Use of stable isotopes and mathematical modelling to investigate human mineral metabolism

Abstract

Individuals have varying needs for minerals that are dependent, amongst other things, on their lifestyle, age and genetic makeup. Knowledge of exact individual nutritional requirements should lead to better health, increased quality of life and reduced need for expensive medical care. Bioavailability, nutrient-gene interactions and whole-body metabolism all need to be investigated further if we are to progress towards the goal of defining optimal health and nutritional status. The discussion which follows will critically review the latest developments in the area of metabolism for several of the minerals that are essential for human health: Ca, Zn, Cu and Se. Stable-isotope tracers and mathematical modelling are some of the tools being used to facilitate the greater understanding in uptake, utilisation and excretion of these minerals. Stable isotopes, administered in physiological doses, present little or no risk to volunteers and allow metabolic studies to be carried out in vulnerable population groups such as children and pregnant women. Intrinsic labelling of foodstuffs ensures that the tracer and the native mineral will behave similarly once inside the body. Advances in computing power and software dedicated to solving nutritional problems have made it possible for investigators to use mathematical modelling in their experimental work. Mineral metabolism is ideally suited to a form of modelling known as compartmental analysis, which allows rates of mineral transfer and sizes of mineral stores to be calculated accurately without the need for invasive sampling of body tissues. Stable isotopes: Mathematical modelling: Mineral metabolismNutrition Research Reviews (2001) , IntroductionMost minerals have several naturally-occurring stable isotopes, all with a fixed abundance. In order to follow the metabolism of a mineral, it is necessary to ingest it in an altered form so that it can be distinguished from the naturally-abundant mineral. The form of the ingested mineral can be altered by enriching one of the low-abundance isotopes. This so-called 'tracer' or 'label' is injected and/or taken orally and its appearance in the plasma, urine and faeces can be monitored over several days. The concept of a tracer is important in isotope work. A true tracer is one that does not perturb the system it is investigating. Only radioisotopes can be called true tracers, since they are administered in extremely small quantities. The term 'label' is more appropriate for stable isotopes, since they are usually given in quantities equivalent to the amount received in the normal diet. The word 'tracer' is, however, still used in some stable-isotope studies with the implicit understanding that it will almost certainly perturb the system under investigation. The underlying assumption in this type of work is that the label (or tracer) behaves in the same kinetic way as the naturally-abundant mineral (sometimes called the tracee), otherwise the use of labels to mimic the behaviour of the native mineral is invalid. There must be no discri...

The use of ICPMS for stable isotope tracer studies in humans: a review

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Analysis of isotope ratios in vitamin K1 (phylloquinone) from human plasma by gas chromatography/mass spectrometry

“…Thirdly, with gas chromatography/mass spectrometry (GC/MS), it is possible to positively identify the compound of interest by its mass spectrum while measuring enrichments. Finally, more than one labelled species can be administered at one time thereby making use of classic dual label absorption models 10, 11…”

Species-Specific Isotope Dilution Analysis and Isotope Pattern Deconvolution for Butyltin Compounds Metabolism Investigations

“…The use of mathematical modeling in nutrition has been concerned mainly with compartmental modeling, which is especially suited to mineral metabolism. 31 Similarly, strategies based on the mathematics of combinatorial probabilities have been employed, including mass isotopomer distribution analysis 32,33 for the quantification of precursor-product events and its application to study in vivo metabolic fluxes. 34 Isotope pattern deconvolution is a mathematical technique that has been applied for the characterization of complex mass spectra containing molecular fragments with polyisotopic elements, [35][36][37][38] for the elucidation of fragmentation pathways for the accurate measurement of isotope ratios from molecular clusters, 39,40 or for the metabolic studies of the serineto-glycine interconversion in humans.…”

“…Metabolic studies using enriched isotopes require adequate mathematical approaches to complete and support the information provided by the experimental work. The use of mathematical modeling in nutrition has been concerned mainly with compartmental modeling, which is especially suited to mineral metabolism . Similarly, strategies based on the mathematics of combinatorial probabilities have been employed, including mass isotopomer distribution analysis , for the quantification of precursor−product events and its application to study in vivo metabolic fluxes .…”