176 replies to this topic

[health_nutty]

I'd think that, either that or the mice were seriously overdosed.  Krillin--you've been taking it for years...have you seen a doctor to see if you may have any potential signs of PAH?  That should be a long enough time to get *something* if there is anything to get.

We already know the dose. It is equivalent to a 600mg human dosage.

[krillin]

Wouldn't you think that someone who supplements with NAC would have come down with PAH by now or even had complications or signs of the beginning stages of PAH?

Krillin--you've been taking it for years...have you seen a doctor to see if you may have any potential signs of PAH? That should be a long enough time to get *something* if there is anything to get.

How do we know that there aren't any PAH cases from NAC use? I wouldn't think that many doctors or epidemiologists know about this effect yet. As for those of us who have been taking it without symptoms, vitamin C may have been providing partial or full protection, or the remodeling effect may not be far enough along to produce symptoms. The stuff has a unique risk but no unique benefits (for me anyway), so I can't justify using it.

[geost]

Thank you all for a very informative and interesting discussion. I am considering adding NAC to my daily supplements after coming upon the following article:

http://www.scienceda...70911120331.htm

Health Food Supplement May Curb Addiction Of Pathological Gamblers, Sep. 12, 2007

In a recent eight-week trial, 27 people were given increasing doses of the amino acid, N-acetyl cysteine, which has an impact on the chemical glutamate -- often associated with reward in the brain. At the end of the trial, 60 percent of the participants reported fewer urges to gamble.

and

Similar studies using N-acetyl cysteine have shown its ability to curb drug addictions in animals, and a current University of Minnesota study conducted by Grant is investigating whether the drug could help methamphetamine users quit.

"This research could be encouraging for a lot of addictions," Grant said.

Looking around I see that 600mg. daily is considered to be on the low side. I also see mention of the need for about three times as much vitamin C concurrently. Guess I might just start with the 600mg. daily to avoid any complications. I'm hoping this can help give me an edge to address my nicotine habit.

[hullcrush]

H0W is it equivalent to 600 mg in a human?

I'm guessing the mice were allowed water freely, which in my opinion is a poor decision. Based on data available in a different study of mice weight and water intake let's do calculations:

mean water intake of mice used: 6 ml per day
mean mice weight: 25 g

dilutions of NAC used in study: 1mg/ml and 10mg/ml
so the mice would have ingested 6 and 60 mg of nac a day, assuming the taste of NAC didn't turn them off, it can get pretty nasty.

6 mg / .025 kg = 240 mg/kg in 1mg/ml
2400 mg/kg in 10mg/ml

Average dose in humans 500 mg daily for 80 kg individual (that's a little high, but a bodybuilder so yeah).
Assuming we have same pharmokinetics as said mice (15% oral bioavailability)
which may or may not be true...

The problem is that the mice's NAC was dissolved in h20 for a day which might have weakened it, which would be scarier.

Human recommended dose is 6.25 mg/kg, significantly less than 240 mg/kg in said mice.

Bottom Line: 3 Weeks of 240mg/kg can raise systolic bp 10 points in one mouse species (irreversibly?). This equates to an oral intake of 14.4 g of NAC per day for my underweight ass. IM0, the benefits outweigh the side effects for now.

So, just in case you hear the opposite, point to this post. I'd use 500 mg / day until further research comes out.

Edited by hullcrush, 24 September 2007 - 08:45 PM.

[krillin]

H0W is it equivalent to 600 mg in a human?

It might have the same effect. Health Nutty was probably referring to the human study in which 600 mg/day increased the hypoxic ventilatory response and EPO. It's not a stretch to say that HIF-1 was involved (the authors mentioned it in the discussion section), and HIF-1 also plays a role in the remodeling that causes PAH.

[chipdouglas]

http://articles.merc...of-trouble.aspx


Researchers at the University of Virginia Health System have discovered troubling side effects of N-acetylcysteine (NAC), a common antioxidant used in nutritional and bodybuilding supplements.

NAC can form a red blood cell-derived molecule called nitrosothiol that fools your body into thinking there’s an oxygen shortage, which can lead to pulmonary arterial hypertension (PAH).

