LONGECITY

A type of antioxidant may not be as safe as once thought
By University of Virginia Health System
Sep 4, 2007 - 9:01:29 PM


Charlottesville, Va., Sept. 4, 2007 - Certain preparations taken to enhance athletic performance or stave off disease contain an anti-oxidant that could cause harm. According to new research at the University of Virginia Health System, N-acetylcysteine (NAC), an anti-oxidant commonly used in nutritional and body-building supplements, can form a red blood cell-derived molecule that makes blood vessels think they are not getting enough oxygen. This leads to pulmonary arterial hypertension (PAH), a serious condition characterized by high blood pressure in the arteries that carry blood to the lungs. The results appear in the September issue of the Journal of Clinical Investigation.

“NAC fools the body into thinking that it has an oxygen shortage,” said Dr. Ben Gaston, UVa Children’s Hospital pediatrician and researcher who led the study. “We found that an NAC product formed by red blood cells, know as a nitrosothiol, bypasses the normal regulation of oxygen sensing. It tells the arteries in the lung to ‘remodel’; they become narrow, increasing the blood pressure in the lungs and causing the right side of the heart to swell.”

Gaston notes that this is an entirely new understanding of the way oxygen is sensed by the body. The body responds to nitrosothiols, which are made when a decreased amount of oxygen is being carried by red blood cells; the response is not to the amount of oxygen dissolved in blood. He says that this pathway was designed much more elegantly than anyone had previously imagined. “We were really surprised”, he said.

The research team administered both NAC and nitrosothiols to mice for three weeks. The NAC was converted by red blood cells into the nitrosothiol, S-nitroso-N-acetylcysteine (SNOAC). The normal mice that received NAC and SNOAC developed PAH. Mice missing an enzyme known as endothelial nitric oxide synthase did not convert NAC to SNOAC, and were protected from the adverse effects of NAC, but not SNOAC. This suggests that NAC must be converted to SNOAC to cause PAH.

Could regular use of NAC produce the same effects in humans" The next step is to determine a threshold past which antioxidant use becomes detrimental to heart or lung function, according to Dr. Lisa Palmer, co-researcher of the study.

“The more we understand about complexities in humans, the more we need to be aware of chemical reactions in the body,” said Palmer.

According to Gaston and Palmer, NAC is being tested in clinical trials for patients with cystic fibrosis as well as other conditions; and clinical trials with nitrosothiols are being planned. These results, Palmer says, should motivate researchers to check their patients for PAH.

The results also open up a range of possibilities in treating PAH. Palmer added that the signaling process could be restorative and healing if they figured out how to keep NAC from fooling the body.

“From here we could devise new ways for sensing hypoxia or we could in theory modify signaling to treat PAH,” Palmer said.

http://foodconsumer....e_thought.shtml

Here

Zoo, I don't have access to the link you posted. What is your opinion on NAC given the new research?

Eek! It takes just 600 mg/day to increase hypoxic ventilatory response in humans.

But on the bright side, the link Zoo provided said

It is reassuring that the NAC dose that caused PAH in mice was higher than the hypoxia-mimetic dose [600 mg/day] used in humans.

I'm still chucking it.
Edited by krillin, 10 September 2007 - 05:49 PM.

This sounds very bad. Thank god I haven't tried this supplement yet.

This sounds bad to me too.

Well, I wonder what I should do with my 3 year supply of bulk NAC now...

Do 600 mgs a day and if you feel side-effects, stop.

I've been taking...between 600 mg and 1200 mg/day for I dunno perhaps a decade, perhaps more. This certainly merits looking into, but the chicken little mentality of the board is not helpful.

Zoo--any further thoughts?

Do 600 mgs a day and if you feel side-effects, stop.

Would you be able to feel the side effects mentioned?

Not really qualified to give a respectable answer, but in my opinion, something that would so drastically affect your lungs/heart would be noticeable in terms of side effects. I'm sure it's a gradual process as well, and not something that just hits you like a truck.

Just take 500mg a day and you'll be fine.

I admit this indeed is worth pondering over. Do we have to panic over this, I don't think so, but it'd be interesting to hear more on this topic by those on this board with far more extensive understanding of such topics.

worth consideration IMO

I might finish my bulk powder, and then switch to sylmarin/artichoke/black radis/vitC etc for liver health

I noticed a month ago from looking at my late aunt med list, that NAC was part of it--I know they've used it in medicine, but don't recall what for exactly. I think it's related to pulmonary issues.

I'll try to have a read of the paper today. Glexia you sure have thrown a spanner in the works I have a million and one other papers to read though.

