24 replies to this topic

[beez]

I recently in the past that NAC is linked to pulmonary hypertension.

Recently I read a science blog and the owner was a psychiatrist afaik and he

wrote about positive effects of NAC but he also was concerned that since NAC breaks up

mucus it could as well harm the inner linings in the blood vessels. I don't know if there is anything

to this.

Have you ever heard about this?

 

What kind of NAC dose would be safe to be taken daily?

 

A few weeks ago I had a cold and I was taking 1200mg NAC daily to get rid of the slime

and it might have been a coincidence but I felt like it was helping with my ocd. And I also

read that NAC works against OCD. What I ask myself now is how much NAC would be safe

to take on a daily basis IF in fact it helps with OCD.

[ZHMike]

Great topic, I would love a consensus on NAC.

[beez]

I just read over an article of NAC use in psychiatry. They had different studies ranging from 600mg to 3000mg per day.
But they also said that there are no long term safety studies. That's not good.
I also read that NAC can act as a prooxidant and should not be taken unless you have high oxidative stress. That's confusing.
I also read that psychiatrist disorders often go hand in hand with oxidative stress.
 
http://www.cma.ca/mu...-2/pdf/pg78.pdf

http://onlinelibrary...02/brb3.208/pdf

Edited by beez, 01 May 2014 - 05:17 PM.

[beez]

No ideas?

[Darryl]

90% of the U.S. population has dietary intakes of cysteine between 520 and 1640 mg/d. The essential requirement is smaller, roughly 280 mg for a 70 kg adult. Its only conditionally essential as methionine intake also contributes. I don't have a good sense for how much more bioavailable NAC is over dietary cysteine.

 

Acute adverse effects from IV NAC appear between 100 and 160 mg/kg (11 g for that 70 kg adult). 

 

van de Poll, M. C., Dejong, C. H., & Soeters, P. B. (2006). Adequate range for sulfur-containing amino acids and biomarkers for their excess: lessons from enteral and parenteral nutrition. The Journal of nutrition, 136(6), 1694S-1700S.

 

The typical dosage of N-acCys that is generally used in clinical trials ranges from 300 to 600 mg/d when given as a chronic nutritional supplement, up to 2400 mg/d to treat acute acetaminophen poisoning and to prevent contrastinduced nephrotoxicity. In a study in severely septic patients receiving up to 100 mg/kg N-acCys per day, no adverse events were found that could directly be ascribed to the N-acCys supplementation, although it must be noted that the treatment group showed a decrease in cardiovascular performance. Intravenous infusion of 160 mg/kg per day in healthy volunteers induced significant changes in vitamin K–dependent coagulation factors without actually compromising coagulation itself. Two patients developed epileptic states after high-dose N-acCys administration, 1 with a fatal course after the erroneous administration of 2450 mg/kg N-acCys in 11.5 h (intended dose 208 mg/kg) to an acetaminophen-poisoned child.

 

Obviously any dose is too much if you experience known acute adverse effects: inflamed and sore mouth, nausea, vomiting, fever, runny nose, drowsiness, clamminess, chest tightness, and bronchoconstriction. Some of these may result from increased release of the excitatory neurotransmitter glutamate.

 

Personally, I take 200 mg/day, mostly because I didn't want to impair glutathione synthesis with a low-methionine diet, while not taking so much that it acted as an unregulated direct antioxidant.

Edited by Darryl, 15 May 2014 - 10:53 PM.

[mrnootropic]

I wouldnt bother with NAC until more research comes out. 

Milk Thistle is good supplement to take to help boost Glutathione. Which you can take instead of NAC.

 

BUT, if i was taking NAC, i would Cycle it, i would take it for a short amount of time, about 4 - 6 weeks and then stop. 

 

Take between 200mg and 600mg.. LEF states that 600mg to 1800mg is the recommended dose.

The best thing to do is take it for 6 weeks, enough time for NAC to help you with its positive health effects, but not long enough for it to give you some serious adverse effects. Then stop for 2 months and then take it again and just keep cycling it.

 

I cant see how it can damage you, by taking it for a short amount of time, however:

I wouldn't take it daily for a long period of time.

Edited by Mr.Nootropic, 16 May 2014 - 10:37 AM.

[Turnbuckle]

You can supplement glutathione directly with the reduced (Setria) product. I take a gram every morning on an empty stomach along with 3 grams of time release C. (I also take 2 g of niacin at the same time for other reasons, as that seems to work synergistically.) The effect is the same or better than NAC, and is absent any reflux problem.

 

 

[mrnootropic]

You can supplement glutathione directly with the reduced (Setria) product. I take a gram every morning on an empty stomach along with 3 grams of time release C. (I also take 2 g of niacin at the same time for other reasons, as that seems to work synergistically.) The effect is the same or better than NAC, and is absent any reflux problem.

