Evidence for Supplemental Treatments in Androgenetic Alopecia

July 2014 | Volume 13 | Issue 7 | Original Article | 809 | Copyright © July 2014

Shannon Famenini MD and Carolyn Goh MD

Department of Medicine, Division of Dermatology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA

Biotin supplementation has also been used successfully in the treatment of hair loss in dogs.17 In 119 dogs with symptoms including dull coat, brittle hair, and loss of hair due to unknown factors, 60% showed resolution of all symptoms, 31% showed improvement, and only 9% showed no change. These results suggest that biotin may help improve alopecia in humans, but it is unclear if it would help in all types of alopecia, or only in some cases. In vitro studies have shown no effect on the proliferation and expression of differentiation specific keratins K1 and K10 in cultures of outer root sheath cells after administration of low dose and pharmaceutical doses of biotin.18 Biotin concentrations likewise had no effect on the expression of keratin K16, involucrin, and filaggrin. To date there have been no clinical trials that have evaluated the efficacy of biotin in AGA, or any other type of alopecia. Biotinidase levels also have not been evaluated in AGA.


Caffeine appears to have several medicinal uses. Caffeine citrate has been used in the treatment of idiopathic apnea of prematurity, and caffeine and sodium benzoate have been used in the treatment of acute respiratory depression.19,20 Caffeine has also been evaluated for cosmetic purposes as it has antioxidant properties and appears to increase the microcirculation in the skin.21 Recent studies have elucidated a possible role for caffeine in the treatment of AGA as it was shown to stimulate hair growth in vitro. When cultures of hair follicles from male AGA patients were administered different concentrations of testosterone and caffeine, it was discovered that testosterone at a concentration of 5 mg/ml had an inhibitory effect on hair growth that was reversed by caffeine at a concentration of 0.005% (P<0.001). In addition, caffeine at concentrations of 0.001% significantly induced hair follicle growth when added to a testosterone-containing medium (P<0.001).22 Although in vitro conditions are missing the vitamins, minerals, and other structures present in natural growth conditions, these results suggest a potential benefit of caffeine for AGA treatment, but it is important to note that higher levels of caffeine had an inhibitory effect on hair growth. The authors proposed that caffeine inhibits phosphodiesterase, enhancing cAMP levels, and thereby inducing cell metabolism that results in cellular proliferation.22
The topical application of a caffeine shampoo was evaluated for 6 months in 30 men with AGA.23 Self-reported and dermatological assessments revealed hair loss to be substantially reduced compared to baseline assessments. Furthermore, the hair pull test demonstrated increased tensile strength, with 7.17% reduction in hairs pulled after 3 months and 13.45% reduction after 6 months. However, the results were reported without the performance of statistical analysis and the study was limited by lack of a control group. Placebo controlled randomized trials are needed to better assess the efficacy of caffeine in AGA.


Melatonin is secreted by the pineal gland and regulates the sleep cycle. Indeed, impaired melatonin synthesis is linked to poor quality of sleep among the elderly, and treatment with prolonged release melatonin for three weeks was shown to improve quality of sleep and morning alertness when compared to placebo.24 Melatonin has also been implicated in the hair cycle, growth, and pigmentation across many species. Murine and human follicles express the melatonin membrane receptor and the nuclear melatonin receptor, whose stimulation inhibits keratinocyte apoptosis and estrogen receptor-a expression.17 Murine and human hair follicles are also an important site for melatonin synthesis.17 Melatonin may also reduce DNA damage which can initiate apoptosis in the especially sensitive anagen hair follicle by protecting against free radicals.25-28 Furthermore, melatonin production in hair follicles may play a role in the regulation of pituitary prolactin synthesis.29 Stimulation of prolactin receptors in human hair follicles induces the catagen phase.30,31
In vitro studies have revealed conflicting results on the effect of melatonin on hair growth. In cultures of male and female human hair follicles, hair shaft elongation was observed with administration of 30 μM melatonin and hair growth inhibition occurred with melatonin in the mM range.32 Another in vitro study showed no change in human hair follicle growth or proliferation with different melatonin concentrations.25
Clinical studies have been conducted to evaluate the safety and efficacy of melatonin in humans. In an open-label observational study, 15 men and 15 women with Stage I or II AGA/FPHL showed significant reduction in severity of hair loss (P<0.001) based on dermatological examinations and self-reported questionnaires after 30 days of daily application of a melatonin solution.33 To obtain more objective assessments, an extension of the study utilized the TrichoScan digital software to assess hair count and hair density in 35 men with Stage I or II AGA with daily application of a melatonin shampoo for six months. After three months, 54.8% of patients experienced 29% increase in hair density; after six months, 58.1% of patients showed 41% increase in hair density (P<0.001). Hair count was increased by 29.2% after three months and 41.7% after six months (P<0.001). An open-label, multi-center study of 901 men with stage I or II AGA and 990 women with stage I or II FPHL was also conducted33 The hair pull test was used to measure clinical response. The percentage of patients who were identified as having severe or moderate hair loss decreased from 61.6% to 33.7% after 30 days and to 7.8% after 90 days (P<0.001). The percentage of patients who were assessed as having no hair loss increased from 12.2% to 25.5% after 30 days and 61.5% after 90 days (P<0.001). Treatment with melatonin was also associated with reduction in seborrhea. The percentage of patients experiencing moderately severe or severe seborrhea was reduced from 35.7% to 18% after 30 days, and further decreased to 5.4% after 90 days. The topical melatonin solution was also considered highly tolerable by most physicians and patients.33
A placebo-controlled, double-blind, randomized study was performed in 40 women with FPHL or diffuse alopecia defined as