Ceramides: NP/AP/EOP subtypes and how they work in the skin

Ceramides: NP/AP/EOP subtypes and how they work in the skin

Ceramides: what they really do for your skin and when to use them

Does a ceramide cream work, or is it just marketing? What matters is the ratio of ceramides to cholesterol and fatty acids, and a vehicle that forms a lamellar phase. In atopic dermatitis, ceramide levels in affected (lesional) areas are reduced by approximately 40%, and they gradually decline with age. In this article, we explain what really matters on the label and how to introduce ceramides into your routine.

What are ceramides and what is their role in the skin?

Ceramide structure and where they are found in the skin

Each ceramide consists of two chains joined by an amide bond: a sphingoid base (sphingosine S, phytosphingosine P or 6-hydroxysphingosine H) and a fatty acid (non-hydroxylated N, α-hydroxylated A, or ω-O-acyl esterified EO). The nine possible combinations give rise to the main ceramide subtypes in healthy human skin (Coderch et al., Am J Clin Dermatol, 2003).

In the stratum corneum, ceramides are found in the intercorneocyte space, between dead, cornified cells. Together with other lipids, they organise themselves into lamellar layers. The classic dermatological analogy is that corneocytes are the “bricks” and the lipid matrix is the “mortar”. The proportions of this mortar's components are relatively stable in healthy skin: approximately 50% ceramides, 25% cholesterol and 10–15% free fatty acids (the remainder consists of minor lipid fractions, cholesterol esters and cholesterol sulphate; molar ratio, Elias PM, J Invest Dermatol, 2005). The quality of the “mortar”, or lamellar phase, determines whether the barrier works (Bouwstra & Ponec, Biochim Biophys Acta, 2006).

Ceramide subtypes: why not every “ceramide” in an INCI list is the same

Cosmetic labels often list “Ceramide NP”, “Ceramide AP” or “Ceramide EOP” without further explanation.
Yet INCI nomenclature tells us a great deal: the first letter denotes the type of fatty acid (N is non-hydroxylated, A is α-hydroxylated, EO is ester-linked ω-hydroxy), and the second denotes the type of sphingoid base (S is sphingosine, P phytosphingosine, H 6-hydroxysphingosine). The nine subtypes (NS, NP, NH, AS, AP, AH, EOS, EOP, EOH) differ not only in identity but also in physiological role (Coderch et al., 2003).

In healthy human skin, ceramide NP (ceramide 3 in the older numerical nomenclature) is the most abundant individual subtype. Ceramide AP (ceramide 6) is among those frequently listed in cosmetics. However, the ω-O-acyl (EO) ceramides, namely EOS, EOP and EOH, matter most for the lamellar phase. They make up around 20% of the overall ceramide profile and act as “bridges”, linking lipid layers into a stable structure (Coderch et al., 2003; Bouwstra & Ponec, 2006). A cream labelled as containing “Ceramide NP” may not supply the lamellar component the skin needs most. The INCI declaration is precise, but it does not tell you whether the formula mimics the physiological profile or simply adds one isolated subtype.

The ratio to cholesterol and fatty acids — Man et al. 3:1:1

In a model of acetone-damaged skin, a topical ceramide on its own paradoxically slows barrier recovery. Only when it is applied alongside cholesterol and free fatty acids, in an approximately equal molar ratio of the three lipid classes (ceramides : cholesterol : free fatty acids), does recovery accelerate compared with the vehicle. This is the original physiological 3:1:1 mixing rule with cholesterol and fatty acids: the ratio of the three lipid classes matters; ceramide alone is not enough (Man et al., J Invest Dermatol, 1996).

With chronological ageing, the equation reverses. In a group of women with an average age of 75, the best recovery score was achieved with a cholesterol-dominant 3:1:1 ratio, meaning cholesterol : ceramide : fatty acids, with complete barrier normalisation within 24 hours of acetone disruption (Zettersten et al., J Am Acad Dermatol, 1997). In other words, different ceramide creams work for 25-year-old skin and 70-year-old skin.

It is not enough to ask, “Does the product contain ceramides?” A better question is: “Are they accompanied by cholesterol and free fatty acids in a sensible ratio and in a lamellar vehicle?” A cream with plant oils (a source of fatty acids and phytosterols) plus a ceramide complex comes closer to this goal. A standalone ceramide serum in a water-based gel without accompanying lipids probably does not.

Declining ceramide levels: in atopy, eczema and chronological ageing

In 1991, Imokawa and colleagues published a finding that still holds today: the total ceramide content in the lesional skin of patients with atopic dermatitis is reduced by approximately 40% compared with healthy controls (Imokawa et al., J Invest Dermatol, 1991).

