potent natural myostatin antagonists and a candidate muscle-growth agent
In plain English: Administration of a recombinant adeno-associated virus serotype 8 vector encoding follistatin, an inhibitor of myostatin, increased muscle mass and strength but only in Pompe mice that were treated before 10 months of age.
In plain English: Performance, annualized to a median 1-year change, improved +56.0 m/year for treated subjects compared to a decline of -25.8 m/year (p = 0.01) in untreated subjects.
Mendell JR, Sahenk Z, Al-Zaidy S, Rodino-Klapac LR, Lowes LP, Alfano LN, Berry K, Miller N, Yalvac M, Dvorchik I, Moore-Clingenpeel M, Flanigan KM, Church K, Shontz K, Curry C, Lewis S, McColly M, Hogan MJ, Kaspar BK. · Mol Ther (2017)
Second human follistatin GENE-therapy trial: rAAV1.CMV.huFS344 delivered to the quadriceps of six patients with sporadic inclusion-body myositis, with an exercise regimen
6-minute-walk improved +56.0 m/year in treated subjects versus -25.8 m/year in matched untreated subjects (p=0.01)
Four of six treated subjects improved 58-153 m; two were minimally improved; treatment effects included decreased fibrosis and improved regeneration
In plain English: AAV1.CMV.FS344 was delivered to six BMD patients by direct bilateral intramuscular quadriceps injections... Patients 01 and 02 improved 58 meters (m) and 125 m, respectively.
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. · Mol Ther (2015)
The closest human evidence — but it is GENE therapy, not injectable peptide: AAV1.CMV.FS344 (the follistatin gene) injected directly into the quadriceps of six men with Becker muscular dystrophy
Four of six patients improved on the 6-minute-walk test (29-125 m); two showed no change
Biopsies showed reduced endomysial fibrosis, reduced central nucleation, more normal fibre-size distribution and muscle hypertrophy, especially at the higher dose; no adverse effects reported