Topical valproic acid increases the hair count in male patients with androgenetic alopecia: A randomized, comparative, clinical feasibility study using phototrichogram analysis

Abstract

Valproic acid (VPA), a widely used anticonvulsant, inhibits glycogen synthase kinase 3β and activates the Wnt/β-catenin pathway, which is associated with hair growth cycle and anagen induction. To assess the efficacy of topical VPA for treating androgenetic alopecia (AGA), we performed a randomized, double-blind, placebo-controlled clinical trial. Male patients with moderate AGA underwent treatment with either VPA (sodium valproate, 8.3%) or placebo spray for 24 weeks. The primary end-point for efficacy was the change in hair count during treatment, which was assessed by phototrichogram analysis. Of the 40 patients enrolled in the study, 27 (n = 15, VPA group; n = 12, placebo group) completed the entire protocol with good compliance. No statistical differences in age, hair loss duration and total hair count at baseline were found between the groups. The mean change in total hair count was significantly higher in the VPA group than in the placebo group (P = 0.047). Both groups experienced mostly mild and self-limited adverse events, but their differences in prevalence rates were similar between the two groups (P = 0.72). A subject treated with topical VPA developed ventricular tachycardia, but it did not seem to be related to the VPA spray. Topical VPA increased the total hair counts of our patients; therefore, it is a potential treatment option for AGA.

Differential distribution of the epigenetic marker 5‐hydroxymethylcytosine occurs in hair follicle stem cells during bulge activation

“…Use of organ cultures to study HF activation previously has been well documented. For instance, Jo et al explored the effects of valproic acid on HF growth using an in vitro organ culture system . In addition, Kwon et al deployed HF organ cultures to measure follicular activity, correlating hair growth in culture with that occurring in vivo …”

“…The selection of the three agents applied to skin explants, valproic acid, resveratrol, and ascorbic acid, was based on previously established data supporting their capacity to stimulate stem cells with potential impact on hair growth. Specifically, valproic acid has been shown to induce differentiation of stem cells through epigenetic modifications and promote HF growth in human patients . In 2013, Jo et al used valproic acid to induce anagen in HFs of 7‐week‐old female C57BL/6 mice .…”

“…For instance, Jo et al explored the effects of valproic acid on HF growth using an in vitro organ culture system. 19 In addition, Kwon et al deployed HF organ cultures to measure follicular activity, correlating hair growth in culture with that occurring in vivo. 20 The selection of the three agents applied to skin explants, valproic acid, resveratrol, and ascorbic acid, was based on previously Whether the findings provided herein will have diagnostic relevance to human alopecia remains to be evaluated in larger cohorts of experimental and human tissues in which statistically rigorous assessment of quantitative data is possible.…”

Topical application of the Wnt/β‐catenin activator methyl vanillate increases hair count and hair mass index in women with androgenetic alopecia

“…In an organ culture model, valproate increased the viability of human dermal papilla cells, promoted elongation of the hair shaft, and reduced catagen transition of human hair follicles . Interestingly, a 24‐week clinical feasibility study has recently shown that 8.3% topical valproate can increase total hair count of AGA patients . MV is a natural activator of the WNT/ β ‐catenin signaling pathway.…”

“…Further research including men will be necessary to perform a sex‐based analysis of the effects of topically applied MV on hair growth. Our study was also limited by the fact that we did not compare the effect of topically applied MV with that of topical valproate, another molecule known to activate the WNT pathway and potentially useful in AGA . Another significant limitation is the lack of measurement of androgen receptor (AR) expression − a well‐known antagonist of WNT/ β ‐catenin pathway signaling in epidermal stem cells – in scalp biopsies.…”