Mechanisms need to be reviewed.
According to Russell in clinical pharmacology the most common
The most common disease-causing mutation occurs in the superoxide dismutase (SOD1) gene, although other mutations have been identified. The dysfunctional SOD1 enzyme forms a complex with copper and zinc ions within the mitochondria, leading to protein unfolding and aggregation. This accumulation disrupts the mitochondrial membrane potential and acts as a catalyst for further mitochondrial dysfunction. Cellular adenosine triphosphate (ATP) production is decreased and calcium homeostasis is disturbed, triggering apoptosis and leading to cell death.So, the calcium/zinc balance need to be looked at. How does diet affect those. Is it better to increase calcium and reduce zinc, or the opposite. Something as simple as this is probably not monitored at all, is probably easy to have huge ranges in various patients and can probably change outcomes dramatically. So, a patient could be trying something that worked for someone else and another finds it makes no difference.
There are so many different checks and balances taking changing that place in this disease.
My thoughts on the best treatment option at this point is to have a team and that team needs to include a biochemist, a pharmacist, an ALS neurologist, a dietitian, a homeopath, a herbalist, a botanist, a heptologist, a nephrologist, a hematologist, a cytologist, immuologist, someone with expertise in histamines and maybe a few others with expertise. This is just what comes to mind thinking about this based on the research that I've done in the past 10 days.
What I see happening in the literature is one piece being studied at a time, and I think a bigger and broader view of all of the mechanisms and inter-relations need to be worked on. These mechanisms are broken and so diet is critical and can dramatically change perceptions of what is working. I had a thought, which I forgot, but where that thought led me is to Dr Joneja, and her site, the low histamine chef, and that particular link has something about cell methylation, which I've already blogged about. There is also references to DAO all over this site, which I've come across in my reading to learn about ALS, so that mechanism needs to be looked at in diet as well.
Even comments on some of these sites are useful, for example:
"folic acid, which is synthetic, and can block methylation. Methylfolate (Metafolin, Folapro) or Folinic acid," and methylation is important here."
There are even links in a discussion about depression. This article links to this guest editorial about Decreased Mitochondrial Function and Increased Brain Inflammation in BipolarDisorder and Other Neuropsychiatric Diseases. It makes reference to the lack of understand as to how various brain inflammation disorders show up in a whole range of problems, from speech impairments to MS, etc., and the cruncher:
0 In fact, mitochondrial DNA was shown to be secreted from neuroblastoma cells inside membrane-enclosed exosomes.21 All these findings, taken together, may constitute a ‘‘triple jeopardy’’ for the brain: (a) decreased mitochondrial ATP production, (b) further reduction by diversion of ATP to support proinflammatory, and (c) extracellular ATP and mitochondrial DNA release, which can stimulate autoimmune/autoinflammatory reactionsThis study, Gliotoxicity of the cyanotoxin, β-methyl-amino-alanine (BMAA), looks at a number of the mechanisms from BMAA, and has huge supporting evidence of the mechanism of ALS.