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
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
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
