Recombinant Human Stem Cell Factor
SCF
KIT Ligand
Mast Cell Growth Factor
rh-Polypeptide-4
CG-SCF

---
canonical_name: sh-Polypeptide-4
alternate_names: Recombinant Human Stem Cell Factor, SCF, KIT Ligand, Mast Cell Growth Factor, rh-Polypeptide-4, CG-SCF
canonical_topic: sh-Polypeptide-4 for Hair Regrowth
short_topic_lc: sh_polypeptide_4_hair
creation_date: 2026-0708-1913
creator_ai_fullname: Opus 4.8
ep_keywords: Growth Factors, Cytokines
---

# sh-Polypeptide-4 for Hair Regrowth

Evidence Review created on 07/08/2026 using [AI4L](https://github.com/forever-healthy/AI4L) / Opus 4.8

**Also known as:** Recombinant Human Stem Cell Factor, SCF, KIT Ligand, Mast Cell Growth Factor, rh-Polypeptide-4, CG-SCF

## Motivation

sh-Polypeptide-4 is the cosmetic-industry name for a lab-made version of a natural signaling protein called stem cell factor. In the body, this protein tells certain cells — including the pigment-making cells and the stem cells around each hair follicle — to survive, multiply, and move into place. Because those same cells help decide whether hair grows in thick and keeps its color, formulators began adding it to topical scalp serums aimed at thinning and greying hair.

Interest grew from a simple observation: follicles from balding scalps make less of this protein than healthy ones, and the pigment cells that rely on it fade as the hair shrinks. That link between the protein, hair color, and follicle health made it appealing, and it now appears — usually alongside other growth factors — in a range of cosmetic hair products.

This review examines what is actually known about putting synthetic stem cell factor on the scalp for hair regrowth: the biology behind the claims, the strength and limits of the evidence, the practical problem of how such a large protein reaches the follicle, and the possible risks. The aim is to lay out the evidence, not to direct any course of action.

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

## Recommended Reading

This section lists high-level resources that give useful context on hair regrowth, follicle biology, and the role of growth factors such as stem cell factor.

* [The Science of Healthy Hair, Hair Loss and How to Regrow Hair](https://www.hubermanlab.com/episode/the-science-of-healthy-hair-hair-loss-and-how-to-regrow-hair) - Andrew Huberman

  A deep, mechanism-first walk through how hair follicles cycle and how blood flow, hormones, and follicle stem cells govern regrowth, giving essential background for judging any growth-factor-based scalp product.

* [#43 – Alan Bauman, M.D.: The Science of Male and Female Hair Restoration](https://peterattiamd.com/alanbauman/) - Peter Attia

  A hair-restoration surgeon explains what drives pattern hair loss and reviews non-surgical options, including platelet-rich plasma (PRP) and growth-factor-based scalp treatments, providing a clinician's perspective on where these agents fit.

* [Stem cell factor/c-Kit signalling in normal and androgenetic alopecia hair follicles](https://pubmed.ncbi.nlm.nih.gov/18372228/) - Randall et al., 2008

  The most directly relevant primary study, showing that dermal papilla cells from balding follicles secrete less stem cell factor and linking this protein to follicle pigmentation — the core rationale for using it on the scalp.

* [The biology of human hair greying](https://pubmed.ncbi.nlm.nih.gov/32965076/) - O'Sullivan et al., 2021

  A thorough narrative review of how follicle pigment cells are maintained and lost, clarifying why stem cell factor is studied more for hair color than for raw hair count.

* [How to Slow and Reverse Hair Loss](https://www.lifeextension.com/magazine/2025/5/slow-reverse-hair-loss) - Michael Downey

  A consumer-facing overview of the hair-loss landscape that situates growth-factor and regenerative approaches alongside more established options, useful for understanding how these serums are positioned.

Content from prioritized experts Rhonda Patrick (foundmyfitness.com) and Chris Kresser (chriskresser.com) could not be found: neither has published material addressing stem cell factor, sh-Polypeptide-4, or growth-factor serums for hair regrowth.

## Grokipedia

[Stem cell factor](https://grokipedia.com/page/Stem_cell_factor)

Grokipedia's dedicated article on stem cell factor — the signaling protein that sh-Polypeptide-4 is the lab-made cosmetic version of — describes it as a pleiotropic cytokine and growth factor that binds and activates the c-Kit receptor, providing background on the molecule's biology that underlies its use in scalp serums.

## Examine

No Examine article exists for sh-Polypeptide-4 (stem cell factor). Examine.com covers ingestible dietary supplements, and this intervention is a topical cosmetic protein that falls outside that scope.

## ConsumerLab

No ConsumerLab article exists for sh-Polypeptide-4 (stem cell factor). ConsumerLab tests ingestible supplement products, and this intervention is a topical cosmetic protein that falls outside that scope.

## Systematic Reviews

No systematic reviews or meta-analyses for sh-Polypeptide-4 were found on PubMed as of July 8, 2026.

## Mechanism of Action

sh-Polypeptide-4 is a synthetic recombinant form of stem cell factor (SCF), a protein the body uses to guide cell survival, growth, and movement. Its actions in the follicle center on one receptor.

* **Binding to the c-KIT receptor:** SCF is the natural partner (ligand) of c-KIT (a receptor protein sitting on the surface of certain cells that switches on growth and survival signals when SCF binds it). When SCF docks onto c-KIT, the receptor pairs up and activates internal signaling cascades — chiefly the ERK, AKT, and p38 pathways (cell-signaling relay systems that control whether a cell divides, survives, or moves).

* **Pigment-cell (melanocyte) support:** The cells most dependent on SCF/c-KIT signaling in the follicle are melanocytes (the pigment-producing cells) and their precursors. SCF keeps these cells alive, prompts them to multiply, and guides their migration into the growing hair bulb, where they color the hair shaft. Loss of this signal is closely tied to hair greying.

* **Follicle stem-cell niche and blood supply:** SCF is one of several signals in the follicle's dermal papilla (the cluster of cells at the base of each follicle that directs the hair cycle). It has also been reported to raise vascular endothelial growth factor (VEGF, a signal that drives new blood-vessel formation), which could improve the follicle's blood and nutrient supply.

* **Competing views:** The evidence that SCF drives pigmentation is strong and consistent. Whether it meaningfully increases hair *count* or shaft thickness in humans is far less settled — supportive findings come mainly from animal overexpression models, while a competing view holds that follicle stem-cell activation for hair growth depends largely on other, c-KIT-independent signals, with SCF acting mostly on color rather than density.

Key pharmacological properties, as relevant to a recombinant protein rather than a small-molecule drug:

* **Selectivity:** Highly selective for the c-KIT receptor; it does not act on the androgen pathway that drives pattern hair loss.

* **Half-life and distribution:** Soluble stem cell factor circulates with a half-life on the order of hours when given systemically; applied topically, it stays largely at the application site. Tissue distribution in skin centers on melanocytes, mast cells, and keratinocytes, which express c-KIT or produce SCF.

* **Metabolism:** As a protein of up to 273 amino acids (roughly 18–36 kilodaltons, kDa, a unit of molecular weight, in its active dimer form), it is broken down by ordinary proteases (protein-digesting enzymes) in skin and blood rather than by liver enzymes such as the cytochrome P450 (CYP) family.

## Historical Context & Evolution

* **Original intended use:** Stem cell factor was identified and cloned around 1990 (under several names, including Steel factor and KIT ligand). Its first serious therapeutic development was in blood medicine: a recombinant version (ancestim) was studied to mobilize blood-forming stem cells from bone marrow, usually paired with granulocyte colony-stimulating factor (G-CSF, a drug that stimulates white-blood-cell production), to improve stem-cell collection for transplantation.

