Thyroid UK
82,739 members97,770 posts

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

One of the fundamental questions about thyroid hormones is precisely what they do. Even from where we are today, with unbelievably sensitive techniques for investigating biochemical pathways, we end up saying things like "thyroid hormone affects metabolism". That sort of approach, whilst fundamentally true, gives us very little understanding of exactly which pathways are affected, by how much, and so on.

This paper provides a tantalising glimpse of the effects at a low level (which molecules and pathways are affected). I have long thought it worth looking for every identifiable difference between those with no thyroid issues and those with. Who knows what we will find? Without looking, we won't find anything.

We might be able to use some of these effects to fine tune definitions of hypo- and hyper-thyroidism. We might have explanations for some of the many signs and symptoms reported. I hesitate to suggest that some observations might indicate potential targets for treatment because proper thyroid hormone treatment is likely the best answer, but perhaps reduced intake of some, and greater consumption of other, dietary constituents would enhance treatment?

The discussion of amino acid levels made me think that we just might be getting some idea as to why we see mucin (myxoedema) in those who are hypothyroid. If some pathways of amino acid metabolism are affected, we would, perhaps, see an increase in some - and those might result in production of, or retention of, the constituents of mucin.

Far too much optimism there - surely this paper will simply end up in the archive, largely ignored, for the indefinite future. There, a good dose of pessimism or reality. :-(

[ Added as most people have no idea what this substance is!

Trigonelline is an alkaloid with chemical formula C7H7NO2. It is a zwitterion formed by the methylation of the nitrogen atom of niacin (vitamin B3). Trigonelline is a product of niacin metabolism that is excreted in urine of mammals.[1]

Trigonelline occurs in many plants. It has been isolated from fenugreek seeds (Trigonella foenum-graecum, hence the name),[2] garden peas, hemp seed, oats,[3] potatoes, Stachys species, dahlia,[4] Strophanthus species,[5] and Dichapetalum cymosum.[6] Trigonelline is also found in coffee.[7] Higher levels of trigonelline is found in arabica coffee.

Holtz, Kutscher, and Theilmann have recorded its presence in a number of animals.[8] ]

PLoS One. 2017 Mar 2;12(3):e0173078. doi: 10.1371/journal.pone.0173078. eCollection 2017.

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

Friedrich N1,2, Pietzner M2, Cannet C3, Thuesen BH1, Hansen T4, Wallaschofski H2,5, Grarup N4, Skaaby T1, Budde K2, Pedersen O4, Nauck M2, Linneberg A1,6,7.

Author information

1Research Centre for Prevention and Health, The Capital Region of Denmark, Glostrup, Denmark.

2Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.

3Bruker BioSpin, Rheinstetten, Germany.

4Section of Metabolic Genetics, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.

5Private Practice Endocrinology, Erfurt, Germany.

6Department of Clinical Experimental Research, Rigshospitalet, Copenhagen, Denmark.

7Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.



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).


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.


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.


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.

PMID: 28253303

DOI: 10.1371/journal.pone.0173078

Full paper freely available here:

3 Replies

I have never read anything symptom wise regarding urine odour in hypothyroid patients. Before Levo treatment my urine had a very nasty smell, not fishy as in infection, but equally unpleasant so much so that I made sure others in the household who needed the toilet went before me as the odour filled the room. My sister, also hypo, didn't suffer from this. I had no discomfort and was very pleased when Levo treatment resolved the issue.


There is plenty about the general subject - but little that includes any link whatsoever to thyroid. The links below just might be of some interest - unless you are trying to put it all into the past! :-)

1 like


Me too re the foul smelling urine but also my sense of smell went into overdrive and I could smell horrible things everywhere - glad I am not a dog with 1million times better smell than us - It obviously does not repulse them tho! Perhaps my urine was not as bad as I thought - I will never know, but interesting to know I am not alone 😂😂😂🎻


You may also like...