N-Acetyl Cysteine?

[Vanguard]

Hello everyone.

I'm finding conflicting information online about this supplement, N-acetyl Cysteine, and it's affect on PWC's. I know it's involved in the methylation cycle but I'm confused as exactly how. I read that Cheney said "don't take NAC", then other websites say it's definitely beneficial.

Thanks

 

[heapsreal]

Hello everyone.

I'm finding conflicting information online about this supplement, N-acetyl Cysteine, and it's affect on PWC's. I know it's involved in the methylation cycle but I'm confused as exactly how. I read that Cheney said "don't take NAC", then other websites say it's definitely beneficial.

Thanks

When it comes down to trying treatments for ME, all u can do is try it because we all respond differently and if it doesnt agree then just stop using it. NAC is used in hospitals for tylenol/paracetamol overdoses to protected the liver from being damaged and is said to raise liver glutathione levels which is an important antioxidant to protect it from damage. In hospital setting it is used intravenously but have also read studies that say it is just as effective orally. I dont know about it helping me directly with ME symptoms but i use it to protect my liver from medications i use like antivirals which are a long term treatment as well as other meds and over the years my liver function has been good. Also being an antioxidant its going to have general health benefits. I havent had any negative effects from NAC supplements and i have been using this since before i had ME. thats my 2 cents worth.

cheers!!!

 

[richvank]

Hello everyone.

I'm finding conflicting information online about this supplement, N-acetyl Cysteine, and it's affect on PWC's. I know it's involved in the methylation cycle but I'm confused as exactly how. I read that Cheney said "don't take NAC", then other websites say it's definitely beneficial.

Thanks

Hi, Vanguard. N-acetylcysteine is absorbed fairly well by the liver when taken orally, and it supplies cysteine, which is usually the rate-limiting amino acid for the synthesis of glutathione.
It has been helpful to some PWMEs. The concern about NAC is that it has been found to be able to move mercury into the brain. So if a person is likely to have a high body burden of mercury (such as from having a number of amalgam fillings in the teeth over an extended period of illness in which glutathione was depleted), it is wise not to take a large dosage of NAC. Dr. David Quig of Doctors Data Lab has recommended that the dosage be no larger than 300 mg per day under these conditions. Dr. Cheney's warning about NAC comes from his knowledge of two patients who took large dosages (not at his recommendation) and later committed suicide. He believes that there was a connection with taking the large dosages of NAC. Perhaps it a mercury issue, but I don't think this was known for sure in these cases.

In the simplified methylation protocol, the emphasis is on lifting the partial methylation cycle block, which has been found to cause glutathione to come up automatically.

Best regards,

Rich

 

[Tony Mach]

I took higher doses (together with Vitamin D), got "NAC flu" and my ME/CFS got worse. I am slowly recuperating from this 'NAC adventure'. Higher doses are used by the CPNhelp.org and antibiotics people. Unless you have high titers against Chlamydia, I would stay away from high does of NAC. And even then I would not venture into the high dose territory again

Lower doses (600 mg a day or less) should be safe (but I am not a doctor) and are used by the "leaky gut" people. Don't know if it is helpful.

But it only makes sense if you have a doctor that recommends a treatment protocol.

 

[aprilk1869]

I took higher doses (together with Vitamin D), got "NAC flu" and my ME/CFS got worse. I am slowly recuperating from this 'NAC adventure'. Higher doses are used by the CPNhelp.org and antibiotics people. Unless you have high titers against Chlamydia, I would stay away from high does of NAC. And even then I would not venture into the high dose territory again

Lower doses (600 mg a day or less) should be safe (but I am not a doctor) and are used by the "leaky gut" people. Don't know if it is helpful.

But it only makes sense if you have a doctor that recommends a treatment protocol.

Just wondering if you know about Freddd's problems with glutathione, NAC etc? He and some others had been doing very well on B12 and then when they added glutathione or precursors they got worse.

You can read more here:

http://forums.phoenixrising.me/showthread.php?11006-Question-for-Freddd-re-glutathione...

