Ceramides

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What are ceramides?

Ceramides are lipids which make up a large proportion of the lamellar sheets present in the intercellular spaces of the stratum corneum. They are synthesised from two parts: a C18-sphingoid base and a fatty acid, linked together by an amide bond.

 

The stratum corneum is made up of a ‘brick and mortar’ structure. Keratinocytes pushed through from the basal to the horny layer are suspended in a mixture of fatty acids, cholesterol and you guessed it: ceramides.

The stratum corneum is a barrier separating the internal environment from our surroundings. It is designed to keep the internal environment in, and the external environment out. The intercellular space between the keratinocytes in the stratum corneum plays a major role in the skin’s permeability, barrier function and effect on the skin’s structural properties. Ceramides are a major component of this intercellular space.

Skin Cross Section

What is the Structure of a Skin ceramide?

Ceramides are made unique due to the differing C18-sphingoid bases and fatty acid combinations.

 

C18-sphingoid bases:

  • Sphingosine
  • Phytosphingosine
  • 6-hydroxy sphingosine

Fatty acids:

  • Non-hydroxy acids
  • α-Hydroxy acids
  • ω-Hydroxy acids
  • ω-Acyl-oxyacid or Esterified ω-hydroxy acid

An amide bond links a sphingoid base to a fatty acid during a condensation reaction, creating a large fatty molecule with a polar head group attached to a long saturated fatty acid group.

Ceramide Structure

The wide variation of ceramides comes from the differing sphingosine base chain length and fatty acid chain length. Additionally, the fatty acid can contain an α-hydroxy acid, ω-hydroxy acid or no hydroxy acid at all. These features give ceramides unique properties in the stratum corneum intercellular space.

 

The below diagram illustrates different ceramides. The varying regions are the chain lengths of the fatty acid moiety, the chain length of the spingoid base and the alpha hydroxylation position.

What are the types of skin ceramides?

There are eight known skin ceramides, they are abundant in the skin at different percentages, but all essential for maintaining skin barrier functions.

 

Below are outlined all the essential ceramides. Each Ceramide has its own number and abbreviated name, you might see some of these labelled on your cosmetic products.

 

Ceramide

Sphingoid Base

Linked Fatty Acids

% in SC

1

EOS

Sphingosine

Saturated 30-40 carbon chains, amide-linked ω-hydroxy acids

8

2

NS

Sphingosine

Saturated 18, 24, 26 and 28 carbon chains, amide-linked non-hydroxy acids

21

3

NP

Phytosphingosine

Saturated 18, 24, 26 and 28 carbon chains, amide-linked non-hydroxy acids

13

4

EOH

6-Hydroxy Sphingosine

Saturated 30-40 carbon chains, amide-linked ω-hydroxy acids

4

5

AS

Sphingosine

Saturated 30-40 carbon chains, amide-linked α-hydroxy acids

18

6

NH

6-Hydroxy Sphingosine

Saturated 18, 24, 26 and 28 carbon chains, amide-linked non-hydroxy acids

9

7

AP

Phytosphingosine

Saturated 24 and 26 carbon chains, amide-linked α-hydroxy acids

4

8

AH

6_Hydroxysphingosine

Saturated 24 and 26 carbon chains, amide-linked α-hydroxy acids

22

The skin barrier will naturally replenish ceramides during the desquamation process (the shedding of skin). However, exfoliating processes such as excessive use of physical scrubs and α-hydroxy/β-hydroxy acids and anionic surfactants can disturb the stratum corneum structure and remove essential ceramides. This over-exfoliation can lead to an impaired skin barrier, leading to an increased TEWL and skin dehydration. By applying ceramides onto the skin topically, the displaced ceramides can be replenished.

ceramides mechanism of action

Ceramides in the stratum corneum form structures with a low permeability which limit molecular diffusion across the lipid matrix. Ceramides are able to create this barrier due to their unique chemical structures consisting of a polar and non-polar region.

 

Ceramides consist of a polar and non-polar region. The polar heads of the sphingoid base moieties are charged, unlike the fatty acid chains. Particles of the same charge repel each other; therefore, the ceramides orientate themselves with their polar groups facing outwards, with the non-polar region in the middle. This structure is more stable than any other configuration, and with the fatty acid moiety of ceramides having largely saturated carbon chains, they are able to pack very tightly. This leads to the formation of a continuous solid crystalline phase with a diffusion coefficient of <10-4 (which to me and you means: very low).

