Glycine+NAC vs Rapamycin

ITP study showed a 6% life extension in mice by Glycine, another study showed a 20% life extension in mice my Glycine + NAC (N-Acetyl Cysteine), That is close to Rapamycin territory.
Rapamycin inhibits MTOR, and thats the theory on the reasons of longevity. Amino acids activate MTOR and Glycine and NAC are amino acids, so should in theory not be longevity candidates.

I am using Glycine 8mg and NAC 3mg a day, started 3 weeks ago after reading the results from the mouse study and reading about other benefits of this supplement combo. I have to say that after a week or so I felt amazing, much more energy, never tired after exercise and lots of libido.
I will receive my first batch of Rapamycin in a week or 2 from Singapore, hopefully it will not be confiscated in customs.

Can I use Glycine+NAC together with Rapamycin? or should I choose one or the other?

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These are good questions - but of course, as with so many questions we have about these compounds, the research has not been done that would give us a solid answer yet. Nobody has done the studies with these combinations of molecules, or tested different dosing strategies to see if theory matches up with reality.

In theory, it would seem to make sense to supplement with GlyNAC in the later half of the week after taking rapamycin (so you aren’t directly countering the benefits of rapa/mTORC1 suppression) - but who knows whether this is true in reality?

I checked on the study you alluded to - and the control mice are a little shorter lived than I think is normal in the rapamycin trial (840 days vs. 950+ days in the trials Matt cites below), so they are not completely comparable, but still, the GlyNAC mice did well with their 1183 day max lifespan:

Glycine + NAC (N-Acetyl Cysteine)

Note:
Control Mice lived (max lifespan) 120 weeks = 840 days,
GlyNAC ice lived (max lifespan) 169 weeks = 1183 days

Matt has brought up this issue:

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Yep, I was aware of the short lived mice. I think it is used mostly to save running costs in the lab, but it is wrong and I agree with Matt, it can give a lot of false positives.
But anyway ITP got 6% life extension with only Glycine, so it is probably something in it. It would make sense as Glycine and NAC are precursors to Glutathione witch is the most important antioxidant we have. I also believe that we don’t know everything there is to know about MTOR yet, and probably some amino acids would not activate MTOR the same negative way as others.
A ITP trial with Rapamycin and Glycine+NAC would be very interesting as I think Glycine or NAC does not activate AMPK pathway as the diabetic drugs do.
Maybe more interesting would be a combo trial with Rapamycin,Acarbose,Glycine and NAC. That would be the kitchen sink.

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Hi Goran,
I’ve been. using the glyNAC combo for about six months and have very good results, though you can never tell if it is one thing or another that you are doing. I follow the protocol outlined in the following human trial which really showed that you can restore glutathione levels to youthful levels, but the dosage is around 10mg glycine/10 mg NAC a day. as you can see in the paper, it did a lot more than just raise glutathione levels.

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I take Rapamycin as a patient of Dr. Green, and I specifically asked him about adding GlyNAC supplementation.

According to Dr. Green, they address completely different issues - mTOR in the case of Rapa, and Glutathione deficiency in the case of GlyNAC.

Not only was he in favor, but I initially came upon GlyNAC from a write-up he did on his site rapamycintherapy.com

His post also pointed to the original studies showing extraordinary benefits of GlyNAC supplementation.

The basis is that Glutathione, the most abundant and powerful anti-oxident in the body, present in every cell and responsible for a host of cleanup & detoxification funcions, declines markedly with age (I just turned 60).

Glutathione is a tripeptide built from glutamic acid, glycine, and cysteine. The body is able to produce glutamic acid in abundance, but not so with the other two precursors. Supplementing with glycine and cysteine allows the body to build back up glutathione to early-age levels.

According to the initial studies in mice, GlyNAC supplementation “corrected red blood cell GSH deficiency, oxidative stress, and mitochondrial dysfunction; and improved inflammation, endothelial dysfunction, insulin-resistance, genomic-damage, cognition, strength, gait-speed, and exercise capacity; and lowered body-fat and waist-circumference”.

If even half that translates to people, it’s pretty extraordinary!

(Here’s a link to an update of the original study: Glycine and N-acetylcysteine (GlyNAC) supplementation in older adults improves glutathione deficiency, oxidative stress, mitochondrial dysfunction, inflammation, insulin resistance, endothelial dysfunction, genotoxicity, muscle strength, and cognition: Results of a pilot clinical trial - PubMed)

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@mullman99 , what dosage do you use for your GlyNAC supplementation?

