GlyNAC

JGC I don't see the point of overpaying for a designer product if we are talking about simple amino acids.

Just buying their Ajipure version is sufficient if one is concerned about quality.

What I am more concerned about is the large NAC dose which is reported to cause PAH.

Personally, I would stick to max 1800mg /d NAC and 5g/d Glycine and call it a day.

If it helps with boosting GSH to youthful levels, good. If it's insufficient, it is still better than nothing and I am fine with that.

Qimin You PAH= Pulmonary arterial hypertension.

aribadabar I read a study that NAC prevents PAH. Link here:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5996671/

What is your source that it causes PAH?

Andrew 

    The Baylor Med paper says that the 8 old (71-80) and the 8 young (21-30) participants were given prepared capsules containing the GlyNAC dosages, and they were checked periodically to make sure they were taking them.  There is no information in the paper about when they were told to take them (if they were) but it sounds like they took one big dose (in the capsule) at a time of their own choosing.

    Following Aribadabar's suggestion, I searched on Aijpure and found that Swanson has Glycine for $2.99 for 60  x 500 mg caps and N‐acetylcysteine for $6.39 for 100 x 600 mg caps.  That's rather better than the LE prices.

JGC I found glycine at 22 $ for 1 kg. 

Glycine Powder | Amino Acid Supplement | Nonessential Amino Acid — BulkSupplements.com

Staffan Olsson 

BulkSupplements.com also sells NAC powder, but it's a bit more expensive: $50/kg.

Andrew I’m a patient of Dr. Green as well. I just emailed him the same question. Did he get back to you. Is it to be taken everyday at 7 and 9 grams?

Benjamin Schoolman  - in response to my questions regarding senolytics and GlyNac - he replied "If you would like to discuss this in further detail, please schedule a consultation"

JGC There is a bulk powder version of Ajipure Glycine too. 

JGC Also, your link points to the non-Ajipure NAC offering. The correct one is a more expensive but not terribly more so.

Allen Glycine is very pleasant but cysteine isn't.  You need to overwhelm it with something sweet and dilute substantially.

aribadabar Thanks for the info. I have nac capsules and opened one up after reading your post. You're right, it's really strong. I had no idea it was that bad. 

yikes, just tried a gram of NAC powder in my shake and taste is incredibly bad.Not sure how to overwhelm it to get it down

Paul Beauchemin Yeah, its nasty. I just stick with capsules. You can get a big bottle pretty cheap on amazon.

JOHN 

I agree, they got extremely interesting results. But without oxidation we do not get the ROS that at least some senolytic substances rely on to remove senescent cells. Below an easy read that explains what we have to consider before taking huge amount of Acetyl cysteine.

N-Acetyl Cysteine: A Warning Shot | In the Pipeline (sciencemag.org)

Staffan Olsson This article you posted and the one about rats and lung tumors goes against a ton of other articles out there that shows NAC inhibits cancer growth:

Exactly the opposite of what your article claims. 

Please check the real data done in humans, here are only some studies:

https://www.researchgate.net/publication/47699443_Suppression_of_human_prostate_cancer_PC-3_cell_growth_by_N-acetylcysteine_involves_over-expression_of_Cyr61

https://www.researchgate.net/publication/330122763_N-acetylcysteine_decreases_malignant_characteristics_of_glioblastoma_cells_by_inhibiting_Notch2_signaling

http://www.ijcem.com/files/ijcem0096364.pdf

https://onlinelibrary.wiley.com/doi/full/10.1002/1097-0215(20001201)88:5%3C702::AID-IJC4%3E3.0.CO;2-3

And there are many more. Thoughts anyone?  This is why I need to talk to Dr. Green.  He is brilliant at weeding out the nonsense.  

Another thing to consider is the lab rats used in the study you mentioned above received astronomical doses of NAC.  Equivalent of a 75kg man taking around 75g NAC daily and the author of that article had worked at a number of pharmaceutical companies.  That doesn't' mean he is biased but combing through all these studies and articles one should take a lot of it with a grain of salt.  

Another study here for the benefits of NAC against cancer:

https://www.sciencedaily.com/releases/2017/11/171120141534.htm

JOHN The human biology is extremely complex and we seldom get any clear answers. the results from GlyNac are mazing. So I will probably do a limited self experiment for 3-4 weeks. But also try to make an informed decision regarding long term use based on how the “numbers# fall out in the  risk-reward equation.