 

[dannybex]

Plasma Cysteine test...???

I'm just guessing here, but would think that a way to find out if you might need more (and/or) be able to tolerate cysteine is by getting a plasma cysteine test (available by the same lab that does the methylation panel). Any comments Rich?

There's definitely conflicting info out there. This first study suggests that NAC is "an antidote" to methylmercury poisoning:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1533084/

...while this one is a little more confusing (perhaps this is the one Rich was referring to?):

http://www.ncbi.nlm.nih.gov/pubmed/1590471

What I don't quite understand is how direct glutathione supplementation (either by nebulizing, IV's, transdermal) can help some folks, while others have reactions -- and how direct supplementation differs from supplementing with b12/folates, which still results in raising glutathione levels???

Dan

 

[biophile]

I read on PubMed that a superior form of NAC was synthesized circa 2008, N-acetylcysteine amide or NACA, which is perhaps a better antioxidant and passes the brain blood barrier, but it doesn't seem available as a supplement yet. I'm unclear about whether NAC actually passes the BBB per se, rather it provides a readily accessible source of cysteine which does pass through and is of course a precursor to glutathione. NAC is on my list of things to try next as I'm getting very impatient with PEM and PENE, which seems strongly related to oxidative stress.

 

[Vegas]

NAC definitely has the effect of mobilizing Hg in my case

I read on PubMed that a superior form of NAC was synthesized circa 2008, N-acetylcysteine amide or NACA, which is perhaps a better antioxidant and passes the brain blood barrier, but it doesn't seem available as a supplement yet. I'm unclear about whether NAC actually passes the BBB per se, rather it provides a readily accessible source of cysteine which does pass through and is of course a precursor to glutathione. NAC is on my list of things to try next as I'm getting very impatient with PEM and PENE, which seems strongly related to oxidative stress.

As someone with a large Hg burden, I get very foggy-headed on NAC and the symptoms are consistent with bloodborne mercury affecting the CNS. I wasn't able to fully correlate the effects of NAC until I started chelating. If you are highly mercury toxic, you probably don't want more cysteine, eventhough it is probably low. Just my 2 cents as someone who is slowly chelating the CFS symptoms, including 12 years of PEM, away.

 

[dannybex]

It's so frustrating figuring this out, as this study showed that NAC helped REMOVE at least methylmercury from the brain:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1533084/pdf/envhper00528-0071.pdf

Plus, NAC is often used as an adjunct to antiviral and antiretroviral therapy with HIV/AIDS patients...and has been shown to help them.

Rich...if you're reading this...do you have a link to the research that NAC can move mercury into the brain?

Thanks in advance!

Dan

 

[Adster]

NAC was great for me for about 4 months a few years back then it stopped working and I kind of crashed. I tried it again later and couldn't tolerate it. Not sure what to make of that.

 

[Sallysblooms]

I take it, it is in my regimen. I take a small amount. Too much makes my stomach hurt.

 

[Lala]

Danny, very frustrating, I am trying to find the true about NAC and mercury as well. I am on high dose NAC for 5,5 years.

 

[richvank]

Hi, all.

Here's the abstract of David Quig's paper. You can get the full text free from PubMed by typing the PubMed number into the search box and then clicking on the colored box at the upper right of the abstract. The advice on NAC is on page 267 of this paper.

I think there is a more recent paper by Aposhian on a rat study that also has some info on this, but I'm not finding it in the abstract. I have a copy of the full paper at home, but I'm away from home. Maybe that paper dealt with ALA, rather than NAC.

