Synthetic Human Follistatin
Recombinant Follistatin Peptide
Follistatin
sh-Polypeptide-86

---
canonical_name: Sh-Polypeptide-86
alternate_names: Synthetic Human Follistatin, Recombinant Follistatin Peptide, Follistatin, sh-Polypeptide-86
canonical_topic: Sh-Polypeptide-86 for Hair Regrowth
short_topic_lc: sh_polypeptide_86_hair
creation_date: 2026-0630-0038
creator_ai_fullname: Opus 4.8
---

# Sh-Polypeptide-86 for Hair Regrowth

Evidence Review created on 06/30/2026 using [AI4L](https://github.com/forever-healthy/AI4L) / Opus 4.8

**Also known as:** Synthetic Human Follistatin, Recombinant Follistatin Peptide, Follistatin, sh-Polypeptide-86

## Motivation

Sh-Polypeptide-86 is a lab-made protein designed to copy human follistatin, a natural substance the body uses to switch off other proteins that tell cells to stop growing. In hair products it is sold under the name "follistatin" and added to serums applied to the scalp, where the goal is to wake up resting hair follicles and lengthen the active growing phase of the hair. It is best known as one of eight peptides in a widely publicized scalp serum.

Follistatin reached the hair-loss conversation through a different door: it first drew attention for blocking myostatin, a protein that limits muscle size. Researchers later noticed that the same family of "stop-growing" signals also shrinks hair follicles, which raised the question of whether blocking them could help hair. A single early human study that combined follistatin with other growth signals reported thicker, denser hair, fueling interest.

This review examines what is actually known about Sh-Polypeptide-86 applied to the scalp for hair regrowth: how it is thought to work, the strength and limits of the evidence behind it, its safety and sourcing, and the practical questions of whether a large protein in a topical serum can reach the follicle at all.

**[Benefits](#expected-benefits) - [Risks](#potential-risks--side-effects) - [Protocol](#therapeutic-protocol) - [Conclusion](#conclusion)**

## Recommended Reading

This section lists high-level, directly relevant expert and clinical resources that give a useful overview of Sh-Polypeptide-86 and follistatin for hair.

* [Blueprint Haircare Stack: Product Review](https://perfecthairhealth.com/blueprint-haircare-stack-product-review/) - Rob English

A detailed independent analysis of the scalp serum in which Sh-Polypeptide-86 is the headline "follistatin" peptide, concluding that no preclinical or clinical efficacy data exist for the ingredient and that topical delivery of such a large protein is the central unresolved problem.

* [Blueprint Hair Peptides Analysis](https://klaustownsend.com/blueprint-hair-peptides-analysis/) - Klaus Townsend

An ingredient-by-ingredient breakdown of each synthetic peptide in the serum, including Sh-Polypeptide-86, that maps each one to the human protein it imitates and weighs the plausibility of a topical effect.

* [AMA #63: A guide for hair loss: causes, treatments, transplants, and sex-specific considerations](https://peterattiamd.com/ama63/) - Peter Attia

A structured overview of hair-loss biology and the evidence tiers behind mainstream and emerging treatments, useful for placing growth-factor and peptide approaches like follistatin in context against established options.

* [Hair regrowth following a Wnt- and follistatin containing treatment: safety and efficacy in a first-in-man phase 1 clinical trial](https://pubmed.ncbi.nlm.nih.gov/22052313/) - Zimber et al., 2011

The single most-cited human study linking follistatin to hair, reporting increased follicle density and hair-shaft thickness in 26 men after a single injection of a follistatin-and-Wnt growth-factor mixture; it is the origin of the follistatin-for-hair claim but tests injection, not a topical serum.

_Note: Only four resources of sufficient quality and direct relevance could be found, so fewer than five are listed; the list is not padded with marginal content. Of the priority experts, only Peter Attia had directly relevant published content on the topic — no relevant content on Sh-Polypeptide-86 or follistatin for hair was found from Rhonda Patrick, Andrew Huberman, Chris Kresser, or Life Extension._

## Grokipedia

No Grokipedia article exists for Sh-Polypeptide-86.

## Examine

No Examine article exists for Sh-Polypeptide-86. Examine.com focuses on ingestible dietary supplements and does not typically cover topical cosmetic peptide ingredients.

## ConsumerLab

No ConsumerLab article exists for Sh-Polypeptide-86. ConsumerLab tests ingestible supplements and does not typically cover topical cosmetic peptide ingredients.

## Systematic Reviews

No systematic reviews or meta-analyses for Sh-Polypeptide-86 were found on PubMed as of 06/30/2026.

## Mechanism of Action

The primary biological rationale for Sh-Polypeptide-86 rests on what it imitates: follistatin, a naturally occurring glycoprotein that binds and neutralizes members of the TGF-β superfamily (transforming growth factor beta, a large family of signaling proteins that broadly restrain cell growth). Its two most relevant targets in this context are activin and myostatin.

The hair-cycle logic runs as follows:

* **Activin/BMP braking.** In the hair follicle, activin signals interact with bone morphogenetic proteins (BMPs — growth-restraining signals of the same TGF-β family) to govern the timing of the hair cycle. Mouse work showed that follistatin promotes follicle development while activin retards it, and that follistatin-deficient mice have abnormal follicle formation, placing follistatin on the pro-growth side of this balance.

* **Myostatin in the follicle.** Myostatin (the muscle-limiting protein follistatin is most famous for blocking) is also expressed in skin and follicles, where it is associated with follicle miniaturization. By sequestering myostatin and activin, follistatin is proposed to lift these "stop-growing" signals from the follicle.

* **Anagen extension.** Removing these brakes is hypothesized to favor the transition into and maintenance of anagen (the active growing phase), increasing follicle density and hair-shaft caliber — the outcomes reported in the early human injection study.

Two competing considerations weigh against a meaningful effect from a topical serum. First, the dominant mechanistic evidence is in mice or in injected human studies, not topical application. Second, and more fundamentally, follistatin is a large protein (the human form spans up to 344 amino acids); the intact stratum corneum is a formidable barrier to molecules of this size, so whether enough biologically active peptide reaches the dermal papilla through topical application is unresolved and is the central mechanistic objection raised by independent reviewers.

Because Sh-Polypeptide-86 is a recombinant protein rather than a small-molecule drug, classic small-molecule pharmacology (half-life, hepatic metabolism via cytochrome enzymes, tissue distribution) is not the appropriate frame. Protein turnover is governed by local proteases in skin; circulating endogenous follistatin has a very short half-life (on the order of minutes to an hour), and topically applied protein is expected to be degraded locally rather than distributed systemically.

## Historical Context & Evolution

Follistatin was first characterized in the 1980s as an activin-binding protein in ovarian fluid, named for its ability to suppress follicle-stimulating hormone. Its profile changed dramatically when it was found to be a potent natural inhibitor of myostatin, making it a target of intense interest in muscle biology, muscular dystrophy gene therapy, and — informally — the performance-enhancement community.

The leap to hair came indirectly. Mouse studies in the early 2000s established follistatin and activin as regulators of follicle development and cycling. The pivotal translational moment was a 2011 first-in-man phase 1 study (Zimber et al.) in which a wound-healing-derived mixture containing follistatin and Wnt proteins, injected into the scalp, increased follicle density and hair-shaft thickness in men with pattern hair loss. This finding is the historical seed of every subsequent "follistatin for hair" claim.

The current product incarnation — Sh-Polypeptide-86 as a topical cosmetic ingredient — is a much more recent development, arising from the synthetic-biomimetic-peptide and "growth factor serum" trend in cosmetic skincare and haircare. The "sh-" prefix denotes a synthetic human sequence; this particular peptide is produced by expressing the human follistatin gene in *Nicotiana benthamiana* (a tobacco relative used as a plant bioreactor). It gained mainstream visibility as the headline peptide in a heavily publicized multi-peptide scalp serum.

