176 replies to this topic

[Dorian Grey]

PPC is the only substance on earth I've seen that provided 100% protection 100% of the time against advanced liver disease in primates on a high alcohol diet; & rodent studies showed protection even against carbon tetrachloride poisoning.  

 

SAM-e (s-adenosylmethionine) is the only substance on earth I've seen that provided an eye-popping, jaw-dropping (greater than) 50% reduction in death or need for transplant in all but the most advanced cases of alcoholic cirrhosis.  

 

https://www.ncbi.nlm...pubmed/10406187

 

Don't know if NAC or TUDCA can match claims like these.  

 

PPC & SAM-e really are the liver supplement superstars.  Never seen anything that compares to the studies on these supps.  Interestingly, both SAM-e & PPC are usually pharmaceutical grade & not made in China.  All the PPC in the world used to come from one source in Germany (Lipoid).  Don't know if others are manufacturing it now, but PhosChol states it is product of Germany.  Sanofi's Essentiale Forte is a PPC based pharmaceutical that utilizes Lipoid's PPC. 

 

Most of the SAM-e I've seen is made in Italy, and SAM-e (AdoMet) is a prescription product in the EU, so this is likely also pharmaceutical grade.  

Edited by Dorian Grey, 27 May 2019 - 04:27 AM.

[GABAergic]

ive had so much SAM-e its unreal. but i never knew if it works or not. most people swear by its antidepressant qualities, others like me never know what it does. BUT, my question is this regards to how its manufactured and how effective it can be based on that. is blister protection best way to go or any pills will do? ive tried both but the ones that come as free pills in a dark bottle at least do not contain the nasty titanium dioxide. while on the other hand the blister caps do have titanium dioxide but at least protect the ingredient from any damage, mainly heat and sunlight. decisions, decisions....

Edited by GABAergic, 27 May 2019 - 04:36 AM.

[Dorian Grey]

I've read SAM-e is perishable through oxygen exposure, & I always go with the foil blister packs.  I expect small quantity bottles that will be quickly consumed after opening might be OK, but then I really don't know.  

 

This study: https://www.ncbi.nlm.../pubmed/1371980

 

describes how the polyunsaturated fraction of PPC (DLPC) works, through "collagenase" activity, actually preventing the accumulation of fibrosis (while the other fractions had no effect)

 

"Addition of polyunsaturated lecithin (10 mumols/L) was found to prevent the acetaldehyde-induced increase in collagen accumulation by 83% (p less than 0.001). By contrast, a saturated phospholipid (10 mumols/L dilauroyl phosphatidylcholine), a monounsaturated one (10 mumols/L linoleoyl-palmitoyl phosphatidylcholine) or linoleic acid (20 mumols/L bound to albumin) had no such effect"

 

"Polyunsaturated lecithin increased lipocyte collagenase activity by 100% (p less than 0.001), whereas dilauroyl phosphatidylcholine, linoleoyl-palmitoyl phosphatidylcholine and linoleic acid had no such action"

 

"the protective effect exerted by polyunsaturated lecithin against alcohol induced fibrosis in vivo is due at least in part to stimulation of collagenase activity, which may prevent excess collagen accumulation by offsetting increased collagen production."

 

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

 

Halting progression of inflammation related fibrosis?  Sounds good to me!  

[Darryl]

N-acetylcysteine doesn't appear suitable for life extension approaches focusing on methionine restriction. For the benefit of brosci, I'd add that all ketogenic diet research in animals uses protein and methionine restricted chow, which in my opinion is the principal cause of any observed benefits. 

 

Elshorbagy et al, 2011. Cysteine supplementation reverses methionine restriction effects on rat adiposity: significance of stearoyl-coenzyme A desaturase. J lipid research, 52(1), pp.104-112.