* **Why it came to be considered for hair:** Early recombinant SCF studies noted two skin effects — increased pigment cells and mast-cell activity at injection sites. Because the pigment cells of the hair follicle depend on SCF/c-KIT signaling, and because balding follicles were later shown to produce less SCF, cosmetic developers repurposed the protein as a topical ingredient aimed at hair color and follicle health, listing it under the cosmetic naming system as sh-Polypeptide-4.

* **What the early findings actually showed:** In a phase I study, systemically injected recombinant human SCF produced localized areas of increased pigmentation and higher melanocyte numbers, alongside mast-cell activation. These are real, documented biological effects — not disproven — but they were seen with injection at doses far higher than any topical cosmetic exposure, so they establish plausibility rather than proof of a hair-regrowth benefit.

* **Evolution of opinion:** The scientific reading has shifted from broad enthusiasm for "growth factors in a bottle" toward a more cautious position: the pigment-cell biology is well supported, while the leap to topical hair regrowth in humans remains largely untested. New evidence could move the picture in either direction, and no single view should be treated as the final word.

## Expected Benefits

Benefits below are framed for a proactive, health-oriented adult considering a topical growth-factor serum, and they reflect that most human evidence for this protein concerns pigmentation rather than hair count.

### Low 🟩

#### Follicle Pigment-Cell Support and Repigmentation

Stem cell factor is essential for the survival, multiplication, and migration of the follicle's pigment cells, and this is its best-supported effect. Human mechanistic work shows that balding follicles secrete less of it and that the protein maintains the pigment cells that color the hair shaft; a phase I human study of recombinant SCF produced visible new pigmentation where it was applied. The plausible benefit for this audience is slowing or partly reversing greying and supporting the pigment cells of miniaturizing follicles, though no controlled topical trial has confirmed a cosmetic-strength serum can do this on the scalp.

**Magnitude:** In a phase I study of recombinant human stem cell factor, 5 of 10 treated patients developed localized hyperpigmentation with clearly increased melanocyte numbers at treated sites.

### Speculative 🟨

#### Direct Hair Regrowth and Growth-Phase (Anagen) Induction

The claim most often marketed — that the protein regrows hair or thickens shafts — rests mainly on animal models in which stem cell factor was genetically overexpressed, producing changes in hair fiber characteristics and follicle development. For this audience, that translates into a possible but unproven increase in the number of follicles entering the growth phase (anagen). No controlled human study has shown that a topical serum increases hair count or density, so the basis here is mechanistic and preclinical only.

#### Angiogenic Support of the Follicle

By raising vascular endothelial growth factor, stem cell factor could indirectly improve the small blood vessels feeding the follicle, echoing the rationale behind blood-flow-focused hair treatments. This is a plausible secondary mechanism rather than a demonstrated outcome; the basis is mechanistic, with no human hair-specific data isolating this effect.

#### Adjunctive Effect Within Combination Growth-Factor Serums

Stem cell factor is almost never sold alone; it appears in blends with growth factors such as basic fibroblast growth factor, VEGF, and insulin-like growth factor 1 (IGF-1). Any real-world benefit a user notices likely reflects the whole formulation and delivery method rather than this single ingredient. The basis is indirect and anecdotal, and no study has isolated sh-Polypeptide-4's specific contribution within such blends.

## Benefit-Modifying Factors

* **Baseline stem cell factor / follicle status:** People whose follicles already produce adequate stem cell factor may gain little, whereas those with early miniaturization and fading pigment — where the signal is reduced — have the clearest theoretical room to benefit.

* **Genetic polymorphisms:** Variants in the *KIT* and *KITLG* genes (which encode the receptor and the protein itself) influence pigment-cell biology and could plausibly change responsiveness; this has not been studied for topical hair use.

* **Baseline biomarker levels:** Low iron stores (ferritin), low vitamin D, or thyroid imbalance independently drive hair shedding and can blunt any apparent benefit from a topical serum until corrected.

* **Sex-based differences:** Pattern hair loss differs by sex in distribution and hormonal drivers; women more often have diffuse thinning where a pigment/follicle-support agent might be perceived differently than in male frontal recession. No sex-specific data exist for this protein.

* **Pre-existing health conditions:** Active scalp inflammation, dermatitis, or scarring hair loss changes the follicle environment and is likely to limit any benefit.

* **Age-related considerations:** Older adults at the upper end of the target range have fewer active follicle stem cells and pigment-cell reserves, so both regrowth and repigmentation potential decline with age.

## Potential Risks & Side Effects

Risks are framed for a health-aware adult using a topical cosmetic serum; most documented harms come from high-dose systemic exposure and are far less likely with cosmetic topical use.

### Low 🟥

#### Local Skin Irritation and Itching

Topical growth-factor serums can cause redness, itching, or a stinging sensation, and stem cell factor specifically activates mast cells (immune cells that release histamine), which can add an itch or hives-like response at the application site. For most users this is mild and reversible on stopping, but it is the most likely real-world side effect, especially when the serum is driven in with microneedling.

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

### Speculative 🟨

#### Unwanted Pigmentation Changes and Pigment-Cell Overgrowth

Because the protein drives pigment cells, it could in theory cause patchy darkening of skin or existing moles, or localized pigment-cell overgrowth. Injected recombinant SCF produced areas of increased pigmentation and melanocyte hyperplasia (an increase in pigment-cell numbers) in early human studies. Whether a low-dose topical serum reaches concentrations that do this on the scalp is unknown, so the basis is extrapolation from higher-dose injection data.

#### Theoretical Pro-Growth and Melanoma-Related Concern

The SCF/c-KIT signal is active in some melanomas and other proliferating cells, which raises a theoretical concern about repeatedly stimulating it on the skin, particularly over atypical moles. No case of topical serum-related cancer has been documented, and the concern is mechanistic only, but it is the most important reason for caution in people with a personal or family history of melanoma.

#### Systemic Mast-Cell Activation

At the high systemic doses used in blood-medicine studies, recombinant SCF triggered widespread mast-cell degranulation and allergic-type reactions. Topical cosmetic exposure is orders of magnitude lower and systemic effects would be surprising, but individuals with mast-cell disorders remain a theoretical at-risk group; the basis is high-dose injection data, not topical evidence.

#### Immunogenicity or Contamination of Recombinant Proteins

Any recombinant protein carries a theoretical risk of provoking an immune response or of impurities from the manufacturing host, and cosmetic-grade products are not held to pharmaceutical purity standards. Reactions of this kind are not documented for cosmetic sh-Polypeptide-4, so the basis is general to recombinant-protein products rather than specific reports.

## Risk-Modifying Factors

* **Genetic polymorphisms:** Variants in pigment-related genes (*KIT*, *KITLG*, *MC1R*) could influence how strongly pigment cells respond and therefore the likelihood of pigmentation-related effects; this is unstudied for topical use.

* **Baseline biomarker levels:** A high baseline mast-cell burden (as in mast-cell activation disorders) could increase itch and allergic-type responses.

* **Sex-based differences:** No sex-specific safety data exist; general topical-irritation tendencies do not differ meaningfully by sex for this ingredient.

* **Pre-existing health conditions:** A personal or family history of melanoma or many atypical moles raises the theoretical proliferation concern; active mast-cell disease raises the reaction concern; broken or inflamed scalp skin increases absorption and irritation.

* **Age-related considerations:** Older adults accumulate more sun-damaged skin and atypical pigmented lesions, modestly raising the theoretical pigment-cell concern with repeated scalp application.

