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NAD deficiency - is this a major issue for vA toxicity/detox?
I’m just going to try and summarise my thoughts on NAD deficiency in one place as I’ve made comments in different locations which is a bit confusing. (If anyone want to see other comments they are under, ‘NADPH steal’, Mat’s Seborrheic Dermatitis post and I think Beata’s log and maybe elsewhere!?). In the last week or so I’ve made observations and come across work that has linked together disparate pieces of information that I had in my brain. This has convinced me that NAD deficiency is highly significant to us here (and to many other groups with health issues). Of course I may be completely wrong. However, when something links so many unexplained facts, as the discovery of Grant’s vA toxicity work did for me in 2018, I suspect it has legs.
Part 1:
In a nutshell.
ALDH is an important enzyme for processing vitamin A. ALDH depends on the cofactor NAD. NAD is derived from vitamin B3 in the diet and made in the microbiome. It can also be made by a de novo pathway called the tryptophan-NAD or kynurenine pathway.
If demands on NAD outweigh the body’s ability to get from diet/produce it then we get a NAD deficiency. Grant has long said that the ‘detox setback cycle’ could be B vitamin deficiency. I think he is right. I think it’s B3. I think the vA detox can exhaust the supply of NAD.
The de novo pathway to produce NAD, the ‘troublesome tryptophan’ pathway is fraught with issues. Therefore, when this gets upregulated we can get a build up of problematic intermediate metabolites like quinolinic acid that cause extra issues (anxiety, migraines, dry eyes etc). My anxiety got worse not better on the vA detox.
However, simply adding more B3 may not work. It may for some though. The long covid NAD deficiency group recommend the nicotinic acid form of B3 35-100mg x3 a day. It should work unless you have ‘NADPH steal’ going on in your body, where the B3 is taken by an upregulated NOX enzyme. This could make people feel worse. May need to calm NOX first.
I will post some more detail on this later. I want to describe the long covid work which details the negative effects of an upregulated de novo tryptophan-NAD pathway. I also want to describe some of the issues that steal away our NAD by upregulating NOX. I also want to describe the implications of a ‘slow ALDH’ - one that is lacking enough cofactor - as this leads to a slowed vA detox and potential build up of nasty aldehydes. The body can get into some seriously damaging vicious cycles that need care to unpick.
Edit: NB if slow ALDH due to NAD deficiency is slowing your vA detox then addressing this will speed up THIS step. This step is retinaldehyde to retinoic acid. It is a necessary step for removal of excess vA from the body. However, we need to make sure we can cope with the extra retinoic acid. I would advise doing any change very slowly. Snails pace. We don’t want to flood the system with retinoic acid.
Thank you @jaj
After reading your posts which made a lot of sense, for the last 5 days we took 100 mg niacinamide. Deeper sleep at the beginning. A sensation of being back in my old self. The brain is working fast and easy. However, yesterday I had too much energy during the night. We shall see.
Today I received the nicotinic acid I ordered. From tomorrow we will try it.
Your previous posts are here:
@jaj @ourania I have nicotinic acid arriving today as well, will test and post how I do in this thread. Will try 50mg x3 per day. My sleep is disturbed extremely easily so will use that and how my hands and feet react, they get ice cold when I imbalance something.
Thank you @ourania and @orion for trying this experiment and sharing.
It’s very interesting that you felt better Ourania. It could be that the nicotinic acid will be even better for you and not increase other symptoms. Or it could be that another factor needs addressing before the NAD deficiency can be helped without other symptoms escalating. Or of course it could be an incorrect theory. Of interest to you could be that quinolinic acid is very associated with eye issues. Magnesium is the cofactor that helps this convert to NAD. Therefore magnesium could help symptoms and limit the build up of QA, but slowing the production of QA would be getting more to the root cause.
I would always start low and slow with any new supplement.
I look forwards to hearing more. My nicotinic acid should arrive Monday. I’ve been using a B multi containing niacin but a pure supplement will be better as there are too many variables with a multi and I can’t take it x3 a day.
A diagram for those, like me, who like a diagram.
Shows the various things that upregulate NOX and cause a drain on NAD.
Click to access Holmes%2BCycle%2Bwith%2BIngredients2.pdf
Not saying that it’s a good idea to take any of these things but it may give people ideas on where they may have issues.
I wonder if vA toxicity upregulates NOX in some way?
Or is it a completely separate drain on NAD, via ALDH?
Or both?
@jaj So like I said in the other thread I will post here.
I recently did a complete oxydativ stress panel as well as a neuroT one. Sadly, glutamate and gaba results are still pending but I have interesting data to share nonetheless.
