Zinc-thymulin

At a glance

Category

Skin & cosmetic

Status

research chemical

Made from

synthetic Chemically synthesised. In the only published human study the nonapeptide was made by standard Fmoc solid-phase synthesis, purity confirmed above 95 percent by liquid chromatography-mass spectrometry, and the zinc attached by mixing the peptide with zinc oxide in acetic acid before lyophilisation 1.

Route

topical, as a water-based scalp spray

Half-life

Not established for topical scalp application. Circulating thymulin has a plasma half-life on the order of minutes; whether that is relevant to a peptide applied to the scalp surface is unknown and unstudied

Onset

The pilot study found no significant global change at trial end across the whole group; the significant subgroup finding required more than six months of use 1

Molecular weight

approximately 858.9 g/mol for the peptide without zinc 1

Sequence

pGlu-Ala-Lys-Ser-Gln-Gly-Gly-Ser-Asn (pEAKSQGGSN), complexed with zinc

Mechanism of action

The rationale runs through the hair cycle rather than through the immune system. Thymic peptides modulate human hair follicle growth in organ culture, and thymulin specifically was reported to extend anagen, the growth phase 2. Zinc is separately relevant: it is required for thymulin's biological activity in an equimolar complex, without which the peptide does not adopt the correct conformation and is inactive 3, and zinc deficiency is itself a recognised cause of hair loss. Combining the two was intended to deliver an active complex rather than an inert peptide.

What has not been established is anything between the scalp surface and the follicle. There is no published measurement of whether a nonapeptide-zinc complex in a water-based spray penetrates to the hair bulb, at what concentration, or whether the complex survives intact in the vehicle. The organ-culture work that supports the anagen claim applied thymic peptides directly to isolated follicles 2, which bypasses the question entirely.

What the research shows

One open-label pilot in 18 subjects, uncontrolled and unrandomised, published in 2017 by an author who discloses a financial interest and a patent filing on the compound 1. Zinc-thymulin is sometimes described as having more evidence than most hair peptides, and that is true, but it is a very low bar: the comparison class is compounds with no human data at all. On its own terms the study does not establish that this works.

Research in humans

The single human study is Vickers (2017), an open-label trial in 18 consecutive adults — 17 men and one woman, aged 35 to 90, Norwood-Hamilton classification 2 to 7 — applying 1 to 2 ml of a 0.0005 percent zinc-thymulin spray to the scalp twice daily for between 4 and 10 months 1. Two trained assessors graded before and after photographs in single-blind fashion using a visual analogue scale and a hair growth index. The design should be described precisely because the headline is often not: there was no control group, no placebo or vehicle arm, and no randomisation. The primary global measure was not significant across the whole group (P=0.07); significance was reached only in the subgroup of 11 subjects who had used it for at least six months (P=0.045), which is a post-hoc subgroup analysis. The hair growth index analysis was possible in only 10 of the 18 subjects, because the images of the other eight could not be magnified with sufficient clarity — meaning the secondary endpoint was assessed in a subset selected by photograph quality. Within that subset there was significantly less 'absent hair' after treatment (P=0.008) and a significant increase in intermediate hairs (P=0.02); terminal and vellus hair changes were not significant. Three subjects were concurrently using minoxidil or minoxidil with finasteride. Safety was the strongest part of the result: one transient episode of forehead redness, attributed by the investigator to the citric acid buffer on sun-exposed and abraded skin, across roughly 3,300 treatment days 1. The paper is in Hair Therapy & Transplantation, an open-access title from the OMICS/Longdom group, is not indexed in PubMed, and the author discloses a financial interest and an Australian patent application on zinc-thymulin 1.

Animal and lab research

No animal studies of the zinc complex for hair growth. The mechanistic support is ex-vivo human hair follicle organ culture showing that thymic peptides differentially modulate follicle growth, with thymulin extending anagen 2, and the established biochemistry of thymulin's zinc dependence 3.