Methionine-restricted (MR) lowered weight gain and at-pad mass/body-weight% (FM/BW%) despite higher food intake/weight than control-fed (CF), and lowered serum cysteine. Hepatic Scd1 expression was decreased, with decreased serum SCD1 activity indices (calculated from serum fatty acid profile), decreased serum insulin, leptin and triglycerides, and higher adiponectin. Cysteine supplementation (MR+Cys) essentially reversed all these phenotypes and raised serum cysteine but not methionine to CF levels. Adding extra cysteine to control diet (CF+Cys) increased serum taurine but did not affect serum cysteine, lipids, proteins, or total weight gain. FM/BW% and serum leptin were modestly decreased. Our results indicate that anti-obesity effects of MR are caused by low cysteine and that dietary sulfur amino acid composition contributes to SCD1 regulation.

 

 

 

Perrone et al, 2012. Genomic and metabolic responses to methionine-restricted and methionine-restricted, cysteine-supplemented diets in Fischer 344 rat inguinal adipose tissue, liver and quadriceps muscle. Lifestyle Genomics, 5(3), pp.132-157.

Methionine restriction diet with cysteine (MRC) reversed most gene and metabolite changes induced by methionine restriction (MR) in inguinal adipose tissue, but drove the expression of Elovl6, Lpin1, Pc, and Pdk1 below control fed (CF) levels. In liver, MR decreased levels of a number of long-chain fatty acids, glycerol and glycerol-3-phosphate corresponding with the gene expression data. Although MR increased the expression of genes associated with carbohydrate metabolism, levels of glycolytic intermediates were below CF levels. MR, however, stimulated gluconeogenesis and ketogenesis in liver tissue. As previously reported, sulfur amino acids derived from methionine were decreased in liver by MR, but homocysteine levels were elevated. Increased liver homocysteine levels by MR were associated with decreased cystathionine β-synthase (CBS) protein levels and lowered vitamin B6 and 5-methyltetrahydrofolate (5MeTHF) content. Finally, MR upregulated fibroblast growth factor 21 (FGF21) gene and protein levels in both liver and adipose tissues. MRC reversed some of MR’s effects in liver and upregulated the transcription of genes associated with inflammation and carcinogenesis such as Cxcl16, Cdh17, Mmp12, Mybl1, and Cav1 among others. 

 

 

 

Gomez et al, 2015. Cysteine dietary supplementation reverses the decrease in mitochondrial ROS production at complex I induced by methionine restriction. J bioenergetics biomembranes, 47(3), pp.199-208.

The results obtained in liver showed that cysteine supplementation reverses the decrease in mitochondrial ROS generation induced by methionine restriction at complex I.

 

 

 

Dong et al, 2018. Disease prevention and delayed aging by dietary sulfur amino acid restriction: translational implications. Ann NY Acad Sci, 1418(1), pp.44-55.

Dietary sulfur amino acid restriction (SAAR) is characterized by chronic restrictions of methionine and cysteine but not calories and is associated with reductions in body weight, adiposity and oxidative stress, and metabolic changes in adipose tissue and liver resulting in enhanced insulin sensitivity and energy expenditure. SAAR-induced changes in blood biomarkers include reductions in insulin, insulin-like growth factor-1, glucose, and leptin and increases in adiponectin and fibroblast growth factor 21. On the basis of these preclinical data, SAAR may also have similar benefits in humans.

 

[unbreakable]

I agree that PPC is great for liver health. It's called "essential phospholipids" here in Europe and marketed as the drug "Essentiale".

Pure lecithin won't have the same hepatoprotective effect.

 

Betaine powder might be a cost-effective alternative to SAM-e.

 

Otherwise I'd recommend a silybin-phosphatidylcholine complex. A cheap alternative is regular silymarin in powder form dosed relatively high.

 

 

I still use NAC, it's been around for a very long time and the oral form has a good safety record in my opinion.

Acute toxicity is very low and even (sub)-chronic megadoses like ~11g a day for months were considered safe.in humans.

Edited by unbreakable, 09 July 2019 - 03:21 PM.

