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ActiVin

Also known as: Activin, Activin E, Inhibin beta A (INHBA), Inhibin beta E (INHBE), Activin A

Overview

Activins are dimeric protein growth factors belonging to the transforming growth factor-beta (TGF-β) superfamily, naturally produced in various tissues like the liver, muscle, and adipose tissue. They play crucial roles in regulating diverse biological processes, including cell growth, differentiation, metabolism, and inflammation. Specifically, Activin A and Activin E are isoforms encoded by the INHBA and INHBE genes, respectively. Research primarily focuses on their involvement in muscle mass regulation, metabolic diseases such as diabetes and non-alcoholic fatty liver disease (NAFLD), and their potential as therapeutic targets for muscle wasting and metabolic disorders. Activins signal through activin receptors (ActRII) and downstream Smad2/3 pathways, influencing muscle growth, fat metabolism, and glucose homeostasis. It is important to note that activin itself is not a dietary supplement ingredient but a biologically active protein studied for its physiological modulation.

Benefits

Research, primarily in animal models, indicates several potential benefits associated with modulating activin pathways. Dual blockade of activin A and myostatin has been shown in preclinical studies (obese monkeys and mice) to prevent muscle loss and increase lean mass, even during GLP-1 receptor agonist treatment, while also improving metabolic parameters like HbA1c and lipid profiles. This suggests a strong potential for treating muscle wasting and metabolic disorders. Activin E, acting as a hepatokine, has demonstrated protective effects against hepatic steatosis in mouse models by suppressing adipose tissue lipolysis and reducing fatty acid influx into the liver, thereby preventing NAFLD. Furthermore, activin signaling influences mitochondrial function and fatty acid oxidation in muscle and fat tissues, which could lead to improved metabolic health. While these findings are promising, particularly for conditions like obesity, diabetes, and NAFLD, human data are currently limited and inconclusive regarding direct activin supplementation or its circulating levels.

How it works

Activins exert their effects by binding to specific activin type II receptors (ActRIIA and ActRIIB) on cell surfaces. This binding initiates a signaling cascade that primarily activates the Smad2/3 pathway. Once activated, Smad2/3 proteins translocate to the nucleus, where they regulate the expression of various genes involved in cellular processes. In the context of muscle and metabolism, this pathway influences gene expression related to muscle growth, adipose tissue metabolism, and inflammation. Activin signaling is known to suppress mitochondrial function and muscle growth, while its blockade can enhance these processes. Key molecular targets include activin receptors (ActRII), Smad2/3 transcription factors, and downstream metabolic genes like PGC1α, which is crucial for mitochondrial biogenesis. As a protein, activin is not orally bioavailable; therapeutic approaches involve modulating its receptors or gene expression rather than direct supplementation.

Side effects

The safety profile of activin as a direct supplement is not established, as it is not administered in this form. Safety data are primarily derived from experimental models and clinical trials investigating therapeutic blockade of activin/myostatin pathways. Potential risks associated with modulating activin signaling include interference with normal muscle and metabolic regulation, given its widespread physiological roles. Common side effects for direct activin administration are not well characterized. Drug interactions are largely unknown, but theoretical interactions could exist with medications affecting muscle metabolism or other components of the TGF-β signaling pathway. Contraindications are not established. Caution is advised in special populations, particularly those with existing muscle or metabolic disorders, as the long-term effects of altering activin pathways are still under investigation. Clinical trials for activin receptor blockers are ongoing, and their specific side effect profiles are being monitored.

Dosage

Dosing guidelines for activin as a dietary supplement are not applicable because activin is a protein involved in cellular signaling and is not available or used as an oral supplement. Therapeutic interventions, which typically involve monoclonal antibodies or receptor antagonists designed to block activin signaling, are currently in clinical development. The dosing for these investigational drugs is determined through rigorous clinical trials, considering factors such as the specific condition being treated, patient characteristics, and the pharmacokinetics of the therapeutic agent. These are not over-the-counter supplements and require medical supervision.

FAQs

Is activin used as a dietary supplement?

No, activin is a protein involved in cellular signaling and is not available or used as a dietary supplement. Its complex biological role makes it unsuitable for direct oral supplementation.

Can activin levels be modified by supplements?

There is no direct evidence to support that oral dietary supplements can effectively modify activin levels in the body. Activin is a protein, and its systemic levels are tightly regulated.

Are there activin-targeting drugs?

Yes, drugs that target activin receptors, such as bimagrumab, are currently in clinical development. These are being investigated for conditions like muscle wasting, not as supplements.

What is the relationship between activin and diabetes?

The association between activin and diabetes is ambiguous. Some studies show altered activin A levels in diabetes, but the causality and clinical relevance are not yet clear and require more research.

Research Sources

https://www.nature.com/articles/s41467-025-59485-9 – This preclinical study in obese monkeys and mice demonstrated that dual blockade of activin A and myostatin significantly increased lean mass, decreased fat mass, and improved metabolic parameters, including HbA1c and lipid profiles. The findings suggest a promising therapeutic strategy for muscle wasting and metabolic disorders, although human data are still needed.
https://www.nature.com/articles/s12276-025-01403-6 – This preclinical mouse study identified Activin E as a hepatokine that protects against hepatic steatosis. It works by suppressing adipose tissue lipolysis and reducing the influx of fatty acids into the liver, thereby preventing non-alcoholic fatty liver disease (NAFLD). The research provides mechanistic insights into Activin E's role in liver health.
https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2024.1414585/full – This systematic review analyzed 10 human studies on the association between plasma activin A and diabetes. It concluded that the association is ambiguous, with small sample sizes, cross-sectional data, and assay limitations hindering definitive conclusions. The review highlights the need for more robust human clinical trials.
https://pmc.ncbi.nlm.nih.gov/articles/PMC8905337/ – This review article synthesizes current knowledge on activin/myostatin signaling, explaining how it suppresses mitochondrial function and muscle growth. It discusses how blockade of this pathway can lead to improvements in muscle mass and overall metabolic health, providing a comprehensive overview of the underlying biological mechanisms.
https://onlinelibrary.wiley.com/doi/10.1111/ggi.14265 – This report describes a Phase II clinical trial for bimagrumab, an activin receptor blocker. The study showed that bimagrumab improved the 6-minute walk test in populations with impaired mobility, indicating its potential as a therapeutic agent for muscle-wasting conditions. Further published data are anticipated to fully assess its efficacy and safety.