The standing of the evidence has not been settled by later work. The original injection finding has not been replaced or overturned, but it also has not been replicated in large trials, and it has not been shown to transfer to topical application. The honest current position is that the mechanistic rationale is real and the early injection signal is intriguing, while topical efficacy remains unproven.

## Expected Benefits

All benefits below concern scalp application aimed at hair regrowth, the focus of this review.

### High 🟩 🟩 🟩

(No benefits qualify for a High evidence grade. No high-quality human trials of topical Sh-Polypeptide-86 for hair exist.)

### Medium 🟩 🟩

(No benefits qualify for a Medium evidence grade.)

### Low 🟩

#### Increased Follicle Density and Hair-Shaft Thickness (via Follistatin Activity) ⚠ Conflicted

The core proposed benefit is more and thicker hairs through removal of activin/myostatin braking on the follicle. The only direct human evidence is a single small phase 1 study (Zimber et al., 2011, 26 men) in which an *injected* follistatin-and-Wnt mixture increased follicle density and shaft thickness, with effects reported to last up to a year after one treatment. A conflict of interest applies here: this pivotal study was conducted and funded by Histogen Inc., the company developing the injected Hair Stimulating Complex, so the only positive human signal originates from a party with a direct financial stake in a favorable result; the topical serums that now invoke this finding are likewise commercial products (most prominently the Blueprint line) whose vendors benefit from the efficacy claim. The evidence is conflicted for the topical context: the positive signal exists but comes from injection of a multi-component product, not from topical Sh-Polypeptide-86 alone, and independent reviewers note that no preclinical or clinical efficacy data exist for the topical ingredient and that delivery of a large protein across skin is unproven. The grade is Low, not higher, because the human data are single-study, small, injected, confounded by co-administered growth factors, and sponsored by an interested commercial party.

**Magnitude:** In the 2011 injection study, modest increases in follicle density and hair-shaft thickness were reported in 26 men; no comparable magnitude has been demonstrated for the topical ingredient.

### Speculative 🟨

#### Anagen Phase Extension and Reactivation of Dormant Follicles

Marketing positions the peptide as reactivating resting follicles and prolonging the growth phase. Mechanistically this is plausible from mouse follistatin/activin biology, where follistatin promotes follicle development and counters the growth-retarding effect of activin. However, no controlled human study has demonstrated anagen extension from topical Sh-Polypeptide-86; the basis is mechanistic extrapolation from animal models and from the injection study, making it speculative for the topical product.

#### Synergy Within Multi-Peptide Growth-Factor Serums

Sh-Polypeptide-86 is almost always combined with other biomimetic peptides — peptides that mimic the body's growth-signaling proteins such as VEGF (vascular endothelial growth factor, which builds blood vessels), IGF/hGH (insulin-like growth factor and human growth hormone, which drive tissue growth), PDGF (platelet-derived growth factor, which spurs cell proliferation and repair), EGF (epidermal growth factor, which stimulates skin cell growth), and copper tripeptide GHK (a small skin-repair peptide) — together with delivery aids such as nanoliposomes. Proponents argue the combination delivers complementary pro-angiogenic and pro-proliferative signals to the follicle. This is mechanistically coherent but entirely speculative as applied: no controlled trial isolates Sh-Polypeptide-86's contribution, and the finished serums have not been tested in published clinical studies.

## Benefit-Modifying Factors

* **Genetic polymorphisms:** No validated pharmacogenetic markers govern response to topical Sh-Polypeptide-86 specifically. More broadly, androgen-receptor and 5-alpha-reductase genetics drive pattern hair loss severity and may set the ceiling on what any single follicle-stimulating agent can achieve; individuals with strong genetic miniaturization may respond less to a brake-removal strategy.

* **Baseline biomarker levels:** Endogenous scalp myostatin/activin tone and local follistatin levels are not routinely measurable and have no standard assay, so baseline status cannot currently be used to predict response. Baseline follicle miniaturization (caliber on trichoscopy) is the most practical proxy for residual responsiveness.

* **Sex-based differences:** The only direct human evidence (injection study) was in men with pattern hair loss; female pattern hair loss has different hormonal drivers and was not studied, so any benefit in women is unestablished.

* **Pre-existing health conditions:** Scalp conditions that disrupt the skin barrier or follicle (active inflammation, scarring alopecia) would be expected to reduce both delivery and the pool of viable follicles available to respond.

* **Age-related considerations:** Older individuals at the upper end of the target range tend to have a higher proportion of permanently miniaturized or lost follicles and thinner skin; a follicle-stimulating peptide can only act on follicles that still exist, so advanced loss limits achievable benefit.

## Potential Risks & Side Effects

### High 🟥 🟥 🟥

(No risks qualify for a High evidence grade.)

### Medium 🟥 🟥

(No risks qualify for a Medium evidence grade.)

### Low 🟥

#### Local Skin and Scalp Irritation

As with most topical serums, the most realistic adverse effects are local: irritation, redness, itching, or contact sensitivity. These are usually driven by the full formulation (solvents, preservatives, penetration enhancers, and other actives such as salicylic acid and caffeine) rather than the peptide itself. The evidence basis is general cosmetic experience and the formulation contents rather than ingredient-specific reports.

**Magnitude:** Not quantified in available studies.

### Speculative 🟨

#### Theoretical Local Growth-Signal Modulation

Because follistatin alters TGF-β-family signaling involved in cell growth, a theoretical concern is unintended local effects on tissue with chronic application. The basis is mechanistic only; injected follistatin gene therapy and the 2011 scalp-injection study reported no such adverse signal, and there are no reports tied to the topical cosmetic ingredient. It is listed as speculative for completeness, not because of demonstrated harm.

#### Unknown Long-Term Topical Safety

The finished serums containing Sh-Polypeptide-86 are recent and have not been subjected to published long-term safety studies. The basis for any concern is the absence of data rather than a specific signal; the favorable safety record of follistatin in injection and gene-therapy settings is reassuring but does not formally transfer to chronic topical use.

## Risk-Modifying Factors

* **Genetic polymorphisms:** No genetic variants are established to modify the safety of topical Sh-Polypeptide-86. General atopic or contact-allergy predisposition (e.g., filaggrin-related barrier defects) increases the likelihood of irritation from any topical formulation.

* **Baseline biomarker levels:** No biomarker predicts adverse response to this peptide. Baseline barrier integrity (visible eczema, dermatitis) is the practical factor that raises irritation risk.

* **Sex-based differences:** No sex-specific safety differences have been characterized for topical application; the injection literature is predominantly male.

* **Pre-existing health conditions:** Active scalp dermatitis, psoriasis, open lesions, or seborrheic dermatitis raise the risk of irritation and increased absorption from any scalp serum.

* **Age-related considerations:** Thinner, more reactive skin in older individuals at the upper end of the target range may increase susceptibility to local irritation from the overall formulation.

## Key Interactions & Contraindications

* **Prescription drug interactions:** No documented systemic drug interactions exist for topical Sh-Polypeptide-86; meaningful systemic absorption of an intact large protein across intact skin is not expected. Concurrent prescription topicals applied to the same area (e.g., topical minoxidil, topical corticosteroids) have not been studied in combination.

* **Over-the-counter medication interactions:** No specific OTC interactions are documented. Co-applied OTC scalp products containing exfoliants or alcohols could increase irritation from the combined regimen.

* **Supplement interactions:** No documented supplement interactions. Oral supplements marketed to "boost follistatin" or inhibit myostatin have not been studied alongside the topical peptide.

* **Additive-effect agents:** Other topical follicle-stimulating actives commonly co-formulated or co-used — minoxidil, copper tripeptide-1 (GHK-Cu), caffeine, adenosine, and procapil-type peptides — act on overlapping pro-growth pathways; their combined effect with Sh-Polypeptide-86 is additive in intent but unquantified, and stacking multiple irritant-prone topicals raises cumulative irritation risk.

