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does NAC really cause damage?

Lotus97

Senior Member
Messages
2,041
Location
United States
I was reading in Stephen Buhner's new book, Healing Lyme Coinfections Bartonella and Mycoplasma, that NAC in high doses can break up biofilms. This can be a double edged sword since it can release more infectious bacteria into a person's system.

It's possible that some people react badly to NAC due to thiol sensitivity either from mercury toxicity and/or certain CBS mutations.

Also, many people here are low in glutathione and have high glutamate levels. Since cysteine is a rate-limiting factor for glutathione (which is made up of cysteine, glycine, and glutamate) people can potentially both increase glutathione and decrease glutamate by taking either NAC, L-cysteine, or L-Cystine.

For more information about the glutathione and glutamate issues for people with ME/CFS I'd highly recommend Marco's series of articles about the neuroinflammatory model for ME/CFS:
http://www.cortjohnson.org/authors/marco/

I don't believe that the amount of people who react badly to NAC is very high. In fact I think it's quite low. Anyone here can confirm this simply by just going to iherb.com or swansonvitamins.com or vitacost.com and reading the customer reviews. It's true that the people in this community are more likely to react badly to supplements, but that's the case with ALL supplements. We shouldn't exclude supplements just because a small percentage of people react badly to them.

@aquariusgirl
Rich cautioned people with suspected mercury issues from taking NAC, L-cysteine, and l-cystine, but thought it might help others with glutamate-induced excitoxicity
http://forums.phoenixrising.me/inde...excitotoxicity-on-methylation-protocol.18721/
Quite a few PWMEs who have tried the methylation protocol have reported that they have experienced an increase in symptoms associated with excitotoxicity when they began (anxiety, insomnia, nervousness). In the past, I have suggested trying acetyl glutathione or liposomal glutathione to counter this. One or two people reported that they thought this helped them.
Now I would like to suggest something else that I think would help with this, which is less expensive: L-cystine. Note here that I do mean L-cystine, not L-cysteine. (Cystine is the oxidized form of cysteine, consisting of two cysteine molecules bound together by a disulfide bond.) Douglas Laboratories is one producer of L-cystine, and there are at least a couple of suppliers of it
on the internet advertising 60 capsules, 500 mg each, for $16.50. I would suggest starting with a dosage of 500 mg and increasing to as much as 1,500 mg, depending on the response. L-cystine should not be taken by people who have a tendency to develop cystine kidney stones, or people who suspect that they have a high body burden of mercury, because L-cystine may move mercury around. And as always, I recommend working with a physician while on this protocol.

Here is the rationale:

I believe that the increase in excitotoxicity results from a further drop in the glutathione levels in the astrocytes (helper cells) in the brain, when the protocol is begun. (We know
from the recent MRS measurements of Shungu et al. that glutathione is already somewhat depleted in the brain in ME/CFS.) The further drop in glutathione lowers the production of ATP by the mitochondria of these cells, and they then have less energy for pumping glutamate out of the synapses and recycling it. When glutamate builds up, it overexcites the NMDA receptors, and that produces excitotoxicity.

If this is true, then it would seem that we may be able to lower the excitotoxicity if we can support the glutathione levels in the astrocytes as this protocol is begun.

According to the Dringen model, the astrocytes make their glutathione using cystine as their source of cysteine. Cystine is obtained from the blood, and is able to pass through the blood-brain barrier.

How does cystine normally get into the blood? The liver produces glutathione from the constituent amino acids that it receives from the diet via the intestine and the portal vein blood flow. The liver exports some of its glutathione to the circulating blood, and enzymes break down the glutathione into its constituent amino acids. The cysteine is mostly oxidized to cystine, and some of this is taken up from the blood by the brain.

When the methylation protocol is begun, the activity of the methionine synthase enzyme in the liver is increased by supplementing B12 and folate forms. This causes more of the homocysteine to be converted to methionine, so less is available to support synthesis of glutathione. One result of this is that the cystine level in the blood goes down, so that less of it is available to the brain.

It would therefore seem that if L-cystine were supplemented, it would augment the cystine in the blood and increase the supply available to the brain, and hence to the astrocytes. Hopefully, this would raise the glutathione levels in these cells, and increase their ability to remove glutamate from the synapses, lowering the excitotoxicity. Ingested cystine is not metabolized significantly by the liver, because it does not import cystine readily.

