28 replies to this topic

[ironfistx]

A few things I have read have made me wonder if these are nice to use long term. All of these have been in my routine for tinnitus soothing for a few months since April or so. I am wondering though if I can stay on these.

My original regimen was NAC 600mg daily, alcar 500mg daily, vinpocetine 10mg x 2 daily.

THen I read a thread on mandm that alcar might not be alright to use always. 

 

So I stopped taking alcar even though I didn't quite understand eveyrthing in there.  I was now taking alcar only two days a week, on the days that I perform at a night with other bands.

 

NAC and alcar taken before and after exposure to noise are supposed to reduce hearing damage.

 

On this forum I read a few comments that NAC destroys mucuos membranes, and it resulted in me thinking that my nose had been feeling dry for the last little bit, and I thought it was just allergies or whatever, but maybe it was different.  So I stopped taking NAC for like a week.

 

I would like to go back on my plane but I'm trying to figure out if NAC is soetmhthing I shouldn't be using regularly.  The only real document I could find online was the thing that said it caused PAH but that was with a really high dose.  The only other posts I saw were on this forum and that was from a few people saying you shouldn't use it long term.

[niner]

I looked at that M&M thread.  There was a lot of speculation, some Internet mythology, and some misinterpretation of gigadose animal studies.  I didn't make it to the bitter end, but I doubt that there's anything there that hasn't come up here.  A lot of M&Mers seem to like large doses of ALCAR.  I find that 500mg twice a day gets the job done for me, and I don't think it's harmful.  The TMAO scare has been addressed; I'm not worried about it.  It is not necessary to use ALA with reasonable doses of ALCAR.  You should be able to use low dose ALCAR as long as you want.

 

NAC, on the other hand, I am not so comfortable with as a long term drug.

[aribadabar]

NAC, on the other hand, I am not so comfortable with as a long term drug.

 

Is it due to the hypoxia concern?

[niner]

 

NAC, on the other hand, I am not so comfortable with as a long term drug.

 

Is it due to the hypoxia concern?

 

Well, it messes with redox sensors that govern arterial pO2, changing hypoxic ventilatory response and EPO levels in humans, and causing pulmonary arterial hypertension in mice (at high doses), and then there's the people claiming that it messed up their mucous membranes.  It's a known mucolytic.  Seems like some scary off-target effects if all you want is an antioxidant.  I'm not averse to occasional use, but I don't want to use it long term.

[Dorian Grey]

Here's an interesting paper on how "too much of a good thing" like NAC, even at low doses can cause problems...

 

http://www.ncbi.nlm....les/PMC3913600/

 

Long-Time Treatment by Low-Dose N-Acetyl-L-Cysteine Enhances Proinflammatory Cytokine Expressions in LPS-Stimulated Macrophages

 

Abstract

N-acetyl-L-cysteine is known to act as a reactive oxygen species scavenger and used in clinical applications. Previous reports have shown that high-dose N-acetyl-L-cysteine treatment inhibits the expression of proinflammatory cytokines in activated macrophages. Here, we have found that long-time N-acetyl-L-cysteine treatment at low-concentration increases phosphorylation of extracellular signal-regulated kinase 1/2 and AKT, which are essential for the induction of proinflammatory cytokines including interleukin 1β and interleukin 6 in lipopolysaccharide-stimulated RAW264.7 cells. Furthermore, long-time N-acetyl-L-cysteine treatment decreases expressions of protein phosphatases, catalytic subunit of protein phosphatase-2A and dual specificity phosphatase 1. On the other hand, we have found that short-time N-acetyl-L-cysteine treatment at low dose increases p53 expression, which inhibits expressions of proinflammatory cytokines. These observations suggest that long-time low-dose N-acetyl-L-cysteine treatment increases expressions of proinflammatory cytokines through enhancement of kinase phosphorylation.

 

[cuprous]

 

 

NAC, on the other hand, I am not so comfortable with as a long term drug.

 

Is it due to the hypoxia concern?

 

Well, it messes with redox sensors that govern arterial pO2, changing hypoxic ventilatory response and EPO levels in humans, and causing pulmonary arterial hypertension in mice (at high doses), and then there's the people claiming that it messed up their mucous membranes.  It's a known mucolytic.  Seems like some scary off-target effects if all you want is an antioxidant.  I'm not averse to occasional use, but I don't want to use it long term.

 

 

The hypoxia angle has yet to be reproduced and for a supplement that is as widely prescribed and taken as it is it seems odd that we have yet to see epidemiological evidence for pulmonary concerns.  Consider all the folks hooked up to various monitors while they get massive intravenous doses of NAC for tylenol poisoning.  

 

On the flip side, NAC has an excellent track record for a range of positive benefits. 

 

See Conclusions here:  http://www.ncbi.nlm....les/PMC1569588/

 

How is achieving GSH plasma parity between the elderly and young via glycine and NAC supplementation not an astounding achievement?

 

If in doubt taking 600mg every other day will, at the least, give you a slight edge up while still staying within dietary ranges.

 

I scratch my head at how folks are wary of this amino acid but gladly slug down fullerene concoctions that have never seen any sort of controlled study in humans.

 

[aribadabar]

Thank you all for your responses!

 

I hope I didn't open a Pandora box with my question. I guess, given the evidence for either case, taking the middle road - 600mg NAC taken every other day -  is a safe proposition to get the best of both worlds- maintaining elevated GSH levels (when coupled with glycine supplementation) while assuming negligible hypoxia risk.