* **Other interventions:** Combination with microneedling is frequently promoted to improve delivery of large peptides; while microneedling can plausibly raise penetration, it also increases absorption of all co-applied ingredients and the associated irritation risk.

* **Populations who should avoid this intervention:** Individuals with active scalp dermatitis, broken or inflamed scalp skin, scarring alopecia, or known allergy to any formulation component; and, on a precautionary basis given the absence of data, pregnant or breastfeeding individuals.

Each interaction above is best characterized as **caution / monitor** rather than absolute contraindication, the main clinical consequence being local irritation or unverified added benefit. The principal mitigating actions are patch testing before full use, separating the timing of multiple irritant topicals, and discontinuing if irritation develops.

## Risk Mitigation Strategies

* **Patch test before first full application:** Apply a small amount to a discreet area of skin and wait 48 hours to check for redness, itching, or rash before applying to the whole scalp — this mitigates contact irritation and allergic reaction from the peptide or, more likely, the full formulation.

* **Start with reduced frequency:** Begin with application every other day for the first 1–2 weeks rather than the full recommended cadence, increasing only if well tolerated — this limits cumulative irritation, the main realistic adverse effect.

* **Avoid broken or inflamed scalp skin:** Do not apply over active dermatitis, open lesions, or freshly microneedled skin until healed — this prevents heightened irritation and uncontrolled increased absorption.

* **Separate the timing of multiple topicals:** If combining with other scalp actives (e.g., minoxidil, exfoliating treatments), space applications by several hours — this reduces the additive irritation risk identified in the Interactions section.

* **Discontinue on persistent irritation:** Stop use if redness, itching, or flaking persists beyond a few days — this prevents progression to a contact dermatitis from the overall serum.

## Therapeutic Protocol

* **Standard approach (topical serum):** As marketed by the leading commercial products, Sh-Polypeptide-86 is delivered as one component of a multi-peptide scalp serum, typically applied once or twice daily to a clean, dry scalp and left on, with manufacturers stating that visible scalp and hair changes require at least about four months of consistent use. There is no established standalone topical protocol for the isolated peptide.

* **Competing approach (injection / procedural, integrative clinics):** The only human efficacy evidence used injection of a follistatin-containing growth-factor mixture into the scalp (Zimber et al., 2011), an approach pursued in some integrative and cosmetic-dermatology settings rather than at home; this is presented as an alternative delivery route, not as the default. Neither route is framed here as superior, since the injection evidence is single-study and the topical evidence is absent.

* **Originators cited:** The injection-based follistatin/Wnt approach traces to the Histogen wound-healing-derived "hair stimulating complex" program behind the 2011 trial; the topical multi-peptide serum format was popularized by the Blueprint (Bryan Johnson) haircare products, which is where Sh-Polypeptide-86 became publicly prominent.

* **Best time of day:** No chronobiology data exist for this peptide. Practically, application is timed to a clean dry scalp (commonly morning and/or evening) so the serum is not immediately washed off.

* **Half-life consideration (protein, not small molecule):** Endogenous follistatin has a very short circulating half-life (minutes to about an hour), and topically applied protein is expected to be degraded by local skin proteases; this is why repeated, sustained application — rather than a single dose — is the assumed requirement for any topical effect.

* **Single vs. split dosing:** Because the peptide is leave-on and locally acting, "dosing" is a matter of application frequency rather than systemic split dosing; once- or twice-daily leave-on application is the practical pattern.

* **Genetic polymorphisms:** No pharmacogenetic variant guides dosing of this peptide. Androgen-pathway genetics influence overall pattern-hair-loss trajectory and may inform whether the peptide is used alongside an anti-androgen strategy, but do not change the peptide's application itself.

* **Sex-based differences:** Human evidence is male-only; no female-specific protocol exists, and the hormonal drivers of female pattern hair loss differ, so extrapolation of dosing to women is unsupported.

* **Age-related considerations:** Older users at the upper end of the target range have more thinning and barrier-compromised skin and fewer viable follicles; protocol expectations should be tempered accordingly, though application mechanics are unchanged.

* **Baseline biomarker levels:** No baseline lab governs use; trichoscopic follicle caliber is the most practical baseline measure of how much responsive follicle remains.

* **Pre-existing health conditions:** Scalp inflammation or scarring alopecia should be treated or excluded before starting, as they reduce both delivery and the pool of follicles available to respond.

## Discontinuation & Cycling

* **Lifelong vs. short-term:** Pattern hair loss is progressive, so any maintenance effect from a topical follicle-stimulating peptide would, like other topical hair treatments, be expected to require ongoing use; there is no evidence of a durable effect after stopping the topical product (the year-long durability reported in the 2011 study was for an injection, not the serum).

* **Withdrawal effects:** No withdrawal syndrome is known. The realistic outcome of stopping is gradual loss of any gains as the follicle returns to its untreated trajectory, mirroring the pattern seen when other topical hair treatments are discontinued.

* **Tapering:** No tapering protocol is needed or established; the peptide can be stopped without a taper, as there is no pharmacological dependence.

* **Cycling:** No evidence supports cycling to maintain efficacy. Because the proposed mechanism is continuous removal of growth-braking signals, continuous rather than cyclical use is the more coherent expectation, but this is unstudied.

## Sourcing and Quality

* **Form and identity:** Look for the INCI name (International Nomenclature of Cosmetic Ingredients, the standardized labeling system for cosmetic ingredient lists) "sh-Polypeptide-86" on the ingredient list; it is a synthetic/recombinant human follistatin sequence, typically produced by plant-based expression (*Nicotiana benthamiana*). It is a cosmetic ingredient, not an approved drug, so it carries no pharmaceutical purity grade.

* **Third-party testing:** Because finished serums are cosmetics rather than supplements or drugs, independent potency and purity verification is limited; prefer manufacturers that disclose the peptide concentration, provide a delivery rationale (e.g., encapsulation/liposomal system), and publish ingredient sourcing. Be skeptical of products that name the peptide prominently but disclose neither concentration nor any delivery strategy.

* **Reputable sources:** The most visible finished products are the Blueprint (Bryan Johnson) peptide hair serum and shampoo; compounding and cosmeceutical suppliers also offer the raw INCI ingredient. No brand has published clinical validation of the finished product, so brand selection rests on formulation transparency rather than proven efficacy.

* **Delivery is the decisive quality factor:** For a large protein, the formulation's penetration-enhancement strategy matters more than peptide identity; a serum with no credible delivery system is unlikely to get meaningful peptide to the follicle regardless of how much is listed.

* **Avoid grey-market injectables:** "Follistatin" sold as an injectable or as gene therapy outside regulated trials is a distinct and higher-risk category from the cosmetic topical peptide and should not be conflated with it.

## Practical Considerations

* **Time to effect:** Manufacturers state that scalp and hair changes take at least about four months of consistent use, consistent with the hair cycle; any honest expectation of visible change is measured in months, not weeks.

* **Common pitfalls:** Expecting drug-level results from a cosmetic; assuming a large protein automatically penetrates the scalp; conflating the injected 2011 study's results with the topical serum; and using the peptide in place of, rather than alongside, evidence-based options for those seeking maximal results.

* **Regulatory status:** Sh-Polypeptide-86 is regulated as a cosmetic ingredient, not as a drug; it has no approval for treating hair loss, and hair-regrowth claims for cosmetic peptides are not subject to drug-level efficacy review.

* **Cost and accessibility:** The branded multi-peptide serums are positioned at a premium price point relative to commodity hair treatments; the isolated ingredient is accessible to formulators but the finished consumer products are comparatively expensive for an unproven benefit.

* **Realistic framing:** For risk-aware optimizers, the peptide is best viewed as a low-risk, low-proven-benefit add-on rather than a primary intervention.

## Interaction with Foundational Habits

* **Sleep:** The interaction is **indirect**. There is no known direct effect of topical Sh-Polypeptide-86 on sleep, and no mechanism by which a locally acting scalp peptide would affect it. Sleep matters to hair only through general physiology (stress, recovery), so the practical consideration is simply that the peptide neither helps nor harms sleep.

