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Walsh's hypothesis and the NAD recipe revisited

Discussion in 'General ME/CFS Discussion' started by Kimsie, Jan 23, 2015.

  1. Kimsie

    Kimsie Senior Member

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    I have been reading about the ideas of Bill Walsh, PhD., and I have to make some changes in my hypothesis and the NAD recipe in order to integrate his ideas about the methylation state of the histones, which seems to be the most important over and undermethylation effect, and doesn’t have anything to do with SAMe levels.

    First the change in the NAD recipe and then and explanation for those who want the technical part:

    Niacinamide should only be taken by overmethylators. Niacin should be used by undermethylators, but in smaller amounts. We are still experimenting to see what amount is needed. Otherwise the NAD recipe is the same, with ribose being the most important part.

    I know that some people here are familiar with Walsh’s ideas but I will give a brief overview for those who are not.

    How active a gene is depends on the amount of methylation in the histone tails of the histone that it is wrapped around. If the methylation level is high, the gene expression is low, if the methylation is low, the gene expression is high. These histone tails affect many processes, so it really isn't known yet all of the things that are affected by methylation levels that are too high or low, but one thing they are known to control is the number of neurotransmitter transporter proteins, which take the neurotransmitters out of the synapses. When these transporter proteins are more numerous the activity of the neurons will be less and so the methylation state of the histone controls how exposed to serotonin, dopamine and norepinephrine a neuron is. Naturally a person will have symptoms if the levels are either too high or too low.

    Folate is used by an enzyme called Histone Demethylase LSD1 which takes methyl groups off of histone. So folate, specifically THF, or tetrahydrofolate, can increase the expression of the gene which produces the neurotransmitter transporter proteins.

    Niacinamide inhibits sirtuins, which increase methylation of histone tails, so niacinamide has the same basic effect as folate, but sin sirtuins require NAD+, you have to have a large enough NAD/NADH pool so with these illnesses I think some regular niacin is needed, but not too much or the niacinamide levels will rise.

    So people who tend to have overmethylated histones need plenty of folate and niacinamide, and people who are undermethylators shouldn’t take much folate and only a limited amount of regular niacin. Methionine is supposed to help for undermethylators, too.

    I am studying a whole train of thought about how NAD is made and how it might have something to do with PEM (which at the moment I think might be caused by temporary axon damage in the brain) and neurological damage (more axon damage) but I haven't learned enough to post about it yet. I hope to have something in a few days.
     
    nandixon, helen1, Mary and 2 others like this.
  2. drob31

    drob31 Senior Member

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    What do you think about supplementing with NADH directly?
     
    PeterPositive likes this.
  3. Kimsie

    Kimsie Senior Member

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    I thought I should give it a try so I got some today, but I am pretty sure from the lack of results after taking 30 mg sublingually that it doesn't cross the BBB. It might help in the other parts of the body, though.
     
  4. Aerose91

    Aerose91 Senior Member

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    Does Niacin cross the BBB in order to increase NADH levels there?
     
  5. Kimsie

    Kimsie Senior Member

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    Niacinamide and niacin cross the BBB.
     
  6. Aerose91

    Aerose91 Senior Member

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    Thank you. Do you have a reference of what small amounts of niacin are? I am definitely an undermethylator
     
  7. Kimsie

    Kimsie Senior Member

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    Maybe no more than 100-200 mg per day total but I looked at some of your posts and I see you get adrenaline from B12. Have you ever taken say, 500 mg of niacinamide when you get adrenaline to see if it helps? One dose wouldn't do any harm to an undermethylator. It takes weeks to change the histone methylation.

    OCD is supposed to be an undermethylation symptom. My son with Sz has it. Have you ever taken any dessicated thyroid and how did it affect you? It might be that dessicated thyroid would take away the OCD but I will be posting about our experience with thyroid and why I think it helps him, it's not because he can't make a normal amount of thyroid. I don't expect that thyroid would take away ME/CFS symptoms, but some people here might have other symptoms that would be helped by it. I hope to post about it in a few hours.
     
  8. adreno

    adreno PR activist

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    We have talked about why niacinamide inhibits sirt, and this page provides an answer:

    Again, as we have discussed before, nicotinamide riboside activates sirt (and increase the NAD pool), and so might be a better solution. Niacin also activates sirt, but cause nasty flushing. Resveratrol paired with nicotinamide riboside might be even better.
     
    Last edited: Jan 27, 2015
  9. Kimsie

    Kimsie Senior Member

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    I have tried niacin with my son with Sz and it works at first but then it stops working, and I believe that this is because all of these can ultimately inhibit sirtuins unless the pathway to salvage NAD is working well, probably specifically the NAMPT enzyme is the most important. I am going to post about this subject later today. There is another way to activate sirtuins, I think, for those who are undermethylators.
     
  10. adreno

    adreno PR activist

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    Yes, but nicotinamide riboside bypasses this enzyme:

    [​IMG]
     
  11. Aerose91

    Aerose91 Senior Member

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    Yes, taking about 50 mg niacin will calm it down slightly but it Aldo does other uncomfortable things. It will make my brain blank out badly (this whole disease is in my brain)

    I have been given low doses of armor thyroid on 2 occasions now and it made me go INSANE. Brutal adrenaline, anger, crazy OCD, restlessness. It's bad.
     
  12. adreno

    adreno PR activist

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    Thyroid will increase catecholamines, probably not what most people need for OCD. Rather, it seems that OCD is associated with low glutamate.
     
  13. Kimsie

    Kimsie Senior Member

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    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.
     
    Last edited: Jan 27, 2015
  14. Kimsie

    Kimsie Senior Member

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    So you are saying to take enough nicotinamide riboside that the salvage pathway isn't used at all? Where would the niacinamide from sirt and parp go? The vast majority of the NAD in the body is made for those sirt and parp reactions. It's that niacinamide that can accumulate after it has been used that inhibits sirtuins.
     
  15. Kimsie

    Kimsie Senior Member

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    That's interesting. What other things does niacin do to you? It's strange how differently people respond. I can't figure it out. It like cards that keep getting shuffled and you just can't know which one is going to show up.

    I guess that your reaction to thyroid is due to increased sensitivity of the receptors. How long did you take it for and at what dose? I would think the effect would wear off if you could stand it for a few days. Did you start really low and build up?
     
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  16. Kimsie

    Kimsie Senior Member

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    When you took niacin did you have any folate, b12 and magnesium? If you didn't have enough of those three, that might explain the bad effect of the niacin. How much of those 4 were you taking when you took the thyroid?
     
  17. adreno

    adreno PR activist

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    Then your son would have atypical OCD. The research generally shows high dopamine and low glutamate in OCD.
     
  18. adreno

    adreno PR activist

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    Well, if that's the case, niacin won't help either.
     
  19. Aerose91

    Aerose91 Senior Member

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    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
     
  20. Aerose91

    Aerose91 Senior Member

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    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
     

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