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Efficacy of a cosmetic caffeine shampoo in androgenetic alopecia management. II Note
Abstract
Androgenetic alopecia (AGA) is a common, progressive, patterned loss of visible scalp hair. The severity and frequency are greater in men. It causes psychological distress and negative effects on the quality of life and thus the prospect of treating AGA is mandatory. Dihydrotestosterone (DHT) is responsible for hair loss in AGA. At present only two medical treatments, minoxidil and finasteride, are licensed for the treatment of male balding. Caffeine was identified as a stimulator of human hair growth. We report the results of a randomised, controlled, double-blind, parallel group study to assess, in a panel of healthy men suffering from AGA, the skin compatibility of a shampoo containing caffeine and to assess its anti hair loss efficacy and its cosmetic qualities, after application for 6 consecutive months versus placebo. Our data support the beneficial effects of topical application of caffeine in AGA, suggesting it as a cosmetic growth-stimulating agent suitable for AGA treatment.
... Based on the observation from in vitro studies that caffeine might counteract AGA progression, and the results of the skin penetration studies showing that caffeine can efficiently penetrate into the hair follicle and is retained for >24 h, the effect of caffeine-containing formulations on hair loss has been investigated in several in vivo studies [83][84][85][86]. For the evaluation of hair loss, several diagnostic techniques are available, covering noninvasive, semi-invasive, and invasive methods, as briefly described in the following: both the hair pluck and hair pull tests have been employed in the assessment of caffeine and caffeine-containing shampoos. ...
... A randomized, controlled, double-blind, parallel group study of a caffeine-containing shampoo was conducted in males with AGA (n = 66) [85]. The contentment was significantly higher for the caffeine-containing shampoo compared to a caffeine free control (p < 0.001). ...
Caffeine, particularly after ingestion, is well known to exert various pharmacological effects. A growing body of evidence implicates the ingestion of caffeine with beneficial effects on several diseases. The easy penetration of caffeine across the skin barrier and into human skin makes caffeine an ideal compound for topical application. Hair loss is known to negatively affect the quality of life and predispose to depression and anxiety. Androgenetic alopecia (AGA) is the most common type of hair loss in both men and women. To date, only few approved drug-based treatments for AGA exist, and these are inevitably associated with side effects. Therefore, the development of topical treatments based on well-tolerated natural ingredients such as caffeine to alleviate hair loss may provide a much-needed alternative to drug-based approaches.
... Research has focused on the use of topical caffeine for the treatment of AGA. Six months of daily caffeine shampoo use (Alpecin caffeine shampoo C1, unknown concentration, 7 mL, left on scalp for 2 min) resulted in fewer hairs extracted on the hair-pull test and hairs shed during combing, with reduced speed of hair loss progression and overall hair loss intensity [18][19][20]. Caffeine lotion (unknown concentration) has also been tested with similar results, including decrease in hairs released during the hair-pull test and positive treatment response in 75% of patients at 2 months and 83% at 4 months [21]. Comparison of 0.2% caffeine topical liquid to 5% topical minoxidil (MXD) demonstrated noninferiority (n = 210) with 10.59% improvement in anagen ratio compared to 11.68% using MXD (p = 0.574) [22]. ...
... Another topical solution containing 1% caffeine, 5% MXD, and 1.5% azelaic acid was more effective for hair regrowth and decreased shedding after 32 weeks of treatment compared to 5% MXD alone or placebo [24]. Topical caffeine shows potential as a CAM for hair loss; however, studies are limited by lack of quantitative, standardized evaluation [18,19,[21][22][23][24][25]. ...
The treatment of alopecia is limited by a lack of therapies that induce and sustain disease remission. Given the negative psychosocial impact of hair loss, patients that do not see significant hair restoration with conventional therapies often turn to complementary and alternative medicine (CAM). Although there are a variety of CAM treatment options on the market for alopecia, only a few are backed by multiple randomized controlled trials. Further, these modalities are not regulated by the Food and Drug Administration and there is a lack of standardization of bioactive in gredients in over-the-counter vitamins, herbs, and supplements. In this article, we provide a comprehensive review of the efficacy, safety, and tolerability of CAM, including natural products and mind and body practices, in the treatment of hair loss. Overall, there is a need for additional studies investigating CAM for alopecia with more robust clinical design and standardized, quantitative outcomes.
