Vitamin D3 at 50x AI Attenuates the Decline in Paw Grip Endurance, but Not Disease Outcomes, in the G93A Mouse Model of ALS, and Is Toxic in Females

Background: We previously demonstrated that dietary vitamin D-3 at 10x the adequate intake (AI) attenuates the decline in functional capacity in the G93A mouse model of ALS. We hypothesized that higher doses would elicit more robust changes in functional and disease outcomes. Objective: To determine the effects of dietary vitamin D-3 at 50xAI on functional outcomes (motor performance, paw grip endurance) and disease severity (clinical score), as well as disease onset, disease progression and lifespan in the transgenic G93A mouse model of ALS. Methods: Starting at age 25 d, 100 G93A mice (55 M, 45 F) were provided ad libitum with either an adequate (AI; 1 IU D-3/g feed) or high (HiD; 50 IU D-3/g feed) vitamin D-3 diet. Results: HiD females consumed 9% less food corrected for body weight vs. AI females (P = 0.010). HiD mice had a 12% greater paw grip endurance over time between age 60-141 d (P = 0.015), and a 37% greater score during disease progression (P = 0.042) vs. AI mice. Although HiD females had a non-significant 31% greater CS prior to disease onset vs. AI females, they exhibited a significant 20% greater paw grip endurance AUC (P = 0.020) when corrected for clinical score. Conclusion: Dietary D-3 supplementation at 50x the adequate intake attenuated the decline in paw grip endurance, but did not influence age at disease onset, hindlimb paralysis or endpoint in the transgenic G93A mouse model of ALS. Furthermore, females may have reached the threshold for vitamin D-3 toxicity as evidence by reduced food intake and greater disease severity prior to disease onset.