ACE-031

ACE-031 is a soluble activin receptor type IIB (ActRIIB) fusion protein that functions as a potent myostatin inhibitor, promoting significant increases in lean muscle mass, bone mineral density, and reductions in fat mass. Originally developed by Acceleron Pharma for treating muscle-wasting conditions like Duchenne muscular dystrophy (DMD), ACE-031 has gained considerable interest among bodybuilders, athletes, and biohackers seeking enhanced muscle development beyond natural limits. Clinical trials demonstrated a 3.3% increase in total body lean mass and 5.1% increase in thigh muscle volume after a single dose in healthy subjects.https://pubmed.ncbi.nlm.nih.gov/23169607/ Typical dosages range from 0.5 to 3 mg/kg administered subcutaneously every 2-4 weeks, with noticeable effects emerging within 29 days of initial administration.

What Is ACE-031?

ACE-031 (also known as Ramatercept) is a recombinant fusion protein consisting of the extracellular domain of the human activin receptor type IIB (ActRIIB) linked to the Fc portion of human immunoglobulin G1 (IgG1).https://pubmed.ncbi.nlm.nih.gov/27462804/ This engineered protein acts as a "decoy receptor," intercepting and neutralizing myostatin and other members of the transforming growth factor-beta (TGF-β) superfamily before they can bind to their natural receptors on muscle tissue.

What makes ACE-031 unique among myostatin inhibitors is its broad-spectrum approach. Unlike agents that target myostatin exclusively, ACE-031 binds multiple negative regulators of muscle growth, including myostatin, activin A, activin B, and growth differentiation factor 11 (GDF-11).https://pmc.ncbi.nlm.nih.gov/articles/PMC2944638/ This multi-target mechanism potentially offers more comprehensive muscle-building effects than single-target approaches.

The primary human-use benefits observed in clinical research include:

• Increased lean body mass
• Enhanced thigh muscle volume
• Improved bone mineral density
• Reduced fat mass
• Potential maintenance of functional capacity (as measured by 6-minute walk tests)

How It Works

Myostatin Inhibition

Myostatin, also called growth differentiation factor 8 (GDF-8), is a protein that naturally limits muscle growth. It acts as a negative regulator, essentially putting a "brake" on muscle development. ACE-031 functions by binding to circulating myostatin in the bloodstream, preventing it from reaching muscle cell receptors.https://www.mda.org/quest/article/update-ace-031-clinical-trials-duchenne-md When myostatin is neutralized, the inhibitory signal is removed, allowing muscle fibers to grow beyond their normal genetic limits.

ActRIIB Receptor Decoy Mechanism

ACE-031 mimics the extracellular portion of the ActRIIB receptor, which normally binds TGF-β superfamily ligands on cell surfaces. By circulating freely in the bloodstream, ACE-031 intercepts these ligands before they can engage actual cell-surface receptors. This "ligand trap" approach effectively reduces the signaling that would otherwise suppress muscle protein synthesis and promote muscle catabolism.

Effects on Bone Metabolism

Beyond muscle tissue, ACE-031 demonstrates positive effects on bone metabolism. Clinical studies showed statistically significant changes in serum biomarkers associated with bone formation.https://pubmed.ncbi.nlm.nih.gov/23169607/ The compound appears to increase bone mineral density, which may be attributed to the inhibition of activins that negatively regulate bone formation.

Fat Metabolism Modulation

Research indicates ACE-031 influences adipose tissue metabolism, leading to reductions in fat mass. This effect likely results from the inhibition of activin signaling pathways that regulate adipogenesis and lipid storage. The combination of increased lean mass and decreased fat mass contributes to improved body composition.

Dosage Protocols

Clinical trials have evaluated ACE-031 across a range of doses, providing insight into effective dosing parameters:

Phase I Study in Healthy Women:
Doses ranged from 0.02 mg/kg to 3 mg/kg administered as a single subcutaneous injection. The 3 mg/kg dose produced statistically significant increases in lean mass and muscle volume at day 29.https://pubmed.ncbi.nlm.nih.gov/23169607/

Phase II Study in DMD Patients:
Doses of 0.5 mg/kg to 2.5 mg/kg were administered subcutaneously every 2-4 weeks.https://pubmed.ncbi.nlm.nih.gov/27462804/

