sh-Polypeptide-71 for Hair Regrowth

Evidence Review created on 08/25/2026 using AI4L / Grok 4.5

Also known as: sh-Polypeptide-65, Synthetic Human Vasoactive Intestinal Peptide, Recombinant Human VIP, VIP Peptide, Clairesome-VP

Motivation

sh-Polypeptide-71 is a laboratory-made protein fragment sold in leave-on hair serums as a synthetic-human copy of vasoactive intestinal peptide, a nerve-signaling protein that widens blood vessels and quiets local immune activity. Longevity-minded adults meet it on multi-peptide density labels that promise thicker hair without a prescription hormone blocker. The appeal is a follicle-level signal rather than a scalp stimulant alone.

Cosmetic makers moved the analog into hair care after the native protein was mapped as a vessel-widener and, later, as a possible guardian of the follicle’s quiet immune zone. Independent follicle-culture work on the native protein, not on the named serum ingredient, is what now sits behind most of the hair-growth story. Product pages still treat shaft softening and growth as a single package.

This review examines whether sh-Polypeptide-71, as sold for hair, has human outcome evidence for regrowth, what the parent protein actually does in follicle tissue, and what risks follow from vessel widening, immune signaling, and pigment change.

Benefits - Risks - Protocol - Conclusion

Recommended Reading

This section lists high-level sources that name sh-Polypeptide-71 or that cover vasoactive intestinal peptide, the parent nerve-signaling protein copied by this cosmetic analog, at the follicle.

• Overview of Short Peptides for Hair Loss - Fan et al., 2026

  Narrative review of short peptides for hair loss that names vasoactive intestinal peptide as a guardian of the follicle’s immune privilege (the local do-not-attack state), the receptor biology this analog is built to copy.

• Vasoactive intestinal peptide, whose receptor-mediated signalling may be defective in alopecia areata, provides protection from hair follicle immune privilege collapse - Bertolini et al., 2016

  Primary human follicle-culture and alopecia-areata (patchy autoimmune hair loss) biopsy study showing vasoactive intestinal peptide receptors on the follicle and protection from immune-privilege collapse, the core hair mechanism claimed for this analog.

• Vasoactive Intestinal Peptide Operates as a Negative Regulator of Human Hair Follicle Pigmentation Ex Vivo - Gomez et al., 2025

  Human anagen (growth-phase) follicle organ culture showing vasoactive intestinal peptide lowers melanin production, a follicle-level trade-off this analog would copy.

Fewer than five high-level sources name sh-Polypeptide-71 or cover vasoactive intestinal peptide at the follicle in depth; generic hair-loss roundups were not added. No dedicated content from Rhonda Patrick, Peter Attia, Andrew Huberman, Chris Kresser, Life Extension Magazine, or Lifespan.io was found.

Grokipedia

No Grokipedia article for sh-Polypeptide-71 was found.

Examine

No Examine.com article for sh-Polypeptide-71 was found.

ConsumerLab

No ConsumerLab article for sh-Polypeptide-71 was found.

Systematic Reviews

No systematic reviews or meta-analyses for sh-Polypeptide-71 were found on PubMed as of August 25, 2026.

Mechanism of Action

sh-Polypeptide-71 is the International Nomenclature of Cosmetic Ingredients (INCI) name for a synthetic-human analog of vasoactive intestinal peptide (VIP), a 28-amino-acid neuropeptide. CosIng (the EU cosmetic-ingredient inventory) descriptions allow chains up to about 170 residues, matching precursor length; a seller’s U.S. hair-growth patent specifies a 28-residue liposomal equivalent (US10894074B2).

Native VIP binds VPAC1 and VPAC2 (vasoactive intestinal peptide receptors type 1 and type 2), G-protein-coupled receptors that raise cyclic AMP (cAMP, the cell’s short-lived “go” messenger) and protein kinase A (the enzyme that executes that cAMP signal). Human hair-follicle epithelium expresses both receptors. VIP released from perifollicular sensory nerves is immunoinhibitory: in organ culture it protects the follicle’s relative immune privilege (the local “do not attack” state of a growing follicle) from interferon-gamma (IFN-γ)-driven collapse, a step that precedes alopecia areata (patchy autoimmune hair loss) (Bertolini et al., 2016). The same signaling dilates cutaneous vessels, which is the microcirculation rationale in hair serums.