 

 

 

Oral Glutathione is supposedly not bio-available.

 

It is generally recommended to Take Liposomal Glutathione if you want to take any form of Glutathione..

Edited by Mr.Nootropic, 16 May 2014 - 11:26 AM.

[hav]

... safe NAC dosages were discussed a bit in an earlier thread:

 

http://www.longecity...ch-nac-is-safe/

 

When i take it, I go with 300 mg/day myself.

 

Howard

 

[Turnbuckle]

 

You can supplement glutathione directly with the reduced (Setria) product. I take a gram every morning on an empty stomach along with 3 grams of time release C. (I also take 2 g of niacin at the same time for other reasons, as that seems to work synergistically.) The effect is the same or better than NAC, and is absent any reflux problem.

 

 

 

Oral Glutathione is supposedly not bio-available.

 

It is generally recommended to Take Liposomal Glutathione if you want to take any form of Glutathione..

 

 

What is supposedly true is often false. Have you taken both and compared them?

[Phoenicis]

I'm confused, didn't this study show that oral glutathione is bioavailable?

 

ta5, on 06 May 2014 - 04:56 AM, said:

 

Eur J Nutr. 2014 May 5. 

Randomized controlled trial of oral glutathione supplementation on body stores of glutathione.

Richie JP Jr1, Nichenametla S, Neidig W, Calcagnotto A, Haley JS, Schell TD, Muscat JE.

PURPOSE:

Glutathione (GSH), the most abundant endogenous antioxidant, is a critical regulator of oxidative stress and immune function. While oral GSH has been shown to be bioavailable in laboratory animal models, its efficacy in humans has not been established. Our objective was to determine the long-term effectiveness of oral GSH supplementation on body stores of GSH in healthy adults.

METHODS:

A 6-month randomized, double-blinded, placebo-controlled trial of oral GSH (250 or 1,000 mg/day) on GSH levels in blood, erythrocytes, plasma, lymphocytes and exfoliated buccal mucosal cells was conducted in 54 non-smoking adults. Secondary outcomes on a subset of subjects included a battery of immune markers.

RESULTS:

GSH levels in blood increased after 1, 3 and 6 months versus baseline at both doses. At 6 months, mean GSH levels increased 30-35 % in erythrocytes, plasma and lymphocytes and 260 % in buccal cells in the high-dose group (P < 0.05). GSH levels increased 17 and 29 % in blood and erythrocytes, respectively, in the low-dose group (P < 0.05). In most cases, the increases were dose and time dependent, and levels returned to baseline after a 1-month washout period. A reduction in oxidative stress in both GSH dose groups was indicated by decreases in the oxidized to reduced glutathione ratio in whole blood after 6 months. Natural killer cytotoxicity increased >twofold in the high-dose group versus placebo (P < 0.05) at 3 months.

CONCLUSIONS:

These findings show, for the first time, that daily consumption of GSH supplements was effective at increasing body compartment stores of GSH.

PMID: 24791752

 

[Darryl]

Oral glutathione works as an expensive cysteine + glutamic acid + glycine supplement, as the majority breaks down upon digestion. As cysteine is the limiting amino acid for GSH synthesis in humans, long-term administration of just about any high cysteine source, like oral GSH or whey protein (2.3% Cys, 1.9% Met) may elevate GSH levels.

Edited by Darryl, 16 May 2014 - 03:47 PM.

[Turnbuckle]

Oral glutathione works as an expensive cysteine + glutamic acid + glycine supplement, as the majority breaks down upon digestion. As cysteine is the limiting amino acid for GSH synthesis in humans, long-term administration of just about any high cysteine source, like oral GSH or whey protein (2.3% Cys, 1.9% Met) may elevate GSH levels.

 

I take whey protein, and it doesn't have the effect of Setria. I've also made liposomal glutathione out of Setria, and I didn't see any difference compared to Setria in capsules. As for the assertion that the "majority breaks down upon digestion," do you have any data on that? Or is it just a supposition? I suspect that if you took it with a meal, it might get digested, but if you take it on an empty stomach, it might survive.

 

Though now I see a trial with Protectamin (a whey protein brand) that looks interesting, and I will definitely try it (assuming I can find it). It's not clear, however, that it dramatically increases the glutathione levels in healthy adults--

 

 

Supplementation with [Protectamin] whey proteins persistently increased plasma glutathione levels in patients with advanced HIV-infection. The treatment was well tolerated. A larger long-term trial is clearly warranted to evaluate whether this positive influence on the glutathione metabolism translates into a more favorable course of the disease.

 

Effects of long-term supplementation with whey proteins on plasma glutathione levels of HIV-infected patients.

