GlyNAC Improves Many Age-Associated Defects in Older Humans

[mitoMAN]

GlyNAC (Glycine and N-Acetylcysteine) Supplementation in Mice Increases Length of Life by Correcting Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Abnormalities in Mitophagy and Nutrient Sensing, and Genomic Damage


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8912885/
https://www.technologynetworks.com/...age-associated-defects-in-older-humans-364882

Anyone tried these high dosages? 8 Grams of NAC, 8 Grams of Glycine per day for 80kg weight.

Supplement Details
Glycine and N-acetylcysteine and alanine were purchased commer-
cially, and quality verified via certificates of analyses. These supple-
ments are filled into capsules by a pharmacist, and provided monthly
to study participants at doses of 100 mg/kg/d each of glycine and
NAC,. The participants and the study
team were blinded to the identity of the capsules, which were of the
same size, shape, color, and taste. Supplement randomization was
done using a computerized program provided by the statistician.
Compliance with supplementation was assessed with intermittent
phone calls, verification at monthly visits and by capsule-counting.


Full paper attached:

 

[hapl808]

Those are pretty high dosages - haven't tried anything like that for NAC, although did experiment with maybe 5g+ of Glycine (one of Goldstein's treatments, although he used much higher dosages than that).

 

[mitoMAN]

GlyNAC (Glycine and N-Acetylcysteine) Supplementation in Mice Increases Length of Life by Correcting Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Abnormalities in Mitophagy and Nutrient Sensing, and Genomic Damage


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8912885/
https://www.technologynetworks.com/...age-associated-defects-in-older-humans-364882

Anyone tried these high dosages? 8 Grams of NAC, 8 Grams of Glycine per day for 80kg weight.

Supplement Details
Glycine and N-acetylcysteine and alanine were purchased commer-
cially, and quality verified via certificates of analyses. These supple-
ments are filled into capsules by a pharmacist, and provided monthly
to study participants at doses of 100 mg/kg/d each of glycine and
NAC. The participants and the study
team were blinded to the identity of the capsules, which were of the
same size, shape, color, and taste. Supplement randomization was
done using a computerized program provided by the statistician.
Compliance with supplementation was assessed with intermittent
phone calls, verification at monthly visits and by capsule-counting.


Full paper attached:

 

[Mary]

@mitoMAN - I tried I think 3600 mg NAC a few months ago (in 3 divided doses) as I read it was supposed to help lower glutamate as I recall. I had been taking 1200 mg a day for years with no problem. Anyways, I rather quickly became extra fatigued and stopped it and my "regular energy" returned within 2 days or so. The same thing had happened a few years ago when someone said that high dose NAC helped them a lot - I tried it then too, with the same negative result. I thought I had read that it lowers creatine levels but a brief look shows an interaction with creatiinine - I don't know the chemistry but it's possible that the NAC did affect my creatine levels negatively.

I started taking glycine in 2015 or so for sleep and had a very strong detox reaction from it. I was taking probably 1000 mg. If I hadn't been familiar with detoxing, I probably would have assumed it was bad for me because it wiped me out and made me extremely spacey. It's a long story but I was able to determine that glycine was actually good for me, but that I had to go very slowly with it, starting with a much lower dose. It helped a lot in getting my detox pathways working properly. I can't remember the last time I had a detox reaction and it used to happen several times a month. Glycine is involved in Phase II liver detoxification.

My point is I would start carefully and slowly with the glycine because of the detox potential. I others have had the same detoxing experience. If I had started out with 8 grams, I don't like to think about how I would have felt!

And I'd be careful with the NAC also, building up the dose gradually to see how you react.

 

[Pyrrhus]

I tried I think 3600 mg NAC a few months ago (in 3 divided doses) as I read it was supposed to help lower glutamate as I recall. I had been taking 1200 mg a day for years with no problem. Anyways, I rather quickly became extra fatigued and stopped it and my "regular energy" returned within 2 days or so.

Note that high-dose NAC (>1600mg/day) is currently used in psychiatry as a sedative:

There may be another complication related to supraphysiological NAC doses - supraphysiological doses of cysteine (NAC) can have a sedative effect. This is why high-dose NAC is currently of interest in psychiatry for treating anxiety. A 2005 paper [1] provided evidence for a possible mechanism of action for the observed sedative effect:

1. At high concentrations in the nervous system, cysteine self-reacts to form cystine.
2. Cystine in the synaptic cleft binds to the pre-synaptic cystine-glutamate antiporter and is taken into the pre-synaptic neuron, simultaneously releasing glutamate by the pre-synaptic neuron.
3. The glutamate binds to the inhibitory pre-synaptic mGluR2 receptor.
4. Synaptic transmission is reduced.

Since the average dietary intake of cysteine is somewhere between 600mg-1200mg, and 1000mg NAC = 740mg cysteine, I would probably consider any NAC dose above 1600mg/day to be supraphysiological...

Reference:
[1] https://www.jneurosci.org/content/25/27/6389.long

 

[lenora]

@mitoMAN - I tried I think 3600 mg NAC a few months ago (in 3 divided doses) as I read it was supposed to help lower glutamate as I recall. I had been taking 1200 mg a day for years with no problem. Anyways, I rather quickly became extra fatigued and stopped it and my "regular energy" returned within 2 days or so. The same thing had happened a few years ago when someone said that high dose NAC helped them a lot - I tried it then too, with the same negative result. I thought I had read that it lowers creatine levels but a brief look shows an interaction with creatiinine - I don't know the chemistry but it's possible that the NAC did affect my creatine levels negatively.

I started taking glycine in 2015 or so for sleep and had a very strong detox reaction from it. I was taking probably 1000 mg. If I hadn't been familiar with detoxing, I probably would have assumed it was bad for me because it wiped me out and made me extremely spacey. It's a long story but I was able to determine that glycine was actually good for me, but that I had to go very slowly with it, starting with a much lower dose. It helped a lot in getting my detox pathways working properly. I can't remember the last time I had a detox reaction and it used to happen several times a month. Glycine is involved in Phase II liver detoxification.

My point is I would start carefully and slowly with the glycine because of the detox potential. I others have had the same detoxing experience. If I had started out with 8 grams, I don't like to think about how I would have felt!

And I'd be careful with the NAC also, building up the dose gradually to see how you react.

Hello @Mary.....Do you happen to remember the lower doses of glycine you were taking for sleeplessness?

I've been much better since my bad fall in January (I wouldn't even take a guess as to why, except that I did hit my head), but if the insomnia does return, it would be good to have another weapon in my arsenal. That's also supposed to help a pre-diabetic state, isn't it? I haven't looked it up, but it's in my mind, cluttered as it is.
Yours, Lenora