## Key Interactions & Contraindications

* **Prescription drug interactions:** Tyrosine kinase inhibitors that block c-KIT (imatinib, sunitinib, nilotinib) act in direct opposition to stem cell factor and would be expected to neutralize any effect; severity — pharmacologic antagonism, consequence — loss of the serum's intended action. Systemic hair drugs such as oral finasteride or dutasteride work on a different pathway and are not known to interact; severity — none expected.

* **Over-the-counter medication interactions:** Oral antihistamines could mask the itch/hives that would otherwise signal mast-cell irritation; severity — caution, consequence — a local reaction may go unnoticed. Topical hydrocortisone may blunt both irritation and any intended pigment-cell effect at the site.

* **Supplement interactions:** No systemic supplement is known to interact meaningfully with a topical protein; severity — none expected.

* **Additive-effect supplements/topicals:** Other topical growth-factor serums, copper peptides (copper tripeptide-1, GHK-Cu), and topical minoxidil applied to the same area may have additive follicle-stimulating or vascular effects; severity — monitor, consequence — greater scalp irritation when layered. Combining with microneedling markedly increases delivery and therefore both potential effect and irritation.

* **Other intervention interactions:** Microneedling and fractional laser dramatically raise absorption of the protein; severity — caution, consequence — stronger local reactions and unknown deeper exposure. Separating aggressive procedures from serum application, or lowering frequency, mitigates this.

* **Populations who should avoid this intervention:** People with a personal history of melanoma or many atypical (dysplastic) moles on the scalp; people with mast-cell activation syndrome or systemic mastocytosis; those with active scalp infection, dermatitis, or open wounds; and, on precautionary grounds given the absence of safety data, those who are pregnant or breastfeeding. A mitigating action where use is still chosen is to avoid application directly over pigmented lesions and to patch-test first.

## Risk Mitigation Strategies

* **Patch-test before scalp-wide use:** Apply a small amount to a discreet area for several days to detect itching, hives, or redness before broader use — directly targeting the local irritation and mast-cell reaction risk.

* **Avoid application over moles and pigmented lesions:** Keep the serum off atypical or changing moles on the scalp and hairline — targeting the theoretical pigment-cell overgrowth and melanoma concern.

* **Have the scalp skin-checked first in high-risk people:** Those with a melanoma history or many atypical moles should obtain a dermatologist skin exam before starting and at roughly 6–12 month intervals if continuing — targeting the proliferation concern.

* **Separate from aggressive delivery procedures:** If using microneedling or fractional laser, avoid stacking the serum on freshly and deeply injured skin; space application by at least 24 hours or reduce needling depth/frequency — targeting the excess-absorption and systemic-exposure risk.

* **Start with low frequency and one product at a time:** Begin at the lowest labeled frequency and avoid layering multiple growth-factor or copper-peptide serums initially — targeting additive irritation and making any reaction easier to attribute.

* **Correct the fundamentals first:** Screen and correct iron, vitamin D, and thyroid status before judging the serum — targeting the risk of wasted use and misattributed shedding rather than a direct harm.

## Therapeutic Protocol

There is no validated clinical protocol for sh-Polypeptide-4; the guidance below reflects how growth-factor serums are generally used by aesthetic practitioners and how the biology suggests they should be approached.

* **Standard practical approach:** Most cosmetic use involves a leave-on topical serum applied once or twice daily to a clean, dry scalp, often as part of a multi-growth-factor blend rather than as a single ingredient.

* **Competing approaches:** Two broad camps exist without one being the default — a conservative topical-only approach (serum applied to intact skin), and a delivery-enhanced approach that pairs the serum with microneedling or fractional laser to overcome poor penetration. The enhanced approach may increase effect but also increases irritation and unknown deeper exposure.

* **Who popularized each approach:** Delivery-enhanced growth-factor protocols were popularized largely by aesthetic dermatology and medical-spa practice, building on microneedling and platelet-rich plasma (PRP) work in hair restoration.

* **Best time of day:** Timing is not critical for a topical protein; applying to a clean scalp when the hair will be left undisturbed (commonly evening) is practical.

* **Half-life consideration:** Because soluble stem cell factor is short-lived (hours) and is degraded by skin proteases, repeated regular application rather than a single dose is the rationale behind daily use.

* **Single versus split dosing:** For a topical serum, "split dosing" means once- versus twice-daily application; twice daily is common, but no evidence establishes that it outperforms once daily.

* **Genetic polymorphisms:** No pharmacogenetic testing guides dosing; variants in *KIT*/*KITLG* are of theoretical interest only.

* **Sex-based differences:** No sex-specific dosing exists; women with diffuse thinning and men with patterned recession use the same topical approach.

* **Age-related considerations:** Older users at the upper target range should expect diminished response and apply the same precautionary skin-check steps.

* **Baseline biomarker levels:** Iron (ferritin), vitamin D, and thyroid status should be assessed first, as deficiencies undermine any topical effort.

* **Pre-existing health conditions:** Active scalp disease should be treated before starting, and the contraindicated populations above should not use it.

## Discontinuation & Cycling

* **Lifelong versus short-term:** Like other cosmetic hair actives, any effect is expected to depend on continued use; the protein does not permanently reprogram the follicle, so benefits are presumed to fade after stopping.

* **Withdrawal effects:** No withdrawal syndrome is known. Because pattern hair loss is progressive, stopping simply returns the follicle to its underlying trajectory rather than causing a rebound.

* **Tapering:** No tapering is required for a topical cosmetic protein; it can be stopped abruptly.

* **Cycling:** No evidence supports or refutes cycling. Some users pause periodically to reassess irritation or benefit, but there is no efficacy rationale for scheduled cycling.

* **Practical discontinuation trigger:** Persistent itching, new or changing pigmented lesions, or no perceptible change after a fair trial are reasonable reasons to stop.

## Sourcing and Quality

* **Formulation and stability:** Because it is a large, fragile protein, look for products that address stability (cool-chain shipping, opaque or airless packaging, and a stated concentration) rather than vague "growth factor" labeling.

* **What to look for:** Prefer products that disclose the specific INCI (International Nomenclature of Cosmetic Ingredients) name sh-Polypeptide-4, name the production source, and provide third-party or in-house purity and identity testing; cosmetic growth factors are not held to drug-grade purity, so transparency matters.

* **Reputable sources:** Buy from established cosmeceutical brands or compounding/aesthetic suppliers that publish specifications, rather than unbranded marketplace peptides sold as "research" material, which carry unverified identity and purity.

* **Realistic expectations of delivery:** Recognize that a serum listing the ingredient does not guarantee the protein reaches the follicle intact; delivery technology (liposomal carriers, microneedling) is often the deciding factor and should be part of the sourcing decision.

## Practical Considerations

* **Time to effect:** Any pigment or hair-cycle change would unfold over the follicle's timescale — generally at least 3–6 months of consistent use before a fair judgment, mirroring other hair actives.

* **Common pitfalls:** Expecting drug-like regrowth from a cosmetic serum; ignoring poor skin penetration of a large protein; layering many irritating actives at once; and failing to correct iron, vitamin D, or thyroid problems that drive shedding regardless of any serum.

* **Regulatory status:** In the United States and European Union, sh-Polypeptide-4 is a cosmetic ingredient, not an approved drug for hair growth; marketing claims are cosmetic, and it has not undergone drug efficacy or safety review for this use.

* **Cost and accessibility:** Growth-factor serums are generally expensive relative to established topicals and are widely available without prescription; cost and unproven benefit are the main accessibility considerations rather than scarcity.

## Interaction with Foundational Habits

* **Sleep:** Indirect interaction. A topical protein has no direct effect on sleep and sleep does not degrade it, but poor sleep worsens stress-related shedding, which can mask any benefit; no timing considerations apply.

