Editing Methylcobalamin

[[Information on nutritional supplements people with ALS have been taking]]

* [http://www.tandfonline.com/doi/full/10.3109/21678421.2015.1070574 ALSUntangled evaluation report]  

* [http://examine.com/supplements/Vitamin+B12/ Examine.com article on Vitamin B12] 

== Effects on ALS ==

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 ==
Do not confuse methylcobalamin to cyanocobalamin, another less effective form of Vitamin B12.

== Cautions ==

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. ([http://www.webmd.com/vitamins-supplements/ingredientmono-926-Vitamin+B12.aspx?activeIngredientId=926&activeIngredientName=Vitamin+B12&source=1 Source: WebMD])
 
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== References ==

[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 = {{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}
}
</bibtex>

[[Category:Supplement data pages]]
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-== ALSUntangled evaluation ==
-''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).''{{#pmid:26203660|Alsuntangled2015}}
 == References ==