A competing organ-culture finding is that VIP lowers melanin production and can shrink the follicle melanocyte pool, so any growth-phase support may arrive with less pigment (Gomez et al., 2025). Intact VIP is a poor topical drug. Plasma half-life is about one minute, volume of distribution about 14 mL/kg, metabolic clearance about 9 mL/kg/min, and skin peptidases including neprilysin (a membrane enzyme that cuts peptides) and dipeptidyl peptidase-4 (DPP-4) are expected to destroy free peptide unless a vehicle delivers it to the follicle (Domschke et al., 1978).

Historical Context & Evolution

VIP was isolated in the 1970s from gut extracts as a potent vasodilator and secretory hormone. High circulating levels in VIPoma disease (a tumor that secretes vasoactive intestinal peptide; Verner-Morrison syndrome) produced flushing, watery diarrhea, and hypotension (low blood pressure), which defined the safety envelope of the native peptide. Synthetic VIP (aviptadil) later entered sexual-medicine combinations with phentolamine and pulmonary trials; those uses are injection or inhalation, not scalp cosmetics (Dinsmore et al., 1999).

The cosmetic INCI sequence was first listed as sh-Polypeptide-65 and later renamed sh-Polypeptide-71 (CosIng reference 90068; hair conditioning and skin conditioning). Hair-care brands folded the analog into multi-peptide serums in the 2010s, citing shaft conditioning and, in patents such as US10894074B2, anagen-stage (growth-phase) “vasoactive” support. That commercial literature is produced by parties who sell the peptide.

Independent follicle biology moved on a separate track. Bertolini, Paus and colleagues showed VIP receptors on human follicle epithelium and a guardian role against immune-privilege collapse in alopecia areata (Bertolini et al., 2016). In 2025 the same research line reported VIP as a negative regulator of follicle pigmentation (Gomez et al., 2025). Neither finding is a trial of the INCI ingredient on living scalp, and neither has closed the question of whether a leave-on analog changes hair counts.

Expected Benefits

High 🟩 🟩 🟩

No benefit reaches High: no randomized trial has measured a clinical hair-count, density, or validated scale endpoint for topical sh-Polypeptide-71 in people.

Medium 🟩 🟩

No benefit reaches Medium: the human findings are a single organ-culture series and biopsy receptor mapping, not one clinical trial of this ingredient.

Low 🟩

Speculative 🟨

Follicle immune-privilege protection

Vasoactive intestinal peptide receptors sit in human follicle epithelium. Organ culture shows marker protection from interferon-gamma collapse. The basis is organ-culture and biopsy markers, not hair counts in people (Bertolini et al., 2016).

Hair density or anagen extension

Patents and multi-peptide serums present sh-Polypeptide-71 as an anagen-stage support via vessel tone and follicle signaling. No controlled human density endpoint exists for the isolated INCI ingredient; the basis is mechanism and marketing blends only.

Shaft film, shine, and breakage reduction

CosIng lists hair conditioning. Consumer explainers describe a thin film on damaged cuticle. No tensile or breakage trial of this peptide was found; the basis is cosmetic function language only.

Scalp microvascular perfusion

Native vasoactive intestinal peptide is a potent vasodilator in people given intravenous infusions. Whether a leave-on analog raises scalp perfusion enough to change hair outcome has not been measured.

Benefit-Modifying Factors

• VPAC receptor genotype: Variants in VIPR1 and VIPR2 (the genes for the two vasoactive intestinal peptide receptors) exist, but no hair-protocol dose table uses them. Alopecia-areata bulbs already show low receptor protein, which may blunt a topical analog (Bertolini et al., 2016).

• Baseline follicle immune status: Benefit, if any, is more plausible where immune-privilege collapse is part of the story (alopecia areata) than where dihydrotestosterone (DHT, a potent androgen) miniaturizes follicles (androgenetic alopecia).

