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ISSN: 2155-9554
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Research Article Open Access

The Evaluation of the Efficacy of Derivatives of Vitamin K

Agata Markiewicz1*, Bożena Tyszczuk2, Monika Pasikowska-Piwko2, Konrad Zieliński3, Anna rkiert-Polguj4 and Elżbieta Budzisz1
1Department of Cosmetic Raw Materials Chemistry, Faculty of Pharmacy, Medical University of Lodz, Lodz, Poland
2Dr Irena Eris Cosmetic Laboratories, Dr Irena Eris Centre for Science and Research, Warsaw, Poland
3Minisynthesis Department, Pharmaceutical Research Institute, Rydygiera 8, Warsaw, Poland
4Department of Cosmetology and Aesthetic Dermatology, Faculty of Pharmacy, Medical University of Lodz, Lodz, Poland
*Corresponding author: Agata Markiewicz, Department of Cosmetic Raw Materials Chemistry, Faculty of Pharmacy, Medical University of Lodz, Lodz, Poland, Tel:
607164008; E-mail: [email protected]
Received date: May 21, 2018; Accepted date: June 15, 2018; Published date: June 20, 2018
Copyright: ©2018 Markiewicz A, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Objectives: The aim of the study was to evaluate the safety and effectiveness of cosmetic products containing
two derivatives of vitamin K on skin with vascular problems.

Materials and methods: The study was conducted in two groups, 24 people, and the other included 22
participants, mean age 50. The participants applied creams twice a day for a period of 4 weeks. Creams were
applied on the right half of the face-concentration of 0.5% and 0.1%-on the left. The participants completed a
questionnaire and a measurement was performed using standardized equipment Multi Probe Adapter (MPA)
Courage-Khazaka and VISIA Canfield.

Results: Application creams with MQ and Epoxy MQ derivatives at a concentration of 0.1% and 0.5% had the
effect of reducing redness of the skin at a comparable level. All of formulations did not contribute to decrease
melanin level. The hydration was increased after application MQ (0.1% and 0.5%) adequately 14% and 13% in
about 60% participants. The elasticity was significantly improved in all groups.

Conclusion: Derivatives of vitamin K such as Epoxy MQ and MQ used in 0.1% and 0.5% give comparable
results reducing redness of the skin. The improvement of erythema was more significant with 0.1% concentration
(MQ and Epoxy MQ).

Keywords: Vascular skin; Erythema; Vitamin K; Cosmetic form is Phylloquinone and it can be found in green vegetables and
formulation; Teleangiectasia vegetable oil; vitamin K2 is found in animal products, whereas
Menadione has an artificial source. A lot of studies indicate that long-
Introduction chain menaquinones have a longer halftime, which makes them more
bioavailable [2]. Vitamin K is involved in a series of biochemical
Dermocosmetics are especially designed to treat facial skin transformations in the liver. Its most prominent function is the role of
problems of various etiology. Capillary skin problems more and more a cofactor for gamma-glutamyl carboxylation of certain glutamate
frequently affect middle-aged people. Such lesions are mostly situated (Gla) residues which are present in coagulation factors II, VII, IX, X.
on cheeks, nose and chin. Transient flushing is a predominantly Vitamin K antagonists contribute to suppressing carboxylation of
observed sign. Additionally, characteristic skin lesions such as coagulation factors and lessening blood coagulation. Extra-hepatic
teleangiectasias and permanent erythema may develop on the central Gla-proteins appear in osteocalcin (known as bone gamma-
facial area. The pathophysiology of these features may be associated carboxyglutamic acid-containing protein) and in the vascular wall (as
with impaired vasomotor system functions, responsible for matrix Gla-protein). The Gamma-glutamyl carboxylase enzyme is
constriction of blood vessels. The formation of characteristic skin activated by vitamin K; it initiates the coagulation cascade and leads to
lesions may be triggered by environmental and lifestyle factors such as formation of a blood clot. GGC is located in the liver, pancreas, spleen,
stress, sun exposure, frequent temperature changes, hot meals and kidney, thymus, fibroblasts and cancer cells of different origin.
alcohol consumption. Unfortunately, exact pathophysiology of Moreover, proteins containing Gla residues are involved in the
transient and persistent erythema still remains unknown. In regulation of coagulation action, have an impact on metabolism of
consequence, the presence of facial redness may impair the emotional bones and blood vessels and prevent calcification of blood vessel [3].
well-being of patients, embarrass them and decrease their self-esteem Vitamin K2 is engaged in bone formation by stimulating osteoclast
and self-awareness. Moreover, people with facial redness often tend to activity and carboxylation of osteocalcin [4]. High intake of vitamin K
withdraw from social contacts [1]. prevents from arterial calcification, coronary heart diseases and plays
Vitamin K is a fat-soluble vitamin and it occurs in 3 forms, i.e. an important role in reducing the risk of prostate cancer [5].
Vitamin K1 (Phylloquinone, Phytonadione), Vitamin K2 Only recently vitamin K in cosmetics used for treatment of vascular
(Menaquinone) and Vitamin K3 (Menadione). The most common skin. For a long time it was considered a vitamin K-dependent enzyme