* **Nutrition:** Indirect, potentiating interaction. The serum cannot compensate for the nutrient inputs follicles need — adequate protein, iron, zinc, and vitamin D — so correcting diet and deficiencies is the practical prerequisite that lets any follicle-support effect show; no specific food needs to be avoided.

* **Exercise:** Indirect interaction. Exercise-driven scalp blood flow is broadly favorable for follicle health and does not blunt the serum; sweat and vigorous washing simply argue for applying to a clean, dry scalp after training rather than before.

* **Stress management:** Indirect interaction. Chronic stress can push follicles into shedding through cortisol and related pathways, counteracting perceived benefit; stress reduction supports the same goal, with no direct chemical interaction with the protein.

## Monitoring Protocol & Defining Success

Because this is a topical cosmetic with no drug-level monitoring requirements, baseline testing focuses on the treatable drivers of hair loss that would otherwise confound results, plus a skin check in higher-risk users. The following baseline labs establish whether shedding has a correctable cause before a serum is judged.

| Biomarker | Optimal Functional Range | Why Measure It? | Context/Notes |
|-----------|--------------------------|-----------------|---------------|
| Ferritin (iron stores) | 40–70 ng/mL | Low iron is a common, correctable cause of shedding | Conventional labs flag "low" only below ~15–30 ng/mL; hair benefits from higher stores. Best drawn fasting; avoid during acute illness (falsely high) |
| 25-hydroxy vitamin D | 40–60 ng/mL | Low vitamin D is linked to hair-cycle disruption | Conventional "sufficient" starts at 30 ng/mL; not fasting; pair with a metabolic panel if supplementing |
| Thyroid-stimulating hormone (TSH) | 0.5–2.5 mIU/L | Thyroid imbalance causes diffuse shedding | Conventional upper limit ~4.0–4.5 mIU/L is looser than the functional target; best drawn in the morning |
| Scalp/mole skin exam (qualitative) | No new or changing pigmented lesions | Screens the theoretical pigment-cell concern before repeated application | Not a blood test; performed by a dermatologist in higher-risk users at baseline and periodically |

Ongoing monitoring is mostly visual and self-directed rather than lab-based: reassess at 3 months, 6 months, then every 6–12 months, checking standardized scalp photos, tolerability, and any pigmented-lesion changes; repeat ferritin, vitamin D, and TSH every 6–12 months only if they were abnormal or symptoms persist.

Qualitative markers of success or trouble:

* Shedding rate (hairs lost when washing or brushing) trending down.
* Visible density or coverage on consistent, same-lighting photos.
* Hair color at the roots (any slowing of greying, the effect with the strongest biological rationale).
* Scalp comfort — absence of persistent itching, redness, or hives.
* Any new or changing mole on the scalp (a reason to stop and seek review).

## Emerging Research

Research framed for a health-oriented adult weighing whether this ingredient will earn stronger evidence:

* **Growth-factor scalp serums under formal testing:** A completed controlled study of a scalp essence containing the growth factors IGF-1 and FGF-7 (fibroblast growth factor 7) ([NCT06985121](https://clinicaltrials.gov/study/NCT06985121); 60 participants) tested whether defined growth factors in a topical base improve scalp and hair measures — the closest trial design to how sh-Polypeptide-4 is marketed, and a template that could either validate or undercut growth-factor topicals broadly.

* **Regenerative exosome topicals for pattern hair loss (recruiting):** A randomized study of umbilical-cord stem-cell-derived exosomes — which carry a mix of growth factors — for androgenetic alopecia (the common hormone- and genetics-driven pattern thinning) is enrolling ([NCT07373054](https://clinicaltrials.gov/study/NCT07373054); 18 participants, comparing exosome preparations against minoxidil with microneedling). Positive results would strengthen the general "growth factors on the scalp" thesis; null results would weaken it.

* **Larger exosome program (active):** A further exosome study in androgenetic alopecia is active and not recruiting ([NCT06697080](https://clinicaltrials.gov/study/NCT06697080); 50 participants), adding scale to the regenerative-topical evidence base that sh-Polypeptide-4 rides on.

* **Mechanistic direction that supports the pigment rationale:** The foundational human work linking reduced stem cell factor to balding follicles (Randall et al., 2008, [PMID 18372228](https://pubmed.ncbi.nlm.nih.gov/18372228/)) anchors why repigmentation is the most defensible target; deeper follow-up here could sharpen which users, if any, benefit.

* **Adjacent growth-factor reviews that could reframe expectations:** A 2025 review of IGF-1 in hair regeneration ([PMID 41020895](https://pubmed.ncbi.nlm.nih.gov/41020895/)) and a systematic review of exosome-based hair regrowth ([PMID 42377704](https://pubmed.ncbi.nlm.nih.gov/42377704/)) map the wider growth-factor field; both could shift expectations up or down as controlled human data accumulate, and neither yet supports stem cell factor as a proven standalone regrowth agent.

## Conclusion

sh-Polypeptide-4 is a lab-made copy of a natural body signal called stem cell factor, added to scalp serums in the hope of regrowing and re-coloring hair. Its biology is genuinely interesting: this signal keeps the follicle's pigment cells alive and guides them into the growing hair, and follicles from balding scalps make less of it. That gives a real, well-supported rationale for one specific effect — supporting hair color — and a weaker, mostly animal-based rationale for actually growing more hair.

The gap between that biology and proof in people is wide. There are no controlled human trials showing that a cosmetic-strength serum regrows hair, and a central practical problem is that such a large protein struggles to reach the follicle without aggressive delivery methods. The main downsides are local irritation and, more theoretically, unwanted pigment changes and pigment-cell overgrowth, which matter most for anyone with a history of skin moles or melanoma.

Overall, the evidence base is thin and leans on laboratory and animal work rather than human outcomes. The color-related biology is the strongest part of the story, the hair-count claims remain unproven, and the honest summary is one of plausible mechanism paired with genuine uncertainty.

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


---
canonical_name: sh-Polypeptide-59
alternate_names: Synthetic Human Platelet-Derived Growth Factor B, PDGF-B, PDGF-BB, Recombinant Human PDGF-BB, rh-PDGF
canonical_topic: sh-Polypeptide-59 for Hair Regrowth
short_topic_lc: sh_polypeptide_59_hair
creation_date: 2026-0708-1916
creator_ai_fullname: Opus 4.8
ep_keywords: Growth Factor Peptides, Cosmetic Peptides, Topical Peptides
---

# sh-Polypeptide-59 for Hair Regrowth

Evidence Review created on 07/08/2026 using [AI4L](https://github.com/forever-healthy/AI4L) / Opus 4.8

**Also known as:** Synthetic Human Platelet-Derived Growth Factor B, PDGF-B, PDGF-BB, Recombinant Human PDGF-BB, rh-PDGF

## Motivation

sh-Polypeptide-59 is a laboratory-made copy of a natural human signaling protein called platelet-derived growth factor B. It is produced by fermentation in engineered bacteria and belongs to a growing family of "growth factor" ingredients added to leave-on hair serums that aim to wake dormant follicles and thicken thinning hair.

The parent protein helps regulate the specialized cells at the base of each hair follicle and supports the follicle's active growing phase. Interest in it for hair grew alongside the popularity of platelet-rich scalp treatments, which are naturally rich in the same protein and which some clinicians use to nudge resting follicles back into growth. Cosmetic formulators responded by adding the isolated protein directly to serums, often paired with tiny needling devices meant to help it reach its target.