ScottL, I'm in a similar boat to you. I've been taking between 600-1200mg for quite a few years now.

I wonder ; would you think L-cysteine would have the same outcome, or is it the acetyl molecule that's responsible for this ?

ScottL, I'm in a similar boat to you. I've been taking between 600-1200mg for quite a few years now.

Have you experienced any particular side-effects that would now make sense in light of this study above in this thread ?

I take 200mg 2x a day and was thinking about switching to one pill of 500mg a day.

This is weird. NAC has been found to protect against hypoxia-induced PH in previous studies. And, if this was going to happen in humans, I would think it would have already been reported as this should affect high-level athletic performance.

This is weird. NAC has been found to protect against hypoxia-induced PH in previous studies. And, if this was going to happen in humans, I would think it would have already been reported as this should affect high-level athletic performance.

What does PH stand for here ?

Thanks

What does PH stand for here ?

pulmonary hypertension

A type of antioxidant may not be as safe as once thought
By University of Virginia Health System
Sep 4, 2007 - 9:01:29 PM


Charlottesville, Va., Sept. 4, 2007 - Certain preparations taken to enhance athletic performance or stave off disease contain an anti-oxidant that could cause harm. According to new research at the University of Virginia Health System, N-acetylcysteine (NAC), an anti-oxidant commonly used in nutritional and body-building supplements, can form a red blood cell-derived molecule that makes blood vessels think they are not getting enough oxygen. This leads to pulmonary arterial hypertension (PAH), a serious condition characterized by high blood pressure in the arteries that carry blood to the lungs. The results appear in the September issue of the Journal of Clinical Investigation.

“NAC fools the body into thinking that it has an oxygen shortage,” said Dr. Ben Gaston, UVa Children’s Hospital pediatrician and researcher who led the study. “We found that an NAC product formed by red blood cells, know as a nitrosothiol, bypasses the normal regulation of oxygen sensing. It tells the arteries in the lung to ‘remodel’; they become narrow, increasing the blood pressure in the lungs and causing the right side of the heart to swell.”

Gaston notes that this is an entirely new understanding of the way oxygen is sensed by the body. The body responds to nitrosothiols, which are made when a decreased amount of oxygen is being carried by red blood cells; the response is not to the amount of oxygen dissolved in blood. He says that this pathway was designed much more elegantly than anyone had previously imagined. “We were really surprised”, he said.

The research team administered both NAC and nitrosothiols to mice for three weeks. The NAC was converted by red blood cells into the nitrosothiol, S-nitroso-N-acetylcysteine (SNOAC). The normal mice that received NAC and SNOAC developed PAH. Mice missing an enzyme known as endothelial nitric oxide synthase did not convert NAC to SNOAC, and were protected from the adverse effects of NAC, but not SNOAC. This suggests that NAC must be converted to SNOAC to cause PAH.

Could regular use of NAC produce the same effects in humans" The next step is to determine a threshold past which antioxidant use becomes detrimental to heart or lung function, according to Dr. Lisa Palmer, co-researcher of the study.

“The more we understand about complexities in humans, the more we need to be aware of chemical reactions in the body,” said Palmer.

According to Gaston and Palmer, NAC is being tested in clinical trials for patients with cystic fibrosis as well as other conditions; and clinical trials with nitrosothiols are being planned. These results, Palmer says, should motivate researchers to check their patients for PAH.

The results also open up a range of possibilities in treating PAH. Palmer added that the signaling process could be restorative and healing if they figured out how to keep NAC from fooling the body.

“From here we could devise new ways for sensing hypoxia or we could in theory modify signaling to treat PAH,” Palmer said.

http://foodconsumer....e_thought.shtml

Dear glexia,

Thank you very much for sharing this story with us. My advise to you would be to make a list of all of the supplements/drugs you may take, and write them down. Then write down your diet and exercise program, and bring these into a doctor that is aware of your medical history as well.

I recall before these studies came out:

o Antioxidant Supplementation Increases the Risk of Skin Cancers in Women but Not in Men

o JAMA: Vitamin E, A, beta-caro increases mortality

o Archives of Internal Medicine: Vitamins C and E and Beta Carotene: No benefit, in the Secondary Prevention of Cardiovascular Events in Women

A lot of folks seemed to believe that there was some guaranteed benefit from multivitamins and other misc. antioxidants (NAC is an antioxidant).

Not to mention, if you check out Testing finds lead in vitamins, other problems, it seems about fifty percent (or 1/2) of multivitamins may be contaminated with lead or it appears may otherwise be unable to match their label claims.

