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

Research output: Contribution to journalArticle

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

Fingerprint

Docosahexaenoic Acids
Fatty Liver
Biomarkers
Pediatrics
Vitamin E
Arachidonic Acid
Therapeutics
Choline
Vitamin D
Fatty Acids
Lipids
alpha-Linolenic Acid
Tocopherols
Cues
Randomized Controlled Trials
Placebos

Cite this

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

In: Scientific Reports, Vol. 9, No. 1, 14.02.2019, p. 2045.

Research output: Contribution to journalArticle

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, vol. 9, no. 1, pp. 2045. https://doi.org/10.1038/s41598-018-37209-y
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. / Nutritional and lipidomics biomarkers of docosahexaenoic acid-based multivitamin therapy in pediatric NASH. In: Scientific Reports. 2019 ; Vol. 9, No. 1. pp. 2045.
@article{80d19e5d23714ea9a341741ce02f63d6,
title = "Nutritional and lipidomics biomarkers of docosahexaenoic acid-based multivitamin therapy in pediatric NASH",
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.",
author = "Pierangelo Torquato and Danilo Giusepponi and Anna Alisi and Roberta Galarini and Desir{\'e}e Bartolini and Marta Piroddi and Laura Goracci and {Di Veroli}, Alessandra and Gabriele Cruciani and Annalisa Crudele and Valerio Nobili and Francesco Galli",
year = "2019",
month = "2",
day = "14",
doi = "10.1038/s41598-018-37209-y",
language = "English",
volume = "9",
pages = "2045",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Nutritional and lipidomics biomarkers of docosahexaenoic acid-based multivitamin therapy in pediatric NASH

AU - Torquato, Pierangelo

AU - Giusepponi, Danilo

AU - Alisi, Anna

AU - Galarini, Roberta

AU - Bartolini, Desirée

AU - Piroddi, Marta

AU - Goracci, Laura

AU - Di Veroli, Alessandra

AU - Cruciani, Gabriele

AU - Crudele, Annalisa

AU - Nobili, Valerio

AU - Galli, Francesco

PY - 2019/2/14

Y1 - 2019/2/14

N2 - 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.

AB - 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.

U2 - 10.1038/s41598-018-37209-y

DO - 10.1038/s41598-018-37209-y

M3 - Article

C2 - 30765737

VL - 9

SP - 2045

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

ER -