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

• Published in: Scientific reports 2019-02, Vol.9 (1), p.2045-2045, Article 2045
• Main Authors: Torquato, Pierangelo, Giusepponi, Danilo, Alisi, Anna, Galarini, Roberta, Bartolini, Desirée, Piroddi, Marta, Goracci, Laura, Di Veroli, Alessandra, Cruciani, Gabriele, Crudele, Annalisa, Nobili, Valerio, Galli, Francesco
• Format: Article
• Language: English
• Subjects: 101/58; 13/51; 692/4020/4021; 692/53/2423; Arachidonic acid; Biomarkers; Biopsy; Choline; Clinical trials; Docosahexaenoic acid; Fatty acids; Humanities and Social Sciences; Linolenic acid; Lipid metabolism; Metabolites; multidisciplinary; Patients; Pediatrics; Science; Science (multidisciplinary); Vitamin D; Vitamin E
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-37209-y

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.