This review examines the evidence for and against applying sh-Polypeptide-59 to the scalp for hair regrowth. It looks at how the protein is thought to work, how strong the human data actually are, the potential risks, and how the ingredient is typically used, so the picture can be weighed against more established hair options.

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

## Recommended Reading

This section collects high-level, expert-driven overviews of hair-loss biology and the growth-factor approach that provide context for evaluating sh-Polypeptide-59.

* [The Science of Healthy Hair, Hair Loss and How to Regrow Hair](https://www.hubermanlab.com/episode/the-science-of-healthy-hair-hair-loss-and-how-to-regrow-hair) - Andrew Huberman

  A structured tour of hair biology and the mechanisms behind common treatments, including the central role of follicle stem cells and blood flow that growth-factor serums such as sh-Polypeptide-59 are designed to target. It is useful for placing an unproven ingredient beside established options like minoxidil, finasteride, microneedling, and platelet-rich plasma (PRP).

* [AMA #63: A Guide for Hair Loss: Causes, Treatments, Transplants, and Sex-Specific Considerations](https://peterattiamd.com/ama63/) - Peter Attia

  A practical clinician's overview of androgenetic alopecia (male- or female-pattern hair loss) and its treatment ladder, including where platelet-rich plasma and other regenerative options fit and how much data actually support them. It frames the realistic expectations and cost trade-offs against which a cosmetic growth-factor serum should be judged.

* [Support Hair and Scalp Regeneration](https://www.lifeextension.com/magazine/2014/6/support-healthy-hair-and-scalp-regeneration) - Goldfaden & Goldfaden

  A consumer-facing article centered on the same follicle dermal stem cells that platelet-derived growth factor acts on, describing how activating these cells can drive hair formation. It illustrates the mechanistic logic behind topical "regeneration" products while relying largely on early-stage and preliminary evidence.

* [Platelet-derived growth factor signaling modulates adult hair follicle dermal stem cell maintenance and self-renewal](https://pubmed.ncbi.nlm.nih.gov/29302347/) - González et al., 2017

  A primary study showing that platelet-derived growth factor signaling is required to maintain and expand the dermal stem cells that repopulate the follicle and that its ligand improves their ability to induce new follicles. It is the closest direct mechanistic support for why this specific protein might matter to hair, albeit in mice and isolated cells rather than human scalp.

* [Role of platelet-derived growth factors in physiology and medicine](https://pubmed.ncbi.nlm.nih.gov/18483217/) - Andrae et al., 2008

  An authoritative narrative review of the entire platelet-derived growth factor family, its receptors, and its roles in development, tissue repair, and disease. It is valuable both for understanding the intended biology and for appreciating the protein's documented involvement in fibrosis and tumor stroma, which underpins the safety questions raised later in this review.

Note: Among the prioritized experts, substantial coverage was found for Andrew Huberman, Peter Attia, and Life Extension; Rhonda Patrick's and Chris Kresser's platforms did not contain material specific to growth factors for hair regrowth at the time of writing.

## Grokipedia

No dedicated Grokipedia article exists for sh-Polypeptide-59.

## Examine

No dedicated Examine article exists for sh-Polypeptide-59. Examine.com focuses on ingestible supplements and does not cover topical cosmetic growth-factor ingredients such as this one.

## ConsumerLab

No dedicated ConsumerLab article exists for sh-Polypeptide-59. ConsumerLab tests ingestible supplements and does not cover topical cosmetic growth-factor ingredients.

## Systematic Reviews

No systematic reviews or meta-analyses for sh-Polypeptide-59 were found on PubMed as of July 8, 2026.

## Mechanism of Action

sh-Polypeptide-59 is the cosmetic-nomenclature name (under the International Nomenclature of Cosmetic Ingredients, or INCI) for a recombinant, single-chain copy of the B subunit of platelet-derived growth factor (PDGF), made by bacterial fermentation. In the body, two B subunits pair to form the active protein PDGF-BB, a member of a family of signaling proteins that direct the growth and movement of connective-tissue and blood-vessel cells.

* **Receptor signaling:** PDGF-BB binds PDGF receptors (PDGFR-α and PDGFR-β) on the surface of target cells. These receptors are receptor tyrosine kinases — enzymes that, once switched on, add phosphate tags to themselves and trigger internal cascades. The main downstream routes are the PI3K/Akt pathway (a cell-survival and growth signal), the MAPK/ERK pathway (a proliferation signal), and phospholipase C-gamma (a lipid-signaling enzyme that helps relay the receptor's message inside the cell). The net effect is to make certain cells divide, survive, and migrate.

* **Relevance to the hair follicle:** The follicle grows through a repeating cycle — anagen (active growth), catagen (regression), and telogen (rest). Its behavior is directed by the dermal papilla, a small cluster of cells at the base of the follicle. Platelet-derived growth factor helps maintain the dermal stem cells that rebuild the papilla, promotes proliferation of dermal papilla cells, and is thought to help push resting follicles into the growth phase. It also encourages angiogenesis (new small-blood-vessel formation), which improves the follicle's blood supply.

* **Why it appears in hair products:** The same protein is a major component released by platelets, which is why platelet-rich plasma (PRP) — concentrated from a person's own blood — delivers it to the scalp. Cosmetic serums instead supply the isolated recombinant protein, frequently alongside other recombinant growth factors such as vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), insulin-like growth factor 1 (IGF-1), and basic fibroblast growth factor (bFGF).

* **Competing mechanistic views:** Supporters argue the follicle biology above justifies topical use, especially when penetration is enhanced by microneedling. Skeptics counter that PDGF-BB is a large protein — its active form is roughly 25 kilodaltons (kDa, a unit of molecular weight), far above the approximately 500-dalton limit usually cited for passive absorption through intact skin — so it may never reach the dermal papilla without a delivery aid. The same proliferative signaling is also a double-edged feature: platelet-derived growth factor is a recognized driver of fibrosis (scar-like tissue) and of the supportive tissue around some tumors, so its actions are not uniformly desirable.

**Pharmacological properties:** sh-Polypeptide-59 is a protein, not a small molecule. It is therefore not metabolized by liver CYP (cytochrome P450) enzymes; instead it is broken down by proteases (protein-cleaving enzymes) in tissue. Its circulating half-life as a free protein is very short (on the order of minutes), and any systemic exposure from correct topical use is expected to be minimal. Its target selectivity is for the PDGF receptors, and its tissue distribution after topical application is intended to be local to the scalp.

## Historical Context & Evolution

* **Original purpose:** Platelet-derived growth factor was first identified as the component of serum that stimulates fibroblasts and smooth-muscle cells to divide during wound repair. Its recombinant B-subunit form, becaplermin, was developed as a wound-healing therapy and approved by the U.S. Food and Drug Administration (FDA) in 1997 as a topical gel (marketed as Regranex) for diabetic foot ulcers — not for hair.

* **Route into hair care:** The move toward hair began indirectly. Clinicians using platelet-rich plasma — which is naturally rich in platelet-derived growth factor — reported improvements in some patients with pattern hair loss, and aesthetic dermatology adopted recombinant growth-factor cocktails first for skin rejuvenation and then for the scalp. As these ingredients entered consumer cosmetics, the standardized INCI name "sh-Polypeptide-59" was assigned to the recombinant PDGF-B protein.

* **What the historical wound-healing evidence actually showed:** In its approved wound use, topical recombinant PDGF-BB modestly improved ulcer closure. A later safety question arose when a matched cohort study found more cancer deaths among heavy users of the wound gel (three or more tubes). This prompted an FDA boxed warning in 2008.

* **How the picture was reassessed:** Rather than being simply "debunked," the safety signal was re-examined with longer follow-up and additional post-marketing studies, which did not confirm an overall increase in cancer or cancer death. On that basis, the FDA removed the boxed warning in 2018. Both the initial signal and its later softening are described in the Risks section so the reader can weigh the current standing directly.

