The Science of Ceramides in Skin Care

Skin cream with ceramides on a pregnant woman's belly

Ceramides are gaining popularity as an ingredient in skincare products and it’s not without reason: your body produces certain types of ceramides to form the outermost layer of your skin called the skin barrier. For most healthy, young people, about 50% of their skin barrier is made up of ceramides.

Your skin barrier is your shield against the nasty things out in the world and your body’s way to lock in good things like moisture. A healthy skin barrier can keep your skin balanced, radiant, and smooth, while protecting against pollution and invaders.

Does including ceramides in skin care products make a real difference though?

Read on to learn about the many different types of ceramides in your skin and skincare products, and which ones are right for you.

What Are Ceramides?

Ceramides are a class of bioactive waxy-fats, called lipids, involved in major molecular mechanisms in the body. They are made by the body in dynamic processes involving at least 28 different enzymes and several complex regulatory mechanisms.

Ceramides are constructed in your skin from a sphingosine  and a fatty acid. 

 

Ceramide NDS Chemical Diagram
Figure 1. Ceramide NDS Chemical Diagram
(One of the many ceramides your skin needs)

 

A sphingosine looks like a long chain with a head. You can think of sphingosines as messengers. 

A fatty acid also looks like a long chain with a smaller head. Fatty acids are used as the building blocks for fats in our bodies.

A ceramide is formed when a sphingosine attaches to a fatty acid and forms a new head with two tails. Essentially, the messenger connects to their mailbag.

Both the head of the ceramide and the length of both chains matter to the overall function of the ceramide, which we’ll cover later. 

When it comes to classifying ceramides at the highest level, there are two main things to be aware of: the head of the ceramide and its chain length.

Sub-Classifying Ceramides By Head Type

We mentioned above that a ceramide is made up of a sphingosine and a fatty acid connected at both of their heads to make a new combined head, with two tails.

There are 4 types of sphingosine head-types in the human body that can be assembled with 3 head-types of fatty acids, creating 12 total classes of ceramides categorized by their combined head.

The 12 different subclasses of ceramides by head type are listed below.

  • Ceramide 1, also known as EOS
  • Ceramide 2, also known as NS
  • Ceramide 3, also known as NP
  • Ceramide 4, also known as EOH
  • Ceramide 5, also known as AS
  • Ceramide 6, also known as AP
  • Ceramide 7, also known as AH
  • Ceramide 8, also known as NH
  • Ceramide 9, also known as EOP
  • Ceramide 10, also known as NdS
  • Ceramide 11, also known as AdS
  • Ceramide 12, also known as EOdS

When ceramides were first discovered, they were numbered. Later, when scientists understood the 4 sphingosine and 3 fatty acid pairings better, we started using the letters shown above. Both are used in literature and skin care ingredient labels.

You may also see ceramides written as “ceramide 6/AP”, which is just a combination of the ‘6’ and ‘AP’.

 

12 Sub-Classes of Ceramides

Figure 2: The 12 Sub-Classes of ceramides that make up your skin

In Figure 2, we have the 3 fatty acid types (N, A, and EO) and the 4 sphingosine types (S, DS, P, and H) and we show how they come together to form ceramides like AP (a combination of the ‘A’ fatty acid head with the ‘P’ sphingosine head), or EOS (‘EO’ fatty acid combining with ‘S’ sphingosine type).

Extending the analogy that ceramides are a sphingosine messenger with a fatty acid mailbag, the 12 different sub-classes are sort of like different mail carriers - FedEx, UPS, and USPS for example. While there is overlap, each is best at a certain type of delivery and package.

Classifying By Short And Long Chain Ceramides

When we talk about the sphingosine or fatty acid chain, we are talking about the series of up-down lines in the chemical figure below. Those lines represent carbon atoms that are bonded together into what looks like a chain extending out from the head. 

 

Ceramide NDS has variable chain length

Figure 3. Note the variable chain length of both the fatty acid and sphingoid

The length of the chain of carbon atoms can vary for each of the ceramides described above. Some fatty acids are short, 16 to 18 carbon atoms long, and some are long, between 20 and 32 carbon atoms long. Sphingosines can have shorter or longer chains as well.