* **Nutrition:** The interaction is **indirect**. No nutrient depletion or dietary requirement is associated with the topical peptide. Adequate protein, iron, and overall nutritional status are foundational for hair growth generally, so correcting deficiencies is a more impactful lever than the peptide; there is no specific food to include or avoid for the peptide itself.

* **Exercise:** The interaction is **indirect and potentially confounded**. Notably, follistatin is also released systemically with exercise as part of muscle-myostatin biology, but this is unrelated to topical scalp application; exercise will not augment a topical serum's local effect, and the topical serum has no effect on exercise. The practical point is to avoid attributing exercise-related changes to the serum.

* **Stress management:** The interaction is **indirect**. Chronic stress can worsen hair shedding through separate hormonal pathways; the topical peptide does not modulate cortisol or the stress response. Stress reduction is a complementary habit for hair generally but operates independently of this peptide.

## Monitoring Protocol & Defining Success

Because Sh-Polypeptide-86 is a topical cosmetic with negligible expected systemic absorption, laboratory monitoring is not driven by safety the way a systemic drug would be; monitoring is primarily about objectively tracking hair response and ruling out treatable contributors to hair loss before and during use.

Before starting, a baseline assessment is advised: standardized scalp photographs and, where available, trichoscopy to document follicle caliber, plus baseline labs to exclude common reversible contributors to hair loss (especially iron status and thyroid function). Ongoing monitoring is about consistency over time rather than frequent testing: repeat standardized photographs at roughly 4 weeks (baseline irritation check), 4 months (first realistic efficacy read-out), and then every 4–6 months, with labs rechecked only if baseline abnormalities were found or shedding changes.

| Biomarker | Optimal Functional Range | Why Measure It? | Context/Notes |
|-----------|--------------------------|-----------------|---------------|
| Ferritin (iron stores) | 50–100 ng/mL (functional target for hair) | Low iron stores drive diffuse hair shedding and blunt any treatment response | Conventional lab "normal" often starts at ~15–30 ng/mL, well below the hair-functional target; an acute-phase reactant, so interpret alongside inflammation markers; fasting not required |
| TSH | 0.5–2.5 mIU/L (functional) | Thyroid dysfunction is a common reversible cause of hair loss that can mimic or mask treatment effect | TSH (thyroid-stimulating hormone) reflects thyroid activity; conventional upper limit (~4–4.5 mIU/L) is higher than the functional target; best paired with free T4/free T3; morning draw preferred for consistency |
| Vitamin D, 25-OH | 40–60 ng/mL (functional) | Low vitamin D is associated with hair-cycle disturbances and follicle health | Conventional "sufficient" starts at ~30 ng/mL; fat-soluble, so timing/fasting not critical; pair with a baseline metabolic panel if supplementing high doses |

Qualitative markers of success or trouble are tracked alongside the photographs:

* Reduced daily shedding (hairs in brush, shower, or pillow)
* Visible new short regrowth (vellus-to-terminal transition) at the hairline or part
* Increased perceived density or scalp coverage in consistent lighting
* Improved hair-shaft thickness and manageability
* Absence of scalp irritation, redness, or flaking as a tolerability marker

## Emerging Research

Research relevant to Sh-Polypeptide-86 sits across two fronts — follistatin biology (mostly aimed at muscle and aging) and topical peptide delivery for hair — and includes work that could either strengthen or weaken the case.

* **Follistatin gene and plasmid therapy trials (systemic, not hair):** Several registered trials test follistatin delivery for muscle and aging conditions, establishing follistatin's human safety profile but not its hair efficacy. Examples include a completed phase 1 injectable follistatin plasmid gene-therapy study in frailty and aging ([NCT06411366](https://clinicaltrials.gov/study/NCT06411366), 43 participants) and a recruiting follistatin/klotho gene-therapy safety study in healthy adults ([NCT07285629](https://clinicaltrials.gov/study/NCT07285629), early phase 1, 30 participants). These could strengthen confidence in follistatin's safety while leaving the hair question open.

* **Earlier follistatin gene-transfer dystrophy trials:** Completed muscular-dystrophy gene-transfer studies ([NCT01519349](https://clinicaltrials.gov/study/NCT01519349), phase 1) contribute long-run human safety data for follistatin overexpression, indirectly reassuring for the cosmetic peptide but unrelated to scalp efficacy.

* **The unreplicated hair signal:** The pivotal human hair finding remains the single 2011 phase 1 injection study (Zimber et al., [PMID 22052313](https://pubmed.ncbi.nlm.nih.gov/22052313/)); the most decisive emerging need is an adequately powered, placebo-controlled replication — and, critically, a head-to-head test of *topical* versus injected delivery. Absence of such a trial is the single biggest weakness in the case.

* **Growth-factor and IGF-1 hair biology:** Reviews of growth-factor signaling in hair regeneration (e.g., Hsieh et al., 2025, [PMID 41020895](https://pubmed.ncbi.nlm.nih.gov/41020895/)) map the broader pathway space (IGF-1, VEGF, PDGF) in which follistatin's brake-removal sits and highlight delivery innovations (liposomal and exosome carriers) that could, if they translate, make large-protein topical delivery more credible — strengthening the rationale if they succeed and weakening it if they continue to fail.

* **Comparator evidence base:** Network meta-analysis of alopecia treatments (Mateos-Haro et al., 2023, [PMID 37870096](https://pubmed.ncbi.nlm.nih.gov/37870096/)) underscores how much of the hair-loss field rests on low-certainty evidence and how high the bar is for a new agent to demonstrate benefit — context that tempers expectations for an unproven cosmetic peptide.

## Conclusion

Sh-Polypeptide-86 is a lab-made copy of human follistatin, a natural protein that switches off other signals telling cells to stop growing. The idea behind using it on the scalp is appealing: by lifting these "stop-growing" brakes on hair follicles, it might wake resting follicles and lengthen the active growing phase, producing more and thicker hairs.

The reality is that the supporting evidence is thin and mostly indirect. The one piece of human data linking follistatin to hair comes from a single small study that injected it together with other growth signals — not the leave-on serum sold today — and it has never been repeated in a large trial. That study was run and paid for by the company developing the treatment, and the serums sold today are commercial products, so the few favorable findings come from parties with money at stake. Animal studies make the mechanism believable, but no controlled human study shows that the topical product actually works, and a real practical problem hangs over it: follistatin is a large protein, and large proteins struggle to pass through skin to reach the follicle at all.

On safety, the picture is reassuring at the level of local skin tolerance, with the main realistic downsides being irritation from the overall formulation; long-term topical safety is simply untested. The honest summary is that the rationale is plausible and the early signal is intriguing, while proof that the topical peptide regrows hair does not yet exist.

**[Top](#top) - [Benefits](#expected-benefits) - [Risks](#potential-risks--side-effects) - [Protocol](#therapeutic-protocol)**


---
canonical_name: Sh-Polypeptide-9
alternate_names: CG-VEGF, rh-Polypeptide-9, Recombinant Human Vascular Endothelial Growth Factor A, sh-Polypeptide 9
canonical_topic: Sh-Polypeptide-9 for Hair Regrowth
short_topic_lc: sh_polypeptide_9_hair
creation_date: 2026-0628-0004
creator_ai_fullname: Opus 4.8
---

# Sh-Polypeptide-9 for Hair Regrowth

Evidence Review created on 06/28/2026 using [AI4L](https://github.com/forever-healthy/AI4L) / Opus 4.8

**Also known as:** CG-VEGF, rh-Polypeptide-9, Recombinant Human Vascular Endothelial Growth Factor A, sh-Polypeptide 9

## Motivation

Sh-Polypeptide-9 is a lab-made copy of one of the body's main blood-vessel-growth signals — the molecule that tells the body to build new blood vessels. It is added to topical scalp serums and to injectable "hair cocktails" with the idea that better blood supply to the hair root can wake up sluggish follicles and support regrowth. Because hair follicles need a rich blood supply during their growth phase, boosting this signal at the scalp is an appealing target for people troubled by thinning hair.