What it is used for

• Topical application to the scalp for androgenetic alopecia, in the pattern used in the pilot study 1
• Sold online as a ready-made scalp spray and as raw peptide for users to prepare themselves, with no validated formulation or stability data
• Occasionally combined by users with minoxidil, finasteride or microneedling, which makes any personal observation uninterpretable — three subjects in the pilot were on such drugs concurrently 1

Dosing

• This is a description of what one uncontrolled study did, not a validated protocol. No dose-response research exists: a single concentration was tested, against nothing.
• The concentration is very low — 0.0005 percent is five parts per million — and no published work establishes that this is the right figure rather than simply the figure that was tried.
• Formulation matters more than the number here. The study solution was buffered to pH 5.4 with defined preservatives 1; a peptide-zinc complex mixed at home in water has no stability data behind it and may not remain a complex at all.
• Anything sold for injection is outside anything that has been studied. The human data concern a topical spray only, and injecting a scalp product is not supported by any evidence on this page.

Protocols

Schedules are reproduced as their source states them. Units, IU and milligrams explains why the figures are not interchangeable between products.

Reconstitution

Vial sizes

Supplied in the study as a 100 ml spray bottle of aqueous solution

Solvent

distilled water with preservatives and buffers in the studied formulation; not bacteriostatic water for injection

Storage

The study product was kept away from direct sunlight and heat, and subjects were resupplied with fresh solution every 6 to 8 weeks — which implies limited stability in solution and is worth noting for anyone mixing their own.

Safety

Side effects

• Local tolerability was good in the only human study: one transient episode of forehead redness in one subject over roughly 3,300 treatment days, attributed to the citric acid buffer rather than the peptide, and no reports of scalp irritation or hair deterioration 1
• No systemic effects were reported, though none were systematically sought and no blood testing was described 1
• Darkening of newly grown hair was described by the investigator in several older subjects 1; this is an uncontrolled photographic observation, not a measured outcome
• Long-term safety data are absent. Eighteen people for up to ten months is the entire human exposure that has been documented
• Theoretical: thymulin is an immune-active peptide, and although systemic absorption from a topical scalp spray is expected to be minimal it has never been measured

Do not use if

• Broken, inflamed or infected scalp skin, and application after microneedling, which greatly increases delivery of a compound with no absorption data
• Known hypersensitivity to the peptide or to the preservatives and buffers in the formulation
• Pregnancy and breastfeeding: no data
• Children and adolescents: no data
• Autoimmune disease: theoretical only, on the basis of thymulin's role in T cell differentiation, and unmeasured for topical use
• Anyone expecting it to substitute for treatments with controlled evidence — minoxidil and finasteride have randomised placebo-controlled trials behind them and this does not

Interactions

Not studied. Three subjects in the pilot used minoxidil or minoxidil with finasteride concurrently and the investigator reported no observable interaction 1; three people is not a safety assessment, and their inclusion also confounds the efficacy result. Because activity depends entirely on an equimolar bound zinc ion 3, anything affecting the zinc complex in the formulation — pH, chelating agents, other actives applied at the same time — is theoretically relevant, and none of it has been tested.

Sources

• An Analysis of the Safety and Efficacy of Topical Zinc-Thymulin to treat Androgenetic AlopeciaHair Therapy & Transplantation, 2017;7(1):147 — Vickers ER; open-label, uncontrolled, 18 subjects. Not indexed in PubMed; published by the OMICS/Longdom group; the author discloses a financial interest and a patent application on the compound
• Thymic peptides differentially modulate human hair follicle growthJournal of Investigative Dermatology, 2012 — Meier N et al.; ex-vivo human hair follicle organ culture, the basis for the anagen-extension rationale; PMID 22402437
• Interactions between zinc and thymulinMetal-Based Drugs, 1994 — Dardenne and Pleau; zinc dependence of thymulin activity in an equimolar complex

Related entries

• ThymulinZinc-dependent nine-amino-acid thymic hormone; well-described physiology, almost no modern clinical research.