Abstract
Dietary metabolomics is a relatively objective approach to identifying new biomarkers of dietary intake and for use alongside traditional methods. However, methods used across dietary feeding studies vary, thus making it challenging to compare results. The objective of this study was to synthesize methodological components of controlled human feeding studies designed to quantify the diet-related metabolome in biospecimens, including plasma, serum, and urine after dietary interventions. Six electronic databases were searched. Included studies were as follows: 1) conducted in healthy adults; 2) intervention studies; 3) feeding studies focusing on dietary patterns; and 4) measured the dietary metabolome. From 12,425 texts, 50 met all inclusion criteria. Interventions were primarily crossover (n = 25) and parallel randomized controlled trials (n = 22), with between 8 and 395 participants. Seventeen different dietary patterns were tested, with the most common being the "High versus Low-Glycemic Index/Load" pattern (n = 11) and "Typical Country Intake" (n = 11); with 32 providing all or the majority (90%) of food, 16 providing some food, and 2 providing no food. Metabolites were identified in urine (n = 31) and plasma/serum (n = 30). Metabolites were quantified using liquid chromatography, mass spectroscopy (n = 31) and used untargeted metabolomics (n = 37). There was extensive variability in the methods used in controlled human feeding studies examining the metabolome, including dietary patterns tested, biospecimen sample collection, and metabolomic analysis techniques. To improve the comparability and reproducibility of controlled human feeding studies examining the metabolome, it is important to provide detailed information about the dietary interventions being tested, including information about included or restricted foods, food groups, and meal plans provided. Strategies to control for individual variability, such as a crossover study design, statistical adjustment methods, dietary-controlled run-in periods, or providing standardized meals or test foods throughout the study should also be considered. The protocol for this review has been registered at Open Science Framework (https://doi.org/10.17605/OSF.IO/DAHGS).