Nutritional and lipidomics biomarkers of docosahexaenoic acid-based multivitamin therapy in pediatric NASH

Pierangelo Torquato, Danilo Giusepponi, Anna Alisi, Roberta Galarini, Desirée Bartolini, Marta Piroddi, Laura Goracci, Alessandra Di Veroli, Gabriele Cruciani, Annalisa Crudele, Valerio Nobili, Francesco Galli

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Abstract

Two recent randomized controlled trials demonstrated improved radiographic, histological and hepatometabolic cues of non-alcoholic steatohepatitis (NASH) in pediatric patients treated with the ω-3 fatty acid docosahexaenoic acid (DHA) in combination with vitamin D (VD) or with choline (CHO) and vitamin E (VE), the DHA-VD and DHA-CHO-VE trials, respectively). In the present study we verified the nutritional compliance to these DHA-based multivitamin treatments; lipidomics biomarkers of the reported outcome on NASH indicators were also investigated. Samples were obtained from 30 biopsy-proven pediatric NASH patients of the DHA-CHO-VE trial randomized in multivitamin treatment group and placebo group (n = 15 each), and from 12 patients of the treatment group of the DHA-VD trial. All patients underwent 6-month therapy plus 6 months of follow-up. Plasma samples and clinical data were obtained at baseline and at the end of the study (12 months). Selected biomarkers included the free form of DHA and other ω-3 fatty acid arachidonic acid (AA), indices of the vitamin E status, and some hepatic metabolites of these lipids. Radiographic and histological improvements of treated patients were associated with increased concentrations of DHA, α-linolenic acid and α-tocopherol (i.e. VE), and with decreased AA that was also investigated in complex lipids by untargetd lipidomics. As a result a significantly lowered AA/DHA ratio was observed to represent the main indicator of the response to the DHA-based therapy. Furthermore, baseline levels of AA/DHA showed strong association with NAS and US improvement. A stable correction of DHA AA metabolism interaction is associated with the curative effect of this therapy and may represent a key nutritional endpoint in the clinical management of pediatric NASH.

Original languageEnglish
Pages (from-to)2045
JournalScientific Reports
Volume9
Issue number1
DOIs
Publication statusPublished - Feb 14 2019

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    Torquato, P., Giusepponi, D., Alisi, A., Galarini, R., Bartolini, D., Piroddi, M., Goracci, L., Di Veroli, A., Cruciani, G., Crudele, A., Nobili, V., & Galli, F. (2019). Nutritional and lipidomics biomarkers of docosahexaenoic acid-based multivitamin therapy in pediatric NASH. Scientific Reports, 9(1), 2045. https://doi.org/10.1038/s41598-018-37209-y