Will you be using the high doses they used in the study? Let me know how you feel.  If you don't mind me asking how old are you? 

JOHN Yes, I will use high doses and report my experience here. I am not used to converting mmol/kg/day to mg/day so I have to make sure I get the numbers right. And I recently added another intervention to my protocol, so I must wait at least a couple of weeks before adding a new. 

Per the papers, the daily intake of each supplement is: ~100 mg/kg for glycine (~6 grams for a 60kg human) and ~130 mg/kg for N-acetylcysteine (~8 grams for a 60kg human), split into two doses.

Staffan Olsson did you end up doing this experiment? How'd it go?

J Oh A late reply, but here it is.

I bought everything (500 gr of each substance). But I decided against the above mentioned protocoll. So I am not using NACand I did not do the experiment. Now I only use  the glycine (approx 2-3 gr /day) for other reasons than the above mentioned GlyNac protocoll. 

Staffan Olsson thanks. Any particular reason you decided against the protocol? 

J Oh I am not sure how to implement  the GlyNac in my personal anti aging strategy  Oxidation is an important part of the signaling in the cell.  And this strategy might be disrupting important intracellular signaling.  But yet again, the approach looks very promising. I wait for more data.

Staffan Olsson did you see the newest study? Increased mice lifespan by 24%. I think it prob makes sense once we get older 

J Oh Yes I saw that study. And it looks very promising.

Staffan Olsson J Oh

My thinking is in this case much in line with Dr Brad's. 

https://www.youtube.com/watch?v=f7f1oaVtE0M&ab_channel=DrBradStanfield

Btw I like his videos. They are usually only around 10 minutes and not to speculative. 

Andrew Excellent questions!  I'm surprised that you felt a surge of energy, since glycine is a known somnorific.  The devil must be either in the high NAC dosage or some confounding variable.  I take 3g each of glycine and NAC at night and usually sleep rather well. 

Brian Valerie since that post I've found that the Thorne labs NAC does not contain stearate and I don't have the stomach issues with it that I previously had.  The NAC / Glycine combo as I understand it is 9g / 7g respectively.  I've been trying to follow that and take it during the day.  Have you tried using the higher dose either during the day or at night?  

Andrew Glad you found some NAC that agrees with you.  No, I haven't taken more than 3g.  Since more human trials are no doubt soon forthcoming, I'd rather be cautious about the higher doses.  As with almost all of my supplements, I even regularly abstain for a day or more in the hope of diminishing any potential homeostatic response.   Of course, even 3g would until very recently have been considered a high dose!  Do you think that there may be a benefit to taking it during the day?  It may be at least partially a placebo effect, but I believe that by taking it at night the glycine does help me sleep better.

Brian Valerie Before starting this experiment I had previously always taken 600mg NAC prior to bed.  My sleep has been on / off lately.  Perhaps what I'll do is split it up with 6g Nac during the day and 3g at night and see how that goes.  I do think there is a benefit during the day - when I take it consistently my overall energy levels are higher - and I like what the study said about grip strength considering I'm working out with X3 Bar (variable resistance bands).  Glad to hear it's working for you the way you've been taking it.  

Charles Richardson I appreciate your response. 

In terms of N Acetyl Cysteine (NAC)- the question is, is it the correct way to raise endogenous glutathione production or should it be increased through SKN-1 activation (biosynthesis) in which NAC has shown to decrease as in itself is an antioxidant. Some research suggests negative associations with NAC supplementation. 

https://www.nature.com/articles/s41467-021-24634-3

Of course I think we need enough NAC through diet and supplementation to provide sufficient amino acids, but what about the doses specified in the NAC/GLY study which had amazing results. 

Geoff Welch Yeah, I'm not that enamored with those amounts. That seems to me to be a pharmaceutical dosage. On the other hand, NAC has other functions such as protecting the lungs. But I'm not jumping on the bandwagon to take as much as was in that study.

Curt Lizzi  Glutathione does not absorb well through the digestive system from the research I've seen.

Charles Richardson I thought that might be the reason. Also wondering why they only used 2 of the 3 AAs that make up Glutathione?

this would be a protocol that would be hard to follow long term just because of the volume!

Curt Lizzi I think it would be hard to be deficient in glutamic acid (that's my understanding).

Charles Richardson They used to think that but current research has debunked it and apparently it is absorbed which is why they started selling it as a supplement now. Now having said that, it may pass the first obstacle in the gut, but it may only enter circulation and not penetrate the cell membrane. But still therapeutic for the liver etc.

