Metabolomics

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Identification and validation of poly-metabolite scores for diets high in ultra-processed food: An observational study and post-hoc randomized controlled crossover-feeding trial.


ABSTRACT:

BACKGOUND: Ultra-processed food (UPF) accounts for a majority of calories consumed in the United States, but the impact on human health remains unclear. We aimed to identify poly-metabolite scores in blood and urine that are predictive of UPF intake.

METHODS AND FINDINGS: Of the 1082 Interactive Diet and Activity Tracking in AARP (IDATA) Study (clinicaltrials.gov ID NCT03268577) participants, aged 50-74 years, who provided biospecimen consent, n=718 with serially collected blood and urine and one to six 24-hour dietary recalls (ASA-24s), collected over 12-months, met eligibility criteria and were included in the metabolomics analysis. Ultra-high performance liquid chromatography with tandem mass spectrometry was used to measure >1000 serum and urine metabolites. Average daily UPF intake was estimated as percentage energy according to the Nova system. Partial Spearman correlations and Least Absolute Shrinkage and Selection Operator (LASSO) regression were used to estimate UPF-metabolite correlations and build poly-metabolite scores of UPF intake, respectively. Scores were tested in a previously conducted randomized, controlled, crossover-feeding trial (clinicaltrials.gov ID NCT03407053) of 20 subjects who were admitted to the NIH Clinical Center and randomized to consume ad libitum diets that were 80% or 0% energy from UPF for 2 weeks immediately followed by the alternate diet for 2 weeks; eligible subjects were between 18-50 years old with a body mass index of >18.5 kg/m2 and weight-stable. IDATA participants were 51% female, and 97% completed 4 ASA-24s. Mean intake was 50% energy from UPF. UPF intake was correlated with 191 (of 952) serum and 293 (of 1044) 24-hour urine metabolites (FDR-corrected P-value < 0.01), including lipid (n=56 serum, n=22 24-hour urine), amino acid (n=33, 61), carbohydrate (n=4, 8), xenobiotic (n=33, 70), cofactor and vitamin (n= 9, 12), peptide (n=7, 6), and nucleotide (n=7, 10) metabolites. Using LASSO regression, 28 serum and 33 24-hour urine metabolites were selected as predictors of UPF intake; biospecimen-specific scores were calculated as a linear combination of selected metabolites. Overlapping metabolites included (S)C(S)S-S-methyl cysteine sulfoxide (rs= -0.19, -0.23), N2-N5-diacetylornithine (rs= -0.26, -0.27), pentoic acid (rs= -0.28, -0.31), and N6-carboxymethyllysine (rs=0.15, 0.21). Within the cross-over feeding trial, the poly-metabolite scores differed, within individual, between UPF diet phases (P-value for paired t-test <0.001). IDATA Study participants were older US adults whose diets may not be reflective of other populations.

CONCLUSIONS: Poly-metabolite scores, developed in IDATA participants with varying diets, are predictive of UPF intake and could advance epidemiological research on UPF and health. Poly-metabolite scores should be evaluated and iteratively improved in populations with a wide range of UPF intake.

INSTRUMENT(S): Liquid Chromatography MS - - - Q Exactive

PROVIDER: MTBLS12705 | MetaboLights | 2025-07-12

REPOSITORIES: MetaboLights

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Identification and validation of poly-metabolite scores for diets high in ultra-processed food: An observational study and post-hoc randomized controlled crossover-feeding trial.

Abar Leila L   Steele Eurídice Martínez EM   Lee Sang Kyu SK   Kahle Lisa L   Moore Steven C SC   Watts Eleanor E   O'Connell Caitlin P CP   Matthews Charles E CE   Herrick Kirsten A KA   Hall Kevin D KD   O'Connor Lauren E LE   Freedman Neal D ND   Sinha Rashmi R   Hong Hyokyoung G HG   Loftfield Erikka E  

PLoS medicine 20250520 5


<h4>Background</h4>Ultra-processed food (UPF) accounts for a majority of calories consumed in the United States, but the impact on human health remains unclear. We aimed to identify poly-metabolite scores in blood and urine that are predictive of UPF intake.<h4>Methods and findings</h4>Of the 1,082 Interactive Diet and Activity Tracking in AARP (IDATA) Study (clinicaltrials.gov ID NCT03268577) participants, aged 50-74 years, who provided biospecimen consent, n = 718 with serially collected blood  ...[more]

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