If anybody decides to try this, I would be interested to hear the results, whatever they turn out to be. Thanks.

Best regards,

Rich
 

dannybex

Senior Member
Messages
3,561
Location
Seattle
Kimsie,

Thanks for your story! I feel better with NADH sublingual 20 mg once a day. Maybe I'll experiment with spacing it out or increasing dose. I am ultra-sensitive to things like cinnamon, tomatoes, spinach, cream cheese.

Hi @Critterina

I realize this is an ancient post, but I'm really confused on the niacin/niacinamide/NADH issue as it relates to histamine intolerance. So much conflicting info out there, so I'm hoping you might be able to help me. I'm convinced that histamine intolerance has been an issue for me from even before I 'officially' got sick, but even more so during the past year (after being sick for 16 years).

Rich Vank and Ben Lynch (among others) have said that methylation lowers histamine levels, especially if active folates and b12s are used. And I realize above that NADH is also necessary, but I wonder about the amounts, as niacin/niacinamide inhibits methylation (or absorbs, soaks up methyl groups), and niacinamide has been shown in relatively small amounts to increase histamine:

http://www.ncbi.nlm.nih.gov/pubmed/23426511

So I'm curious, besides, avoiding high histamine or histamine-releasing foods, what does your protocol look like now, and what's your opinion on the niacin/niacinamide/NADH issue?

Thanks so much. :)

Dan
 

Critterina

Senior Member
Messages
1,238
Location
Arizona, USA
Hey @dannybex ,

Sorry I have almost no time to write. My issue has to do with dietary histamine. I do not react to histamine-releasing foods and I don't have any of the signs of histadelia (just the opposite!). So, I'm just guessing here, but perhaps it's possible that blood levels of histamine are not the issue in at least MY histamine intolerance.

If you look at the article on Histamine and Histamine Intolerance in the American Journal of Clinical Nutrition (Maintz), they call out NAC (N-acetyl-cysteine) as something that aggravates and should be avoided by people with HI. (I mention because NAC is the topic of this post).

But you mention NADH. I have no histamine intolerance reaction from it. Maybe the histamine my body produces (like from the histamine-releasing foods) doesn't bother me, or maybe my reserves are low so I don't produce much, or maybe I only react to dietary histamine. NADH has been instrumental to me during my winters in the Denver, CO and Washington DC areas, in keeping the circulation in my extremities. I have had Reynaud's and sometimes in the cold I have a hard time with that. NADH seems to help a lot.

My protocol now, if you mean supplements, is way paired back. Since my diet improved (now that I don't have to avoid histamines, I figured I was getting near-sufficient nutrition, so I cut back the expenses of my supplements. My diet, after the 3-day fast, seems again to tolerate a complete range of foods without symptoms. But it's only been 24 hours. (And I did break my fast with pizza and a brownie plus fruit and veg, following half an hour after a glass of coconut water. I seem none the worse for it.) Did you see I've been posting in "Critterina's Histamine Intolerance Journal" or some such title?

If you want more details on anything (like my supplements), let me know, but I can really only talk about my own experience. I guess at the causes/effect at this point.
 

Critterina

Senior Member
Messages
1,238
Location
Arizona, USA
Dan,
I just looked more closely at that article. They were using men. They were using 5x the NADH I take. The result was a decrease in betaine; since I'm BHMT-08 +/+ and MTRR A66G +/+ and I take sublingual methylB12, it's not like my betaine is going to be missed, since it's not doing that much anyway. They say "These results suggest that excess nicotinamide can disturb monoamine-neurotransmitter metabolism." Yep. Probably so. But whatever immune system bad behaviors I get/got from histamines, the NADH didn't bother me, however, 1/4 of the thinnest slice of a tomato would make me sick for 3 days. Go figure. Maybe it would be different for everyone else.
 

heyitisjustin

Senior Member
Messages
162
Hi @Critterina

Rich Vank and Ben Lynch (among others) have said that methylation lowers histamine levels, especially if active folates and b12s are used. And I realize above that NADH is also necessary, but I wonder about the amounts, as niacin/niacinamide inhibits methylation (or absorbs, soaks up methyl groups), and niacinamide has been shown in relatively small amounts to increase histamine:

http://www.ncbi.nlm.nih.gov/pubmed/23426511

So I'm curious, besides, avoiding high histamine or histamine-releasing foods, what does your protocol look like now, and what's your opinion on the niacin/niacinamide/NADH issue?