... Clinical evidence highlights the efficacy of caffeinecontaining shampoo products in the treatment of AGA [17•, 20, 21]. In a comparative study by Sisto et al.,84.8% of AGA patients treated with caffeine shampoo had a higher rate of satisfaction compared to 36.4% of patients treated with placebo shampoo (p < 0.05) [20]. Additionally, within three cohort studies, the daily use of caffeine shampoo and lotion resulted in a decrease in hair shedding as assessed by the hair-pull test [17•, 21, 22]. ...
Purpose of Review
Androgenic alopecia (AGA) is the most common form of non-scarring alopecia, affecting millions of men and women in the United States (U.S.). This review highlights alternative and complementary treatment options for AGA.
Recent Findings
The treatment regimens for AGA have increased in pharmacotherapeutics, surgical, and complementary (CAM) categories. Each of the different treatment approaches can now be utilized by dermatologists to combat patient hair loss.
Summary
The U.S. Food and Drug Administration (FDA) has approved only two agents to treat AGA: prescription-only, oral finasteride and over-the-counter (OTC), topical minoxidil. Increased availability of therapies claiming hair regrowth properties, coupled with limited pharmacotherapeutic options for AGA, lead patients to seek alternative treatments. Increased awareness of the current evidence supporting complementary and alternative therapies among dermatologists will facilitate appropriate and timely education of AGA patients.
Caffeine is a bitter, white crystalline purine, a methylxanthine alkaloid, chemically related to the adenine and guanine bases of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). Caffeine is found in different concentrations in seeds, leaves, and nuts of more than 60 different plant species. It acts as a naturally occurring pesticide since it can paralyze and kill predator insects feeding on the plant [1]. Humans consume caffeine as a stimulant, mainly in coffee beans, tea extracts, in products containing kola or guarana seeds, in the form of soft drinks or energy drinks, or even in everyday food. Caffeine is the world’s most widely consumed psychoactive compound or central nervous system (CNS) stimulant, and in the USA, more than 90% of adults consume an average of 2.4 mg/kg of caffeine daily [2].
Background: Hair loss encompasses a group of scarring and nonscarring diseases with limited treatment options. Understanding the pathogenesis of alopecias has led to the experimental use of phosphodiesterase inhibitors (PDEi).
Objective: To perform a systematic review of literature surrounding the use of PDEi for alopecia.
Materials and methods: A search was conducted using PubMed in February 2019 on PDEi and alopecia. Inclusion criteria were clinical trials, prospective or retrospective studies, case series and case reports written in English, using PDEi in human subjects for the treatment of alopecia.
Results: Fifteen articles were included for review – eight discussing the use of topical caffeine 0.2%–2.5% for the treatment of androgenetic alopecia (AGA) and telogen effluvium (TE), one using injectable caffeine for AGA, one using topical sildenafil for pediatric alopecia areata (AA), and five using oral apremilast for adult AA.
Conclusions: Preliminary results using topical caffeine for AGA or TE are promising with minimal adverse events. However, these studies are primarily single-center trials with few patients. Studies using topical or systemic PDEi for AA demonstrate limited success. Current research using PDEi for alopecia is limited, however new clinical trials are being conducted.
Background:
Female pattern hair loss (FPHL), or androgenic alopecia, is the most common type of hair loss affecting women. It is characterised by progressive shortening of the duration of the growth phase of the hair with successive hair cycles, and progressive follicular miniaturisation with conversion of terminal to vellus hair follicles (terminal hairs are thicker and longer, while vellus hairs are soft, fine, and short). The frontal hair line may or may not be preserved. Hair loss can have a serious psychological impact on women.
Objectives:
To determine the efficacy and safety of the available options for the treatment of female pattern hair loss in women.
Search methods:
We updated our searches of the following databases to July 2015: the Cochrane Skin Group Specialised Register, CENTRAL in the Cochrane Library (2015, Issue 6), MEDLINE (from 1946), EMBASE (from 1974), PsycINFO (from 1872), AMED (from 1985), LILACS (from 1982), PubMed (from 1947), and Web of Science (from 1945). We also searched five trial registries and checked the reference lists of included and excluded studies.
Selection criteria:
We included randomised controlled trials that assessed the efficacy of interventions for FPHL in women.
Data collection and analysis:
Two review authors independently assessed trial quality, extracted data and carried out analyses.
