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Effect of cheese and butter intake on metabolites in urine using an untargeted metabolomics approach

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Abstract

Cheese intake has been shown to decrease total cholesterol and LDL cholesterol concentrations when compared to butter of equal fat content. An untargeted metabolite profiling may reveal exposure markers of cheese but may also contribute with markers which can help explain how the intake of cheese affects cholesterol concentrations. Twenty-three subjects collected 2 × 24 h urine samples after 6 weeks of cheese and 6 weeks of butter intake with equal amounts of fat in a cross-over intervention study. The samples were analyzed by UPLC-QTOF/MS. A two-step univariate data analysis approach using linear mixed model was applied separately for positive and negative ionization mode: In the first step a total of 44 features related to treatment were identified and in the second step 36 of these features were related to total cholesterol concentrations. Cheese intake resulted in increased urinary indoxyl sulfate, xanthurenic acid, tyramine sulfate, 4-hydroxyphenylacetic acid, isovalerylglutamic acid and several acylglycines including isovalerylglycine, tiglylglycine and isobutyrylglycine when compared to butter intake of equal fat content. The biological mechanisms of action linking the metabolites to cholesterol concentrations need to be further explored.

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Abbreviations

CVD:

Cardiovascular disease

ESI:

Electrospray ionization

LDL:

Low-density lipoprotein

PABA:

Para-aminobenzoic acid

RT:

Retention time

UPLC-QTOF/MS:

Ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry

XA:

Xanthurenic acid

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Acknowledgments

We would like to thank Sarah Schultz John for preparing the samples for analysis, Ümmühan Celik for preprocessing of data in MZmine, Maj-Britt Scmidt Andersen and Daniella Rago for laboratory assistance and Göezde Gürdeniz and Jan Stanstrup for sharing scripts in MATLAB. The research was supported by the Danish Dairy Research Foundation, DK-8260 Viby J, Denmark and the Dairy Research Institute, Rosemont, IL, USA.

Conflicts of interest

Julie Bousgaard Hjerpsted, Christian Ritz, Simon Stubbe Schou, Tine Tholstrup, Lars Ove Dragsted declared that they have no conflict of interest.

Ethical standards

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all participants being included in the study.

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Authors and Affiliations

  1. Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, 1958, Frederiksberg, Denmark

    Julie Bousgaard Hjerpsted, Christian Ritz, Simon Stubbe Schou, Tine Tholstrup & Lars Ove Dragsted

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  1. Julie Bousgaard Hjerpsted
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  2. Christian Ritz
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  3. Simon Stubbe Schou
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  4. Tine Tholstrup
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  5. Lars Ove Dragsted
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Correspondence to Lars Ove Dragsted.

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Hjerpsted, J.B., Ritz, C., Schou, S.S. et al. Effect of cheese and butter intake on metabolites in urine using an untargeted metabolomics approach. Metabolomics 10, 1176–1185 (2014). https://doi.org/10.1007/s11306-014-0657-7

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