NAC, Glutathione, Methylation, and Elevated Liver Enzymes

[tdog333]

Hey all,
I'm trying to understand something about NAC and methylation, I hope someone can give me some insight.
I have a good understanding of methylation and it's pathways, but I can't wrap my head around something.

Why is NAC bad while taking methylation supplements? I've heard it methyl-traps and squeezes methylfolate out of cells and rids the body of b12 quickly. What I don't understand is why this doesn't happen naturally?

It is my understanding that when methylation is started up again that glutathione levels will eventually rise. Wouldn't this rise in glutathione methyltrap? I'm a bit confused here.

Why is supplementing with oral glutathione precursors different than the body naturally raising levels in terms of methyl-trap?

I have elevated liver enzymes and low Glutathione levels. I know NAC is a great way to support the liver, that is why I ask.

Thanks!

 

[Martial]

Because NAC artificially raises glutathione levels in the body by means of supplemented additional glutathione, correct methylation function is the bodies natural producer of glutathione. Now a healthy person without impaired methylation will have no issue producing this anti oxidant, however many people with chronic illness acquire methylation issues secondary because of illness until the system settles, or some others are born with certain genetic mutations that put them at risk for methylation issues unless supplemented.

If you have elevated liver enzymes I would stop all supplements until you find the underlying cause though, a lot of different supplements can raise liver enzyme levels.

maybe post a list of what you take now and see if there is anything you can pinpoint, a lot of different herbs can do this especially.

 

[tdog333]

@Martial

Okay that makes a little more sense. So is it because it's a synthetic form of glutathione basically? I'm guessing it would probably be a bad idea to take l-glutamine as well then

Yeah that's what I figured too. I've cut out everything except the safer stuff. I ordered liv 52 and some other liver protecting herbs which people have used to lower liver enzymes.
Supplements

Vitamin E- 400IU
Vitamin C- Varies, but atleast 2 grams a day
SF722
Methylfolate 1800-2400mcg
AdenosylCobalamin ADB12 1MG
Methyl B12 3-4MG
L Carnatine Fumurate 1000MG
Creatine 5G
CoQ10 400-600MG
D-Ribose 10-15G

Peak ATP 600MG
NAD B3 2x 25 MG sublingual

Niagen NAD Booster 500MG
Tryptophan before bed 1G
Melatonin 3MG
Liver Support with Milk Thistle(coincidentally I haven't been taking this for a few weeks but I started again today)
NT Factor-Phophotidylcholine 3 scoops a day
BodyBioPC 2-3 pills with each scoop of NT factor
Trace Minerals
O.N.E Pure Encapsulations Multi Vitamin 1/2 pill every other day
Selenium Cruciferate 800 mcg
GABA(before bed) 500mg
Pantothenic Acid 500 mg
Cod Liver Oil 2 pills every other day
Digestive enzymes with food

Betaine HCL with food
Vitamin D 5000-10000 IU/day
Zinc 50mg/day
Potassium varies
Monolaurin varies

Bacillus Coagulans and Multi Strain probiotic

Monolaurin as lauricidin 3 scoops a day (9Grams)
Gymnema Sylvestre 2x week
Oil of Oregano 15-20 drops a day(possible reason for elevation due to die off??)

Peppermint Oil 3x day before meals (Die off also maybe?)
Colostrum 1g/day

PQQ 20mg/day

 

[Martial]

Wow that is a pretty sophisticated and impressive supplement regime! Well it could be die off then, maybe you should focus on de toxing whatever toxins are being released in your system. It could be a sign that your liver is just working extra hard, though using supplements in general tends to work the liver too..

DId you have homocysteine and methionine levels tested? Could be possible that you have very elevated methionine from all the supplements and this could cause issues and raise liver enzymes as a result.
I would use P5P alongside the methylation supplements so you can convert the methionine, this is necessary for people with a certain CBS mutation I believe, but 10mg a day will help a lot and low enough of a dose to not cause issues for other people without the mutation regardless, you should also supplement a basic b complex with low levels of the vitamins, with folate instead of folic acid added; taking high doses of b12 and folate can deplete other b vitamin levels. Thorne has a great basic b complex for this too. You can even empty out part of the pills powder to get a smaller dose.

