Assessment of the efficacy and tolerability of a topical formulation containing caffeine and Procapil 3% for improvement of male pattern hair loss

Androgenetic alopecia (AGA) is one of the most common hair loss pattern featured by the alteration of terminal follicles to vellus ones. A combination of complementary and alternative therapies can provide suitable treatment in many cases.1 This study evaluated the efficacy and tolerability of a topical formulation containing caffeine and Procapil for improving male pattern hair loss. It was a single-group, before and after clinical trial. The study protocol and informed consent were reviewed and approved in March 2020 (code: IR.TUMS.MEDICINE.REC.1399.1256). During the 12-week study, 20 eligible males with a mean age of 36.8 ± 9.1 years (range: 18–57) and hair loss types II–IV according to the Hamilton–Norwood stages received daily topical treatment with Siseh®Caffeine plus liquid, manufactured by Sina Trading Company (Chabahar Free Zone, Iran). It contains Procapil™ 3%, caffeine, and zinc PCA. The total number of patients analyzed was 19. Participants were excluded in case of known allergies to the product ingredients as well as using the prescribed or OTC hair loss treatments, in the last 3 months. Standard scalp photography, combing test and trichoscale assessment were performed before the treatment and 6 and 12 weeks later, as previously described by the authors.2, 3 Adverse reactions and patient satisfaction were also documented. The combing test showed a 26.9% decrease in hair loss at Week 12 (p = 0.026), which demonstrates a higher efficiency compared to monotherapy with the caffeine-based formulation (7.17% and 13.15% reduction after 3 and 6 months, respectively).4 According to Global Photographic Review by the independent physician, 68.5% and 68.4% of patients showed slight/much improvement in hair growth at Weeks 6 and 12, respectively (Figure 1). Tricoscale assessment showed a 53% increase in terminal/vellus hair ratio at Week 12 (p = 0.028) (Table 1). It could be explained by the role of caffeine in inhibiting the 5-alpha-reductase enzyme as well as its inhibiting effect on the intracellular phosphodiesterase (PDE) enzyme, which regulates cyclic nucleotide signaling and decreases the expression of testosterone-induced transforming growth factor (TGF)-β1. Caffeine also has an increasing effect on the level of intracellular cAMP and the expression of insulin-like growth factor (IGF)-1, which boosts cell proliferation by stimulating cellular metabolism.5 Procapil™ also contains oleanolic acid, which has an inhibitory effect on 5α1 and 5α2 reductase enzymes.6 Apigenin is a flavonoid derived from citrus peel and has vasodilatory effects1; and biotinyl-GHK (a vitamin-carrying peptide), which is a form of biotin (vitamin H), is effective in preventing hair thinning and alopecia. A randomized controlled study that investigated the use of either Redensyl, Capixyl, and Procapil (RCP) or 5% minoxidil for the treatment of AGS during a 24-week course demonstrated a significantly higher score in global photographic evaluation for RCP (88.9%), compared to minoxidil (60%). Higher self-evaluation scores were also detected in patients who used RCP.1 After 12 weeks of treatment, a 12.8% increase in the anagen/telogen ratio was also observed; however, this did not reach statistical significance. No statistically significant change was detected in total hair count/density at Weeks 6 and 12 (Table 1). At Weeks 6 and 12, 79% and 84.2% of participants rated their hair loss as "improved" or "improved very much," respectively. No adverse effects, such as dryness, itching, redness, scaling, folliculitis, or burning, were observed or reported during the full course of therapy. In conclusion, this study found a 12-week treatment course with a topical formulation containing caffeine and Procapil 3% a beneficial and promising treatment for AGA. Further controlled trials are required to compare the efficacy of caffeine combination therapy with topical minoxidil, which is the only FDA-approved topical treatment. Alireza Firooz, Saman Ahmad Nasrollahi, and Aniseh Samadi performed the research. Alireza Firooz and Aniseh Samadi designed the research study. Zahra Saffarian, Elnaz Rokhsat, and Mehdi Moazzami Goudarzi contributed essential reagents or tools. Aniseh Samadi analyzed the data. Aniseh Samadi, and Sina Kardeh. wrote the paper. All the authors confirm that they have read and approved this version of the article. This study was funded by Sina Company (Chabahar Free Zone, Iran). This funding was used for lab equipment, personal costs, travel and transportation, and author stipends. One of the authors, Mr. Mehdi Moazzami Goudarzi, is the Regulatory Affairs of sponsor company (Sina Company). The other authors confirmed that they have no conflict of interest in this article. Informed written consent was obtained from each participant in this study. The study protocol and informed consent were reviewed and approved in March 2020 (code: IR.TUMS.MEDICINE.REC.1399.1256). Research data are not shared.