The Comparison of the Effects of Caffeine Topical 0.25% and 0.5%

as Anti-wrinkle Therapy

Susanti Rosmala Dewi, Aris Cahyono, Anggana Rafika P., and Prasetyadi Mawardi

Department of Dermatovenereology Medical Faculty of Sebelas Maret University, Dr. Moewardi General Hospital

Surakarta

Keywords: aging, elasticity, caffeine, TEWL

Abstract: This 4-weeks, double-blind, randomized, controlled clinical study was conducted to compare the effects of

topical caffeine 0.25% with 0.5% on barrier function and elasticity in the skin. A total of 41 healthy subjects

consisted of male and female aged 20-60 y.o. The subjects were grouped into two. Each group received a

topical caffeine with different concentrations of 0.25% and 0.5%. Hydroxyethylcellulose (HEC) gel as the

placebo has 97.5% water content. Physical stability test was conducted at the preparation. The treatment was

performed on the forehead and periorbital by applying a topical caffeine 0.25% on one forehead and

periorbital and 0.5% on the others. Application of gels was performed 2 times daily for 4 weeks. Measurement

of Transepidermal Water Loss (TEWL) using Tewameter® TM300 and elasticity using Elastometer® EM25

were performed before and after treatment. Clinical evaluations for efficacy were made at baseline and after

two and 4 weeks of gel use. The measurements results were analyzed using one-way Annova. Overall, the

results of the study showed that topical caffeine applications can improve skin barrier function and increase

the elasticity the skin especially as anti wrinkle.

1 INTRODUCTION

The process of aging or aging is a natural process and

will affect every individual. Aging is a gradual

process of organ decadence and its function

associated with aging after undergoing a maturation

process characterized by decreased ability, gradual

deterioration of organs and functions that eventually

will experience the tendency of death (Saghrani &

Baumann, 2002). The aging process begins when the

growth ends, where the process is characterized by

gradual negative effects of age in the organ system,

decreased organ function, degeneration and changes

in the structure of proteins and enzymes. The main

features are organ and tissue dysfunction and

decreased ability or total loss of adaptation to

environmental changes. There are many factors that

interact in this aging process, whether social,

economic, diseases, nutrition, hereditary, lifestyle

and others (Brandner et al., 2008).

There are two main processes that trigger aging of

the skin or skin aging. They are intrinsic and extrinsic

factors. Stochastic processes implicate random cell

damage as a result of mutations during the metabolic

process due to free radical production.

While extrinsic aging is caused by environmental

factors such as exposure to sunlight, air pollution,

smoking, alcohol abuse and poor nutrition. Intrinsic

aging refers to a genetic and time-dependent

background. Various expressions on intrinsic aging

include smoothing and thinning of the skin that

exacerbate the appearance of expression lines. In

aging skin is extrinsically characterized by

photodamage such as wrinkles, pigmented lesions,

hypopigmented patches and actinic keratosis

(Zegarska et al., 2010).

Caffeine is one of the alkaloids which can be

found in coffee, tea and some soft drinks. Caffeine

which has the name of chemical compound 1,3,7-

trimethylxanthine has been widely used in making

various kinds of cosmetic products (Herman &

Herman, 2013). Topical caffeine has been produced

in the form of creams and lotions since it is known to

have many effects on the skin as it can slow the aging

process due to ultraviolet light, absorb ultraviolet

radiation, prevent skin cancer, an active component in

anti-cellulite preparations, potent antioxidants,

increase blood microcirculation in skin and also

stimulates the growth of hair through inhibition of the

5-α-reductase activity (Fischer et al., 2008;

Kawasumi et al., 2011 Kim et al., 2002; Krutmann &

The Comparison of the Effects of Caffeine Topical 0.25 .

DOI: 10.5220/0008152001130117

In Proceedings of the 23rd Regional Conference of Dermatology (RCD 2018), pages 113-117

ISBN: 978-989-758-494-7

113

Gilchrest, 2014; Salminen & Kaarniranta, 2010). The

use of caffeine in cosmetic products with

concentrations up to 3% is still considered safe, not

toxic, and easily absorbed into human skin (Brandner

et al., 2006). Caffeine’s ability to augment

elimination of UV-damaged cells via apoptosis may

be relevant for its protective effects on UV-induced

skin tumor development (Kawasumi et al., 2011).

This study is expected to show the effects of

caffeine in inhibiting the effects of ultraviolet

radiation on the skin by measuring the elasticity of the

skin. The mechanism of action of caffeine in the

cosmetic field is not fully known, thus it needs a lot

of studies to prove whether caffeine is proven to

improve skin appearance. The ability to penetrate

caffeine through the skin barrier is a basic principle

that must be known before (Kim et al., 2002). The

objective of this study was to determine the efficacy

of topical caffeine with concentrations of 0.25% and

0.5% to skin elasticity so that it can be as anti-wrinkle

therapy.

