Methylcobalamin
Information on nutritional supplements people with ALS have been taking
Effects on ALS[edit]
Efficacy and safety of ultra-high dose (25mg or 50mg i.m. twice weekly) of methylcobalamin compared with placebo for ALS patients has been assessed. For the patients who were given diagnosis of ALS within 12 months after the onset, the event-free survival was prolonged in a dose-dependent manner and ALSFRS-R changes were smaller in active group than in placebo. No adverse events of particular concern were noted. Patients are less likely to benefit from ultra-high dose methylcobalamin treatment if more than 2 to 3 years have passed since the onset of ALS. CONCLUSION: The study demonstrated for the first time that ultra-high dose methylcobalamin can significantly prolong survival and retard progression in ALS if administered early. [1]
Already earlier high-dose methylcobalamin showed the increase in compound muscle action potential in a trial for ALS (Kaji et al.1998).
In cell culture studies, methylcobalamin ameliorates oxidative stress, glutamate toxicity and apoptosis. High doses can inhibit DNA methylation. Lowers plasma homocysteine levels.
Forms[edit]
Do not confuse methylcobalamin to cyanocobalamin, another less effective form of Vitamin B12.
Cautions[edit]
Vitamin B12 use is unsafe at least in following medical conditions: High numbers of red blood cells (polycythemia vera), abnormal red blood cells (megaloblastic anemia), Leber’s disease (a hereditary eye disease), allergy or sensitivity to cobalt or cobalamin, post-surgical stent placement, pregnancy or breast-feeding. (Source: WebMD)
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ALSUntangled evaluation[edit]
MeCbl has promising mechanisms and positive pre-clinical data from two different ALS models. Unfor-tunately, the anecdotal data we found did not identify any clear specific benefit, and the best of three clin-ical trials was unable to show an overall difference in ALSFRS-R progression or survival between PALS treated with MeCbl and those treated with placebo (26). A sub-group of patients with very specific pre-treatment progression rates of 1–3 ALSFRS-R points over 12 weeks, and very early disease (less than 12 months from symptom onset) may have had benefit (26). This finding needs to be replicated, especially since an earlier study suggested patients with longer disease duration were more likely to benefit (20). We would like to see a full traditional sub-group analysis (28) carried out on the data from the third trial (26). This sub-group analysis could then be used to design inclusion criteria for a new phase III trial comparing MeCbl 50 mg twice a week IM to placebo. The new trial could measure serum B12 and homocysteine, and have pre-planned sub-group analyses that are both logical and practical. While we wait for this, PALS who wish to try MeCbl are reminded that the above studies used very high, injected doses, which appear to be available only by prescription. Lower over-the-counter doses administered orally have not been studied. It is well established that over-the-counter oral supplements may be of poor and inconsistent quality (32). Some over-the-counter oral vitamin B supplements contain not only B12 but also B6, which in large quantities can be harmful to the nervous system (33).[1]
References[edit]
[1] <bibtex> @article{Kaji2015, abstract = {OBJECTIVE: To investigate the efficacy and safety of ultra-high dose (25mg or 50mg i.m. twice weekly) of methylcobalamin compared with placebo for amyotrophic lateral sclerosis (ALS) patients. BACKGROUND: High-dose methylcobalamin showed neuroprotective effects in acrylamide neuropathy (Watanabe et al.1994) and the increase in compound muscle action potential in a trial for ALS (Kaji et al.1998). DESIGN/METHODS: Patients (373) who were diagnosed with definite, probable, or probable-laboratory-supported ALS by revised El Escorial criteria were enrolled in this study. Those with [percnt]FVC less than 60[percnt] and the disease duration more than 3 years were excluded. Patients were randomly assigned to receive placebo, 25mg, or 50mg methylcobalamin i.m. twice weekly for 182weeks. Primary endpoints were event-free survival (time until death, TIPPV or all-day NIPPV) and ALS Functional Rating Scale-Revised (ALSFRS-R) changes. RESULTS: Of 373 patients, 370 (placebo 123, 25mg 124, 50mg 123) constituted the full analysis set. In both endpoints, there was no statistical significance in the comparison for the two dose response contrasts (linear and saturate hypothesis). For the patients who were given diagnosis of ALS within 12months after the onset (placebo 48, 25mg 54, 50mg 42), the event-free survival was prolonged in a dose-dependent manner (P=0.010, hazard ratio [95[percnt]CI] vs 25mg, 50mg were 0.640 [0.377, 1.085], 0.498 [0.267, 0.929], respectively) and ALSFRS-R changes were smaller in active groups (P=0.003) than in placebo. No adverse events of particular concern were noted. DISCUSSION: The diagnosis of ALS with revised El Escorial criteria is often delayed but newly-devised Awaji criteria have enabled earlier diagnosis. Patients are less likely to benefit from ultra-high dose methylcobalamin treatment if more than 2 to 3 years have passed since the onset of ALS. CONCLUSION: The present study demonstrated for the first time that ultra-high dose methylcobalamin can significantly prolong survival and retard progression in ALS if administered early. Disclosure: Dr. Kaji has received research support from GlaxoSmithKline and Eisai Inc. Dr. Kuzuhara has nothing to disclose. Dr. Iwasaki has nothing to disclose. Dr. Okamoto has nothing to disclose. Dr. Nakagawa has nothing to disclose. Dr. Imai has nothing to disclose. Dr. Takase has nothing to disclose. Dr. Shimizu has nothing to disclose. Dr. Tashiro has nothing to disclose.}, author = {Kaji, Ryuji and Kuzuhara, Shigeki and Iwasaki, Yasuo and Okamoto, Koichi and Nakagawa, Masanori and Imai, Takashi and Takase, Takao and Shimizu, Hiroki and Tashiro, Kunio}, journal = {Neurology}, mendeley-groups = {b12}, month = apr, number = {14\_Supplement}, pages = {P7.060--}, title = Template:Ultra-high dose methylcobalamin (E0302) prolongs survival of ALS: Report of 7 years' randomised double-blind, phase 3 clinical trial (ClinicalTrials.gov NCT00444613) (P7.060), url = {http://www.neurology.org/content/84/14\_Supplement/P7.060.short}, volume = {84}, year = {2015} }
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