• Sex: Organ-culture pigmentation work used male donor follicles for the melanin drop; earlier female pilot notes differed. Hair-count response by sex is untested for this ingredient (Gomez et al., 2025).

• Pre-existing hair diagnosis: Androgenetic alopecia is androgen-driven; this analog does not block 5-alpha-reductase (the enzyme that converts testosterone to DHT). Telogen effluvium (resting-phase shedding) tracks triggers (iron, thyroid, stress) that a peptide serum does not correct.

• Baseline iron, thyroid, and vitamin D: Low ferritin (iron-storage protein), off-target thyroid-stimulating hormone (TSH), or low vitamin D drive shedding that can overwhelm any analog signal.

• Age: Older scalps often combine androgenetic thinning, lower local growth-factor tone, and a thinner barrier that could change absorption. No age-stratified outcome data exist for sh-Polypeptide-71.

Potential Risks & Side Effects

High 🟥 🟥 🟥

No risk reaches High: replicated adverse-event data exist for intravenous and intracavernosal vasoactive intestinal peptide, not for topical sh-Polypeptide-71.

Medium 🟥 🟥

No risk reaches Medium: no observational series has quantified scalp or systemic events from this cosmetic peptide in people using hair serums.

Low 🟥

Speculative 🟨

Reduced follicle melanin

In cultured human anagen follicles, vasoactive intestinal peptide at 100 nM and 1 μM lowered melanin production. That is organ-culture tissue, not a pigment-loss trial on living scalp (Gomez et al., 2025).

Flushing or hypotension after absorption

Intravenous vasoactive intestinal peptide lowers peripheral resistance and mean arterial pressure and causes cutaneous flushing (Frase et al., 1987; Domschke et al., 1978). Intact peptide has a one-minute plasma half-life; topical systemic exposure is unmeasured.

Increased heart rate after absorption

Intravenous vasoactive intestinal peptide raises heart rate in healthy volunteers as vessels widen. Topical analog exposure is unmeasured; the basis is infusion physiology, not scalp use (Frase et al., 1987; Domschke et al., 1978).

Headache after absorption

Intravenous vasoactive intestinal peptide can provoke headache and cranial-vessel change in healthy volunteers. Topical analog exposure is unmeasured; the basis is infusion physiology, not scalp use (NCT03989817).

Watery diarrhea after absorption

Native vasoactive intestinal peptide drives intestinal water secretion, the watery diarrhea of VIPoma disease. Leave-on analog absorption is unmeasured; the basis is parent-peptide pharmacology, not a serum series (Domschke et al., 1978).

Local redness, itch, or contact dermatitis

Consumer INCI explainers list transient redness, warmth, itch, and rare allergic dermatitis. No published case series of sh-Polypeptide-71 contact allergy was found; the basis is class expectation for leave-on cosmetics.

Immunogenicity of a recombinant peptide

A laboratory-made copy of a human neuropeptide can raise antibodies or irritate barrier-broken scalp. Cosmetic peptide frameworks flag that hazard; this analog has no dedicated Cosmetic Ingredient Review (CIR) file (Bjerke et al., 2026).

Risk-Modifying Factors

• Receptor and barrier genetics: Low VPAC protein on lesional alopecia-areata bulbs may reduce on-target signaling and, with it, on-target risk. Filaggrin or other barrier variants that raise percutaneous absorption are unstudied for this peptide.

• Baseline blood pressure: People with low resting pressure or who already use vasodilators have less reserve if intact peptide reaches the circulation. Topical exposure remains unquantified (Frase et al., 1987).

• Sex: The organ-culture melanin drop was shown in male donor follicles. Whether pigment risk differs in female scalp is unknown (Gomez et al., 2025).

• Inflamed or broken scalp: Dermatitis, microneedling, or open follicles increase the chance that a large peptide reaches dermis and vessels, which is the intended delivery trick in some patents and a risk amplifier.

• Age: Older adults more often combine vasodilator medications, thinner skin, and pigmented-hair preservation goals. No geriatric topical series exists for this ingredient.

Key Interactions & Contraindications

• Minoxidil and other topical vasodilators: Caution. Both widen cutaneous vessels. Combined redness or light-headedness is plausible if the analog is absorbed; no interaction trial exists. Staggering application and watching blood pressure are the usual cosmetic work-arounds.

