Metabolites of milk intake: a metabolomic approach in UK twins with findings replicated in two European cohorts
Metabolites of milk intake: a metabolomic approach in UK twins with findings replicated in two European cohorts
Tess Pallister 0 1 2 4 5 6
Toomas Haller 0 1 2 4 5 6
Barbara Thorand 0 1 2 4 5 6
Elisabeth Altmaier 0 1 2 4 5 6
Aedin Cassidy 0 1 2 4 5 6
Tiphaine Martin 0 1 2 4 5 6
Amy Jennings 0 1 2 4 5 6
Robert P. Mohney 0 1 2 4 5 6
Christian Gieger 0 1 2 4 5 6
Alexander MacGregor 0 1 2 4 5 6
Gabi Kastenmüller 0 1 2 4 5 6
Andres Metspalu 0 1 2 4 5 6
Tim D. Spector 0 1 2 4 5 6
Cristina Menni 0 1 2 4 5 6
0 Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health , Ingolstädter Landstraße 1, 85764 Neuherberg , Germany
1 Estonian Genome Center, University of Tartu , Tartu , Estonia
2 Department of Twin Research and Genetic Epidemiology, St Thomas Hospital, King's College London , London SE1 7EH , UK
3 Cristina Menni
4 Research Unit of Molecular Epidemiology, Helmholtz Zentrum München , 85764 Neuherberg , Germany
5 Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health , Ingolstädter Landstraße 1, 85764 Neuherberg , Germany
6 Institute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health , Ingolstädter Landstraße 1, 85764 Neuherberg , Germany
Purpose Milk provides a significant source of calcium, protein, vitamins and other minerals to Western populations throughout life. Due to its widespread use, the metabolic and health impact of milk consumption warrants further investigation and biomarkers would aid epidemiological studies. Methods Milk intake assessed by a validated food frequency questionnaire was analyzed against fasting blood metabolomic profiles from two metabolomic platforms in females from the TwinsUK cohort (n = 3559). The top metabolites were then replicated in two independent populations (EGCUT, n = 1109 and KORA, n = 1593), and the results from all cohorts were meta-analyzed.
Department of Nutrition, Norwich Medical School, University of East Anglia, Norwich, UK
Metabolon, Inc., Durham, NC, USA
Conclusions We identified and replicated in
independent populations four novel biomarkers of milk intake:
trimethyl-N-aminovalerate, uridine,
hydroxysphingomyelin C14:1 and diacylphosphatidylcholine C28:1. Together,
these metabolites have potential to objectively examine and
refine milk-disease associations.
Abbreviations
DZ
EGCUT
KORA
PC aa C28:1
MZ
SM(OH) C14:1
Introduction
Dizygotic
Estonian Genome Center of the
University of Tartu
Cooperative Health Research in the
Region of Augsburg
Diacylphosphatidylcholine C28:1
Monozygotic
Hydroxysphingomyelin C14:1
Milk and dairy products have been consumed throughout
life by lactase-producing cultures for thousands of years,
aided by the lactase persistence/dairying co-evolution
estimated to have occurred 7500 years ago [
1
]. They provide
excellent sources of calcium and other micronutrients for
many populations around the world [
2
]. Studies of the
long-term health and metabolic implications of dairy
product consumption based on recall have, however, yielded
inconsistencies [
3
]. Epidemiological studies have mainly
explored relationships with combined dairy product intake,
though different products may promote different
physiological effects, which may be due to varying
macronutrient contents (reduced lactose and whey fraction),
microbiological species (and their metabolic products) or altered
nutrient absorption as a result of processing [
3
]. Of all
dairy products, fluid milk is consumed the most frequently
in many Western countries though consumption has been
declining in some, such as the USA [
4
] and UK [
5
] likely
due to health concerns about fat. Milk consumption is
generally encouraged throughout life, for the growth of strong
bones and teeth during childhood through to aging women
for the prevention of osteoporosis and fractures [
6
]. The
evidence for the long-term consumption of milk on health
outcomes from observational studies has been somewhat
inconsistent, with a meta-analysis of 17 prospective studies
suggestive of a protective effect on CVD and no
relationship with mortality [
7
], while two large Swedish cohorts
identified associations with mortality [
8
]. Usage of
different questionnaires to measure milk intake as well as
recall bias complicates large population comparisons; thus,
incorporation of objective biomarkers into epidemiological
methods is essential.
Metabolomics provides a snapshot of the metabolic
status of an individual by high-throughput measurement of
small metabolites and has the potential to refine
diet–disease associations, primarily through food biomarker
identification and providing insight into novel nutrient and
disease pathways [
9
]. A recent example involved using
metabolites of alcohol to predict indices of cardiovascular
health [
10
]. A limiting factor in many metabolomic
studies is the amount of inter-indivi (...truncated)