When biochemists label a ceramide, they will sometimes add a number to the end of it to describe the chain length of the fatty acid, the sphingosine, or both. So you may see something like “Ceramide AS32”, “Ceramide AS(C32)”, or “Ceramide A(18)S(14) if you read scientific literature.

The difference between short and long-chain is critical to their function in the body.

Short chain ceramides are involved in sending messages that control cell death, inflammation response, and insulin resistance. In the layer of skin below the skin barrier, the ceramides tend to be shorter and act as messengers.

Long ceramides help form the “glue” between skin cells, bolstering your skin barrier’s strength, suppleness, and smoothness. The skin barrier in healthy people tends to be made up of more long chain ceramides.

When long chain ceramides bond together in the skin barrier, they are less permeable because they have a higher melting point - it takes more energy to move them aside and get past them. So long chain ceramides are the best for barrier enhancement.

 

Extending the now stretched-too-thin analogy of messengers, the chain length is sort of like the contents of the message. It could be a letter with an order to “attack at dawn!” or it could be a box with new bungee cords meant to tie-down and hold loose materials.

Why Ceramides Are Important To The Skin

Ceramides are an integral part of the skin barrier (epidermis), the outer layer of your skin which acts as your largest connection to the outside world. They are categorized as a type of chemical called lipids and work to maintain the health of your skin barrier, which protects your body against diseases, toxins, and moisture loss. 

Over 340 unique ceramides have been identified in the skin each with a distinct function. But in general, they work for your skin in two very important ways:

  1. They create a flexible glue to hold your skin barrier together
  2. They act as messengers for the cells in the layers of skin below the skin barrier

As a result, ceramides in your skin are responsible for, or contribute to:

  • Protection against environmental damage, harmful microbes, and viruses (long chain ceramides via skin barrier strength)
  • Prevent dryness and redness by sealing moisture in your skin (long chain ceramides via skin barrier strength)
  • Have anti-aging effects like firming, smoothing, and suppleness ( long chain ceramides via skin barrier strength)
  • Defend against inflammation and inflammatory skin disorders, such as atopic dermatitis, eczema, psoriasis, acne and others (long chain via skin barrier strength & short-chain messengers)
  • Maintaining normal functioning of skin cells in the layers of skin below the skin barrier (dermis and hypodermis short chain ceramides)

Long Chain Ceramides As Flexible Glue

The skin barrier resembles a microscopic, flexible brick wall. Dead skin cells act as bricks and ceramides, along with several other fats, act as mortar to connect those bricks. The strength, smoothness, and suppleness of your skin is largely controlled by the ceramides and fats. 

 

How long chain ceramides organize into the skin barrier

Figure 4. How long-chain ceramides form the skin barrier

A strong skin barrier is the result of two factors: the organization of the ceramides in the skin barrier, and the ceramide chain length. In general, the tighter the ceramides are packed, and the longer the ceramides are, the more supple, smooth, and strong your skin barrier will be.

We will talk about how density and chain length can go awry later.

Short Chain Ceramides As Messengers

Ceramides can also be messengers in cells throughout the body, including the skin. The skin barrier contains dead skin cells but just below it are living skin cells that rely on ceramides for regulating various cellular processes like cell death, inflammation response, and insulin resistance (Hannun and Obeid, 2011, Hannun and Obeid, 2008, Charruyer et al., 2008).

Messenger ceramides are generally shorter-chain ceramides, which are described below.

Ceramides And The Microbiome

The microbiome is the bacteria, single-celled organisms, and viruses that live as a community on and in your skin.

An excess of short chain ceramides is also associated with an imbalance in your skin microbiome and an increase in the abundance of harmful microbes, which can cause inflammation, infection, or slow wound healing. 

An imbalanced microbiome may lead to a cycle of inflammation, where as a result of an immune response, short chain ceramides are created, which then encourage harmful bacteria, which in turn lead to more inflammation. 