Thanks so much. :)

Dan

It appears that NAC was worsening my histamine issues. However, I stopped several things at once so it could've been doing nothing. I've read in a few histamine places that NAC was a bad idea.

Why would one take NADH? Is it supposed to lower histamines?
 

heyitisjustin

Senior Member
Messages
162
Some people use NADH to help the krebs cycle / mitochondrial function.
My main problem seems to be controlling high histamine via methylation. When I saw
Nicotinamide in NADH I guessed that it wasn't for me. I am not too familiar with krebs cycle / mitochondrial function.
Could NADH improve my methylation/histamine?
 

dannybex

Senior Member
Messages
3,561
Location
Seattle
My main problem seems to be controlling high histamine via methylation. When I saw
Nicotinamide in NADH I guessed that it wasn't for me. I am not too familiar with krebs cycle / mitochondrial function.
Could NADH improve my methylation/histamine?

That's the same thing I've been wondering. Niacinamide/nicotinamide does increase histamine...

http://www.ncbi.nlm.nih.gov/pubmed/23426511

…but not sure if NADH would do the same thing.
 

heyitisjustin

Senior Member
Messages
162
That's the same thing I've been wondering. Niacinamide/nicotinamide does increase histamine...

http://www.ncbi.nlm.nih.gov/pubmed/23426511

…but not sure if NADH would do the same thing.

I've seen people say that some niacin is useful for things that pertain to me (I think sleep). If there isn't too much it might not be bad. I am not sure what krebs cycle / mitochondrial function. It sounds like that would increase energy, which wouldn't be something useful for me, but might be worth a trial for you. Has anyone else on PR tried it?
 

Freddd

Senior Member
Messages
5,184
Location
Salt Lake City
Anyone have bowel issues with just 500mg of NAC? I do take it at night before bed, not with food.

@soccor_dude,

NAC affects some percentage of people by them have a reaction sometimes called "NAC detox" which has the same symptoms as "Glutathione detox". Those symptoms are generally those of l-methylfolate deficiency caused by the glutathione combining with the human active B12s, MeCbl and AdoCbl, and being rapidly flushed from the body in the urine causing methyltrap, which causes l-methylfolate to be flushed from the cell when there is no MeCbl to combine with it.causing folate deficiency symptoms for pragmatic severe B12 deficiency. The percentage is unknown with this response. I have observed the NAC and glutathione "DETOX" symptoms start in 2 hours to several weeks after starting to dose with NAC and/or other precursors or glutathione. NAC or glutathione causes me IBS-D every time and takes me days of extra MeCbl to get things back to healing. Good luck.

Version 2.21 12/06/2016 A work in process, incomplete, limited testing, people come in many variations, use at your own risk.
INDUCED DEFICIENCY SYMPTOMS FROM REFEEDING SYNDROME
. This can follow 5 days of food deprivation, anorexia, or sort of a pinpoint starvation via vitamin or mineral or amino acid deficiencies. Whatever the “most needed” item is will often cause a strong response. The first usual notable symptoms occur on typically the third day of starting a previously insufficient nutrient. For instance it was noted in the 50s with injections of B12 with potassium deficiency (hypokalemia) as a side effect. It is dangerous and can be unpredictably fatal if not corrected and the cause is continued. When they say people are dying in Syria after they have been starved and given food, they are often suffering REFEEDING SYNDROME. When previous symptoms return

Group 3 - Induced and/or Paradoxical Folate deficiency or insufficiency, partial methylation block to methyltrap on 1 or more internal triage levels. Frequently called “NAC DETOX” or “GLUTATHIONE DETOX”. Can be caused by folic acid, folinic acid and for some people, like me and quite a few others, excess vegetable folates. Further excess B1, B2, B3 and/or inositol can increase methylfolate deficiency symptoms. Methylfolate, MeCbl and just about anythjing else that starts healing can cause the folate deficiency symptoms.

These symptoms appear in 2 forms generally, the milder symptoms that start with partial methylation block and the more severe symptoms that come on as partial methylation block gets worse or very quickly with methyltrap onset.

