More information about text formats
Kaji et al. evaluated the efficacy and safety of intramuscular ultra-high-dose methylcobalamin in 373 patients with amyotrophic lateral sclerosis (ALS) (1). The primary endpoints were death or full ventilation support. Although there was no significant difference between treated and control group, 50 mg methylcobalamin-treated patients with early start within 12 months' duration of diagnosis showed longer time intervals to the primary event and keep the Revised ALS Functional Rating Scale (ALSFRS-R) score than the placebo group. The adverse effects by this treatment were similar and low prevalence among placebo, 25 mg or 50 mg groups. The authors recommend to verify the prognosis by this medication, and I have some concerns about their study.
First, the authors did not allow the change of riluzole administration and did not handle patients with edaravone treatment. I think that the vitamin B12 analog treatment in combination with recent neuro-protective drugs might be acceptable for future trials (2). In addition, the efficacy for ALS by methylcobalamin should be specified by adjusting several confounders for the analysis.
Relating to vitamin therapy for ALS, Rosenbohm et al. investigated the association of serum retinol-binding protein 4 (RBP4) with the onset and prognosis of ALS (3). Adjusted ORs (95% C) of the highest quartile of RBP4 against lowest quartile for incident ALS was 0.36 (0.22-0.59). In addition, serum RBP4 was inversely associated with m...
Relating to vitamin therapy for ALS, Rosenbohm et al. investigated the association of serum retinol-binding protein 4 (RBP4) with the onset and prognosis of ALS (3). Adjusted ORs (95% C) of the highest quartile of RBP4 against lowest quartile for incident ALS was 0.36 (0.22-0.59). In addition, serum RBP4 was inversely associated with mortality by survival analysis. RBC4 can be considered as a biomarker for insulin resistance and vitamin A metabolism, and the lack of vitamin A and insulin resistance might also be related to the pathogenesis of ALS.
Finally, other medications for ALS treatment can be considered for the analysis. Freedman et al. examined the association between lipid-lowering medication and ALS risk (4). Adjusted odds ratios (ORs) (95% confidence interval [CI]) of statins and fibrates for ALS were 0.87 (0.83-0.91) and 0.88 (0.80-0.97), respectively. In contrast, other three cholesterol-lowering medications such as nitrates, bile acid sequestrants and ezetimibe did not significantly associate with ALS. Although confounders and mediators cannot be clearly identified for the prognosis of ALS, basic parameters such as smoking and body mass index might be important variables for the adjustment.
1 Kaji R, Imai T, Iwasaki Y, et al. Ultra-high-dose methylcobalamin in amyotrophic lateral sclerosis: a long-term phase II/III randomised controlled study. J Neurol Neurosurg Psychiatry 2019;90:451-7.
2 Ito S, Izumi Y, Niidome T, et al. Methylcobalamin prevents mutant superoxide dismutase-1-induced motor neuron death in vitro. Neuroreport 2017;28:101-7.
3 Rosenbohm A, Nagel G, Peter RS, et al. Association of serum retinol-binding protein 4 concentration with risk for and prognosis of amyotrophic lateral sclerosis. JAMA Neurol 2018;75:600-7.
4 Freedman DM, Kuncl RW, Cahoon EK, et al. Relationship of statins and other cholesterol-lowering medications and risk of amyotrophic lateral sclerosis in the US elderly. Amyotroph Lateral Scler Frontotemporal Degener 2018;19(7-8):538-46.