Walsh's hypothesis and the NAD recipe revisited

[adreno]

It seems that someone else is way ahead of us, and has been discussing this issue at length, here:

http://www.longecity.org/forum/topic/27350-resveratrol-and-nampt-what-is-resveratrols-true-target/

Apparently, resveratrol upregulates NAMPT, and so it is suggested to combine resveratrol with niacin to increase NAD. They also agree with @Kimsie that niacin > niacinamide.

The post is 6 years old, I can't believe I haven't seen it before now.

 

[Kimsie]

I have the opposite, I have very high glutamate. I had an extremely severe benzo withdrawal which caused all of my anxiety and OCD. Actually the benzo I was only on for 2 weeks to calm me down from the thyroid med.s. It was an absolute disaster and is what brought me into ME

That's the same as my son, at least he has tested for high glutamate in the urine. I should have said that I thin OCD is caused by too low of some neurotransmitters or else an imbalance of neurotransmitters. Being undermethylated doesn't seem to stop adrenaline in my sons either, just the other ones.

Why were you taking thyroid meds? Did you test low?

 

[Tammy]

As far as I can tell with my son, OCD is caused by a lack of catecholamines in the synapses. But maybe it can be caused by something else in other people.

Kimsie............I am probably way out of my league here as far as this discussion goes..........but off the top of my head I thought there was a connection between too much dopamine and schizophrenia..........I know you were referring to OCD but I'm curious as to how you came to the conclusion that your son lacks catecholamines? Edit: I just saw your above reply which I didn't see when I was writing this. Right now you are hypothesizing based on symptoms? I didn't know if your son had his neurotransmitters tested or not?...........and please other members.......I know this is controversial...(testing for neurotransmitter levels).

 

[Kimsie]

Well, if that's the case, niacin won't help either.

A little bit can probably help somewhat along with some ribose, but large doses don't. As I said we already tried that and it actually can work for a while if you take it with enough magnesium and ribose etc, but it doesn't keep working. That's why we are using the thyroid now but there are so many other factors that I have no way of knowing if it would help for any particular individual.

You may wonder why I know that the thyroid works for my son. Well, over 6 years ago I decided to try giving my son S thyroid in the off chance that it might make it easier to stay away from energy drinks. If that seems strange and over the top to you, I guess you don't know what it is like to have schizophrenia. You are willing to try almost anything.

Nothing seemed to be happening and so I figured it wasn't doing anything and so when I learned that he had stopped taking medications a couple of months later and was doing just great, I stupidly didn't connect it with the thyroid. Later he ran out and he did tell me, but I didn't think his recovery had anything to do with the thyroid and so I didn't get any more.

It took a number of weeks for his symptoms to start returning, and so I still didn't connect the dots, and for all these years I have wondered why this happened but with the NAD recipe, etc, lately his thinking has been pretty good even though he hasn't been completely well, and he was able to remember about taking the thyroid and he was convinced it was the thyroid that had made him well before. When he told me I didn't believe it but he went out and got some on his own and his response to it made me check the dates when I ordered the thyroid and I can see that he is right about it.

My other son with depression responds to the exact same protocols as S, so I am pretty sure it will work with him, too, and he certainly feels a lot better with it, but I expect it will take a couple of months because it took about 6 weeks for the depression to gradually begin when he was taking large doses of folate.

 

[Kimsie]

Kimsie............I am probably way out of my league here as far as this discussion goes..........but off the top of my head I thought there was a connection between too much dopamine and schizophrenia..........I know you were referring to OCD but I'm curious as to how you came to the conclusion that your son lacks catecholamines?

I used to assume that it was simply too much dopamine, but lately I have become convinced that it is too little norepinephrine or an imbalance of neurotransmitters. Probably it can be various imbalances of neurotransmitters. Not all schizohrenia is the same. Some are overmethylators and others are undermethylators.

 

[Aerose91]

That's the same as my son, at least he has tested for high glutamate in the urine. I should have said that I thin OCD is caused by too low of some neurotransmitters or else an imbalance of neurotransmitters. Being undermethylated doesn't seem to stop adrenaline in my sons either, just the other ones.

Why were you taking thyroid meds? Did you test low?

The first time was speculative because of my adrenal fatigue (bad idea because it caused me to use benzos) and the second time, my total T3 measured low right after the onset of ME

 

[Kimsie]

I wasn't on any of those when I took the thyroid, but it was only a 5 mg dose and by the second one I was going nuts. It went away a day or two after I stoped.

