- Ceramides are fatty molecules that health experts associate with cardiovascular disease.
- Research in animals suggests that drugs that reduce ceramide synthesis could prevent not only cardiovascular disease but also diabetes.
- Statins, which lower serum cholesterol levels to prevent heart disease and stroke, may increase the risk of or worsen existing type 2 diabetes.
- A review article argues that more scientists should investigate ceramides with a view to developing a new class of drug that could complement statins.
Around 38% of adults in the United States have high levels of cholesterol in their blood, which puts them at increased risk of heart disease and stroke.
One of the ways to reduce serum cholesterol levels is to take cholesterol-lowering drugs called statins.
However, while multiple studies have shown that the drugs prevent cardiovascular disease, some research suggests that they may worsen type 2 diabetes.
A review article in the journal Trends in Pharmacological Sciences argues for the development of drugs to reduce levels of another class of lipids. Scientists call these drugs ceramides.
Like cholesterol, ceramides are a type of fatty molecule, or lipid, that play a vital role in the structure of cell membranes and in the synthesis of other lipids.
The authors of the review point out that there is a strong association between high serum concentrations of ceramides and heart disease and diabetes in humans, independently of cholesterol.
They also write that some clinics now measure ceramide levels to assess patients’ risk of these conditions.
Moreover, laboratory experiments on rodents eating high fat diets suggest that ceramides are partly responsible for heart disease and diabetes, rather than being incidental byproducts of these conditions.
When scientists use drugs or genetic means to reduce the synthesis of ceramides in animals, this prevents the animals from developing cardiovascular disease and diabetes.
Other animal studies have found that ceramides can increase fat storage, decrease glucose use, and reduce the efficiency of mitochondria, which are the power plants of cells.
These are all hallmarks of metabolic syndrome — a combination of diabetes, high blood pressure, and diabetes — which puts an individual at greater risk of cardiovascular disease and stroke.
“Basically, we want to get as many labs as possible studying this important molecule,” says senior author Dr. Scott Summers, Ph.D., of the University of Utah College of Health in Salt Lake City.
“Several companies, including one I co-founded (Centaurus Therapeutics), have been trying to develop ceramide-lowering interventions,” Dr. Summers told Medical News Today.
“Thus far, none have entered the clinics, but I think some companies are close,” he added.
Shortcomings of statins
Statins reduce the level of ceramides in the bloodstream, in addition to cholesterol.
However, the drugs do not stem the production of ceramides in the body. Rather, they reduce the production of lipoproteins, which are the molecules that carry them in the bloodstream.
“Statins block cholesterol synthesis, which in turn leads to secondary inhibition of lipoprotein production and secretion,” Dr. Summers explained to MNT.
“Statins don’t block ceramide synthesis directly. Rather, they lower circulating ceramides because of the effects on lipoproteins,” he said.
So why go to all the trouble of developing new drugs for ceramides?
Dr. Summers explained that ceramides exert their harmful effects in tissues such as the liver rather than in the bloodstream.
“The problem is, ceramides do most of their actions in tissues, not in the blood,” he said.
“As a result, for people on statins, the ceramides likely accumulate in the liver, which is potentially problematic,” he added.
He said this could account for some of the side effects of statins, such as an increase in the risk of type 2 diabetes.
“Adding a ceramide-lowering therapy to statin therapy is definitely something that should be investigated,” he said.
Exercise as treatment
Not everyone is convinced of the need to develop a new class of drugs to reduce the synthesis of ceramides.
Dr. Justin Carrard, a specialist in sports and exercise medicine at the University of Basel in Switzerland, recently published a review article in the journal Metabolitesabout the effect of physical exercise on ceramide levels.
The article points to preliminary evidence that regular exercise reduces ceramides. In addition, individuals with good cardiorespiratory fitness tend to have low levels of several types of ceramide.
“There is now robust scientific evidence that ceramides have a future as biomarkers to stratify cardiovascular risks,” Dr. Carrard told MNT.
He said more research is necessary to establish whether physical activity can lower ceramide levels.
“However, I strongly believe that this will become a new area of global interest in the medical community,” he added.
Dr. Carrard questioned the need to develop new drugs if an exercise program could achieve the same effects.
He said:
“Working in the field of sport and exercise medicine, I am personally convinced that exercise is one of the best drugs we have on the market. Exercise is cheap, safe, accessible to most patients (there is very little contraindication to exercising), and patient-empowering.”
He explained that exercise has favorable effects all over the body. By contrast, drugs target a particular receptor in one or a few organs.
“Consequently, I am not so sure how much we need a ceramide-lowering drug,” he concluded.
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