J Clin Exp Dermatol Res, an open access journal Volume 9 • Issue 4 • 1000455
ISSN:2155-9554
Citation: Markiewicz A, Tyszczuk B, Piwko M, Zielinski K, Polguj AR, et al. (2018) The Evaluation of the Efficacy of Derivatives of Vitamin K. J
Clin Exp Dermatol Res 9: 455. doi:10.4172/2155-9570.1000455

Page 2 of 5

(gamma-glutamyl carboxylase), exclusively active in the liver. Hence, The Mexamater ® is based on the analysis of two physico-chemical
vitamin K was administered only orally. Due to the presence of this phenomena-absorption and reflection of light. The probe sends three
enzyme in the skin, the method of administration changed. Vitamin K, waves of the following lengths: λ=568 nm-green, λ=660 nm-red and
contained in cosmetics has an impact on Gamma-glutamyl λ=870 nm-infrared. The obtained result indicates the level of erythema
carboxylase, accelerates the blood coagulation process and makes and melanin [9].
dilated blood vessels less visible. Additionally, vitamin K strengthens
Cutometer® measures the elasticity (R2) and firmness (R0) of the
blood vessel walls and decreases their fragility [6].
skin. The device operation involves creating vacuum inside the device.
Capillary skin requires complex and holistic care. Appropriate facial The device has an in-built optical measuring system, consisting of the
skin care involves minimizing exposure to external and internal factors source and receptor of light, and the two prisms are located opposite
which contribute to the emergence of vascular changes. Active each other. Light covers the distance from the transmitter to the
ingredients contained in cosmetic formulations should strengthen receptor. Resistance of the skin, induced by the action of the vacuum,
blood vessels, make skin lesions less visible, have anti-inflammatory and the time needed to return to a resting state, is a measure of the
and anti-clotting properties. Vitamin K could be one of such elasticity of the skin. The measurements that we made allowed us to
ingredients. The aim of the study was to evaluate the safety and obtain the following values:
effectiveness of cosmetic products containing two derivatives of
• R0-is used to determine the firmness of the skin. This is the passive
vitamin K, encoded as MQ and Epoxy MQ in two concentrations on
behaviour of the skin, measured at the time of the maximum
skin with vascular problems.
amplitude.
• R2-determines skin elasticity gross-it is a measure of its overall
Materials and Methods flexibility. In other words, it regards resistance to deformation and
The study was conducted in two groups. The first one consisted of predisposition to return to its original state.
22 people (Test 2 and 2A of MQ derivate), and the other one included Five participants of test 2 and 2A and 3 participants of test 3 and 3A
24 people (Test 3 and 3A of epoxy MQ derivate). All the participants had a photographic documentation taken by VISIA®. The VISIA
had vascular lesions. The mean age of the people included in the test Complexion Analysis System allowed monitoring the progress of
was 49. Volunteers were selected in accordance with the guidelines of treatment with topical vitamin K. The photographic system VISIA®
the Helsinki Declaration. Consent for the study was given by the Ethics takes pictures of the left and right profiles, and the entire surface of the
Commission of the Medical University of Lodz (RNN/268/15/KE). face. By comparing images before and after the therapy, we can
Cosmetic formulations were tested in the following manner: a product perform a detailed analysis of the same area of the face and evaluate
containing 0.5% of vitamin K derivate was applied on the right half of the efficacy of the therapy. Besides, the results are compared to results
the volunteers’ faces, whereas on the left half of the face the volunteers of statistical data regarding a particular population, race, gender and
were applied a product containing 1% of vitamin K derivate. All the age. The data introduce results and the number of features present. The
participants used the creams twice a day for a period of 4 weeks. The amount of features only show the number of changes without