[hav]

 

 

 

NAC, on the other hand, I am not so comfortable with as a long term drug.

 

Is it due to the hypoxia concern?

 

Well, it messes with redox sensors that govern arterial pO2, changing hypoxic ventilatory response and EPO levels in humans, and causing pulmonary arterial hypertension in mice (at high doses), and then there's the people claiming that it messed up their mucous membranes.  It's a known mucolytic.  Seems like some scary off-target effects if all you want is an antioxidant.  I'm not averse to occasional use, but I don't want to use it long term.

 

 

The hypoxia angle has yet to be reproduced and for a supplement that is as widely prescribed and taken as it is it seems odd that we have yet to see epidemiological evidence for pulmonary concerns.  Consider all the folks hooked up to various monitors while they get massive intravenous doses of NAC for tylenol poisoning.  

 

On the flip side, NAC has an excellent track record for a range of positive benefits. 

 

See Conclusions here:  http://www.ncbi.nlm....les/PMC1569588/

 

How is achieving GSH plasma parity between the elderly and young via glycine and NAC supplementation not an astounding achievement?

 

If in doubt taking 600mg every other day will, at the least, give you a slight edge up while still staying within dietary ranges.

 

I scratch my head at how folks are wary of this amino acid but gladly slug down fullerene concoctions that have never seen any sort of controlled study in humans.

 

 

I was taking 1200 mg/day of NAC last year when I went into high elevation for a month in Colorado and seemed to develop a raised heart rate which continued for a few months after my return till I scaled back on the NAC.  Since then I've been doing 600 mg/day on alternate weeks and the condition did not reoccur on this year's trip to the same area.

 

Howard

[cuprous]

I was taking 1200 mg/day of NAC last year when I went into high elevation for a month in Colorado and seemed to develop a raised heart rate which continued for a few months after my return till I scaled back on the NAC.  Since then I've been doing 600 mg/day on alternate weeks and the condition did not reoccur on this year's trip to the same area.

 

Howard

 

 

That's an anecdote but a worthy one seeing as NAC affects hypoxic response.  Interesting, though, that NAC has been shown to improve athletic performance as well.  I know this doesn't specifically address cardiac concerns but there's some comfort in knowing NAC does not, at least as tested, impair performance.

 

Effects of N-acetylcysteine on respiratory muscle fatigue during heavy exercise.

Kelly MK1, Wicker RJ, Barstow TJ, Harms CA.

Abstract

Respiratory muscle fatigue (RMF) occurs during heavy exercise in humans. N-acetylcysteine (NAC) infusion has been shown to reduce RMF, suggesting that oxidative stress is a contributing factor. The purpose of the present study was to determine the effect of an acute oral dose of NAC on RMF during heavy exercise. Subjects (n=8) were given either placebo (PLA) or NAC (1,800 mg) 45 min prior to a 30 min constant load (85V(O)(2peak)), discontinuous exercise test. Maximum respiratory pressures (inspiratory, PI(max); expiratory, PE(max)) and venous blood samples were made prior to and following each 5 min of exercise. There was no difference (p>0.05) in PI(max) between NAC (127.9+/-34.1 cm H(2)O) or PLA (134.1+/-28.1cm H(2)O) at rest. During exercise, PI(max) was significantly lower with PLA ( approximately 14%) compared to NAC at 25 and 30 min suggesting less RMF with NAC. There were no differences (p>0.05) between groups in PE(max), V(O)(2), V(E), or heart rate at rest or throughout exercise. These results suggest that an acute dose of NAC reduces RMF during heavy exercise.

[krillin]

NAC impairs liver healing, impairs eardrum healing, interferes with angiotensin receptor blockers, and abolishes glucosamine's lifespan extension in nematodes. Glucosamine also helped mice, but they didn't try NAC with it. The mechanism isn't clearly laid out, but I think this is accurate: glucosamine ---| glycolysis ---| AMPK ---> NAD+ ---> SIRT1 ---> PGC-1alpha ---> mitochondrial biogenesis ---> mitochondrial ROS ---> p38/PMK-1 ---> NRF2/SKN-1 ---> expression of amino acid transporters ---> autophagy.

 

Thus, I think it's a better idea to consume a normal amount of cysteine from protein sources and rely on NRF2 activation to squeeze more glutathione out of it in a controlled manner.

[aribadabar]

I can't help but notice that the NAC-positive studies so far have been in humans while the NAC-negative ones are in cell cultures, mice and worms which, to me, have lower weight.

[niner]

I can't help but notice that the NAC-positive studies so far have been in humans while the NAC-negative ones are in cell cultures, mice and worms which, to me, have lower weight.

 

As well they should.  However, because the bioavailability of NAC is so good, the usual problem with cell culture work, that of the cells getting a vastly higher exposure to the compound than they ever would in a human, is less of a problem here.  Studies in cells and lower animals point to things that should be looked at in more sophisticated systems.  Mice are mammals, and are a lot closer to humans than they are to worms, flies, or cells, so they are a good place to explore those things.   They should carry more weight than the lower species, but they aren't humans.  In all cases, dose matters.