With the amount of supplements you are taking it is hard to pinpoint anything specific because those all don't look like things that would cause issues, but everyone is different and side effect profiles for supplements are not very well known. Though it seems you have been using them for a while and this has only been a recent problem.. Has there been anything recently added since it happened?

 

[Adster]

NAC isn't a synthetic form of glutathione, it's a glutathione precursor. Some people find it really useful, others have trouble with it. There is no good evidence that I know of to say that it is bad for everyone. I use it when I can feel I am struggling after chem exposures and it's really helpful. One way to see how it affects you is to just start with single low doses when you are stable and see if you have any ill effects. The other option is Acetyl Glutathione, but it is super expensive. The one known downside to NAC is that it can irritate mucous membranes.

 

[Martial]

NAC isn't a synthetic form of glutathione, it's a glutathione precursor. Some people find it really useful, others have trouble with it. There is no good evidence that I know of to say that it is bad for everyone. I use it when I can feel I am struggling after chem exposures and it's really helpful. One way to see how it affects you is to just start with single low doses when you are stable and see if you have any ill effects. The other option is Acetyl Glutathione, but it is super expensive. The one known downside to NAC is that it can irritate mucous membranes.

I think it works great, just contridicted while using certain methylation protocols, because a methylation protocol is supposed to charge the body to create more on its own, NAC produces liver reduced glutathione as well, the combo of the two together can cause a contradiction it seems.

If I was not on a methylation protocol I would jump on NAC very quick. Along with whey protein powder.

I didn't mean to say synthetic, just supplemental, because it raises the liver reduced levels of glutathione substantially through a supplemented form.

 

[Adster]

For some of us though, a methylation protocol doesn't appear to produce enough glutathione to meet demands. So for some, NAC is clearly a useful thing to add in, when used at the right doses. Just like SAM-E and ALA can be, which also raise glutathione. I think it's good to be wary of blanket statements. If I had avoided NAC after reading this forum my quality of life would be much worse. Just my 2c

 

[Valentijn]

NAC definitely helps me, even when getting 2 mega doses of hydroxoB12 per week, and normal amounts of B vitamins, C, etc.

 

[tdog333]

Wow that is a pretty sophisticated and impressive supplement regime! Well it could be die off then, maybe you should focus on de toxing whatever toxins are being released in your system. It could be a sign that your liver is just working extra hard, though using supplements in general tends to work the liver too..

DId you have homocysteine and methionine levels tested? Could be possible that you have very elevated methionine from all the supplements and this could cause issues and raise liver enzymes as a result.
I would use P5P alongside the methylation supplements so you can convert the methionine, this is necessary for people with a certain CBS mutation I believe, but 10mg a day will help a lot and low enough of a dose to not cause issues for other people without the mutation regardless, you should also supplement a basic b complex with low levels of the vitamins, with folate instead of folic acid added; taking high doses of b12 and folate can deplete other b vitamin levels. Thorne has a great basic b complex for this too. You can even empty out part of the pills powder to get a smaller dose.

With the amount of supplements you are taking it is hard to pinpoint anything specific because those all don't look like things that would cause issues, but everyone is different and side effect profiles for supplements are not very well known. Though it seems you have been using them for a while and this has only been a recent problem.. Has there been anything recently added since it happened?

Good idea, I was thinking of asking for a hcy test but I will also ask for methionine!

Well I actually haven't had my liver enzymes tested in about a year, and I wasn't taking any of the supplement above except creatine a year ago haha. So pretty hard to say.

I think I just need to speed up phase II detox of my liver, cut out the antimicrobials and all unneccesary supplements for now and hope that helps. The detox like you mentioned will be good too, maybe I'll do a liver flush

I still don't quite get the whole glutathione methyltrap theory.
What about stuff like l-glutamine, milk thistle(silymarin), glycine, taurine, and selenium?