So it's important to keep up to date on all of the latest research findings and to watch out for sales "hype" -- and most importantly, you should work with a licensed health care professional that is aware of your entire medical history before changing anything in your diet or exercise program.

I saw a story recently published in the press: Doctors flunk quiz about supplements their patients use:

Before the testing, which was administered early last year, many doctors knew little about supplements: One-third did not know that they do not need to be approved by the Food and Drug Administration or that safety and efficacy data are not required as a condition of sale. One-third of doctors also did not know that the quality of supplements is not regulated, while 60 percent were unaware that adverse reactions to them should be reported to the FDA.

So I am determined to find physicians that are competent on these matters, a few health care professionals individuals that may be able to help folks make the best decisions with respect to their health are as follows (and if they cannot, they may be able to provide you with a referral to someone in your area or outside of their specialty who can):

I understand you don't live in the United States, but for folks who do:

(Allopathic) Medical Doctors (MDs):

o Suraj Achar MD (CA)
o Mitchell Gibson MD (NC)
o Bernd Wollschlaeger MD (FL) *Online consultation available* -- maybe for you, glexia?

Naturopathic Doctors (NDs)

o Joe Brown, ND (AZ)

Chiropractic Doctors (DCs)

o Bill F. Puglisi DC (NJ)

If you're just looking for diet/exercise advise, specialists from all fields listed above will likely give you similar advise. If you've already got cancer or heart disease, you might consider working with an MD and an ND to get the both of both worlds.

Take care.

worth consideration IMO

I might finish my bulk powder, and then switch to sylmarin/artichoke/black radis/vitC etc for liver health

Don't forget sublingual glutathione or alpha lipoic acid; both which have been proven to also increase liver glutathione levels like NAC. I will continue taking NAC and ALA though. NAC at 500mg on empty stomach in morning and 2 X 300mg ALA a day. I also take 800mg of Milk Thistle right now also. I figure that is adequate for optimal liver health, along with all the other necessities that is .

What does PH stand for here ?

pulmonary hypertension

Thanks cnorwood

Don't forget sublingual glutathione or alpha lipoic acid; both which have been proven to also increase liver glutathione levels like NAC.

where did you read that? We've discussed the bioavailability of oral glutathione before Aaron. It was pointed out on many occasions that it's not very bioavailable. The availability of sublingual glutathione hasn't yet been established as far as I know.

Any references from peer review medical sources?

I read same thing many times that oral Glutathione isn't well absorbed.

Without confusing everyone I will just skim the surface of what I have read.

The problematic compound here is either NAC itself or most likely it's converted byproduct S-nitroso-N-acetyl cysteine (SNOAC). Whilst SNOAC works centrally like others SNO's such as GSNO (S-Nitroso-glutathione) to control respiration, SNOAC somehow bypasses important regulatory process in the pulmonary endothelium (i.e at the lungs where the blood becomes reoxygenated) that makes the blood appear deoxygenated (hypoxic-mimetic effect). This is what subsequently causes changes to the pulmonary vasculature resulting in the PAH. NOTE: The hypoxic memetic effects of NAC supplementation has also been show in humans (Hildebrandt et al. 2002) however there was no mention of PAH. It was suggested by the authors of the study conducted with mice that this could be because large doses were used in the mice when compared with the human study (600mg/day). If you read the human study you can see that they only supplemented for 5 days with the humans compared to 3 weeks in mice. Additionally the study conducted by Hilderbrandt et al. (2002) doesn't appear to have measured or even considered a hypertensive scenario.

SHIT! What a pickle?

For now I'm going to stop supplementing with NAC. I use NAC because it's an affective cysteine donor however I don't like what I'm reading (i.e formation of SNOAC and it's consequences). There are other stable cysteine donors out there for example, undenatured whey protein. Heck the main reason why most people would use NAC or whey is because oral cystine and cysteine are poorly absorbed. So if someone where to give you the choice of 2 effective cysteine donors

1. N-acetyl cysteine: caveat emptor may cause subclinical thickening of right ventricular wall and eventual PAH
2. Undenatured whey protein

I know what I would choose

I will leave you with a nice little reveiw paper about the benefits of a cysteine rich diet. Hopeful that will calm everyone's nerves

Philos Trans R Soc Lond B Biol Sci. 2005 Dec 29;360(1464):2355-72.

    Oxidative stress and ageing: is ageing a cysteine deficiency syndrome?


    Dröge W.

    Deutsches Krebsforschungszentrum Division of Redox Physiology and Aging Research Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.

