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Cited by 13Thyroid Disorders and TreatmentsMetabolomics and Mass Spectrometry StudiesCoffee research and impacts

A Thyroid Hormone-Independent Molecular Fingerprint of 3,5-Diiodothyronine Suggests a Strong Relationship with Coffee Metabolism in Humans

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Pietzner, Maik, Köhrle, Josef, Lehmphul, Ina, Budde, Kathrin, Kastenmüller, Gabi, Brabant, Georg, Völzke, Henry, Artati, Anna +5 more·2019·Thyroid®
DOI 10.1089/thy.2018.0549PMC PMC6918876
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Abstract

Background: In numerous studies based predominantly on rodent models, administration of 3,5-diiodo-L-thyronine (3,5-T2), a metabolite of the thyroid hormones (TH) thyroxine (T4) and triiodo-L-thyronine (T3), was reported to cause beneficial health effects, including reversal of steatohepatosis and prevention of insulin resistance, in most instances without adverse thyrotoxic side effects. However, the empirical evidence concerning the physiological relevance of endogenously produced 3,5-T2 in humans is comparatively poor. Therefore, to improve the understanding of 3,5-T2-related metabolic processes, we performed a comprehensive metabolomic study relating serum 3,5-T2 concentrations to plasma and urine metabolite levels within a large general population sample. Methods: Serum 3,5-T2 concentrations were determined for 856 participants of the population-based Study of Health in Pomerania-TREND (SHIP-TREND). Plasma and urine metabolome data were generated using mass spectrometry and nuclear magnetic resonance spectroscopy, allowing quantification of 613 and 578 metabolites in plasma and urine, respectively. To detect thyroid function-independent significant 3,5-T2—metabolite associations, linear regression analyses controlling for major confounders, including thyrotropin and free T4, were performed. The same analyses were carried out using a sample of 16 male healthy volunteers treated for 8 weeks with 250 μg/day levothyroxine to induce thyrotoxicosis. Results: The specific molecular fingerprint of 3,5-T2 comprised 15 and 73 significantly associated metabolites in plasma and urine, respectively. Serum 3,5-T2 concentrations were neither associated with classical thyroid function parameters nor altered during experimental thyrotoxicosis. Strikingly, many metabolites related to coffee metabolism, including caffeine and paraxanthine, formed the clearest positively associated molecular signature. Importantly, these associations were replicated in the experimental human thyrotoxicosis model. Conclusion: The molecular fingerprint of 3,5-T2 demonstrates a clear and strong positive association of the serum levels of this TH metabolite with plasma levels of compounds indicating coffee consumption, therefore pointing to the liver as an organ, the metabolism of which is strongly affected by coffee. Furthermore, 3,5-T2 serum concentrations were found not to be directly TH dependent. Considering the beneficial health effects of 3,5-T2 administration observed in animal models and those of coffee consumption demonstrated in large epidemiological studies, one might speculate that coffee-stimulated hepatic 3,5-T2 production or accumulation represents an important molecular link in this connection.

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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 [45]

    The Discussion (page unavailable) reports a clear link between the thyroid hormone metabolite 3,5-T2 and coffee-related metabolites, and calls it the first clear association between 3,5-T2 and a physiologically relevant trait in a larger human sample. It does not establish the broader claim that this was the first link between coffee consumption and any thyroid hormone metabolite. (LLM, conf=0.78)

    Experimental — accuracy not yet measured

  • There was a lack of a clear association between 3,5-T2 concentrations and serum T4 and/or T3 concentrations.

    “Of special interest was, similar to the previous studies, the lack of a clear association with serum T4 and/or T3 concentrations (44, 45).”

    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 [45]

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Authors
Pietzner, M., Köhrle, J., Lehmphul, I., Budde, K., Kastenmüller, G., Brabant, G., Völzke, H., Artati, A., Adamski, J., Völker, U., Nauck, M., Friedrich, N., & Homuth, G.
Affiliations
  • University of Cambridge (GB)
  • Humboldt-Universität zu Berlin (DE)
  • Universitätsmedizin Greifswald (DE)
  • Helmholtz Munich (DE)
  • University of Lübeck (DE)
  • National University of Singapore (SG)
Corresponding author
  • Pietzner, Maik
  • Homuth, Georg
ORCID
Venue
Thyroid®
Publisher
SAGE Publications
Published
2019-12
Volume
29
Issue
12
Pages
1743-1754
ISSN
  • 1050-7256 (ISSN-L)
  • 1557-9077
DOI
10.1089/thy.2018.0549
PMC
PMC6918876
OpenAlex
W2978913985
Cited by
13
References
8
Citations by year
2025: 2 · 2024: 1 · 2023: 4 · 2022: 1 · 2021: 1 · 2020: 4
FWCI
0.79
Type
journal article
Language
en
Open access
Licence
Locations
  • Thyroid (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion, cc-by)
  • mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion, other-oa)
  • Site cant be reached (submittedVersion, cc-by)
  • Apollo (University of Cambridge) (submittedVersion, cc-by)
  • Apollo (cc-by)
Funders
  • Deutsche Forschungsgemeinschaft
  • Bundesministerium für Bildung und Forschung (01ZZ0403, 01GI0883, 01ZZ0403, 01ZZ0103, 01GI0883, AtheroSysMed 03IS2061B, 01ZZ0103, AtheroSysMed 03IS2061B)
  • Medical Research Council (MC_UU_12015/1)
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
  • Health Sciences › Medicine › Pharmacology › Coffee research and impacts
Keywords
thyroid hormone metabolites, caffeine, paraxanthine, thyrotoxicosis, levothyroxine, hepatic metabolism, plasma metabolome, urinary metabolome, molecular fingerprints, thyroid function, insulin resistance, healthy volunteers
MeSH terms
Adult, Caffeine, Coffee, Diiodothyronines, Female, Humans, Male, Middle Aged, Magnetic Resonance Spectroscopy, Reference Values, Mass Spectrometry, Thyroid Function Tests, Thyroid Hormones, Thyrotoxicosis, Thyrotropin, Thyroxine, DNA Fingerprinting, Metabolomics, Healthy Volunteers

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Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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