Moisturizers and skin barrier repair

There are dozens of skin care products that claim to repair the barrier that do not have the science or ingredient content to back them up.

Does a skin barrier repair moisturizer really repair?

First, let’s briefly review what the skin barrier is. The stratum corneum (SC), the most superficial layer of the epidermis, averages approximately 15-cell layers in thickness.^1,2 The keratinocytes reside there in a pattern resembling a brick wall. The “mortar” is composed of the lipid contents extruded from the lamellar granules. This protective barrier functions to prevent transepidermal water loss (TEWL) and entry of allergens, irritants, and pathogens into deeper layers of the skin. This column will focus briefly on the structure and function of the skin barrier and the barrier repair technologies that use synthetic lipids such as myristoyl-palmitoyl and myristyl/palmityl-oxo-stearamide/arachamide MEA.

Dr. Leslie S. Baumann

Structure of the skin barrier

SC keratinocytes are surrounded by lamella made from lipid bilayers. The lipids have hydrophilic heads and hydrophobic tails; the bilayer arises when the hydrophobic tails face the center and the hydrophilic heads face out of the bilayer. This formation yields a disc-shaped hydrophobic lamellar center. There are actually several of these lamellar layers between keratinocytes.

^{Dr. Leslie S. Baumann}

The pink “bricks” represent keratinocytes. The blue heads are hydrophilic, and the yellow tails are hydrophobic. This image shows three bilayer lamellae situated between keratinocytes. These bilayers completely surround keratinocytes when the skin barrier

The naturally occurring primary lipids of the bilayer lamellae are made up of an equal ratio of ceramides, cholesterol, and free fatty acid. Arranged in a 1:1:1 ratio, they fit together like pieces of a puzzle to achieve skin barrier homeostasis. The shape and size of these puzzle pieces is critical. An incorrect shape results in a hole in the skin barrier resulting in dehydration, inflammation, and sensitivity.

Ceramides

Ceramides are a complex family of lipids (sphingolipids – a sphingoid base and a fatty acid) involved in cell, as well as barrier, homeostasis and water-holding capacity. In fact, they are known to play a crucial role in cell proliferation, differentiation, and apoptosis.³ There are at least 16 types of naturally occurring ceramides. For years, they have been included in barrier repair moisturizers. They are difficult to work with in moisturizers for several reasons:

• Ceramides are abundant in brain tissue and the ceramides used in moisturizers in the past were derived from bovine brain tissue. Prior to the emergence of bovine spongiform encephalopathy (mad cow disease), many ceramides in skin-care products were animal derived, which made them expensive and undesirable.
• Ceramides in skin care that are made from plant sources are referred to as phyto-derived ceramides. Although they share a similar structure with ceramides that occur in human skin, there are differences in chain length, hydroxylation pattern, and the degree of unsaturation that lead to structural diversity.⁴ The shape of ceramides is critical for a strong skin barrier because the lipids in the skin barrier must fit together like puzzle pieces to form a water-tight barrier. Natural sources of ceramides include rice, wheat, potato, konjac, and maize. Standardization of ceramide shape and structure makes using phyto-derived ceramides in skin care products challenging.
• Ceramides, because of their waxy consistency, require heat during the mixing process of skin care product manufacturing. This heat can make other ingredients inactive in the skin care formulation. (Ceramides are typically added early in the formulation process, and the heat-sensitive ones are added later.)
• Many forms of ceramides are unstable in the product manufacturing and bottling processes.
• Skin penetration of ceramides depends on the shape and size of ceramides.

Synthetic ceramides have been developed to make ceramides safe, affordable, and more easily formulated into moisturizers. These formulations synthesized in the lab are sometimes called pseudoceramides because they are structurally different compounds that mimic the activity of ceramides. They are developed to be less expensive to manufacture, safer than those derived from animals, and easier to formulate, and they can be made into the specific shape of the ceramide puzzle piece.

Ceramides in skin care

The naturally occurring intercellular lipids of the SC are composed of approximately equal proportions of ceramides, cholesterol, and fatty acids (referred to in this article as the “three barrier lipids” for simplicity).^5-9 Alterations in any of these three barrier lipids or their regulatory enzymes result in impairments in the function of the epidermal barrier. Therefore, any synthetic ceramide must mimic the shape of natural ceramides, or the three barrier lipids in the moisturizer must mimic the shape of the entire bilayer lamella. Unfortunately, most barrier repair moisturizers do not meet these criteria and are not true barrier repair moisturizers.

How do you know if a moisturizer repairs the skin barrier?

Clinical tests such as measuring transepidermal water loss (TEWL) with a Tewameter are usually done to support the barrier repair claim. However, occlusive ingredients like oils can lower TEWL without affecting the barrier. In fact, we believe that sebum on the skin can make an impaired barrier and result in normal TEWL even when the barrier is impaired. So, just because a product improved TEWL does not necessarily mean that it repairs the barrier.

One way to test the ability of a moisturizer to repair the barrier is to look at a structural analysis of the moisturizer to see if it forms the requisite bilayer lamellar shape. An easy way to do this testing is to look for the cross pattern under a cross polarized microscope. The cross pattern is known as optical anisotropy. ⁸

^{Dr. Leslie S. Baumann}

Maltese cross

The best barrier repair creams

Optimal barrier repair creams either feature a 1:1:1 ratio of epidermal lipids or form a cross structure when viewed with a cross-polarized microscope.⁸ There are several categories of barrier repair moisturizers that meet these criteria.

^{Baumann L Cosmetic Dermatology Ed 3 (McGraw Hill) 2022 in press}

Maltese cross pattern seen under a cross-polarized microscope.

Barrier repair creams with a 1:1:1 ratio of lipids:

Peter Elias, MD, holds the patent on barrier repair moisturizer technology that has a 1:1:1 ratio. His well-established technology is used in a prescription barrier repair cream called EpiCeram^® which is approved by the Food and Drug Administration to treat eczema. There are no other moisturizers that I know of that contain this 1:1:1 lipid ratio.

There is a barrier repair cream on the market that contains a 2:4:2 ratio of lipids based on a study that showed that this ratio is effective in older skin with an impaired barrier. It is unknown if this moisturizer forms a cross pattern.