• Nitrates and antihypertensives (nitroglycerin, amlodipine, lisinopril): Caution. Systemic vasoactive intestinal peptide drops peripheral resistance (Frase et al., 1987). Intact analog plus a blood-pressure medication could, if absorbed, add hypotension; topical absorption is unmeasured.

• Janus kinase (JAK) inhibitors (tofacitinib, baricitinib): Monitor. Both aim at follicle immune quieting by different routes. Additive infection or off-target immune effects are theoretical; no combination study exists.

• Copper peptides and other leave-on hair peptides (GHK-Cu / copper tripeptide-1): Monitor. Stacked serums are the commercial norm. Allergen load and barrier irritation rise with blend complexity; efficacy is not shown to be additive.

• DPP-4 inhibitors (sitagliptin) and neprilysin inhibitors (sacubitril): Caution. These enzymes degrade vasoactive intestinal peptide. Slowed breakdown could raise local or systemic exposure if the analog is absorbed.

Populations who should avoid sh-Polypeptide-71:

• Known hypersensitivity to recombinant peptides or to other ingredients in the finished serum.

• Uncontrolled hypotension (sitting systolic pressure below 90 mmHg), or current use of stacked systemic vasodilators, until topical bioavailability is known.

• People whose primary goal is to keep existing hair pigment, given organ-culture melanin reduction with the parent protein (Gomez et al., 2025).

• Broken scalp, active infection, or same-day deep microneedling unless the protocol is designed around that delivery route.

Risk Mitigation Strategies

• Patch test on intact skin: Typical practice is one 24–48 hour post-auricular application before first scalp use, to catch contact dermatitis before a full-head application.

• Intact barrier first: Typical protocols skip eroded, infected, or freshly microneedled scalp unless a clinician-run microneedling protocol is the delivery plan, to limit unintended dermal uptake and flushing.

• Blood-pressure check in vasodilator users: Sitting pressure is recorded at baseline and after the first week if minoxidil or antihypertensives are already in use, to catch additive hypotension.

• Systemic VIP-effect watch: First-week log of flushing, light-headedness, increased heart rate, new headache, or diarrhea, to catch absorbed-peptide effects early.

• Pigment watch: The same scalp sites are photographed in consistent light at day 0, week 8, and month 6, to detect pigment loss or shaft-color fade early.

• Single-variable start: The analog is added alone for 8–12 weeks before other peptides are combined, so irritation or shedding can be attributed.

Therapeutic Protocol

• No isolated clinic standard: Leading hair practices that use peptides generally deploy blends, not sh-Polypeptide-71 alone. Documented approaches are leave-on serums and patent blends such as US10894074B2, not a named medical protocol.

• Leave-on serum versus microneedling blend: Conventional cosmetic use is a daily leave-on scalp serum. Microneedling-plus-growth-factor series (Gentile, 2022) do not isolate this ingredient; they are a parallel method, not proof of this analog.

• Time of day: No chronobiology data exist. Leave-on hair serums are commonly applied to a dry scalp in the evening so the film is not washed off.

• Half-life and splitting: Native vasoactive intestinal peptide plasma half-life is about one minute (Domschke et al., 1978). Free peptide does not justify split systemic dosing; topical films are usually once daily, with liposomes in some patents.

• Genetics: No VPAC, MTHFR (folate-processing gene), or APOE (lipid-transport gene) dose exists. Alopecia-areata tissue with low receptor protein may simply not respond (Bertolini et al., 2016).

• Sex: No sex-specific dose. Male-follicle organ culture showed a melanin drop; female outcome data for the INCI ingredient do not exist.

• Age: No geriatric dose. Older users more often have androgenetic thinning plus vasodilator drugs; published use is the labeled cosmetic amount, not a compounded high load.

• Baseline biology: Low ferritin, off-target TSH, or low vitamin D will dominate any peptide signal. Those are confounders to measure, not targets of this analog.

• Pre-existing disease: Androgenetic alopecia is not a VIP-receptor disease. Alopecia areata is the mechanistic match and still lacks a topical sh-Polypeptide-71 trial.