[cuprous]

NAC impairs liver healing, impairs eardrum healing, interferes with angiotensin receptor blockers, and abolishes glucosamine's lifespan extension in nematodes. Glucosamine also helped mice, but they didn't try NAC with it. The mechanism isn't clearly laid out, but I think this is accurate: glucosamine ---| glycolysis ---| AMPK ---> NAD+ ---> SIRT1 ---> PGC-1alpha ---> mitochondrial biogenesis ---> mitochondrial ROS ---> p38/PMK-1 ---> NRF2/SKN-1 ---> expression of amino acid transporters ---> autophagy.

 

Thus, I think it's a better idea to consume a normal amount of cysteine from protein sources and rely on NRF2 activation to squeeze more glutathione out of it in a controlled manner.

 

The liver healing argument is very flawed IMHO.  First, we're talking about oral supplementation here, not IV supplementation.  The mice were being treated for poisoning via IV and at doses that would equate to roughly 700mg/day if taken intravenously.  The oral bioavailability of NAC though is 4%.  Assuming plasma clearance wasn't a factor (which of course it is), you'd need supplementation starting at 14 g/day which is well over an order of magnitude more than anyone takes.   Realistically I would have to believe you would need to consume some multiple of 14g/day more to think about achieving an equivalent plasma reading via the oral route.

 

Interestingly enough, though, a study showed that NAC before drinking is a big help whereas after it was pro-oxidative.  Once again, though, we're dealing with IV routes.

 

Eardrums - who on Earth would think about soaking a perforated eardrum in an NAC solution?  "0.6 mg/0.1 ml NAC" or 600mg/L is also some impossibly high dose to achieve via plasma.  At any rate, I'll skip NAC if I ever go to another rock concert.

 

Angiotensin receptor blockers - this is a drug interaction, duly noted.  The abstract doesn't mention NAC dosages.  This is good info for someone taking angiotensin receptor blocking drugs but otherwise I'm not sure what relevance it has to those of us popping 600mg/day.

 

Glucosamine life extension nullification -  First, nematodes.  Second, NAC eliminated life span longevity because .. "this indicates that the transient increase in ROS (Fig. 1i,j) is required for the extension of life span caused by GlcN, thus providing additional support for adaptive ROS signalling or mitohormesis or both."   Maybe that's what keeps nematodes around a while longer.. I don't know that it has anything to do us with bipeds.

 

If this argument applies then why are we taking c60oo or any other ROS mediator?  

 

I appreciate you bringing these studies up and hope others have more to share.  I'm still going to be taking my 600mg NAC once a day or so when I remember in light of extensive evidence in humans that shows numerous positive benefits.  If you want to share some strategies for NRF2 activation I'm all (unperforated) ears.

[krillin]

The liver healing argument is very flawed IMHO.  First, we're talking about oral supplementation here, not IV supplementation.  The mice were being treated for poisoning via IV and at doses that would equate to roughly 700mg/day if taken intravenously.  The oral bioavailability of NAC though is 4%.  Assuming plasma clearance wasn't a factor (which of course it is), you'd need supplementation starting at 14 g/day which is well over an order of magnitude more than anyone takes.   Realistically I would have to believe you would need to consume some multiple of 14g/day more to think about achieving an equivalent plasma reading via the oral route.

 

Interestingly enough, though, a study showed that NAC before drinking is a big help whereas after it was pro-oxidative.  Once again, though, we're dealing with IV routes.

 

Eardrums - who on Earth would think about soaking a perforated eardrum in an NAC solution?  "0.6 mg/0.1 ml NAC" or 600mg/L is also some impossibly high dose to achieve via plasma.  At any rate, I'll skip NAC if I ever go to another rock concert.

 

Angiotensin receptor blockers - this is a drug interaction, duly noted.  The abstract doesn't mention NAC dosages.  This is good info for someone taking angiotensin receptor blocking drugs but otherwise I'm not sure what relevance it has to those of us popping 600mg/day.

 

Glucosamine life extension nullification -  First, nematodes.  Second, NAC eliminated life span longevity because .. "this indicates that the transient increase in ROS (Fig. 1i,j) is required for the extension of life span caused by GlcN, thus providing additional support for adaptive ROS signalling or mitohormesis or both."   Maybe that's what keeps nematodes around a while longer.. I don't know that it has anything to do us with bipeds.

 

If this argument applies then why are we taking c60oo or any other ROS mediator?  

 

I appreciate you bringing these studies up and hope others have more to share.  I'm still going to be taking my 600mg NAC once a day or so when I remember in light of extensive evidence in humans that shows numerous positive benefits.  If you want to share some strategies for NRF2 activation I'm all (unperforated) ears.

 

 

People shouldn't be drinking at all. There is no safe dose of alcohol with respect to cancer. It has even been argued that the alcohol in mouthwash is a real risk, albeit too low for epidemiology to be able to detect.

 

The glucosamine also increased maximum lifespan in mice.  They didn't even start giving it until the mice were 100 weeks old and just about to start dying off. (Granted, the curve for the glucosamine mice looks similar to the control groups of more-competent labs, so glucosamine could be like resveratrol and only increase maximum lifespan in metabolically-morbid mice.) NAC was such a joke that when given alone it couldn't even increase mean lifespan (let alone maximum) in nematodes. Autophagy is considered relevant to biped longevity and glucosamine is associated with reduced human mortality, so you can't blow it off.

 

C60oo would probably interfere with glucosamine too. But C60oo seems to be way better than what you get from NRF2 (catalase, superoxide dismutase, glutathione peroxidase, heme oxygenase-1, NAD(P)H quinone oxidoreductase, and glutamate-cysteine ligase) so that's probably OK. (I haven't taken the plunge yet, since I'm still pretty young and can afford to wait and see the science unfold.)

