Addressing NAD+ sensitivities, problems, and solutions

Dear All,

We reached page 12 on the NAD+ thread, when Nov posted questions that eloquently framed the direction the thread was taking, so I thought it would be a good idea to start a new one.  I will copy Nov's post and put it here right below this one:

For the record, 3 things:

First, I think that NAD+ still holds promise for many of us.  I am still convinced that the majority of our pain is glutamate reception, and this potent niacin metabolite holds promise in lessening both the quantity of glutamate transmitted presynaptically, the clearance of glutamate by EAAT, postsynaptically, and the reductoin of evoked Excitory POst Synaptic Current (eEPSC) as was shown in the paper I posted on NAD+ for Bilirubin Excitotoxicity.

Second, I was PAINFULLY reminded that histamine is very important to our pain as well, as in, we also need to reduce our histamine, but

Third, MANY things, from niacin to NAD+ to plain old ethyl alcohol, that are great at slowing glutamate, also simultaneously raise histamine.

While most of us know the pitfalls of alcohol use in bzd withdrawal, we might not have thought of niacin and all its metabolites in this way.  Well I sure am now, and I liked Nov's post so much it inspired me to give us a separate place to hash this out.

I will be spending the next several weeks (months?) looking at histamine, what we in general can do about it, what mutants in specific can do about it, and if, once optimally managed, one would be able to tolerate NAD+ to help with glutamate aspect of this mess.

I will post what I learn, and hope to see what thoughts you all may have.

Ramcon1

From Nov3 from the previous thread below.  There are pluses and minuses to literally everything he suggested.

Let's have at it.

Ramcon1

So let's assume one has all of the aforementioned genetic mutations that make them potentially sensitive to NAD+. Would adequate supplementation be sufficient enough in addressing those genetic shortcomings to make NAD+ safe and tolerable?

 

Slow COMT for example, can be addressed by supplementing SAMe, Magnesium, NAC, and Vitamin D and following a lower protein diet.

 

There are various Methylation supplements on the internet. Which contain 5-MTHF (folate), Methylcobalamin (B12), Pyridoxal 5'-Phosphate (B6), Riboflavin 5'-Phosphate (B2), etc.

 

And one could supplement fish oil, curcumin, resveratrol and Vitamin D for a VDR Bsm mutation & acetyl-L-carnitine, fish oil, and amino acids for an AKT1 mutation, if those indeed play some role...

 

If we supplement all of the above prior to doing NAD+, do you think we would be safe and prepared even if our genes aren't optimal?

Ramcon, and others...

I think I'm going to try to address the potentiality of these gene variations with a protocol similar to the one I mentioned in the above quote.

I ordered a SelfDecode genetics kit, but it'll take at least 2 months before I have results, and honestly, I don't think I have the patience to wait. I'd like to get into an NAD+ clinic in a month or so.

I don't seem to have as severe of histamine issues as others. I feel like crap all of the time, but my symptoms aren't, at least super apparently, in correspondence with things that elevate histamine. I don't know if I have the genetics for methylation issues, though, I have read that it is beneficial for ANYONE to methylate when doing NAD+, given its direct impact on the methylation process. Plus, these supplements are, for the most part, generally safe and innocuous (may have to take it slow with the B vitamins and look more into SAMe). So I might as well!

I recall Sky suggesting you address your under-methylation. Sky, ramcon, or anyone who knows... Is this a matter of simply taking these supplements while doing NAD+, or would it take a certain amount of time taking said supplements to build up your methylation?

How long would you all suggest I follow a methylation boosting protocol prior to jumping into NAD+?

From Nov3 from the previous thread below.  There are pluses and minuses to literally everything he suggested.

 

Let's have at it.

 

Ramcon1

 

So let's assume one has all of the aforementioned genetic mutations that make them potentially sensitive to NAD+. Would adequate supplementation be sufficient enough in addressing those genetic shortcomings to make NAD+ safe and tolerable?

 

Slow COMT for example, can be addressed by supplementing SAMe, Magnesium, NAC, and Vitamin D and following a lower protein diet.

 

There are various Methylation supplements on the internet. Which contain 5-MTHF (folate), Methylcobalamin (B12), Pyridoxal 5'-Phosphate (B6), Riboflavin 5'-Phosphate (B2), etc.

 

And one could supplement fish oil, curcumin, resveratrol and Vitamin D for a VDR Bsm mutation & acetyl-L-carnitine, fish oil, and amino acids for an AKT1 mutation, if those indeed play some role...

 

If we supplement all of the above prior to doing NAD+, do you think we would be safe and prepared even if our genes aren't optimal?

we often search for answers within the genetic mutations however our bodies are so much more than them, many people have these mutations and never have a problem ever, their bodies adapt and find work arounds.    It about listening to the body, dealing with one thing at a time, testing one thing at a time, maybe methylation, maybe histamine, maybe allergies, maybe maybe maybe.  Healing takes many forms and we eash have to listen to our bodies as we adjust and heal.

Do all gene mutations affect health and development?

No; only a small percentage of mutations cause genetic disorders—most have no impact on health or development. For example, some mutations alter a gene's DNA sequence but do not change the function of the protein made by the gene.

Often, gene mutations that could cause a genetic disorder are repaired by certain enzymes before the gene is expressed and an altered protein is produced. Each cell has a number of pathways through which enzymes recognize and repair errors in DNA. Because DNA can be damaged or mutated in many ways, DNA repair is an important process by which the body protects itself from disease.

