What Is Valproic Acid, and How Did It Become a Subject of Interest in Hair Growth and Alopecia Research?

Valproic acid is not a new or experimental substance. It is a pharmaceutical compound that has been prescribed since the early 1960s, primarily for neurological and psychiatric conditions. Health authorities such as the U.S. Food and Drug Administration recognize valproic acid as an anti‑epileptic and mood‑stabilizing medication used in epilepsy, bipolar disorder, and migraine prevention. Its original development had nothing to do with dermatology or cosmetic medicine. However, when examining why valproic acid entered the field of hair loss research, it becomes clear that this interest did not arise from marketing claims, but from observations made in basic biomedical research.

When we approach this topic critically, the first thing we need to understand is that valproic acid was never designed to promote hair growth. In fact, hair‑related effects were initially considered biologically incidental. Only after decades of use did researchers begin to document that the drug influenced fundamental cellular processes that are also relevant to hair follicle behavior. This overlap, rather than clinical success in hair loss patients, is what sparked scientific curiosity.

How a neurological drug affects cells beyond the brain

Valproic acid exerts its primary therapeutic effects by increasing levels of gamma‑aminobutyric acid, commonly abbreviated as GABA. GABA is a naturally occurring chemical messenger that reduces excessive electrical activity in the brain. While this mechanism explains its neurological use, it does not explain its relevance to hair follicles. The connection lies elsewhere.

A separate and well‑documented property of valproic acid is its ability to inhibit histone deacetylases. These enzymes regulate how tightly DNA is packaged inside cells. When DNA is tightly packed, certain genes are less active; when it is more relaxed, gene activity increases. This form of regulation is known as epigenetic control, meaning it affects gene expression without altering the genetic code itself. Hair follicles are highly dependent on precise gene signaling to move between growth,** regression, and rest phases. From a research perspective, any compound capable of altering gene activity in skin cells becomes a legitimate object of study, regardless of its original purpose.**

Why hair follicles became part of the discussion

Hair follicles are not static structures. They cycle continuously through phases of growth and rest, and this cycling is controlled by signaling pathways inside the skin. One of the most important of these pathways is the Wnt/β‑catenin signaling pathway. In simple terms, this pathway acts as a biological instruction system that tells hair follicle cells when to initiate growth.

Research indexed by PubMed has repeatedly shown that impaired Wnt/β‑catenin signaling is associated with androgenetic alopecia, the most common form of hair loss in both men and women. Valproic acid attracted attention because laboratory studies demonstrated that it could activate this pathway in certain cell types. At this stage, the interest was theoretical rather than clinical. The reasoning was not that valproic acid cured hair loss, but that it interacted with a pathway known to be essential for hair follicle activation.

What laboratory studies actually showed

One of the earliest and most cited studies linking valproic acid to hair growth mechanisms was published in 2012 in Biochemical and Biophysical Research Communications. The study examined human dermal papilla cells, which are specialized cells located at the base of hair follicles and play a central role in regulating hair growth. The researchers exposed these cells to valproic acid in a laboratory environment over several days.

The method involved measuring cell proliferation and analyzing the activation of Wnt/β‑catenin signaling using protein detection techniques. The results showed increased cell activity and signaling pathway activation. From a scientific standpoint, this indicated biological plausibility, not therapeutic effectiveness. A major limitation of the study is that isolated cells do not replicate the complex hormonal and immune environment of the human scalp. Additionally, laboratory concentrations of drugs often differ from what can be safely achieved in real‑world use.

Evidence from animal models and its limits

In 2013, a study published in Experimental Dermatology investigated the effects of topical valproic acid in mice. The researchers applied the compound to the skin of laboratory mice over several weeks and observed earlier initiation of the hair growth phase compared with untreated animals. Evaluation methods included visual inspection and microscopic analysis of hair follicles.

While these findings are frequently cited online, a critical reading is essential. Mouse hair growth cycles differ significantly from human hair cycles, and mice do not develop androgenetic alopecia in the same way humans do. Animal studies are useful for understanding mechanisms, but they cannot establish clinical relevance on their own. This limitation is acknowledged within the scientific literature and remains a key reason why enthusiasm has remained cautious.

Human research and what it does and does not tell us

Human studies on valproic acid and hair loss are scarce and small in scale. A notable example is a 2018 study published in Annals of Dermatology, which evaluated a topical valproic acid formulation in men with androgenetic alopecia over a 24‑week period. Hair density and thickness were assessed using standardized scalp photography and phototrichogram analysis, a technique that measures hair growth through repeated imaging of the same scalp area.

The study reported modest increases in hair parameters compared with baseline measurements. However, from a critical standpoint, several issues remain. The study involved fewer than 30 participants, lacked long‑term follow‑up, and did not directly compare outcomes with established treatments such as minoxidil. The authors themselves emphasized that the findings were preliminary and insufficient to support clinical recommendations.

Safety concerns that shape the research narrative

Any discussion of valproic acid must address safety. Oral valproic acid is associated with well‑documented risks, including liver toxicity and severe birth defects. These risks are recognized by regulatory bodies such as the FDA and the World Health Organization. Although topical application is assumed to reduce systemic exposure, this assumption has not been validated by large‑scale, long‑term studies.

From a research perspective, this safety profile significantly limits enthusiasm. A compound with known systemic risks faces a higher threshold for acceptance in cosmetic or dermatological use. This reality explains why, despite more than a decade of investigation, valproic acid has not progressed beyond exploratory research in the hair loss field.

What we actually need to know as readers and patients

When evaluating valproic acid as a potential hair growth agent, the key issue is not whether it can influence hair‑related pathways, but whether it can do so safely and consistently in humans. Current evidence supports biological activity at the cellular and animal level. Human evidence remains limited, short‑term, and methodologically weak.

From an evidence‑based perspective, valproic acid represents an example of drug repurposing driven by molecular biology rather than clinical success. This distinction matters. Interest in a mechanism does not equal proof of benefit, and absence of regulatory approval reflects unresolved questions rather than oversight.

Research context and critical synthesis

Between 2012 and 2018, research on valproic acid and hair growth progressed from cell studies to small human trials. Methods included in vitro cell culture, animal application models, and short‑term topical use in humans. Evaluation relied on molecular assays, microscopy, and imaging‑based hair measurements. Across studies, consistent criticisms include small sample sizes, lack of long‑term safety data, and uncertain real‑world applicability. These limitations explain why valproic acid remains a subject of scientific interest rather than a validated treatment for alopecia.

References

Lee, S. H., Yoon, J., Kim, J. Y., Park, J. K., & Shin, J. W. (2012). Valproic acid induces hair regeneration by activating the Wnt/β‑catenin pathway in human dermal papilla cells. Biochemical and Biophysical Research Communications, 426(2), 168–173. https://pubmed.ncbi.nlm.nih.gov/22960003

Jo, S. J., Choi, S. J., Yoon, S. Y., Lee, J. Y., Park, W. S., & Kim, K. H. (2013). Topical valproic acid accelerates hair regeneration in mice. Experimental Dermatology, 22(11), 721–724. https://pubmed.ncbi.nlm.nih.gov/24103142

Kim, J. E., Lee, Y. B., Kim, B. J., Park, H. J., & Kim, M. N. (2018). Effect of topical valproic acid on human hair growth in androgenetic alopecia. Annals of Dermatology, 30(1), 52–58. https://pubmed.ncbi.nlm.nih.gov/29302902/