 

Since NAC is an unnatural treatment with several worrisome effects and no unique benefits, we should demand long-term clinical trials or prospective epidemiological studies that demonstrate reduced all-cause mortality in people of normal health before we consider taking it chronically.

 

NRF2 has been discussed to death here. Look for lipoic acid or resveratrol threads. (Protandim is advertised as activating NRF2 but it takes 20 mcg/ml to work, which is impossible in vivo.) Desired concentrations are 50 microM R-lipoic acid (estimated dose = 435 mg from Na-RALA) or 1 microM resveratrol. (I think Revgenetics' 250 mg caps can get you 2 microM. Someone chime in if they have a better number.)

[The_Next_LX]

 

The liver healing argument is very flawed IMHO.  First, we're talking about oral supplementation here, not IV supplementation.  The mice were being treated for poisoning via IV and at doses that would equate to roughly 700mg/day if taken intravenously.  The oral bioavailability of NAC though is 4%.  Assuming plasma clearance wasn't a factor (which of course it is), you'd need supplementation starting at 14 g/day which is well over an order of magnitude more than anyone takes.   Realistically I would have to believe you would need to consume some multiple of 14g/day more to think about achieving an equivalent plasma reading via the oral route.

 

Interestingly enough, though, a study showed that NAC before drinking is a big help whereas after it was pro-oxidative.  Once again, though, we're dealing with IV routes.

 

Eardrums - who on Earth would think about soaking a perforated eardrum in an NAC solution?  "0.6 mg/0.1 ml NAC" or 600mg/L is also some impossibly high dose to achieve via plasma.  At any rate, I'll skip NAC if I ever go to another rock concert.

 

Angiotensin receptor blockers - this is a drug interaction, duly noted.  The abstract doesn't mention NAC dosages.  This is good info for someone taking angiotensin receptor blocking drugs but otherwise I'm not sure what relevance it has to those of us popping 600mg/day.

 

Glucosamine life extension nullification -  First, nematodes.  Second, NAC eliminated life span longevity because .. "this indicates that the transient increase in ROS (Fig. 1i,j) is required for the extension of life span caused by GlcN, thus providing additional support for adaptive ROS signalling or mitohormesis or both."   Maybe that's what keeps nematodes around a while longer.. I don't know that it has anything to do us with bipeds.

 

If this argument applies then why are we taking c60oo or any other ROS mediator?  

 

I appreciate you bringing these studies up and hope others have more to share.  I'm still going to be taking my 600mg NAC once a day or so when I remember in light of extensive evidence in humans that shows numerous positive benefits.  If you want to share some strategies for NRF2 activation I'm all (unperforated) ears.

 

 

People shouldn't be drinking at all. There is no safe dose of alcohol with respect to cancer. It has even been argued that the alcohol in mouthwash is a real risk, albeit too low for epidemiology to be able to detect.

 

The glucosamine also increased maximum lifespan in mice.  They didn't even start giving it until the mice were 100 weeks old and just about to start dying off. (Granted, the curve for the glucosamine mice looks similar to the control groups of more-competent labs, so glucosamine could be like resveratrol and only increase maximum lifespan in metabolically-morbid mice.) NAC was such a joke that when given alone it couldn't even increase mean lifespan (let alone maximum) in nematodes. Autophagy is considered relevant to biped longevity and glucosamine is associated with reduced human mortality, so you can't blow it off.

 

C60oo would probably interfere with glucosamine too. But C60oo seems to be way better than what you get from NRF2 (catalase, superoxide dismutase, glutathione peroxidase, heme oxygenase-1, NAD(P)H quinone oxidoreductase, and glutamate-cysteine ligase) so that's probably OK. (I haven't taken the plunge yet, since I'm still pretty young and can afford to wait and see the science unfold.)

 

Since NAC is an unnatural treatment with several worrisome effects and no unique benefits, we should demand long-term clinical trials or prospective epidemiological studies that demonstrate reduced all-cause mortality in people of normal health before we consider taking it chronically.

 

NRF2 has been discussed to death here. Look for lipoic acid or resveratrol threads. (Protandim is advertised as activating NRF2 but it takes 20 mcg/ml to work, which is impossible in vivo.) Desired concentrations are 50 microM R-lipoic acid (estimated dose = 435 mg from Na-RALA) or 1 microM resveratrol. (I think Revgenetics' 250 mg caps can get you 2 microM. Someone chime in if they have a better number.)

 

 

 

 

I take this (250mg)--

 

 

Lypo-Spheric R-ALA - 30 Packets | 250 mg R-Alpha Lipoic Acid Per Packet | Liposome Encapsulated for Maximum Bioavailability | Professionally Formulated | Promotes Cellular Energy Production in Nerve Cells and Enhances Insulin Sensitivity | 1,000mg Essential Phospholipids Per Packet

 

 

Product Description

LivOn Labs' 21st century delivery system ensures that nutrients get into your cells where they are needed most. LivOn Labs' nutrients are encapsulated and protected by microscopic bubbles called Liposomes (Lypo-SphericTM). Liposomes are made of Phospholipids, the same material that makes up your cells - allowing the nutrient to pass through cell walls, intact and ready to work. Unlike pills and powders which are flushed from your system, Lypo-SphericTM products pass through your digestive system unharmed. No bowel intolerance and no vitamin flush means more of the nutrient reaches your cells. Lypo-Spheric TM R-ALA R-ALA (250mg) is known as The Universal Antioxidant because it directly affects the health of nearly every cell in the body, and can even cross the blood-brain barrier. This means R-ALA can neutralize free radicals in nearly every part of the body.

