Metabolomic profiling of an ultraprocessed dietary pattern in a domiciled randomized controlled crossover feeding trial

Authors: O'Connor, Lauren; HALL, KEVIN - National Institutes Of Health (NIH); HERRICK, KIRSTEN - National Institutes Of Health (NIH); REEDY, JILL - National Institutes Of Health (NIH); CHUNG, STEPHANIE - National Institutes Of Health (NIH); STAGLIANO, MICHAEL - National Institutes Of Health (NIH); COURVILLE, AMBER - National Institutes Of Health (NIH); SINHA, RASHMI - National Institutes Of Health (NIH); FREEDMAN, NEAL - National Institutes Of Health (NIH); ALBERT, PAUL - National Institutes Of Health (NIH); LOFTFIELD, ERIKKA - National Institutes Of Health (NIH)

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/2/2023
Publication Date: 6/3/2023
Citation: O'Connor, L.E., Hall, K.D., Herrick, K.A., Reedy, J., Chung, S.T., Stagliano, M., Courville, A.B., Sinha, R., Freedman, N.D., Albert, P.S., Loftfield, E. 2023. Metabolomic profiling of an ultraprocessed dietary pattern in a domiciled randomized controlled crossover feeding trial. Journal of Nutrition. 153:2181-2192. https://doi.org/10.1016/j.tjnut.2023.06.003.
DOI: https://doi.org/10.1016/j.tjnut.2023.06.003

Interpretive Summary: Ultra-processed foods and human health is an emerging and controversial issue in nutrition research. Improved methods for measuring intakes of ultra-processed foods, including objective biomarkers, have the potential to clarify our understanding of how ultra-processed foods influence health. This is, to the best of our knowledge, the first biomarker discovery project for a dietary pattern high in ultra-processed foods. We used a metabolomics approach to measure a broad range of chemical compounds in plasma and urine samples that were collected and stored as a part of a domiciled, randomized, controlled, crossover feeding trial in which participants consumed dietary patterns high in or void of foods that are classified as ultra-processed according to the NOVA classification system. We found that a dietary pattern high in ultra-processed foods meaningfully influenced the plasma and urine metabolome after two weeks of controlled feeding. Notably, metabolites related to artificial sweeteners, benzoate preservatives, and flavoring agents were higher after consumption of the ultra-processed vs minimally processed dietary pattern. These ingredients are hallmarks of ultra-processed foods according to the NOVA classification system. Our study reveals promising candidate biomarkers of ultra-processed foods that may serve as objective measures for correcting measurement error inherent to self-reported dietary intake data and ultimately improving study reproducibility. Moreover, ultra-processed food associated metabolites may shed light on how various aspects of food processing and formulation impact chronic disease.

Technical Abstract: Objective markers of ultraprocessed foods (UPF) may improve the assessment of UPF intake and provide insight into how UPF influences health. Objectives: To identify metabolites that differed between dietary patterns (DPs) high in or void of UPF according to Nova classification. In a randomized, crossover, controlled-feeding trial (clinicaltrials.gov NCT03407053), 20 domiciled healthy participants (mean standard deviation: age 31 7 y, body mass index [kg/m2]22 11.6) consumed ad libitum a UPF-DP (80% UPF) and an unprocessed DP (UN-DP; 0% UPF) for 2 wk each. Metabolites were measured using liquid chromatography with tandem mass spectrometry in ethylenediaminetetraacetic acid plasma, collected at week 2 and 24-h, and spot urine, collected at weeks 1 and 2, of each DP. Linear mixed models, adjusted for energy intake, were used to identify metabolites that differed between DPs. After multiple comparisons correction, 257 out of 993 plasma and 606 out of 1279 24-h urine metabolites differed between UPF-DP and UN-DP. Overall, 21 known and 9 unknown metabolites differed between DPs across all time points and biospecimen types. Six metabolites were higher (4-hydroxy-L-glutamic acid, N-acetylaminooctanoic acid, 2-methoxyhydroquinone sulfate, 4-ethylphenylsulfate, 4vinylphenol sulfate, and acesulfame) and 14 were lower following the UPF-DP; pimelic acid, was lower in plasma but higher in urine following the UPF-DP. Consuming a DP high in, compared with 1 void of, UPF has a measurable impact on the short-term human metabolome. Observed differential metabolites could serve as candidate biomarkers of UPF intake or metabolic response in larger samples with varying UPF-DPs.