Ceramides and Cholesterol – The Invisible Link Between Metabolism and Heart Health
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When discussing cholesterol, the focus is almost always on LDL and HDL values. A less well-known, but increasingly studied factor in the context of cholesterol metabolism and heart health is ceramides – biologically active fat molecules that play a key role in cellular function and metabolic regulation.
But what exactly are ceramides? And why is their connection to cholesterol and heart disease so important?
What are ceramides?
Ceramides are sphingolipids, which are fatty molecules found in all body cells.They are particularly abundant:
In cell membranes – they maintain the structure of the membrane and protect cells
In the outermost layers of the skin – they prevent moisture loss
In metabolism – they act as signaling molecules that regulate, among other things, the life cycle of cells, inflammatory responses, and insulin sensitivity
Although ceramides are essential, their excess accumulation can cause problems – particularly related to metabolism and heart health.
Ceramides and cardiovascular health
New studies show that blood ceramide levels have a strong correlation with the risk of heart disease – even stronger than traditional cholesterol levels.
High ceramide levels predict the risk of heart attack and stroke
Certain ceramide profiles (e.g. C16:0, C18:0, and C24:1 have been associated with the instability of arterial plaques
They increase the oxidation of LDL cholesterol and promote inflammatory responses in the arteries
Ceramides thus act as "a factor that enhances inflammation and the harmfulness of cholesterol", especially in situations where there are many small, dense LDL particles in the blood.
The connection between cholesterol and metabolism
Ceramides and cholesterol are related to each other on many levels:
The synthesis of ceramides requires saturated fatty acids and cholesterol → A diet high in sugar and saturated fats accelerates the production of ceramides in the liver.
Ceramides can disrupt the function of HDL → HDL no longer transports cholesterol away from tissues as effectively (reverse cholesterol transport is impaired).
Ceramides reduce insulin sensitivity → This leads to an increased risk of fatty liver, diabetes, and cholesterol disorders.
Low-grade inflammation and gut imbalance can increase ceramides → In particular, endotoxins (LPS) can stimulate the formation of ceramides.
Ceramides are like "silent fats"
They do not appear in standard laboratory tests such as LDL or HDL, but can still be a key factor behind heart diseases, especially in the context of metabolic syndrome.
Currently, ceramide-based risk tests (Ceramide Risk Score™) have been developed to assess heart disease risk more accurately than just cholesterol levels.
How can ceramides be measured?
The measurement of ceramides is not yet included in standard cholesterol laboratory tests, but it is possible through specialized studies.
Options for ceramide measurement:
Ceramide Risk Score™ (or CERT status): – Developed specifically for assessing the risk of cardiovascular diseases – Measures the concentrations of certain ceramides (e.g., Cer16:0, Cer18:0, Cer24:1) in the blood – Often combined with clinical risk scoring systems (e.g., CERT1, CERT2) – Used in certain specialized laboratories (e.g.Mayo Clinic, Cleveland HeartLab, United States) – Not yet widely available in Finland, but it may be possible to have a test sent abroad
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Comprehensive lipid profile for research use (NMR lipid tests): – Does not directly measure ceramides, but may provide indications of lipid metabolism imbalance – Used especially in research and functional medicine
Are elevated ceramides treated with medications?
Currently, there are no specifically approved medications for lowering ceramides, but:
Statins can indirectly affect ceramides , as they reduce the production of cholesterol and other lipid structures in the liver.
GLP-1 analogs (e.g., semaglutide) and SGLT2 inhibitors, which are used in the treatment of type 2 diabetes and heart diseases, have shown effects on lowering ceramide levels in some studies.
New investigational drugs (e.g., ceramide synthase inhibitors) are under development but are not yet in clinical use.
How can ceramides be influenced?
Although ceramide levels are not yet routinely measured, recommendations for lowering their levels are very much in line with general lifestyle changes:
1.Nutrition
Avoid: high saturated fats, sugar, and processed foods
Prefer: soft fats (omega-3), vegetables, berries, whole grains, and fermented foods
Beta-glucan and polyphenols may reduce ceramide production indirectly through the gut
2. Exercise
Aerobic exercise and strength training improve insulin sensitivity and lower ceramide levels
3. Weight Management
Weight loss reduces liver fat and decreases ceramide synthesis
4.Gut health
Prebiotics and probiotics reduce endotoxins, which can stimulate the production of ceramides
5.Beta-glucan, gut, and ceramides
The effects of beta-glucan are not limited to lowering cholesterol:
It promotes the growth of beneficial gut bacteria, which in turn can produce short-chain fatty acids (such as butyrate)
These fatty acids affect the liver and reduce inflammatory markers and ceramide production
Thus, beta-glucan can indirectly balance ceramide levels and reduce the harmfulness of cholesterol
Summary
Ceramides are central yet underrated fat molecules that have a direct connection to cholesterol, metabolism, and cardiovascular health.High ceramide levels increase the risk of arterial narrowing, inflammation, and metabolic diseases, even if cholesterol levels appear normal.
Lifestyle, nutrition, and gut health – particularly through the use of pre- and probiotics – can influence ceramide levels and thus heart health at a deeper level than what LDL levels alone indicate.