Based on available clinical data, users in the research community typically follow protocols of:

• Starting dose: 0.5-1 mg/kg
• Maintenance dose: 1-3 mg/kg
• Frequency: Every 2-4 weeks (based on the 10-15 day half-life)
• Cycle length: 8-12 weeks, followed by an equal off-period

The extended half-life of 10-15 days allows for less frequent dosing compared to many other peptides.https://www.bioworld.com/articles/610791-ace-031-increases-lean-body-mass-and-muscle-volume-in-healthy-postmenopausal-women

Administration

ACE-031 is administered via subcutaneous injection. The compound is supplied as a lyophilized (freeze-dried) powder that requires reconstitution before use.

Injection Protocol:

1. Reconstitute the lyophilized powder with bacteriostatic water
2. Gently swirl (do not shake) until fully dissolved
3. Draw the appropriate dose into an insulin syringe
4. Inject subcutaneously into the abdominal area, thigh, or upper arm
5. Rotate injection sites to prevent lipodystrophy

The subcutaneous route was used in all clinical trials and provides consistent absorption with the documented pharmacokinetic profile.

Results Timeline

Based on clinical trial data and pharmacokinetic properties:

Week 1-2: ACE-031 reaches peak serum concentrations. Initial binding to myostatin and related ligands begins.

Week 3-4 (Day 29): Measurable increases in lean body mass (3.3%) and thigh muscle volume (5.1%) were documented in clinical trials at this timepoint.https://pubmed.ncbi.nlm.nih.gov/23169607/

Week 4-8: Continued accumulation of effects with repeated dosing. Trends toward improved functional capacity and further body composition changes.

Week 8-12: Maximum effects typically observed with consistent administration. Changes in bone mineral density markers become more pronounced.

Animal studies demonstrated significant increases in body weight and muscle mass after 14 weeks of administration.https://www.biorxiv.org/content/10.1101/2025.10.01.679778v1.full.pdf

Research Evidence

The clinical evidence for ACE-031 comes primarily from two key human trials:

Phase I Study (Attie et al., 2013):
A double-blind, placebo-controlled study in 48 healthy postmenopausal women evaluated single doses ranging from 0.02-3 mg/kg. Results showed ACE-031 was generally well-tolerated with linear pharmacokinetics. At the 3 mg/kg dose, statistically significant increases in total body lean mass (3.3%, P=0.03) and thigh muscle volume (5.1%, P=0.03) were observed at day 29. Serum biomarkers suggested improvements in bone and fat metabolism.https://pubmed.ncbi.nlm.nih.gov/23169607/

Phase II Study (Campbell et al., 2017):
A randomized, double-blind, placebo-controlled trial in ambulatory boys with Duchenne muscular dystrophy. ACE-031 was administered subcutaneously every 2-4 weeks. The study demonstrated trends for increased lean body mass, bone mineral density, and reduced fat mass. A trend for maintenance of 6-minute walk test distance was noted in ACE-031 groups compared to decline in placebo groups, though not statistically significant. The study was discontinued due to non-muscle-related adverse events (epistaxis and telangiectasias).https://pubmed.ncbi.nlm.nih.gov/27462804/

Preclinical Evidence:
Animal studies have consistently demonstrated that ACE-031 and related ActRIIB-Fc constructs produce significant increases in muscle mass across multiple species, including mice and non-human primates.https://pmc.ncbi.nlm.nih.gov/articles/PMC2944638/

Stacking

ACE-031 may be combined with other compounds to potentially enhance muscle-building effects, though such combinations have not been evaluated in clinical trials:

With Follistatin:
Both compounds inhibit myostatin through different mechanisms. Follistatin binds myostatin directly, while ACE-031 acts as a decoy receptor. Some users combine these for potentially synergistic myostatin inhibition.https://www.purepeptides.co.za/peptides/follistatin

With Growth Hormone Secretagogues:
Combinations with CJC-1295 and Ipamorelin may complement ACE-031's effects by stimulating growth hormone release, potentially enhancing overall anabolic signaling.

With BPC-157:
Some protocols include BPC-157 for its tissue-healing properties, potentially supporting recovery during intensive training periods.

It should be noted that stacking protocols are based on theoretical mechanisms and user reports rather than controlled clinical research.