Ceramide in Lipid Matrix

This low coefficient of diffusion means that molecules struggle to penetrate the barrier. A healthy skin barrier will help prevent trans epidermal water loss (TEWL), from the dermis to the external environment, meaning it helps to keep the skin hydrated.

the benefits of ceramides

Maintain the natural skin barrier

The skin barrier will naturally replenish ceramides during the desquamation process (the shedding of skin). However, exfoliating processes such as excessive use of physical scrubs and α-hydroxy/β-hydroxy acids and anionic surfactants can disturb the stratum corneum structure and remove essential ceramides. This over-exfoliation can lead to an impaired skin barrier, leading to an increased TEWL and skin dehydration. By applying ceramides onto the skin topically, the displaced ceramides can be replenished.

Improves Skin Elasticity and hydration

Ceramides prevent TEWL from the dermis to the external environment due to the low coefficient of diffusion across the lipid matrix. This means that the water in the dermis and epidermis will remain in the skin. High levels of hydration increase skin elasticity, which is associated with a youthful look.

 

Ceramide production is at its peak until the age of 30 for most people, so skin hydration and elasticity will not improve for consumers with peace ceramide production (unless the stratum corneum is disturbed).

protects against UV radiation

Studies have been conducted to investigate the benefits of ceramides in sunscreen products, one study found:

 

“We showed that treatment with ceramide-containing sunscreen alone or in combination with moisturizing cream prevented the initial erythema response, as well as reduced skin darkening at all time points compared to ultraviolet (UV) only and moisturizer alone.”

 

So opting for a ceramide containing sunscreen can increase the efficacy of the UV filter. The mechanism is still under investigation, but it is proposed that the improved barrier function helps mitigate the damage caused by UV radiation.

Clinical Evidence

Clinical studies have substantiated the efficacy of ceramides in skin care. Research indicates that topical application of ceramide-containing formulations can significantly enhance skin hydration and restore barrier function in individuals with dry or compromised skin.

 

Furthermore, ceramide-based treatments have been shown to alleviate symptoms of eczema (atopic dermatitis) and reduce skin sensitivity, underscoring their therapeutic potential in managing skin disorders associated with impaired barrier function.​ Literature can be found here.

Regulatory Status

Ceramides have a well-documented history of safe use in cosmetic products. Regulatory frameworks, such as the European Union’s EC Regulation 1223/2009 on cosmetics, ensure that ingredients used in cosmetic formulations meet stringent safety standards to protect consumer health. While ceramides are not specifically listed in the annexes of restricted or prohibited substances, their inclusion in cosmetic products must comply with general safety assessments. Manufacturers are responsible for conducting thorough safety evaluations, including assessments of potential skin irritation and sensitization, to substantiate the safe use of ceramides in their products.

The CIR has reviewed  ceramides and states: According to information supplied to FDA, ceramide 3 has the most reported uses in cosmetic and personal care products, with a total of 359; the majority of the uses are in leave-on skin care preparations.

Ceramide 2 has the second greatest number of overall uses reported, with a total of 110; the majority of those uses are also in leave-on skin care preparations. In the Personal Care Products Council’s use concentration survey, ceramide 3 had a maximum-use concentration range of 1.0 x 10-8% to 0.2%, with 0.2% reported in lipstick and face and neck skin care preparations. Ceramide 2 had a maximum-use concentration range of 5 x 10-6% to 0.2%, with 0.2% reported in eye lotion and face and neck skin care preparations. Most of the other use concentrations that were reported had similar ranges. Data on the toxicokinetics, acute and repeated dose toxicity, genotoxicity, carcinogenicity, reproductive and developmental toxicity, or irritation and sensitization of ceramides were not found in the published literature.

Formulation Considerations

Incorporating ceramides into cosmetic formulations requires careful consideration of their chemical stability and bioavailability. Ceramides are lipophilic molecules, which can present challenges in achieving homogeneous distribution within aqueous-based formulations. To address this, formulators often employ delivery systems such as liposomes or nanocarriers to encapsulate ceramides, enhancing their stability and facilitating effective skin penetration and delivery.

Additionally, combining ceramides with other lipid components, like cholesterol and free fatty acids, in ratios that mimic the skin’s natural lipid composition can synergistically improve the skin barrier function and hydration.

Ceramide Lipsome
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