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T01048 Effect of cruciferous vegetable dietary intervention in humans on urinary metabonomic profile

Monday 25 June 2007

This short research project aims to add to existing information on the reported anticancer effects of eating cruciferous vegetables using samples collected as part for a previous FSA project.

Study Duration : March to December 2007

Contractor : Department of Biomolecular Medicine, Imperial College, London

Background

There is a strong association between diet and cancer and notably with the consumption of well cooked red meat. Cooking of red meat or fish at high temperatures leads to the formation of heterocyclic amines, which have been found to cause cancer in laboratory animals. The most abundant of these compounds is 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Studies have shown that PhIP needs activation by metabolism before it exerts its harmful effects. Cruciferous vegetables (such as Brussels sprouts, cabbage, broccoli) are reported to protect against cancer by modifying the metabolism of carcinogens such as PhIP.

Project T01009: Can cruciferous vegetables alter the genotoxicity of heterocyclic amines following human consumption of cooked meat? , set out to test this assumption. This was done by looking for PhIP metabolites found in urine samples collected from human volunteers who had eaten cooked burgers either after a cruciferous vegetable free period or after consuming cruciferous vegetables for 14 days. The project was able to demonstrate that dietary intervention with cruciferous vegetables modified the metabolic handling of PhIP and identified the need for further work.

Since T01009 ended in 2002, advances in technology, and notably in metabonomics have made it possible to carry out detailed analysis of biofluids using nuclear magnetic resonance (NMR) and mass spectroscopy (MS) combined with sophisticated bioinformatic data analysis. These techniques have made it possible to identify metabolic changes due to disease, homeostasis or the administration of exogenous chemicals.

Research Approach

The current project seeks to use these techniques to carry out additional urine analyses on archived urine samples collected as part of the dietary intervention trial carried out as part of the earlier project (T01009).

Urine samples will be analysed using flow injection 1H NMR spectroscopy coupled to computer based pattern recognition. This should identify biomarkers that can be correlated with the consumption of well cooked meat together with cruciferous vegetables. Ultimately these data should make it possible to identify metabolic pathways modified by cruciferous vegetable intervention.

Additional Information

For further information on project T01009 see the link below. Final report is available from the FSA Information Centre.

Results and findings

Two singlets were identified in the urine 1H-NMR spectra which correlated with the period of high cruciferous vegetable intake and are likely to be biomarkers of cruciferous vegetable intake. Efforts were made to positively identify the candidate biomarkers associated with the singlets; however this work has so far been unsuccessful. Future studies will involve a strategy for the identification of the various unknown peaks detected in the 1H-NMR spectra.

Alterations of urinary metabolites were seen to occur soon after the consumption of meat, including increased urinary excretions of a number of meat derived biomarkers; these biomarkers declined in the subsequent 10-24 hours urine collection, it is hypothesised this is representative of the digestive transit of meat from the higher duodenum and small intestine.

Ten to twenty four hours following meat consumption, increases in the urinary excretion of a number of metabolites known to derive from the human gut microbiota were also noted. These increases in urinary concentration of bacterial associated metabolites are consistent with gut physiology further along the digestive transit in the lumen of the lower small intestine and large intestine.

As a result of this project metabolic pathways modified by cruciferous vegetable intervention have been identified and it is has been possible to characterise metabotype alterations following the consumption of meat, although additional work is still required to identify the various unknown peaks detected in the 1H-NMR spectra

select this link to view the (External) Final report for project T01048

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