 

 

 

Edited by Turnbuckle, 16 May 2014 - 05:01 PM.

[Darryl]

Some GSH is indeed absorbed intact in the intestinal lumen, but its still broken down before entry into brain and blood cells. The vast majority of GSH is generated from the precursor amino acids in the liver or peripheral tissues. See pg 170 in:

 

Kidd, Parris M. "Glutathione: systemic protectant against oxidative and free radical damage." Altern Med Rev 2.3 (1997): 155-176.

 

I'm perplexed as to why anyone bothers with preformed GSH. Other cysteine containing foods/supplements work as well, and none of them elevate the sum of GSH + GSSG beyond the normal range, which appears to be under homeostatic control. Its where GSH is catastrophically consumed (as in the liver during acetaminophen overdose) that high doses of GSH precursors like NAC can make a substantial difference. But beyond ensuring cysteine is replete, the main intervention to ensure high intracellular GSH is the hormetins (dietary polyphenols like flavonoids, stilbenoids, curcuminoids, isothiocyanates, lots of adaptogens fall into this category) to increase glutathione reductase expression, activity and the GSH / GSSG ratio.

 

 

 

Edited by Darryl, 16 May 2014 - 06:22 PM.

[ZHMike]

anybody get upset stomach with NAC?

[cuprous]

Personally I pop 600mg NAC a few times a week.

 

I've never had any stomach issues with NAC though I don't typically have to deal with acid reflux or the like.

 

I'm not informed enough to say that this really matters but consider that NAC allows your body to manufacture endogenous GSH whereas direct supplementation may overwhelm ROS pathways.  And do we know that this oral GSH will appear in all the places that GSH gets manufactured in the body?  I don't know.

 

I also wonder if oral GSH results in the same immune boost that comes from NAC supplementation.

Proc Nutr Soc. 2000 Nov;59(4):595-600.

Glutathione and immune function.

 

Dröge W1, Breitkreutz R.

Abstract

 

The immune system works best if the lymphoid cells have a delicately balanced intermediate level of glutathione. Even moderate changes in the intracellular glutathione level have profound effects on lymphocyte functions. Certain functions, such as the DNA synthetic response, are exquisitely sensitive to reactive oxygen intermediates and, therefore, are favoured by high levels of the antioxidant glutathione. Certain signal pathways, in contrast, are enhanced by oxidative conditions and favoured by low intracellular glutathione levels. The available evidence suggests that the lymphocytes from healthy human subjects have, on average, an optimal glutathione level. There is no indication that immunological functions such as resistance to infection or the response to vaccination may be enhanced in healthy human subjects by administration of glutathione or its precursor amino acid cysteine. However, immunological functions in diseases that are associated with a cysteine and glutathione deficiency may be significantly enhanced and potentially restored by cysteine supplementation. This factor has been studied most extensively in the case of human immunodeficiency virus (HIV)-infected patients who were found to experience, on average, a massive loss of S equivalent to a net loss of approximately 4 g cysteine/d. Two randomized placebo-controlled trials have shown that treatment of HIV-infected patients with N-acetyl-cysteine caused in both cases a significant increase in all immunological functions under test, including an almost complete restoration of natural killer cell activity. It remains to be tested whether cysteine supplementation may be useful also in other diseases and conditions that are associated with a low mean plasma cystine level and impaired immunological functions.

 

 

 

Edited by cuprous, 16 May 2014 - 07:14 PM.

[deeptrance]

Some of these may result from increased release of the excitatory neurotransmitter glutamate.

This statement caught my eye. I've been taking NAC a few times a day for at least a year, at a dose of around 200 mg. I usually take a dose at bedtime. I've had trouble with what feels like glutamate overactivity affecting my ability to sleep. It used to be much worse, back when I was in a habit of eating nutritional yeast at night, then I learned about the high level of free glutamic acid in yeast so I stopped that. It helped. I will stop taking NAC except first thing in the AM and see if that's helpful.

Given that I was unaware of NAC being a glutamatergic substance, I wonder if I take other things that have a similar effect. It's hard to track down all the info on a substance from any one source, although Examine.com is doing a good job of trying to provide such a resource.

[beez]

I'm confused. NAC is supposed to help with excessive glutamate. Then how can NAC cause excessive release of glutamate?
I read that NAC can be helpful in OCD because of its actions on glutamate.

 

And what do you think about this here?

 

What are the downsides of NAC? I can think of two problems that might be biggies - first off, NAC is a mucolytic that thins mucus by cutting disulfide bonds. I suspect that might raise risks - one wouldn't want too little mucus. Mucus is important. Paul Jaminet mentions this issue and links a study here. Also, cutting disulfide bridges within the body is what that inflammatory baddie homocysteine is supposed to do, leading to crispy collagen and inelastic elastin in the arteries (which would possibly first show up as high blood pressure).

