Work

Acute changes in saliva metabolomic profile after drinking water instead of apple juice or no drink signal improved insulin-related metabolism in healthy children: a randomized controlled trial

Year: 2026

Type: article

Abstract: Objective: In the Saliva Insulin as Biomarker (SIB) randomized controlled trial (RCT), saliva insulin increased more, within 60 min, after one serving of apple juice, and normalized less, after no drink, compared to the acute change after one serving of drinking water. This paper tested for corresponding drink treatment effects on metabolomic profile, recognizing that effects on insulin, a metabolic switch, imply co-occurring effects on many metabolic pathways, simultaneously, and potential for school-based drinking water interventions to efficiently target risk factor profiles. Metabolic pathways potentially impacted by each drink treatment were described by baseline weight condition to generate hypotheses about potential metabolic targets for drinking water intervention. Methods: Untargeted metabolomic assays were completed for saliva from 105 healthy children (5-10y), who participated in the 3-arm parallel group SIB RCT (NCT05211843), prior to a routine dental check-up on a weekday morning or afternoon. Unstimulated saliva was collected, at baseline, before study participants were randomly assigned to drink 500 mL water (W), 200 mL apple juice (AJ), or no drink (ND), and 45-60 min post-drink treatment. Randomization and analysis were stratified by age-and-sex-specific BMI percentile (5-85th or >85th). Drink treatment effects on change in saliva metabolomic profiles were compared using orthogonal partial least squares discriminant analysis (OPLS-DA), permutational multivariate analysis of variance (PERMANOVA), and Metaboanalyst 6.0 pathway module. Results: = 0.02). Increases or decreases of 1.5-fold or more in over 100 metabolites with KEGG IDs, after W instead of either AJ or ND, potentially impacted dozens of metabolic pathways. Conclusion: In healthy children, with normal weight, overweight or obesity, W instead of AJ or ND caused acute changes in saliva metabolomic profile that signal potential for multiple weight- and drink treatment-specific metabolic targets for drinking water intervention. The results warrant further research to pursue potential metabolic benefits of drinking water. Clinical trial registration: NCT05211843, clinicaltrials.gov.

Source: Frontiers in Nutrition

DOI: 10.3389/fnut.2026.1812940

Authors: Jodi D. Stookey, Mimansa Cholera, Rowena Cape

Institutions: San Francisco Department of Public Health, University of California, San Francisco

Language: English

Topic: Diet, Metabolism, and Disease

Subfield: Endocrinology, Diabetes and Metabolism

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801