Why Do You Need Ceramides In Skin Care?

Ceramides are critical to proper skin and skin barrier function, and sometimes the body just isn’t producing enough, or it produces too many short chain ceramides.

If there are too many short chain ceramides in the skin barrier it can weaken it to the point where it struggles with normal functions like moisture control and protecting against aggressors. 

Ceramides can become unbalanced and/or ceramide levels can drop for several reasons. Read more about how ceramides are affected and what you can do about it below.

Ceramides And Aging

Overall ceramides levels decrease as you age. The drop in total ceramides contributes to skin concerns like wrinkles, itchiness, and dryness. 

With a thinner, less supple skin barrier, older people tend to bruise and have cuts more frequently on their shins and hands than they did in their youth.

Ceramides And Seasons

The levels of ceramides in the skin change seasonally with reduced ceramides in the autumn and winter. This may be part of the reason skin is dryer and itchier in those seasons. With fewer long chain ceramides, the skin barrier is weaker and more susceptible to disruption as well.

Ceramides And UV/Radiation Exposure

UV light is a form of ionizing radiation, meaning it can create molecular changes (sometimes resulting in a sunburn). There is evidence that UV light can also shift the balance of ceramides to include more short chain ceramides, potentially weakening the skin barrier. 

Ionizing radiation can also come from radiation treatments for cancer and other concerns. Often cancer patients are offered topical treatments that aim to strengthen the skin barrier.

Ceramides And Medications

This section is intended for educational purposes only. It is not intended to be medical advice. Please consult with a physician regarding your individual circumstances. Rulo is happy to provide resources for people seeking a referral to a physician who may understand the concepts below.

Chemotherapies to treat certain conditions tend to shift the ceramide balance to include more short chain ceramides. With fewer long chain ceramides, the skin barrier is weakened and more prone to disruption. 

Ceramides And Allergies/Irritants

Irritants and foreign invaders to the skin can trigger an immune response. An immune response in turn can lead to an excess of short chain ceramides, weakening the skin barrier and making it more susceptible to the irritants that eventually cause more flare ups.

Learn more about how that affects eczema below.

Ceramides And Autoimmune Diseases (Psoriasis, Multiple Sclerosis)

This section is intended for educational purposes only. It is not intended to be medical advice. Please consult with a physician regarding your individual circumstances. Rulo is happy to provide resources for people seeking a referral to a physician who may understand the concepts below.

The body’s immune system is complex, with specialized cells and processes. Immune responses in the skin are associated with higher levels of short chain ceramides being produced in the skin.

Autoimmune diseases that are characterized by overactive immune responses like psoriasis or multiple sclerosis are also associated with more short chain ceramides and fewer long chain ceramides in the skin barrier. 

Fewer long chain ceramides can lead to a weakened skin barrier that is more susceptible to disruption. A weakened skin barrier may then increase localized inflammation through allowing more irritants to enter the dermis.

The skin has a role to play in systemic (whole body) inflammation as well. As our connection to the world, the body will take signals from it on how responsive it should be to invaders.

Our skin is essentially a watch tower for our body and there is evidence that a weakened skin barrier, which will allow more irritants through, will cause an increase in systemic inflammation.  

Ceramides And Diabetes

This section is intended for educational purposes only. It is not intended to be medical advice. Please consult with a physician regarding your individual circumstances. Rulo is happy to provide resources for people seeking a referral to a physician who may understand the concepts below.

Diabetes patients tend to have an excess of short chain ceramides weakening the skin barrier.

A weakened skin barrier in patients with diabetes is associated with a significantly increased risk for wounds, cuts, and infections that can take longer to heal. 

Ceramides And Other Genetic Diseases

This section is intended for educational purposes only. It is not intended to be medical advice. Please consult with a physician regarding your individual circumstances. Rulo is happy to provide resources for people seeking a referral to a physician who may understand the concepts below.

Ceramide creation in the skin is a dynamic process that involves a group of at least 28 individual enzymes and complex regulatory mechanisms. These enzymes and regulatory mechanisms allow the skin to manufacture the ceramides it requires to be healthy.