 

 

 

 

And I also take this (900mg)--

 

 

 

 

PharmaNac 900mg NEW SIZE (32 Effervescent Tabs) N.A.C. Brand: BioAdvantex

 

Product Description

 

Immune System and Respiratory Health

WHAT IS PharmaNAC? 

PharmaNAC is an advanced immune system booster and the only preparation of its kind available in North America. N-acetylcysteine or "NAC" for short, is a derivative of the amino acid L-cysteine, which is an essential precursor used by the body to produce glutathione. Glutathione is an extremely important and powerful antioxidant produced by the body to help protect against free radical damage, and is a critical factor in supporting a healthy immune system.

PharmaNAC:

• Certified European GMP grade NAC 
• Effective way to help boost glutathione levels. 
• Effervescent, quick-dissolving tablets allow NAC to enter cells readily ensuring rapid absorption. 
• Quality controlled according to pharmaceutical guidelines. 
• Compliant to the standards of European Pharmacopoeia and United States Pharmacopoeia. 
• High quality, extremely stable, great tasting and odorless NAC. 
• Individually wrapped tablets in a special 4-layer (paper/plastic/foil plastic) air-tight material to prevent moisture and air from destabilizing and degrading the NAC; a major problem with most other over the counter (OTC) NAC products bottled in capsule form.

PharmaNAC delivers Thiolex, BioAdvantex Pharma's high-quality and trusted preparation of pure N-acetylcysteine (PATENT PROTECTED. Exclusive licensee of US patent # 6,566,401). Thiolex brand NAC has been trusted and used by various members of the academic community in clinical studies examining the role of NAC in supporting a healthy immune system and good respiratory function. This unique high-quality preparation of pure NAC has been trusted and used by various members of the academic community, and is currently in Phase 1 of clinical studies in the United States, examining the role of NAC in supporting a healthy immune system and good respiratory function.

 

 

 

[cuprous]

People shouldn't be drinking at all. There is no safe dose of alcohol with respect to cancer. It has even been argued that the alcohol in mouthwash is a real risk, albeit too low for epidemiology to be able to detect.

 

The glucosamine also increased maximum lifespan in mice.  They didn't even start giving it until the mice were 100 weeks old and just about to start dying off. (Granted, the curve for the glucosamine mice looks similar to the control groups of more-competent labs, so glucosamine could be like resveratrol and only increase maximum lifespan in metabolically-morbid mice.) NAC was such a joke that when given alone it couldn't even increase mean lifespan (let alone maximum) in nematodes. Autophagy is considered relevant to biped longevity and glucosamine is associated with reduced human mortality, so you can't blow it off.

 

C60oo would probably interfere with glucosamine too. But C60oo seems to be way better than what you get from NRF2 (catalase, superoxide dismutase, glutathione peroxidase, heme oxygenase-1, NAD(P)H quinone oxidoreductase, and glutamate-cysteine ligase) so that's probably OK. (I haven't taken the plunge yet, since I'm still pretty young and can afford to wait and see the science unfold.)

 

Since NAC is an unnatural treatment with several worrisome effects and no unique benefits, we should demand long-term clinical trials or prospective epidemiological studies that demonstrate reduced all-cause mortality in people of normal health before we consider taking it chronically.

 

NRF2 has been discussed to death here. Look for lipoic acid or resveratrol threads. (Protandim is advertised as activating NRF2 but it takes 20 mcg/ml to work, which is impossible in vivo.) Desired concentrations are 50 microM R-lipoic acid (estimated dose = 435 mg from Na-RALA) or 1 microM resveratrol. (I think Revgenetics' 250 mg caps can get you 2 microM. Someone chime in if they have a better number.)

 

 

 

Here's a study showing NAC having a protective effect on human hearing.  Not some tissue in a petri dish but actual, walking-around humans.

 

LEF just noted another study showing NAC improving liver transplantation success.

 

Regarding ALA, it appears it improves GSH levels by upregulating GSH expression.  This would presumably be a complementary strategy to NAC supplementation as cysteine is the rate-limiting factor to GSH synthesis.  Regardless, I don't get why you view NAC supplementation as an "unnatural treatment" versus resveratrol concentrates or ALA dosing.

 

Alcohol - epidemiological evidence indicates moderate drinking has a net positive effect on all-cause mortality.  Queue usual philosophical aside about why bothering to live forever if you can't enjoy wine and (not too loud) song along the way.

 

I'm not holding my breath on your hopes for studies on all-cause mortality regarding NAC supplementation.  Nor for ALA or c60 for that matter.  The best we've got is the usual array of experimentation that focuses on specific conditions or pathways.  My own opinion (stating the obvious) is that the preponderance of evidence shows moderate NAC supplementation as being an effective strategy for keeping the body's antioxidant systems well supplied with a necessary substrate amongst an array of other benefits.

[krillin]

Here's a study showing NAC having a protective effect on human hearing.  Not some tissue in a petri dish but actual, walking-around humans.

 

LEF just noted another study showing NAC improving liver transplantation success.

 

Regarding ALA, it appears it improves GSH levels by upregulating GSH expression.  This would presumably be a complementary strategy to NAC supplementation as cysteine is the rate-limiting factor to GSH synthesis.  Regardless, I don't get why you view NAC supplementation as an "unnatural treatment" versus resveratrol concentrates or ALA dosing.

