Yes, it gives a false result in blood tests. But for those of us who take NAC daily…
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GlyNAC versus TMG-NAC?
I’m considering adding TMG (Betaine) as a supplement. It’s said to be useful for muscle growth, mental health, DNA methylation, etc. and it is a form of glycine. Any thoughts on using TMG as a replacement for glycine making the combination TMG-NAC instead of GlyNAC?
I keep trying to find ways to reduce or consolidate useful supplements and this may be one way to do it.
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Isn’t that too big of a daily dose? Did you start small and then ramped up?
Hi Ruben, I chose the dose based on the following study. GlyNAC (Glycine and N-Acetylcysteine) Supplementation Improves Impaired Mitochondrial Fuel Oxidation and Lowers Insulin Resistance in Patients with Type 2 Diabetes: Results of a Pilot Study. They used 100mg/kg/day of both glycine and Nac. I am 80kg so that equates to 8gms of each per day. Other studies were in the same ballpark with most being a bit lower.
I scaled down the Nac to 6gms daily.
I started out with the full dose of each, but I can see the wisdom of working up to the final dose over a week or two.
I have since added 1gm of taurine to the bedtime dose and have added 5 more grams of glycine each morning.
Sleep is almost always much better than my baseline even after 4 or so weeks. Pickleball endurance also better.
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Its interesting you mention about the sleep and glycine. I tried taking magnesium with glycine
My sleep pattern got distorted with too much of light and REM sleep and yes disturbingly vivid dreams. The deep sleep went way down.
I have since reverted back to Magtein which works way better for me. Almost 2 hrs of deep sleep.
I do take NAC 800 mg in AM and small amount of glycine in AM.
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Sex Differences in Response to Diet Enriched with Glutathione Precursors in the Aging Heart 2024
We found that the GlyNAC diet was beneficial for old male but not old female mice, leading to an increase of Ndufb8 expression (a subunit of the mitochondrial respiratory chain complex), and higher enzymatic activity for CPT1b and CrAT, two carnitine acyltransferases that are critical to cardiomyocyte metabolism. Although no quantifiable change of collagen turnover was detected, hearts from GlyNAC-fed old males exhibited a slight but significant enrichment in Fmod, a protein that can inhibit collagen fibril formation, possibly reducing extracellular matrix (ECM) stiffness and thus improving diastolic function. Cardiac diastolic function was modestly improved in males but not females, and surprisingly GlyNAC-fed female mice showed a decline in exercise performance.
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- If Glycine has a proven longevity benefit and mimics the methionine restriction phenotype.
- Taurine with methionine restriction increase the MR phenotype.
- NAC completly reverses the phenotype of Methionin Restriction.
Based on these studies I will not take NAC until more studies prove me otherwise. Also, my diet is super clean full of antioxidants and I supplement with Astaxanthin (that activates the NRF2 pathway and increase Glutathione production) so my guess is whatever increase I can get from Cystine is marginal in comparison with the full benefit of Methionine Restriction (it also activates the NRF2 pathway).
NAC increases lifespan in many animal models:
- N-acetyl-L-cysteine and its possible anti-ageing properties
- https://onlinelibrary.wiley.com/doi/full/10.1111/acel.14392
Isn’t this better than some mechanistic explanation @Viracocha?
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Thanks for the studies! This is not my area of expertise but this summarize my overall philosophy:
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if you are young and healthy activate as much as possible the survival pathway (NRF2, FGF21, autophagy, etc). This includes Glycine/MR,etc.
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if you are in a disease state (the metastudy you provided are done in disease mice models and also I am sure the more old you are the more you benefit from NAC) you should not restrict any aminoacid and you should not be in a calory deficit. Provide Cystine (NAC) as well as Glycine to increase innate GH production.
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adssx, I have recently started taking 2 grams TMG, 2 grams Glycine and 3.5 grams NAC for the GLYNAC combination, substituting the 2 grams TMG for 2 grams of pure Glycine in order to get the methylation benefits of TMG.