2 METHODS

An analytical observational, randomized control

study with clinical test approach, before after design

in dermatovenereology outpatient clinic Dr.

Moewardi general hospital Surakarta, from

November to December 2017. A total of 41 subjects

were randomized into 2 groups. The inclusion criteria

were age 20-60 y.o, no allergic reaction, no skin

lesions or suffering from certain skin diseases, did not

have chronic metabolic disease and were willing to

follow the study by signing informed consent. Each

group received topical caffeine with different

concentrations. The concentrations of caffeine gel

were 0.25% and 0.5%. Caffeine gel applied on the

forehead and periorbital region 2 times a day for 4

weeks and measurements was done every 2 weeks.

The active ingredient of caffeine from anhydrous

caffeine crystalline powder with 100% content and no

water content. The crystalline powder is dissolved

into a hydroxyl cellulose (HES) solvent with a

moisture content of 97.5%. Preparation of HES gel by

mixing 2.5 mg of HES powder into 1 liter of water

(H2O), then stand for 4-5 hours, Topical caffeine is

made by adding anhydrous caffeine powder

according to the concentration required in HES gel.

The process produces topical caffeinated caffeine

with a concentration of 0.25%, and 0.5%. Physical

stability tests were performed on the material before

being applied to the study subjects.

The TEWL measurement using Tewameter®

TM300 (Courage & Khazaka electronic GmbH

Cologne Germany) was conducted before and after

treatment. Measurements were performed in a room

with a temperature of 23 - 27

C and humidity of 56 -

62%. The acclimation process is done for 15 minutes.

The measurement area is cleaned with water and

dried with a tissue, then divided into 3 areas vertically

and each area is measured for 30 seconds. The value

recorded was the average value of the three

measurements.

Elasticity measurement using Elastometer®

EM25 (Courage & Khazaka electronic GmbH

Cologne Germany) was performed before and after

treatment. Prior to measurement, the area is cleaned

with water and dried with a tissue and then the probe

was vertically mounted and pressed slightly until a

sign sounds along with the appearance of the result

value on the monitor. The measurements were made

4 times at different locations and then recorded the

mean value.

The data were processed and analyzed using a

computerized statistical program using the One-Way

Annova test.

3 RESULTS

The demographic data in our study showed that the

study subjects characteristics of each group based on

sex and age had the same ratio of 50%. (Figure 1)

After caffeine gel preparation with concentrations of

0.25 and 0.5%, TEWL measurement results in all

groups showed a decrease in TEWL. The TEWL

measurement in forehead showed that after

application 0.25% caffeine gel in the 1

visit 33.60 g

hm-2 to 27.05 g hm-2 and the last visit become 33.60

g hm-2 with p-value 0.492 and after 0.5% caffeine gel

from 34.9 g hm-2 to 27.10 g hm-2 and 4

week

become 29.50 g hm-2 (p-value 0.351). (Figure 2A).

While, the 0.25% caffeine group showed a decrease

of TEWL at the crow’s feet of 19.77± 10.72 (1

visit)

to 15.30 ± 6.80 in 2

week and become 17.34 ± 7.04

g hm-2 (4

week) while the 0.05% caffeine group

decreased TEWL which 1

visit was 16.76 ±8.43 g

hm-2 to 13.62±6.96 (2

week) and 12.73 ± 4.69 g

hm-2 (3

visit) with p-value p=0.16 and 0.25 (Figure

2B). In the 0.25% caffeine group showed an increase

in elasticity forehead from 64.24 ± 9.64% to 2

visit

become 68.82±9.60% and last visited become 69.09

± 13.36% with p-value 0.301 and 0.5% caffeine group

showed an elasticity increase from 61.35 ± 8.31% to

visit 67.32±6.45 and 3

visit become 69.54 ±

13.36% with p value 0.024 (significant) (Figure 3.A).

114

Crow’s feet elasticity in 0.25% caffeine group

resulted an elasticity increase 62.17±14.7% at 1

visit

to 66.98±13.2 % and last visit become 64.22±20.76%

with p value =0.656. On the other hand, 0.5% caffeine

group showed elasticity at 1

visited 60.85+12% to

67+11.44% and the 3

visit become 68+17.22% (p

value= 0.165) (Figure 3.B).

Figure.1 demographic data of research subjects by sex and age have the same distribution

Figure 2. A. Results Measurement of TEWL between caffeine 0.25% and 0.5% on forehead. B. Results measurement of

TEWL on crow’s feet.

