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Am J Clin Nutr (October 28, 2009). doi:10.3945/ajcn.2009.28234
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© 2009 American Society for Clinical Nutrition

Effects of a prolonged standardized diet on normalizing the human metabolome1,2,3

Jason H Winnike, Marjorie G Busby, Paul B Watkins and Thomas M O'Connell

1 From the Department of Biomedical Engineering (JHW); the Clinical and Translational Research Center (MGB); the Department of Gastroenterology and Hepatology, School of Medicine (PBW); the Division of Pharmacotherapy and Experimental Therapeutics, School of Pharmacy (TMO), University of North Carolina, Chapel Hill, North Carolina; and the Hamner-University of North Carolina Institute for Drug Safety Sciences, Research Triangle Park, North Carolina (TMO and PBW).

2 Supported in part by the National Institutes of Health (grant numbers GM38147, P30ES10126, and RR000046).

3 Address correspondence to TM O'Connell, The Hamner Institutes for Health Sciences, PO Box 12137, 6 Davis Drive, Research Triangle Park, NC 27709. E-mail: tom_oconnell{at}med.unc.edu.

ABSTRACT

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 1H nuclear magnetic resonance (NMR) spectroscopy and multivariate statistical analyses.

Results: NMR spectra were collected to globally profile the higher-concentration metabolites (>µmol/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.

Received for publication June 15, 2009. Accepted for publication September 18, 2009.







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