Reconstitution, Storage & Prep

Storage of Lyophilized Powder:

• Store at -20°C for long-term stability (until expiration date)
• Protect from light and moisture
• Lyophilized form remains stable for extended periods when properly storedhttps://purepeptidesuk.com/product/ace-031-1mg/

Reconstitution:

1. Allow the vial to reach room temperature
2. Add bacteriostatic water slowly along the vial wall
3. Gently swirl until completely dissolved—do not shake vigorously
4. The solution should be clear and free of particulates

Storage of Reconstituted Solution:

• Store at 2-8°C (refrigerator)
• Use within 2-4 weeks of reconstitution
• For extended storage, -20°C is recommended for up to 1 month; -80°C for up to 6 monthshttps://www.medchemexpress.com/ace-031.html

Important Considerations:
Research has identified that black market ACE-031 products often contain His-tags (histidine tags used in manufacturing) and some products have been found to be mislabeled, containing follistatin instead.https://www.wada-ama.org/en/resources/scientific-research/administration-study-black-market-ace-031-ramatercept Source verification is critical.

Side Effects

Clinical trials identified several adverse events associated with ACE-031:

Common Side Effects:

• Injection site erythema (redness)
• Minor injection site reactions

Serious Safety Concerns (leading to trial discontinuation):

• Epistaxis (nosebleeds)
• Gingival bleeding (gum bleeding)
• Telangiectasias (dilated blood vessels visible on skin)

The Phase II DMD trial was halted after the second dosing regimen due to these vascular-related adverse events, which occurred at higher doses.https://pubmed.ncbi.nlm.nih.gov/27462804/ These effects were described as reversible upon discontinuation.

Potential Concerns:
The vascular side effects may be related to ACE-031's inhibition of activin receptor ligands involved in vascular homeostasis. The TGF-β superfamily plays important roles in blood vessel development and maintenance, and broad inhibition may disrupt these processes.

Risk Mitigation:

• Start with lower doses
• Monitor for signs of bleeding or vascular changes
• Discontinue use if telangiectasias or unexplained bleeding occurs
• Avoid use in individuals with bleeding disorders or vascular conditions

Legal Status & FDA

ACE-031 is not approved by the FDA for any indication. Clinical development was discontinued by Acceleron Pharma in May 2013 following safety concerns identified in Phase II trials.https://www.mda.org/quest/article/update-ace-031-clinical-trials-duchenne-md

In the United States, ACE-031 exists in a regulatory gray area:

• It is not a controlled substance
• It is not approved for human use
• It may be legally purchased for "research purposes only"
• Sale for human consumption is prohibited

No approved pharmaceutical ACE-031 products are currently available. Products sold online are manufactured by research chemical suppliers and peptide synthesis companies, not pharmaceutical manufacturers.

Sports & WADA Status

ACE-031 is explicitly prohibited by the World Anti-Doping Agency (WADA). It appears on the Prohibited List under Section S4.4 as a "Metabolic Modulator" and specifically as a "Decoy activin receptor."https://www.wada-ama.org/en/prohibited-list

The prohibition applies:

• In-competition
• Out-of-competition
• At all times for athletes subject to anti-doping regulations

WADA has conducted research on black market ACE-031 products to develop detection methods for anti-doping testing.https://www.wada-ama.org/en/resources/scientific-research/administration-study-black-market-ace-031-ramatercept Athletes should be aware that use of ACE-031 constitutes a doping violation regardless of whether it is detected.

Conclusion

ACE-031 represents one of the most promising approaches to myostatin inhibition studied in human clinical trials. The documented increases in lean body mass and muscle volume, combined with improvements in bone density and fat metabolism, demonstrate its potential as an anabolic agent. However, the emergence of vascular-related side effects during clinical development led to discontinuation of the program, leaving ACE-031 without regulatory approval.

For individuals who choose to use ACE-031 despite its unapproved status, understanding the clinical evidence, proper administration protocols, and potential risks is essential. The compound's long half-life allows for convenient dosing schedules, but the safety concerns that halted clinical trials warrant careful consideration and monitoring.

The future of myostatin inhibition as a therapeutic strategy remains active, with other compounds in development that may offer improved safety profiles while maintaining efficacy.