skin parameters were measured before, and after 4 weeks (D0 and D28 considering their size and intensity. The VISIA system generates a
respectively). In the present study, we used in vivo techniques series of photographs using standard, ultraviolet and cross polarized
(corneometer, mexametr, cutometer and VISIA®) to evaluate the lighting-RBX®. Canfield’s patented RBXTM (Red/Brown/X)
outcome of the tested cosmetic formulations on the skin tone, technology provides assessment of the amount of melanin and
hydration and elasticity. In addition, the participants filled in a survey hemoglobin content. The hemoglobin serves as a measure of the
in which they gave a subjective evaluation of the effect. During the amount of redness in the skin, including erythema, vascular lesions
study all the participants were provided with dermatological and telangiectasias [10].
consultations.
The inclusion criteria for testing the creams were the occurrence of Results
redness and dilated blood vessels on the face. The exclusion criteria
were viral infection, bacterial and fungal infections, pregnancy and Questionnaire results
breastfeeding, acute and chronic inflammation on the face, sun
exposure and use of cosmetics or other oral formulations which seal The results of the survey demonstrated that tested creams did not
blood vessels and contribute to skin lightening. An analysis of cause adverse reactions manifesting with redness, burning, itching,
effectiveness of cosmetics was carried out on the base of objective papules and pustules any other alarming changes that might indicate
measurements, made by Multi Probe Adapter (Courage-Khazaka skin sensitization. Preparations were very well tolerated by sensitive
Electronic GmbH, Cologne, Germany) and a subjective survey. All and vascular skin. All of the participants were also satisfied with the
measurements were taken in a measuring room with controlled use of the cosmetics, the vast majority of respondents expressed the
humidity (H=30%-50%) and temperature (T=19°C-21°C) [7]. desire to use them in the future.
Corneometer® CM 825, included in the MPA580 device, was used for Subjective assessment showed positive changes in reducing: redness,
measuring the degree of hydration of the stratum corneum. Thanks to the presence of dilated capillaries and feeling of tension and irritation
the device, the average capacitance of the dielectric was measured. The of the skin. Creams provided the feeling of skin softness and freshness.
probe measures the moisture at a depth of about 10-20 µm [8]. Over 50% of the respondents stated that the creams have not reduced
Mexameter® MX probe 18 is designed to perform a simultaneous hypersensitivity of the skin to external factors such as sudden
measurement of the level of melanin-dye responsible for skin temperature change, stress, alcohol and hot spices. 40% of the
pigmentation as well as hemoglobin, i.e.–pigment, responsible for the participants noticed dark circles and bags under the eyes became less
colour of blood. The latter blood component might cause skin redness. visible (Figure 1 and 2).

J Clin Exp Dermatol Res, an open access journal Volume 9 • Issue 4 • 1000455
ISSN:2155-9554
Citation: Markiewicz A, Tyszczuk B, Piwko M, Zielinski K, Polguj AR, et al. (2018) The Evaluation of the Efficacy of Derivatives of Vitamin K. J
Clin Exp Dermatol Res 9: 455. doi:10.4172/2155-9570.1000455

Page 3 of 5

level of melanin remained unchanged. Skin hydration increased only

in test 2 and 2a by 15% in 60% patients. Elasticity improved by 20% in
all groups, but the most significant improvement was noticed in Test 3
and 3a (Table 1). VISIA analysis indicated significant reduction of red
areas (Table 2 and Figure 3).

Figure 3: Patient before and after 4 weeks of application of cream

with MQ, on the left half of the face 0.1% (Test 2) and on the right
half of the face 0.5% (Test 2A), twice a day. Reduced amount of red
areas viewed from the right and left profiles. Cross-polarization
Figure 1: Subjective assessment of the efficiency of applied images in RBX®.
cosmetics with MQ in test 2 (0.1%) and 2A (0.5%) after 4 weeks.