 

Alcohol - epidemiological evidence indicates moderate drinking has a net positive effect on all-cause mortality.  Queue usual philosophical aside about why bothering to live forever if you can't enjoy wine and (not too loud) song along the way.

 

I'm not holding my breath on your hopes for studies on all-cause mortality regarding NAC supplementation.  Nor for ALA or c60 for that matter.  The best we've got is the usual array of experimentation that focuses on specific conditions or pathways.  My own opinion (stating the obvious) is that the preponderance of evidence shows moderate NAC supplementation as being an effective strategy for keeping the body's antioxidant systems well supplied with a necessary substrate amongst an array of other benefits.

 

 

OK, here's one for supplement-levels of NAC impairing healing in humans.

 

ALA's upregulation of GSH comes from: oxidizes a cysteine residue in Keap-1 -> Nrf2 doesn't get degraded -> glutamate-cysteine ligase upregulated -> more GSH production. NAC will reduce Keap-1 back to normal and thus neutralize ALA's effect.

 

NAC, resveratrol, and lipoic acid are all unnatural and thus should receive greater scrutiny than things that humans have traditionally eaten. Resveratrol and lipoic acid don't have any drawbacks that bother me, so I think using one of them is a good risk. (But not both, since you just want a hormetic amount of oxidative stress. I use resveratrol because it appears to have more benefits than lipoic acid.)

 

When you separate non-drinkers from ex-drinkers, drinking no longer appears beneficial.

[cuprous]

 

 

When you separate non-drinkers from ex-drinkers, drinking no longer appears beneficial.

 

 

You omit that the conclusion was "in men with established coronary heart disease."  PubMed has dozens of papers citing the beneficial effects of moderate drinking on CVD and stroke.

I'm curious as to what supplements you take (this being a supplement forum and all) if you regard dietary-present supps like NAC to be unnatural.

[niner]

The liver healing argument is very flawed IMHO.  First, we're talking about oral supplementation here, not IV supplementation.  The mice were being treated for poisoning via IV and at doses that would equate to roughly 700mg/day if taken intravenously.  The oral bioavailability of NAC though is 4%.  Assuming plasma clearance wasn't a factor (which of course it is), you'd need supplementation starting at 14 g/day which is well over an order of magnitude more than anyone takes.   Realistically I would have to believe you would need to consume some multiple of 14g/day more to think about achieving an equivalent plasma reading via the oral route.

 

I wonder how they came up with 4% bioavailability?   The bioavailability of NAC varies depending on the dose, with higher doses showing better bioavailability.   This paper reports a 100% bioavailability for NAC in a troche formulation.  That doesn't seem quite right either...

[krillin]

 

 

 

When you separate non-drinkers from ex-drinkers, drinking no longer appears beneficial.

 

 

You omit that the conclusion was "in men with established coronary heart disease."  PubMed has dozens of papers citing the beneficial effects of moderate drinking on CVD and stroke.

I'm curious as to what supplements you take (this being a supplement forum and all) if you regard dietary-present supps like NAC to be unnatural.

 

 

Then cite one where they controlled for ex-drinker vs non-drinker. (CVD is much easier to prevent and treat than cancer, so I don't think it would be a good trade-off even if it turned out to be real.)
 

NAC isn't found in food. Neither is free cysteine. The cysteine is in proteins which are absorbed as peptides that don't mess with redox signalling. Cysteine is a nasty free amino acid, which is probably why it's used to make glutathione instead of being used on its own.

[hav]

 

The liver healing argument is very flawed IMHO.  First, we're talking about oral supplementation here, not IV supplementation.  The mice were being treated for poisoning via IV and at doses that would equate to roughly 700mg/day if taken intravenously.  The oral bioavailability of NAC though is 4%.  Assuming plasma clearance wasn't a factor (which of course it is), you'd need supplementation starting at 14 g/day which is well over an order of magnitude more than anyone takes.   Realistically I would have to believe you would need to consume some multiple of 14g/day more to think about achieving an equivalent plasma reading via the oral route.

 

I wonder how they came up with 4% bioavailability?   The bioavailability of NAC varies depending on the dose, with higher doses showing better bioavailability.   This paper reports a 100% bioavailability for NAC in a troche formulation.  That doesn't seem quite right either...

 

 

I think they're using pretty different definitions of bioavailability.  The 1st study actually claims a 9.1% total NAC oral bioavailability (the 4% figure says it pertains to "reduced NAC") and it looks like that's defined by the abstract to represent how much appears in the bloodstream after oral compared to injection. The only way I could imagine this kind of method being relevant would be if the blood were drawn ahead of the liver, like directly from the portal vein. I suspect that's not a very routine blood draw. 

 

The 2nd study actually claims a 103% bioavailability and that looks like some sort of ratio between amounts absorbed by sub lingual administration compared with swallowing sachets;  I guess another way to describe it would be a 3% increase.

 

Howard

[ironfistx]

So instead of taking NAC what about taking glutathione?

[krillin]

So instead of taking NAC what about taking glutathione?

 

An Nrf2 activator would give you glutathione and more. Glutathione would interfere with an Nrf2 activator just like NAC does, so they shouldn't be combined.

 

Cancer Res. 2006 Nov 15;66(22):10983-94.