The most pronounced reduction was observed in ceramide 1 (EOS), the long-chain ω-O-acyl subtype most important for lamellar phase stability. This deficit provides a quantitative explanation for the increased transepidermal water loss (TEWL), dryness and greater permeability to allergens seen in atopic skin.

In a 2005 review, Choi and Maibach showed that a similar pattern of ceramide reduction also occurs in psoriasis, ichthyosis, contact dermatitis and chronically irritated skin (Choi & Maibach, Am J Clin Dermatol, 2005). Ceramide deficiency is a consistent shared consequence across these conditions, although it may not be their primary cause. This makes topical replenishment of barrier lipids a sensible complement to specialist treatment.

In healthy chronological ageing, the decline is slower and more gradual. It is primarily the cholesterol-to-ceramide ratio and the overall rate of lipid renewal that change. This is precisely why Zettersten 1997 suggests a cholesterol-dominant formulation for older skin.

Practical note: if you or your child have moderate to severe eczema with lesions, recurrent infections or a persistently impaired barrier, a cosmetic ceramide cream is a supportive addition to dermatological care. Seek specialist advice. This article is educational and does not replace a professional consultation. For mild dryness and sensitivity, ceramide products can be a demonstrably effective part of a daily routine, particularly when formulated with a physiological lipid ratio.

Ceramides in cosmetics: what really works and how to introduce them into your routine

Topical ceramides: what clinical studies show
How much hydration can you expect? In 2018, Spada and colleagues tested a cream designed to mimic the physiological ceramide profile, formulated with Ceramide NP, cholesterol and a free fatty acid in a ratio close to the natural composition of the lipid matrix. In n = 30 healthy volunteers, stratum corneum hydration (measured by corneometry) increased by approximately 30% within 2 hours of application, and the effect was maintained at the 24-hour measurement.

The reduction in TEWL was statistically significant (p < 0.05), but smaller than the increase in hydration (Spada et al., Clin Cosmet Investig Dermatol, 2018). In a review of 23 clinical studies, Kono and colleagues confirmed that SC hydration increases consistently, while reductions in TEWL vary (Kono et al., J Dermatol, 2021). The marketing claim “ceramides reduce TEWL” is therefore a simplification; a more accurate statement is “ceramides reorganise the lamellar phase, which often (but not always) also reduces TEWL”.

The evidence is stronger for clinically compromised skin. In a multicentre study, Berardesca and colleagues included n = 580 patients with irritant contact dermatitis, allergic contact dermatitis or atopic dermatitis. The topical product contained a pseudoceramide, cholesterol and a free fatty acid in a lamellar emulsion system. After 4 weeks of application, clinical scores improved significantly in more than 70% of patients across all three diagnostic groups (Berardesca et al., Contact Dermatitis, 2001). The study is clear: ceramide products work across different underlying causes and disease processes, and pseudoceramide performs comparably to naturally derived ceramide in measures of barrier recovery, with clinically relevant effects emerging over weeks rather than hours.

Ceramide products have moderate, well-documented efficacy: in healthy skin, they improve hydration and comfort; in dry, sensitive skin or skin with a compromised barrier, they serve as a supportive intervention. In moderate to severe skin conditions (active atopic dermatitis, psoriasis, severe forms of eczema), they act as an adjunct to specialist dermatological treatment. For more detail on how ceramides fit into broader barrier repair, read our guide to the skin barrier and eczema.

Natural, synthetic and pseudoceramides — INCI alone is not a measure of quality

In the cosmetics industry, ceramides come from three sources: natural plant extracts (wheat germ, rice bran, Saccharomyces yeast), fermentation using genetically modified yeast (allowing more precise structural control), and the synthesis of so-called pseudoceramides, molecules that imitate ceramide architecture but are chemically simplified (typically without the rare EO motif).

Functionally, all three categories show comparable results in barrier recovery studies. Berardesca 2001 tested a pseudoceramide, Spada 2018 a biosynthetic ceramide NP, and Schild 2024 explicitly states in a review that synthetic and naturally derived ceramides provide comparable barrier recovery results when the ratio and vehicle are controlled (Schild et al., Int J Cosmet Sci, 2024). What matters most is not the ceramide's origin, but whether it is accompanied by cholesterol and fatty acids in a vehicle that forms a lamellar phase.
An INCI declaration of “Ceramide NP” is therefore a necessary condition, but does not in itself guarantee efficacy. It tells you that the formula contains a specific chemical molecule. It does not tell you its concentration, its ratio to cholesterol and fatty acids, or the vehicle used. A cream with ceramide listed in 6th place in the INCI list and accompanying plant oils is very likely to be more effective than a cream with ceramide in 22nd place without accompanying lipids, even though both “contain ceramides”. From the perspective of certified natural cosmetics, what matters is whether the ceramide comes from a plant source and whether the entire formula complies with natural cosmetics standards.

