Effects of a prolonged standardized diet on normalizing the human metabolome.

BACKGROUND Although the effects of acute dietary interventions on the human metabolome have been studied, the extent to which the metabolome can be normalized by extended dietary standardization has not yet been examined. OBJECTIVE We examined the metabolic profiles of healthy human subjects after extended dietary standardization to see whether the inherent variation in the human metabolome could be decreased. DESIGN A cohort of 10 healthy volunteers was admitted to a clinical research center for 2 wk of dietary standardization. Daily serum and urine samples and serum samples at a 2-wk follow-up visit were collected. The samples were analyzed by (1)H nuclear magnetic resonance (NMR) spectroscopy and multivariate statistical analyses. RESULTS NMR spectra were collected to globally profile the higher-concentration metabolites (>micromol/L concentrations). Metabolic changes were observed in some serum samples after day 1 or the 2-wk follow-up visit. For each subject, the samples from all other days had similar profiles. The urinary metabolome reflected no effects from dietary standardization. Pooled 24-h urine samples were studied, which indicated that any normalization that does occur would do so in <24 h. CONCLUSIONS For both the urinary and serum metabolome, a single day of dietary standardization appears to provide all of the normalization that is achievable within the strict controls implemented in a clinical research setting. After 24 h, the subjects remain in their metabolic space; the remaining intra- and intersubject variations appear to be influenced by variables such as genetics, age, and lifestyle.