Reliability of Serum Metabolites over a Two-Year Period: A Targeted Metabolomic Approach in Fasting and Non-Fasting Samples from EPIC.
OBJECTIVE
Although metabolic profiles have been associated with chronic disease risk, lack of temporal stability of metabolite levels could limit their use in epidemiological investigations. The present study aims to evaluate the reliability over a two-year period of 158 metabolites and compare reliability over time in fasting and non-fasting serum samples.


METHODS
Metabolites were measured with the AbsolueIDQp180 kit (Biocrates, Innsbruck, Austria) by mass spectrometry and included acylcarnitines, amino acids, biogenic amines, hexoses, phosphatidylcholines and sphingomyelins. Measurements were performed on repeat serum samples collected two years apart in 27 fasting men from Turin, Italy, and 39 non-fasting women from Utrecht, The Netherlands, all participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Reproducibility was assessed by estimating intraclass correlation coefficients (ICCs) in multivariable mixed models.


RESULTS
In fasting samples, a median ICC of 0.70 was observed. ICC values were <0.50 for 48% of amino acids, 27% of acylcarnitines, 18% of lysophosphatidylcholines and 4% of phosphatidylcholines. In non-fasting samples, the median ICC was 0.54. ICC values were <0.50 for 71% of acylcarnitines, 48% of amino acids, 44% of biogenic amines, 36% of sphingomyelins, 34% of phosphatidylcholines and 33% of lysophosphatidylcholines. Overall, reproducibility was lower in non-fasting as compared to fasting samples, with a statistically significant difference for 19-36% of acylcarnitines, phosphatidylcholines and sphingomyelins.


CONCLUSIONS
A single measurement per individual may be sufficient for the study of 73% and 52% of the metabolites showing ICCs >0.50 in fasting and non-fasting samples, respectively. ICCs were higher in fasting samples that are preferable to non-fasting.
International Agency for Research on Cancer, Lyon, France.
Marion
M
Carayol
International Agency for Research on Cancer, Lyon, France; Institute of Community Medicine, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway.
Idlir
I
Licaj
International Agency for Research on Cancer, Lyon, France.
David
D
Achaintre
Unit of Cancer Epidemiology, AO Citta' della Salute e della Scienza-University of Turin and Center for Cancer Prevention (CPO-Piemonte), Turin, Italy.
Carlotta
C
Sacerdote
Human Genetics Foundation (HuGeF), Turin, Italy; School of Public Health, Imperial College London, London, United Kingdom.
Paolo
P
Vineis
Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
Timothy J
TJ
Key
Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, The Netherlands.
N Charlotte
NC
Onland Moret
International Agency for Research on Cancer, Lyon, France.
Augustin
A
Scalbert
International Agency for Research on Cancer, Lyon, France.
Sabina
S
Rinaldi
International Agency for Research on Cancer, Lyon, France.
Pietro
P
Ferrari
D000328:Adult; D005215:Fasting / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D055442:Metabolome; D055432:Metabolomics; D008875:Middle Aged