At Dulcia: Ceramide Complex CLR™ in our products

At Dulcia, we formulate with Ceramide Complex CLR™, a water-based, multi-fraction complex of plant-derived phospholipids and sphingolipids. We deliberately chose it over isolated ceramide NP because it combines several sphingolipid fractions with phospholipids in one complex. This more closely mimics the physiological lipid matrix described by Elias (50% ceramides, 25% cholesterol, 10–15% free fatty acids) than a single isolated ceramide. We use the complex towards the upper end of the supplier's recommended range. It is compatible with certified natural cosmetics, and we use it in our Moisturising Cream with Ceramides, in Hydra Ceramide Face Cream and in the Plus Rosacea. range. You can find a detailed breakdown of the ingredient, including its plant origin, on our ingredient page.

Ceramide cream and serum: how to introduce them into your routine

Ceramides do not compete with most other active ingredients and complement some of them, particularly panthenol, hyaluronic acid and soothing extracts such as centella asiatica. A simple rule applies when layering your routine: thinner layers first, richer ones last; water-soluble products before lipid-based ones. A ceramide cream is usually the final moisturising layer.

```
Product typeWhen to applyWhat to combine it with / what to avoid
Ceramide cleanser
gel or cream
Morning and evening. After an oil-based pre-cleanse; ideally pH 4.5 to 5.5; gentle, barrier-friendly surfactants.
Ceramide serum
serum with a sphingolipid complex
After cleansing, before moisturiser. Apply hyaluronic acid beforehand; when using AHA or BHA, leave a 20 to 30 minute interval between applications.
Ceramide cream
day or night
As the final moisturising layer. Works synergistically with panthenol; with intensive retinol use, it soothes irritation by acting as a protective barrier buffer.

In practice, this looks like:
Morning: cleanser, toner or hyaluronic acid layer, serum (vitamin C or niacinamide), ceramide cream, SPF.
Evening: cleanser, toner or hyaluronic acid, targeted active (retinol, AHA or BHA, depending on the night), ceramide cream. When using retinol, apply the ceramide cream 10 to 15 minutes afterwards, once it has absorbed; the cream reduces irritation without “diluting” the retinol. If your barrier is compromised after an overly intensive exfoliation routine, a ceramide cream acts as a rescue layer for 7 to 14 days.
For context on barrier recovery, it is also useful to explore related topics in our content: facial cleansing (because an unsuitable cleanser disrupts the ceramide layer at the very first step), seborrhoea (where an impaired barrier plays a role) and the Plus prvá pomoc hydratácia, range, which is based primarily on ectoin and glycoin (not ceramides), but is a “first aid” partner for acute barrier disruption.

Frequently asked questions

Are ceramides safe for sensitive skin?
Yes. Ceramides are physiological components of your own skin; replenishing them topically does not trigger an immune response and has no clinically relevant irritation potential. When using a new product for the first time, we recommend a standard patch test — 24 hours on the inner forearm — because the vehicle or other ingredients in the formula (preservatives, fragrances, essential oils), rather than the ceramide itself, may cause a reaction.

Do ceramides help with eczema?
Topical ceramide formulations are a well-documented supportive intervention for atopic dermatitis and eczema. Imokawa 1991 documented an approximately 40% reduction in ceramide content in lesional skin, and Berardesca 2001 showed clinical improvement in more than 70% of patients with various forms of dermatitis. However, ceramides are an adjunct to specialist treatment. For moderate to severe eczema, recurrent infections or a persistently impaired barrier, consult a dermatologist; a ceramide cream complements treatment, it does not replace it.

Are natural ceramides better than synthetic ones?
They are functionally comparable in measures of barrier recovery. Clinical studies consistently show this (Berardesca 2001 on pseudoceramide; Spada 2018 and the Schild 2024 review). More important than origin is the ratio of ceramides to cholesterol and fatty acids, together with a vehicle that forms a lamellar phase. For our natural cosmetics, we choose plant-derived sphingolipid complexes because they meet our certification standards; synthetic ceramides are nevertheless fully functional.

Can I combine ceramides with retinol?