[GABAergic]

N-acetylcysteine doesn't appear suitable for life extension approaches focusing on methionine restriction. For the benefit of brosci, I'd add that all ketogenic diet research in animals uses protein and methionine restricted chow, which in my opinion is the principal cause of any observed benefits. 

 

Elshorbagy et al, 2011. Cysteine supplementation reverses methionine restriction effects on rat adiposity: significance of stearoyl-coenzyme A desaturase. J lipid research, 52(1), pp.104-112.

 

Perrone et al, 2012. Genomic and metabolic responses to methionine-restricted and methionine-restricted, cysteine-supplemented diets in Fischer 344 rat inguinal adipose tissue, liver and quadriceps muscle. Lifestyle Genomics, 5(3), pp.132-157.

 

Gomez et al, 2015. Cysteine dietary supplementation reverses the decrease in mitochondrial ROS production at complex I induced by methionine restriction. J bioenergetics biomembranes, 47(3), pp.199-208.

 

Dong et al, 2018. Disease prevention and delayed aging by dietary sulfur amino acid restriction: translational implications. Ann NY Acad Sci, 1418(1), pp.44-55.

 

so it would be wise to supplement b complex supplement if you consume large quantity of methionine and cysteine, that is in regard to lowering homocystein levels. am i assuming correct here?

[brosci]

so it would be wise to supplement b complex supplement if you consume large quantity of methionine and cysteine, that is in regard to lowering homocystein levels. am i assuming correct here?

 

Or, perhaps glycine and creatine. If glycine improves the metabolization of methionine and a lot of glycine is wasted making creatine.

 

TMG is great for lowering HCy, but I'm not sure what to make of the TMAO issue.

[GABAergic]

i experienced muscle compartment syndrome where way too much creatine was in my kidneys and i could have had serious damage. im pretty sure i do not need any more creatine for a while. and glycine, i never liked it. it makes me feel weird sublingual, and orally, it doesnt do anything at all up to 3 grams

maybe its best to stick with b complex...

[smithx]

I'd love to protect the liver from alcohol, thanks for the references.

 

The part about "stilulating collagenase" seems a bit troubling perhaps. Could that cause breadown of collagen in the face, for example? Liver's more important of course, but the face makes a difference too (if you're alive).

 

Various people have suggested supplements here intended to do exactly the reverse, for that reason.

 

 

 

 

I used to take NAC, but got spooked by the pulmonary hypertension issue.  Looked around and it seems like S-Adenosylmethionine (SAM-e) was my best alternative.  

 

https://academic.oup...5/1151S/4824259

 

For liver health, PPC (polyenylphosphatidylcholine) is also remarkably good.  The only substance I've seen that was 100% effective 100% of the time at preventing alcoholic liver damage in primates.  

 

https://www.ncbi.nlm.../pubmed/8276177

 

The reference to dilinoleoylphosphatidylcholine in the paper indicates it was PPC lecithin used in the study, and the polyunsaturated fraction was the effective component.  

 

Apparently PPC even works against carbon tetrachoride poisoning:

 

https://www.scienced...168827897803613

 

Interestingly, the only thing PPC can't protect the liver from seems to be excess iron:

 

https://www.ncbi.nlm...pubmed/10698372

 

For liver health, keep ferritin out of triple digits (under 100)!  

 

[unbreakable]

 It's hepatic collagenase to be more specific.

[Dorian Grey]

Good point about the collagenase.  Collagen is important!  

 

I've been taking PPC at fairly low doses (900 to 1800mg/day) for over a decade.  I'm almost 63, & haven't noticed any issues with facial skin, wrinkles or sagging. 

 

I'm actually aging remarkably well, & co-workers were shocked when I retired last October.  No one thought I was anywhere near retirement age.  I of course chalk this up to my bloodletting / iron homeostasis, but perhaps I'm just a lucky dog.  

