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Vitamin B12 and effects on mitochondria


Senior Member
Premission to repost by Prof. Gavin Giovannoni

There are some in the ME/CFS medical field that believe ME/CFS is 'MS Light' or 'Atypical MS'. The reason I post these articles is the fact that research in one area may spill over into another area of research or the fact that researchers reviewing a site may look at the research in another disease category that could be related to theirs and it might raise their interest level.

Futhermore, research may be further ahead in another field that ME/CFS researchers wish to explore if they had the funding and the researchers to explore such as EBV, HERVs, Autoimmune diseases, Fibromyalgia, Lyme etc.

Vitamin B12 and effects on mitochondria:

Changes in Methionine Metabolism and Histone H3 Trimethylation Are Linked to Mitochondrial Defects in Multiple Sclerosis.Singhal NK, Li S, Arning E, Alkhayer K, Clements R, Sarcyk Z, Dassanayake RS, Brasch NE, Freeman EJ, Bottiglieri T, McDonough J.J Neurosci. 2015 Nov 11;35(45):15170-86.

Mitochondrial changes, including decreased expression of electron transport chain subunit genes and impaired energetic, have been reported inmultiple sclerosis (MS), but the mechanisms involved in these changes are not clear. To determine whether epigenetic mechanisms are involved, we measured the concentrations of methionine metabolites by liquid chromatography tandem mass spectrometry, histone H3 methylation patterns, and markers of mitochondrial respiration in gray matter from postmortem MS and control cortical samples.

We found decreases in respiratory markers as well as decreased concentrations of the methionine metabolites S-adenosylmethionine, betaine, and cystathionine in MS gray matter. We also found expression of the enzyme betaine homocysteine methyltransferase in cortical neurons.

This enzyme catalyzes the remethylation of homocysteine to methionine, with betaine as the methyl donor, and has previously been thought to be restricted to liver and kidney in the adult human. Decreases in the concentration of the methyl donor betaine were correlated with decreases in histone H3 trimethylation (H3K4me3) in NeuN+ neuronal nuclei in MS cortex compared with controls.

Mechanistic studies demonstrated that H3K4me3 levels and mitochondrial respiration were reduced in SH-SY5Y cells after exposure to the nitric oxide donor sodium nitroprusside, and betaine was able to rescue H3K4me3 levels and respiratory capacity in these cells. Chromatin immunoprecipitation experiments showed that betaine regulates metabolic genes in human SH-SY5Y neuroblastoma cells.

These data suggest that changes to methionine metabolism may be mechanistically linked to changes in neuronal energetics in MS cortex.

For decades, it has been observed that vitamin B12 deficiency and multiple sclerosis (MS) share certain pathological changes, including conduction disturbances.

In the present study, we have found that vitamin B12-dependent methionine metabolism is dysregulated in the MS brain. We found that concentrations of the methyl donor betaine are decreased in MS cortex and are correlated with reduced levels of the histone H3 methyl mark H3K4me3 in neurons.

Cell culture and chromatin immunoprecipitation-seq data suggest that these changes may lead to defects in mitochondria and impact neuronal energetics. These data have uncovered a novel pathway linking methionine metabolism with mitochondrial respiration and have important implications for understanding mechanisms involved in neurodegeneration in MS.

Old Bones

Senior Member
With the exception of rapidly-progressing MS that results in early death, I'm not sure I'd characterize my severe (but not very severe) ME as "MS Light". Although I'm sure they feel worse than they look (like most of us), and have many challenges that aren't outwardly visible (again like us), all but one of the MS patients I've encountered have been much more functional than I've been for 25 plus years, and they have enjoyed a better quality of life -- with jobs, kids, social lives, hobbies, travel, etc. I've been trying to find a recent blog post either here, or on Cort's website, that supported this position by comparing various medical conditions according to "illness burden". ME/CFS scored worse than MS, I seem to recall.