38 replies to this topic

[Lazarus Long]

Here's another supplement combo that appears to be effective. I wish that I could get on a trial for something like this. Arthritis feels like punishment for an active life.

GlyNAC—a combination of glycine and N-acetylcysteine (NAC) as precursors of the natural antioxidant glutathione (GSH)—


Genetic Engineering & Biotechnology News: Human Trial Finds Supplement Improves Age-Related Defects to Improve Cognition, Muscle Strength.
https://www.genengne...uscle-strength/

Edited by Lazarus Long, 01 April 2021 - 12:06 PM.

[Oakman]

Why bother with the trial, just buy it outright > https://www.celltrie...ight-on-glynac/

 

"GlyNAC (Glycine + N‐acetyl cysteine), found in Celltrient™ Cellular Protect, provides building blocks to help cells make the antioxidant glutathione in response to cellular needs. "

[Phoebus]

how is this any different than taking glycine and NAC at the same time? 

[Oakman]

how is this any different than taking glycine and NAC at the same time? 

 

According to the label, it's 600 mgs each of the two ingredients. Easy peasie, I'd make my own, not pay >$1 capsule / 2 per serving.

[Lazarus Long]

Thanks. I appreciate the perspectives. Is the third ingredient, glutathione included?

I had the impression from the article that it is.

[Oakman]

Thanks. I appreciate the perspectives. Is the third ingredient, glutathione included?

I had the impression from the article that it is.

 

 No, the articles state they gave GlyNAC (as glutathione precursors) and that corrected glutathione deficiency in old adults.

 

https://www.genengne...uscle-strength/

[AlbertN]

According to the label, it's 600 mgs each of the two ingredients. Easy peasie, I'd make my own, not pay >$1 capsule / 2 per serving.

 

Dosages in the supplement don't match up with what was used in the study.  

 

From:  https://www.fightagi...d-inflammation/

 

"Per the papers, the daily intake of each supplement is large: ~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."

 

I checked the actual paper (linked to below) and that is correct. 

 

https://onlinelibrar...0.1002/ctm2.372

 

 (1.33 mol of glycine is equivalent to 100 grams of glycine)

[Oakman]

Dosages in the supplement don't match up with what was used in the study.  

 

From:  https://www.fightagi...d-inflammation/

 

"Per the papers, the daily intake of each supplement is large: ~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."

 

I checked the actual paper (linked to below) and that is correct. 

 

https://onlinelibrar...0.1002/ctm2.372

 

 (1.33 mol of glycine is equivalent to 100 grams of glycine)

 

Good find. To take that amt, I'd buy bulk powder, @Amazon lowest cost ~$20/kg for glycine, ~$75/kg for N-A. Cost would be ~$.75/day total, perhaps in a smoothie of some sort. Whether many peps would do that for 36 wks running, as per the study, is an open question.

[smithx]

It's not clear at all that those dosages are safe on a chronic basis.

[AlbertN]

No question the dosage of glycine is safe.   We used to get that much from food when we ate the whole carcass of an animal rather than just the muscle meat.  Our current diets are usually very deficient in glycine,  especially if you get a lot of protein from animal sources.

 

Also from Alan Green at https://rapamycintherapy.com/

 

The dose for a 70 kilo man was 9 gram of cystine and 7 grams of glycine (about the amount of these two amino acids in 1.5 pounds of steak). 

 

 

[Hebbeh]

I think the concern is with NAC. I use NAC and there is no way I would use 8 grams. 2 grams is questionably safe. Read about NAC and irreversible pulmonary hypertension. I'd tread cautiously with doses of NAC exceeding 1.8 grams max.

Edit: and I wouldn't take all 1.8 grams at once but stagger 3 doses of 600 mg throughout the day.

Edited by Hebbeh, 08 April 2021 - 03:01 PM.

[AlbertN]

 

Also from Alan Green at https://rapamycintherapy.com/

 

The dose for a 70 kilo man was 9 gram of cystine and 7 grams of glycine (about the amount of these two amino acids in 1.5 pounds of steak). 

 

This is wrong, at least for cystine.  1.5 pounds of steak has only 2.5 grams of cystine.  (https://www.myfoodda...stine-foods.php)

 

Edited by AlbertN, 08 April 2021 - 04:53 PM.

[Synbion]

There have been a number of follow up studies to the Palmer study that found evidence of NAC-induced pulmonary hypertension in mice. From a 2015 study conducted at Stanford on cystic fibrosis:

 

"Our study commenced with an initial safety cohort to ascertain whether NAC at doses utilized in this trial could cause pulmonary arterial hypertension (PH) because Palmer and colleagues had previously reported that chronic, systemic administration of either NAC or SNOAC (S-nitroso-acetylcysteine) caused hypoxia-mimetic PH in a murine model."