Rich



Altern Med Rev. 1998 Aug;3(4):262-70.
Cysteine metabolism and metal toxicity.
Quig D.
Source

Doctor's Data, Inc., West Chicago, IL, USA. dquig@doctorsdata.com
Abstract

Chronic, low level exposure to toxic metals is an increasing global problem. The symptoms associated with the slow accumulation of toxic metals are multiple and rather nondescript, and overt expression of toxic effects may not appear until later in life. The sulfhydryl-reactive metals (mercury, cadmium, lead, arsenic) are particularly insidious and can affect a vast array of biochemical and nutritional processes. The primary mechanisms by which the sulfhydryl-reactive metals elicit their toxic effects are summarized. The pro-oxidative effects of the metals are compounded by the fact that the metals also inhibit antioxidative enzymes and deplete intracellular glutathione. The metals also have the potential to disrupt the metabolism and biological activities of many proteins due to their high affinity for free sulfhydryl groups. Cysteine has a pivotal role in inducible, endogenous detoxication mechanisms in the body, and metal exposure taxes cysteine status. The protective effects of glutathione and the metallothioneins are discussed in detail. Basic research pertaining to the transport of toxic metals into the brain is summarized, and a case is made for the use of hydrolyzed whey protein to support metal detoxification and neurological function. Metal exposure also affects essential element status, which can further decrease antioxidation and detoxification processes. Early detection and treatment of metal burden is important for successful detoxification, and optimization of nutritional status is paramount to the prevention and treatment of metal toxicity.

PMID:
9727078
[PubMed - indexed for MEDLINE]

Free full text

 

[Vegas]

I think the Aposhian article you are referring to discusses ALA among other

substances, but not NAC. See abstract below. Cutler has roundly criticized this study for its design, methodology, conclusions, etc. Here are a few things he has written about this study:

"The conclusions in the abstract do not legitimately flow from the
content of the paper due to improper study design.

150-300 mg/kg of DMPS and DMSA were used on the rats in a single dose.
In fact this was so much it killed a few of them. With this horrific
dose a modest reduction in mercury was noted in the kidneys.

10 mg/kg of ALA was used on the rats once, and unsurprisingly it did
not reduce brain mercury levels significantly. Nobody would ever have
expected them to. If 10 mg/kg of DMSA and DMPS had been used they
would also not have led to a noticeable reduction in kidney mercury
levels which would have "proved" that DMPS and DMSA are not mercury
chelators just like the paper "proves" that ALA isn't.

In addition, the DMPS and DMSA were injected (ensuring 100%
absorption) and the ALA was ingested leading to lower absorption. So
30-100 times as much DMPS and DMSA got into the bloodstreams of the
animals as ALA did, and these chelators are all of roughly equal
chelating power per unit weight.

I didn't do the numbers for the other materials, but a cursory reading
suggests similar problems regarding dosage as with ALA. Also the
vitamin C was not adminsitered intravenously, as is uniformly done in
treating humans.

The authors actually do offer some discussion of the use of ALA to
treat autistic children but it is off point and quite misinformed.
They did prove that a protocol nobody actually uses on autistic
children would be ineffective if it were used. This is quite
different than studying the protocols that people have found
clinically effective.

This paper highlights the difficulties of doing research as well as
the need to read and analyze papers (and to have the basic knowledge
to be able to do that) in order to use them to make good decisions."


J Toxicol Clin Toxicol. 2003;41(4):339-47.
Vitamin C, glutathione, or lipoic acid did not decrease brain or kidney mercury in rats exposed to mercury vapor.
Aposhian HV, Morgan DL, Queen HL, Maiorino RM, Aposhian MM.
Source

Department of Molecular and Cellular Biology, The University of Arizona, Tucson, Arizona 85721-0106, USA. aposhian@u.arizona.edu
Abstract

Some medical practitioners prescribe GSH and vitamin C alone or in combination with DMPS or DMSA for patients with mercury exposure that is primarily due to the mercury vapor emitted by dental amalgams.
HYPOTHESIS:

This study tested the hypothesis that GSH, vitamin C, or lipoic acid alone or in combination with DMPS or DMSA would decrease brain mercury.
METHODS:

Young rats were exposed to elemental mercury by individual nose cone, at the rate of 4.0 mg mercury per m3 air for 2 h per day for 7 consecutive days. After a 7-day equilibrium period, DMPS, DMSA, GSH, vitamin C, lipoic acid alone, or in combination was administered for 7 days and the brain and kidneys of the animals removed and analyzed for mercury by cold vapor atomic absorption.
RESULTS:

None of these regimens reduced the mercury content of the brain. Although DMPS or DMSA was effective in reducing kidney mercury concentrations, GSH, vitamin C, lipoic acid alone, or in combination were not.
CONCLUSION:

One must conclude that the palliative effect, if any, of GSH, vitamin C, or lipoic acid for treatment of mercury toxicity due to mercury vapor exposure does not involve mercury mobilization from the brain and kidney.