Main results:
We included 47 trials, with 5290 participants, of which 25 trials were new to this update. Only five trials were at 'low risk of bias', 26 were at 'unclear risk', and 16 were at 'high risk of bias'.The included trials evaluated a wide range of interventions, and 17 studies evaluated minoxidil. Pooled data from six studies indicated that a greater proportion of participants (157/593) treated with minoxidil (2% and one study with 1%) reported a moderate to marked increase in their hair regrowth when compared with placebo (77/555) (risk ratio (RR) = 1.93, 95% confidence interval (CI) 1.51 to 2.47; moderate quality evidence). These results were confirmed by the investigator-rated assessments in seven studies with 1181 participants (RR 2.35, 95% CI 1.68 to 3.28; moderate quality evidence). Only one study reported on quality of life (QoL) (260 participants), albeit inadequately (low quality evidence). There was an important increase of 13.18 in total hair count per cm² in the minoxidil group compared to the placebo group (95% CI 10.92 to 15.44; low quality evidence) in eight studies (1242 participants). There were 40/407 adverse events in the twice daily minoxidil 2% group versus 28/320 in the placebo group (RR 1.24, 95% CI 0.82 to 1.87; low quality evidence). There was also no statistically significant difference in adverse events between any of the individual concentrations against placebo.Four studies (1006 participants) evaluated minoxidil 2% versus 5%. In one study, 25/57 participants in the minoxidil 2% group experienced moderate to greatly increased hair regrowth versus 22/56 in the 5% group (RR 1.12, 95% CI 0.72 to 1.73). In another study, 209 participants experienced no difference based on a visual analogue scale (P = 0.062; low quality evidence). The assessments of the investigators based on three studies (586 participants) were in agreement with these findings (moderate quality evidence). One study assessed QoL (209 participants) and reported limited data (low quality evidence). Four trials (1006 participants) did not show a difference in number of adverse events between the two concentrations (RR 1.02, 95% CI 0.91 to 1.20; low quality evidence). Both concentrations did not show a difference in increase in total hair count at end of study in three trials with 631 participants (mean difference (MD) -2.12, 95% CI -5.47 to 1.23; low quality evidence).Three studies investigated finasteride 1 mg compared to placebo. In the finasteride group 30/67 participants experienced improvement compared to 33/70 in the placebo group (RR 0.95, 95% CI 0.66 to 1.37; low quality evidence). This was consistent with the investigators' assessments (RR 0.77, 95% CI 0.31 to 1.90; low quality evidence). QoL was not assessed. Only one study addressed adverse events (137 participants) (RR 1.03, 95% CI 0.45 to 2.34; low quality evidence). In two studies (219 participants) there was no clinically meaningful difference in change of hair count, whilst one study (12 participants) favoured finasteride (low quality evidence).Two studies (141 participants) evaluated low-level laser comb therapy compared to a sham device. According to the participants, the low-level laser comb was not more effective than the sham device (RR 1.54, 95% CI 0.96 to 2.49; and RR 1.18, 95% CI 0.74 to 1.89; moderate quality evidence). However, there was a difference in favour of low-level laser comb for change from baseline in hair count (MD 17.40, 95% CI 9.74 to 25.06; and MD 17.60, 95% CI 11.97 to 23.23; low quality evidence). These studies did not assess QoL and did not report adverse events per treatment arm and only in a generic way (low quality evidence). Low-level laser therapy against sham comparisons in two separate studies also showed an increase in total hair count but with limited further data.Single studies addressed the other comparisons and provided limited evidence of either the efficacy or safety of these interventions, or were unlikely to be examined in future trials.
Authors' conclusions:
Although there was a predominance of included studies at unclear to high risk of bias, there was evidence to support the efficacy and safety of topical minoxidil in the treatment of FPHL (mainly moderate to low quality evidence). Furthermore, there was no difference in effect between the minoxidil 2% and 5% with the quality of evidence rated moderate to low for most outcomes. Finasteride was no more effective than placebo (low quality evidence). There were inconsistent results in the studies that evaluated laser devices (moderate to low quality evidence), but there was an improvement in total hair count measured from baseline.Further randomised controlled trials of other widely-used treatments, such as spironolactone, finasteride (different dosages), dutasteride, cyproterone acetate, and laser-based therapy are needed.
Follicular drug delivery is the prerequisite for an effective treatment of androgenetic alopecia or other reasons of premature hair loss.
The follicular penetration of caffeine, applied topically in a shampoo formulation for 2 min, was measured with highly sensitive surface ionization in combination with mass spectroscopy, a selective method for the detection of very small quantities of transcutaneously absorbed substances in the blood. An experimental protocol, developed to selectively block the follicular pathway within the test area, was used. Based on this principle, a clear distinction between interfollicular and follicular penetration of topically applied caffeine was feasible.
After 2 min, caffeine penetrated via the hair follicles and stratum corneum.
It was found that the penetration via hair follicles was faster and higher compared with the interfollicular route and that hair follicles are the only pathway for fast caffeine absorption during the first 20 min after application.