The idea grew out of basic biology showing that follicles with more surrounding blood vessels grow larger, thicker hairs, and that blocking this growth signal shrinks them. This led cosmetic chemists to package a look-alike of the signal into scalp products, often alongside copper peptides and other growth factors, and it now appears in several premium hair lines and clinic injection blends.

This review examines what is actually known about Sh-Polypeptide-9 for hair regrowth: the laboratory and human evidence, how it is thought to work, its expected benefits and risks, how it is used in practice, and where the science is still thin. It separates what has been tested from what remains theoretical.

**[Benefits](#expected-benefits) - [Risks](#potential-risks--side-effects) - [Protocol](#therapeutic-protocol) - [Conclusion](#conclusion)**

## Recommended Reading

This section lists high-level expert and academic resources that discuss Sh-Polypeptide-9 or peptides based on VEGF (vascular endothelial growth factor, the body's main signal for growing new blood vessels) for hair growth in substantial depth.

* [sh-Polypeptide-9 – Vascular Endothelial Growth Factor A (VEGFA)](https://ci.guide/peptides/sh-polypeptide-9) - Ghochikyan

  A physician-authored cosmetic-ingredient monograph that describes what Sh-Polypeptide-9 is, its proposed mechanism in restoring scalp microcirculation, and its comparison to minoxidil in laboratory work. It is the single most focused overview of the ingredient itself.

* [Blueprint Haircare Stack: Product Review](https://perfecthairhealth.com/blueprint-haircare-stack-product-review/) - Williams

  A critical, evidence-focused review on Rob English's hair-science platform of a commercial peptide serum containing Sh-Polypeptide-9, examining how much of its formula is supported by human data versus marketing claims.

* [Peptides and Hair Growth: Scientific Mechanisms, Clinical Evidence, and Practical Applications in Modern Trichology](https://trichology.com/trichologyjournal/peptides-for-hair-growth/) - Sarmiento, 2025

  A trichology-focused overview placing VEGF-mimetic and copper peptides in the broader landscape of peptide hair therapies, useful for understanding where Sh-Polypeptide-9 sits among alternatives and how strong the supporting evidence is.

* [The human tri-peptide GHK and tissue remodeling](https://pubmed.ncbi.nlm.nih.gov/18644225/) - Pickart, 2008

  A foundational narrative review by the discoverer of the copper-peptide field, explaining how peptides that raise VEGF and other growth factors increase hair follicle size, providing the mechanistic backdrop for VEGF-mimetic hair peptides.

* [Control of hair growth and follicle size by VEGF-mediated angiogenesis](https://pubmed.ncbi.nlm.nih.gov/11181640/) - Yano et al., 2001

  The landmark primary study showing that increasing VEGF enlarges hair follicles and accelerates regrowth while blocking it does the opposite — the core biological rationale on which Sh-Polypeptide-9 rests.

_Note: No content from the prioritized experts (Rhonda Patrick, Peter Attia, Andrew Huberman, Chris Kresser, Life Extension) addressing Sh-Polypeptide-9 or VEGF-peptide hair products could be located despite both web and on-site searches; the list above is therefore drawn from the next-most-relevant expert and academic sources._

## Grokipedia

No Grokipedia article exists for Sh-Polypeptide-9.

## Examine

No Examine article exists for Sh-Polypeptide-9. Examine.com focuses on orally ingested dietary supplements and does not cover topical or injectable cosmetic peptides such as this one.

## ConsumerLab

No ConsumerLab article exists for Sh-Polypeptide-9. ConsumerLab tests orally ingested supplements for purity and does not cover topical cosmetic peptides.

## Systematic Reviews

No systematic reviews or meta-analyses for Sh-Polypeptide-9 were found on PubMed as of 28 June 2026.

## Mechanism of Action

Sh-Polypeptide-9 is a biotechnology-produced analog of human VEGF-A (vascular endothelial growth factor A, the body's master signal for growing new blood vessels). Its proposed action on hair rests on the well-established link between follicle blood supply and hair growth.

* **Perifollicular angiogenesis (growth of blood vessels around the follicle):** During the active growth phase of a hair (anagen), the follicle is wrapped in an expanding network of tiny blood vessels that deliver oxygen and nutrients to the rapidly dividing hair-matrix cells. VEGF is the principal driver of this vessel growth. Animal work showed that raising VEGF enlarges follicles and produces thicker hairs, while neutralizing VEGF shrinks them — establishing vascular supply as a rate-limiting factor for follicle size.

* **Dermal papilla signaling:** The dermal papilla is the cluster of cells at the follicle base that orchestrates the hair cycle. In laboratory coculture of human dermal papilla cells with microvascular endothelial cells, Sh-Polypeptide-9 increased cell proliferation and modulated signaling molecules (including β-catenin, a hub of the Wnt pathway that promotes the growth phase, and a reduction in the inflammatory signal IL-1α). This suggests the peptide may act not only on vessels but on the follicle's own control center.

* **Comparison with minoxidil:** Minoxidil, the most studied topical hair drug, is itself thought to work partly by upregulating VEGF. Laboratory comparisons reported that encapsulated Sh-Polypeptide-9 raised VEGF, basic fibroblast growth factor (bFGF, another growth signal), and β-catenin, and offered some protection against oxidative stress — overlapping with minoxidil's proposed pathway but via direct VEGF mimicry rather than indirect induction.

Competing interpretation: critics note that topically applied VEGF-mimetic peptides are large molecules that penetrate intact skin poorly, so a key open question is whether enough reaches the dermal papilla to reproduce the effects seen when the peptide is added directly to cells in a dish. Formulators address this with encapsulation or by injecting the peptide, but the penetration question remains a genuine point of mechanistic debate.

As a peptide rather than a small-molecule drug, Sh-Polypeptide-9 does not have a conventional oral pharmacology profile (half-life, CYP metabolism). Native VEGF-A has a short circulating half-life (on the order of tens of minutes) and is broken down by general proteases; it acts locally at the VEGFR-2 receptor (the main VEGF docking site on blood-vessel cells) rather than being distributed and metabolized like an ingested drug.

## Historical Context & Evolution

* **Original purpose of VEGF biology:** VEGF was first characterized in the context of blood-vessel growth, wound healing, and tumor biology. Its central role in hair was uncovered around 2001, when transgenic and antibody experiments in mice demonstrated that VEGF-driven blood-vessel growth controls follicle size — research that reframed scalp blood supply as a lever for hair growth.

* **Translation into cosmetics:** Because recombinant human VEGF protein is expensive and unstable, cosmetic developers turned to engineered VEGF analogs and "biomimetic peptides" that imitate growth-factor signaling. Sh-Polypeptide-9 (also marketed as CG-VEGF) emerged as one such ingredient, given an International Nomenclature of Cosmetic Ingredients (INCI) name and incorporated into topical serums and clinic injection blends, frequently paired with copper tripeptide-1 and other growth factors.

* **What the early research actually showed:** The first dedicated follicle study (a 2016 coculture letter) reported that Sh-Polypeptide-9 increased proliferation of human dermal papilla and endothelial cells and shifted signaling toward the growth phase. This was promising in-vitro evidence but did not, by itself, demonstrate regrowth on a human scalp.

* **Evolving opinion:** Enthusiasm for VEGF-mimetic hair peptides remains tempered. The biological rationale is robust and the laboratory signals are consistent, yet rigorous human trials of Sh-Polypeptide-9 as an isolated ingredient have not been performed. Newer human studies test it only inside multi-ingredient cosmetic blends, so its independent contribution is still unresolved rather than settled in either direction.

