Effect of high-caloric nutrition on serum neurofilament light chain levels in amyotrophic lateral sclerosis
Johannes Dorst, Joachim Schuster, Jens Dreyhaupt, Simon Witzel, Jochen H. Weishaupt, Jan Kassubek, Ulrike Weiland, Susanne Petri, Thomas Meyer, Torsten Grehl, Andreas Hermann, Berit Jordan, Julian Großkreutz, Daniel Zeller, Matthias Boentert, Bertold Schrank, Johannes Prudlo, Andrea Sylvia Winkler, Stanislav Gorbulev, Francesco Roselli, Luc Dupuis, Markus Otto, Albert C. Ludolph
Abstract
Recent publications showed that circulating neurofilaments (Nfs) may be used as a diagnostic biomarker distinguishing amyotrophic lateral sclerosis (ALS) from ALS mimics with high sensitivity and specificity.1–3 Furthermore, it has been shown that patients with higher Nf levels show faster disease progression1 and shorter survival.2 3 Nf levels remain rather stable during the course of disease.2 Current literature suggests that the diagnostic value of neurofilament light chains (NfL) and phosphorylated neurofilament heavy chains in cerebrospinal fluid is about equal, whereas in blood NfL seems to be superior.4 In this study, we investigated the effect of a high-caloric fatty diet (HCFD) on NfL serum levels, using blood samples collected during the LIPCAL-ALS (efficacy, safety and tolerability of high lipid and caloriesupplementation in amyotrophic lateral sclerosis) study, a randomised, double-blind, parallel-group, placebo-controlled, multicentre trial, which investigated the therapeutic effect of HCFD in ALS.5 In LIPCAL-ALS, 201 patients (80 women, 121 men, age 62.4±10.8) were randomly assigned (1:1) to receive either HCFD (405 kcal/day, 100% fat) or placebo in addition to riluzole (100 mg/day) for 18 months.Although the primary outcome overall survival was negative in the whole study population (p=0.44), the post hoc analysis revealed a significantly longer survival for fast-progressing patients (ie, patients with an Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R) slope >median between disease onset and baseline) in the HCFD group compared with placebo.5To further corroborate our hypothesis of a disease-modifying effect of HCFD, we analysed NfL serum levels from LIPCAL-ALS participants.