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I see dosages of “mg” in this feed but it’s actually “g” (grams), not mg. I wish it were mg!:grimacing: Glycine is cheap and easy to take in gram doses (sweet taste, dissolves easily in coffee/tea/water/etc) but NAC is more tricky (contains sulfur, tastes nasty, lots of capsules to get multi gram doses). I hope this combo works as well as the preliminary studies show! I also hope supplement manufacturers win the battle against Big Pharma and the FDA to be able to legally sell NAC without threat of legal repercussions.

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Information on this was post on this forum earlier this year{2022]

On Dr Greens web site, he wrote about this giving a dosing schedule by the person’s weight.

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A lot lol…

If you do the math (correctly) from the actual study, for a 70-kg person (about 155 lbs), it comes out to 9 grams of cystine and 7 grams of glycine. Daily.

I haven’t seen 155 lbs in quite a few years, but as Dr. Green pointed out to me, 60 isn’t yet in the bottomed-out-deficient level, so that’s what I was taking.

It’s a lot of capsules to take; fortunately, you can now get liposomal Glutathione (Glutathione that has a nano-scale coating so that it doesn’t get ‘lost’ in early stomach digestion), both in capsule & liquid, and there are now reports showing that oral supplementation with liposomal Glutathione is effective.

With that, I’m now taking 1000mg, appx. 2 tablespoons, of a liquid liposomal Glutathione.

I get mine at Vitamin Shoppe, I think the brand is “Aurora”. I know GNC also carries “Codeage” liposomal Glutathione that are dry capsules.

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I started Glycine plus NAC several months ago after that article came out. However, after investigating NAC a bit further I decided there was way too much serious negative research associated with NAC. I wish someone would show that the following papers are inaccurate or not applicable. But I have posted them on several sites and gotten no response so I continue to just take Glycine and hope that taking it alone is sufficient.

The antioxidant N-acetylcysteine protects from lung emphysema but induces lung adenocarcinoma in mice

" NAC treatment decreased lung oxidative damage and cell senescence and protected from lung emphysema but concomitantly induced the development of lung adenocarcinoma in 50% of JunD-deficient mice and 10% of aged control mice."

Antioxidants can increase melanoma metastasis in mice

"These results demonstrate that antioxidants and the glutathione system play a previously unappreciated role in malignant melanoma progression. "

Increased risk of knee osteoarthritis in patients using oral N-acetylcysteine: a nationwide cohort study

“Also, in analyses stratified by age group and sex, all subgroups exhibited a significantly higher incidence of knee osteoarthritis (P < .0001) among NAC users than among NAC nonusers. The use of oral NAC was associated with nearly four-fold increased the risk of knee OA in the young age group.”

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Thanks for the heads up drgathard, appreciated.
I was aware of the lung cancer study in mice, but NAC supplements has been used by people for so many years now, and I have not come across any papers on humans yet, so I assumed it could be something that differs from mice/humans. Metabolism plays a part maybe?

I have never seen the osteoarthritis findings, that is a real worry.
I firmly believe that supplementation for long term health/longevity is best and less risky if you pulse it. 1 week on 1 week off, or even 2 weeks on and 2 weeks off.

But 9 grams of cystine and 7 grams of glycine sounds a bit over the top when it comes to cystine. I am not going to take that. Maybe lower my dose of cystine to 2 grams.
(in my post in the beginning I wrote mg, it is of course grams.)

“Some trials show that antioxidants actually increase cancer risk and a study in mice showed that antioxidants accelerate the progression of primary lung tumors”
I believe this is true, there is a reason why cancer doctors don’t recommend supplementations of antioxidants during cancer treatment. Antioxidants and NAD+ precursors seems to power up your cells, normal and cancerous cells. Hyperbaric oxygen treatment is the same thing.
So if you have cancer or tumors, definitely stay away from any antioxidants and NMN/NR.

Sounds like Liposomal Glutathione is the better way to approach it. I just bought it online at GNC

Your order details.

Liposomal Glutathione
Item #: 585022
Size:
Price: $39.99
Quantity: 3

$87.97

|Discount||-$41.99|
|Shipping||FREE!|
|Tax||$0.00|
|Total||$87.97||

Yes, unfortunately, there seems to be a dark side to many of the things we do.