The body’s production of enzymes and management of regulatory processes are controlled by the body’s genes. 

Several genetic mutations have been shown to be associated with skin diseases and there may be a host of lesser-known genetic conditions where ceramide formation is altered leading to a weakened skin barrier.

Ceramides In Skin Disorders

This section is intended for educational purposes only. It is not intended to be medical advice. Please consult with a physician regarding your individual circumstances. Rulo is happy to provide resources for people seeking a referral to a physician who may understand the concepts below.

A weakened skin barrier is a precursor to skin diseases, and ceramide imbalances are associated with multiple skin disorders.

To understand the role of ceramides in skin disorders, let’s first take a look at what ceramides look like in healthy skin.

Count of free ceramides in the dermis and epidermis

 

The above figure shows the free ceramide concentrations in the epidermis and in the layer below that, the dermis, by chain length. The epidermis includes the skin barrier.

This shows that the epidermis and skin barrier skin barrier have far more free ceramides, and those ceramides tend to have longer chain length

This makes intuitive sense because shorter chain ceramides are used for cellular signaling and the dermis has live skin cells. Longer chain ceramides are used as flexible glue between dead skin cells in the skin barrier, and are more present in the epidermis.

What’s important to note here is that since the skin barrier does not have live skin cells, the long chain ceramides are being formed in the dermis and ‘pushed’ into the skin barrier. That means the shorter chain ceramides are “up-cycled” into the longer chain ceramides in the uppermost layers of the skin.

% increase of free ceramides in the epidermis vs the dermis
Figure 6. Percent increase of free ceramides in the skin barrier vs the dermis.

  

The chart above shows the ratio of a total count of ceramide sub-classes across all chain lengths in the skin barrier to the sub-classes in the dermis. In other words, the above chart shows how much of each type of sub-class needs to be up-cycled from the dermis to the skin barrier.

Note: the EO* ceramide subclasses are not shown in the chart as we cannot divide by 0, as there were none present in the dermis. However, those are found in low levels in the epidermis and play an important role in the skin barrier.

Taking the two figures above together, it seems that the ceramide chain length is the dominant difference between the dermis and skin barrier as it relates to ceramides.

Imbalances, particularly in short vs long chain ceramides can lead to a weakened skin barrier that is prone to disruption which in turn leads to a number of skin concerns.

We dive into each of these skin diseases below.

Sensitive Skin 

Sensitive skin is not a medical diagnosis but rather a common term used to describe when skin is hyper-reactive and prone to redness, itching, or irritation. 

The latest research has shown that if the skin barrier has too few long chain ceramides, that it is more reactive and weaker at rejecting irritants

If an irritant does get through the skin barrier, living skin cells are more permeable, and therefore reactive, when in the presence of an excess of short chain ceramides

In addition, the skin plays a role in regulation of our systemic (whole body) immune response. A weaker barrier has shown to lead to more systemic inflammation

Flaking Or Dry Skin

Long chain ceramides in the skin barrier both hold the skin together and help prevent water loss.

Dry skin and flaking can occur when the overall level of ceramides has declined, or when the skin barrier does not have enough long chain ceramides. 

Dry and flaking skin therefore is a sign of a weakened skin barrier, which can lead to more serious conditions, such as eczema. With the weakened skin barrier, irritants can more through the skin barrier more easily and trigger an immune response.

Eczema (And Atopic Dermatitis)

Eczema, or atopic dermatitis, is a common chronic, inflammatory skin condition. One of the features of the condition is dryness, disturbed skin barrier, and increased moisture loss. Underlying these pathologies is a:

  • Decreased abundance of long-chain ceramides
  • Increased quantity of short-chain ceramides

Because the otherwise healthy skin of eczema patients shows a lower level of long chain ceramides and increased short chain ceramides, and it is believed that the condition arises from some factor in the body’s ability to make long chain ceramides, rather than a localized irritant breaking through the skin barrier or a problem with the immune system in general.

