Follistatin

    aka
    • sh-Polypeptide-86

    TLDR glycoprotein that inhibits TGF-β and promotes hair growth by antagonizing activin

    Follistatin is a naturally occurring glycoprotein found in high concentrations in the skin that regulates cell growth. Its primary role is to bind to and neutralize members of the TGF-β superfamily, particularly activin, which are proteins that inhibit cell proliferation.

    The cosmetic ingredient sh-Polypeptide-86 is a bio-engineered version of human Follistatin. It is produced using the Nicotiana benthamiana plant as a "bioreactor" to create a protein designed to be identical to the human version, intended for use in hair and skin conditioning products.

    The Molecular Mechanism of Action in the Hair Cycle

    The hair follicle cycles through growth (anagen) and rest (telogen) phases. This cycle is controlled by various signaling proteins. Key members of the TGF-β family, like Activin and Bone Morphogenetic Proteins (BMPs), act as "stop" signals, keeping hair follicles dormant in the telogen phase.

    Follistatin's mechanism is to act as a powerful antagonist to these signals. It physically binds to Activin and BMPs, effectively removing them from the environment. This action releases the natural brake on the hair cycle, allowing dormant hair follicle stem cells to awaken and transition into the active anagen growth phase.

    Clinical Evidence in Alopecia

    The most significant clinical evidence for Follistatin comes from a double-blind, placebo-controlled Phase 1 trial of a formula called Hair Stimulating Complex (HSC). The study involved 26 men with androgenetic alopecia who received a single intradermal injection. The HSC formula contained Follistatin along with other growth factors like Vascular Endothelial Growth Factor (VEGF) and Keratinocyte Growth Factor (KGF).

    After 12 weeks, the HSC-treated group showed statistically significant increases in hair shaft thickness, terminal hair density, and overall thickness density compared to the placebo group. Positive effects on total hair count were still observed one year after the single injection. The treatment was very safe, with no adverse reactions reported. It is important to note that these results are from an injectable cocktail of ingredients, and there are currently no peer-reviewed clinical trials specifically for a topical formulation of sh-Polypeptide-86.

    Secondary Mechanisms for Scalp Health

    Beyond stimulating the hair cycle, Follistatin contributes to overall scalp health. It plays a role in regulating skin homeostasis and wound repair by modulating inflammation. This is relevant for many types of alopecia that are associated with chronic microinflammation and fibrosis around the follicle. By helping to create a healthier scalp environment, Follistatin can support the foundation needed for robust hair growth.

    Follistatin does not affect hormones or blood vessels directly; instead, it releases a natural brake on the hair cycle. Because these treatments target three distinct biological pathways, they are not mutually exclusive. Follistatin-based therapies could potentially be used in a synergistic combination with existing treatments for a more comprehensive approach.

    Safety and Future Directions

    The safety profile for Follistatin appears excellent. The clinical trial involving direct scalp injections showed no adverse events. For topical cosmetic use, peptides are generally considered safe.

    The primary challenge for any topical product containing sh-Polypeptide-86 is delivery. As a large protein, its ability to penetrate the skin barrier to reach the hair follicle is limited. Therefore, the effectiveness of a topical serum is highly dependent on its formulation and delivery system.

    Research

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