Metabolic biomarkers in urine demonstrate quality of diet in European children

A large metabolic study of over 1000 children provides further evidence for the benefits of the Mediterranean diet and proposes urinary analysis as a method of assessing metabolic health and diet adherence.

The Mediterranean diet, which consists of fresh fruits, vegetables and cereals and olive oil, as well as moderate consumption of fish, poultry and dairy products, is commonly recommended by public health institutions as a dietary pattern that may reduce the risk of cardiovascular disease, type 2 diabetes and obesity. Though much research on the links between diet and disease has been conducted in this field, objective assessment of diet across large cohorts is difficult as studies often rely on self-reported data that may be inaccurate.

To complement survey data, an international team of researchers led by Hector Keun, professor of Biochemistry at Imperial College London (London, UK), and Leda Chatzi, professor of Population and Public Health Sciences at Keck School of Medicine of University of Southern California (CA, USA), utilized proton NMR spectroscopy to analyze samples of urine from over 1147 European children in six research cohorts to investigate correlations between urinary metabolites and dietary patterns. Adherence to the Mediterranean diet or an ‘Ultra Processed Food’ diet consisting of foods that result from a series of industrial processes such as fractioning of whole foods and use of food additives and modifications was assessed via questionnaires completed by the children’s parents.

The researchers also assessed the concentrations of C-peptide – a short protein that is co-secreted with insulin by the pancreas and which is a useful biomarker for how much insulin the body produces – in blood plasma samples from the same children. The literature suggests that C-peptide levels in the blood are indicative of insulin resistance, which is implicated in the development of obesity and type 2 diabetes.

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Results from this study, published in eLife in January, demonstrated that high levels of hippurate, N-methylnicotinic acid and urea, as well as low levels of sucrose, were correlated with adherence to the Mediterranean diet, whereas the opposite trends were associated with diets including ultra-processed foods. C-peptide levels in the blood were also negatively correlated with the Mediterranean diet, and positively correlated with the ultra-processed food diet. This methodology and the correlations that it has identified could be employed in future studies on diet and health to allow a more objective assessment of food intake.

The study was carried out in children as the authors identified a gap in the literature regarding children; most previous studies in this area have focused on adult metabolic profiles despite the importance of childhood diet on future health and the variations in metabolite profiles between children and adults. The researchers hope that these data provide evidence of the biological pathways that characterize healthy and unhealthy diets, and that future work will be able to utilize these methods to further elucidate the mechanistic link between diet and disease progression, particularly in children.

Although large, statistical studies can generate spurious correlations, this study controlled for sociodemographic and lifestyle factors that may be associated with diet (such as affluence, sedentary behavior and parental educational qualifications) and cross-checked the correlations across the six cohorts to validate them. Additionally, there are theoretical justifications for the biomarkers-diet correlations; hippurate is a product of fruit and vegetable intake via phenol catabolism, N-methylnicotinic acid is a product of the metabolism of niacin which is commonly found in legumes such as lentils and peanuts, and urea is the main end-product of protein catabolism and therefore indicates protein intake.

Alexandros Siskos, a research associate at Imperial College London, commented:

“The objective assessment of dietary habits is important for the prevention of chronic diseases. Public health organizations typically base their recommendations on research on dietary habits.”

Chatzi added:

“Further studies examining the association of diet quality and related metabolomic profiles with C-peptide will also be needed to replicate our findings. For now, our work provides further evidence to support efforts by public health authorities to recommend increased adherence to a Mediterranean diet. Limiting the consumption of ultra-processed foods in childhood could lower the risk of disease later on.”

Sources: Stratakis N, Siskos AP, Papadopoulou E, et al. Urinary metabolic biomarkers of diet quality in European children are associated with metabolic health. eLife 11, e71332 (2022).eLife press release https://elifesciences.org/for-the-press/ed1eb45e/urinary-metabolic-signatures-predict-diet-quality-and-metabolic-health-in-european-children