 

"The Stanford cohort of 16 subjects served as an initial safety cohort to evaluate if long-term treatment with NAC was associated with the development of PH in subjects with CF. There was no evidence for the development of PH in these subjects by the following biomarker and clinical measurements: levels of plasma NAC, SNOAC, HIF-1α, VEGF, bFGF, cardiac echocardiogram and diffusion capacity for carbon monoxide. These indices were assessed at the first interim safety analysis by the Data Safety Monitoring Committee (DSMC) review of PH data after 8 subjects had completed week 8 visit. Review of the data revealed no evidence for the development of PH, thus the other sites began enrollment. A second interim analysis for safety performed after half of all subjects had completed 12 weeks of therapy similarly demonstrated no evidence that PH had developed in any study participant."

 

In my lab, we use NAC to break down mucin, so my first thought was what the impact of continually taking such large doses would be on the gut microbiome. It appears not much reaches the large intestines however, and I would think you would see an increase in inflammatory markers if gut integrity has compromised. Still, may make sense to slowly ramp up dose for those wanting to try this.

[Hebbeh]

What were the dosages trialed at the Stanford study?

[AlbertN]

What were the dosages trialed at the Stanford study?

 

Not that large.  It looks like a total 2.7 grams per day in 3 divided doses (for 24 weeks).  See section 2.4 in the paper below.

 

https://herzenbergla...ions/lah563.pdf

[Hebbeh]

Not that large.  It looks like a total 2.7 grams per day in 3 divided doses (for 24 weeks).  See section 2.4 in the paper below.

 

https://herzenbergla...ions/lah563.pdf

 

2.7 grams (3 x 900mg) isn't terribly outside the 1.8~2 gram (3 x 600mg) window that I mentioned earlier but still a far cry from the 8 grams suggested originally.  Based on this study, I don't see any guaranteed redemption from the mouse pulmonary hypertension study to justify risking any dose in excess of the 2.7g tested and certainly not doses in the neighborhood of 8 grams.

 

But if anybody is feeling adventurous, it would be an interesting data point for the community and I would look forward to hearing the result.

[Synbion]

Yeah, Stanford study used lower doses. By body weight I would need to take almost 10 g per day if replicating the Baylor study. Though interesting to note they are currently recruiting for two more clinical trials. I've emailed the PI to see if he would provide any clarification regarding how that dose was determined, or if lower doses could be effective. I mean, Baylor is a good medical school and the trial had to be approved, so I'm sure there is a good reason. Right?

 

Personally, if I try this, it will be at the lower doses (~3 g/d), but it should be noted that NAC is provided at > 10 g doses by IV when used for treating acetaminophen overdoses. Of course that is for a short-term treatment and not over 24 weeks....Anyway, if anyone is trying this out would love to hear about the experience.

[Hebbeh]

Good point on the NAC IV treatment for acetaminophen overdoses.  Is that a single one time IV drip?

[Synbion]

Good point on the NAC IV treatment for acetaminophen overdoses.  Is that a single one time IV drip?

 

Found this:

 

Solution for IV Injection: For the loading dose, dilute 150 mg/kg (maximum 15 g) in 5% dextrose in water (D5W) 200 mL and infuse over 60 minutes. For the second dose, dilute 50 mg/kg (maximum 5 g) in D5W 500 mL and infuse over 4 hours. For the third dose, dilute 100 mg/kg (maximum 10 g) in D5W 1,000 mL and infuse over 16 hours. To avoid fluid overload in patients weighing <40 kg and in those requiring fluid restriction, decrease the volume of D5W proportionally and discard the unused portion.

 

So someone could be getting 30 g over the course of treatment, which is about one day. But this is IV and NAC has low oral bioavailability (4 - 9%). Hopefully I'll get some clarification from the PI on dose, but my experience is there is about a 50% chance of hearing back. His office is about a 10 min walk from mine though...

[Michael Lustgarten]

Video based on the published glycine+NAC data:

[brundall]

Does anyone know whether you can take Glycine and NAC separately to get the same effect or do they have to be taken together at the same time? I currently take NAC in the morning and Glycine before bed.

[Michael Lustgarten]

Likely together is best, because if you take one without the other, submaximal GSH synthesis would be expected.

[pamojja]

Recycling might be just as important:

https://drknews.com/...immune-disease/

... Boosting glutathione levels though a liposomal cream or intravenously—as glutathione taken orally is ineffective—is a key strategy in combating the damage of stress. However these levels can be quickly depleted if the body cannot recycle glutathione to keep the supply on hand to meet the many stressors.