Test 2A with Test 3 with Test 3A with

Parameters Test 2 with
0.5% MQ 0.1% Epoxy 0.5% Epoxy
of skin 0.1% MQ
after 4 MQ after 4 MQ after 4
condition after 4 weeks
weeks weeks weeks

decrease by decrease by decrease by decrease by

Skin tone
14% in 71% 14% in 63% 12% in 77% 15% in 73%
(erythema)
participants participants participants participants

Skin tone lack of lack of lack of lack of

(melanin) improvement improvement improvement improvement

increase by increase by
lack of lack of
Hydration 14% in 58% 13% in 67%
improvement improvement
participants participants

increase by increase by increase by increase by

Elasticity 24% in 71% 21% in 88% 26% in 68% 23% in 73%
participants participants participants participants

Figure 2: Subjective assessment of the efficiency of applied Table 1: Analysis of the skin condition after 28 days of treatment (Test
cosmetics with Epoxy MQ in Test 3 (0.1%) and 3A (0.5%) after 4 2, 2A, 3, 3A).
weeks.

Result of instrumental analysis of skin condition

Skin color measured by the Mexameter® MX18 showed amount of
erythema was reduced by nearly 15% in 75% patients in all tests. The

Parameters of skin Test 2 with 0.1% MQ , after Test 2A with 0.5% MQ, Test 3 with 0.1% Epoxy MQ Test 3A with 0.5% Epoxy
condition 4 weeks after 4 weeks after 4 weeks MQ after 4 weeks

decrease by 27% in 60% decrease by 17% in 60% decrease by 11% in 80%

VISIA-redness Red areas lack of improvement
participants participants participants

Table 2: Results of measurements using VISIA®.

A comparative analysis carried out by means of VISIA® showed a

more significant reduction in the number of red areas on the left facial
profile. A study of the effectiveness of cosmetics with different
derivatives of vitamin K revealed that creams containing a lower
concentration of active substance made the therapy more effective
(Table 3 and Figure 4).

J Clin Exp Dermatol Res, an open access journal Volume 9 • Issue 4 • 1000455
ISSN:2155-9554
Citation: Markiewicz A, Tyszczuk B, Piwko M, Zielinski K, Polguj AR, et al. (2018) The Evaluation of the Efficacy of Derivatives of Vitamin K. J
Clin Exp Dermatol Res 9: 455. doi:10.4172/2155-9570.1000455

