Side-by-side · Research reference
Follistatin-344vsPE 22-28
Side-by-side comparison across mechanism, dosage, evidence, side effects, administration, and stack synergies. Citations on every claim where available.
AHuman-MechanisticHUMAN-REVIEWED4/58 cited
BAnimal-StrongHUMAN-REVIEWED16/47 cited
Follistatin-344
Myostatin/Activin Antagonist · Research Use
15–25%FST/MSTN ratio ↑
344 AACirculating isoform
ResearchPhase status
Research · No approved protocol
PE 22-28
TREK-1 Antagonist · Pre-Clinical
IP · SQ · Once Daily (animal models)Djillani 2017Pietri 2019
01Mechanism of Action
Parameter
Follistatin-344
PE 22-28
Primary target
Myostatin (MSTN/GDF-8) and Activin A
TREK-1 two-pore-domain potassium channelDjillani 2017Ma 2020
Pathway
FST-344 binds MSTN/Activin → prevents ActRIIB receptor engagement → disinhibits muscle anabolism
TREK-1 channel blockade → Neuronal membrane depolarisation → Enhanced hippocampal excitability → Increased neuroplasticity
Downstream effect
Elevated follistatin/myostatin ratio, increased muscle protein synthesis, attenuated muscle atrophy signalingJeong 2026
Antidepressant-like activity in forced swim test and tail suspension test; reduced A1-like reactive astrocyte activation; neuroprotection via NF-κB pathway modulationDjillani 2017Cong 2023Wu 2021
Feedback intact?
Yes — indirect antagonist, preserves endogenous regulation
N/A — direct ion channel blockade; not receptor-mediated endocrine axis
Origin
Endogenous glycoprotein, 344-AA isoform lacking heparin-binding domain (vs FST-315)
Synthetic truncation of spadin (PE 12-28), itself derived from the sortilin propeptide C-terminus. Residues 22-28: Val-Val-Arg-Gly-Trp-Leu-Arg.Djillani 2017Mazella 2018
Antibody development
Not documented in available trials (endogenous protein)
Not reported in animal studies
02Dosage Protocols
Parameter
Follistatin-344
PE 22-28
Clinical protocol
None — no approved dosing regimen
Follistatin-344 measured as endogenous biomarker, not administered exogenously in cited trials.
—
Research context
Endogenous modulation via exercise + nutrition
Resistance training + EAA intake elevated FST/MSTN ratio by 15–25% in 12-week RCT (older women).
—
Evidence basis
Human observational / biomarker studies
Multiple rodent RCTs; behavioral + electrophysiology endpointsDjillani 2017Qi 2018Wu 2021
Half-life
Not established
Circulating isoform; lacks tissue-binding domain of FST-315.
—
Animal dose (antidepressant)
—
0.3–3 µg/kg IP
Effective in forced swim test, tail suspension test, CUMS models.
Animal dose (neuroprotection)
—
0.03 µg/kg IPPietri 2019
Low-dose TREK-1 activation post-stroke for 7 days, then high-dose blockade.
Frequency
—
Once daily
Sustained antidepressant effect over 7+ days.
Onset (animal)
—
Within hours (acute); full effect 4–7 days
Comparison to fluoxetine
—
PE 22-28 outperforms fluoxetine in CUMS-sensitive rats by day 7
Chronic administration shows superior long-term efficacy.
Human equivalent (extrapolated)
—
Not established — no clinical trials
Allometric scaling from rodent data unavailable.
03Metabolic / Fat Loss Evidence
Parameter
Follistatin-344
PE 22-28
Primary target
Muscle mass preservation, not direct lipolysis
—
Indirect fat effect
Increased lean mass → elevated resting metabolic rate
Not primary mechanism. Muscle-sparing during deficit.
—
Clinical evidence
Lorcaserin trial (6 mo) showed no MAFI axis changes during fat lossRamirez-Cisneros 2026
Suggests follistatin not primary driver of fat loss in weight-reduction interventions.
—
GLP-1RA studies
Liraglutide (35 days) — no significant MAFI axis modulation despite fat/lean changes
—
04Side Effects & Safety
Parameter
Follistatin-344
PE 22-28
Clinical safety data
None — no human exogenous administration trials in literature
—
Theoretical risks
Excessive myostatin inhibition → muscle overgrowth, impaired glucose tolerance
Based on myostatin-null animal models and clinical myostatin inhibitor trials.
