The Biological Variability of Plasma Ceramides in Healthy Subjects

Paola Ramos, Sarah M. Jenkins, Leslie J. Donato, Stacy J. Hartman, Amy Saenger, Nikola A. Baumann, Darci R. Block, Allan S. Jaffe, Jeffrey W. Meeusen

Research output: Contribution to journalArticlepeer-review


Background: Ceramides are bioactive lipid species that mediate numerous cell-signaling events. Elevated plasma ceramides concentration constitutes a risk factor for several pathologies. Multiple studies have affirmed the plasma concentrations of 4 specific ceramides (Cer16:0, Cer18:0, Cer24:0, and Cer24:1) can predict cardiovascular disease risk. Furthermore, these ceramides can be altered by many lipid-lowering therapies. Understanding the biological variability within an individual, and within a population, will further inform the clinical use of plasma ceramides as a biomarker. In this study, we aimed to define the intra- and interbiological variability of ceramides in a healthy reference population in a weekly and monthly manner. Methods: Fasting plasma from 24 healthy adults was collected daily (5 days), weekly (4 weeks), and monthly (7 months). Ceramide concentrations were measured with liquid chromatography-mass spectrometry (LC-MS). For analysis, we used random-effects regression models to estimate variance components. Results: The analytical variability was smaller compared to the biological variability overall. The greatest variation reported was between-subject variation for all ceramide species. The critical difference-reference change value (RCV) for within-subject variations monthly were 0.07 mcmol/L (Cer16:0), 0.04 mcmol/L (Cer18:0), 1.09 mcmol/L (Cer24:0), and 0.27 mcmol/L (Cer24:1). The index of individuality (IOI) of ceramides were 0.82 (Cer16:0), 0.96 (Cer18:0), 1.06 (Cer24:0), and 0.89 (Cer24:1). The most consistent ceramide species was Cer18:0 with the lowest within- and between-subject critical differences in weekly and monthly measurements. Conclusions: Overall, this study demonstrates that the variability of ceramide concentrations at different time points is minimal within individuals, allowing a single draw to be sufficient at least in a yearly time frame.

Original languageEnglish (US)
Pages (from-to)863-870
Number of pages8
JournalThe journal of applied laboratory medicine
Issue number4
StatePublished - Jul 1 2022


  • RCV
  • atherosclerotic cardiovascular disease
  • reference change value
  • sphingolipids

ASJC Scopus subject areas

  • General Medicine


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