Edema - An additional thing I would like to mention. I would never have found it without 5 years of watching the onset of paradoxical folate insufficiency and trying to catch it earlier and earlier and to figure out what was causing it and to reverse it. For me the onset order goes back to the day of onset now with edema and a sudden increase of weight. I noticed that within 2 hours of taking sufficient Metafolin I would have an increase in urine output.
Old symptoms returning in a general sense, a person may have had onset of these hundreds of time if they are on the borderline
Edema
Angular Cheilitis, Canker sores,
Skin rashes, increased acne, Increased itchy acne on scalp and face, Skin peeling around fingernails, Skin cracking and peeling at fingertips, painful cracks in the skin at the corner of fingernails at approximate right angles to nails, can take months to occur and it may be only non mood or neurological symptoms.
IBS – Diarrhea alternating with constipation, IBS – Normal alternating with constipation
Headache, Increased malaise, Fatigue
Increased hypersensitive responses, Runny nose, Increased allergies, Increased Multiple Chemical Sensitivities, Increased asthma, rapidly increasing Generalized inflammation in body, Increased Inflammation pain in muscles, Increased Inflammation pain in joints, Achy muscles, Flu like symptoms
IBS – Steady diarrhea, IBS – Diarrhea alternating with normal, Stomach ache, Uneasy digestive tract,
Coated tongue, Depression, Less sociable, Impaired planning and logic, Brain fog, Low energy, Light headedness, Sluggishness, Increase irritability, Heart palpitations,
Longer term, very serious:
Loss of reflexes, Fevers, Forgetfulness, Confusion, Difficulty walking, Behavioral disorders, Dementia, Reduced sense of taste, bleeding easily.
 

pattismith

Senior Member
Messages
3,931
@soccor_dude,

NAC affects some percentage of people by them have a reaction sometimes called "NAC detox" which has the same symptoms as "Glutathione detox". Those symptoms are generally those of l-methylfolate deficiency caused by the glutathione combining with the human active B12s, MeCbl and AdoCbl, and being rapidly flushed from the body in the urine causing methyltrap, which causes l-methylfolate to be flushed from the cell when there is no MeCbl to combine with it.causing folate deficiency symptoms for pragmatic severe B12 deficiency. The percentage is unknown with this response. I have observed the NAC and glutathione "DETOX" symptoms start in 2 hours to several weeks after starting to dose with NAC and/or other precursors or glutathione. NAC or glutathione causes me IBS-D every time and takes me days of extra MeCbl to get things back to healing.

Thank you Freddd,

your answer was not meant to me, but you gave me the answer I just needed :)

I was very bad with methyl folate and had to stop it a week ago, but still had headache issue after a week...

Then today, I started Gluthation liposomal + MethylB12, 5000 ug/folate three time a day sublingual (Solgar), and tonight I feel much much better!

I was doing Hydroxocobalamine injections for several weeks, without any success, It seems that sublingual MethylB12 works better for me, let's hope I found I found another brick for my healing wall!
Thank you for your contribution to PR :heart:
 

Freddd

Senior Member
Messages
5,184
Location
Salt Lake City
Thank you Freddd,

your answer was not meant to me, but you gave me the answer I just needed :)

I was very bad with methyl folate and had to stop it a week ago, but still had headache issue after a week...

Then today, I started Gluthation liposomal + MethylB12, 5000 ug/folate three time a day sublingual (Solgar), and tonight I feel much much better!

I was doing Hydroxocobalamine injections for several weeks, without any success, It seems that sublingual MethylB12 works better for me, let's hope I found I found another brick for my healing wall!
Thank you for your contribution to PR :heart:

Hi Pattismith,

In the N=10 trial some of us did with glutathione, the negative reaction to glutathione appeared in anywhere from 2 hours to 3 weeks or so and may be dose related or accumulated dose related. In any case we had 100% of people doing the trial all had serious side effects up to and including nerve demyelination. It took several days after discontinuation of the glutathione for it to go down to a low enough level that I (we) were able to have resumed b12 function even with extra large doses. A couple of mg of glutathione is enough, chemically speaking, to disable all the B12 in somebody's body. Be careful.
 

pattismith

Senior Member
Messages
3,931
@Freddd ,

I woke up this morning still with an headache, took my subling. B12 /folate, together with my Glutathione, to see what would happen. The headache was still there. So three hours later, I took another losange of B12/folate and 30 mn after I felt better.

it may be that Glutathione or NAC are not the right supplements for me.

I would like to have a try with the protocole that you were successful with, would you tell me where I can find it?

I understood that you have to take Methylfol + adenosyl cobalamine + Methyl B12 + Carnitine (I have currently ALCAR and also Tartrate), but I would like to know if there is specific dosage?