 

I imagine with PPC as with all supps, moderation is wise.  Don't know if there have been problems with those taking higher doses.  I've read some of the Hep-C patients were taking 6, 900mg cap's per day.  

[GABAergic]

why is PPC not sold in US? its very expensive too. its good you can afford it but i think we should try to find other things that can help the liver that are more widely available, at least in the US.

[unbreakable]

I believe as a supplement PPC is available in the US ("PhosChol", "HepatoPro"). In Europe it's available as a drug ("Essentiale").

[unbreakable]

 
NAC is known to break disulfide bonds, which may be a great thing when dealing with thick mucous discharge, but the same mucolytic activity may also be detrimental, at least in some cases.  After all, mucus is secreted for protection from both, irritating agents and pathogens. A user noticed this in another thread:
 

 

But maybe it depends on the dosage -? I discovered how unpleasant concentrated NAC can be when I tested its use as a mouthwash (people were saying it was a great biofilm disruptor for dental plaque -- not a good idea!). It left inside of my mouth feeling sorta 'stripped' (very unpleasant). This makes me wonder what it does to the stomach mucosa when the capsule dissolves sitting in one spot -? It's probably better taken with lotsa food, no?

 

I too would like to hear more opinions on this.

 

they have sustained release NAC now. i would think IF NAC causes problems as mentioned, the quick release which is only hour long is the better choice but not the sustained release which claims it can work for a whole day. i tasted one of those NAC caps and they were like acid, because of the sulfur. that could be a reason for digestion issues FOR SOME but not ALL.

im pretty certain people sensitive to NAC might be sensitive to anything containing sulfur, like garlic. garlic is known to cause severe digestive issues, epesecially if taken on empty stomach (as i have found out painfully enough). as Eva says, maybe its best with food. interestingly enough, the label says on empty stomach... hmm

anyway, im more interested in any science against NAC than just personal experiences. the guy Eva quotes could have had stomach issues from dozens of things. including the most common additive in pills, titanium dioxide, which just recently has been show to cause severe gut ssue. although its in so many products EVERYONE uses https://www.frontier...2019.00057/full and since i had NAC with this crap in there, now i wouldnt even know at this point

 

I believe even high doses of N-Acetylcysteine in the form of pharmaceutical effervescent tablets could be tolerated without problems. They adjust the pH value of the resulting solution with e.g. sodium bicarbonate / natron / baking soda.

 

But simply dissolving higher doses of pure NAC in water and drinking that could irritate the teeth / mouth and possibly the GI tract. That's at least my experience. If I add the same amout of baking soda to the NAC + water solution I can tolerate it without problems. Nevertheless, maybe I will simply take the effervescent tablets in the future again instead of mixing stuff like some rookie chemist. 

 

 

I used to take NAC, but got spooked by the pulmonary hypertension issue.

 

Interestingly newer studies show that NAC might actually be helpful for pulmonary hypertension:

 

Mechanisms of N‑acetylcysteine in reducing monocrotaline‑induced pulmonary hypertension in rats: Inhibiting the expression of Nox1 in pulmonary vascular smooth muscle cells. https://respiratory-research.biomedcentral.com/articles/10.1186/1465-9921-15-65

 

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.

 

Interventions and mechanisms of N-acetylcysteine on monocrotaline-induced pulmonary arterial hypertension: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5996671/

 

These results indicate that ALK-1 and Smad1 participate in the formation of PAH and the process of PVR, and suggest that NAC may inhibit PAH by inhibiting the expression of ALK-1 and Smad1 in the pulmonary artery.

 

[VP.]

Maybe you should not take NAC. 

This paper, from a multicenter French team, looked at three populations of aging mice: normal controls (+/+ for JunD), others that had had the JunD gene knocked out (-/-), and heterozygotes (+/-) who had reduced expression of the protein. JunD is recognized to regulate a whole suite of antioxidant responses in cells – Nrf2 is another example of this, and both of those have been found to be deficient (at both the mRNA and protein level) in the lung tissue of human patients with COPD.