* **Evolution of opinion:** Early caution about the mitogenic (cell-division-promoting) nature of growth factors has eased somewhat as reassuring wound-care data accumulated, but this history is specific to an open-wound, high-dose setting and does not by itself establish that a low-dose cosmetic scalp serum is either effective or safe.

## Expected Benefits

Benefits are framed for a proactive, health-focused adult evaluating an early-stage cosmetic option rather than as population-level outcomes. Because no controlled human study has tested topical sh-Polypeptide-59 for hair, no benefit rises above "Low," and most are "Speculative."

### Low 🟩

#### Support of Dermal Papilla and Hair Follicle Stem Cell Activity

The most defensible benefit is biological rather than cosmetic: platelet-derived growth factor helps maintain and activate the dermal stem cells and dermal papilla cells that drive follicle regeneration and the growth phase. This is supported by mouse genetic studies and isolated-cell experiments in which the protein sustained stem-cell self-renewal and improved the cells' capacity to induce new follicles. The evidence is preclinical, and whether a topically applied protein of this size actually reaches these cells in human scalp is unproven, so any real-world benefit remains inferential.

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

### Speculative 🟨

#### Increased Hair Density and Thickness

The headline consumer claim — visibly fuller, thicker hair — has no isolated-ingredient trial behind it. The basis is analogy to platelet-rich plasma and to multi-ingredient growth-factor serums, which have shown modest density gains in small studies but always as mixtures, so the specific contribution of sh-Polypeptide-59 cannot be separated out.

#### Prolongation of the Anagen (Growth) Phase

By acting on the dermal papilla, the protein is proposed to lengthen the active growth phase and delay the shift to resting, which would reduce shedding and support longer, thicker shafts. This rests on mechanistic and animal data rather than on human scalp measurements.

#### Improved Perifollicular Blood Supply

Platelet-derived growth factor recruits the support cells of blood vessels and promotes new-vessel formation, which could improve the blood supply feeding each follicle — a plausible contributor to hair growth. No human study has demonstrated this effect from the topical cosmetic ingredient.

#### Enhanced Results When Combined with Microneedling or Minoxidil

Because microneedling creates transient channels that could let a large protein penetrate, and because minoxidil independently promotes growth, sh-Polypeptide-59 is often positioned as an add-on. Any synergy is currently a reasonable hypothesis rather than a demonstrated outcome for this ingredient.

## Benefit-Modifying Factors

* **Degree of androgen-driven miniaturization:** In pattern hair loss the follicle shrinks under the influence of dihydrotestosterone (DHT, the androgen that miniaturizes genetically sensitive follicles). A growth-factor push may be overridden by ongoing DHT signaling, so any benefit is likely greater when the underlying androgen driver is also addressed.

* **Baseline follicle viability:** The protein can only act on follicles that still exist. Miniaturized-but-living follicles are more plausible responders than long-dormant zones or scarred (fibrosed) bald areas where follicles are gone.

* **Baseline biomarker status:** Low iron (ferritin), low vitamin D, thyroid dysfunction, or active scalp inflammation can independently cap any hair-growth response, blunting the apparent effect.

* **Sex-based differences:** Male- and female-pattern hair loss differ in distribution and hormonal context, and women and men may respond differently; however, no sex-specific data exist for this ingredient.

* **Genetic variation in signaling:** Variants affecting the androgen receptor or the platelet-derived growth factor receptors could, in theory, modify how strongly a follicle responds, though this has not been studied for topical use.

* **Age:** The dermal stem-cell pool and regenerative capacity decline with age, so older users — including those at the upper end of a health-focused adult audience — may see less response than younger users.

## Potential Risks & Side Effects

Risks are framed for a proactive adult applying a cosmetic serum to the scalp. Because the isolated ingredient has no dedicated safety trials in hair, most concerns are theoretical or extrapolated from the same molecule in its wound-care form.

### Low 🟥

#### Local Skin Irritation and Contact Dermatitis

The most common realistic issue is local intolerance — redness, itching, stinging, or small bumps (folliculitis) — driven by the serum's preservatives, carrier, the protein itself, or accompanying actives. Reactions are usually mild and reversible on stopping. Enhanced-penetration methods such as microneedling can increase both absorption and irritation.

**Magnitude:** Broadly comparable to other leave-on cosmetic scalp serums; reactions are typically mild and resolve on discontinuation.

#### Documented Malignancy-Mortality Signal from the Same Molecule ⚠ Conflicted

The identical recombinant protein, sold as a wound gel, was linked in one matched cohort study to more cancer deaths among heavy users (three or more tubes), which led to an FDA boxed warning in 2008. This is the strongest safety signal that exists for the molecule, but it is genuinely conflicted: extended follow-up in the same and later studies found no overall increase in cancer or cancer death, and the warning was removed in 2018. The setting also differs sharply from cosmetic use — open ulcers, high cumulative doses, and an older, sicker population — so the relevance to low-dose intact-skin scalp use is uncertain but cannot be dismissed.

**Magnitude:** Up to roughly a 5-fold higher cancer-mortality rate was reported among the heaviest wound-gel users in one cohort; extended follow-up showed no overall increase (hazard ratio — a measure comparing the risk between groups, where 1.0 means no difference — near 1.0–1.2).

### Speculative 🟨

#### Fibrosis or Excess Scar-Tissue Formation

Platelet-derived growth factor is a recognized driver of fibroblast proliferation and fibrosis in several diseases. Chronic scalp application could in theory promote unwanted connective-tissue changes, though no such reports exist for the cosmetic ingredient and normal topical exposure is far lower than in disease states.

#### Immunogenicity to a Recombinant Protein

As a bacterially produced human protein, sh-Polypeptide-59 could in principle provoke a local immune or allergic response, and residual bacterial endotoxin from manufacturing could contribute to irritation. The risk from intact-skin topical use is expected to be low but has not been formally characterized.

#### Stimulation of Pre-Existing Skin Lesions

Because the protein promotes cell division and blood-vessel growth, there is a theoretical concern that applying it over sun-damaged skin, actinic keratoses (rough, scaly precancerous patches caused by long-term sun exposure), or undiagnosed skin cancers in the treatment field could encourage their growth — a concern amplified if penetration is increased by needling.

#### Infection or Folliculitis with Microneedle-Assisted Delivery

When paired with microneedling, the barrier is breached, so poor hygiene, unclean devices, or contaminated product can introduce infection or worsen folliculitis. This is a procedure-related risk rather than a property of the protein itself.

## Risk-Modifying Factors

* **Personal or family history of skin cancer:** A history of skin cancer, actinic keratoses, or other pre-malignant lesions in the treatment field raises the theoretical concern about stimulating unwanted growth and warrants clinician review before use.

* **Baseline skin and scalp condition:** Active scalp infection, inflammatory scalp disease, or broken skin increases the chance of irritation, infection, and greater-than-intended absorption.

* **Baseline biomarkers:** Unlike their influence on the likelihood of benefit, no routine blood biomarker (e.g., ferritin, vitamin D, or thyroid markers) meaningfully changes the local risk profile of a minimally absorbed topical serum; such labs bear on interpreting response rather than on predicting harm.

* **Sex and hormonal state:** No sex-specific safety data exist. Pregnancy and breastfeeding are a separate precaution given the complete absence of safety data for a growth-factor protein during these periods.

* **Age:** Older skin is more likely to harbor undiagnosed sun-damaged or pre-malignant lesions, which is the population subgroup in whom the theoretical proliferation concern is most relevant.