A very small percentage of all mutations actually have a positive effect. These mutations lead to new versions of proteins that help an individual better adapt to changes in his or her environment. For example, a beneficial mutation could result in a protein that protects an individual and future generations from a new strain of bacteria.

Because a person's genetic code can have a large number of mutations with no effect on health, diagnosing genetic conditions can be difficult. Sometimes, genes thought to be related to a particular genetic condition have mutations, but whether these changes are involved in development of the condition has not been determined; these genetic changes are known as variants of unknown significance (VOUS) or (VUS). Sometimes, no mutations are found in suspected disease-related genes, but mutations are found in other genes whose relationship to a particular genetic condition is unknown. It is difficult to know whether these variants are involved in the disease.

Ramcon, and others...

 

I think I'm going to try to address the potentiality of these gene variations with a protocol similar to the one I mentioned in the above quote.

I ordered a SelfDecode genetics kit, but it'll take at least 2 months before I have results, and honestly, I don't think I have the patience to wait. I'd like to get into an NAD+ clinic in a month or so.

 

I don't seem to have as severe of histamine issues as others. I feel like crap all of the time, but my symptoms aren't, at least super apparently, in correspondence with things that elevate histamine. I don't know if I have the genetics for methylation issues, though, I have read that it is beneficial for ANYONE to methylate when doing NAD+, given its direct impact on the methylation process. Plus, these supplements are, for the most part, generally safe and innocuous (may have to take it slow with the B vitamins and look more into SAMe). So I might as well!

 

I recall Sky suggesting you address your under-methylation. Sky, ramcon, or anyone who knows... Is this a matter of simply taking these supplements while doing NAD+, or would it take a certain amount of time taking said supplements to build up your methylation?

 

How long would you all suggest I follow a methylation boosting protocol prior to jumping into NAD+?

https://kresserinstitute.com/treating-methylation-supplementing/

from this article link above Published: June 9, 2020.  research and listen to your own body.

It is never just one thing as I said in last post, and we need info for ourselves individually.

Many other links at the bottom of that article.   

The Perils of Over-Supplementing

For several years, high-dose methyl donors have been viewed as the standard method for treating methylation issues. In the last several years, the viewpoint has evolved, and  we now believe there is sufficient evidence to suggest that long-term high-dose methyl donor supplementation can be harmful. Like many nutrients, methylation appears to follow a U-shaped curve, where both deficiency and excess cause pathology. While hypomethylation is associated with many different problems, hypermethylation may be equally problematic. What we really need is methylation balance.

While genetic information can certainly be useful, it’s important to look at genetic results alongside functional methylation markers. Markers of impaired methylation on a typical functional blood chemistry panel include low serum folate, low serum B12, high serum MMA, and high serum homocysteine. Additional indicative markers include low RBC folate, high urine MMA, and high urine FIGLU.

https://kresserinstitute.com/treating-methylation-supplementing/

 

from this article link above.  research and listen to your own body.

 

It is never just one thing as I said in last post, and we need info for ourselves individually. 

 

The Perils of Over-Supplementing

For several years, high-dose methyl donors have been viewed as the standard method for treating methylation issues. In the last several years, the viewpoint has evolved, and  we now believe there is sufficient evidence to suggest that long-term high-dose methyl donor supplementation can be harmful. Like many nutrients, methylation appears to follow a U-shaped curve, where both deficiency and excess cause pathology. While hypomethylation is associated with many different problems, hypermethylation may be equally problematic. What we really need is methylation balance.

 

 

While genetic information can certainly be useful, it’s important to look at genetic results alongside functional methylation markers. Markers of impaired methylation on a typical functional blood chemistry panel include low serum folate, low serum B12, high serum MMA, and high serum homocysteine. Additional indicative markers include low RBC folate, high urine MMA, and high urine FIGLU.

Thanks, Sky!

I'll take a look at that article and review my past blood panels as well!

I definitely don't intend to take any supplementation on a long term basis. Just a short period prior to and during NAD+. I've read a lot of articles suggesting such supplementation while doing NAD+ would be beneficial, even for people that aren't hypomethylators, and prevent any negative side effects associated with NAD+/methyl issues...which can seemingly even happen to people with balanced methylation during NAD+ infusions or high doses of niacin or nicotinamide riboside.

Dear All,

I am still in pain from the small dose of NAD+ in the nasal spray.  I think it revealed just how big a problem I personally have with histamine.

I have been so preoccupied with glutamate, I forgot that piece of the puzzle.  I apologize to those who have looked to me for guidance to whom I have given incomplete information.

Thanks to Sky for the good information.  I will be researching and testing things that might help my own histamine issues, take some of Sky and Chris Kessler's advice and other info I will gather and report it here.  I think, with few exceptions, once histamine issues are resolved, including methylation which is part of how we clear histamine, then NAD+ can do its job on glutamate.

Ramcon1

Dear All,

 

I am still in pain from the small dose of NAD+ in the nasal spray.  I think it revealed just how big a problem I personally have with histamine.

 

I have been so preoccupied with glutamate, I forgot that piece of the puzzle.  I apologize to those who have looked to me for guidance to whom I have given incomplete information.

 

Thanks to Sky for the good information.  I will be researching and testing things that might help my own histamine issues, take some of Sky and Chris Kessler's advice and other info I will gather and report it here.  I think, with few exceptions, once histamine issues are resolved, including methylation which is part of how we clear histamine, then NAD+ can do its job on glutamate.

 

Ramcon1

What if you take Rameron to help with the histamine? My CNS is so fried and I think I’m gonna try the nad IV in a few weeks. I just started remeron. It helps a lot but I hear it craps out and causes other problems. Who knows