Metabolites of milk intake: a metabolomic approach in UK twins with findings replicated in two European cohorts

Tess Pallister, Toomas Haller, Barbara Thorand, Elisabeth Altmaier, Aedin Cassidy, Tiphaine Martin, Amy Jennings, Robert P. Mohney, Christian Gieger, Alexander MacGregor, Gabi Kastenmüller, Andres Metspalu, Tim D. Spector, Cristina Menni

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Abstract

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. Results Four metabolites were significantly associated with milk intake in the TwinsUK cohort after adjustment for multiple testing (P < 8.08 × 10−5) and covariates (BMI, age, batch effects, family relatedness and dietary covariates) and replicated in the independent cohorts. Among the metabolites identified, the carnitine metabolite trimethyl-N-aminovalerate (β = 0.012, SE = 0.002, P = 2.98 × 10−12) and the nucleotide uridine (β = 0.004, SE = 0.001, P = 9.86 × 10−6) were the strongest novel predictive biomarkers from the non-targeted platform. Notably, the association between trimethyl-N-aminovalerate and milk intake was significant in a group of MZ twins discordant for milk intake (β = 0.050, SE = 0.015, P = 7.53 × 10−4) and validated in the urine of 236 UK twins (β = 0.091, SE = 0.032, P = 0.004). Two metabolites from the targeted platform, hydroxysphingomyelin C14:1 (β = 0.034, SE = 0.005, P = 9.75 × 10−14) and diacylphosphatidylcholine C28:1 (β = 0.034, SE = 0.004, P = 4.53 × 10−16), were also replicated. 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.
Original languageEnglish
Pages (from-to)2379–2391
JournalEuropean Journal of Nutrition
Volume56
Issue number7
Early online date28 Jul 2016
DOIs
Publication statusPublished - 01 Oct 2017

Bibliographical note

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Keywords

  • Nutrition
  • Metabolomics
  • Twins
  • Biomarkers
  • Milk

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    Pallister, T., Haller, T., Thorand, B., Altmaier, E., Cassidy, A., Martin, T., Jennings, A., Mohney, R. P., Gieger, C., MacGregor, A., Kastenmüller, G., Metspalu, A., Spector, T. D., & Menni, C. (2017). Metabolites of milk intake: a metabolomic approach in UK twins with findings replicated in two European cohorts. European Journal of Nutrition, 56(7), 2379–2391. https://doi.org/10.1007/s00394-016-1278-x