Discontinuation & Cycling

• Duration: Cosmetic leave-on use is typically open-ended while the person wants the cosmetic effect. Nothing in the literature frames this analog as a finite drug course or a lifelong hormone.

• Withdrawal: No withdrawal syndrome is described for topical sh-Polypeptide-71. Native peptide effects (flushing, pressure drop) end when infusion stops, consistent with a one-minute half-life (Domschke et al., 1978).

• Taper: No taper is described. Stopping a leave-on serum is abrupt; hair-cycle lag means density, if it changed, would drift over months, not days.

• Cycling: No receptor-desensitization study supports on/off cycles for this analog. Commercial serums are labeled for continuous use; cycling is an untested preference, not a maintenance finding.

Sourcing and Quality

• INCI identity: Finished labels list sh-Polypeptide-71 (former sh-Polypeptide-65). CosIng reference 90068 lists hair conditioning and skin conditioning, not a drug indication for alopecia.

• Sequence and vehicle: Native VIP is 28 amino acids; some listings allow up to ~170. Liposomal or refrigerated (2–8 °C) lots in US10894074B2 aim to protect a short-lived peptide. Chain length and encapsulation define the lot.

• Purity and testing: Identity is shown by third-party HPLC (high-performance liquid chromatography) or mass spectrometry, plus endotoxin and microbial certificates. Cosmetic production is not a licensed aviptadil drug file.

• Trade names: Clairesome-VP appears as a vendor name for a VIP analog. Finished “growth-factor” serums often list this peptide only as one component of a blend; isolation lets a user know the actual dose.

• Conflict on the label: Many claims originate with manufacturers who sell the peptide. Independent follicle papers used research-grade VIP, not a named serum lot.

Practical Considerations

• Time to effect: Anagen lasts months. Even proven hair drugs are scored at 3–6 months. This analog has no timed density curve; judging it at two weeks confuses ordinary shedding variation with outcome.

• Common pitfalls: Treating a blend trial as evidence for this INCI name; expecting DHT-blockade from a vasodilatory neuropeptide analog; microneedling over an irritant formula; ignoring pigment change; skipping iron and thyroid checks.

• Regulatory status: In the EU and U.S. this is a cosmetic ingredient, not a Food and Drug Administration (FDA)-approved alopecia drug. CosIng permits hair and skin conditioning. Aviptadil drug uses (injection, inhalation) are a different legal object.

• Cost and access: Peptide serums are widely sold. Insurers have no stake in this analog and sometimes cover minoxidil or finasteride, a payer bias in guidelines, not a quality ranking.

Interaction with Foundational Habits

• Sleep: Indirect. Follicle immune privilege and neuropeptide tone track circadian and sleep-loss stress. Poor sleep can blunt the quiet-immune story this analog is sold to copy; no trial times the serum to sleep stage.

• Nutrition: Indirect, possibly blunting. Low protein, iron, zinc, or energy availability drives shedding that a topical peptide does not correct. Adequate protein and iron are the background against which any serum is judged, not a synergy trial.

• Exercise: Indirect, possibly potentiating. Endurance work already raises cutaneous blood flow. Stacking a vasodilatory analog on heavy training plus oral minoxidil is unstudied; light-headedness is the practical adverse event to monitor.

• Stress management: Indirect, possibly potentiating. Psychological stress and IFN-γ tone are part of alopecia-areata collapse. Lowering that background is mechanistically aligned with VIP’s guardian story; it is not a substitute for outcome data (Bertolini et al., 2016).

Monitoring Protocol & Defining Success

Baseline work-up checks that shedding is not driven by iron, thyroid, or vitamin D depletion, and captures photos plus trichoscopy (close-up imaging of scalp hairs) of the same scalp sites. Those values are confounders and endpoints, not a claim that this analog changes blood chemistry. Trichoscopy and photos are repeated at 8–12 weeks, at 6 months, then every 6–12 months if use continues. Sitting blood pressure belongs in the first-week check for anyone already on minoxidil or antihypertensives. Circulating vasoactive intestinal peptide is not a cosmetic-serum target: plasma half-life is about one minute. Success is a within-person rise in terminal-hair density or a fall in shedding versus that person’s baseline. Ferritin, thyroid-stimulating hormone, and 25-hydroxyvitamin D follow at 6 months if low, and at any new shedding episode; the analog is not titrated to those numbers.