 The total level of ceramides or ceramide sub-classes, seems to not be associated with eczema, rather a reduction in the chain length of the ceramides has a stronger association with severity of the condition.

Eczema sufferers have a weakened skin barrier due to lower long chain ceramides. This allows irritants to break through the barrier, triggering a natural inflammatory response from the skin.

Flareups like this are hard to quiet because the skin barrier is further weakened by the inflammatory response itself producing more short chain ceramides. Those short chain ceramides attract microbiome species that further inflammation delaying resolution of the inflammation. 

Allergies, Rashes

The latest research has shown that if the skin barrier has too little long chain ceramides, that it is more reactive and weaker at rejecting irritants. 

If an irritant gets through the skin barrier, either because it is weak, or at a junction like a hair follicle, increased short chain ceramides allow living skin cells to be more permeable, and therefore reactive.

In addition, the skin plays a role in regulation of our systemic immune response. A weaker barrier has shown to lead to more systemic inflammation in the whole body. 

Fine Lines, Wrinkles, & Skin Tone

An overall decrease in ceramides is associated with the appearance of fine lines, wrinkles, and a dull skin tone.

Overall decreases of ceramides are associated with aging and seasonal changes.

Easily Bruised And Broken Skin

An overall decrease in ceramides is associated with easily bruised and broken skin due to a weaker skin barrier and thinner skin.

Microbiome Concerns

Ceramide imbalance is also associated with a skin microbiome imbalance and an increase in the abundance of harmful microbes. 

Eczema sufferers may see an increase in duration of symptoms and in secondary infections as a result of the microbiome imbalance combined with physical scratching.

Picking The Right Ceramide Skin Care Products

Many skincare products contain a single ceramide, mixes of ceramides, and/or other essential substances that make up the skin barrier. These can help correct an imbalance of ceramides associated with seasonal change, aging, and skin diseases.

We recommend careful consideration of the ingredient list. Less expensive products can lead to inflammation and accelerate aging. 

How To Prevent The Loss Of Ceramides

Ceramides decline as we age and in the winter. We can't control time or season but there are a few ways that we can prevent the loss of ceramides.

Ionizing radiation, like UV, cause a loss of long chain ceramides. Wearing a high-quality sunscreen that does not harm the microbiome is a good way to avoid a weakening of the skin barrier from UV light. 

Exfoliation is touted as a way to "remove dead skin" with a host of proposed benefits, however, while removing dead skin cells, you are also breaking down the ceramides holding those cells in the skin barrier.

If you do exfoliate, once or twice a week is good enough. Listen to your skin. If it is red, sensitive, flaking, or painful, re-examine the frequency, duration, and type of product you are using. Reduce or replace as needed.

In Rulo's view, the benefits of exfoliation, including improved skin tone, evenness, and reducing flakiness, can be accomplished through adding long chain ceramides instead.

There is no need to remove dead skin cells, if those cells are making up a healthy part of the skin barrier. Instead, maintaining the long chain ceramide glue can create the improvements in skin tone and flaking that is desired, while improving overall skin barrier function at the same time.

How Rulo Skin Uses Ceramides In Our Skin Care Products

Rulo has a revolutionary, evidence-based approach to repairing and strengthening the skin barrier. 

Our products induce the microbiome on your skin to time-release native, long chain ceramides in your skin barrier which leads to:

  • A stronger skin barrier in as little as 3 days
  • Added protection with a healthier microbiome
  • No disruption of the skin from foreign ceramides or chemicals

Learn more about our Skinfluence Calming Serum here.

 

References

We are a team of scientists and physicians who deeply research to bring you the latest accurate information. Wherever possible we cite 3rd party research that is not backed by industry labs. Below are the papers we used to bring you this article.