    Reactive oxygen species (ROS) are constantly produced in biological tissues and play a role in various signalling pathways. Abnormally high ROS concentrations cause oxidative stress associated with tissue damage and dysregulation of physiological signals. There is growing evidence that oxidative stress increases with age. It has also been shown that the life span of worms, flies and mice can be significantly increased by mutations which impede the insulin receptor signalling cascade. Molecular studies revealed that the insulin-independent basal activity of the insulin receptor is increased by ROS and downregulated by certain antioxidants. Complementary clinical studies confirmed that supplementation of the glutathione precursor cysteine decreases insulin responsiveness in the fasted state. In several clinical trials, cysteine supplementation improved skeletal muscle functions, decreased the body fat/lean body mass ratio, decreased plasma levels of the inflammatory cytokine tumour necrosis factor alpha (TNF-alpha), improved immune functions, and increased plasma albumin levels. As all these parameters degenerate with age, these findings suggest: (i) that loss of youth, health and quality of life may be partly explained by a deficit in cysteine and (ii) that the dietary consumption of cysteine is generally suboptimal and everybody is likely to have a cysteine deficiency sooner or later.

    PMID: 16321806 [PubMed - indexed for MEDLINE]

Without confusing everyone I will just skim the surface of what I have read.

The problematic compound here is either NAC itself or most likely it's converted byproduct S-nitroso-N-acetyl cysteine (SNOAC). Whilst SNOAC works centrally like others SNO's such as GSNO (S-Nitroso-glutathione) to control respiration, SNOAC somehow bypasses important regulatory process in the pulmonary endothelium (i.e at the lungs where the blood becomes reoxygenated) that makes the blood appear deoxygenated (hypoxic-mimetic effect). This is what subsequently causes changes to the pulmonary vasculature resulting in the PAH. NOTE: The hypoxic memetic effects of NAC supplementation has also been show in humans (Hildebrandt et al. 2002) however there was no mention of PAH. It was suggested by the authors of the study conducted with mice that this could be because large doses were used in the mice when compared with the human study (600mg/day). If you read the human study you can see that they only supplemented for 5 days with the humans compared to 3 weeks in mice. Additionally the study conducted by Hilderbrandt et al. (2002) doesn't appear to have measured or even considered a hypertensive scenario.

SHIT! What a pickle?

For now I'm going to stop supplementing with NAC. I use NAC because it's an affective cysteine donor however I don't like what I'm reading (i.e formation of SNOAC and it's consequences). There are other stable cysteine donors out there for example, undenatured whey protein. Heck the main reason why most people would use NAC or whey is because oral cystine and cysteine are poorly absorbed. So if someone where to give you the choice of 2 effective cysteine donors

1. N-acetyl cysteine: caveat emptor may cause subclinical thickening of right ventricular wall and eventual PAH
2. Undenatured whey protein

I know what I would choose

I will leave you with a nice little reveiw paper about the benefits of a cysteine rich diet. Hopeful that will calm everyone's nerves

Philos Trans R Soc Lond B Biol Sci. 2005 Dec 29;360(1464):2355-72.

    Oxidative stress and ageing: is ageing a cysteine deficiency syndrome?


    Dröge W.

    Deutsches Krebsforschungszentrum Division of Redox Physiology and Aging Research Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.

    Reactive oxygen species (ROS) are constantly produced in biological tissues and play a role in various signalling pathways. Abnormally high ROS concentrations cause oxidative stress associated with tissue damage and dysregulation of physiological signals. There is growing evidence that oxidative stress increases with age. It has also been shown that the life span of worms, flies and mice can be significantly increased by mutations which impede the insulin receptor signalling cascade. Molecular studies revealed that the insulin-independent basal activity of the insulin receptor is increased by ROS and downregulated by certain antioxidants. Complementary clinical studies confirmed that supplementation of the glutathione precursor cysteine decreases insulin responsiveness in the fasted state. In several clinical trials, cysteine supplementation improved skeletal muscle functions, decreased the body fat/lean body mass ratio, decreased plasma levels of the inflammatory cytokine tumour necrosis factor alpha (TNF-alpha), improved immune functions, and increased plasma albumin levels. As all these parameters degenerate with age, these findings suggest: (i) that loss of youth, health and quality of life may be partly explained by a deficit in cysteine and (ii) that the dietary consumption of cysteine is generally suboptimal and everybody is likely to have a cysteine deficiency sooner or later.

    PMID: 16321806 [PubMed - indexed for MEDLINE]

I didn't know L-Cysteine was poorly absorbed.

I'll stick to undenatured Whey protein too for the time being, until further developements.

This last post of yours was helpful to me, and probably will to many others.

Cheers chip. Always happy to help matey