One of the key mechanisms by which silymarin enhances detoxification is by preventing the depletion of glutathione. Silymarin not only prevents the depletion of glutathione induced by alcohol and other toxic chemicals, but has been shown to increase the level of glutathione of theliver by up to 35%, even in normal individuals. In human studies, silymarin has been shown to have positive effects in treating liver diseases of various kinds, includingcirrhosis, chronic hepatitis, fatty infiltration of the liver, and inflammation of the bile duct. The standard dosage for silymarin is 70-210 mg three times/day.
http://www.diagnose-me.com/treatment/liver-detoxification-phase-II-support.html

 

[tdog333]

Nevermind I found out why, it looks like it's a backregulation method. So if Glutathione rises too high b12 is used to remove it from the body. So I think it should be fine to supplement with precursors since my glutathione levels were very low before. I just have to be careful once my glutathione goes up.

Since precursors as well as glutathione have been demonstrated to cause identical effects the difference is not a qualitative factor of "naturally" formed or anything. It appears to be strictly a dose related quantitative item. Presumably there is an ideal level of glutathione that is enough for the body's needs without leaving so much excess that it is immediately bound to the cobalamins. This appears to be a simple chemical reaction that directly happens taking the b12 to a more oxidized state and requires no enzyme for this downhill transaction. If the conversion of the inactive glutathionylcibalamin is the same as in converting the inactive hydroxycobalamin and the inactive cyanocobalamin methylb12 then to convert the glutathionylcobalamin back to the active form of mb12 requires an input of energy in the form of ATP and an enzyme. The ATP is produced by adb12 which is also destroyed by the glutathione so that the ability to create the ATP to change it back also becomes impaired. Since the methylb12 is an effective detoxifier it might be said that the mb12 is part of the feedback system maintaining glutathione below a certain level or it is removed from the body by the mb12 which, like when mb12 detoxifies cyanide, the mb12 is destroyed in the process. It is converted to the inactive cyanocobalamin or in this case, the inactive glutathionylcobalamin. The mb12 is also part of the operation to create the glutathione in the first place. It is a delicate balance that is destroyed by too much glutathione.

 

[Martial]

Good idea, I was thinking of asking for a hcy test but I will also ask for methionine!

Well I actually haven't had my liver enzymes tested in about a year, and I wasn't taking any of the supplement above except creatine a year ago haha. So pretty hard to say.

I think I just need to speed up phase II detox of my liver, cut out the antimicrobials and all unneccesary supplements for now and hope that helps. The detox like you mentioned will be good too, maybe I'll do a liver flush

I still don't quite get the whole glutathione methyltrap theory.
What about stuff like l-glutamine, milk thistle(silymarin), glycine, taurine, and selenium?

Those are great but avoid L Glutamine for sure, people with CFS, among other chronic illnesses have a toxic load of glutamate and quinolinic acid and glutamine can make it worse, in response to the other posts I suppose NAC can be helpful for some, I am no professional so just answering off what I learned so far.

I believe Rob Lynch mentioned it can be helpful for some people and disastrous for others. I do not understand why though, something to do with CBS mutations, and similar traits in genetic mutations though. I think it really comes down to personal genetics again though and this is why getting genetic testing is so important, hard to work with new ideas when you are not sure what needs to be fixed.

 

[tdog333]

Thanks for the heads up! But for some reason my quinolinic acid is very low, my organic acids test showed it being below normal 0.o Pretty weird, I'm still trying to figure it out

 

[Martial]

Thanks for the heads up! But for some reason my quinolinic acid is very low, my organic acids test showed it being below normal 0.o Pretty weird, I'm still trying to figure it out

Well you are taking a bunch of system assisting supplements, perhaps the massive amounts of phospolipids has something to do with it lol

 

[tdog333]

Well you are taking a bunch of system assisting supplements, perhaps the massive amounts of phospolipids has something to do with it lol

Yeah that would make sense, but I actually got the OAT done a few months ago when I was only on about half of those supplements haha(no phospholipids of mitochondria stuff)