* **Genetic variation in growth-factor signaling:** Variants in the platelet-derived growth factor receptor pathway could in principle alter tissue sensitivity, but no clinically actionable data exist for topical cosmetic use.

## Key Interactions & Contraindications

* **Topical minoxidil (over-the-counter):** Additive by design — both aim to promote growth. Severity: generally safe combination; the main consequence is additive scalp irritation. Mitigation: introduce one product at a time and separate application times if irritation appears.

* **Topical retinoids (tretinoin, adapalene) and chemical exfoliants (salicylic acid, glycolic acid):** These thin or disrupt the outer skin barrier and can increase both penetration and irritation of the serum. Severity: caution. Consequence: dermatitis, stinging, unpredictable absorption. Mitigation: separate application by hours or days and reduce frequency if irritation occurs.

* **Topical corticosteroids:** May blunt local growth-factor and inflammatory signaling. Severity: caution (possible reduced effect). Mitigation: separate use in time; discuss with a clinician if a steroid is medically needed.

* **Microneedling, low-level laser therapy, and platelet-rich plasma:** Additive or potentiating combinations frequently marketed together; all increase delivery or growth signaling. Severity: caution. Consequence: greater irritation and, with needling, infection risk. Mitigation: sterile technique, conservative needle depth, and staged introduction.

* **Other recombinant growth-factor or peptide serums:** Additive growth-factor exposure. Severity: caution. Consequence: cumulative stimulation and irritation. Mitigation: avoid stacking multiple undocumented growth-factor products simultaneously.

* **Populations who should avoid it:** People who are pregnant or breastfeeding (no safety data); anyone with a personal history of scalp or skin cancer, or with actinic keratoses or other pre-malignant lesions in the treatment field; those with active scalp infection (for example, tinea capitis or bacterial folliculitis) or active inflammatory scalp disease; and anyone with known hypersensitivity to the product. Severity for these groups: relative contraindication (avoid or use only under clinician supervision) because the consequence — from unknown developmental risk to potential stimulation of abnormal tissue or worsened infection — outweighs the unproven cosmetic benefit.

## Risk Mitigation Strategies

* **Patch testing before full use:** A patch test — a small amount applied to a discreet area for 48–72 hours and observed for redness, itching, or bumps before whole-scalp use — reduces the risk of a widespread contact-dermatitis reaction.

* **Screening the treatment field for skin lesions:** A clinician evaluation of suspicious spots, actinic keratoses, or non-healing lesions before starting, with the serum kept away from those areas, addresses the theoretical concern that a growth-promoting protein could stimulate pre-malignant or malignant tissue.

* **Sterile, conservative microneedling technique:** Disinfecting the device, keeping home needle depth at or below roughly 0.5–1.0 mm, following label timing, and avoiding needling over broken or infected skin together mitigate infection, folliculitis, and greater-than-intended penetration.

* **Modest cumulative exposure:** Staying within the manufacturer's small-volume directions rather than heavy off-label dosing serves as a deliberate hedge against the malignancy-mortality signal seen with high cumulative doses of the same protein in wound care.

* **Avoidance during pregnancy and breastfeeding:** Withholding the serum until safety data exist is a precaution grounded in the unknown effects of a growth-factor protein during these periods and the unproven benefit.

* **Discontinuation on any persistent reaction:** Stopping the serum and seeking evaluation when irritation, spreading redness, or new lesions appear limits progression of both dermatitis and infection.

## Therapeutic Protocol

There is no standardized medical protocol, because sh-Polypeptide-59 is a cosmetic ingredient rather than an approved hair drug. The patterns below reflect how growth-factor serums are typically used in aesthetic practice and by informed consumers.

* **Typical formulation and concentration:** sh-Polypeptide-59 usually appears as one of several recombinant growth factors in a leave-on serum; exact concentrations are rarely disclosed on cosmetic labels, which is a key transparency limitation.

* **Application routine:** Serums are commonly applied once or twice daily to a clean, dry scalp, or on a 1–2 times per week schedule when paired with in-clinic microneedling or mesotherapy delivery.

* **Competing approaches (presented without a default):** The main alternatives are (a) daily leave-on serum for at-home use, (b) in-clinic microneedle or mesotherapy delivery to improve penetration, and (c) platelet-rich plasma, which supplies the same growth factor from the user's own blood. Each has different cost, invasiveness, and evidence profiles, and none is clearly established as superior for this ingredient.

* **Practitioners and products that popularized the approach:** Growth-factor cosmetic lines used in dermatology practices (for example, AnteAGE and Calecim, named only as representative products, not endorsements) helped popularize topical growth-factor serums, while platelet-rich plasma was popularized within hair-restoration clinics.

* **Best time of day:** No chronobiology data exist; timing is chosen for routine adherence rather than for any demonstrated advantage.

* **Half-life and dosing frequency:** Because the free protein has a very short half-life and limited local residence, repeated application (daily or per-session) is the norm; there is no depot effect that would justify infrequent dosing.

* **Single versus split dosing:** Use is effectively split across the day (once or twice daily) rather than a single large application, consistent with the short residence time.

* **Genetic considerations:** Response is expected to depend more on androgen-receptor and DHT sensitivity than on the serum itself; platelet-derived growth factor receptor variants are of theoretical interest only.

* **Sex-based considerations:** Protocols are not sex-specific, though the underlying pattern-hair-loss context differs between men and women and should shape expectations.

* **Age considerations:** Older users may need longer, more consistent use for any effect and should be more vigilant about screening the scalp for sun-damaged skin.

* **Baseline biomarker considerations:** Correcting iron, vitamin D, and thyroid status before or alongside use gives any growth-factor effect the best chance to show.

* **Pre-existing conditions:** Underlying scarring alopecia, active scalp disease, or nutritional deficiency should be addressed first, as they will otherwise limit response.

## Discontinuation & Cycling

* **Lifelong versus short-term:** Like other topical hair actives, any benefit depends on continued use; the ingredient does not "cure" hair loss, and gains would be expected to fade over subsequent hair cycles once it is stopped.

* **Withdrawal effects:** There is no pharmacological dependence or withdrawal syndrome. The main consequence of stopping is a gradual return toward the untreated baseline, including any shedding that treatment had slowed.

* **Tapering:** No taper is needed; the product can be stopped abruptly without a rebound beyond loss of any accrued benefit.

* **Cycling:** There is no evidence that cycling on and off preserves or enhances efficacy. Some users pair intermittent microneedling sessions with continuous serum use, but this is a delivery choice rather than a validated cycling strategy.

## Sourcing and Quality

* **Protein stability and packaging:** Recombinant proteins degrade with heat, light, and time. Prefer products in opaque, airless, or single-use packaging, and note whether the manufacturer recommends refrigeration; serums stored improperly may contain little active protein.

* **Concentration and source transparency:** Most cosmetics do not disclose how much sh-Polypeptide-59 they contain. Favor brands that state the amount and the recombinant source, since ingredient-list presence alone says nothing about a meaningful dose.

* **Manufacturing and purity testing:** Because the protein is produced in engineered *E. coli*, endotoxin (a bacterial contaminant) is a relevant quality concern. Look for manufacturers that reference good manufacturing practices and endotoxin or purity testing.

* **Reputable brands and compounding:** Established aesthetic growth-factor lines and reputable compounding sources are preferable to anonymous marketplace sellers. Be skeptical of products that make drug-level regrowth claims, which are not permitted for a cosmetic.

* **Realistic labeling:** Prefer products that describe the ingredient's status honestly (a cosmetic with mechanistic rationale) over those implying proven, drug-equivalent results.