Figure 3. A. Results Measurement of elasticity between caffeine 0.25% and 0.5% on forehead. B. Results measurement of

elasticity on crow’s feet.

34.9

27.1

29.5

33.6

27.05

30.85

0weeks 2ndweek 4thweek

TEWLForehead

caffeine0.5% caffeine0.25%

16.75

13.63

12.73

19.76

15.31

17.35

0week 2ndweek 4thweek

TEWLCrow'sfeet

caffeine0.5% caffeine0.25%

A B

10 10 10 10

men women <35th >35th

sex age

sexmen

sexwomen

age<35th

age>35th

61.35

67.33

69.54

64.24

68.83

69.09

0weeks 2ndweek 4thweek

ElasticityForehead

caffeine0.5% caffeine0.25%

60.85

62.17

66.98

64.22

0weeks 2ndweek 4thweek

Elasticity Crow'sfeet

caffeine0.5% caffeine0.25%

The Comparison of the Effects of Caffeine Topical 0.25

115

4 DISCUSSION

Aging skin is important because it has a social impact.

The skin is a real organ model that represents an aging

process. Biological clocks on both skin and internal

organs on the same path cause irreversible

degeneration processes (Krutmann & Gilchrest,

2014). The aging process begins at the end of growth,

which is marked by the gradual negative effect of age

in the organ system, decreased organ function,

degeneration and changes in the structure of proteins

and enzymes. The main features are organ and tissue

dysfunction and decreased ability or total loss of

adaptation to environmental changes. There are many

factors that interact in this aging process, whether

social, economic, diseases, nutrition, hereditary,

lifestyle, and others (Salminen & Kaarniranta, 2010).

Currently caffeine is known to be effective for aging

skin care, especially related to cardiovascular disease

and cognitive function improvement (Takahashi &

Ishigami, 2017).

Coffee and caffeine have been widely used in

cosmetic production lately. The use of caffeine in

cosmetic products with concentrations of up to 3% is

still considered safe, not toxic, and easily absorbed

into human skin. Caffeine topically proves safe and

does not damage liver cells. In the Gajewska et al.

Study, there was no caffeine effect on liver cell

survival after peroral and transdermal uptake (up to

5.33mg / kg BW) (Gajewska et al., 2015).

Active compounds in cosmetic ingredients should

have the ability affecting cell metabolism and other

processes that occur in the skin. It largely depends on

the capacity of the molecule to penetrate the skin

barrier. Caffeine in the form of hydrophilic

preparations is often used in studies of caffeine

penetration in the skin (Saghrani & Baumann, 2002).

The use of preparations in the form of

microemulsions accompanied by higher water

concentrations may also increase the absorption of

caffeine (Ma et al., 2015). In this study we used HEC

in the form of gel and more moisture content high

(97.5%) than previous study (87.5%) (Brandner et al.,

2006). This study found a decrease in TEWL in the

use of caffeine 0.5% compared to 0.25% caffeine.

Several studies have suggested that topical caffeine

effects will improve the function of epidermal barrier,

as indicated by a decrease in TEWL starting in the

second week (Brandner et al., 2006).

The role of free radicals is known in the

replicative senescens phase, intrinsic and extrinsic

aging shown in various biological processes. The role

of topical caffeine improves the function of epidermal

cellular so as to also play an active role in the aging

process (Kochanek et al., 2000). In Magdalena et al

study, there is a decrease in the elastin index,

indicating that in aging with various wrinkle

formations, caffeine decreases collagen synthesis in

human fibroblast cultures (Herman & Herman, 2013).

Fibroelastic skin can be influenced by many things,

such as sun exposure, fat tissue enlargement,

decreased circulatory system and lymphatics. The

effect of caffeine on this is as lipolytic (Herman &

Herman, 2013). By inhibiting phosphodiesterase,

there will be an increase in cAMP which stimulates

the degradation of triglycerides into free fatty acids

by triglyceride lipase, thus inhibiting fat

accumulation (Vogelgesang et al.,2011). In addition,

caffeine also increases catecholamines in adipose

tissue that stimulate peripheral lipolysis by acting on

adrenaline-sensitive lipases (Bertin et al., 2001). In

this study, topical caffeine in all groups had a

decrease effect of TEWL and increased elasticity on

the skin especially in the 0.5% caffeine group during

the second week.

5 CONCLUSIONS

Our findings proved that topical caffeine

administration can improve skin barrier function by

decreasing TEWL and increasing skin elasticity

index. Further research is needed to prove the efficacy

of topical caffeine in wrinkle therapy, using larger

samples.

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