The human plasma-metabolome: Reference values in 800 French healthy volunteers; impact of cholesterol, gender and age

• Published in: PloS one Vol. 12; no. 3; p. e0173615
• Main Authors: Trabado, Séverine, Al-Salameh, Abdallah, Croixmarie, Vincent, Masson, Perrine, Corruble, Emmanuelle, Fève, Bruno, Colle, Romain, Ripoll, Laurent, Walther, Bernard, Boursier-Neyret, Claire, Werner, Erwan, Becquemont, Laurent, Chanson, Philippe
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 09.03.2017; Public Library of Science (PLoS)
• Subjects: Adolescent; Adult; Age; Age Factors; Aged; Aged, 80 and over; Aging; Amines; Amino acids; Atherosclerosis; Biogenic amines; Biological markers; Biology and Life Sciences; Biomarkers; Biomarkers - blood; Blood; Blood plasma; Chain branching; Cholesterol; Cholesterol - metabolism; Creatinine; Cross-Sectional Studies; Demographic aspects; Drugs; Family medical history; Female; France; Gender; Geriatrics; Health aspects; Healthy Volunteers; Hexose; Humans; Insulin-like growth factors; Laboratory tests; Life Sciences; Lipids; Male; Mass spectrometry; Mass spectroscopy; Medical research volunteers; Medicine and Health Sciences; Metabolism; Metabolites; Metabolome; Metabolomics; Metabolomics - methods; Middle Aged; Nutrition research; Older people; Oxidative stress; Plasma; Plasma levels; Population; Principal Component Analysis; Principal components analysis; Reference Values; Sex Characteristics; Studies; Variability; Young Adult; France
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0173615

Metabolomic approaches are increasingly used to identify new disease biomarkers, yet normal values of many plasma metabolites remain poorly defined. The aim of this study was to define the "normal" metabolome in healthy volunteers. We included 800 French volunteers aged between 18 and 86, equally distributed according to sex, free of any medication and considered healthy on the basis of their medical history, clinical examination and standard laboratory tests. We quantified 185 plasma metabolites, including amino acids, biogenic amines, acylcarnitines, phosphatidylcholines, sphingomyelins and hexose, using tandem mass spectrometry with the Biocrates AbsoluteIDQ p180 kit. Principal components analysis was applied to identify the main factors responsible for metabolome variability and orthogonal projection to latent structures analysis was employed to confirm the observed patterns and identify pattern-related metabolites. We established a plasma metabolite reference dataset for 144/185 metabolites. Total blood cholesterol, gender and age were identified as the principal factors explaining metabolome variability. High total blood cholesterol levels were associated with higher plasma sphingomyelins and phosphatidylcholines concentrations. Compared to women, men had higher concentrations of creatinine, branched-chain amino acids and lysophosphatidylcholines, and lower concentrations of sphingomyelins and phosphatidylcholines. Elderly healthy subjects had higher sphingomyelins and phosphatidylcholines plasma levels than young subjects. We established reference human metabolome values in a large and well-defined population of French healthy volunteers. This study provides an essential baseline for defining the "normal" metabolome and its main sources of variation.