Vitamin D as a potential therapy in amyotrophic lateral sclerosis

Abstract

Vitamin D has been demonstrated to influence multiple aspects of amyotrophic lateral sclerosis (ALS) pathology. Both human and rodent central nervous systems express the vitamin D receptor (VDR) and/or its enzymatic machinery needed to fully activate the hormone. Clinical research suggests that vitamin D treatment can improve compromised human muscular ability and increase muscle size, supported by loss of motor function and muscle mass in animals following VDR knockout, as well as increased muscle protein synthesis and ATP production following vitamin D supplementation. Vitamin D has also been shown to reduce the expression of biomarkers associated with oxidative stress and inflammation in patients with multiple sclerosis, rheumatoid arthritis, congestive heart failure, Parkinson's disease and Alzheimer's disease; diseases that share common pathophysiologies with ALS. Furthermore, vitamin D treatment greatly attenuates hypoxic brain damage in vivo and reduces neuronal lethality of glutamate insult in vitro; a hallmark trait of ALS glutamate excitotoxicity. We have recently shown that high-dose vitamin D3 supplementation improved, whereas vitamin D3 restriction worsened, functional capacity in the G93A mouse model of ALS. In sum, evidence demonstrates that vitamin D, unlike the antiglutamatergic agent Riluzole, affects multiple aspects of ALS pathophysiology and could provide a greater cumulative effect.

Keywords: Amyotrophic lateral sclerosis; Apoptosis; Calcidiol; Calcitriol; D3; Excitotoxicity; G93A mice; Inflammation; Motor neuron death; Neurodegenerative disease; Neuromuscular disease; Oxidative stress; Vitamin D.

Figure 1

Schematic outlining the multifaceted nature of ALS pathology. ALS, amyotrophic lateral sclerosis.

Figure 2

Schematic of the potential amyotrophic lateral sclerosis (ALS) pathophysiologies modulated by vitamin D and the possible subsequent mitigation of ALS. (TNF‐α, tumor necrosis factor‐ α; IL‐1β, interleukin‐1β; NOS, nitric oxide synthase; MAP, microtubule‐associated protein; GAP, growth‐associated protein).