Yes, this is a well-tolerated combination. Retinol increases cell turnover and often causes irritation and desquamation (known as retinisation) during the first 4 to 8 weeks. Ceramides in the final cream layer reduce this effect, acting as a protective barrier buffer. In practice: apply retinol to clean skin, allow 10 to 15 minutes for it to absorb, then layer a ceramide cream over it. If irritation is severe, reduce retinol use to every second or third night.

What concentration of ceramides in a product is sufficient?
Studies demonstrating clinical efficacy use a wide range. Spada 2018 tested a cream mimicking the physiological ceramide profile with a total lipid content of a few per cent. Berardesca 2001 used a pseudoceramide blend in a similar range. More important than a single “ceramide concentration” figure is the completeness of the lipid blend (ceramides plus cholesterol plus fatty acids) and the type of vehicle (a lamellar emulsion system versus a standard oil-in-water cream). If the manufacturer lists Ceramide Complex or Ceramide NP in the first third of the INCI list, and the ingredients also include plant oils and lipids, the formula has a good chance of working.

Conclusion

Ceramides have strong clinical support for barrier recovery. They make up approximately 50% of barrier lipids in healthy skin; in atopic dermatitis, their levels fall by around 40% (Imokawa 1991), and natural and synthetic forms perform comparably (Schild 2024). Topical replenishment works when the ceramide is accompanied by cholesterol and fatty acids in a sensible ratio and in a vehicle that forms a lamellar phase. For everyday hydration, try the Moisturising Cream with Ceramides; for drier or more mature skin, choose the richer Hydra Ceramide Face Cream. Both combine Ceramide Complex CLR™ with plant oils that supply accompanying fatty acids. At Dulcia, we formulate both with accompanying plant oils so that ceramides are not left on their own — the ratio determines whether the barrier really holds.

References

Elias PM. “Stratum corneum defensive functions: an integrated view.” Journal of Investigative Dermatology 2005, 125(2):183–200. PMID: 16098026.

Imokawa G, Abe A, Jin K, Higaki Y, Kawashima M, Hidano A. “Decreased level of ceramides in stratum corneum of atopic dermatitis: an etiologic factor in atopic dry skin?” Journal of Investigative Dermatology 1991, 96(4):523–526. PMID: 2007790.

Man MQ, Feingold KR, Thornfeldt CR, Elias PM. “Optimization of physiological lipid mixtures for barrier repair.” Journal of Investigative Dermatology 1996, 106(5):1096–1101. PMID: 8618046.

Zettersten EM, Ghadially R, Feingold KR, Crumrine D, Elias PM. “Optimal ratios of topical stratum corneum lipids improve barrier recovery in chronologically aged skin.” Journal of the American Academy of Dermatology 1997, 37(3 Pt 1):403–408. PMID: 9308554.

Spada F, Barnes TM, Greive KA. “Skin hydration is significantly increased by a cream formulated to mimic the skin's own natural moisturizing systems.” Clinical, Cosmetic and Investigational Dermatology 2018, 11:491–497. PMID: 30410383.

Coderch L, López O, de la Maza A, Parra JL. “Ceramides and skin function.” American Journal of Clinical Dermatology 2003, 4(2):107–129. PMID: 12553851.

Schild J, Kalvodová A, Zbytovská J, Schroeter A, Lunter D. “The role of ceramides in skin barrier function and the importance of their correct formulation for skincare applications.” International Journal of Cosmetic Science 2024 (online-first; volume/issue/page range pending — pre-publish editors verify final locator from DOI). DOI: 10.1111/ics.12972.

Berardesca E, Barbareschi M, Veraldi S, Pimpinelli N. “Evaluation of efficacy of a skin lipid mixture in patients with irritant contact dermatitis, allergic contact dermatitis or atopic dermatitis: a multicenter study.” Contact Dermatitis 2001, 45(5):280–285. PMID: 11722486.

Kono T, Miyachi Y, Kawashima M. “Clinical significance of the water retention and barrier function-improving capabilities of ceramide-containing formulations: A qualitative review.” Journal of Dermatology 2021, 48(11):1807–1816. DOI: 10.1111/1346-8138.16175.

Bouwstra JA, Ponec M. “The skin barrier in healthy and diseased state.” Biochimica et Biophysica Acta 2006, 1758(12):2080–2095. PMID: 16945325.

Choi MJ, Maibach HI. “Role of ceramides in barrier function of healthy and diseased skin.” American Journal of Clinical Dermatology 2005, 6(4):215–223. PMID: 16060709.

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