Although knowledge of normal scalp anatomy, the hair follicle, and the dynamics of hair cycling is substantial,1–3 the histopathology of male-pattern baldness (MPB), also called premature baldness or androgenetic alopecia, is uncertain. Textbook accounts are uninformative,4,5 and controversies are plentiful. Disputes exist about matters that seem quite simple, for example, whether the sebaceous glands are enlarged or shrunken. There are also opposing views on the fate of the arrector pili muscles. All agree that hair follicles become progressively smaller (miniaturized), but whether there is an actual loss of follicles is in contention. Two important publications on various cutaneous aspects of aging do not even include chapters on hair.6,7
Androgenetic alopecia (AGA) is the combined result of an androgen-dependent process and genetic transmission. These characteristics have mainly, if not exclusively, been demonstrated in men and perhaps improperly extended to women. When considering the androgen-dependent process, AGA must only be limited to the androgen receptor areas. In the scalp, these receptors have only been detected in the frontal and vertex areas but never in the temporal or the occipital areas. Male AGA exhibits these clinical features, whereas in women hair loss is rarely limited to this localization, even when large areas of hair loss often appear with age. It is now commonly accepted that male AGA is associated with an increase in 5 alpha reductase activity leading to an increase in local production of dihydrotestosterone. The mechanism by which the local dihydrotestosterone increase leads to hair follicle loss is not clearly demonstrated. Inhibition of cell proliferation in the dermal papilla and a vascular process based on the inhibition in local production of vascular endothelial growth factor (VEGF) have been proposed. The increase in 5 alpha reductase activity is genetic and depends on androgen receptor polymorphism, characterized by a decrease in the number of CAG sequences on the exon 1. Male AGA is associated with an insulin-resistant process and to a higher risk of polycystic ovary in the lineage. Therapeutically, this hormone-dependent process explains the well demonstrated efficacy of 5 alpha reductase inhibitors. In women, except in some rare cases, alopecia is diffuse and the mechanisms are different. Their origin is unknown, and probably ambiguous. Based on an association with Hashimoto's thyroiditis, an auto-immune origin could be suggested in some cases. Alopecia is unaffected by thyroid substitution. Pharmacological doses of oestrogens (pregnancy, contraception) have a beneficial effect on such alopecia, probably through different mechanisms: anti-androgen effect, increased VEGF, proliferative effect of dermal papilla cells. However, it is important to mention that the dermal papilla has an aromatase, particularly in the occipital area, the activity of which has not been assessed in female alopecia. In practice 5 alpha reductase inhibitors are ineffective in women. It is likely that the predominance observed in the frontal and vertex areas, occasionally in elderly women, is a result of the two combined disorders, the almost physiological androgen-dependent hair loss combined with diffuse loss. Pharmacological doses of oestrogens associated with anti-androgen progesterone-like agents are widely used with positive results, but not demonstrated by clinical trials.
This study was conducted to evaluate the effect of caffeine on the meiotic maturation of porcine oocytes. Oocyte-cumulus complexes were collected from slaughterhouse-derived ovaries and cultured for 24, 32 or 48 h in medium 199 supplemented with 10% fetal calf serum, 10 microg/ml FSH, 50 microg/ml sodium pyruvate and 50 microg/ml gentamicin in the presence or absence of 2.5 mM caffeine. Caffeine inhibited the meiotic resumption of pig oocytes effectively after 24 h of culture, and 95.5% of oocytes were arrested at the germinal vesicle (GV) stage (control 17.8%, p < 0.05). Prolonged culture with caffeine up to 32 h or 48 h, however, resulted in a significant decrease in the inhibitory effect (GV: 13.8% and 8.2%). The number of oocytes at metaphase II after 48 h of culture in the presence of caffeine was significantly lower than that in the control medium (65.3% vs 94.7%, p < 0.05). The withdrawal of caffeine after 24 h of culture resulted in the resumption of meiotic maturation, and the oocytes reached metaphase II after 48 h. However, the ability of caffeine-treated oocytes to develop to blastocysts after artificial activation was lower than that of the control (5.5% vs 9.1%, p < 0.05). Caffeine treatment significantly increased cAMP levels in the oocytes after 24 h of culture, while both Cdc2 kinase and MAP kinase activation were inhibited in the oocytes. These results suggest that caffeine, similarly to other purine derivatives, prolongs the meiotic arrest of porcine oocytes at the GV stage, perhaps by its action of increasing the cAMP level and by the suppression of Cdc2 kinase and MAP kinase activities in the oocytes.