PAH is a serious condition, where the arteries in the lungs narrow, increasing the blood pressure in your lungs, causing the right side of your heart to swell.

Lead researcher Dr. Ben Gaston, noted that this is an entirely new understanding of how oxygen is sensed by the body. As it turns out, your body responds to the nitrosothiols, which are created when a decreased amount of oxygen is carried by red blood cells -- not to the amount of oxygen dissolved in the blood.

So far, studies have only been performed on mice. The next step is to determine the threshold at which the antioxidant becomes detrimental to heart and lung function in humans.

Journal of Clinical Investigation September, 2007; 117(9):2592-601 (Free Full Text Report)

Physorg.com September 4, 2007












N-acetylcysteine (NAC) is an acetylated amino acid and a precursor of glutathione, another potent antioxidant that prevents free radical damage from toxic exposures.

NAC is also a common emergency room treatment for people who have overdosed on acetaminophen (the active ingredient in pain relievers like Tylenol).

Interestingly, NAC is actually used to treat several types of lung disease, and although this animal study connects it with constriction of lung arteries, at least one other study has linked NAC with improved blood flow, stating NAC might increase the biologic effects of nitric oxide by combining with it to form S-nitrosothiol, which is a potent vasodilator. They found that NAC also increases the expression of nitric oxide synthase and may thus improve blood flow as well.

Since I don’t frequently use supplements, I consulted one of my friends, Dr. William LaValley from Austin, Texas, who is an expert in this area and has reviewed the literature thoroughly. He successfully uses supplements as a therapeutic tool in many chronic conditions including cancer.

He felt that PAH may be species specific and possibly won’t happen in humans, and more importantly, the study used much higher doses than are generally used in humans. As mentioned, there are many studies supporting the anti-oxidant benefit of NAC for pulmonary function in cystic fibrosis, post-radiation, and other high oxidant conditions. His conclusion, and I agree, is that a little is probably ok - even good for you. He has used NAC liberally in his therapeutic protocols for nearly 20 years and has not observed any problems with it. However using large quantities is probably not good for you. Long-term high doses are probably not so good for several reasons - including the possibility of PAH.


The study says that the doses are higher than usual in humans - but we know that the supplement manufacturers have been making 500mg NAC caps and selling them by the truckload for years. My biggest concern is the use of NAC by cancer patients who think it is helping - when in fact it may be harmful to them by protecting cancer cells and counteracting what potential benefit they may get from some conventional treatments. It's a thorny issue.

So, if used therapeutically, it should be used in low doses for 'prevention.' High doses should be restricted to disease/stress states that have high likelihood of high reactive oxygen species generation (such as trauma, certain types of infection, malnutrition, and certain types of toxicity).

Dr. LaValley feels that 200-500mg once a day is probably ok in most non-cancer cases. NAC is an important consideration for inclusion, at some reasonable dose, in anti-aging formulas.

However, please remember that the best way to get your antioxidants is to make sure you’re getting them from whole foods, not from supplements, which are often isolated synthetics rather than the readily bioavailable version. What you need is the Goldilock’s equation – not too many and not too few antioxidants – to achieve and maintain optimal health, and it is quite easy to overdose when you take supplements. Fortunately, your body does a phenomenal job of self-regulating many of these levels if you supply it with wholesome, healthy foods and limit your intake of processed foods, which are frequently loaded with artificial chemicals.

Normalizing your insulin and leptin levels is also quite helpful, as elevated insulin and leptin levels cause absolute biochemical havoc in your body and worsen nearly every major part of your physiology. Normalizing your blood sugar will raise your glutathione levels naturally, rather than taking glutathione or precursor supplements.

Glutathione, along with vitamin E, vitamin C and alpha lipoic acid are the basic antioxidants. Some nutritional authorities recommend you take it as a supplement, or take an NAC supplement. There are problems with both. First, the form of glutathione that works best is the reduced form, which is very difficult to absorb orally. Secondly, I advise against using NAC if you still have mercury amalgam fillings because it could interfere with the detoxification of the mercury.