FAQ

What is the half-life of ACE-031?
ACE-031 has an average half-life of 10-15 days, allowing for dosing every 2-4 weeks rather than daily administration.https://www.bioworld.com/articles/610791-ace-031-increases-lean-body-mass-and-muscle-volume-in-healthy-postmenopausal-women

Why were ACE-031 clinical trials discontinued?
Clinical trials were halted in 2011 and officially discontinued in 2013 due to safety concerns including epistaxis (nosebleeds) and telangiectasias (dilated blood vessels) observed at higher doses in the Phase II DMD study.https://www.mda.org/quest/article/update-ace-031-clinical-trials-duchenne-md

How quickly does ACE-031 work?
Clinical studies demonstrated measurable increases in lean body mass (3.3%) and thigh muscle volume (5.1%) within 29 days of a single dose at 3 mg/kg.https://pubmed.ncbi.nlm.nih.gov/23169607/

Is ACE-031 the same as follistatin?
No. While both inhibit myostatin, they work through different mechanisms. ACE-031 is a decoy receptor that traps multiple TGF-β ligands, while follistatin is a binding protein that directly binds myostatin. Some black market products labeled as ACE-031 have been found to contain follistatin instead.https://www.wada-ama.org/en/resources-scientific-research/administration-study-black-market-ace-031-ramatercept

Can ACE-031 be used by athletes?
ACE-031 is prohibited by WADA both in-competition and out-of-competition. Its use constitutes a doping violation for athletes subject to anti-doping regulations.https://www.wada-ama.org/en/prohibited-list

What is the recommended dose of ACE-031?
Clinical trials used doses ranging from 0.02-3 mg/kg subcutaneously. The 3 mg/kg dose showed significant effects in healthy subjects, while doses of 0.5-2.5 mg/kg were used in the DMD trial administered every 2-4 weeks.

Does ACE-031 require cycling?
While no official cycling guidelines exist, users typically follow 8-12 week cycles based on the compound's pharmacokinetics and the need to monitor for adverse effects.

How should ACE-031 be stored after reconstitution?
Reconstituted ACE-031 should be stored at 2-8°C (refrigerator) and used within 2-4 weeks. For longer storage, -20°C is recommended for up to 1 month.https://www.medchemexpress.com/ace-031.html

References:

1. Attie KM, et al. A single ascending-dose study of muscle regulator ACE-031 in healthy volunteers. Muscle Nerve. 2013;47(3):416-423. https://pubmed.ncbi.nlm.nih.gov/23169607/
2. Campbell C, et al. Myostatin inhibitor ACE-031 treatment of ambulatory boys with Duchenne muscular dystrophy: Results of a randomized, placebo-controlled clinical trial. Muscle Nerve. 2017;55(4):458-464. https://pubmed.ncbi.nlm.nih.gov/27462804/
3. Cadena SM, et al. Administration of a soluble activin type IIB receptor promotes skeletal muscle growth independent of fiber type. J Appl Physiol. 2010;109(3):635-642. https://pmc.ncbi.nlm.nih.gov/articles/PMC2944638/
4. Muscular Dystrophy Association. UPDATE: ACE-031 Clinical Trials in Duchenne MD. 2013. https://www.mda.org/quest/article/update-ace-031-clinical-trials-duchenne-md
5. World Anti-Doping Agency. The Prohibited List. 2025. https://www.wada-ama.org/en/prohibited-list
6. World Anti-Doping Agency. Administration study of black market ACE-031 (Ramatercept). https://www.wada-ama.org/en/resources/scientific-research/administration-study-black-market-ace-031-ramatercept
7. ClinicalTrials.gov. Study of ACE-031 in Subjects With Duchenne Muscular Dystrophy. https://clinicaltrials.gov/study/NCT01099761
8. BioWorld. ACE-031 Increases Lean Body Mass And Muscle Volume In Healthy Postmenopausal Women. 2009. https://www.bioworld.com/articles/610791-ace-031-increases-lean-body-mass-and-muscle-volume-in-healthy-postmenopausal-women
9. MedChemExpress. ACE-031 Product Information. https://www.medchemexpress.com/ace-031.html
10. Neuromuscular Disorders Journal. A phase 2, randomized, placebo-controlled, multiple ascending-dose study of ACE-031 in boys with Duchenne muscular dystrophy. 2011. https://www.nmd-journal.com/article/S0960-8966(11)01163-1/fulltext