Page 4 of 5

substance reduces the risk of side effects, such as irritation, rash,

itching, burning and hyperpigmentation. Derivatives of vitamin K
(MQ and Epoxy MQ) were examined in creams in concentration 0.1%
and 0.5%. An in vivo analysis confirmed that the derivatives effectively
reduce erythema and additionally, improve hydration and elasticity of
the skin.
Anti-redness treatment has a significant impact on capillary skin.
One of the most common ways to reduce facial redness is using Intense
pulsed light Therapy (IPL). A study by Hassan el at. evaluated the
Figure 4: Patient before and after 4 weeks of application of cream
efficacy of the IPL treatment. Measurement performed after four IPL
with Epoxy MQ twice a day. Reduced amount of red areas viewed
treatment sessions revealed substantial reduction of erythema [12].
from the right and left profiles. Cross-polarization images in RBX®.
The efficacy of the PDL therapy in reducing erythema and
strengthening blood vessel was analyzed by Kim et al. [13]. Beauty
treatments are alternative methods of reducing vascular lesions.
Test 2 and 2A-MQ derivatives
Neuhause et al. compared the efficacy and safety of IPL and PDL
Amount of red Amount of red treatments in rosacea. Both treatments contributed to a significant
Disparity after 4
Location areas before areas after 4
weeks
improvement, but the difference between the treatments was
application weeks insignificant [14].
Left profile High price of beauty procedures, contradictions and frequent
191 95 96
(0.1%-test 2) occurrence of side effect are limiting factors to the light therapy. In
response to great demand, cosmetic industry looks for innovative
Right profile
(0.5%-test 2a)
174 94 80 methods which would reduce facial skin redness. Application of
products with vitamin K proved to be alternative methods to reduce
redness, skin color and improve elasticity. A randomized study by
Table 3: Results of measurements using VISIA® of patient shown on Hemmati el al. confirmed that vitamin K1 strengthens blood vessels,
Figure 3 tested 0.1% (test2) and 0.5% (test 2A). increases an amount of fibroblast cells, collagen fibers, improves skin
tone and reduces redness [15]. Cream containing 1% phytonadione
Test 3 and 3A-derivatives MQ and 0.15% retinol was tested by Melvin et al. Photographs show a
significant decrease in the amount of periorbital dark circles [16].
Amount of Amount of
Location features before features after 4
Disparity after Ahmadraji F. et al. tested 1 eye counter pad with 1% vitamin K and
4 weeks
of application weeks caffeine. They noted that the amount of dark circles and depth of
wrinkles decreased and skin elasticity improved [17].
Left profile (0.1%-test
316 204 112
2) A study conducted by Shah et al. compare the efficacy of cream with
vitamin K compared with pre-treatment or post-treatment pulsed dye
Right profile (0.5%-
test 2a)
251 204 47 laser therapy. The post-treatment laser therapy significantly reduces
bruising [18]. Derivatives of vitamin K have comprehensive
application in medial and cosmetic field. Lou et al. examined the safety
Table 4: Results of measurements using VISIA® patient shown on
and efficacy of vitamin K creams in shortening the duration of laser-
Figure 4 tested 0.1% (Test 3) and 0.5% (Test 3A).
induced purpura. Cream containing 1% vitamin K and 0.3% retinol
contribute to hasten the occurrence of laser-induced purpura [19].
Discussion
The effectiveness of active substance is associated with a selection of
Facial skin redness is a common aesthetic problem. Vascular skin is appropriate cosmetic formulation. Campani el at. tested vitamin K in
an equally frequent and embarrassing condition, especially for women, different cosmetic formulation. The study compare effectiveness
and is associated with age. The pathogenesis of vascular skin might be liposome-base formulation for VK1 before or after being nebulized
related to genetic, hormonal and environmental factors. Moreover, with a fatty ointment with VK1. The results perform increase enhanced
alcohol, stress, eating spicy meals, drinking hot drinks and excessive VK1 accumulation in epidermis and dermis when compared with a
sun exposure predispose to occurrence of skin lesions [11]. marketed VK1-containing fatty ointment. It suggested that the newly
The main objective of the study was to measure efficacy and safety developed formulation can be considered a valid alternative to fatty
of cosmetic products, containing derivatives of vitamin K, on capillary ointments [20]. A randomized study by Lopes et al. demonstrated
skin condition. In order to verify subjective satisfaction with differences between accumulation and transdermal penetration of
application of cosmetics with vitamin K, the authors conducted a vitamin K, containing three diverse lipid formulations. Numerous
survey. Cosmetic formulation had been created to improve the scientific studies have shown that the effectiveness of active ingredients
condition of blood vessels and decrease redness. The authors analyzed is dependent on the selection of appropriate penetration promoters,
different biologically active derivatives of vitamin K, used in various which facilitate intercellular transport [21].
concentrations and compared the effectiveness of their action. The Many active substances are also used in cosmetics for vascular skin.
total quantity of active substance was unusually low in contrast to the Khan et al. tested derivatives of vitamin C present in many cosmetic
number of cosmetic products, currently available on the market. formulations. The amount of melanin and erythema was decreased
Undoubtedly, an application of a lower concentration of active [22]. Serum tested by Dupton et al. consisted of active substances, such

J Clin Exp Dermatol Res, an open access journal Volume 9 • Issue 4 • 1000455
ISSN:2155-9554
Citation: Markiewicz A, Tyszczuk B, Piwko M, Zielinski K, Polguj AR, et al. (2018) The Evaluation of the Efficacy of Derivatives of Vitamin K. J
Clin Exp Dermatol Res 9: 455. doi:10.4172/2155-9570.1000455

Page 5 of 5

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J Clin Exp Dermatol Res, an open access journal Volume 9 • Issue 4 • 1000455
ISSN:2155-9554