—
Endogenous elevation (exercise)
No adverse effects reported in 12-week resistance + EAA trials
—
Cancer risk (theoretical)
Myostatin inhibition may promote tumor growth in malignancy (preclinical data)
—
Regulatory status
Not approved for human use — research peptide only
—
Toxicity (animal)
—
No adverse effects reported at therapeutic doses
Cardiovascular (theoretical)
—
TREK-1 expressed in cardiac tissue; arrhythmia risk unclear
Weight change
—
Not reported in animal studies
Neurological
—
No seizures or behavioral abnormalities noted
Long-term safety
—
Unknown — longest animal study 28 days
Absolute Contraindications
Follistatin-344
- ·Active malignancy
- ·No approved protocol — research use only
PE 22-28
- ·Human use — no clinical safety data available
Relative Contraindications
Follistatin-344
- ·Insulin resistance / Type 2 diabetes (monitor glucose)
- ·Pregnancy / lactation (unknown safety profile)
PE 22-28
- ·Cardiac arrhythmia or channelopathy (theoretical TREK-1 cardiac role)
05Administration Protocol
Parameter
Follistatin-344
PE 22-28
1. Regulatory status
Follistatin-344 is not approved for human administration. All cited studies measure endogenous serum follistatin as a biomarker, not as an exogenous therapeutic agent.
Dissolved in sterile saline or vehicle. Intraperitoneal injection, 0.3–3 µg/kg body weight. Once daily administration in rodent behavioral studies.
2. Endogenous modulation
Resistance exercise combined with essential amino acid (EAA) supplementation elevated the follistatin/myostatin ratio by 15–25% in 12-week randomized trials. Protein intake (1.2–1.5 g/kg/day) synergizes with training to upregulate endogenous follistatin.
Shorter peptide length (7 AA) confers improved plasma stability vs 17-AA spadin. Exact storage conditions not detailed in published protocols.Djillani 2017
3. Measurement context
Serum follistatin and follistatin/myostatin ratio are used diagnostically in sarcopenia screening and as biomarkers of muscle anabolic balance in clinical trials.
Enhanced CNS bioavailability vs full spadin, likely due to smaller size. Mechanism (passive diffusion vs active transport) not fully characterized.
4. Research consideration
Gene therapy and recombinant follistatin delivery are under preclinical investigation for muscular dystrophy and sarcopenia. No human safety or efficacy data for exogenous FST-344 administration.
Not established — peptide synthesis methods for research use only. No pharmaceutical-grade formulation available.
06Stack Synergy
Follistatin-344
+ BPC-157
Multi-pathwayFollistatin-344 (myostatin antagonist) and BPC-157 (tissue repair peptide) address complementary pathways in muscle recovery. FST-344 promotes muscle protein synthesis by disinhibiting myostatin signaling, while BPC-157 accelerates healing of tendons, ligaments, and microtears via angiogenesis and collagen synthesis. Combined, they may support both hypertrophy and structural repair during high-volume training or injury recovery.
- Follistatin-344
- No approved protocol — endogenous modulation via resistance exercise + EAA
- BPC-157
- 250–500 mcg SQ · twice daily · near injury site or systemic
- Duration
- 4–8 weeks
- Primary benefit
- Muscle hypertrophy + accelerated soft tissue repair
+ TB-500
ModerateTB-500 (thymosin beta-4 fragment) promotes cell migration, angiogenesis, and anti-inflammatory signaling in muscle and connective tissue. Follistatin-344's anabolic signaling may synergize with TB-500's regenerative effects during muscle damage or overtraining, particularly in older adults where both myostatin inhibition and tissue repair are rate-limiting.
- Follistatin-344
- Endogenous upregulation (resistance training + protein)
- TB-500
- 2–5 mg SQ · twice weekly · loading phase 4 weeks, then maintenance
- Frequency
- Twice weekly TB-500, daily training stimulus for FST
- Primary benefit
- Enhanced recovery, reduced inflammation, muscle growth support
PE 22-28
— no documented stacks