## Expected Benefits

Benefits are framed for proactive, risk-aware adults considering Sh-Polypeptide-9 as part of a hair-optimization regimen. A central caveat applies throughout: nearly all human evidence comes from multi-ingredient blends, so benefits attributable to Sh-Polypeptide-9 alone are difficult to isolate.

### Medium 🟩 🟩

#### Increased Perifollicular Blood Supply (Anagen Support)

The strongest and most consistent rationale is that Sh-Polypeptide-9, as a VEGF mimic, promotes growth of the small blood vessels surrounding the follicle, which in turn supports the active growth phase and larger follicle size. This is grounded in landmark animal work showing VEGF directly controls follicle size, plus human cell-culture data showing the peptide raises proliferation and pro-growth signaling in dermal papilla and endothelial cells. The evidence basis is strong mechanistically but indirect for finished-product scalp outcomes.

**Magnitude:** In animal models, VEGF overexpression increased follicle size and hair-shaft diameter by roughly 25–70%; no equivalent isolated human figure exists for the peptide.

### Low 🟩

#### Reduced Hair Shedding and Increased Density Within Peptide Blends ⚠ Conflicted

When Sh-Polypeptide-9 is included in PRP-like (platelet-rich plasma-like) cosmetic peptide solutions, randomized and pilot human studies report meaningful regrowth and reduced shedding. A randomized controlled trial in alopecia areata using a biomimetic-peptide cosmetic (containing Sh-Polypeptide-9 among others) reported about 57% mean scalp regrowth at three months versus about 28% with placebo; this trial was run by the industry-linked International Hair Research Foundation, a conflict of interest to weigh when reading the result. The conflict is twofold: the effect cannot be attributed to Sh-Polypeptide-9 specifically rather than the copper peptide or other growth factors in the blend, and alopecia areata (an autoimmune patchy hair loss) responds to many interventions including placebo, so generalization to common pattern hair loss is uncertain.

**Magnitude:** Blend studies report roughly 57–68% regrowth in alopecia areata and an 83% reduction in hair-pull-test positivity in an injectable growth-factor pilot; the isolated contribution of Sh-Polypeptide-9 is unquantified.

#### Thicker Terminal Hair and Improved Graft Survival

A first-in-man injectable growth-factor formulation (including a copper tripeptide and VEGF) reported a shift from fine vellus hairs toward thicker terminal hairs and increased shaft diameter, and a separate study used a biomimetic peptide solution as a storage medium that improved hair-follicle graft survival during transplantation. These point to a plausible follicle-strengthening and tissue-supportive effect consistent with the VEGF mechanism, though again within combination products.

**Magnitude:** Increased terminal-hair counts and shaft diameter reported qualitatively; a one-year total-hair-count increase reached statistical significance (P = 0.002) in the injectable pilot, but not isolated to Sh-Polypeptide-9.

### Speculative 🟨

#### Antioxidant and Anti-Inflammatory Scalp Support

Laboratory observations suggest Sh-Polypeptide-9 may reduce the inflammatory signal IL-1α (a known inhibitor of hair growth) and protect scalp cells from oxidative stress. If real on the human scalp, this could create a more favorable micro-environment for follicles, but the basis is cell-culture and mechanistic only, with no controlled human data isolating this effect.

#### Synergy With Minoxidil-Like Pathways

Because both minoxidil and Sh-Polypeptide-9 are thought to raise VEGF, the peptide is sometimes proposed as a complement or alternative to minoxidil for people who cannot tolerate it. This is mechanistically reasonable and supported by laboratory comparisons, but no head-to-head human trial has tested whether Sh-Polypeptide-9 matches or adds to minoxidil's regrowth.

## Benefit-Modifying Factors

* **Genetic polymorphisms:** No genetic variants have been established that modify the benefit of Sh-Polypeptide-9; as a topical/injectable peptide it is not subject to the drug-metabolizing enzyme variation relevant to oral drugs, and no VEGF-pathway polymorphism has been validated as a predictor of response.

* **Baseline scalp vascular and follicle status:** Individuals with miniaturizing-but-living follicles and reduced perifollicular blood flow have the most theoretical room to benefit from a VEGF-driven approach; scarring alopecia with destroyed follicles would not be expected to respond.

* **Type of hair loss:** The human blend evidence is strongest in alopecia areata (autoimmune patchy loss). Benefit in common androgenetic (pattern) hair loss is extrapolated and unproven, because pattern loss is hormone-driven and a vascular signal alone may be insufficient.

* **Delivery method and penetration:** Because the peptide is a large molecule, benefit is highly dependent on formulation. Encapsulated topicals or intradermal injection are expected to outperform simple aqueous serums that may not reach the dermal papilla.

* **Baseline biomarker levels:** There is no validated blood biomarker that predicts response; scalp VEGF status is not routinely measurable, so baseline biomarkers are not currently a practical guide to benefit for this peptide.

* **Sex-based differences:** No reliable sex-specific efficacy data exist for Sh-Polypeptide-9; the injectable growth-factor pilot included both male and female pattern loss and reported benefit in both, but did not isolate this ingredient or formally compare sexes.

* **Age-related considerations:** Older adults at the upper end of the target range tend to have more advanced follicle miniaturization and reduced dermal vascularity, which may blunt response; conversely, earlier-stage loss with viable follicles is more likely to respond. No age-stratified data are available.

## Potential Risks & Side Effects

Risks are framed for proactive adults; the overall safety signal in published cosmetic and pilot studies is favorable, but data are limited and almost always from blended products.

### Low 🟥

#### Local Application and Injection-Site Reactions

Topical scalp peptide products and intradermal growth-factor injections can cause transient redness, itching, stinging, or mild irritation at the application or injection site. Injectable use additionally carries the generic risks of needling — bruising, brief tenderness, and a small infection risk. In the published human pilot and RCT data, treatments were generally well tolerated with no serious adverse events, and reactions were mild and self-limited.

**Magnitude:** Mild, transient local reactions; in the injectable growth-factor pilot of 1,000 patients, treatment was reported as well tolerated with no serious adverse events.

### Speculative 🟨

#### Theoretical Concern in VEGF-Sensitive Conditions (Psoriasis, Active Skin Cancer)

Because VEGF drives blood-vessel and tissue growth, ingredient guidance recommends that people with psoriasis (where excess VEGF activity contributes to plaques) avoid Sh-Polypeptide-9 products, and that they not be used on sunburned skin or after high-dose ultraviolet exposure. By extension, a theoretical concern exists about applying a vessel-growth signal over skin with active or suspected skin cancer, since tumors exploit angiogenesis. These cautions are mechanistic and precautionary; no human cases of harm from cosmetic Sh-Polypeptide-9 have been documented.

#### Uncertain Long-Term Local Effects of Repeated VEGF Signaling

Sustained, repeated stimulation of an angiogenic signal in the scalp has not been studied for long-term safety. Whether chronic use could produce unwanted changes in scalp vasculature or skin is unknown, with no controlled long-term data; the basis for flagging it is biological plausibility and the absence of long-duration trials.

#### Allergic or Hypersensitivity Reactions to Formulation Components

As with any topical or injectable cosmetic containing peptides, preservatives, and carriers, allergic contact dermatitis or hypersensitivity is possible in susceptible individuals. Reports are isolated and not specific to Sh-Polypeptide-9, so this is flagged as speculative.

## Risk-Modifying Factors

* **Genetic polymorphisms:** No pharmacogenetic variants are known to modify the risk profile of Sh-Polypeptide-9; as a topical/injectable peptide it is not subject to the liver-enzyme variation relevant to oral drugs.

* **Baseline biomarker levels:** No blood biomarker predicts adverse response. People with conditions of dysregulated angiogenesis (e.g., active proliferative retinopathy) have no validated marker to guide safety here, but the underlying condition itself is the relevant flag.

* **Sex-based differences:** No sex-specific differences in side effects have been established for this peptide.

* **Pre-existing health conditions:** Psoriasis, active or recently treated skin cancer of the scalp, and other VEGF-driven dermatologic conditions raise the theoretical risk and are the main reasons to avoid use; recent sunburn or high UV exposure to the scalp is a temporary contraindication per ingredient guidance.