The role of epidermal sphingolipids in dermatologic diseases

Exploring mechanisms involved in the biosynthesis of cutaneous ceramides in health and disease

Altered Levels of Sphingosine, Sphinganine and Their Ceramides in Atopic Dermatitis Are Related to Skin Barrier Function, Disease Severity and Local Cytokine Milieu

Ceramide in apoptosis: an overview and current perspectives

Bilayer Structure and Lipid Dynamics in a Model Stratum Corneum with Oleic Acid

Alterations of Ultra Long-Chain Fatty Acids in Hereditary Skin Diseases—Review Article

Characterization of overall ceramide species in human stratum corneum

Many ceramides

Principles of bioactive lipid signalling: lessons from sphingolipids

Decreased Ceramide Transport Protein (CERT) Function Alters Sphingomyelin Production following UVB Irradiation

Stratum corneum lipidomics analysis reveals altered ceramide profile in atopic dermatitis patients across body sites with correlated changes in skin microbiome

Increased Levels of Short-Chain Ceramides Modify the Lipid Organization and Reduce the Lipid Barrier of Skin Model Membranes

Enrichment of Short-Chain Ceramides and Free Fatty Acids in the Skin Epidermis, Liver, and Kidneys of db/db Mice, a Type 2 Diabetes Mellitus Model

Decreased Level of Ceramides in Stratum Corneum of Atopic Dermatitis: An Etiologic Factor in Atopic Dry Skin?

Age-related and seasonal changes in covalently bound ceramide content in forearm stratum corneum of Japanese subjects: determination of molecular species of ceramides

Ceramides (CER) are classified based on a letter code, which portrays the chemical modifications of the different CER classes

Ultraviolet (UV) and Hydrogen Peroxide Activate Ceramide-ER Stress-AMPK Signaling Axis to Promote Retinal Pigment Epithelium (RPE) Cell Apoptosis

Ceramides (CER) are classified based on a letter code, which portrays the chemical modifications of the different CER classes

The role of epidermal sphingolipids in dermatologic diseases

Ceramide composition of the psoriatic scale

Epidermal Dysfunction Leads to an Age-Associated Increase in Levels of Serum Inflammatory Cytokines

Recent advances in understanding inherited disorders of keratinization

Significance of Skin Barrier Dysfunction in Atopic Dermatitis

Atopic dermatitis: a disease of altered skin barrier and immune dysregulation

Skin Barrier Function in Psoriasis and Atopic Dermatitis: Transepidermal Water Loss and Temperature as Useful Tools to Assess Disease Severity

Lipids and skin barrier function – a clinical perspective

Lipid functions in skin: Differential effects of n-3 polyunsaturated fatty acids on cutaneous ceramides, in a human skin organ culture model

Increase in short-chain ceramides correlates with an altered lipid organization and decreased barrier function in atopic eczema patients

The role of ceramide chain length distribution on the barrier properties of the skin lipid membranes

Increased Levels of Short-Chain Ceramides Modify the Lipid Organization and Reduce the Lipid Barrier of Skin Model Membranes

Increased Levels of Short-Chain Ceramides Modify the Lipid Organization and Reduce the Lipid Barrier of Skin Model Membranes

Increase in short-chain ceramides correlates with an altered lipid organization and decreased barrier function in atopic eczema patients

Epidermal Dysfunction Leads to an Age-Associated Increase in Levels of Serum Inflammatory Cytokines

Skin Barrier Disruption: A Requirement for Allergen Sensitization?

Stratum corneum lipidomics analysis reveals altered ceramide profile in atopic dermatitis patients across body sites with correlated changes in skin microbiome

Alterations of Ultra Long-Chain Fatty Acids in Hereditary Skin Diseases—Review Article

Derailed Ceramide Metabolism in Atopic Dermatitis (AD): A Causal Starting Point for a Personalized (Basic) Therapy

Increase in short-chain ceramides correlates with an altered lipid organization and decreased barrier function in atopic eczema patients

Increased Levels of Short-Chain Ceramides Modify the Lipid Organization and Reduce the Lipid Barrier of Skin Model Membranes 

About The Author

Dr. Nicole Scott, PhD, MPH has published 29 peer-reviewed papers regarding human biology and the microbiome. Her work has been cited over 4000 times.

She is the Founder of Cybele Microbiome and Rulo Skin

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