 

[dannybex]

Hi, all.

Here's the abstract of David Quig's paper. You can get the full text free from PubMed by typing the PubMed number into the search box and then clicking on the colored box at the upper right of the abstract. The advice on NAC is on page 267 of this paper.

Hi Rich,

That is an interesting review. I'm not sure of course if I'm interpreting it even remotely correctly, but this caught my attention, (in the diagram in Figure 3 on page 268):

"Co-infusion of L-cysteine with MeHg accerates MeHg uptake into brain."

So the cysteine moved mercury into the brain, but only when it was co-infused? Also...does that mean he's' talking about methylmercury, and not stored, inorganic mercury?

Also: "Uptake is non-linear, saturable and inhibited by L-methionine; L(leucine-preferring) AA transport system."

He continues: "Therefore, it seems prudent to provide small amounts of cysteine in conjunction with sufficient quantities of leucine and the other amino acids which compete for the L-amino acid transport system, including valine, isoleucine, phenylalanine, tyrosine and tryptophan."

So I guess my mushy-brained question/comment is this: Doesn't this study suggest that if one takes higher doses of l-cysteine or NAC completely separate from any other sources of other proteins, then the cysteine might move the methylmercury into the brain -- but if one is eating other protein as most everyone does, or taking whey powder as he suggests, then it isn't a problem?

And does NAC or l-cysteine move inorganic mercury into the brain?

Thanks again,

Dan

 

[dannybex]

Does ALA move mercury into the brain?

Hi Vegas,

After many trials and tribulations regarding chelation, and the (here's that word again) frustrating lack of cohesive info on the subject, I've been starting to wonder about Cutler's theories/hypothesis and insistence that ALA is the best chelator, or if not best, one of the safest, and that it's the only one that crosses the blood brain barrier.

Here's another review that suggests yes, it does move it out of the brain, but can also move it into the brain, and elsewhere (along with other toxic metals):

http://www.ncbi.nlm.nih.gov/pubmed/12495372

Quoting:

"There was disconcerting evidence from this study, however, that ALA may also alter the tissue distribution of mercury and other heavy metals.

Although levels of inorganic mercury and methylmercury in the kidney dropped significantly, levels of inorganic mercury also increased significantly in the brain, lung, heart, and liver tissue.

Methylmercury levels had also increased in the brain, intestine and muscle of the rats given ALA.

The same phenomenon occurred in rats exposed to cadmium and given the same doses of ALA. Levels of cadmium in the liver dropped (where cadmium is most frequently stored) but increased in the kidney and muscle. The same was true in rats given copper and ALA; all tissues examined had increased levels of copper, except for the liver (where copper usually accumulates) where levels had dropped.

In all cases the pattern was the same; the tissues that concentrated the metal (blood, spleen, and kidneys in the case of methylmercury) had reduced concentrations, while other tissues appeared to have a greater concentration."


Yes, frustrating.

 

[markmc20001]

My experience was I could tolerate NAC while on antibiotics. Not sure if I ever developed complications/problems over time or not. Did have problems while not taking antibiotics.

ALA also seemed to work synergistically with NAC for me.

 

[Vegas]

Hi Vegas,

After many trials and tribulations regarding chelation, and the (here's that word again) frustrating lack of cohesive info on the subject, I've been starting to wonder about Cutler's theories/hypothesis and insistence that ALA is the best chelator, or if not best, one of the safest, and that it's the only one that crosses the blood brain barrier.