Both the normal mice and the JunD-deficient ones got either NAC-laced water along with their mouse chow, or just water+vehicle as a control: a perfectly reasonable experimental design to assess the effects of aging, JunD levels, and NAC supplementation across each combination of these. And as each cohort aged, there were several interesting changes (which have been noted in some other studies as well). For example, JunD was upregulated with age in the mice who still had the gene, and its down stream oxidative-stress proteins (such as superoxide dismutase, Hmox, and others) increased as well (although not in the -/- animals, as you might have figured). Consistent with an earlier study from this same group, loss of JunD exacerbated oxidative stress in the lungs as the animals aged, as well.

Here’s the good part: the animals who got NAC supplementation really did show significantly fewer of those signs of oxidative damage in their lung tissue. It also reduced signs of cell senescence and overt histological damage of aging as well, such as emphysema lesions (all of these were markedly worse in the JunD knockouts, but NAC improved them as well). So far, so good, and this is exactly the case you’d make if you were pitching NAC as something people should take for healthy lungs as they age. But hold on.

None of the aged normal mice showed signs of adenocarcinoma developing in their lung tissue. But 10% of the aged normals getting NAC supplementation showed it. None of the aged JudD knockouts showed any, either, but 50% of the aged JunD knockouts getting the NAC supplementation had it. The best guess is that cell senescence pathway that seemed to be inhibited with the NAC: some of these are in fact cells that should have died and didn’t, and went on to become cancerous:

Our results therefore support a direct role for NAC in tumor initiation. This role seems independent from antioxidant gene expression, since opposite variations in antioxidant enzyme expression were seen in healthy mice and JunD–/– mice during aging. The protective effect of NAC against lung emphysema is an expected consequence of the decrease in lung senescent-cell accumulation. Altering the cell senescence process, however, may produce undesirable consequences, since senes- cent cells are well known to constitute a barrier to cell transformation and tumorigenesis.

 

 

https://blogs.scienc...-a-warning-shot

[Mr Serendipity]

NAC will be a mainstay for me. I’ve only learnt about and taken it from June 2019, and within 5 months of around 500mg a day, I now no longer suffer from OCD (which I’ve had all my life). Or at least my OCD has been reduced so significantly that I have a hard time identifying it now. I originally took it along with Sarcosine to see if it helps with anhedonia (which I believe it does to a degree), but I dropped the sarcosine cause it would cause hypomania (which at the time I mistook for increased motivation).

 

NAC is a Godsend for OCD, and I can’t believe I only started taking it now and not 15 years ago.

 

Oh and it’s great for erections too. Though I usually stick to the low dose of 500mg, if I end up taking higher doses like 2g+, I’ll get mechanical erections from the histamine release NAC causes. And when I say mechanical, I mean no sexual thoughts and yet suddenly I end up sporting a super hard boner.

[Kalliste]

 

 

A study in mice has found that two commonly used antioxidants — vitamin E and a compound called N-acetylcysteine (NAC) — speed the growth of lung cancer rather than curb it.

The results, published today in Science Translational Medicine¹, may be contrary to the expectations of the millions of people who gulp down vitamin E supplements each day. A survey published in 2005² found that about 11% of US adults took vitamin E supplements, at doses of 400 international units (IU) or higher. The recommended daily intake is 22.4 IU.

The rationale had been that vitamin E and other antioxidants could prevent certain reactive compounds in the body from damaging cellular components, including DNA. Because DNA damage has been linked to cancer, it stood to reason that reducing DNA damage might prevent or slow the disease.

Studies in animals and small clinical trials in humans supported this conclusion, but larger trials have not. When antioxidants such as vitamin E and β-carotene were rigorously tested in randomized, double-blind, placebo-controlled clinical trials, the results were ambiguous at best. A 1994 study³ of 29,133 male smokers even found a higher incidence of lung cancer in those who received β-carotene supplements.