It is much better to get your glutathione through items like alpha lipoic acid that regenerates glutathione. It also has the added ability to generate other antioxidants such as vitamins C and E. The best sources of alpha lipoic acid are red meat and organ meats. Just make sure to stick with grass-fed organic meats, to get the maximum nutrient content and none of the added antibiotics or pesticides.

Glutamine is also a useful nutrient that improves intestinal health and also serves as a direct precursor to glutathione, and some investigators believe it to be the rate-limiting nutrient for glutathione formation. However, in large quantities it can be problematic as Dr. Blaylock outlines in his book “Excitotoxins.”






Related Articles:


NAC Protects Kidneys From Dye-Related Failure

Could Too Many Antioxidants be as Bad as Too Few?

Antioxidants and the Fountain of Youth

[spacetime]

H0W is it equivalent to 600 mg in a human?

I'm guessing the mice were allowed water freely, which in my opinion is a poor decision. Based on data available in a different study of mice weight and water intake let's do calculations:

mean water intake of mice used: 6 ml per day
mean mice weight: 25 g

dilutions of NAC used in study: 1mg/ml and 10mg/ml
so the mice would have ingested 6 and 60 mg of nac a day, assuming the taste of NAC didn't turn them off, it can get pretty nasty.

6 mg / .025 kg = 240 mg/kg in 1mg/ml
2400 mg/kg in 10mg/ml

Average dose in humans 500 mg daily for 80 kg individual (that's a little high, but a bodybuilder so yeah).
Assuming we have same pharmokinetics as said mice (15% oral bioavailability)
which may or may not be true...

The problem is that the mice's NAC was dissolved in h20 for a day which might have weakened it, which would be scarier.

Human recommended dose is 6.25 mg/kg, significantly less than 240 mg/kg in said mice.

Bottom Line: 3 Weeks of 240mg/kg can raise systolic bp 10 points in one mouse species (irreversibly?). This equates to an oral intake of 14.4 g of NAC per day for my underweight ass. IM0, the benefits outweigh the side effects for now.

So, just in case you hear the opposite, point to this post. I'd use 500 mg / day until further research comes out.

Don't we need to factor in the human equivalency dose? I can't recall if it's 6 times the rat dose or 1/6th, but obviously this makes a huge difference. Either 100mg or 3.6g would be the equivalent dose.

[health_nutty]

1/6.

Remember the resveratrol studies that showned you needed 30mg/kg and then the 1/6 scaling factor was applied to get 5mg/kg?

[michaelscott]

Here's how Dr. David Wheldon over at cpnhelp.org responded when it was posted over there:

Thanks for posting; if confirmed it is worrying. However, it seems doubtful: there have been literally hundreds of animal studies (mostly rats and mice) with NACi; Pulmonary Hypertensioni (PH) has never been reported. One such study is this: [Arfsten D, Johnson E, Thitoff A et al., Impact of 30-day oral dosing with N-acetyl-L-cysteine on Sprague-Dawley rat physiology. Int J Toxicol. 2004 Jul-Aug; 23(4): 239-47.] The doses used were huge; by weight they were 50 times greater than that recommended as a human dietary supplement. In fact, NAC was found to protect rats from hypoxia-induced PH [Hoshikawa Y, Ono S, Suzuki S, et al., Generation of oxidative stress contributes to the development of pulmonary hypertension induced by hypoxia. J Appl Physiol. 2001 Apr;90(4):1299-306.] This protectective effect in PH was confirmed by another group [Lachmanova V, Hnilickova O, Povysilova V, et al., N-acetylcysteine inhibits hypoxic pulmonary hypertension most effectively in the initial phase of chronic hypoxia. Life Sci. 2005 May 27;77(2): 175-82.] Also, NAC is used extensively by athletes for long periods; there are no reports of PH. As shortness of breath on exercise is an early symptom of PH this disease should be readily apparent in athletes. Indeed, NAC is a very commonly used supplement, and there have never been any reports of PH. Further, NAC has been used as a sputum thinner for long periods in persons with cystic fibrosis and chronic bronchitis, again without any reports of PH. It was used for 6 months in a group of persons with Chronic Obstructive Pulmonary Disease with apparent benefit. [Pela R, Calcagni AM, Subiaco S, et al., N-acetylcysteine reduces the exacerbation rate in patients with moderate to severe COPD. Respiration. 1999 Nov-Dec;66(6):495-500.] On this evidence I shall still be taking it (but am prepared to change if new evidence appears.)