These days I take magnesium, potassium, calcium and hydroxyb12. Its the only b12 I can tolerate

I don't really understand this dose of thyroid. 5 mg would be a tiny dose of dessicated thyroid, is that what you mean?

 

[Aerose91]

I don't really understand this dose of thyroid. 5 mg would be a tiny dose of dessicated thyroid, is that what you mean?

Yup. Started low and after just a couple doses it was intolerable.

 

[Kimsie]

The first time was speculative because of my adrenal fatigue (bad idea because it caused me to use benzos) and the second time, my total T3 measured low right after the onset of ME

I am not very knowledgeable about adrenal fatigue, but I guess I ought to try to learn about it.

 

[Tunguska]

If I go about taking only small doses of nicotinic acid during the day, what kind of d-ribose intake would go with that, how many grams? I don't want to overdo the ribose, various reasons

Also this is a better fit for me. Last time things were working I was taking small <50mg doses of nicotinic acid, not niacinamide. I'm forced to small doses because the flush is too painful. I took niacinamide ~1000mg (a?) month(s?) after that but it only worked for one day and then never again. I had the impression niacinamide was better in whatever dose. So I'm going to go with small nicotinic acid doses again even if it seems less natural.

 

[adreno]

A little bit can probably help somewhat along with some ribose, but large doses don't. As I said we already tried that and it actually can work for a while if you take it with enough magnesium and ribose etc, but it doesn't keep working. That's why we are using the thyroid now but there are so many other factors that I have no way of knowing if it would help for any particular individual.

You may wonder why I know that the thyroid works for my son. Well, over 6 years ago I decided to try giving my son S thyroid in the off chance that it might make it easier to stay away from energy drinks. If that seems strange and over the top to you, I guess you don't know what it is like to have schizophrenia. You are willing to try almost anything.

Nothing seemed to be happening and so I figured it wasn't doing anything and so when I learned that he had stopped taking medications a couple of months later and was doing just great, I stupidly didn't connect it with the thyroid. Later he ran out and he did tell me, but I didn't think his recovery had anything to do with the thyroid and so I didn't get any more.

It took a number of weeks for his symptoms to start returning, and so I still didn't connect the dots, and for all these years I have wondered why this happened but with the NAD recipe, etc, lately his thinking has been pretty good even though he hasn't been completely well, and he was able to remember about taking the thyroid and he was convinced it was the thyroid that had made him well before. When he told me I didn't believe it but he went out and got some on his own and his response to it made me check the dates when I ordered the thyroid and I can see that he is right about it.

My other son with depression responds to the exact same protocols as S, so I am pretty sure it will work with him, too, and he certainly feels a lot better with it, but I expect it will take a couple of months because it took about 6 weeks for the depression to gradually begin when he was taking large doses of folate.

Not really sure where you are going with this. I'm glad if thyroid helps your son, but what works for him isn't an indication of a condition in general. In general (on group basis) the research shows high dopamine and low glutamate (simplification) in both OCD and schizophrenia.

Urinary neurotransmitter tests are essentially worthless and don't tell you anything about what's going on in the brain.

 

[Kimsie]

Not really sure where you are going with this. I'm glad if thyroid helps your son, but what works for him isn't an indication of a condition in general. In general (on group basis) the research shows high dopamine and low glutamate (simplification) in both OCD and schizophrenia.

Urinary neurotransmitter tests are essentially worthless and don't tell you anything about what's going on in the brain.

I never said anything about urinary neurotransmitter tests, unless you mean the glutamine. You say yourself that you have high glutamine, did you have a CSF test done? Maybe you did, but I imagine that you hypothesize or have come to the conclusion that your glutamine is high through experimentation and reasoning, and that's how I know about my son, too.

There has been a study done where about 45% of the people with schizophrenia responded very well to high doses of dessicated thyroid so my son isn't such an isolated case as you might think. This was before the drugs came out. If there was a ton of money to be made in desiccated thyroid it would probably be a pretty popular treatment right now, but you can't really patent dried pig body parts.

 

[adreno]

I never said anything about urinary neurotransmitter tests, unless you mean the glutamine.

But you did:

That's the same as my son, at least he has tested for high glutamate in the urine.

As I said, this is no indication that glutamate is high in the brain (or certain regions of the brain) as well.

You say yourself that you have high glutamine, did you have a CSF test done?

I don't remember saying anything like this. I have said that I don't tolerate glutamine.

 

[adreno]

There has been a study done where about 45% of the people with schizophrenia responded very well to high doses of dessicated thyroid so my son isn't such an isolated case as you might think. This was before the drugs came out. If there was a ton of money to be made in desiccated thyroid it would probably be a pretty popular treatment right now, but you can't really patent dried pig body parts.

