Higher Glycemic Index and Glycemic Load Diet Is Associated with Slower Disease Progression in Amyotrophic Lateral Sclerosis

Objective: High-caloric diets may slow the progression of amyotrophic lateral sclerosis; however, key macronutrients have not been identified. We examined whether dietary macronutrients are associated with the rate of progression and length of survival among the prospective cohort study participants. Methods: Participants with a confirmed diagnosis of sporadic amyotrophic lateral sclerosis enrolled in the Multicenter Cohort Study of Oxidative Stress were included (n = 304). We evaluated baseline macronutrient intake assessed by food frequency questionnaire in relation to change in revised amyotrophic lateral sclerosis functional rating scale total-score, and tracheostomy-free survival using linear regression and Cox proportional hazard models. Baseline age, sex, disease duration, diagnostic certainty, body mass index, bulbar onset, revised amyotrophic lateral sclerosis functional rating scale total-score, and forced vital capacity were included as covariates. Results: Baseline higher glycemic index and load were associated with less decline of revised amyotrophic lateral sclerosis functional rating scale total score at 3-month follow-up (β = −0.13, 95% CI −0.2, −0.01, p = 0.03) and (β = −0.01, 95% CI −0.03, −0.0007, p = 0.04), respectively. Glycemic index second-quartile, third-quartile, and fourth-quartile groups were associated with less decline at 3 months by 1.9 (95% CI −3.3, −0.5, p = 0.008), 2.0 (95% CI −3.3, −0.6, p = 0.006), and 1.6 (95% CI −3.0, −0.2, p = 0.03) points compared with the first-quartile group; the glycemic load fourth-quartile group had 1.4 points less decline compared with the first-quartile group (95% CI −2.8, 0.1, p = 0.07). Higher glycemic index was associated with a trend toward longer tracheostomy-free survival (HR 0.97, 95% CI 0.93, 1.00, p = 0.07). Interpretation: Higher dietary glycemic index and load are associated with slower disease progression in amyotrophic lateral sclerosis. ANN NEUROL 2024;95:217–229.