Learn how Stratum Corneum lipids affect skin health and possible treatments against the depletion of these lipids.
The skin is the largest organ of the human body whose main function is to protect it against the loss of physiological components and against harmful environmental conditions. It is divided in three layers: epidermis, dermis and hypodermis.
The epidermis, the most superficial layer of the skin, is subdivided into four other layers: stratum corneum, stratum granulosum, stratum spinosum and stratum basale. The barrier function mainly occurs in the outermost layer of the epidermis, the stratum corneum.
This stratum corneum is composed by cells called corneocytes that are embedded in a lipid matrix existing in the form of lipid bilayers. Lipid bilayers are the only way through the stratum corneum and are responsible for the formation and maintenance of the skin barrier function. Therefore, any depletion or disturbance in the lipids that make up the stratum corneum can impair its barrier function.
Similarly, some diseases are associated with the depletion of these lipids. Consequently, the replacement of absent lipids can be exploited as treatment of affected skin.
The lipid layers are composed of ceramides, free fatty acids and cholesterol specifically organized in the lipid matrix at concentrations of 40-50, 20-33 and 7-13%, respectively. However, these concentrations vary according to sex, age, individual’s condition and seasons.
In addition, there are other external and internal factors that can modify the organization and composition of lipids in the stratum corneum. Studies have shown that exposure to some chemicals used in cleaning products and sanitizers, environmental pollutants, pharmacological ingredients and some physical adversity can affect the stratum corneum.
It has been proven that the application of acetone and ethanol to the skin can cause disruption in the skin barrier due to the removal of part of the lipids from the stratum corneum. The same happen with the application of a 5% solution of sodium lauryl sulphate that has also been shown to affect intercellular lipids such as cholesterol, free fatty acids and sphingolipids.
The level of the skin barrier disturbance depends on the nature of the chemicals and the level of exposure to them. Internal factors such as inappropriate diet, ageing and high levels of stress can also alter the levels of lipids in the matrix.
Depletion or disturbance in the lipids of the stratum corneum is known to be the main cause of dryness and rupture of the skin. As a result, it loses water, becomes dry and cracked. The cracks allow the entry of allergens, toxins and microorganisms that can cause inflammation and irritation. The inflammation may cause even more disturbances in the stratum lipids, forming a vicious cycle.
This situation can result in other conditions such as severe dryness of the skin and itching, and its consequences can lead to secondary infections caused by viruses, bacteria or fungi. Other diseases may be associated with depletion of stratum corneum lipids, such as eczema, psoriasis, atopic dermatitis, ichthyosis, xerosis, among others.
Under normal circumstances, if the skin barrier function is compromised, a repair sequence is rapidly initiated by increasing the synthesis of all lipids in the stratum corneum in order to restore homeostasis. However, under abnormal conditions, the rate of synthesis of these lipids is impaired and a rapid reestablishment of depleted lipids may not be possible, impairing the barrier function of the skin. Studies show how the function can be restored and the main approaches include restoring lost lipids or administering agents that facilitate the production of these lipids.
Several studies have demonstrated that the application of lipid mixtures containing ceramides, cholesterol and free fatty acids in an adequate proportion facilitates the process of skin barrier recovery in skins that suffered extraction from lipids by acetone, petroleum ether or some detergents. Even so, the application of these lipids was not effective in skins treated with some detergent agents such as sodium lauryl sulphate. The negative result was attributed to the protein denaturation effect of the surfactants used and their penetration into deeper layers of skin.
Some researchers suggest that for lipid treatment to be effective, these lipids must cross the stratum corneum and reach the interface between the stratum corneum and the stratum granulosum (a layer just below the stratum corneum). Therefore, efficient diffusion between these layers is an important variable for treatment.
Besides to the stratum corneum lipids, attempts to administer their analogues were made. At a university in the Czech Republic, researchers found that a cream containing ceramide analogue (N-tetracosanoyl- (L) -serine tetradecyl ester) showed an excellent result in repairing the cutaneous barrier in skins that underwent lipid extraction in vivo tests and ex vivo. Unlike natural ceramides, the analogue was synthesized by a low cost, with two-step method that offers the advantage of minimizing enzymatic inactivation.
Ceramides are synthesized and transformed into keratinocyte differentiation process. Synthesis involves precursors of ceramides and various enzymes such as serine palmitoyltransferase. Components that may increase the activity of these enzymes increase the level of ceramides in the stratum corneum. On the other hand, ceramides can be degraded by enzymes called ceramidases, so components that inhibit these degradative enzymes may produce an increase in the concentration of ceramides in the stratum corneum. Some of these components are:
Nicotinamide and his derivatives have been shown to increase the synthesis of ceramides, glucosylceramides, sphingomyelin, free fatty acids and cholesterol. This result was attributed by a positive regulation of the serine palmitoyltransferase enzyme. Ursolic acid has also been classified as an agent capable of increasing the production of ceramide in the skin.
An American study showed that lactic acid significantly increased the level of ceramides in the stratum corneum that was associated with the transformation by the metabolism of lactic acid in Acetyl CoA, which is a source of carbon for the synthesis of lipids. However, another study has proved that the application of eucalyptus extract has improved the skin barrier, which is associated with macrocarpal active A. Macrocarpal A is one of the main active ingredients of the eucalyptus extract. According to the authors, this active increases the amount of ceramides by stimulating the expression of enzymes that stimulate their synthesis, for example serine palmitoyltransferase, glycosyltransferase, sphingomyelinase, and glucocerebrosidase.
Sodium dl-α-tocopherol-6-O-phosphate, a stable derivative against oxidation of vitamin E is another component that increases ceramide levels, as it induces the differentiation of keratinocytes by increasing the entry of calcium into their cells and stimulates expression of the genes that perform the synthesis of ceramides. Besides having antioxidant and anti-inflammatory effect that reduces lipid degradation in the stratum corneum.
The skin has great importance to protect the human body and the barrier function is mainly due to the stratum corneum, more specifically to his composition and organization of the lipid matrix. Therefore, depletion of the stratum corneum lipids, which can occur due to a variety of reasons, such as the use of certain chemicals, alters their functioning and can lead to different diseases and infections. Studies show that the replacement of these lipids directly or increasing their synthesis indirectly, are effective treatments.
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The aim of this article is to contribute to the elevation of the technical level of professionals in the area. For any orientation always look for a qualified professional like a dermatologist or pharmacist.
References:
Sahle F.F; et al. [Skin Diseases Associated with the Depletion of Stratum Corneum Lipids and Stratum Corneum Lipid Substitution Therapy]. Skin Pharmacol Physiol 2015;28:42-55. Available:
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