Generation of a stable antioxidant response element-driven reporter gene cell line and its use to show redox-dependent activation of nrf2 by cancer chemotherapeutic agents.

Wang XJ, Hayes JD, Wolf CR. 

Abstract 

The NF-E2 p45-related factor 2 (Nrf2) regulates cytoprotective genes that contain an antioxidant response element (ARE) in their promoters. To investigate whether anticancer drugs can induce ARE-driven gene expression, we have developed a stable human mammary MCF7-derived reporter cell line called AREc32, which contains a luciferase gene construct controlled by eight copies of the cis-element. In these cells, luciferase activity was increased up to 50-fold following treatment with 50 mumol/L tert-butylhydroquinone (t-BHQ). Basal and inducible luciferase activities in AREc32 cells were increased by forced overexpression of Nrf2 and reduced by knockdown of endogenous Nrf2 expression with RNA interference. Depletion of cellular reduced glutathione (GSH) by treatment of AREc32 cells with l-buthionine-S,R-sulfoximine (BSO) did not influence basal levels of luciferase activity, but pretreatment with BSO augmented induction of luciferase activity by t-BHQ. Induction of reporter activity by t-BHQ in AREc32 cells was suppressed markedly by the antioxidants N-acetylcysteine and GSH but only modestly by vitamins C or E, suggesting that ARE-luciferase expression is induced primarily by thiol-active electrophiles rather than free radicals. The anticancer drugs cisplatin, etoposide, mitoxantrone, chlorambucil, melphalan, and carmustine [1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU)] weakly induced luciferase activity in AREc32 cells. Moreover, treatment of AREc32 cells with BSO immediately before exposure to anticancer drugs enhanced induction of ARE-driven luciferase activity by cisplatin, BCNU, chlorambucil, and melphalan and also induced endogenous AKR1C (AKR1C refers to AKR1C1 and AKR1C2), a target gene of Nrf2. Our findings show that Nrf2 can be activated by certain anticancer agents, and this will influence the effectiveness of chemotherapy. 

PMID:     17108137

[cuprous]

NAC isn't found in food. Neither is free cysteine. The cysteine is in proteins which are absorbed as peptides that don't mess with redox signalling. Cysteine is a nasty free amino acid, which is probably why it's used to make glutathione instead of being used on its own.

 

 

 

 

 Key line in the two papers you linked to:

 

Oocytes expressing LAT1-4F2hc or LAT2-4F2hc demonstrated enhanced uptake of [(14)C]MeHg when administered as the L-cysteine or D,L-homocysteine complexes, but not when administered as the D-cysteine, N -acetyl-L-cysteine, penicillamine or GSH complexes.

 

 

I'm also skeptical about the relevance of pumping creatures full of methylmercury and subsequently pumping them full of different amino acids.  Let's also note that NAC has been shown to alleviate lead toxicity.    in real, walking-around humans.

 

Meanwhile there are dozens of studies with some profoundly positive effects of regular NAC supplementation.

 

Eur Respir J. 1997 Jul;10(7):1535-41.

Attenuation of influenza-like symptomatology and improvement of cell-mediated immunity with long-term N-acetylcysteine treatment.

 

NAC supplementation at 1,200mg/day was "well tolerated" and resulted in an over 2/3 reduction of flu symptoms.  Any pharma would drop a billion dollars to achieve even a quarter of that result and with an enviable safety profile to boot.

 

There are always two sides to a supplement and NAC is inadvisable in certain situations (cancer treatment) but your claim that it is a "nasty free amino acid" is so far wholly unsubstantiated.  And you're still mum on whether and which supplements you take yourself.

[krillin]

 

 Key line in the two papers you linked to:

 

Oocytes expressing LAT1-4F2hc or LAT2-4F2hc demonstrated enhanced uptake of [(14)C]MeHg when administered as the L-cysteine or D,L-homocysteine complexes, but not when administered as the D-cysteine, N -acetyl-L-cysteine, penicillamine or GSH complexes.

 

 

I'm also skeptical about the relevance of pumping creatures full of methylmercury and subsequently pumping them full of different amino acids.  Let's also note that NAC has been shown to alleviate lead toxicity.    in real, walking-around humans.

 

Meanwhile there are dozens of studies with some profoundly positive effects of regular NAC supplementation.

 

Eur Respir J. 1997 Jul;10(7):1535-41.

Attenuation of influenza-like symptomatology and improvement of cell-mediated immunity with long-term N-acetylcysteine treatment.

 

NAC supplementation at 1,200mg/day was "well tolerated" and resulted in an over 2/3 reduction of flu symptoms.  Any pharma would drop a billion dollars to achieve even a quarter of that result and with an enviable safety profile to boot.

 

There are always two sides to a supplement and NAC is inadvisable in certain situations (cancer treatment) but your claim that it is a "nasty free amino acid" is so far wholly unsubstantiated.  And you're still mum on whether and which supplements you take yourself.

 

 

You are wrong. I called cysteine a "nasty free amino acid", not NAC. (NAC is a nasty N-acetylated amino acid.) I also said that I take resveratrol in post #17, so in fact I was not mum on the subject.

 

I wasn't attacking NAC with the abstract you excerpted, so why did you highlight NAC in it? It not being harmful with respect to mercury poisoning does not negate the harm from its interference with healing, Nrf2 activation, and other redox-sensitive processes.

 

There are safer methods of boosting the immune system and dealing with lead poisoning. AHCC is so effective that it gives mice a chance to survive a 100% lethal dose of H5N1 bird flu. Lead poisoning can be treated with EDTA, DMSA, or a variety of safer supplements.
 