Biomarker	Optimal Functional Range	Why Measure It?	Context/Notes
Trichoscopic hair density	Change from the person’s own baseline; no established functional target for this analog	Only direct hair endpoint available	Same sites, same device, dry scalp; pair with global photos
Ferritin	70–150 ng/mL	Low iron drives shedding that can mimic peptide failure	Conventional lower bound is often ~30 ng/mL; draw fasting if possible
TSH (thyroid-stimulating hormone)	0.5–2.5 mIU/L	Hypo- or hyperthyroid shedding confounds density	Conventional range ~0.4–4.5 mIU/L; pair with free T4 (thyroxine) if off-target
25-hydroxyvitamin D	40–60 ng/mL	Low vitamin D is common in shedding work-ups	Conventional sufficiency often ≥30 ng/mL; not a VIP pathway marker
Sitting systolic/diastolic blood pressure	Keep at the person’s usual treated target	Catch additive vasodilatation	First week if minoxidil or antihypertensives are in use; not a hair biomarker

Qualitative markers:

• Daily shed count on a pillow or drain versus the person’s own pre-serum week
• Shaft feel (breakage, shine) on the same lighting and wash schedule
• Scalp redness, itch, or flushing after application
• New headache or diarrhea in the first week of use
• Subjective density at the temples and crown on standardized photos
• Hair-color change at the same sites, given organ-culture melanin data

Emerging Research

• No registered hair trial of this INCI name: ClinicalTrials.gov search for sh-Polypeptide-71 returned no studies. Native VIP/aviptadil records cover acute lung injury, chronic obstructive pulmonary disease, headache, and erectile dysfunction, not scalp density.

• VPAC1 agonist plus microneedles: A 2026 mouse and dermal-papilla paper on palmitoylated Pal-MPAPO, delivered by hydrogel microneedles, reported hair regrowth comparable to minoxidil via VPAC1-linked cAMP and Wnt/β-catenin (a follicle growth-signal pathway) (Ma et al., 2026). That could strengthen a receptor-level hair story or remain a different molecule.

• Pigmentation as a falsifier: Gomez et al., 2025 found VIP to be a negative regulator of human follicle melanin ex vivo. Replication on living scalp would weaken cosmetic “density without trade-off” claims.

• Completed VIP infusion physiology: NCT03989817 infused VIP in healthy volunteers for headache and cranial hemodynamics. It confirms native-peptide bioactivity in people and does not test topical sh-Polypeptide-71 for hair.

• Peptide cosmetic safety methods: Bjerke et al., 2026 outline a weight-of-evidence safety frame for cosmetic peptides. Applying it to this analog could either support current leave-on use or expose a data gap the CIR file still lacks.

Conclusion

sh-Polypeptide-71 is a cosmetic, laboratory-made copy of a nerve-signaling protein that widens vessels and can quiet immune activity around the hair follicle. The named ingredient itself has no controlled human trial that counts hairs, measures density, or tracks shedding on the scalp. What exists is permission, under cosmetic naming rules, to condition hair and skin; commercial blends that mix the analog with other peptides; and careful studies of living follicles grown in the lab with the native protein. That tissue work shows protection of the follicle’s quiet immune zone, and, in a later follicle-culture study, less pigment. Those are tissue findings, not a density result in people.

Hoped-for benefits for a health-optimizing adult are therefore still theoretical: calmer autoimmune attack on the follicle, more local blood supply, a smoother shaft. Documented concerns travel with the parent protein: flushing, faster pulse, headache, watery stools, and lower blood pressure when the native peptide is infused, and darker-hair fading if the culture pigment result holds on a living scalp. Independent follicle laboratories produced the biology. Companies that sell peptide serums produced most of the growth claims. That split in who pays for which story is part of the evidence.

For someone already willing to run a demanding hair protocol, the evidence class for this analog is not the same as the class for interventions with human hair-count trials. Uncertainty is the accurate summary of the present file.

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