 

 

http://www.psycholog...lems-i-have-nac

[Turnbuckle]

 

I'm perplexed as to why anyone bothers with preformed GSH. Other cysteine containing foods/supplements work as well, and none of them elevate the sum of GSH + GSSG beyond the normal range, which appears to be under homeostatic control.

 

 

See post #11 above--These findings show, for the first time, that daily consumption of GSH supplements was effective at increasing body compartment stores of GSH.

 

This dates from less than 2 weeks ago. It's not mentioned on the pubmed site, but the brand was Setria. The following comes from an info page on the lead author--

 

And as glutathione stores increased in the high-dose group, so did the function of natural killer (NK) cells, a marker for increased immune defense, said John P. Richie, Jr., Ph.D., professor of Public Health Sciences and Pharmacology at Penn State College of Medicine.

 

"A battery of immune function markers was examined after three months of glutathione supplementation and NK cytotoxicity was enhanced more than two-fold for participants taking 1000mg daily doses," Dr. Richie said. "We believe GSH supplementation may represent an effective intervention strategy for disease prevention and may enhance immune function."

 

There is a school of thought that contends that glutathione is broken down in the stomach and intestine and effective increases of GSH must come via intravenous administration. However, previous animal studies showed that orally administered glutathione is bioavailable and will enhance tissue GSH levels, Dr. Richie said.

 

"Our research showed that in most cases increases were dose and time dependent, and levels returned to baseline after a one-month washout," he said. "By taking daily GSH supplements, we believe efficacious levels will persist, and that oral intake is an effective means of chronically enhancing the body's stores."

 

http://www.zoominfo....chie/1063533955

 

 

 

Edited by Turnbuckle, 17 May 2014 - 04:31 PM.

[Darryl]

Aside from the high levels in tongue scrapings, the GSH levels in that study were only elevated 30-35%, which is in the range of elevation seen in studies with NAC.

 

1 600 mg NAC/d: plasma GSH ↑ 70-80%

2 600 mg NAC/d: bronchoalveolar lavage GSH ↑ 30%, epithelial lining fluid GSH ↑ 70%, 

3 600-1000 mg NAC/d: neutrophil GSH ↑ 23%, whole blood GSH ↑ 12%

4 avg 7000 mg/d (!!) in HIV patients: whole blood GSH ↑ 12%

5 0.5 mmol/kg/d in severely malnurished children: erythrocyte GSH ↑ 150%

 

As cellular GSH concentrations provide negative feedback to γ-glutamylcysteine ligase (the rate limiting enzyme in GSH synthesis), there's a soft-limit to how much effect either exogenous GSH or supplemental NAC can have. The main problem with preformed GSH, besides cost, is that unlike cysteine from NAC it doesn't pass the blood brain barrier. If I were looking for a more effective GSH precursor than NAC, I'd look into γ-glutamylcysteine ethyl ester, which does pass the BBB.

[airplanepeanuts]

You can supplement glutathione directly with the reduced (Setria) product. I take a gram every morning on an empty stomach along with 3 grams of time release C. (I also take 2 g of niacin at the same time for other reasons, as that seems to work synergistically.) The effect is the same or better than NAC, and is absent any reflux problem.

 

 

I second this. Setria gives similar effect to NAC but no stomach upset.

[Getm]

I take NAC with alcohol to prevent hangovers. 1-3g with 2-4g Vit C spread through evenings. If I take too little I have the hangover. I drink 2-4 beers a day, trying to cut down... For that NAC works very well for me.

I also noticed it took 3 days out from common cold for me if took 3g NAC a day, with 7 days minimum if I didn't. I also noticed my urine smells different (more intense) since I've taken it.

Edited by Getm, 20 May 2014 - 07:48 PM.

[beez]

I take NAC with alcohol to prevent hangovers. 1-3g with 2-4g Vit C spread through evenings. If I take too little I have the hangover. I drink 2-4 beers a day, trying to cut down... For that NAC works very well for me.

 

Are you sure this is safe NAC + alc?

[Getm]

 

I take NAC with alcohol to prevent hangovers. 1-3g with 2-4g Vit C spread through evenings. If I take too little I have the hangover. I drink 2-4 beers a day, trying to cut down... For that NAC works very well for me.

 

Are you sure this is safe NAC + alc?

 

 

No I'm not sure It's based on the hypothesis about acetaldehyde toxicity. There was an experiment with rats, they were administered leathal dose of AH. Only those who took NAC survived with 0% death rate and Vit C 27% death rate. Alc is metabolised to AH and excess AH causes hangovers. You can read more about it here http://intelegen.com...effects_of_.htm

[beez]

Interesting, thanks.