Biofactors. 2015 Nov 12; 41(6): 383–390.

Topical treatment with coenzyme Q10-containing formulas improves skin’s Q10 level and provides antioxidative effects

Anja Knott, Volker Achterberg, Christoph Smuda, Heiko Mielke, Gabi Sperling, Katja Dunckelmann, Alexandra Vogelsang, Andrea Krueger, Helge Schwengler, Mojgan Behtash, Sonja Kristof, Heike Diekmann, Tanya Eisenberg, Andreas Berroth, Janosch Hildebrand, Ralf Siegner, Marc Winnefeld, Frank Teuber, Sven Fey, Janne Moebius, Dana Retzer, Thorsten Burkhardt, Juliane Luettke, Thomas Blatt.

Beiersdorf AG, Research & Development, Hamburg, Germany.

 

Abstract

Ubiquinone (coenzyme Q10, Q10) represents an endogenously synthesized lipid-soluble antioxidant which is crucial for cellular energy production but is diminished with age and under the influence of external stress factors in human skin. Here, it is shown that topical Q10 treatment is beneficial with regard to effective Q10 replenishment, augmentation of cellular energy metabolism, and antioxidant effects. Application of Q10-containing formulas significantly increased the levels of this quinone on the skin surface. In the deeper layers of the epidermis the ubiquinone level was significantly augmented indicating effective supplementation. Concurrent elevation of ubiquinol levels suggested metabolic transformation of ubiquinone resulting from increased energy metabolism. Incubation of cultured human keratinocytes with Q10 concentrations equivalent to treated skin showed a significant augmentation of energy metabolism. Moreover, the results demonstrated that stressed skin benefits from the topical Q10 treatment by reduction of free radicals and an increase in antioxidant capacity.

PMID: 26648450, DOI 10.1002/biof.1239

Keywords: coenzyme Q10; energy metabolism; mitochondrial activity; antioxidant; topical Q10 treatment; skin; skin aging

 

Supplement: 

Coenzyme Q10 (Q10, CoQ10), also known as ubiquinone, is a fat-soluble substance (Fig. 1), that is ubiquitously present in the human body where it exhibits vitamin-like functions. Cells require this coenzyme not only to generate energy but also in its reduced form, ubiquinol, as a powerful antioxidant to help fight free radicals that can damage cells and DNA.

 

Fig. 1: Coenzyme Q10 powder

 

Coenzyme Q10 is present in every membrane of all cells in the body with a preferential accumulation in mitochondria, plasma membranes, Golgi vesicles and lysosomes (Gille & Nohl, 2000). It was originally shown to be an essential component of the mitochondrial respiratory chain, where it functions as an electron carrier from complex I and II to complex III (Bentinger, 2010; Mitchell, 1975). Since then it has been well established, that Q10 has many other important functions for example as a native constituent of the lysosomal electron transport chain, promoting proton translocation across the lysosomal membrane (Gille & Nohl, 2000) or as the only endogenously synthesized lipid soluble antioxidant exceeding both in amount and efficiency that of other antioxidants (Bentinger, 2007).

In skin Q10 is not only found in living cells, but also in the skin surface lipids, that are a mixture of sebum and lipids originating from keratinizing epidermal cells, mainly corneocytes. On this outermost level of the body – which is in permanent contact with external stress factors causing reactive oxygen species (ROS) – Q10 is apart from vitamin E, the only lipophilic antioxidant serving important functions in the defense against oxidative stress. Both were found to inhibit synergistically the UV induced depletion of squalene (Passi, 2002).

Thus, the presence of Q10 is widespread in skin, both within living cells and skin lipids. However, endogenous Q10 levels decline with increasing age (Hoppe, 1999) and due to external stress like UV-damage (Podda, 1998). This lack in Q10 may have impact on the mitochondrial activity of skin cells, but also on the effectiveness of antioxidant protection against ROS within the tissue and on the skin surface. Along these lines two important points of action arise in order to strengthen skin in its natural functions. First, maintenance of sufficient cellular energy levels to stop the decline of mitochondrial activity and, second, antioxidant protection against ROS originating from any source.

In this context, the objective of this study was to investigate whether human skin may benefit from a topical Q10 (ubiquinone) treatment with regards to the two aforementioned important points of action: increase in cellular energy metabolism as well as antioxidant effects.

In order to investigate total Q10 (ubiquinone plus ubiquinol) levels in human skin, suction blister epidermis material was used and Q10 concentrations were determined in samples from donors of different age (Fig. 2). As a result the age-dependent decline of Q10 in human epidermis was confirmed.

 

 

Fig. 2: Age-dependent decline of total Q10 levels in human epidermis. Total Q10 concentrations from young (20-25 years; n = 28) and aged (60-66 years; n = 28) volunteers were measured using suction blister epidermis obtained from untreated forearm skin. Data are depicted as mean ± SEM. Significant differences are marked with an asterisk (* for p ≤ 0.05).