... Glutathione recycling is a separate function from just boosting glutathione levels through a liposomal cream, intravenously, a nebulizer, a suppository, or other means. These forms of glutathione delivery will help one’s antioxidant status but they do not raise levels of glutathione inside the cells. ..

... Supporting glutathione recycling

So how do we support glutathione recycling? The first thing is to reduce the stressors depleting this vital system. The bulk of my thyroid book is devoted to this: balancing blood sugar, addressing food intolerances, restoring gut health, and managing adrenal function are foundational.

Other considerations are neurotransmitter imbalances and hormonal imbalances, which may require specialized guidance from a qualified health care practitioner. And of course making any lifestyle changes you can, such as getting enough sleep, paring down an overactive schedule, making exercise a priority each day, creating time to do things you love, and so on.

Once you have addressed these factors (which for many people can actually take care of the problem) and autoimmune dysfunction persists, then boosting glutathione recycling may be necessary. Below I cover the basic botanicals and nutritional compounds researchers have found support glutathione recycling pathways.

N-acetyl-cysteine (NAC): NAC is a key compound to glutathione activity. It is rapidly metabolized into intracellular glutathione.

Alpha-lipoic acid (ALA): ALA directly recycles and extends the metabolic life spans of vitamin C, glutathione, and coenzyme Q10, and it indirectly renews vitamin E, all of which are necessary for glutathione recycling.

L-glutamine: Research has shown that l-glutamine is important for the generation of glutathione. It is transported into the cell, converted to glutamate, and readily available to intracellular glutathione synthesis.

Selenium: Selenium is a trace element nutrient that serves as the essential cofactor for the enzyme glutathione peroxidase, which converts GSH to GSSG so glutathione can “take the hit” by free radicals to spare cells.

Cordyceps: Cordyceps has been shown to activate both glutathione and peroxidase synthesis in the body. It has also been shown to protect cells by engaging the glutathione enzyme cycle.

Gotu kola (Centella Asiatica): Research has clearly demonstrated that oral intake of gotu kola rapidly and dramatically increases the activity and amount of glutathione peroxidase and the quantity of glutathione.

Milk thistle (Silybum marianum): Milk thistle has been shown to significantly increase glutathione, increase superoxide dismutase (another powerful antioxidant) activity, and positively influence the ratios of reduced and oxidized glutathione.

Taken together these botanicals and compounds activate the glutathione peroxidase and reductase enzymes that promote a healthy glutathione recycling system.

[whileitravel]

I began taken this under the guidance of a physician. I am blending 7g Glycine/9g NAC split twice per day. So far so good. Will keep ya'll posted.

[ironfistx]

EIGHT GRAMS of NAC per day?

 

Holy fuck.

[AlbertN]

I had a couple of ideas that I wanted to hear comments on.

 

1)  Maybe in the researchers used more NAC then they needed to. See below,  taken from Table 2 of https://www.ncbi.nlm...les/PMC3155927/

 

Red blood cell concentrations of Cysteine (umol/L)

(n = 8) Young control subjects  =  26.2 ± 1.44

(n = 8) Elderly subjects before supplementation = 19.8 ± 1.35 

(n = 8) Elderly subjects after supplementation = 30.6 ± 2.2

 

The levels of cysteine after supplementation were higher than that of the young controls    Assuming a linear relationship between dose and increase, to get the mean back up to a youthful level, you would only have to supplement with 59% of the dose they gave (130 mg/kg * .59 = 78 mg/kg) which works out to 4.7 g per day for a 70 kg individual.

 

2) One of the worries with Cysteine supplementation is pulmonary hypertension.  But that was obtained with large amounts of cysteine which probably caused blood levels to be far higher than normal.  Maybe supplementing so that levels do not rise past the normal levels for youthful subjects would not be problem?

 

In any case,  I don't think I'm going past 2-3 g of NAC per day but I was interested in people's thoughts.

 

[PAMPAGUY]

 

I had a couple of ideas that I wanted to hear comments on.

 

1)  Maybe in the researchers used more NAC then they needed to. See below,  taken from Table 2 of https://www.ncbi.nlm...les/PMC3155927/

 

Red blood cell concentrations of Cysteine (umol/L)

(n = 8) Young control subjects  =  26.2 ± 1.44

(n = 8) Elderly subjects before supplementation = 19.8 ± 1.35 

(n = 8) Elderly subjects after supplementation = 30.6 ± 2.2

 

The levels of cysteine after supplementation were higher than that of the young controls    Assuming a linear relationship between dose and increase, to get the mean back up to a youthful level, you would only have to supplement with 59% of the dose they gave (130 mg/kg * .59 = 78 mg/kg) which works out to 4.7 g per day for a 70 kg individual.