“The results have been mixed,” says Martin Bergö, a molecular biologist at the University of Gothenburg in Sweden, and a co-author of the latest study. “The take-home message is that they do not decrease the risk of cancer and may even increase risk of some cancers in some populations.”

https://www.nature.c...in-mice-1.14606

[protoject]

NAC also seems to be increasing the activity of the HPA axis. https://www.ncbi.nlm.../PMC5457771/  

There is some evidence that it may be helpful in bipolar disorder, but avoid it if you have unipolar depression.

 

Remind me where the chart is that translates dosage equivalents from rats to humans based on metabolism. 

[Malf]

I used to take this stuff years ago, when Id get Bronchitis after 5 days of taking it it help loosen the phlegm in my chest

 

But Im scared to take it again after I read about it causing heart issues in a study and increasing cancer risk

 

Its supposed to be good for the lungs and liver, especially for lungs when you are working out.

 

 

[ironfistx]

Seemingly it promotes glutathione and is therefore helpful for tinnitus, specifically if taken before and after noise exposure.  Possibly it's not the best for a daily use thing.  But, wasn't the heart thing like peculiar circumstances with a mouse or something?  Hold on there's another thread about it

[ironfistx]

https://www.longecit...ry-bad-for-you/

[ironfistx]

https://www.longecit...d-back-in-2007/

https://www.longecit...steine-nacsafe/

[Malf]

Seemingly it promotes glutathione and is therefore helpful for tinnitus, specifically if taken before and after noise exposure.  Possibly it's not the best for a daily use thing.  But, wasn't the heart thing like peculiar circumstances with a mouse or something?  Hold on there's another thread about it

 

helpful for Tinnitus? thats funny because when I took NAC just last week I felt I could hear some ringing in my ear like it caused tinnitus. I only took one pill

 

I was wondering if I should drink it in powder form with water or will that burn my throat?

Edited by Malf, 10 April 2020 - 12:56 AM.

[Malf]

I don't think there's another "base" supplement (it's an amino acid) that has more perceived uncertainty around it than NAC.  I've yet to see epidemiological evidence of any dangers other than possible PAH from either acute dosage or long-term supplementation.  The negative studies that people sometimes reference are almost always irrelevant -- bathing nematodes in ultra-high NAC solutions or cell-line studies using similarly outlandish concentrations.

 

On the other hand the positive effects of NAC in real, walking-around humans are astounding.  Slashing homocysteine levels in the blood, dramatically reducing incidence of flu (your immune system uses a lot of glutathione), raising GSH levels in blood of the elderly to that of youth, and on.  Pretty amazing stuff.  In the flu study they gave 1,200mg daily for six months to the elderly and reported it was "well tolerated."

 

And yet it is somehow often regarded with suspicion on this forum even though it is one of the more studied supplements out there.

 

Personally I take 600mg/day a few times a week.  If I'm going out drinking I'll pop a few.  Hangover - tremendously reduced.

 

When Id get Bronchitis id take this for 5 days straight and it would loosen up my cough. But im scared to take it after that article came out saying it can cause cancer. My friend introduced me to NAC years ago because he said he used to take one capsule every other day and he never got sick. He said NAC was the reason.

[Malf]

This is scary study that I wish I found about before,  but I rember taking two 700mg capsules a day one in morning and one at night  before, and on the 3rd day my heart started pounding fast and loud and  I stopped taking it because of that.

 

Maybe the dosage was too much? thats 1400 mg a day.

Edited by Malf, 10 April 2020 - 01:05 AM.

[micro2000]

NAC "may" have potential side effects, but I have yet to see compelling evidence for it. Studies in genetically altered mice do not extrapolate to humans, if the history of pharmaceuticals is any evidence.

[micro2000]

I have significant skepticism regarding these studies as being proof of danger from a whole category of substances called "antioxidants". Are we to ignore the mountains of evidence of anti-carcinogenic activity of antioxidants?

One or two studies don't overturn decades of evidence to the contrary.