I’m considering making it even simpler with 4 grams TMG (instead of pure Glycine) and 4 grams NAC to get the GLYNAC, plus the added methylation benefits of TMG.
Since you tend to do good research I’ll ask if you have any thoughts about this altered GLYNAC combination.
I don’t know enough about these agents I’m sorry. Combinations are also hard and poorly studied…
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I have not seen this paper being posted here.
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 Clinical Trial.
Key Results. Extracted using ai. Please correct if there are misstakes.
Key Results**
1. Cellular Restoration
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Glutathione (GSH):
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Increased by 87% in peripheral blood mononuclear cells (PBMCs). - Normalized to levels seen in healthy controls.
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Mitochondrial Function:
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+44% improvement in mitochondrial fuel oxidation (fatty acids/glucose).
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+35% higher ATP production in muscle biopsies.
- Reduced mitochondrial oxidative stress.
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2. Metabolic & Inflammatory Markers
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Insulin Resistance:
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HOMA-IR dropped by 45% (near-normalization).
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Inflammation:
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CRP reduced by 45%, IL-6 by 40%, TNF-α by 25%.
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Endothelial Dysfunction:
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FMD (flow-mediated dilation) improved by 30% (vascular health marker).
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3. Physical & Cognitive Function
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Muscle Strength:
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Grip strength increased by 30%.
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Exercise Capacity:
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6-minute walk distance improved by 25%.
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Cognitive Tests:
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Executive function + attention improved by 15-20% (MoCA test).
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4. Genetic Repair Pathways
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DNA Damage:
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Oxidative DNA damage (8-OHdG) reduced by 50%.
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Mitochondrial Biogenesis:
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PGC-1α gene expression increased 2.5-fold (master regulator of mitochondria).
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Post-Trial Washout (Critical Finding!)
- All benefits reversed within 8 weeks after stopping GlyNAC:
- Glutathione dropped to pre-trial levels.
- Insulin resistance, inflammation, and mitochondrial dysfunction returned.
- Proves effects were directly caused by GlyNAC, not spontaneous recovery.
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This is interesting. I cycle Glynac-ET with a compound supplement from Youth And Eath, V14, that has NMN-H, Ca-AKg, Lithium, astaxanthin etc. 3 months of V14 and then 1 month of Glynac-ET (Nacet, or ethyl ester Nac), as I do not want to take NAC on a regular basis, and more generally, don’t want to get “hooked” on any supplement
But if Glynac effects reverse after 8 weeks, this might not be optimal. Then again, I’m not an aging HIV patient, but a rather fit 58 year old.
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I’d just take everything at the same time and not stop. I never saw any compelling reason to start and stop anything.
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Most certainly a very well designed designed study. Thanks for sharing. The results are also highly encouraging. All the patients had undetectable viral load on a stable anti viral regimen. I couldnt find which anti-retrovirals were they taking. NRTI are known to cause mitochondrial dysfunction through inhibition of mtichondrial polymerase.
To that extent GlyNac worked and stimulated mito-biogenesis under stressful conditions.
It is hard to extrapolate these findings to nonHIV population though where there is no identical stress.
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I wonder how your GlyNAC regiment looks like now days( in case you still use it). Do you still take it at night before sleep?
Since I weigh 64 kg my dose on this protocol would be,
GLYCINE = 64kg x 98mg = 6.3 gm per day
NAC = 64kg x 136mg = 8.7gm per day
For a 1 kg body-weight dose:
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Glycine
- Molar mass ≈ 75.07 g/mol
- 1.31 mmol=0.00131 mol
- mg per kg per day ≈ 0.00131×75.07×1000 ≈ 98 mg/kg/day
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Cysteine (as NAC)
- The paper doses “cysteine (provided as NAC)”, so mmol refers to cysteine equivalents. NAC molar mass ≈ 163.19 g/mol; cysteine ≈ 121.16 g/mol.