Several studies has been done lately using glycine, serine and sarcosine, which isn't exactly patentable either. Especially sarcosine seems helpful for schizophrenia and OCD as it is an allosteric modulator of the NMDA receptor. See for example:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3792577/

 

[adreno]

Oral administration of nicotinamide riboside (NR), a vitamin B3 and NAD+ precursor, was previously shown to boost NAD+ levels in mice and to induce mitochondrial biogenesis. Here, we treated mitochondrial myopathy mice with NR. This vitamin effectively delayed early- and late-stage disease progression, by robustly inducing mitochondrial biogenesis in skeletal muscle and brown adipose tissue, preventing mitochondrial ultrastructure abnormalities and mtDNA deletion formation. NR further stimulated mitochondrial unfolded protein response, suggesting its protective role in mitochondrial disease.

Effective treatment of mitochondrial myopathy by nicotinamide riboside, a vitamin B3

 

[Kimsie]

But you did:

As I said, this is no indication that glutamate is high in the brain (or certain regions of the brain) as well.

I don't remember saying anything like this. I have said that I don't tolerate glutamine.

OK, I guess I mistook what you meant by that.

I have been looking at LSD1 and it turns out that one of the things it "turns on" is dopamine cells, so it's probable that it is high dopamine in my son with Sz. LSD1 helps "turn on" a lot of genes so since it can turn on dopamine cells and neurotransmitter transporters it can have fairly opposite effects in different people, depending on their genetics, as far as I can see.

 

[Kimsie]

Effective treatment of mitochondrial myopathy by nicotinamide riboside, a vitamin B3

I wish they had compared NR with niacinamide, that's the question I would like to have answered. Also, we don't know which enzymes are affected in the mice or how those enzymes compare with people with these illnesses.

However, I checked out one of the studies that this study used as a reference and it said something very interesting. It appears that low NAD in the nucleus "resulted in a specific reduction in the expression of mitochondrially encoded OXPHOS, mtDNA content, and ATP levels".

Here's another interesting quote "Reducing NAD+ levels, either by knocking down NMNAT1 or by treating cells with lactate (which decreases the NAD+/NADH ratio)" So maybe this has something to do with PEM, because if PEM is caused by an increase in lactate due to using the glycolysis pathway for energy, then that would explain the time lag after exertion and why rest periods can prevent PEM because it would take some time for the lower NAD level to change the expression of the DNA and for symptoms to appear. Of course lactate should not be able to get into the nucleus, but so many other things are going wrong in people with ME/CFS that maybe there is a problem with the nuclear envelope that allows lactate to get in. The nucleus is supposed to maintain its own supply of NAD.

If you take this along with the previous quote, it might explain the vicious cycle of these illnesses at least in part.

It also said that "mRNA levels of all 13 mitochondrially encoded OXPHOS genes and the two rRNAs were reduced in the SIRT1 iKO mice compared to wild-type controls". This was in adult sirt1 knockout mice so that they had normal development. So if SIRT1 activity is reduced, it changes the oxidative phosphorylation capacity in the mitochondria (it also said that complex IV was especially reduced.)

So the question might be, "is lowered sirt1 activity causing lower NAD or is lower NAD causing lowered sirt1 activity?" I am going to be thinking about this more.

 

[nandixon]

So the question might be, "is lowered sirt1 activity causing lower NAD or is lower NAD causing lowered sirt1 activity?" I am going to be thinking about this more.

I think this 2012 article is indicating the latter, at least under their experimental conditions:

The NAD+ precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet induced obesity

These observations highlight how NR can only induce sirtuin activity in tissues where NAD+ accumulates.

Also, I didn't look at other references (I'm not very interested in NR because supplementation with it did nothing for me), but the one above is indicating a tissue-specific effect for NR, i.e., no increase in brain NAD+.

Also see Figs. 1C and1D, showing that nicotinic acid (NA) was as effective as NR at increasing NAD+.

 

[adreno]

Also see Figs. 1C and1D, showing that nicotinic acid (NA) was as effective as NR at increasing NAD+.

Yes, I guess the only problem with nicotinic acid is the flush. It's certainly cheaper than NR. I have read somewhere that oral NR is cleaved to niacinamide in the intestines anyway. It's hard to get a clear picture.

 

[adreno]

So the question might be, "is lowered sirt1 activity causing lower NAD or is lower NAD causing lowered sirt1 activity?" I am going to be thinking about this more.

Well, sirt activity uses up NAD, so I agree with @nandixon that it must be the latter.