Effects of Dietary Supplementation with Conjugated Linoleic Acid on Redox Marker Profiles and Neuroaxonal Degeneration in Amyotrophic Lateral Sclerosis

The revised ALS Functional Rating Scale (ALSFRS-R) and the blood plasma accumulation of neurofilament light chain (NfL) are key markers for tracking amyotrophic lateral sclerosis (ALS) progression. Based on recent studies indicating that dietary supplementation with conjugated linoleic acid (CLA) may boost antioxidant enzyme activity in ALS patients, in this study, ALSFRS-R scores (and subscores), NfL and thiol-bound protein (P-SH) levels, and intracellular activity of antioxidant enzymes (G6PD and GSR) were measured in ALS patients after 6 months (T6) of treatment with riluzole (R) or riluzole + CLA (R + CLA); we also investigated the correlations between these markers. At baseline (T0), G6PD activity in the R group was positively correlated with ALSFRS-R score (p < 0.001), whereas plasma P-SH levels in the R + CLA group were inversely correlated with ALSFRS-R score (p = 0.033). No significant baseline association was found between NfL levels and total ALSFRS-R score in the R group. At six months (T6), GSR and G6PD activities in the R + CLA group were significantly higher than in the R group (p < 0.05). Furthermore, a significant inverse correlation between plasma NfL levels and ALSFRS-R total score emerged at T6 exclusively in the R group (p = 0.002). Subscore analysis at T6 showed that plasma NfL levels negatively correlated with bulbar function in both groups (R: p = 0.010; R + CLA: p = 0.020) and with fine motor function in the R group (p = 0.031); whereas no significant correlation was observed for the respiratory subscore in either treatment group. These findings are consistent with an enhanced antioxidant activity associated with CLA supplementation. Overall, these preliminary exploratory results suggest that systemic redox biomarkers and plasma NfL may provide complementary, non-redundant information on distinct aspects of ALS pathobiology, though their precise temporal and mechanistic interactions require confirmation by dedicated longitudinal studies. The need for the combined use of neurodegeneration and oxidative-stress biomarkers for monitoring the progression of ALS is highlighted.