The Effects of a Mediterranean Diet on Metabolic Hormones and Cytokines in Amyotrophic Lateral Sclerosis Patients: A Prospective Interventional Study

<b>Background</b>: Amyotrophic lateral sclerosis (ALS) is a prevalent neurodegenerative disease but lacks effective treatments. Dietary interventions, notably the Mediterranean diet, promise to modulate disease pathways. This study aimed to investigate the impact of the Mediterranean diet on gut hormones and cytokines in patients with amyotrophic lateral sclerosis (ALS). <b>Methods</b>: We conducted a 12-month, single-center prospective study on a total of 44 ALS patients. After a 6-month observation period, the patients were placed on a dairy-free Mediterranean diet for the next 6 months. We evaluated the patients at baseline (T0), 6 months (T1), and 12 months (T2). We measured the ALS Functional Rating Scale-Revised (ALSFRS-R) scores and a panel of metabolic hormones and cytokines. <b>Results</b>: The ALSFRS-R scores declined over 12 months (37.59 ± 6.32 at T0 vs. 30.23 ± 8.91 at T2, <i>p</i> < 0.001), indicating expected disease progression with no significant difference in the rate of decline before and after the dietary intervention. The leptin levels significantly decreased from T0 to T1 (T0: 4956 ± 3994 pg/mL vs. T1: 3196 ± 2807 pg/mL, <i>p</i> = 0.038). The insulin and GLP-1 levels showed significant drops at T2 (insulin T0: 480 ± 369 vs. T2: 214 ± 213 pmol/L, <i>p</i> < 0.01; GLP-1 T0: 118 ± 76 vs. T2: 60 ± 57 pg/mL, <i>p</i> < 0.01). C-peptide increased at T2 (T0: 3814 ± 1967 vs. T2: 9532 ± 4000 pg/mL, <i>p</i> < 0.001). Among the cytokines, the levels of IL-12P70, IL-13, IL-9, and IL-2 significantly decreased from T0 to T2 (all <i>p</i> < 0.05), while IL-17A and TNFα significantly increased between T1 and T2 (<i>p</i> < 0.01). <b>Conclusions</b>: The Mediterranean diet intervention in ALS patients modulated several metabolic hormones and cytokines but with no evidence of impacting the disease's evolution or of a slowed clinical progression. These findings suggest a potential role for dietary intervention, particularly the Mediterranean diet, in modulating gut hormones and cytokines in ALS patients, but its impact on disease course is unclear. Future randomized studies are needed to confirm these changes and to determine whether dietary intervention can have any benefit in ALS.