Here's another review that suggests yes, it does move it out of the brain, but can also move it into the brain, and elsewhere (along with other toxic metals):

http://www.ncbi.nlm.nih.gov/pubmed/12495372

Quoting:

"There was disconcerting evidence from this study, however, that ALA may also alter the tissue distribution of mercury and other heavy metals.

Although levels of inorganic mercury and methylmercury in the kidney dropped significantly, levels of inorganic mercury also increased significantly in the brain, lung, heart, and liver tissue.

Methylmercury levels had also increased in the brain, intestine and muscle of the rats given ALA.

The same phenomenon occurred in rats exposed to cadmium and given the same doses of ALA. Levels of cadmium in the liver dropped (where cadmium is most frequently stored) but increased in the kidney and muscle. The same was true in rats given copper and ALA; all tissues examined had increased levels of copper, except for the liver (where copper usually accumulates) where levels had dropped.

In all cases the pattern was the same; the tissues that concentrated the metal (blood, spleen, and kidneys in the case of methylmercury) had reduced concentrations, while other tissues appeared to have a greater concentration."


Yes, frustrating.

It is frustrating and there is a lot of bad information. Not to mention the stakes are very high for someone who has been chronically ill for a very long time because as you know seemingly innocuous events/supplements can cause major harm. When one's health is already so vastly compromised and they have experienced numerous set-backs, I think most become gun shy, and honestly with chelation, a healthy level of respect is warranted. Nevertheless, if you have a metal burden, you just cannot ignore it (not saying you were but speaking in general.) It is just too fundamental a problem.

My confidence in Cutler's protocol was partly related to the testimonials of many veterans of chelation and the references cited by Dr. Cutler, but it was mostly created by my response to the protocol. It really works. You have to give it a few months, if it is too onerous, try a smaller dosage. I did have some periods of worsening, but the overall improvement has been dramatic.

The irony of the passages that you quoted is that some of them came from a study that Cutler used for the very foundation of his protocol, which I think he developed in the mid 90's. Some of your concerns are valid, but these are recognized and accounted for with the protocol, such as the undesirable movement of mercury into the brain for which he has suggested no chelation w/ ALA until three months post-removal along with the recommendation to use DMSA to essentially clear the blood and reduce the "retro-diffusion" of mercury. ALA does open the door with greater brain and intracellular permeability, but if you want something to come out, you have to open the door. It is not a risk-less proposition, but proper chelation techniques are designed to minimize the risk.

As for your point about the displacement of metals, this too has been accounted for by Cutler, most notably in his strategies about handling zinc & copper...E.G.--halving zinc dose (something you are likely deficient in anyway), taking high dose molyb, limiting dietary copper, etc. This is what makes understanding the protocol so important.

Also, per Cutler, some of the inferences people have made from the rat studies are completely invalid because the rat BBB cannot be compared to that of a human. I have no idea if this is true, but I have no reason to doubt him.

 

[biophile]

NAC is used to treat acute paracetamol/acetaminophen overdose, by increasing glutathione synthesis in the liver. Does anyone here have an increased sensitivity to the side effects of paracetamol/acetaminophen even at low doses? I do, and it seems to be different to and last longer than the side effects of aspirin. It isn't often I take these and I only take low doses, but this year I had a few negative experiences which make me want to avoid paracetamol/acetaminophen altogether. I have a bottle of Jarrow's sustained release 600mg NAC waiting to be trialled.

 

[merylg]

Yes. Just this year I have noticed I have an increasing intolerance to Paracetamol. I became aware of it when my Endocrinologist advised me to take a max continual dose to try to down-regulate the chronic spine pain!

I also sense when it compounds another sensitivity reaction. I am sensitive to Salicylates, Amines, Glutamates, Preservatives etc and most drugs.....so why should I be surprised?

I cannot use it on a continual basis, so now rarely use it. Concentrating now on Methylation Protocol in hope of supporting my liver to make more of it's own glutathione.

Also exploring other ways of reducing pain.