Link

[rflalonde]

From Life Extension News, November 2007

The following is from a long article on glutathione by Durk and Sandy:

Why We Choose Cysteine Rather Than N-Acetylcysteine

N-acetylcysteine (NAC) is a potent nonphysiological (i.e., it is not found naturally in the body) precursor of GSH that increases GSH levels by donating cysteine. The problem with NAC is that, as reported in many papers, it is such a powerful antioxidant that it can inhibit reactive oxygen species (ROS) signaling that is a necessary part of many normal chemical pathways. Hence, we have been very reluctant to use it, at least as an everyday supplement. For example, one recent paper8 reported that NAC interfered with the ROS (reactive oxygen species) signaling pathway by which erythropoietin stimulates the creation of red blood cells. This was in a study of erythropoietin-induced differentiation of erythroid progenitors derived from mouse fetal liver. Treatment with another potent antioxidant, pyrrolidine dithiocarbamate (PDTC), also caused the attenuation of expression of TER119 (an erythroid-specific antigen). The authors conclude, “The results suggest reactive oxygen species are involved in Epo [erythropoietin]-mediated erythroid differentiation.” In fact, this may have happened to one of us (Sandy), who was taking N-acetylcysteine (but no longer does). Upon having her regular lab tests during her NAC supplementation period, she discovered that her red blood cell levels had declined to half of their previous amount.

[Alien65]

I've been taking L-Cysteine or N-Aceytl Cysteine for decades in the 500mg to 1000mg range. The only side effect I've had is a full head of thick hair. It's still there at age 65.

[zoolander]

Nocturnal oxygen desaturation is common in patients with PAH and this is commonly measured using pulse oximetry (1)

If you want to do a preliminary test on yourself then simply try and get your hands on a software compatible pulse oximeter

Edited by zoolander, 24 February 2008 - 04:00 PM.

[TheFountain]

take it with some kind of NO supplement and I'm guessing you'll be fine

What is a NO supplement?

[pycnogenol]

take it with some kind of NO supplement and I'm guessing you'll be fine

What is a NO supplement?

Nitric Oxide

[TheFountain]

take it with some kind of NO supplement and I'm guessing you'll be fine

What is a NO supplement?

Nitric Oxide

Now I have to google some studies.

[yoyo]

Nocturnal oxygen desaturation is common in patients with PAH and this is commonly measured using pulse oximetry (1)

If you want to do a preliminary test on yourself then simply try and get your hands on a software compatible pulse oximeter

has noone done this?

[JLL]

I ordered some NAC for the purpose of counteracting some of the harmful effects of alcohol. I read it's good for dealing with acetaldehyde.

[tunt01]

I ordered some NAC for the purpose of counteracting some of the harmful effects of alcohol. I read it's good for dealing with acetaldehyde.

we know the real reason you ordered it....

http://www.scienceda...91023102504.htm

[NeverSayDie]

I emailed LEF about this study and this is their reply:


Thank you for your recent correspondence.

Here is a link to the entire study in the September issue of the Journal of Clinical Investigation. http://www.jci.org/articles/view/29444 As you can see, this study involved high-dose administration of NAC to mice. We have seen no evidence that pulmonary arterial hypertension occurs in humans taking the much lower doses commonly suggested for this important antioxidant. If you have any additional questions, please e-mail us or call the advisor helpline at (800) 226-2370.

[NDM]

I emailed LEF about this study and this is their reply:


Thank you for your recent correspondence.

Here is a link to the entire study in the September issue of the Journal of Clinical Investigation. http://www.jci.org/articles/view/29444 As you can see, this study involved high-dose administration of NAC to mice. We have seen no evidence that pulmonary arterial hypertension occurs in humans taking the much lower doses commonly suggested for this important antioxidant. If you have any additional questions, please e-mail us or call the advisor helpline at (800) 226-2370.

that's asking the barber if you need a haircut...

What if high dose for a short term (Mice) equals low dose for a long term (Humans)? If the effect of NAC is linear and cumulative, then low dose/long term is equally bad.