Curt Lizzi They only use 2 of the 3 as those are the only ones that decrease with age.  The third one is found in young and old at similar levels and does not decrease with age.

Jack Black For info I've noticed something else recently. Based on discussions on this forum I decided to raise my daily dose of AKG from 300mg a day to 1200mg. As such I now bundle a 300mg capsule with the glycine/serine/NAC detailed above just before bedtime. Since starting that I've been sleeping like a baby! 

Not seen anything saying that AKG would be synergistic with the sleep promoting aspects of l-serine but that's the experience these past two weeks. Would be interested if anyone else has experienced this?

Jack Black I take 4200mg of NAC along with 4000mg of the reportedly somnorific glycine every other day (alternating with 3000mg of the somnorific anti-inflammatory ashwagandha in the perhaps vain hope of diminishing potential homeostatic responses), and believe that the reported somnorific effect of glycine is indeed valid.  I also take 1200mg of AKG and 3mg of 6 hour extended release melatonin on a nightly basis, so must caution that my anecdotal evidence is suspiciously full of confounding variables.

Reversaroni I can't speak to the Celltrient version, but I can tell you that without any doubt, the quality of NAC on the market varies wildly. I've seen reports of some products (commonly available on sites like Amazon at relatively cheap prices) containing little to no NAC it all, which is very disturbing, but points to the fact that we must be cognizant of the quality of products we choose. Far too often I find people choosing cost over quality and from what I've seen, the old age that you get what you pay for is very true. With that said, in all studies I've seen regardless of what subject we're discussing, the higher doses of NAC are required in order to achieve the same outcomes found in the research (I've seen some people take 600-1200mg for COPD for a month and claim the product doesn't work, but the research points to much higher doses of 3-3.6g/daily, so it's no wonder these individuals had dismal results - not withstanding the fact that they are likely consuming substandard products). In addition to that, the research seems to suggest that it takes time for it to work. In one of the studies of GlyNAC I was reading, the study lasted for 24 weeks which is a sufficient amount of time to demontrate the efficacy of a protocol. Given the complexity of the situation, you're not  going to improve COPD symptoms in a matter of 3-4 weeks, no are you going to experience any miraculous anti aging benefits in the same time period. So for people that think that 3-4 weeks is enough time to allow for this protocol to work, they're fooling themselves and likely throwing money down the drain 

Reversaroni I am buying the NOW brand of NAC and glycine as I have found their brand to be pretty good.  Has anyone had problems with NOW supplements?  I get them through Walmart online.

Chris M 

NOW is a good brand. (Speaking of someone who has been in or around the supplement business for a long time.)

Stevan Lieberman interesting. Wonder why the conflicting results. Dosage maybe? Also concerning that it says NAC negates the benefits of exercise.

Stevan Lieberman I can't derive an equivalent human dose from the paper, but these are usually way higher than people would take. I would imagine some ROS action in humans would indeed be beneficial. My approach is small top-ups of GlyNAC in my 50s, working up to 9mg or so in later life. It does seem there's an increasing antioxidant deficit through age related decline.

Jack Black I'm guessing you meant to write 9 grams rather than 9mg (?).  As noted above, I'm taking four grams qod, and admit to being shy about taking more chronically until we have more human research results.

Brian Valerie Absolutely! Grams not mg. :)  I'd say taking a week off the supplements every month sounds like a good move for most of these substances.

Stevan Lieberman Sounds like a good case for senolytics?

Jack Black Yes, that is def why we need senolytics

Stevan Lieberman Another thought; It's been shown that human glutathione levels tend to start declining dramatically around age 45. Correlation does not mean causation but it is interesting how many nasty age related diseases start to gather steam after about that same point. Mediating that decline in glutathione just seems sensible. 

Taking NAC before bed time as some recommend also sounds good. Some ROS from the morning exercise and day of sun exposure and eating will have stressed something by the time you call it a night.

Also, these animal studies are usually very high dose and lifelong. I suspect there's a big difference giving these supplements lifelong compared to e.g. after age 45 in humans in moderation. Though firm data would indeed be very nice.

My reading of the origin of most cancers is that they result from chronic non-fatal stressors on cells, that eventually make the cell flip out and revert to the single celled [selfish] organism programming [to survive] instead of part of a multicellular lifeform. (Because all life was single celled before multi cellular life evolved so it seems reasonable there is still the selfish programming in all cells buried somewhere). 