 

Out of this reason, we set out to investigate whether the epidermal Q10 content can be improved by topical application. A two week treatment with Q10-containing formulas (formula 2 containing more than twice as much ubiquinone than formula 1) effectively delivers Q10 to the living layers of the epidermis (Fig. 3A) and replenishes the Q10 level.

 

 

Fig. 3: Total Q10 content as well as ubiquinone and ubiquinol content are increased within the epidermis after treatment with Q10-containing formulas. Following a 14-day treatment with Q10 containing formulas 1 and 2, total Q10 (A), ubiquinone (B), and ubiquinol (C) levels were assessed within the epidermis using suction blister material. Results are depicted as mean ± SEM (n = 73). Significant differences are marked with an asterisk (* for p ≤ 0.05).

 

In order to investigate the fate of topically applied Q10 within the epidermis, ubiquinone (Fig. 3B) and ubiquinol (Fig. 3C) levels were analyzed separately. Both formulas significantly increased epidermal ubiquinone level, whereas also the epidermal ubiquinol level was significantly elevated by formula 2 which indicates that the topically applied ubiquinone is not only able to enter the deeper layers of the epidermis but also may in part be reduced to the antioxidant form ubiquinol.

Thus, we asked the question whether an increase of ubiquinone content might stimulate the energy metabolism in skin cells. For this purpose an in vitro experiment with cultured human keratinocytes that were treated with ubiquinone was performed. The oxygen consumption rate (OCR) as a parameter for energy metabolism was determined by using the Seahorse technology (Ferrick et al. 2008) (Fig. 4).

 

 

Fig. 4: Energy metabolism of cultured human keratinocytes is increased after treatment with Q10. A) Schematic representation of Q10’s role in the mitochondrial respiratory chain, working as an electron carrier during energy production. B) Cultured human keratinocytes were supplemented with 18µM ubiquinone (representing the amount of Q10 which was determined in the tissue after topical treatment) and the oxygen consumption rate (OCR) was determined. Results are depicted as mean ± SEM (n = 6). Significant differences are marked with an asterisk (* for p ≤ 0.05).

 

Compared with the untreated control cells treatment with Q10 (ubiquinone) significantly increased the OCR, thus augmenting cell’s energy metabolism.

Furthermore, we were able to show by analysis of suction blister fluids that topical Q10 application reduces free radicals in stressed skin and increases its antioxidant capacity. The augmented post-treatment ubiquinol levels in the epidermis are likely to be responsible for this reduction in oxidative stress.

To summarize, this study shows beneficial effects of topical Q10 treatment in terms of penetrating into the epidermis, replenishing age- and/or UV-dependent Q10 loss, increasing skin cell’s energy metabolism, and improving antioxidant properties of stressed skin. Thus, people of all ages can benefit from regular treatment with Q10-containing formulas to cope more effectively with short-term insults inflicted by UV irradiation and stress to foster long-term anti-aging effects for their skin.

 

References:

M. Bentinger, K. Brismar, G. Dallner, The antioxidant role of coenzyme Q, Mitochondrion 7S (2007) 41-50.
M. Bentinger, M. Tekle, G. Dallner, Coenzyme Q – Biosynthesis and functions, Biochem. Biophys. Research Comm. 396 (2010) 74-79.
D.A. Ferrick, A. Neilson, C. Beeson, Advances in measuring cellular bioenergetics using extracellular flux, Drug Discovery Today 13 (2008) 268-274.
L. Gille, H. Nohl, The Existence of a Lysosomal Redox Chain and the Role of Ubiquinone, Arch. Biochem. Biophys. 375 (2000) 347-354.
U. Hoppe, J. Bergemann, W. Diembeck, J. Ennen, S. Gohla, I. Harris, J. Jacob, J. Kielholz, W. Mei, D. Pollet, D. Schachtschabel, G. Sauermann, V. Schreiner, F. Stäb, F. Steckel, Coenzyme Q10, a cutaneous antioxidant and energizer. Biofactors 9 (1999) 371–378.
P. Mitchell, Protonmotive redox mechanisms of cytochrome b-c1 complex in the respiratory chain: protonmotive ubiquinone cycle, FEBS Lett. 56 (1975) 1-6.
S. Passi, O. de Pità, P. Puddu, G.P. Littarru, Lipophilic Antioxidants in Human Sebum and Aging, Free Radical Research 36 (2002) 471-477.
M. Podda, M.G. Traber, C. Weber, L.J. Yan, L. Packer, UV-irradiation depletes antioxidants and causes oxidative damage in a model of human skin. Free Radic. Biol. Med. 24 (1998) 55–65.

 

Contact:

Anja Knott, Ph.D.

Beiersdorf AG

Unnastrasse 48

20245 Hamburg

Germany

E-mail: anja.knott@beiersdorf.com

 

Julia Weise, Ph.D.

Beiersdorf AG

Unnastrasse 48

20245 Hamburg

Germany

E-mail: julia.weise@beiersdorf.com

 

 

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