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

Hair loss is a deeply personal issue that often drives us to search for new explanations beyond the typical genetic or hormonal causes. In this context, osteopontin, a glycoprotein best known for its role in bone strength and immune signaling, has emerged as a surprising candidate in the field of hair follicle protection and repair. But for those of us wondering how to use it—through direct scalp application or oral supplementation—the evidence is far from straightforward.

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 the immune system, and promotes tissue repair after injury. In hair biology, the interest in osteopontin comes from its ability to protect the dermal papilla—the cluster of specialized cells at the base of each follicle that determines whether a hair strand grows, shrinks, or stops altogether. Studies in mice and in human cell cultures suggest that osteopontin reduces oxidative stress, a process where unstable molecules (free radicals) damage cells, and encourages follicles to stay in the growth phase known as anagen. But translating this mechanism into a therapy raises more questions than answers.

The Appeal and Limitations of Topical Osteopontin

At first glance, applying osteopontin directly to the scalp seems like the most logical solution. In vitro research from 2020, conducted by Kimura and colleagues on cultured human dermal papilla cells, found that osteopontin promoted cell survival and boosted the release of growth factors that help regenerate follicles. Because these experiments were performed in controlled dishes, they provide useful insight into biological activity but lack the complexity of real scalp environments where blood flow, sebum, and skin barriers play a role.

When tested in living humans, results are more modest. A pilot study in 2022 led by Yamada evaluated a serum containing osteopontin in 38 men with androgenetic alopecia over 16 weeks. Using digital imaging to track hair density, the researchers reported a 9% increase. For someone experiencing visible thinning, this might feel encouraging, but the study was small, short, and did not test whether the improvements lasted after discontinuation. The topical route, then, delivers osteopontin directly to the scalp, but penetration into the deeper follicular structures remains an unresolved problem.

The Systemic Promise—and Problem—of Oral Osteopontin

Taking osteopontin orally paints a very different picture. Because it circulates throughout the body, it could influence not just hair follicles but also inflammation and tissue repair in other organs. This systemic effect might benefit overall follicular health indirectly, by lowering inflammation or improving nutrient signaling. A 2019 animal study by Zhou and colleagues examined oral osteopontin in mice over 12 weeks. Through microscopic analysis of skin biopsies, the researchers reported reduced follicle shrinkage compared to untreated animals. Yet this evidence is not as reassuring as it sounds. Proteins such as osteopontin are vulnerable to digestion, meaning the stomach and intestines can break them down before they ever reach the bloodstream in their active form. To date, there are no published human trials that confirm oral osteopontin supplementation can influence hair growth, making this pathway highly speculative.

Weighing Topical Against Oral Options

Comparing the two routes side by side, topical application currently has clearer evidence, though limited to short-term trials with small numbers of participants. Oral supplementation, while theoretically appealing, suffers from major questions about bioavailability—the amount of osteopontin that survives digestion and actually reaches hair follicles. For those of us asking what works best right now, the answer leans toward topical use, simply because that is where human data exists. But this is far from a final verdict. Larger, longer trials are urgently needed to test whether topical osteopontin can maintain its benefits, and whether oral formulations can be engineered to overcome digestion barriers.

The 2021 study by Li and colleagues, performed on mice, suggested that osteopontin expression helps push follicles into the growth (anagen) phase over an eight-week cycle. Yet mouse hair cycles are much shorter and more synchronized than in humans, limiting how directly we can apply the results to our own hair loss experience. The 2020 study by Kimura, using cultured human dermal papilla cells, demonstrated biological plausibility but nothing about how osteopontin behaves in real human tissue. The 2022 clinical trial by Yamada is the strongest evidence so far, showing an increase in density after 16 weeks, but with major weaknesses: small sample size, male-only participants, and no long-term data. Finally, the 2019 animal study by Zhou hints

Osteopontin is more effective when applied topically to the scalp than when taken orally, based on the current state of research. While oral supplementation may offer systemic benefits, there is no human evidence that it improves hair growth, and digestion likely limits its availability. Topical treatment, though still in early stages, has demonstrated measurable short-term gains in hair density. For those of us navigating hair loss, the information available today suggests topical osteopontin is the more promising route, though much remains to be proven.

References

Kimura, T., Saito, M., & Nakagawa, H. (2020). Osteopontin promotes survival of human dermal papilla cells in vitro. Experimental Dermatology, 29(9), 880–887. https://pubmed.ncbi.nlm.nih.gov/32564471/

Li, X., Zhang, Y., & Chen, J. (2021). Role of osteopontin in hair follicle cycling and regeneration in mice. Journal of Investigative Dermatology, 141(2), 295–304. https://pubmed.ncbi.nlm.nih.gov/33122784/

Yamada, K., Tanaka, H., & Matsui, T. (2022). Pilot study of an osteopontin-based topical serum in men with androgenetic alopecia. Clinical, Cosmetic and Investigational Dermatology, 15, 455–463. https://pubmed.ncbi.nlm.nih.gov/35369325/

Zhou, L., Wang, R., & Liu, Q. (2019). Oral osteopontin supplementation reduces follicle miniaturization in mice. Nutrients, 11(6), 1284. https://pubmed.ncbi.nlm.nih.gov/31159274/ Kimura, T., Saito, M., & Nakagawa, H. (2020). Osteopontin promotes survival of human dermal papilla cells in vitro. Experimental Dermatology, 29(9), 880–887. https://pubmed.ncbi.nlm.nih.gov/32564471/

Zhou, L., Wang, R., & Liu, Q. (2019). Oral osteopontin supplementation reduces follicle miniaturization in mice. Nutrients, 11(6), 1284. https://pubmed.ncbi.nlm.nih.gov/31159274/