There is truth that stressors in moderation turn on protection mechanisms, and it's all about finding that balance. As stated above, past the age of 45 you're heading in the wrong direction and need support.

On the topic of cancer itself, there are interesting resources. Check out "Eat to Beat" which studies how various foods seem to disrupt cancer angiogenesis (forming blood vessels). The usual foods talked about for e.g. stopping bowel cancer are all there.

At the risk of me entering the "too much information for a single post" category; A diet rich in certain beans (soya, black eye and others) was recently shown to help stop cancer cells from metastasizing, which is the reason for most cancer fatalities. I mention this just to say diet can be used in conjunction with things like GlyNAC to alleviate possible downsides and enjoy the upsides.

There's a lot of information out there to process and combine...  

Jack Black I actually agree with everything you said above and believe the key point is finding the balance.  I have been taking Glynac at a lower dosage (2g each), but every morning as I found that taking it in the evening kept me from sleeping. (But then I am very sensitive re sleep and even eating a burger after 6pm will disrupt my sleep.) I also take rapamycin (currently cut back to 2g once a week as I am trying to find my non-toxic mtor limiting level) as well as a host of other things including resveratrol.  My theory on what to take has been based initially on the statistics of what slows aging and then once I have taken it a while based on how I react to it.

I would love it if there was a way for all of us to share what we take and why on a regular basis that wasn't public as then we could statistical analysis on all of our experiences.

Stevan Lieberman   There are many preclinical studies showing the opposite i.e. beneficial effect of NAC against cancer. But more valid are human studies like this one showing effect of against breast cancer. 

Stevan Lieberman here is the link https://pubmed.ncbi.nlm.nih.gov/29248134/

Juan Daw Agreed. I think the real question are what substances, in what amounts, when and how do they react to each other. We know lots of things that extend life, but we also know that taken incorrectly could kill us. Here is an article from 2017 which summarizes a long list of them: https://link.springer.com/article/10.1007/s13659-017-0135-9

Karl I take a constellation of substances targeting glutathione production, support of the mitochondria, brain health, folate cycle, skin and joints health, bone strength, and of course Rapa. 

No idea if this will extend lifespan, however quality of life has improved. My exercise performance is the best it's been in years. My memory is good and cognitive tests are way easier. Skin elasticity has improved by the equivalent of several years.

In short, whether I live to 95 or not I'm hopeful that my later years will be more active and fulfilling than might otherwise occur.

Stevan Lieberman Had the same positive impact on me. There's still a risk profile  however and why CJC and similar peptides are alternatives, esp for older people.

Stevan Lieberman I started with 1-2 ius daily for 6 months and maxed at 3-4 ius daily for the next 6 months. During one of the second 6 months, I took 6ius daily.

I then took a serostim break for 3- 6 months while experimenting with peptides: CJC, tb-500, bpc-157, etc... while also trying different versions of gh.

1. I began using the peptides after doing some more research on the dangers of using exogenous gh, as well seeing an increase in moles  & existing moles becoming darker -  which might have been coincidental. 

2. I began trying different versions of gh as serostim is so expensive.

My conclusion is serostim is an awesome product however, depending on your goals and age,  peptides might be just as effective. 

As an aside, only recently (one year next month) have I begun an elevated version of trt: 300 ml a week of sustanon.

Testosterone is by far the most efficacious exogenous product I've used. Everything from sleep, strength, focus, gaining size, etc...

Stevan Lieberman I initially tried gh to mimic Greg Fahys Triim Trial.

I used Metformin, GH and DHEA to see if it would reduce/reverse my gray hair as it did with one of his participants.  And it worked! 

Michael I suspect that either HGH or Testosterone in some form would give me the benefits of better sleep, mood, and well-being.  And, God knows I certainly do need those things.  However, I've avoided them because I've gotten the impression from what I've read that they would be counter-productive to living a healthier and possibly longer life.  Any thoughts?

Jay Orman I've read similar things so, I can't say it's not a consideration. I do know     when I turned 50, I started to feel and look old - almost as if a switch was flipped. It was such a drastic and alarming change, I began researching things like those mentioned above and joining forums like this. My conclusion is QUALITY of life is at the moment, as important to me as longevity and the quality of my life has certainly improved.

Michael Yes, I see your point. 

Jay Orman Yes, my 75 yo mother has been following it for 2 months and her diabetes factors have decreased by about 10%