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Comparing the effectiveness of local solution of minoxidil and caffeine 2.5% with local solution of minoxidil 2.5% in treatment of androgenetic alopecia
Abstract
Background and purpose: Androgentic alopecia (AGA) is physiological hair loss induced by androgens in genetically predisposed persons. Different medications have been suggested to treat AGA until now but there is no certain treatment. This study aimed to compare the effect of caffeine + minoxidil topical solution 2.5% and minoxidil topical solution 2.5% in AGA treatment. Materials and methods: In this double-blind randomized clinical trial study 60 patients were enrolled. The sampling method was simple classification and patients were divided to 2 equal groups. The first group received minoxidil topical solution 2.5% and the second group received caffeine + minoxidil topical solution 2.5%. Method of treatment was the same in both groups (one milliliter of solution was applied twice a day) and follow-up was by computation of hair numbers on alopecia area in scalp. Both groups were followed in 7 stages: at the beginning of study and the days 7, 30, 60, 90, 120, and 150. Results: Caffeine + minoxidil topical solution 2.5% was more effective than minoxidil topical solution 2.5%. There was a significant statistical difference between the groups. Conclusion: This study overtly showed that the effect of caffeine + minoxidil topical solution 2.5% to treat AGA was better than minoxidil topical solution 2.5%. We suggest more studies with greater sample size and longer priod of follow-up.
... Furthermore, caffeine can enhance hair shaft elongation, prolonging anagen duration and hair matrix keratinocyte proliferation. Caffeine inhibits the activity of the 5α-reductase enzyme and allows a renewed growth phase of hair [49]. Some studies described the benefits of the association between caffeine and minoxidil in comparison with monotherapy of minoxidil in the treatment of hair loss [49]. ...
... Caffeine inhibits the activity of the 5α-reductase enzyme and allows a renewed growth phase of hair [49]. Some studies described the benefits of the association between caffeine and minoxidil in comparison with monotherapy of minoxidil in the treatment of hair loss [49]. ...
Objective:
Coffee is one of the most consumed beverages worldwide, and its production and consumption generate large amounts of byproducts annually. Coffee byproducts and coffee beans are rich in bioactive compounds of great commercial value, including potential applications as active ingredients in skin care products and cosmetic formulations. In addition, there has been growing interest in the use of natural ingredients for cosmetic purposes. Considering the importance of coffee in the world economy, its chemical constituents with potential for cosmetic and dermatological application, and the importance of patents for innovation and technological development, the present study aimed to review recent patents involving coffee and coffee byproduct use in cosmetics.
Methods:
This review was carried out using Espacenet. The following inclusion criteria were established: patents that included the terms "coffee" and "skin" in the title, abstract and claims and belonged to the classification A61Q, which is related to the "specific use of cosmetics or similar toilet preparations" considering the International Patent Classification (IPC) or Cooperative Patent Classification (CPC).
Results:
Considering the 52 patents analyzed, the bean was the main way to obtain extracts (39), followed by green beans (7), silverskin (3), peel and pulp (1), pulp (1) and beans and leaves (1). The formulations are mainly intended for use in nonspecific areas of skin (29), eye areas (12), scalp hair (9) and lip skin (2) with claims of antiaging, moisturizers, sun protection, hair growth, anti-dandruff, etc. CONCLUSION: Coffee and its residues have high amounts of phenolic compounds, caffeine, fatty acids and other substances known to have important biological properties for the skin. Coffee and its byproducts are promising ingredients to be incorporated into topical formulations, ensuring skin health benefits and reducing the environmental impact.
... A topical solution containing both caffeine and 2.5% MXD was compared to 2.5% MXD alone in 60 patients with AGA. After 120 days of treatment, the combined solution was more effective than MXD alone, with 58.33% of patients satisfied versus 41.37% in the MXD cohort [23]. 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]. ...
... 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.
... In parallel, combined MXD 2.5% and caffeine was compared to MXD alone. The combination therapy achieved superior efficacy to MXD alone [24]. Similarly, 12 weeks of triple therapy with azelaic acid 1.5%, MXD 5%, and caffeine demonstrated superior efficacy in decreasing hair loss when compared to MXD 5%. ...
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.
... Additionally, two further studies have been conducted with topically applied caffeine in combination with conventional hair loss treatments [96,97]. Within a randomized, double-blind, controlled clinical trial, the topical solution consisting of 25 mg/mL caffeine with 25 mg/mL minoxidil was more effective for male and female patients suffering from AGA than the 25 mg/mL minoxidil alone in terms of patients' satisfaction (58.33% in combined treatment vs. 41.37% in minoxidil alone control group) after 150 days of treatment. ...
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.
... There was a significant statistical difference between the groups. 3 A study by Davis et al. examined the ability of a novel leaveon technology combination of caffeine, niacinamide, panthenol, dimethicone, and an acrylate polymer (CNPDA) to affect the diameter and behavior of individual terminal scalp hair fibers as a new approach to counteract decreasing fiber diameters. Their conclusion was that CNPDA significantly increased the diameter of individual, existing terminal scalp hair fibers by 2-5μm, which yields an increase in the cross-sectional area of approximately 10%. ...
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].
