Is Osteopontin more effective in topical treatments or oral supplements for hair loss?

Hair loss drives a lot of searching for explanations beyond the usual genetic and hormonal ones. In that context osteopontin, a glycoprotein best known for its role in bone and immune signalling, has drawn attention after laboratory work linked it to hair follicle activation. The short answer to the question in the title is that neither route has been tested: there is no published human trial of topical osteopontin and no published human trial of oral osteopontin for hair loss, so the two cannot be compared.

Understanding Osteopontin's Role in Follicle Biology

Osteopontin is not a simple nutrient but a multifunctional glycoprotein, meaning it is made of proteins and sugar molecules working together. In the body, it helps cells survive under stress, coordinates immune signalling, and takes part in tissue repair after injury.

The hair interest traces to a specific piece of research. In 2023, Wang and colleagues reported in Nature that clusters of senescent melanocytes in mouse skin nevi secrete osteopontin, and that osteopontin acting on the CD44 receptor pushes hair follicle stem cells out of quiescence. Injecting osteopontin, or overexpressing it genetically, produced robust hair growth in mice, and deleting either osteopontin or CD44 removed the effect. The authors also reported that osteopontin is overexpressed in human hairy nevi and that it stimulated growth in human hair follicles studied outside the body. That is a mechanism paper in mice and isolated human follicles — not a treatment study in people. Several of its authors are connected to a company developing the finding commercially, which is disclosed in the paper.

What "Topical Osteopontin" Actually Rests On

There is no published clinical trial of a topical osteopontin serum in people with androgenetic alopecia. No study has reported a hair-density figure for such a product. Descriptions of a pilot trial in men with androgenetic alopecia circulate online, but they do not correspond to a paper that can be found in PubMed, and this article no longer cites one.

The practical obstacle is also worth stating. Osteopontin is a large glycoprotein. In the research that produced hair growth, it was delivered by injection into the skin or expressed by cells already sitting in the dermis — not spread on the skin surface. Whether an intact protein of that size can cross the skin barrier and reach the follicle in a useful amount is an unanswered question, not a solved one. Any product sold as "topical osteopontin" for hair is being sold ahead of the evidence.

The Systemic Problem With Oral Osteopontin

Oral supplementation has an obvious biological objection: osteopontin is a protein, and proteins are broken down by digestion. There is no published human trial of oral osteopontin for hair growth, and no animal study we could locate that tested oral osteopontin against follicle miniaturisation. "Oral osteopontin supplement" is not an established product category, and anyone searching for one should know there is nothing behind it.

The Finding That Points the Other Way

Any comparison of routes has to account for a result that cuts against the whole premise. In 2020, Alam and colleagues reported in the British Journal of Dermatology that an osteopontin-derived peptide (FOL-005) inhibits human hair growth. Tested on organ-cultured human hair follicles, human scalp skin, and human scalp skin grafted onto mice, the peptide pushed follicles prematurely into the catagen (regression) phase, apparently by reducing production of fibroblast growth factor-7. The authors proposed it as a candidate treatment for unwanted hair growth — hirsutism and hypertrichosis. That work was funded and co-authored by the company developing the peptide.

So the two most relevant pieces of human-tissue research point in opposite directions: the full protein injected into skin promoted growth in mice and isolated follicles, while a fragment of the same protein applied to human follicles suppressed it. Which effect a given preparation would produce on a human scalp is genuinely unknown.

Weighing Topical Against Oral Options

Neither route has clearer evidence, because neither route has evidence. Topical osteopontin has no completed human trial. The closest test is of the osteopontin-derived peptide FOL-005, not the whole protein: the peptide's developer, Follicum, tested a topical FOL-005 formulation for 16 weeks in 210 men with hair loss; its 2021 top-line press release reported no significant difference from placebo (p=0.83), and the results have not been published in a journal. Oral osteopontin has no human trial and a strong prior reason to expect digestion to destroy it. What exists is preclinical work in mice, isolated human follicles, and cell culture — plus one human-tissue study showing an osteopontin fragment doing the opposite of what buyers of a hair product would want.

Osteopontin is an experimental research subject, not an available medicine. It is not approved for hair loss anywhere, its long-term safety in this use is unknown, and no dose, formulation or route has been established. Mouse hair cycles are shorter and more synchronised than human ones, so mouse results do not transfer directly. Larger human trials would be needed before anything could be said about either route.

Talk to a doctor or dermatologist before starting, stopping or combining any hair-loss treatment, and before using an unapproved compound sold on the strength of preclinical research.

References

Wang, X., Ramos, R., Phan, A. Q., et al. (2023). Signalling by senescent melanocytes hyperactivates hair growth. Nature, 618(7966), 808–817. PMID: 37344645. https://pubmed.ncbi.nlm.nih.gov/37344645/

Alam, M., Bertolini, M., Gherardini, J., et al. (2020). An osteopontin-derived peptide inhibits human hair growth at least in part by decreasing fibroblast growth factor-7 production in outer root sheath keratinocytes. British Journal of Dermatology, 182(6), 1404–1414. PMID: 31487385. https://pubmed.ncbi.nlm.nih.gov/31487385/

Follicum AB. (2021, May 6). Follicum reports top-line results from Phase IIa study of FOL-005 for treatment of hair loss (alopecia) [Press release]. https://news.cision.com/follicum/r/follicum-reports-top-line-results-from-phase-iia-study-of-fol-005-for-treatment-of-hair-loss--alopec,c3341890