As an 81 yr old cohort of one, it has been my life experience that moderation in all things is generally a good practice.

I have been leaning more towards anti-inflammatory supplements.

Antioxidants: Friend or foe?
“Antioxidants have been continually investigated for their health benefits in terms of their scavenging potential of free radicals. Nevertheless simultaneous research findings reveal the dark side of antioxidants which could be detrimental to human health. A proper balance in the existing treatment with antioxidants should exist based on the accumulating evidence of the recent research reports.”

Antioxidants Accelerate Lung Cancer Progression in Mice
“However, a number of studies have shed doubt on this claim in recent years, as emerging evidence has suggested that antioxidants may actually increase the risk of some forms of cancer.”
https://www.science.org/doi/abs/10.1126/scitranslmed.3007653

Antioxidants prevent health-promoting effects of physical exercise in humans
“Most importantly, these changes in gene expression and the increase in insulin sensitivity following physical exercise are almost completely abrogated by daily ingestion of the commonly used antioxidants vitamin C and vitamin E. Thus, antioxidant supplementation blocks many of the beneficial effects of exercise on metabolism.”
https://www.pnas.org/doi/full/10.1073/pnas.0903485106

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Dr Gathard, Thanks for this new information. I did not find the exact dosage being used in the mouse studies. If you know what it is please post it. This is discouraging news, but at least it will reduce my daily pills if I decide to drop the glycine/NAC combination.

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Adding to the confusion and the difficulty even studying “antioxidants” is the term itself. Some antioxidants directly quench free radicals, but some are actually weak pro-oxidants which stimulate the body’s own antioxidant defenses (thus the end result is antioxidant even though the molecule itself is pro-oxidant. Also as previously mentioned, 1) antioxidants work together in a network and 2) balance is important. Dump in huge amounts of one specific antioxidant and you don’t get the effect you’re looking for (i.e. mega doses of vitamin C and/or E and exercise adaptations). Reductive stress is a thing, too.

Complicating things even more is the question of how much “oxidative stress” is the organism currently experiencing and in which tissues, and how do we measure that? The same antioxidant may show amazing health benefits in an aging, obese type 2 diabetic but may actually harm a younger average-weight non-diabetic. Similarly, too many antioxidants might harm an unhealthy person if he overdoes it and becomes reductively stressed.

It’s tough to know which supplemental “antioxidants” to take and how much, for any one person with a unique health status and age and dietary intake of antioxidants from whole foods. Are antioxidants such as grape seed extract safer, since it’s an extract of a whole food rather than one isolated molecule? I sure hope so because it’s my go-to antioxidant.

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I am also a patient of Dr. Green, and I have not been taking glutathione precursors yet. The studies that Dr. Green refers to show an increase in grip strength for older people taking Glysine + NAC. If glutathione benefits mitochondria as seems to be the case this should be a benefit regardless of whether rapamycin is also taken. I lift weights, but my recovery between sets takes a lot longer than it did when I was younger; perhaps due to tired mitochondria taking longer to make ATP. I’m going to take Glysine + NAC for a while and see if it makes a difference in my workouts. Even if glynac does not show a benefit in mice, it could still be valuable for older strength trainees. Glynac may fall in the category of things like creatine mononhydrate. I doubt that creatine would make mice live much longer, but it could cause an average lifespan increase in older people who exercise since falls are a common cause of death in the elderly.

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I think the bad reviews of antioxidants has gotten, is because either Vitamin E or NAC. Other antioxidants taken the same time as those has gotten bad rep because of that.

Antaxanthin, CoQ10, Lycopene etc, I think should be very safe. I have not read too much alarming stuff about them. I stay away from too much Vitamin E, as there is indications of prostate problems with taken too much of it.

I will lower my dose of NAC, but still take high doses of Glycine.

ITP indicated that there will be positive outcome of their test of Astaxanthin, The trial is not finished yet as all mice has yet to die. I am looking forward to see the result of that.

It is an assumption that “amino acids” activate mTOR which is not accurate. Each amino acid has various and different biological effects.

High-dose NAC will significantly suppress mTOR.

We do not know the outcomes of this combination.

BCAA are potent mTOR activators. Leucine is king.

Yes, different amino acids have differential mTOR impact, but activators nonetheless.

“amino acids are the most crucial signals for mTORC1 activation”

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