* **Age-related considerations:** Older adults more commonly have actinic (sun-damaged) scalp skin and a higher background risk of scalp skin cancers, which is relevant to the precautionary VEGF cautions; no age-specific toxicity data exist.

## Key Interactions & Contraindications

* **Prescription drug interactions:** No formal drug-interaction studies exist for Sh-Polypeptide-9. A theoretical pharmacodynamic interaction exists with systemic anti-angiogenic cancer drugs (VEGF inhibitors such as bevacizumab, or tyrosine-kinase inhibitors like sunitinib and pazopanib), where a topical VEGF-mimetic could in principle act opposite to therapy; relevance to scalp-applied cosmetic doses is unestablished. Severity: caution.

* **Over-the-counter medication interactions:** No established interactions with OTC oral medications. Topically, concurrent use of strong scalp irritants or exfoliating acids could increase local irritation. Severity: caution.

* **Supplement interactions:** No documented systemic supplement interactions.

* **Supplements/agents with additive effects:** Other VEGF-raising or angiogenic hair actives — copper peptides (copper tripeptide-1 / GHK-Cu), procyanidins, and topical minoxidil — may have additive pro-angiogenic effects when layered, which is generally the intended pairing in commercial formulations rather than a hazard. Severity: monitor (for cumulative irritation).

* **Other intervention interactions:** Frequently combined with microneedling or intradermal injection to improve delivery; combining with these increases penetration and therefore both potential benefit and local reaction.

* **Populations who should avoid it:** People with psoriasis, active or suspected scalp skin cancer, sunburned scalp skin, and those on systemic anti-VEGF cancer therapy should avoid use. Pregnant and breastfeeding individuals should avoid it given the absence of safety data.

* **Severity and consequence detail:** The psoriasis caution is treated as a relative-to-absolute contraindication (consequence: potential disease aggravation via excess VEGF activity); active scalp malignancy is an absolute contraindication (consequence: theoretical tumor angiogenesis support).

* **Mitigating actions:** Where caution applies, separating application from irritant scalp products, patch-testing before full use, and avoiding application to broken or sunburned skin reduce risk.

* **Population thresholds:** Avoid in psoriasis with active scalp plaques, any active scalp non-melanoma or melanoma skin cancer, scalp sunburn within the preceding days, and during pregnancy or lactation.

## Risk Mitigation Strategies

* **Patch test before first scalp use:** Apply a small amount to a discreet area of skin and wait 24–48 hours to check for redness or itching, mitigating allergic contact dermatitis and hypersensitivity reactions before full-scalp exposure.

* **Avoid compromised or sun-exposed scalp skin:** Do not apply to sunburned, broken, or recently high-UV-exposed scalp, mitigating the precautionary VEGF-over-damaged-skin concern flagged in ingredient guidance.

* **Screen for VEGF-sensitive conditions first:** Confirm absence of active psoriasis and active or suspected scalp skin cancer before starting, mitigating the theoretical risk of aggravating angiogenesis-driven disease.

* **Use validated, encapsulated, or clinic-administered formulations:** Choosing professionally formulated encapsulated topicals or clinician-delivered injections rather than ad-hoc raw-peptide mixtures mitigates both contamination/infection risk and the unpredictability of poorly absorbed product.

* **Separate from irritant scalp actives:** Apply at a different time from exfoliating acids, retinoids, or other strong scalp irritants — for example several hours apart — to mitigate cumulative local irritation.

* **Maintain aseptic technique for injectable use:** If used as an intradermal injection, ensuring sterile technique and trained administration mitigates injection-site infection, bruising, and bleeding.

## Therapeutic Protocol

There is no standardized, evidence-validated protocol for Sh-Polypeptide-9 as an isolated intervention; the following reflects how it appears in practice within products and clinic regimens.

* **Topical serum use (most common):** Marketed in leave-on scalp serums applied once or twice daily to the affected scalp, typically as part of a multi-peptide formula. Leading cosmetic formulators emphasize encapsulation to aid penetration.

* **Intradermal injection ("hair cocktail"):** In clinic settings the peptide appears in injectable growth-factor blends delivered into the scalp roughly every 2–3 weeks for a course of several sessions (the published growth-factor pilot used eight sessions every three weeks), often by dermatologists or facial-plastic clinicians who popularized these formulations.

* **Competing approaches:** A conventional approach favors established drugs (topical minoxidil, oral finasteride) as first line, positioning peptides as adjuncts; an integrative/cosmetic approach uses peptide blends and PRP-like cosmetics as a stand-alone or combination option. Neither is framed here as the default; the peptide's independent efficacy versus these is unproven.

* **Best time of day:** No circadian timing advantage is established; topical products are generally applied to a clean, dry scalp, and consistency matters more than time of day.

* **Half-life consideration:** As a VEGF-mimetic peptide, it acts locally and is broken down by tissue proteases over a short period (native VEGF half-life is on the order of tens of minutes), which is the rationale for repeated daily topical application or spaced repeat injections rather than single dosing.

* **Single versus split dosing:** Practical regimens favor repeated low-dose exposure (daily topical, or repeated injection sessions) over a single application, consistent with the peptide's short local persistence.

* **Genetic polymorphisms:** No pharmacogenetic variant is known to guide dosing for this peptide.

* **Sex-based differences:** No validated sex-based dosing differences; mixed-sex pilot data did not define separate protocols.

* **Age-related considerations:** Older adults with advanced miniaturization may require combination with established therapies for any meaningful effect; no age-specific dose is defined.

* **Baseline biomarker levels:** No baseline lab value guides dosing.

* **Pre-existing health conditions:** Protocol should be withheld in the contraindicated conditions (psoriasis, active scalp malignancy, sunburned scalp, pregnancy/lactation) rather than dose-adjusted.

## Discontinuation & Cycling

* **Lifelong versus short-term:** Like other non-curative hair actives, any benefit is expected to depend on continued use; the underlying drivers of hair loss are unaddressed, so stopping is likely to allow gradual reversion. This is inferred from the broader hair-active literature, not from dedicated discontinuation studies of Sh-Polypeptide-9.

* **Withdrawal effects:** No specific withdrawal syndrome is documented; unlike the well-known temporary shedding seen when stopping some drugs, no such effect has been characterized for this peptide.

* **Tapering-off protocol:** No tapering is required for a topical cosmetic peptide; it can be stopped abruptly, with the expectation that any gains fade over subsequent hair cycles.

* **Cycling:** No evidence supports or refutes cycling for maintained efficacy; there is no established cycling protocol, and continuous use is the implicit model in product instructions.

## Sourcing and Quality

* **Identity and labeling:** Look for the INCI name "sh-Polypeptide-9" (or the synonym CG-VEGF) on the ingredient list, with a clearly stated concentration where possible; reputable brands disclose that the peptide is recombinant/biotechnologically produced.

* **Formulation and delivery:** Prefer products that specify a penetration-enhancing system (e.g., liposomal or double-layer encapsulation), since an unencapsulated large peptide in a simple aqueous serum is unlikely to reach the dermal papilla.

* **Purity and third-party testing:** Because this is a cosmetic peptide rather than a regulated drug, choose manufacturers that provide certificates of analysis or third-party testing for identity, purity, and microbial contamination; raw "research peptide" powders of uncertain origin carry contamination and mislabeling risk.

* **Reputable sources:** Established cosmeceutical brands and licensed compounding or aesthetic clinics that source from recognized peptide suppliers are preferable to unverified online resellers of bulk peptide.

* **Storage:** Peptide products are typically sensitive to heat and light; follow refrigeration or cool-storage instructions to preserve activity, as degraded peptide loses any potential benefit.

## Practical Considerations

* **Time to effect:** Hair interventions act over hair-cycle timescales; in the blended human studies, regrowth was assessed at three to four months, and any topical effect would similarly be judged over a minimum of three to six months rather than weeks.

