How and why your skin makes ceramides

Ceramides are a family of waxy (cera means wax in Latin) lipids that vary in chemical structure but are basically made of N-acetyl sphingosine and a fatty acid.

Why does the skin make ceramides? Three main functions: the one we are more familiar with is as part of the “glue” that sticks epidermal dead cells to each other making up the skin barrier, which prevents trans-epidermal water loss.

Second, ceramides form part of the cell membranes, in the form of other lipids called sphingomyelin, a major component of the lipid bilayer, crucial to the permeability properties of the membranes.

The third? Ceramides, in the skin and other organs, can act as molecular messengers, participating in processes like differentiation, proliferation, and programmed cell death. As molecular messengers, they are tightly regulated and produced from scratch.Why? Because molecular messengers that will push cells toward death must be carefully regulated and built.

The skin barrier and ceramides

Ceramides are crucial to the effectiveness of the skin barrier, because they make up more than half the lipids that glue the dead epidermal cells to each other, giving the skin barrier its water retention properties. Ceramides, fatty acids, and cholesterol are the major lipids of the granular layer of the epidermis, and the health of the rest of the skin depends on how effective that layer is. This fact has little to do with the enormous importance attributed to the (minute amounts of) ceramides included in some skin care products. The nanograms of plant ceramides in fancy skin care products are a con.

Why are “fancy” ceramides a con?

The ceramides in the epidermis are made in the lamellar bodies of the stratum granulosum during the process of keratinocyte differentiation, which involves terminally differentiated corneocytes and desmosomes that connect keratinocytes. These lipids create a multilamellar barrier between corneocytes, increasing the adhesion and slowing down the movement of material between cells: they are creating the epidermal barrier. The major lipids that form the multilamellar barrier of the skin consist of 50% ceramide, 25% cholesterol, and 15% fatty acids.  Ceramides, fatty acids, and cholesterol applied topically strengthen the skin barrier. They will diffuse into the skin and contribute to the lipids already there. This is why Skin Actives produces the Every Lipid Serum (ELS), which is especially useful for dry, aged skin. The cholesterol, fatty acids, and ceramide in ELS rapidly traversed the stratum corneum with uptake into the epidermal nucleated layers. However, we shouldn’t overestimate the role of ceramides per-se included in fancy skin care products on the skin barrier. You can mimic a good epidermal barrier using occlusive products, and they will slow down water loss and alleviate skin discomfort. But the contribution of ceramides applied topically is not more important than, say, essential fatty acids or cholesterol (also included in every version of Every Lipid Serum we offer). And minute (micrograms) of plant-derived or synthetic ceramides will not make a huge difference.

Ceramide biosynthesis de novo (from scratch) has been studied in the skin. Skin Actives products include the vitamins, amino acids, and fatty acids the skin needs to make ceramides, however complex they may be. It’s likely that the precise chemical structure of the ceramides used to glue dead cells to each other is not a priority: minor changes in the length of the fatty acids will not impact much the effectiveness of the skin barrier. Actually, the ceramides in skin have the greatest molecular heterogeneity in terms of sphingoid base and fatty acid composition in the body. The metabolism of these dying cells, the terminally differentiated corneocytes, is more likely to be “let’s use what’s around” than wasting precious carbon skeletons and energy in precise chemical structures made from scratch. The ceramides and fatty acids constituting the cell membrane of active skin cells will be used to make the “cement”, binding it to whatever proteins are around, mainly elastin and collagen.

How do we know?

Because synthetic ceramides, like pseudoceramide (used by Skin Actives), are chemically very different from skin ceramides, but they do work. They do, however, behave in a similar way, like how they form layers. And they do work in alleviating dry skin and eczema. Because they are synthetic (although still very expensive) they are less expensive than purifying plant ceramides out of crude plant oils. And, in any case, they are not chemically that similar to human skin ceramides anyway!

Actives that stimulate ceramide synthesis by the skin

Nicotinamide, a.k.a. niacinamide: Nicotinamide improved the permeability barrier by stimulating de novo synthesis of ceramides, and other intercellular lipids.

Pantothenic acid (Vitamin B5), necessary for the cell to make Coenzyme A

Essential fatty acids, including linoleic acid.

References

The Lipid Web. https://www.lipidmaps.org/resources/lipidweb/lipidweb_html/lipids/sphingo/ceramide/index.htm

Cha, H.J., He, C., Zhao, H., Dong, Y., An, I., & An, S. (2016). Intercellular and intracellular functions of ceramides and their metabolites in skin (Review). International Journal of Molecular Medicine, 38, 16-22. https://doi.org/10.3892/ijmm.2016.2600

Fujii M. The Pathogenic and Therapeutic Implications of Ceramide Abnormalities in Atopic Dermatitis. Cells. 2021 Sep 10;10(9):2386. doi: 10.3390/cells10092386. PMID: 34572035; PMCID: PMC8468445.

Mizutani, Y., Mitsutake, S.,  Tsuji, K., Kihara, A., Igarashi, Y. (2009) Ceramide biosynthesis in keratinocyte and its role in skin function, 6:  784-790, ISSN 0300-9084, doi: 10.1016/j.biochi.2009.04.001.

Novotný J, Hrabálek A, Vávrová K. Synthesis and structure-activity relationships of skin ceramides. Curr Med Chem. 2010;17(21):2301-24. doi: 10.2174/092986710791331068. PMID: 20459376.

Ponec, M., Gibbs, S., Weerheim, A. et al. Epidermal growth factor and temperature regulate keratinocyte differentiation. Arch Dermatol Res 289, 317–326 (1997). https://doi.org/10.1007/s004030050198

Tamura E, Ishikawa J, Yasuda Y, Yamamoto T. The efficacy of synthetic pseudo-ceramide for dry and rough lips. Int J Cosmet Sci. 2021 Apr;43(2):158-164. doi: 10.1111/ics.12677. Epub 2021 Mar 31. PMID: 33258166; PMCID: PMC8252384.

Tanno O, Ota Y, Kitamura N, Katsube T, Inoue S. Nicotinamide increases biosynthesis of ceramides as well as other stratum corneum lipids to improve the epidermal permeability barrier. Br J Dermatol. 2000 Sep;143(3):524-31. doi: 10.1111/j.1365-2133.2000.03705.x. PMID: 10971324.