[Atropy]

So,what is the current general consensus regarding using NAC with amalgum fillings?I have amalgum fillings.I haven't ordered NAC as yet.Should I order Alpha-Lopoic acid instead?

[Climactic]

So,what is the current general consensus regarding using NAC with amalgum fillings?I have amalgum fillings.I haven't ordered NAC as yet.Should I order Alpha-Lopoic acid instead?

I have such fillings, and I have been taking 600 mg NAC and 50 mg x2 r-ALA for years without issue. Whey protein too. My personal actions don't signify a consensus, however.

[renfr]

Don't take NAC if you got amalgam fillings, they must be removed and after removal you must wait a certain period before starting to even think about taking NAC.

[Atropy]

Thanks.Can ALA be used as a safe alternative?

[niner]

Don't take NAC if you got amalgam fillings, they must be removed and after removal you must wait a certain period before starting to even think about taking NAC.

Lots of people with amalgam fillings use NAC without apparent problems. What's the evidence that it's bad?

[Kevnzworld]

Don't take NAC if you got amalgam fillings, they must be removed and after removal you must wait a certain period before starting to even think about taking NAC.

NAC can chelate and reduce the bodies mercury load caused by amalgam fillings. Some people have " dental metal allergies, so a cautious approach should be used at first.
" Mercury from Dental Amalgam Fillings: Studies on Oral Chelating Agents for Assessing and Reducing Mercury Burdens in Humans "
http://informahealth.../13590849861998
" N-acetylcysteine (NAC) has been found to be effective at increasing cellular glutathione levels and chelating mercury (54)."
http://www.mouthbody...am-Research.pdf
Title: Effect of monothiol along with antioxidant against mercury-induced oxidative stress in rat
" Single mercury exposure also resulted in a significant increase in lipid peroxides with a concomitant decrease in reduced glutathione level in liver, kidney and brain. A decrease in the enzymatic activities of acetyl cholinesterase in different regions of the brain was observed. These parameters were restored considerably with chelating agents along with nutritional supplementation, but NAC+Se and DPA+Mg offered significant protection in comparison with other combinations "
http://nopr.niscair..../123456789/5363
Regarding adverse effects with chelation agents and dental filling removal, there are some reports of adverse reactions related to dental metal filling allergies.
" Title: Adverse Effects of Antioxidants in Patients with Dental Metal Allergy "
http://air.unimi.it/handle/2434/198023

[Atropy]

Wow,ok.That sucks.Will Alpha-Lopoic Acid have a similar effect on Amalgam fillings?
Is ALA safer than NAC?

[niner]

Wow,ok.That sucks.Will Alpha-Lopoic Acid have a similar effect on Amalgam fillings?
Is ALA safer than NAC?

You might be misreading those refs that Kevnzworld posted. They're saying that NAC is good at chelating mercury and getting it out of the body. The big concern is if a chelating agent will help to transport mercury across the blood brain barrier. I don't see any evidence that NAC does that. If anything, I would expect ALA to be worse in that regard due to its increased hydrophobicity. I think this whole amalgam filling problem is way overblown, particularly if you only have a couple fillings. The writeup from mouthbodydoctor.com (neither peer reviewed nor published, as far as I could tell) mentions patients with up to 45 amalgam surfaces. It goes on to make some dubious claims like treating cancer or ALS by removing fillings. It also mentioned improvements in "irrational fears", which I found amusing, since there's a lot of that going around in the filling-removal patient population.

Mammals evolved in a world that contains a lot of natural sources of heavy metals, and they evolved a lot of internal systems for dealing with and disposing of those metals. If you are worried about mercury, make sure you are getting the RDA of selenium, since it is involved in the endogenous mercury-handling system. It is well known to be protective against mercury poisoning.

[renfr]

NAC does penetrate the BBB, it has an acetyl ring.

[john1960]

Heres the study from the thread back in 2007:

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

 

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.

 

Anways, what is the current verdict on NAC. Is it safe? I was taking 600 2x/day.

 

 

------------------

 

 

Thanks in advance for any feedback!

Edited by john1960, 29 January 2015 - 01:33 AM.