 

2) One of the worries with Cysteine supplementation is pulmonary hypertension.  But that was obtained with large amounts of cysteine which probably caused blood levels to be far higher than normal.  Maybe supplementing so that levels do not rise past the normal levels for youthful subjects would not be problem?

 

In any case,  I don't think I'm going past 2-3 g of NAC per day but I was interested in people's thoughts.

 

Young controls in this very small trial were 30-40 yo.  What if you want to restore RBC back to 20 somethings vs 30-40 yo.  2011 study and 2021 study both same researcher.  I am 74 yo., and strive to restore back or as close to 20 yo if possible.  I believe the protocol for young and healthy young people and elderly are completely different.  I will continue to take .13 g/NAC per kg. and .10g/Cysteine per kg. per day.  To date, no side effects, except must break up daily dosing due the NAC gastric effects, which go away with 2-3 doses a day. .  In these 2021 studies, they were tested at 2 wks., 12 wks., and 24 wks.  Young controls at 2 week trial were 30-40 yo., and young controls on 12 and 24 weeks were 20-30 yo. "There were no adverse side effects out to 24 weeks."  Another opinion on this protocol, read his 2021 update on this new protocol.  https://rapamycintherapy.com/ Thoughts?

[Michael Lustgarten]

Yes, definitely. Beyond blind supplementation based on positive results from published studies, measuring these biomarkers, to see if NAC+ cysteine is effective (and at what dose) is essential, imo.

Edited by Michael Lustgarten, 18 May 2021 - 01:30 PM.

[AlbertN]

Young controls in this very small trial were 30-40 yo.  What if you want to restore RBC back to 20 somethings vs 30-40 yo.  2011 study and 2021 study both same researcher.  I am 74 yo., and strive to restore back or as close to 20 yo if possible.  I believe the protocol for young and healthy young people and elderly are completely different.  I will continue to take .13 g/NAC per kg. and .10g/Cysteine per kg. per day.  To date, no side effects, except must break up daily dosing due the NAC gastric effects, which go away with 2-3 doses a day. ...  Another opinion on this protocol, read his 2021 update on this new protocol.  https://rapamycintherapy.com/ Thoughts?

 

Bunch of points below, not arguing toward any particular conclusion.  If any of them are wrong, please correct me.

 

1) The NAC dose of .13 g/kg would mean that someone my size would take 12 grams daily.  Other than these authors, I have never seen anyone give more than 2 to 3 grams per day.  Large doses of NAC could help the body in some ways and hurt it in others.  Would love to see a lot more people taking higher doses to insure it's safe.

 

2) One of the potential side effects of NAC is pulmonary hypertension (with a believable mechanism for bringing it about).   The problem with that side effect is that you have no idea if you're getting it without getting something like an echocardiogram.  You could be feeling perfectly fine but be causing long term irreversible damage.

 

3) I just saw Dr. Green (who is the author at your link) a month ago.  He did not think that the mouse study that showed hypertension was something to worry about.

 

4) I have not seen any studies that show what the levels of Cysteine are for 20 year old's, only for 30-40 year old's.  If anyone knows those levels, please let me know.

 

2) I am 59 years old so I can wait a bit.  Even with the same info and opinions, the things that I would try now are different than what I might do if I was 74.

[PAMPAGUY]

My protocol is Rapa 10 mg. weekly last 4 years.  Metformin?Berberine 1500 mg daily. (A1c 5.2) Control blood pressure to under 110.  Resting heart rate of 52 bpm.  Take Dasatinib 100 mg with 2000 mg Fistein twice a month for senolytic clearing, Started the  (GlyNAC) supplementation 8 weeks ago and feel great.  It has raised by RBC count, and I can walk further.  Feel that I have more NAD.  I track all my longevity interventions via the Phenotype Age Calculator with at 95% accuracy rate.  I turn 75 in 2 months and have a Phenoage of 60 yo.  I know what works and what does not.  Been at this for many years.  I would suggest that people should heed the teachings of professionals who use these interventions with many patients and themselves for many, many years.  No substitute for experience.  Here is a uTube video on the GlyNAC supplementation, and using the Phenoage calculator developed by Dr. Steve Horvath of UCLA.  All of these tools have been rigorously perfected over thousands of patient years.   If you watch the one video on GlyNAC it shows you the 20 somethings levels of NAC and Glycine in the 12/24 weeks trial.

 

 

 

Edited by PAMPAGUY, 19 May 2021 - 07:10 PM.