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Inter-individual response to dietary interventions remains a major challenge to successful weight loss among older adults. This study applied metabolomics technology to identify small molecule signatures associated with a loss of fat mass and overall weight in a cohort of older adults on a nutritionally complete, high-protein diet. A total of 102 unique metabolites were measured using liquid chromatography-mass spectrometry (LC-MS) for 38 adults aged 65-80 years randomized to dietary intervention and 36 controls. Metabolite values were analyzed in both baseline plasma samples and samples collected following the six-month dietary intervention to consider both metabolites that could predict the response to diet and those that changed in response to diet or weight loss.Eight metabolites changed over the intervention at a nominally significant level: D-pantothenic acid, L-methionine, nicotinate, aniline, melatonin, deoxycarnitine, 6-deoxy-L-galactose, and 10-hydroxydecanoate. Within the intervention group, there was broad variation in the achieved weight-loss and dual-energy x-ray absorptiometry (DXA)-defined changes in total fat and visceral adipose tissue (VAT) mass. Change in the VAT mass was significantly associated with the baseline abundance of α-aminoadipate ( p = 0.0007) and an additional mass spectrometry peak that may represent D-fructose, myo-inositol, mannose, α-D-glucose, allose, D-galactose, D-tagatose, or L-sorbose ( p = 0.0001). This hypothesis-generating study reflects the potential of metabolomic biomarkers for the development of personalized dietary interventions.

Use of Metabolomic Profiling to Understand Variability in Adiposity Changes Following an Intentional Weight Loss Intervention in Older Adults