Ceramides - the future of emollients?

Dry skin is a familiar topic on this blog but considering it affects a lot of our patients it's always worth discussing. In past articles, I have looked at skin pH (Click Here) and covered emollient selection for patients (Click Here). In this blog, I will focus on ceramides, the most abundant lipid in the epidermis and how they may become centre stage in management of dry skin.

Skin Structure

The bricks and mortar analogy of how the outer epidermis functions as a barrier have been used for many years to explain how the skin maintains integrity. Put simply, a brick wall, is constructed of bricks bound with cement as a binding mortar [1]. When well-constructed, it can function as an effective barrier against the elements and minor physical assaults.

The epidermis is an auto renewing layered structure, with the outer aspects functioning in a similar way to a brick wall. The predominant cell of the epidermis, the keratinocyte acts as the brick with extracellular lipids acting as a mortar which combined offer a barrier against a range of threats including water loss.

The keratinocytes (bricks) maintain their rigidity and shape through their keratin cytoskeleton and by drawing water in with natural moisturising factors [2] (including amino-acids, pyrrolidone carboxylic acid, urea and lactic acid)  which inflates them like water filled balloons to maintain apposition between them forming a barrier. Between these cells, water loss is reduced by a coating of lipids. The intracellular lipid contains a combination of fats including ceramides, fatty acids and cholesterol.

The Lipid Layer

Research over the years has highlighted the lipid layer is highly organised and layered to fulfil its many functions – not least as a barrier to water loss. Lipids are extruded from the keratinocytes in the stratum spinosum and granulosum and undergo enzymatic changes as they enter the inter-epidermal spaces to create organised lipids layers or lamella – ceramides (50%), fatty acids (10%) and cholesterol (25%) by weight.

Skin structure demonstrating bricks and mortar and demonstrating lipid bilayers trapping moisture between keratinocytes (after Sakai [3]; used under Creative Commons Licence)  

Ceramides are a specific group of lipids known as sphingolipids – long fatty acid chains with an amide bond and a waxy texture (“cera”- meaning wax in Latin). They are amphipathic meaning they have hydrophilic (water attracting) and hydrophobic (water repelling) components within their structure. In small quantities they form part of plasma membranes of cells and are also present within many human cells in small amounts. The numbers of identified ceramides in the epidermis has increased recently as more precise molecular technology is being employed. Around 20-25 classes are known to exist with many more ceramides within each group [4-6]. The ceramide layers have been shown to replenish (autonomously from systemic influences) within two days after chemical removal [7].

Functions of Ceramides

Antimicrobial

Recent research has demonstrated the multifunctional benefits of ceramides in the skin. The lipid layer not only acts to retain water but also adds to the inhospitable environment on the surface of the skin. Alongside the antimicrobial peptides (the skins natural antibiotics) the sphingoid lipid bases, which form part of the ceramide structure of the skin, have a range of antimicrobial activities against such common organisms as staphylococcus aureus, strep. pyogenes and E coli for example [8, 9]. As studies have shown, decreased ceramides in the skin of patients with atopic eczema [1, 10] may contribute to water loss and increased risk of colonisation or infection with decreases in epidermal ceramide. In addition, in the presence of antimicrobial threats, ceramides act as signals to induce defensive chemical pathways including TNF-α and other chemicals [11].

Xerosis

Skin which is deficient in ceramide is drier, as observed in patients with atopic dermatitis [10]. The clinical evidence of the effectiveness and importance of ceramides in restoring water content is increasing. Research has shown that ceramide containing emollients can outperform non-ceramide preparations [12, 13] and has shown superiority in treating dryness in older patients [12] and those with diabetes [14]. A consensus paper highlighted the benefits of ceramide being well tolerated and significant in maintaining good skin health [15].

In addition, ceramides have been shown to contribute to the acid mantle of the skin, vital for normal skin integrity. At a lower pH ceramides form a much more resilient and multi-layered water barrier. Application of ceramide-containing creams demonstrate a rapid repair mechanism to restore skin function compared to bland emollients.

Probably the most interesting avenue of research has been examining skin inflammation associated with conditions such as eczema. Often driven by the cytokine IL-4, inflammation inhibits ceramide production consequently reducing skin barrier function. This has been shown in studies where IL-4 activity has been inhibited, and ceramide function has been restored [16]. In addition, exogenous ceramide can reduce cytokine activity and subsequent inflammation and itching.

In terms of what we don't know, the ceramides are a large group and the properties and functions of each alone and in combination, require further work to elucidate the best formulations to achieve healthy skin. 

 

Ceramides in the Emollient Market

Many high street skin care products utilise ceramides in their formulations. Despite the many types of ceramides known to exist, the skincare market focuses on three main types -Ceramides NP, AP and EOP being abundant in healthy skin as illustrated below:

Ceramides in Podiatry

Ask most podiatrists what the key ingredients for a foot moisturiser are and the answer will be urea (in varying concentrations). Its relatively cheap, widely available and a common ingredient in foot creams based on the good evidence of its effectiveness [17-19] which I have covered in previous articles (Click Here).

