Science

Ceramides are lipids and they belong to the sphingolipid class. Sphingolipids and ceramides were discovered as early as in the 19th century. In the 1990s, ceramides were found to be signaling molecules as they were found to induce apoptosis and inhibit insulin-mediated glucose absorption. Since then, ceramides have been studied in connection with diabetes and cancer.

In 2010s ceramides ability to predict cardiovascular death and severe myocardial infarctions was discovered from German LURIC-trial. 600 different lipid molecules were analyzed from the trial, and four ceramides and their ratios were identified as best predictors for cardiovascular death and severe myocardial infarctions. (Tarasov et al. 2014)

Thereafter, ceramides and CERT-test were validated in Finnish COROGENE- and FINRISK 2002 -studies as well as in Norwegian BECAC-study and Swiss SPUM-ACS-studies (Laaksonen et al. 2016, Havulinna et al. 2016). Cardiovascular risk ceramides have been also validated in Norwegian WECAC-study, German KAROLA-study and in LIPID-trial originated from Australia and New Zealand (Hilvo et al. 2019). Mayo Clinic validated ceramides and CERT Score in their own study where ceramides were measured from 500 Mayo Clinic patients. In the study, ceramides predicted cardiovascular events both in healthy and in coronary artery disease patients (Meeusen et al. 2018).

Furthermore, ceramides have been analyzed and CERT validated in a large global STABILITY-trial consisting of 11 222 stable coronary heart disease patients. The results confirmed the association of CERT and cardiovascular events and its robust performance in a global population. In addition, the study shows association of CERT with strokes and heart failure hospitalization. (Hilvo et al. 2020)

Interestingly, STABILITY results show that CERT is associated with biomarkers indicating inflammation, myocardial necrosis, myocardial dysfunction, renal dysfunction, and dyslipidemia. CERT was strongly associated with LDL-cholesterol and triglycerides, which confirms that ceramides are associated with hyperlipidemia. CERT Score was also associated with inflammatory markers hs-CRP and interleukin-6, suggesting the role of ceramides in vascular inflammation. Thus, the findings show that CERT could reflect both lipid and inflammatory residual risk in heart disease patients. Also, CERT can be used in evaluating residual risk in patients, who are already on optimal medical therapy. The study shows that coronary heart disease patients are not on similar risk level although being on optimal medical therapy. (Hilvo et al. 2020)

Additionally, we have analyzed various clinical studies and trials (yet unpublished) from the United States, Sweden, Netherlands, Norway, Germany and from Finland. So far in total, we have analyzed cardiovascular risk ceramides from 100 000 clinical study samples. The aim is to continue the high-quality clinical research work, and especially to concentrate on treatment outcome trials.      

The follow-up times in the studies analyzed so far vary from one year up to 13 years. Patients have been selected to studies based on their symptoms, event history, angiography findings, or due to their acute cardiovascular events. During the follow-up time, some of the patients have experienced myocardial infarction or died due to cardiovascular disease. The studies also provide background information on treatments and, in some cases, lifestyle, such as diet.

What are ceramides?

Ceramides are lipids and they belong to the sphingolipid class. Ceramides are essential structural part of cell membrane, but also ceramides are bioactive signaling lipids participating in many biologically crucial functions. Ceramides participate in regulation of many cellular and biochemical functions such as cell differentiation and proliferation, adhesion, inflammation and apoptosis (programmed cell death). 

Ceramides are transported in circulation by different lipoproteins. Ceramides are located on the surface of lipoprotein particles together with phospholipids, unesterified cholesterol, and apolipoproteins.

Ceramides have significant role in the development of unstable atherosclerotic cardiovascular disease and in the onset and type 2 diabetes. Ceramides accumulate in the atherosclerotic plaques and are involved in the formation of unstable plaques. Also, ceramides participate in the development of insulin resistance.

Read more on ceramides.

Publications by others:

Meeusen et al. 2018 Plasma Ceramides – A Novel Predictor of Major Adverse Cardiovascular Events After Coronary Angiography. ATVB 2018; 38:1933–1939. Link to the article

Carvalho et al. 2018 Plasma Ceramides as Prognostic Biomarkers and Their Arterial and Myocardial Tissue Correlates in Acute Myocardial Infarction JACC 2018, 3(2):163-175. Link to the article

Mantovani et al. 2018 Association between plasma ceramides and inducible myocardial ischemia in patients with established or suspected coronary artery disease undergoing myocardial perfusion scintigraphy. Metabolism 2018, 85: 305-312. Link to the article

Peterson et al. 2018 Ceramide Remodeling and Risk of Cardiovascular Events and Mortality. J Am Heart Assoc. 2018, 3;7(10). Link to the article

Summers 2018 Could Ceramides Become the New Cholesterol. Cell Metabolism 27 (2), 276-280. Link to the article

Wang DD et al. 2017 Plasma Ceramides, Mediterranean Diet, and Incident Cardiovascular Disease in the PREDIMED Trial (Prevención con Dieta Mediterránea). Circulation. 2017, 135(21):2028-2040. Link to the article

Chaurasia & Summers 2015 Ceramides – Lipotoxic Inducers of Metabolic Disorders. Trends Endocrinol Metab. 2015, 26(10):538-50. Link to the article

Kasumov et al. 2015 Improved insulin sensitivity after exercise training is linked to reduced plasma C14:0 ceramide in obesity and type 2 diabetes. Obesity (Silver Spring). 2015; 23:1414-21. Link to the article

Chavez & Summers 2012 A ceramide-centric view of insulin resistance. Cell Metab, 2012, 15(5):585-94. Link to the article

Bikman & Summers 2011 Ceramides as modulators of cellular and whole-body metabolism. J Clin Invest. 2011, 121(11):4222-30. Link to the article

Holland & Summers 2008 Sphingolipids, insulin resistance, and metabolic disease: new insights from in vivo manipulation of sphingolipid metabolism. Endocr Rev. 2008, 29(4):381-402. Link to the article