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Cited by 23Thyroid Disorders and TreatmentsMetabolomics and Mass Spectrometry StudiesMetabolism and Genetic Disorders

Urinary metabolomics reveals glycemic and coffee associated signatures of thyroid function in two population-based cohorts

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Friedrich, Nele, Pietzner, Maik, Cannet, Claire, Thuesen, Betina H., Hansen, Torben, Wallaschofski, Henri, Grarup, Niels, Skaaby, Tea +4 more·2017·PLOS ONE
DOI 10.1371/journal.pone.0173078PMC PMC5333857
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Abstract

BACKGROUND: Triiodothyronine (T3) and thyroxine (T4) as the main secretion products of the thyroid affect nearly every human tissue and are involved in a broad range of processes ranging from energy expenditure and lipid metabolism to glucose homeostasis. Metabolomics studies outside the focus of clinical manifest thyroid diseases are rare. The aim of the present investigation was to analyze the cross-sectional and longitudinal associations of urinary metabolites with serum free T4 (FT4) and thyroid-stimulating hormone (TSH). METHODS: Urine Metabolites of participants of the population-based studies Inter99 (n = 5620) and Health2006/Health2008 (n = 3788) were analyzed by 1H-NMR spectroscopy. Linear or mixed linear models were used to detect associations between urine metabolites and thyroid function. RESULTS: Cross-sectional analyses revealed positive relations of alanine, trigonelline and lactic acid with FT4 and negative relations of dimethylamine, glucose, glycine and lactic acid with log(TSH). In longitudinal analyses, lower levels of alanine, dimethylamine, glycine, lactic acid and N,N-dimethylglycine were linked to a higher decline in FT4 levels over time, whereas higher trigonelline levels were related to a higher FT4 decline. Moreover, the risk of hypothyroidism was higher in subjects with high baseline trigonelline or low lactic acid, alanine or glycine values. CONCLUSION: The detected associations mainly emphasize the important role of thyroid hormones in glucose homeostasis. In addition, the predictive character of these metabolites might argue for a potential feedback of the metabolic state on thyroid function. Besides known metabolic consequences of TH, the link to the urine excretion of trigonelline, a marker of coffee consumption, represents a novel finding of this study and given the ubiquitous consumption of coffee requires further research.

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  • This observation is the first one to link a THM to coffee consumption.

    “This observation is the first one to link a THM to coffee consumption, and so far, no clear-cut hypothesis has been tested to challenge a potential causal relationship (45, 46).”

    From 3,5-T2—A Janus-Faced Thyroid Hormone Metabolite Exerts Both Canonical T3-Mimetic Endocrine and Intracrine Hepatic Action (2020) · cites this paper as [46]

    The Discussion (Coffee metabolism) links urinary trigonelline, a marker of coffee consumption, with FT4 and says the reason for the association remains speculative. But it also says an association between trigonelline and the thyroid-hormone metabolite 3,5-T2 had been reported previously, so this paper does not support calling its observation the first link between a thyroid-hormone metabolite and coffee consumption. (LLM, conf=0.84)

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Cited by

Sorted by citations

Authors
Friedrich, N., Pietzner, M., Cannet, C., Thuesen, B. H., Hansen, T., Wallaschofski, H., Grarup, N., Skaaby, T., Budde, K., Pedersen, O., Nauck, M., & Linneberg, A.
Affiliations
  • Universitätsmedizin Greifswald (DE)
  • Bruker (Germany) (DE)
  • Capital Region of Denmark (DK)
  • University of Copenhagen (DK)
Corresponding author
Friedrich, Nele
ORCID
Venue
PLOS ONE
Publisher
Public Library of Science (PLoS)
Published
2017-03-02
Volume
12
Issue
3
Pages
e0173078
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0173078
PMC
PMC5333857
OpenAlex
W2592561541
Cited by
23
References
8
Citations by year
2026: 1 · 2025: 2 · 2024: 1 · 2022: 4 · 2021: 2 · 2020: 2 · 2019: 7 · 2018: 4
FWCI
2.71
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
Funders
European Union’s Horizon 2020 research and innovation programme (657595)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
Keywords
urinary metabolites, thyroid function, free thyroxine, thyroid-stimulating hormone, hypothyroidism, glucose homeostasis, trigonelline, coffee consumption, alanine, lactic acid, glycine, dimethylamine, N,N-dimethylglycine, thyroid hormones
MeSH terms
Adult, Blood Glucose, Coffee, Female, Humans, Male, Middle Aged, Thyroid Function Tests, Metabolomics, Proton Magnetic Resonance Spectroscopy

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