International Alliance

Supports a claim in this answer

in the JETALS study the methylcobalamin group had a 1.97 point difference on the ALSFRS-R over 16 weeks compared with placebo

✓Supports this

“An ultra-high dose form of methylcobalamin was approved for ALS/MND in Japan in 2024.”

Gives the approval and its date, and notes that the dose approved for ALS/MND is far higher than the low-dose methylcobalamin already used in Japan for other nerve conditions.

Based on the outcomes of a Phase 3 clinical trial, an ultra-high dose of methylcobalamin (50 mg) was approved in Japan on September 24, 2024, for the treatment of ALS/MND.

Background

✓Supports this

“The larger, longer trial that came before JETALS did not meet its main endpoints.”

Describes this trial and its result. It ran in 44 Japanese centres in 373 people within three years of symptom onset, testing 25 mg and 50 mg twice weekly against placebo for 182 weeks, with survival and the ALSFRS as primary outcomes. Neither dose met them. A later look suggested a difference in those who joined within a year of onset, and JETALS was built to test that group.

Both concentrations of methylcobalamin were found to be safe and well tolerated however, the primary endpoints were not met in either group.

Clinical Trials

✓Supports this

“JETALS enrolled 130 people in Japan within a year of symptom onset and declining at a defined moderate rate, most already on riluzole, and over 16 weeks the methylcobalamin group differed from placebo by 1.97 points on the ALSFRS-R.”

Gives the figure and the entry criteria the answer now carries: 130 people across 25 Japanese centres, within a year of symptom onset, with progression defined as a 1 to 2 point fall in ALSFRS-R over a 12 week observation period beforehand, and 90% already taking riluzole. Summarised because the sentence carrying the number is grammatically incomplete on the page.

!Qualifies this

“In JETALS, muscle strength and breathing measures showed no significant difference from placebo, the trial lasted only 16 weeks, and participants may have been able to tell which group they were in.”

Lists all three limits itself. Muscle strength, forced vital capacity and Norris scale scores showed no significant difference from placebo, and the page calls the trial shorter than most ALS/MND trials at 16 weeks and notes that methylcobalamin's effect on urine colour may have let participants work out which group they were in.

Additionally, muscle strength, forced vital capacity and Norris scale scores did not show significant differences compared to the placebo group.

Clinical Trials

✓Supports this

“Over-the-counter supplement quality varies, and high doses of vitamin B12 may be harmful.”

Raises this directly alongside the efficacy point, citing an ALSUntangled review from 2015. The Alliance does not say what dose becomes harmful or what the harm is, so the answer states the caution without putting a number on it.

Furthermore, the quality of over-the-counter supplements can be inconsistent, and high doses may be detrimental to health

Current Status

✓Supports this

“Over-the-counter vitamin B12 has not been shown to be effective for ALS/MND, and the trials and the Japanese approval use 50 mg injected into a muscle twice a week.”

Says the efficacy of over-the-counter oral vitamin B12 for ALS/MND is unproven, which is a statement that nothing has shown it works rather than a question of how well it works compared with injections. The same page gives the approved Japanese dose as 50 mg twice a week injected intramuscularly, and both trials used twice weekly intramuscular injections at 25 mg or 50 mg.

While oral formulations of vitamin B12 are easily accessible over-the-counter, their efficacy for ALS/MND remains unproven.

Current Status

Further reading

Trial evidence and current approval status