Quote from Jenny on February 9, 2022, 6:07 am

I come across things in my reading on CFS/ME (for a family member) and my quest to solve the biochemical trigger part of my anxiety, that flash lights of possible relevance here (vA toxicity very relevant for CFS imo so works both ways). I’d hoped my anxiety was purely vA toxicity but I think something else going on for me as although many issues have resolved, this has got worse not better. I’ve written about pyroluria elsewhere (this includes a comment on the related porphyria) and also I’ve done a post on the sulphur pathway and sulphate deficiency, which can lead to heavy metal toxicity. Here I’m just going to summarise a couple of interesting pathways relating to NAD. 

Bob Miller talks about the ‘NADPH steal’. NADPH is made from NAD. NAD is the cofactor for the ALDH enzyme that turns retinaldehyde to retinoic acid. Lacking this cofactor would not be good for our detox. 

He talks about an enzyme called NOX which uses NADPH to make ROS (reactive oxygen species) to fight infections. This then upregulates mast cells and increases histamine. It’s an important enzyme, however, if it gets chronically upregulated it can lead to NADPH being depleted from the system. The ‘NADPH steal’. NAD and NADPH are required for many things. VA metabolism/detox is one. Recycling glutathione from oxidised to reduced is another. 

I can see how anything that chronically upregulates NOX would be unhelpful to health recovery. Many things do this e.g. glutamate, oxalates, histamine, iron, EMF, mold etc. All things we know aren’t good. 

Related to this is the de novo pathway of NAD that uses tryptophan to make either serotonin or NAD (and other molecules - some good, some  bad). There is a CFS theory called the IDO metabolic trap that blocks the production of NAD this way and is hypothesised to be an underlying factor in CFS susceptibility. This is a path impacted by stress and magnesium/B6 deficiency. Things I’m very interested in! 

I just find it interesting that so many fingers are being pointed at NAD. However, taking niacin or other NAD precursors may not help if NOX is upregulated. It could make things worse by adding more fuel to the fire. The body is short of it but it goes to the unhelpful pathway. I think of it as giving a starving drug addict money. You want it to be spent on food but it goes on drugs and makes the situation worse (that’s just me as I like a visual analogy!). Need to calm down NOX first. 

These are just some ideas I’m thinking about. They may be of no interest to anyone else! 

https://www.environmentalhealthsymposium.com/blog/ehs-free-webinars-with-dr-bob-miller-of-nutrigenetic-research-institute-and-functional-genomic-analysis