Alopecia or hair loss is a widespread issue that has significant effects on personal well-being for both genders nationally and internationally. In addition, alopecia causes extreme emotional stress and negatively impacts the psychological health and self-esteem of cancer patients suffering from chemotherapy-induced alopecia. Unfortunately, available synthetic medications are costly, invasive, or have extreme adverse effects. On the contrary, natural and herbal hair loss products are widely available in the local and international markets in variable pharmaceutical forms with different mechanisms of action, namely, androgen antagonists, nutritional supplements, vasodilators, and 5α-reductase inhibitors or dihydrotestosterone blockers. Thus, it is of great importance to encourage researchers to investigate these natural alternatives that can act as potent therapeutic agents having diverse mechanisms of action as well as limited side effects. Currently, natural remedies are considered a fast-rising pharmaceutical segment with demand from a wide range of consumers. In this study, we present a review of reported herbal remedies and herb combinations recommended for hair loss and their mode of action, along with an overview of available market products and formulations, their composition, and declared effects. In addition, a general outline of the different forms of alopecia, its causes, and recommended treatments are mentioned as well. This was all done with the aim of assisting further studies with developing standardized natural formulations for alopecia as many were found to lack standardization of their bioactive ingredients and efficiency confirmation.
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.
Caffeine -a methylxanthine derived from purine- is found in the various plants (coffee, tea, cola) all over the world and is widely used in cosmetics due to its ability to penetrate in skin barriers. In this paper, the mechanism of broad effects of caffeine on skin and hair is discussed. Commercial use of caffeine in the formulation of cosmetics (e.g. sunscreen products) can effectively reduce Ultraviolet (UV) irradiation side effects and devastating UV induced free radicals. It inhibits phosphodiesterase activity, increases the concentration of cyclic adenosine monophosphate (cAMP) and augments apoptosis in damaged keratinocytes of skin. Caffeine inhibits cell cycle and induces apoptosis by inhibition of ataxia-telangiectasia mutated and Rad3-related (ATR), cycle ATR-chk function. On the other hand, Caffeine is topically used in shampoo as an adjuvant for hair loss treatment. Increasing the cAMP concentration caused by caffeine reduces the tension in smooth muscle near the hair follicle and leads to easier delivery of nutrients through blood vessels. It also prevents negative effects of testosterone on hair follicles in men. Most of currently used hair products contain caffeine. Detailed mechanisms of other effects of caffeine in this field are also discussed. © 2016, Isfahan University of Medical Sciences(IUMS). All rights reserved.
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.
Caffeine is being increasingly used in cosmetics due to its high biological activity and ability to penetrate the skin barrier. This alkaloid is frequently used as a hydrophilic model substance in human and animal skin penetration as well as different synthetic membrane using Franz diffusion cell experiments. The commercially available topical formulations of caffeine normally contain 3% caffeine. As for a cosmetic purpose, caffeine is used as an active compound in anti-cellulite products because it prevents excessive accumulation of fat in cells. This alkaloid stimulates the degradation of fats during lipolysis through inhibition of the phosphodiesterase activity. Caffeine has potent antioxidant properties. It helps protect cells against the UV radiation and slows down the process of photoaging of the skin. Moreover, caffeine contained in cosmetics increases the microcirculation of blood in the skin and also stimulates the growth of hair through inhibition of the 5-alpha-reductase activity. Copyright (C) 2012 S. Karger AG, Basel
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.
The predominant form of 5alpha-reductase (5aR) in human scalp is 5aR1. None the less, clinical studies have shown that finasteride, a selective inhibitor of 5aR2, decreases scalp dihydrotestosterone and promotes hair growth in men with androgenetic alopecia. Immunolocalization studies were thus carried out to examine 5aR isozyme distribution within scalp and, in particular, to determine whether 5aR2 might be associated with hair follicles. 5aR2 was localized using both a rabbit polyclonal and a mouse monoclonal antibody. 5aR1 was detected with a mouse monoclonal antibody. The specificity of these reagents was demonstrated both by immunofluorescence and Western blot analyses of COS cells overexpressing human 5aR1 or 5aR2. When cryosections of scalp from men with androgenetic alopecia were stained with antibody against 5aR2, using immunoperoxidase avidin-biotin complex methodology, immunostaining was observed in the inner layer of the outer root sheath and, in more proximal regions of the follicle, in the inner root sheath. Staining was also prominent in the infundibular region of the follicle, with less intense staining extending throughout the granular layer of the epidermis. Some staining was also seen in sebaceous ducts. Similar results were obtained with both the polyclonal and monoclonal 5aR2 antibodies. In contrast, in scalp cryosections stained with antibody to 5aR1, no immunostaining was observed within hair follicles. Intense staining for the type 1 isozyme was, however, detected within sebaceous glands. Our immunolocalization data suggest that the results seen in clinical trials of men with male pattern hair loss treated with finasteride may be due, at least in part, to local inhibition of 5aR2 within the hair follicle.
Androgenetic alopecia (AGA), also known in women as female pattern hair loss, is caused by androgens in genetically susceptible women and men. The thinning begins between ages 12 and 40 years, the inheritance pattern is polygenic, and the incidence is the same as in men. In susceptible hair follicles, dihydrotestosterone binds to the androgen receptor, and the hormone-receptor complex activates the genes responsible for the gradual transformation of large terminal follicles to miniaturized follicles. Both young women and young men with AGA have higher levels of 5α reductase and androgen receptor in frontal hair follicles compared to occipital follicles. At the same time, young women have much higher levels of cytochrome p-450 aromatase in frontal follicles than men who have minimal aromatase, and women have even higher aromatase levels in occipital follicles. The diagnosis of AGA in women is supported by early age of onset, the pattern of increased thinning over the frontal/parietal scalp with greater density over the occipital scalp, retention of the frontal hairline, and the presence of miniaturized hairs. Most women with AGA have normal menses and pregnancies. Extensive hormonal testing is usually not needed unless symptoms and signs of androgen excess are present such as hirsutism, severe unresponsive cystic acne, virilization, or galactorrhea. Topical minoxidil solution is the only drug available for promoting hair growth in women with AGA. Efficacy has been shown in double-blind studies using hair counts and hair weight.