[ta5]

Two recent studies that mention pulmonary hypertension:

 

J Cyst Fibros. 2014 Sep 13.

Long-term treatment with oral N-acetylcysteine: Affects lung function but not sputum inflammation in cystic fibrosis subjects. A phase II randomized placebo-controlled trial.

Conrad C1, Lymp J2, Thompson V2, Dunn C1, Davies Z1, Chatfield B3, Nichols D4, Clancy J5, Vender R6, Egan ME7, Quittell L8, Michelson P9, Antony V10, Spahr J11, Rubenstein RC12, Moss RB1, Herzenberg LA13, Goss CH2, Tirouvanziam R14.

PURPOSE:

To evaluate the effects of oral N-acetylcysteine (NAC), which replenishes systemic glutathione, on decreasing inflammation and improving lung function in CF airways.

METHODS:

A multicenter, randomized, double-blind proof of concept study in which 70 CF subjects received NAC or placebo orally thrice daily for 24weeks. Endpoints: primary, change in sputum human neutrophil elastase (HNE) activity; secondary, FEV1 and other clinical lung function measures; and safety, the safety and tolerability of NAC and the potential of NAC to promote pulmonary hypertension in subjects with CF.

RESULTS:

Lung function (FEV1 and FEF25-75%) remained stable or increased slightly in the NAC group but decreased in the placebo group (p=0.02 and 0.02). Log10 HNE activity remained equal between cohorts (difference 0.21, 95% CI -0.07 to 0.48, p=0.14).

CONCLUSIONS:

NAC recipients maintained their lung function while placebo recipients declined (24week FEV1 treatment effect=150mL, p<0.02). However no effect on HNE activity and other selected biomarkers of neutrophilic inflammation were detected. Further studies on mechanism and clinical outcomes are warranted.

PMID: 25228446

 

Respir Res. 2014 Jun 14;15:65.

N-acetylcysteine improves established monocrotaline-induced pulmonary hypertension in rats.

Chaumais MC, Ranchoux B, Montani D, Dorfmüller P, Tu L, Lecerf F, Raymond N, Guignabert C, Price L, Simonneau G, Cohen-Kaminsky S, Humbert M, Perros F1.

BACKGROUND:

The outcome of patients suffering from pulmonary arterial hypertension (PAH) are predominantly determined by the response of the right ventricle to the increase afterload secondary to high vascular pulmonary resistance. However, little is known about the effects of the current available or experimental PAH treatments on the heart. Recently, inflammation has been implicated in the pathophysiology of PAH. N-acetylcysteine (NAC), a well-known safe anti-oxidant drug, has immuno-modulatory and cardioprotective properties. We therefore hypothesized that NAC could reduce the severity of pulmonary hypertension (PH) in rats exposed to monocrotaline (MCT), lowering inflammation and preserving pulmonary vascular system and right heart function.

METHODS:

Saline-treated control, MCT-exposed, MCT-exposed and NAC treated rats (day 14-28) were evaluated at day 28 following MCT for hemodynamic parameters (right ventricular systolic pressure, mean pulmonary arterial pressure and cardiac output), right ventricular hypertrophy, pulmonary vascular morphometry, lung inflammatory cells immunohistochemistry (monocyte/macrophages and dendritic cells), IL-6 expression, cardiomyocyte hypertrophy and cardiac fibrosis.

RESULTS:

The treatment with NAC significantly decreased pulmonary vascular remodeling, lung inflammation, and improved total pulmonary resistance (from 0.71 ± 0.05 for MCT group to 0.50 ± 0.06 for MCT + NAC group, p < 0.05). Right ventricular function was also improved with NAC treatment associated with a significant decrease in cardiomyocyte hypertrophy (625 ± 69 vs. 439 ± 21 μm2 for MCT and MCT + NAC group respectively, p < 0.001) and heart fibrosis (14.1 ± 0.8 vs. 8.8 ± 0.1% for MCT and MCT + NAC group respectively, p < 0.001).

CONCLUSIONS:

Through its immuno-modulatory and cardioprotective properties, NAC has beneficial effect on pulmonary vascular and right heart function in experimental PH.

PMID: 24929652

Edited by ta5, 09 October 2014 - 12:08 PM.

[TheFountain]

^^^^^ Does that study pretty much vindicate NAC as a safe to use supplement in moderate doses? 

[message]

Any conclusion on NAC? I work with radiation daily and am considering taking 600mg BID.

[lemon_]

 

 

 

 

When you separate non-drinkers from ex-drinkers, drinking no longer appears beneficial.

 

 

You omit that the conclusion was "in men with established coronary heart disease."  PubMed has dozens of papers citing the beneficial effects of moderate drinking on CVD and stroke.

I'm curious as to what supplements you take (this being a supplement forum and all) if you regard dietary-present supps like NAC to be unnatural.

 

 

Then cite one where they controlled for ex-drinker vs non-drinker. (CVD is much easier to prevent and treat than cancer, so I don't think it would be a good trade-off even if it turned out to be real.)
 

NAC isn't found in food. Neither is free cysteine. The cysteine is in proteins which are absorbed as peptides that don't mess with redox signalling. Cysteine is a nasty free amino acid, which is probably why it's used to make glutathione instead of being used on its own.

 

SIR, you are WRONG.

 

NAC is found in GARLIC .