With growing evidence of their effectiveness, you would think that ceramides would be the next  “must have” ingredient in skin care products including foot preparations. Certainly, in the UK you won't find it as an ingredient on the label of most foot emollients. Why is that? Primarily it comes down to cost. Ceramides are expensive ingredients - most ceramides are synthetic, produced in quantity through chemical processes although some are extracted from a diverse range of plants - rice, coffee, wheat, apples and seeds to name a few. Consequently, their premium price means that prescription priced products rarely have any ceramide content. However, visit a pharmacy and look at the mid-priced products and upwards you will find various ceramide-containing brands. As for foot specific brands there are few.

Moreover, ceramides alone on the thickened epidermis of the soles are not sufficient - plantar epidermis requires a more significant formulation to permit penetration and so formulations will require combinations  with the addition of urea and other natural moisturising moisturizing factors to enhance their action on the thicker plantar surface. This area relies on further research but holds promise in improving foot skin health.

Conclusion

Ceramides are a large part of the epidermis, making up 50% of the waterproofing lipid barrier with some impressive functions which help reduction water loss, control inflammation and restore compromised skin. They are widely seen as ingredients in the general emollient marketplace, but little is available in the footcare range. Their inclusion in foot care products may be hampered by their cost but with time and further research they may be the next must-have additive alongside urea with their range of unique benefits on normal skin function.

References

1.            Elias, P.M., Epidermal lipids, membranes and keratinsation. International Journal of Dermatology, 1981. 20: p. 1–19.

2.            McGrath, J.A., Profilaggrin, dry skin, and atopic dermatitis risk: size matters. J Invest Dermatol, 2012. 132(1): p. 10–1.

3.            Sakai, T., Stratum Corneum Ceramide Abnormalities in Atopic Dermatitis: Pathophysiology and Implications for Disease Management. J Dermatol, 2026. 53(3): p. 380–387.

4.            Akiyama, F., et al. Correlations between Skin Condition Parameters and Ceramide Profiles in the Stratum Corneum of Healthy Individuals. International Journal of Molecular Sciences, 2024. 25, 8291 DOI: 10.3390/ijms25158291.

5.            Starr, N.J., et al., Elucidating the molecular landscape of the stratum corneum. Proceedings of the National Academy of Sciences, 2022. 119(12): p. e2114380119.

6.            Suzuki, M., Y. Ohno, and A. Kihara, Whole picture of human stratum corneum ceramides, including the chain-length diversity of long-chain bases. J Lipid Res, 2022. 63(7): p. 100235.

7.            Grubauer, G., P.M. Elias, and K.R. Feingold, Transepidermal water loss: the signal for recovery of barrier structure and function. Journal of Lipid Research, 1989. 30(3): p. 323–333.

8.            Fischer, C.L., et al., Antibacterial activity of sphingoid bases and fatty acids against Gram-positive and Gram-negative bacteria. Antimicrob Agents Chemother, 2012. 56(3): p. 1157–61.

9.            Arikawa, J., et al., Decreased levels of sphingosine, a natural antimicrobial agent, may be associated with vulnerability of the stratum corneum from patients with atopic dermatitis to colonization by Staphylococcus aureus. J Invest Dermatol, 2002. 119(2): p. 433–9.

10.         Imokawa, G., et al., Decreased level of ceramides in stratum corneum of atopic dermatitis: an etiologic factor in atopic dry skin? J Invest Dermatol, 1991. 96(4): p. 523–6.

11.         Uchida, Y., Ceramide signaling in mammalian epidermis. Biochim Biophys Acta, 2014. 1841(3): p. 453–62.

12.         Danby, S.G., et al., The Effect of an Emollient Containing Urea, Ceramide NP, and Lactate on Skin Barrier Structure and Function in Older People with Dry Skin. Skin Pharmacology and Physiology, 2016. 29(3): p. 135–147.

13.         Danby, S.G., et al., An Investigation of the Skin Barrier Restoring Effects of a Cream and Lotion Containing Ceramides in a Multi-vesicular Emulsion in People with Dry, Eczema-Prone, Skin: The RESTORE Study Phase 1. Dermatol Ther (Heidelb), 2020. 10(5): p. 1031–1041.

14.         Kirsner, R. and A. Andriessen, An International Evaluation of a Ceramide-Containing Hydrating Cleanser and Moisturizing Cream for the Improvement of Diabetes Mellitus-Related Xerosis. J Drugs Dermatol, 2023. 22(1): p. 65–73.

15.         Schachner, L.A., et al., A Consensus About the Importance of Ceramide Containing Skincare for Normal and Sensitive Skin Conditions in Neonates and Infants. J Drugs Dermatol, 2020. 19(8): p. 769–776.

16.         Park, J., et al., Inhibitory activity of a ceramide library on interleukin-4 production from activated T cells. Bioorganic & Medicinal Chemistry, 2005. 13(7): p. 2589–2595.

17.         Loden, M., Urea-containing moisturizers influence barrier properties of normal skin. Arch Dermatol Res, 1996. 288(2): p. 103–7.

18.         Celleno, L., Topical urea in skincare: A review. Dermatologic Therapy, 2018. 31(6): p. e12690.

19.         Lacarrubba, F., et al., Clinical evidences of urea at low concentration. International Journal of Clinical Practice, 2020. 74(S187).