Characterization of the metabolic profile associated with serum 25-hydroxyvitamin D: a cross-sectional analysis in population-based data.
Numerous observational studies have observed associations between vitamin D deficiency and cardiometabolic diseases, but these findings might be confounded by obesity. A characterization of the metabolic profile associated with serum 25-hydroxyvitamin D [25(OH)D] levels, in general and stratified by abdominal obesity, may help to untangle the relationship between vitamin D, obesity and cardiometabolic health.



Serum metabolomics measurements were obtained from a nuclear magnetic resonance spectroscopy (NMR)- and a mass spectrometry (MS)-based platform. The discovery was conducted in 1726 participants of the population-based KORA-F4 study, in which the associations of the concentrations of 415 metabolites with 25(OH)D levels were assessed in linear models. The results were replicated in 6759 participants (NMR) and 609 (MS) participants, respectively, of the population-based FINRISK 1997 study.



Mean [standard deviation (SD)] 25(OH)D levels were 15.2 (7.5) ng/ml in KORA F4 and 13.8 (5.9) ng/ml in FINRISK 1997; 37 metabolites were associated with 25(OH)D in KORA F4 at P < 0.05/415. Of these, 30 associations were replicated in FINRISK 1997 at P < 0.05/37. Among these were constituents of (very) large very-low-density lipoprotein and small low-density lipoprotein subclasses and related measures like serum triglycerides as well as fatty acids and measures reflecting the degree of fatty acid saturation. The observed associations were independent of waist circumference and generally similar in abdominally obese and non-obese participants.



Independently of abdominal obesity, higher 25(OH)D levels were associated with a metabolite profile characterized by lower concentrations of atherogenic lipids and a higher degree of fatty acid polyunsaturation. These results indicate that the relationship between vitamin D deficiency and cardiometabolic diseases is unlikely to merely reflect obesity-related pathomechanisms.
Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.|German Center for Cardiovascular Research (DZHK e.V.), Munich Heart Alliance, Munich, Germany.
Susanne
S
Vogt
Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.|Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.|German Center for Diabetes Research (DZD e.V.), München-Neuherberg, Germany.
Simone
S
Wahl
Computational Medicine, University of Oulu and Biocenter Oulu, Oulu, Finland.|NMR Metabolomics Laboratory, University of Eastern Finland, Kuopio, Finland.|National Institute for Health and Welfare, Helsinki, Finland.
Johannes
J
Kettunen
Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
Susanne
S
Breitner
Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
Gabi
G
Kastenmüller
Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.|Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.|German Center for Diabetes Research (DZD e.V.), München-Neuherberg, Germany.
Christian
C
Gieger
Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.|Department of Physiology and Biophysics, Weill Cornell Medical College in Qatar, Education City, Doha, Qatar.
Karsten
K
Suhre
Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.|Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
Melanie
M
Waldenberger
Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Leipzig, Leipzig, Germany.
Jürgen
J
Kratzsch
National Institute for Health and Welfare, Helsinki, Finland.|Institute for Molecular Medicine (FIMM) and Diabetes and Obesity Research Program, University of Helsinki, Helsinki, Finland.|Estonian Genome Center, University of Tartu, Tartu, Estonia.
Markus
M
Perola
National Institute for Health and Welfare, Helsinki, Finland.
Veikko
V
Salomaa
University Heart Center Hamburg, Clinic of General and Interventional Cardiology, Hamburg, Germany.|German Center for Cardiovascular Research (DZHK e.V.), Partner Site Hamburg/Lübeck/Kiel, Hamburg, Germany and.
Stefan
S
Blankenberg
University Heart Center Hamburg, Clinic of General and Interventional Cardiology, Hamburg, Germany.|German Center for Cardiovascular Research (DZHK e.V.), Partner Site Hamburg/Lübeck/Kiel, Hamburg, Germany and.
Tanja
T
Zeller
Computational Medicine, University of Oulu and Biocenter Oulu, Oulu, Finland.|NMR Metabolomics Laboratory, University of Eastern Finland, Kuopio, Finland.
Pasi
P
Soininen
Computational Medicine, University of Oulu and Biocenter Oulu, Oulu, Finland.
Antti J
AJ
Kangas
Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.|German Center for Cardiovascular Research (DZHK e.V.), Munich Heart Alliance, Munich, Germany.|German Center for Diabetes Research (DZD e.V.), München-Neuherberg, Germany.
Annette
A
Peters
Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.|Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.|German Center for Diabetes Research (DZD e.V.), München-Neuherberg, Germany.
Harald
H
Grallert
Computational Medicine, University of Oulu and Biocenter Oulu, Oulu, Finland.|NMR Metabolomics Laboratory, University of Eastern Finland, Kuopio, Finland.|Computational Medicine, School of Social and Community Medicine, University of Bristol and Medical Research Council Integrative Epidemiology Unit at the University of Bristol, Bristol, UK.
Mika
M
Ala-Korpela
Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany, thorand@helmholtz-muenchen.de.|Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
Barbara
B
Thorand
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015992:Body Mass Index; D003430:Cross-Sectional Studies; D005227:Fatty Acids / Q000097:blood*; D005260:Female; D005858:Germany; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D055442:Metabolome; D055432:Metabolomics; D008875:Middle Aged; D056128:Obesity, Abdominal / Q000097:blood* / Q000378:metabolism*; D012044:Regression Analysis; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood; D055105:Waist Circumference
D005227:Fatty Acids; D014807:Vitamin D; C104450:25-hydroxyvitamin D
25(OH)D; metabolomics; molecular epidemiology; obesity; vitamin D