Side-by-side · Research reference
ACE-031vsGlutathione
Side-by-side comparison across mechanism, dosage, evidence, side effects, administration, and stack synergies. Citations on every claim where available.
APhase 2HUMAN-REVIEWED10/44 cited
BHuman-MechanisticHUMAN-REVIEWED6/39 cited
ACE-031
ActRIIB-Fc Fusion · Phase 2 Halted
SQ · Weekly dosing investigated
Glutathione
Endogenous Tripeptide · Antioxidant
IV · Oral · Inhaled
01Mechanism of Action
Parameter
ACE-031
Glutathione
Primary target
Myostatin, GDF11, activin A — TGF-β superfamily ligands
Intracellular redox systems, glutathione peroxidase, glutathione transferase
Pathway
Soluble decoy receptor binds circulating myostatin/TGF-β ligands → prevents ActRIIB activation → SMAD2/3 pathway inhibition
Synthesized via glutamate-cysteine ligase (GCL) → γ-glutamylcysteine → glutathione synthetase (GS) → GSH
Downstream effect
Disinhibition of myogenic signaling, increased skeletal muscle mass and strength
Reduction of reactive oxygen species, conjugation of electrophiles, maintenance of cellular thiol-disulfide balance, GPX4 activation for lipid peroxide reduction
Feedback intact?
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Origin
Recombinant fusion protein: human ActRIIB extracellular domain + IgG1-Fc fragmentReichel 2025
Endogenous tripeptide; predominantly synthesized in liver, exported to extracellular space and tissuesTerrell 2025Hecht 2026
Antibody development
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02Dosage Protocols
Parameter
ACE-031
Glutathione
Clinical dosing
Weekly or biweekly SQ injections (exact doses undisclosed pre-halt)
Phase 2 DMD trial protocol not fully published.
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Black market products
Variable purity; 12/14 tested products contained target protein plus contaminantsReichel 2025
SDS-PAGE revealed multiple protein bands; quality control absent.Reichel 2025
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Evidence basis
Phase 2 trial discontinued — incomplete dataset
Animal mechanistic + human mechanistic
Half-life
Days to weeks (Fc-fusion typical kinetics)
IgG1-Fc domain confers extended circulation time.
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Duration investigated
12–24 weeks (trial cut short)
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Endogenous synthesis
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Hepatic synthesis ~10 g/day (basal rate)
Tissue-specific; demand-driven upregulation via Nrf2 signaling.
Exogenous oral
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250–1000 mg/day
Bioavailability limited; gastric hydrolysis reduces systemic uptake.
IV supplementation
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600–1200 mg (research protocols)
Used in clinical oxidative stress and hepatic detoxification studies.
Precursor strategy
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N-acetylcysteine (NAC) 600–1200 mg/day
Provides cysteine for endogenous GSH synthesis; bypasses GI degradation.
04Side Effects & Safety
Parameter
ACE-031
Glutathione
Epistaxis (nosebleeds)
Significant incidence in Phase 2 DMD trial — primary safety signal
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Telangiectasia
Dilated capillaries / spider veins observed
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Vascular abnormalities
Mechanism: ActRIIB/ALK1 pathway disruption affects vascular homeostasis
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Injection site reactions
Local erythema, induration (biologics class effect)
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Antibody development
Potential for anti-drug antibodies (Fc-fusion proteins); incidence not reported
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Black market contaminants
12/14 tested products contained multiple unidentified proteins alongside ACE-031Reichel 2025
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Oral supplementation
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GI discomfort, bloating (mild, dose-dependent)
IV administration
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Rare hypersensitivity, infusion site reaction
Inhalation
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Bronchospasm risk in asthma (rare)
Tumor metabolism
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Extracellular GSH catabolism supplies cysteine to tumors; theoretical concern in active malignancyHecht 2026
Absolute Contraindications
ACE-031
- ·History of vascular disorders (epistaxis, telangiectasia, HHT)
- ·Pregnancy (TGF-β pathway critical for fetal development)
- ·Active malignancy (myostatin inhibition may affect tumour growth)
- ·Use of non-pharmaceutical grade ACE-031 (contamination risk)Reichel 2025
Glutathione
—Relative Contraindications
ACE-031
- ·Coagulation disorders or anticoagulant use (epistaxis risk)
- ·Hereditary hemorrhagic telangiectasia (HHT) family history
- ·Cardiovascular disease (vascular remodeling effects unknown)
Glutathione
- ·Active malignancy (theoretical cysteine supply risk)Hecht 2026
- ·Severe asthma (inhaled formulations)
05Administration Protocol
Parameter
ACE-031
Glutathione
1. Pharmaceutical status
ACE-031 is not FDA-approved or commercially available. Phase 2 development was discontinued in 2011 due to safety concerns. Any ACE-031 on the black market is unregulated research chemical.
Capsule or liquid form, 250–1000 mg once daily. Take on empty stomach for improved absorption, though GI hydrolysis limits bioavailability. NAC precursor strategy often preferred.
2. Black market quality
12 of 14 tested black market ACE-031 products contained the target protein but also carried multiple unidentified protein contaminants detectable by SDS-PAGE. Two products contained no ACVR2B-immunoreactive material.Reichel 2025
Clinical protocols: 600–1200 mg slow infusion over 30–60 minutes. Used for acute oxidative stress, hepatic detoxification support. Administered in medical settings.
3. Detection in sport
ACE-031 is prohibited under WADA S4.3 (Myostatin Inhibitors). Gel electrophoresis and Western blotting using ACVR2B-specific antibodies can detect the ~58.4 kDa protein in biological samples.Reichel 2025
Nebulized GSH (research protocols). Monitor for bronchospasm in reactive airway patients. Used experimentally for pulmonary oxidative stress.
4. Clinical trial route
Phase 2 protocol used subcutaneous injections at weekly or biweekly intervals. Exact dosing protocols remain unpublished.
N-acetylcysteine (NAC) 600–1200 mg/day PO. Provides cysteine substrate for endogenous GSH synthesis. Bypasses gastric degradation, preferred for chronic supplementation.