Glycine and NAC supplementation increased mice lifespan by 24% and improved health in older adults

[sammmy]

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

Supplementing Glycine and N-Acetylcysteine (GlyNAC) in Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, and Aging Hallmarks: A Randomized Clinical Trial

Results
Compared to Young Adults, Older Adults 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 Older Adults improved/corrected these defects.

 

[Nelson Vergel]

More on NAC

nac

www.excelmale.com

 

[sammmy]

Important clarification: the mice article is talking about Glycine and NAC in 1:1 ratio as precursors for the body to produce the Glutathione (GSH) at the concentrations required for the body. They say, this is not the same as supplementing just NAC (lacks the other precursor Glycine) or directly supplementing Glutathione (leading to too much reduction of oxidation, which is necessary for life - they call this "reductive stress"):

GlyNAC Is Not the Same as NAC-Alone or GSH-Alone​

(a) GSH synthesis requires both cysteine (from NAC) and glycine. Supplementing NAC-alone does not provide glycine, and only GlyNAC provides both the glycine and cysteine needed for GSH synthesis. Proof to support this point comes from data in this study which shows that GlyNAC supplementation improves GSH synthesis and GSH concentrations to correct GSH deficiency in multiple vital organs of the body. No study has reported extension of mammalian life with NAC-alone and, on the contrary, supplementing NAC-alone in C. elegans was found to accelerate aging and shorten lifespan [61]. However, as reported in this manuscript, GlyNAC supplementation in mice extends life.

(b) As discussed above, cells need to combat OxS and simultaneously avoid reductive stress. As seen in this report, the heart, liver and the kidneys have differing GSH concentrations. Indeed, every organ of the body maintains its own GSH concentrations based on their metabolic activity, generation of ROS and cellular needs. Exogenous compounds with antioxidant potential run into the problem of dosing—too much can induce reductive stress, and too little will not combat OxS. This is further complicated by the fact that every organ maintains a different concentration of GSH, and exogenous antioxidant dosing is unlikely to correct GSH deficiency and OxS, while simultaneously avoiding reductive stress in all organs. GlyNAC does not attempt to override or replace cellular defenses to combat OxS and reductive stress. Instead, by providing precursors to boost GSH synthesis and concentration, GlyNAC works by supporting the ability of cells to autoregulate their own GSH—thus GlyNAC can correct GSH deficiency and OxS in every cell and organ in the body, without inducing reductive stress.

(c) No studies have reported an increase in mammalian lifespan by supplementing exogenous glutathione. On the contrary, supplementation of exogenous GSH was found to accelerate aging and shorten life in C. elegans [61]. Because different organs maintain different concentrations of GSH, providing exogenous GSH is associated with the risk of inducing reductive stress. GlyNAC avoids this problem by allowing cells to autoregulate and maintain their required GSH homeostasis, i.e., GlyNAC does not interfere with cellular autoregulation whereby cells make the requisite amount of GSH based on cellular need. This is an important point to understand because the cellular requirement of GSH in each organ is constantly and dynamically changing and is influenced by variations in metabolic activity caused by feeding/fasting, rest/activity and waking/sleep. An additional challenge is that oral GSH is not absorbed well from the gut because it is digested and broken down into its constituent amino-acids, and in this process, cysteine is oxidized by the gut to cystine, which is not a GSH precursor. Even if GSH could be provided in a form which is absorbable, it still runs into dosing issues because cells synthesize their required GSH and do not depend on the plasma to provide GSH. For these reasons, exogenous provision of GSH is impractical and non-physiological, while GlyNAC supplementation corrects GSH deficiency and lowers OxS in vital organs, and extends life.

 

[sammmy]

Also the human doses used in these studies are a bit high compared to the usual:

• 1.33 mmol/kg/d of glycine = 100mg/kg per day
• 0.81 mmol/kg/d of cysteine (as N-acetylcysteine) = 100mg/kg per day
• a 70kg person (154lb) would have to take 7g Glycine and 7g NAC per day.

 

[sammmy]

This is the pilot study with 8 older adults (71-80 years), before the placebo-controlled study quoted above. The pilot study shows the same things and you can read the whole study not just the abstract:

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

 

[sammmy]

Summary in everyday language below. GlyNac was patented to Baylor College of Medicine (where all that research was done) and licensed to Nestle. Probably Nestle are going to market it. However, it is just high daily doses of Glycine and NAC.


GlyNAC supplementation reverses aging hallmarks in aging humans

 

[sammmy]

Nestle is already selling it as "Celltrient Cellular Protect" for $64/month, but it has a lower dose (4 capsules daily = 1.2g Glycine + 1.2g NAC) than the studies (7g Glycine + 7g NAC daily).

Way cheaper is to just buy Glycine and NAC separately.

 

[Nelson Vergel]

NAC tastes like shit in a powder form. Glycine tastes like light sugar. I have not tried both in a shake yet.

 

[gallant]

Nestle is already selling it as "Celltrient Cellular Protect" for $64/month, but it has a lower dose (4 capsules daily = 1.2g Glycine + 1.2g NAC) than the studies (7g Glycine + 7g NAC daily).

Way cheaper is to just buy Glycine and NAC separately.

Way cheaper is correct. I have some bulk powder of both. I haven't done the math but it must be pennies a day compared to that $64/month and with a higher dosage.

 

[Nelson Vergel]

I get the BulkSupplements.com brand from Amazon. I also buy containers for the powder since they keep the powder dry.

 

[sammmy]

Video discussing the same study:

 

[Nelson Vergel]

Dose of both are too high to be practical. I met with this researcher once but got turned off as soon as he told me how many capsules these people had to take.

Supplementing Glycine and N-acetylcysteine (GlyNAC) in Aging HIV Patients Improves Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Endothelial Dysfunction, Insulin Resistance, Genotoxicity, Strength, and Cognition: Results of an Open-Label

Background: Patients with HIV (PWH) develop geriatric comorbidities, including functional and cognitive decline at a younger age. However, contributing mechanisms are unclear and interventions are lacking. We hypothesized that deficiency of the antioxidant ...

www.ncbi.nlm.nih.gov