## Practical Considerations

* **Time to effect:** Hair cycles are slow. Even under optimistic assumptions, no visible change should be expected before about 3–6 months of consistent use, mirroring the timeline of established hair actives.

* **Common pitfalls:** Expecting drug-level regrowth from a cosmetic; stopping before the minimum evaluation window; using the serum as a standalone rather than alongside proven approaches; and ignoring the underlying androgen driver of pattern hair loss.

* **Regulatory status:** sh-Polypeptide-59 is marketed as a cosmetic ingredient, not an FDA-approved drug for hair, so hair-regrowth claims are unapproved. The identical protein is FDA-approved as a drug only in a wound-healing gel, and that approval does not extend to scalp or hair use.

* **Cost and accessibility:** Growth-factor serums are relatively expensive compared with generic minoxidil and are sold widely online without prescription; the cost-to-evidence ratio is unfavorable relative to established options.

## Interaction with Foundational Habits

* **Sleep:** Direction — indirect/none. A topical serum is not expected to affect sleep, and there is no evidence it should be timed around sleep. Adequate sleep supports normal hormonal regulation of the hair cycle, so good sleep is complementary background support rather than a direct interaction.

* **Nutrition:** Direction — indirect, potentially potentiating. Follicle response to any growth signal depends on adequate protein, iron, vitamin D, and zinc; deficiencies can cap results. Practically, correcting these through diet or targeted repletion gives a growth-factor serum its best chance, whereas crash dieting can trigger shedding that masks benefit.

* **Exercise:** Direction — indirect. Regular activity improves overall circulation and may modestly support scalp perfusion, aligning loosely with the protein's blood-vessel-promoting mechanism. There is no need to time application around workouts; applying after washing off sweat is the only practical consideration.

* **Stress management:** Direction — indirect. Chronic stress can push follicles into resting and shedding (telogen effluvium), which would blunt or obscure any benefit, plausibly via cortisol effects on the hair cycle. Managing stress helps keep more follicles in the growth phase where a growth-factor serum could act.

## Monitoring Protocol & Defining Success

Because sh-Polypeptide-59 is a topical cosmetic with minimal systemic exposure, monitoring focuses less on safety labs and more on ruling out treatable causes of hair loss at baseline and on tracking hair objectively over time.

Before starting, a baseline workup is worthwhile to identify contributors to hair loss that would otherwise limit or mimic a response, and to document the starting point with standardized photographs and, ideally, a clinician's assessment.

| Biomarker | Optimal Functional Range | Why Measure It? | Context/Notes |
| --------- | ------------------------ | --------------- | ------------- |
| Ferritin (iron stores) | 40–70 ng/mL | Low iron stores are a common, correctable cause of hair shedding | Conventional labs often flag "low" only below ~15–30 ng/mL; the functional target for hair is higher. Draw when not acutely ill, as ferritin rises with inflammation |
| Vitamin D (25-hydroxyvitamin D) | 40–60 ng/mL | Deficiency is linked to hair-cycle disruption | Conventional "sufficient" starts at 30 ng/mL; no fasting required |
| TSH | 0.5–2.5 mIU/L | Thyroid dysfunction is a reversible driver of diffuse hair loss | TSH (thyroid-stimulating hormone). Best paired with free T4 (thyroxine) if abnormal; morning draw preferred as TSH varies through the day |
| Total and free testosterone | Sex- and age-specific reference | Provides hormonal context for pattern hair loss | Morning, fasting sample; interpret alongside symptoms rather than in isolation |
| Zinc | 90–120 µg/dL | Deficiency can contribute to shedding and poor follicle function | Take fasting and avoid zinc supplements immediately before testing |
| Complete blood count (hemoglobin) | Mid-normal for sex | Screens for anemia that can worsen hair loss | Routine panel; pairs naturally with ferritin |

Ongoing monitoring is primarily visual rather than laboratory-based. A reasonable cadence is a baseline set of standardized photographs, then reassessment at about 3 months and 6 months, and every 6–12 months thereafter, since hair changes slowly and short-term judgments are unreliable.

Qualitative and self-tracked markers of success include:

* Hair density and part width compared with baseline photos taken in consistent lighting
* Daily or weekly shedding counts (for example, hairs in the shower or on the pillow)
* A gentle hair-pull test trend over time
* Subjective texture, coverage, and styling ease
* Absence of scalp irritation, new lesions, or signs of infection during use

## Emerging Research

Research relevant to sh-Polypeptide-59 is framed here for a proactive reader who wants to know both what could validate the ingredient and what could undercut it. Importantly, no registered clinical trial evaluates topical sh-Polypeptide-59 as an isolated ingredient for hair; the closest evidence comes from peptide- and growth-factor serum trials and from safety data on the same molecule in wound care.

* **Peptide growth-factor serum versus minoxidil:** [VENEZE Peptide Factor Hair Serum Compared With Topical 2% Minoxidil for Androgenetic Alopecia](https://clinicaltrials.gov/study/NCT07536100) is a recruiting randomized study of about 80 participants comparing a peptide growth-factor serum head-to-head with standard minoxidil — the nearest analog to how sh-Polypeptide-59 would be used, and a design that could strengthen or weaken the case for topical growth factors.

* **Growth factors combined with laser:** [Thulium Laser and Growth Factors for Androgenetic Alopecia](https://clinicaltrials.gov/study/NCT07079657) is a recruiting study of roughly 30 participants testing whether combining topical growth factors with laser treatment improves outcomes, relevant to the enhanced-delivery strategy often paired with these serums.

* **Growth-factor serum in a different hair-loss setting:** [Keratinocyte Growth Factor Hair Serum for the Prevention of Chemotherapy-Induced Alopecia](https://clinicaltrials.gov/study/NCT04554732) is a completed early-phase study of about 28 participants applying a topical growth-factor serum, offering indirect insight into tolerability and delivery of this class.

* **Delivery and penetration science:** A central open question is whether a protein as large as PDGF-BB can reach the dermal papilla through intact skin at all. Future work on microneedle arrays, nanocarriers, and other delivery systems could determine whether the ingredient is even bioavailable topically — a line of research that could strengthen or fatally weaken the concept.

* **Long-term safety re-evaluation:** The malignancy question for recombinant PDGF-BB remains the key safety uncertainty. The matched cohort analysis [A matched cohort study of the risk of cancer in users of becaplermin](https://pubmed.ncbi.nlm.nih.gov/21173589/) (Ziyadeh et al., 2011) is the most directly relevant human safety dataset and illustrates how additional follow-up shifted the signal; comparable long-term data for cosmetic scalp use do not yet exist.

## Conclusion

sh-Polypeptide-59 is a lab-made copy of a natural human growth-factor protein, added to leave-on scalp serums with the goal of reviving thinning hair. Its rationale is biologically reasonable: the parent protein helps sustain the cells at the base of each follicle, supports the follicle's growing phase, and encourages the small blood vessels that feed it. Laboratory and animal work supports these roles, and the same protein is a natural ingredient of platelet-rich scalp treatments that some clinicians find helpful. What is missing is direct human testing of the ingredient itself. No controlled study has shown that applying sh-Polypeptide-59 to the scalp regrows hair, and it is unclear whether a protein this large can even reach its target through intact skin without needling. The main practical concerns are minor skin irritation and a theoretical, unresolved question about whether growth-factor proteins could encourage unwanted cell growth — a question raised, then largely eased, when the same protein was studied as a prescription wound treatment. Overall, the evidence base is thin and mostly indirect, weighted toward mechanism and analogy rather than results in people seeking hair regrowth. It is best understood as an unproven, early-stage cosmetic option rather than an established treatment, and its true value for hair remains genuinely uncertain.

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