(P10-013-23) Differences in Metabolomic Profiles Between Responders and Non-responders of Prune Supplementation on Bone Health in Postmenopausal Women

Objectives: This study evaluated the plasma, serum, and urine metabolome as a secondary outcome from a randomized controlled trial (RCT), The Prune Study, assessing the effect of prune supplementation on bone health in postmenopausal women. The objective was to explore potential bioactive compounds and biochemical pathways that may be linked to improved bone outcomes.

Methods: In this 12-month parallel-arm RCT, postmenopausal women were assigned to control, 50 g/day prune and 100 g/day prune groups. The primary outcome for the trial was areal bone mineral density (BMD) at several sites. A pooled analysis of the 50 and 100 g/day groups demonstrated preservation of total hip BMD compared to control women. In this pilot study, we conducted untargeted metabolomics in plasma, serum, and urine to compare the metabolomic profile between women who had the most robust bone-protective effect vs. those who did not. Samples were pooled from 10 responders with the greatest percent increase in total hip BMD and 10 non-responders with the greatest percent decrease in total hip BMD from baseline. Processing was done using liquid chromatography mass spectrometry (LC-MS) on an Orbitrap Exploris 120 Mass Spectrometer.

Results: There were 254 known metabolites in the plasma and serum and 571 in the urine. Related to prune consumption, cinnamic acids, hydroxycinnamic acids, hippuric acids, and 3,4-dihydrocoumarins were higher in the urine of non-responders, while 7-hydroxycoumarins, isoflavones, and other flavonoids were higher in the urine of responders. Pathway analysis revealed steroid hormone synthesis, phenylalanine metabolism, bile acid synthesis, and linoleic acid metabolism as pathways that may be altered. Further untargeted metabolomics data will be collected from urine samples of each participant to examine individual differences. Select metabolites associated with prune consumption, bone health, or related biochemical pathways will be chosen for targeted metabolomics.

Conclusions: There were differences in the urinary metabolomic profile and metabolic pathways between women who did and did not respond to the prune intervention. These results can be used to better understand why prunes may have bone-protective effects in some women but not in others.

Funding Sources: The clinical and translational science institute, TL1 training grant, and The California Prune Board.