Metabolomics-based identification of new alkaloids as urinary biomarkers for dietary tomato intake

The goal of this study was the identification of potential urinary biomarkers for the consumption of tomatoes and tomato products. During a dietary intervention study, the human urinary metabolome of a study cohort receiving either a tomato-free diet or tomato juice was compared by application of an HPLC-HRMS-based metabolomics approach. Statistical analysis showed several unique features which were detectable after the intake of tomato juice. The most discriminating markers were identified as metabolites of the steroidal glycoalkaloid esculeoside B recently found in tomato juice. Hydroxylated and sulfonated metabolites of the corresponding aglycone esculeogenin B were detected in urine samples. In addition the β-carboline alkaloids tangutorid E/F and a series of new imidazol alkaloids as well as glucuronidated derivatives thereof were identified in urine. The structures of all mentioned biomarkers were fully elucidated by MS and NMR.
For the quantitative assessment of the tomato biomarker intake a two-week crossover dietary intervention study was performed. Fourteen volunteers obtained a low and high dose of tomato juice after a 3-day washout period and urine samples were analyzed by HPLC MS/MS. Several imidazole alkaloids were shown to specifically indicate the tomato juice consumption for 24 h and partly >24 h. The hydroxylated and sulfonated metabolites of esculeogenin B were were detectable for at least 48 h after consumption and serve as long-term biomarkers for tomato juice. The β carboline alkaloids were identified as supporting, but non-specific dietary biomarkers for tomato juice intake. As β carboline alkaloids are formed during thermal processing they are not detectable in fresh tomatoes and can be used to distinguish between fresh and processed tomato intake.
In summary the results show that the dietary intake of tomato juice is detectable based on the urinary excretion of multiple β-carboline, imidazole and steroidal alkaloids, and can be determined for a period of up to 48 h after consumption. Furthermore, low and high doses of tomato intake can clearly be differentiated based on the urinary excretion of biomarkers.