* **Common pitfalls:** Expecting drug-level results from a cosmetic peptide; using a poorly absorbed simple serum; attributing the regrowth seen in multi-ingredient blends to Sh-Polypeptide-9 alone; and substituting it for proven therapies in significant pattern hair loss.

* **Regulatory status:** Sh-Polypeptide-9 is regulated as a cosmetic ingredient (INCI-listed), not as an approved drug for hair loss; injectable growth-factor use is generally off-label/clinic-based and not approved as a standardized treatment. It has not received drug approval for androgenetic alopecia.

* **Cost and accessibility:** Premium peptide serums and clinic injection courses can be expensive relative to generic minoxidil or finasteride, and clinician-administered injectable blends are the more costly and less accessible route.

* **Overall framing:** Best understood as an adjunctive, mechanistically promising but clinically unproven option rather than a stand-alone treatment.

## Interaction with Foundational Habits

* **Sleep:** Direction — none established. There is no known mechanism by which a topically applied scalp VEGF-mimetic peptide affects sleep, and no data suggest sleep disruption or improvement; practical consideration: none specific.

* **Nutrition:** Direction — indirect, potentiating. Adequate protein, iron, zinc, and overall nutritional status are upstream requirements for hair growth, so correcting deficiencies plausibly enables any peptide benefit to manifest; the peptide itself does not deplete nutrients. Practical consideration: ensure iron and protein sufficiency before expecting topical results.

* **Exercise:** Direction — indirect, potentiating. Exercise improves systemic and cutaneous blood flow, which is mechanistically aligned with the peptide's vascular target, though no study has tested an exercise–peptide interaction; practical consideration: none specific beyond general cardiovascular health.

* **Stress management:** Direction — indirect. Psychological stress can trigger or worsen hair shedding (and alopecia areata in particular), so stress reduction may improve the background condition the peptide is applied to; the peptide has no known direct effect on cortisol or the stress response.

## Monitoring Protocol & Defining Success

Because Sh-Polypeptide-9 is a topical/injectable cosmetic without systemic absorption concerns, monitoring is primarily clinical and photographic rather than laboratory-based. Before starting, a baseline assessment of hair status and a screen for contraindicating skin conditions is appropriate; ongoing monitoring tracks regrowth over hair-cycle timeframes.

Baseline assessment should be performed before the first application: standardized scalp photographs, a hair-pull test, and (where available) trichoscopy or hair-count measurement, plus a skin examination to exclude psoriasis or scalp skin cancer. Ongoing monitoring follows a cadence of reassessment at roughly 3 months, 6 months, and then every 6 months, since meaningful change cannot be judged sooner than one full hair cycle.

The lab table below lists optional bloodwork relevant not to the peptide itself but to ruling out common, treatable contributors to hair loss that would otherwise limit any response.

| Biomarker | Optimal Functional Range | Why Measure It? | Context/Notes |
| --------- | ------------------------ | --------------- | ------------- |
| Ferritin (iron stores) | 50–100+ ng/mL | Low iron stores are a common, correctable cause of hair shedding | Conventional "normal" starts ~15–30 ng/mL, well below the functional hair threshold; fasting not required, but avoid testing during active infection (falsely raised) |
| TSH | 1.0–2.0 mIU/L | Thyroid dysfunction causes diffuse hair loss that mimics or compounds other causes | TSH (thyroid-stimulating hormone); best drawn in the morning, fasting; pair with free T4 if abnormal |
| Vitamin D (25-OH) | 40–60 ng/mL | Low vitamin D is associated with hair-cycle disturbance and alopecia areata | No fasting needed; interpret alongside season and supplementation |
| Zinc | 90–120 µg/dL | Zinc deficiency impairs hair-follicle function and protein synthesis | Draw fasting in the morning; avoid zinc supplements for several hours beforehand to avoid falsely high readings |

* **Functional vs. conventional ranges:** The ferritin target reflects functional-medicine guidance for hair (50–100+ ng/mL) rather than the much lower conventional deficiency cutoff; this distinction is the main reason "normal" labs can still coincide with shedding.

Qualitative markers to track alongside labs and photographs:

* Subjective reduction in daily hair shedding (e.g., hairs on pillow, in shower drain).
* Visible new short regrowth or "baby hairs" along thinning areas or the hairline.
* Improvement in hair-pull test (fewer hairs extracted).
* Perceived increase in overall density, coverage, or hair-shaft thickness.

## Emerging Research

* **No isolated-ingredient trials registered:** A ClinicalTrials.gov search returned no registered trials of Sh-Polypeptide-9 (or CG-VEGF) as a stand-alone hair intervention, which is the central gap: until such a trial exists, its independent efficacy cannot be confirmed.

* **Human blend studies as the current frontier:** The most relevant recent human work tests Sh-Polypeptide-9 inside multi-peptide cosmetics — a randomized controlled trial in alopecia areata ([Rinaldi et al., 2019](https://pubmed.ncbi.nlm.nih.gov/30513014/)) and a study using a biomimetic peptide solution as graft-storage and donor-scalp media in transplantation ([Gold et al., 2025](https://pubmed.ncbi.nlm.nih.gov/40228316/)). Both carry a conflict of interest: the first comes from the industry-linked International Hair Research Foundation, and the second evaluates a named commercial cocktail (QR678 Neo®) whose makers have a direct financial stake in a favorable result. Future work isolating the peptide would strengthen the case; null results in such designs would weaken it.

* **Foundational mechanistic work continues:** Research into VEGF-driven follicle angiogenesis ([Colin-Pierre et al., 2021](https://pubmed.ncbi.nlm.nih.gov/34957110/)) and the dermal-papilla coculture model first applied to this peptide ([Bassino et al., 2016](https://pubmed.ncbi.nlm.nih.gov/26662923/)) continues to clarify whether boosting VEGF signaling translates to durable human regrowth.

* **Delivery innovation:** A recurring theme is improving scalp penetration of large peptides — work on ionic-liquid microemulsions and encapsulation for topical peptide delivery ([Liu et al., 2024](https://pubmed.ncbi.nlm.nih.gov/38026438/)) could determine whether topical Sh-Polypeptide-9 can reach its target in humans, a prerequisite for any non-injected benefit.

* **Direction that could weaken the case:** Evidence that VEGF blockade in skin-organ models harms dermal vasculature ([Luengas-Martinez et al., 2020](https://pubmed.ncbi.nlm.nih.gov/32570235/)) underscores VEGF's importance but also flags that the therapeutic window and long-term safety of chronically stimulating scalp angiogenesis remain unstudied; rigorous safety data could either reassure or temper enthusiasm.

## Conclusion

Sh-Polypeptide-9 is a lab-made copy of the body's main blood-vessel-growth signal, added to scalp serums and clinic injection blends with the goal of feeding hair roots and waking up sluggish follicles. The biology behind it is sound: follicles need a rich blood supply to grow thick hairs, and raising this signal enlarges follicles in animals and stirs growth activity in human cells grown in the lab. That makes it a mechanistically appealing option for people actively working to keep or regrow hair.

The catch is that almost all of the human testing has been done with mixtures that combine this peptide with copper peptides and other growth factors, so it is impossible to say how much of the reported regrowth comes from Sh-Polypeptide-9 itself. Much of that testing also comes from companies and groups that sell or profit from these products, a conflict of interest that weakens how far the findings can be trusted. There are no studies of it on its own, and a real open question is whether enough of this large molecule even reaches the hair root through intact skin. Side effects in the published studies were mild, mostly local irritation, though people with psoriasis or active scalp skin problems are advised to avoid it.

Overall, the evidence is early and indirect. It is best viewed as a promising but unproven add-on rather than a stand-alone answer, with the strongest, most established hair options lying elsewhere.

**[Top](#top) - [Benefits](#expected-benefits) - [Risks](#potential-risks--side-effects) - [Protocol](#therapeutic-protocol)**