- As cysteine equivalents:
- 0.83 mmol=0.00083 mol
- mg cysteine/kg/day ≈ 0.00083×121.16×1000≈101 mg/kg/day
- If calculating NAC itself (less likely what you want):
- mg NAC/kg/day ≈ 0.00083×163.19×1000≈136 mg/kg/day
So the study’s dose is approximately 98 mg/kg/day glycine and 101 mg/kg/day cysteine equivalents (or 136 mg/kg/day as NAC)
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Hey there, desertshores, sending buckets of gratitude for all this information, including the tools we need to implement both supplements on a weight basis. I have a couple of issues that Rapamycin AND GlyNac could potentially help. When I had my frist knee replacement, I ended up being a member of the 4% who develop a rogue scar tissue called "Arthrofibrosis’ that becomes harder than bone eventually. I did seek help from a revision specialist up here in Toronto. He said medicine does not yet have a solution for Arthrofibrosis, but he had a couple of ideas that might help. 24 hrs after the surgery, during which he cleaned out the Arthrofibrosis already present (took 3 hours), I was sent to our cancer hospital around the corner for radiation of the inflammatory cells around the knee joint. Those had been located by imaging a few weeks before. He removed the scar laden ligaments and tendons and installed a rotating metal hinge for balance. For just over a year, I was optimistic, but now I have searing pain down the shin below that knee - the scar tissue has regenerated. It’s apparently an autoimmune reaction. The body overreacts to foreign materials and tries to coat them in the scar tissue for protection. I have been taking Rapamycin, and hoped it would prevent that immune system response. It’s not as bad this time (yet), and I’m hoping it will not reach the level where I have to limp. That affects hips and back - adds to the pain big time. Fingers crossed.
Tha other issue I’m dealing with is something called “Fuchs Dystrophy” that can result in blindness because of faulty cells in the endothelial layer of the Cornea. The only cure (so far) is Cornea transplants. But, with my autoimmune response, the Cornea from another person could be rejected as well. From what I have read, I’m hoping GlyNac can help with the endothelial cells so that I may not have to go the transplant route. I am currently taking GlyNac in the proper doses, thanks to you. Thank you, thank you, thank you!!! This information is vital. I’m so grateful that this post was still visible - it has made a huge difference in my level of hope. By the way, do you have a preferred brand of Glycine and NAC? As you no doubt know, some of them are better than others. Thank you again!!! Lynn
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FWIW…
This has been post on this forum before on other threads
In my view and opinion use NACET( that is what I use) instead of NAC. As the bioavailability is much higher
A quick AI-generated answer.
Please verify critical facts.
NACET (N-Acetyl-L-Cysteine Ethyl Ester) exhibits significantly superior oral bioavailability compared to standard NAC (N-Acetylcysteine) due to its lipophilic structure. While standard NAC has a low oral bioavailability ranging from 4% to 10% , NACET demonstrates bioavailability rates of approximately 58.5% to 60% .
Key differences in absorption and efficacy include:
- Cellular Penetration : NACET’s lipophilicity allows it to easily cross biological membranes, including the blood-brain barrier , which standard NAC struggles to penetrate efficiently.
- Mechanism : NACET acts as a prodrug that is rapidly converted into NAC and cysteine intracellularly, leading to more efficient glutathione synthesis and higher intracellular antioxidant concentrations.
- Clinical Relevance : Although preclinical data strongly favor NACET, direct comparative pharmacokinetic studies in humans are limited, meaning the exact clinical magnitude of this advantage in human subjects remains less defined than in animal models.
AI-generated answer.
Please verify critical facts.
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Thank you for this clarification, and for the AI generated answer, Joseph! This is very helpful !! I will for sure be checking into NACET.
What is your estimation of the difference in number of mg, please? I’m basically a 50 kg person (pretty small) - just wondering if I might take less or more NACET. Thank you for posting this information - had never heard of NACET before!!