So first thing, vA serum is sil at 2,03 umol/L despite 6 month of low vA.
Now within the oxydativ stress panel that I have done there is multiple marker of interest, namely :
- COQ10 is low
- Vit E is low
- SOD is high
- Glutathion is high
To me this is a classic high oxydativ stress environnment. For instance, SOD will adapt and upregulate itself when facing a chronic oxydativ stress.
Then there is several other :
- Tryptophan is high
- Kynurenine is OK tho on the high end of the range
- So the Trypto/Kynu ratio is OK
Like I said I'm still waiting the GABA/Glutamate results. I'm also still waiting the 24h HPU results.
I too wonder if lack of NAD is a driving force behing low/inadequate ALDH activity. I've been using PQQ for a month and nothing improved so I stopped. Never tried NAD+ so I thought about trying Nicotinamide Riboside, but as per what I'm reading here it might not be the best idea ? Not sure why since it should be more efficient a producing NAD.
Here is the pathway in image (IDO/TDO)
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Quote from Mat on February 20, 2022, 1:50 am@jaj So like I said in the other thread I will post here.
I recently did a complete oxydativ stress panel as well as a neuroT one. Sadly, glutamate and gaba results are still pending but I have interesting data to share nonetheless.
So first thing, vA serum is sil at 2,03 umol/L despite 6 month of low vA.
Now within the oxydativ stress panel that I have done there is multiple marker of interest, namely :
- COQ10 is low
- Vit E is low
- SOD is high
- Glutathion is high
To me this is a classic high oxydativ stress environnment. For instance, SOD will adapt and upregulate itself when facing a chronic oxydativ stress.
Then there is several other :
- Tryptophan is high
- Kynurenine is OK tho on the high end of the range
- So the Trypto/Kynu ratio is OK
Like I said I'm still waiting the GABA/Glutamate results. I'm also still waiting the 24h HPU results.
I too wonder if lack of NAD is a driving force behing low/inadequate ALDH activity. I've been using PQQ for a month and nothing improved so I stopped. Never tried NAD+ so I thought about trying Nicotinamide Riboside, but as per what I'm reading here it might not be the best idea ? Not sure why since it should be more efficient a producing NAD.
Here is the pathway in image (IDO/TDO)
I think the issue is that it’s not just lack of NAD that’s the problem. It’s upregulation of the kynurenine pathway (I now think of as the ‘troublesome tryptophan’ pathway). The nicotinic acid form is the one that slows down this pathway the best. The other forms are involved in the salvage pathway. That is my understanding. (I must find out how to post diagrams - so much better than words).
Very interesting about your results Mat. Useful to actually see abnormalities sometimes.
Edit: for some people it’s not an upregulation of the kynurenine pathway that causes problems it’s an inability to activate the pathway. There is a theory of CFS/ME called the IDO metabolic trap where the kynurenine pathway is blocked. This means that there is no emergency supply of NAD available. However, this is associated with serious CFS/ME. You may have a less serious block going on.
I would ask why trptophan is high? Lack of cofactors could prevent kynurenine pathway and serotonin pathway running smoothly (B6 is a big issue for both, also B2 and magnesium). High trptophan and kynurenine would fit with this. Could mean the pathway is stuck and you aren’t making the emergency NAD required. This would fit with NAD deficiency and slow ALDH. I will re-post some of this on your thread as it’s making a clear picture for me now. I really think that low B6 could be an issue for you too. NAD deficiency and B6 deficiency - stopping you making emergency NAD.
After 5 days on 100 mg niacinamide we had a few improvements: deeper sleep, vivid brain, more energy but the last day saw bad detox pains, blurry vision and inability to remember names. Today we took 50 mg x 2 nicotinic acid, the detox went on worse. Maybe an effect of the niacinamide of the previous days? I could mitigate a bit the detox with B6 + B2 and an Epsom salts bath.
We are going to stop for now and start again on nicotinic acid when we feel better. To find out if really nicotinic acid is better for us.
Sorry to hear that Ourania. Sounds like unhelpful pathways have been pushed. A rest sounds like a good idea.
I’m going to start on a low amount of nicotinic acid and increase very slowly. Dr Wentzel said in his interview ‘the body does not like rapid metabolic change’ ‘slow and easy, do no harm’ He suggested 25mg x2 a day of the nicotinic acid, he was adamant about the type.
I think I will go with this suggestion and do low levels. Otherwise it’s hard to know if you are seeing a real negative reaction and the supplement isn’t helpful (or is fueling NOX and this needs addressing) or it’s just the body protesting against too fast a metabolic change.