38 replies to this topic

[AlbertN]

PAMPAGUY,

 

I must not be conveying my ideas very clearly.  I'm already convinced that GlyNAC at the large doses in the 2021 paper has many great effects and I'm glad you're one more data point in its favor. Honestly,  I'm a little surprised that there's not more excitement over the combo.  However, it is possible for GlyNAC to be good for some things and very bad for other things.  Below are my 3 interrelated concerns and questions. (If you read my posts above you will see I'm looking for justifications that will allow me to take the higher doses.)

 

1) I read the 2021 paper and watched Mike Lustgarten's excellent video.  All the blood cysteine levels, I saw in the paper or in the video were for 30-40 year olds  (which I posted above).  Where did you see the numbers for 20 year olds?

 

2)  People have worried about side effects of large daily doses of NAC for things including pulmonary hypertension.  Do you think the risk of this or other bad side effects are extremely low? If so, could you explain why or point me to something explaining your confidence?  In addition although you are currently feeling much better,  the symptoms of pulmonary hypertension are supposed to be undetectable for months or years. Do you think you could tell if you were developing that disease?

 

3) I young enough and not brave enough to want to be one of the first people to try something.  It is my option that the number of people taking Rapamycin and Senolytics may be at least 100 times more than the number of people taking more than 3-4 more grams of NAC per day. Do you agree? 

 

[PAMPAGUY]

Every intervention is a trade off.  Do the benefits out weigh the possible risks of side effects.  In my particular case the benefits do.  The drop off in energy, stamina and insulin sensitivity is profound.  I was doing great until 65 yo., and it was like dropping off a cliff and 10 years later it has got better, but nothing like I felt in my 50's.  I will of course continue to monitor my health for any signs of pulmonary hypertension or any other side effects.  I am of course not the average person taking this protocol.  Have tried and have adopted many interventions while discarding others.  Been doing this for 10 years.  Somewhere you have to take chances with your health in order to move forward.  If not, we all know what the consequence's are.  Frailty, Disease and Death.

 

Yes, I agree that there are more people taking Rapamycin and Senolytics than this protocol, but look at the number of papers and trials on these interventions.

 

You are correct, I could not find any cysteine levels for 20 somethings.  My mistake.

 

I will continue to rigorously monitor my health as I move forward with the GlyNAC intervention.  I feel the science is good.  Have always been a first adopter. 

[ta5]

Nutrients. 2022 Mar 7;14(5):1114. 

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

Premranjan Kumar  1 , Ob W Osahon  1 , Rajagopal V Sekhar  1

Determinants of length of life are not well understood, and therefore increasing lifespan is a challenge. Cardinal theories of aging suggest that oxidative stress (OxS) and mitochondrial dysfunction contribute to the aging process, but it is unclear if they could also impact lifespan. Glutathione (GSH), the most abundant intracellular antioxidant, protects cells from OxS and is necessary for maintaining mitochondrial health, but GSH levels decline with aging. Based on published human studies where we found that supplementing glycine and N-acetylcysteine (GlyNAC) improved/corrected GSH deficiency, OxS and mitochondrial dysfunction, we hypothesized that GlyNAC supplementation could increase longevity. We tested our hypothesis by evaluating the effect of supplementing GlyNAC vs. placebo in C57BL/6J mice on (a) length of life; and (b) age-associated GSH deficiency, OxS, mitochondrial dysfunction, abnormal mitophagy and nutrient-sensing, and genomic-damage in the heart, liver and kidneys. Results showed that mice receiving GlyNAC supplementation (1) lived 24% longer than control mice; (2) improved/corrected impaired GSH synthesis, GSH deficiency, OxS, mitochondrial dysfunction, abnormal mitophagy and nutrient-sensing, and genomic-damage. These studies provide proof-of-concept that GlyNAC supplementation can increase lifespan and improve multiple age-associated defects. GlyNAC could be a novel and simple nutritional supplement to improve lifespan and healthspan, and warrants additional investigation.

Keywords: GlyNAC; lifespan; mitochondria; mitophagy; oxidant damage; oxidative stress.
PMID: 35268089

[Harkijn]

GlyNac remains tempting but this other NAC thread worries me:

 

https://www.longecit...ac/#entry914125

[ambivalent]

Impressive clinical trial:

 

https://academic.oup...8639?login=true

 

Dose:  100 mg/kg/d each of glycine and NAC, and 200 mg/kg/d of alanine

 

Results: "Compared to YA, OA had GSH deficiency, OxS, mitochondrial dysfunction (with defective molecular regulation), inflammation, endothelial dysfunction, IR, multiple aging hallmarks, impaired physical function, increased waist circumference, and systolic blood pressure. GlyNAC (and not placebo) supplementation in OA improved/corrected these defects."

Edited by ambivalent, 29 January 2023 - 07:02 PM.

[Krell]

Impressive clinical trial:

 

https://academic.oup...8639?login=true

 

Dose:  100 mg/kg/d each of glycine and NAC, and 200 mg/kg/d of alanine

 

Results: "Compared to YA, OA had GSH deficiency, OxS, mitochondrial dysfunction (with defective molecular regulation), inflammation, endothelial dysfunction, IR, multiple aging hallmarks, impaired physical function, increased waist circumference, and systolic blood pressure. GlyNAC (and not placebo) supplementation in OA improved/corrected these defects."

 

I weigh 80kg, so for this trial, I would need a daily dose of 8gm glycine, 8gm NAC, and 16gm analine.  

Has anyone here taken those dose levels?  And lived to tell the tale?
And the trial subjects are much younger than my 78yro, is that a problem?

 

It looks rather inexpensive to follow this trial protocol, if these powder sources are ok:

https://zebraorganic...der-5-6-oz.html (this powder source recommends taking 1 of their scoops daily containing 1.6gm NAC and 1.6gm glycine)

https://www.amazon.c...s/dp/B00MWE8WAM (this powder source recommends taking 1 of their scoops daily containing 3gm analine)

So the trial dose could have used about 5 scoops daily of each of these products, for an 80kg subject.

 

I do not remember any comments in the paper about what time of day to take these dosages, or whether to take them with meals or without.

Edited by Krell, 30 January 2023 - 08:31 PM.

[ambivalent]

Krell, it might be worth while taking a look at Fafner55's paper for some additional information - it's a long read (I haven't read it!). But yes, you're numbers seem consistent with the study. 

 

https://www.longecit...ed-individuals/

[ironfistx]

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.

 

Papers?  Is there a glutathione lab you can perform that will tell you what your levels are?

Edited by ironfistx, 31 January 2023 - 08:09 PM.

[ironfistx]

Seems Quest has one at $190 from ultalabs and Labcorp has one for $59 from marekhealth.com.

 

Is this the test you'd get to find glutathione levels?