Kumar, Premranjan, et al. "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." Clinical and translational medicine 11.3 (2021): e372.
Kumar, Premranjan, Ob W. Osahon, and Rajagopal V. Sekhar. "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." Nutrients 14.5 (2022): 1114.
Kumar, Premranjan, et al. "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." The Journals of Gerontology: Series A 78.1 (2023): 75-89.
López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013). The hallmarks of aging. Cell, 153(6), 1194-1217.
Elorinne, Anna-Liisa, et al. "Food and nutrient intake and nutritional status of Finnish vegans and non-vegetarians." PloS one 11.2 (2016): e0148235.
Hoffman, Jay R., and Michael J. Falvo. "Protein–which is best?." Journal of sports science & medicine 3.3 (2004): 118.
Rushton, D. Hugh. "Nutritional factors and hair loss." Clinical and experimental dermatology 27.5 (2002): 396-404.
Hao, Jiaqing, et al. "Consumption of fish oil high-fat diet induces murine hair loss via epidermal fatty acid binding protein in skin macrophages." Cell Reports 41.11 (2022): 111804.
Meldrum, B. S. (2000). Glutamate as a neurotransmitter in the brain: review of physiology and pathology. The Journal of nutrition, 130(4S Suppl), 1007S-15S.
Salminen, A., Kaarniranta, K., Kauppinen, A., & Ojala, J. (2021). Age-related changes in AMPK activation: role for AMPK phosphatases and inhibitory phosphorylation by upstream signaling pathways. Ageing Research Reviews, 66, 101249.
Sekhar, R. V., Patel, S. G., Guthikonda, A. P., Reid, M., Balasubramanyam, A., Taffet, G. E., & Jahoor, F. (2011). Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation. The American Journal of Clinical Nutrition, 94(3), 847-853.
Sekhar, R. V., McKay, S. V., Patel, S. G., Guthikonda, A. P., Reddy, V. T., Balasubramanyam, A., & Jahoor, F. (2020). Glutathione synthesis is diminished in patients with uncontrolled diabetes and restored by dietary supplementation with cysteine and glycine. Diabetes Care, 34(1), 162-167.
Sadowska-Bartosz, I., & Bartosz, G. (2014). Effect of antioxidants supplementation on aging and longevity. BioMed research international, 2014.
Wu, G., Fang, Y. Z., Yang, S., Lupton, J. R., & Turner, N. D. (2004). Glutathione metabolism and its implications for health. The Journal of Nutrition, 134(3), 489-492.
Varani, James, et al. "Decreased collagen production in chronologically aged skin: roles of age-dependent alteration in fibroblast function and defective mechanical stimulation." The American journal of pathology 168.6 (2006): 1861-1868.
Glycine
Razak, Meerza Abdul, et al. "Multifarious beneficial effect of nonessential amino acid, glycine: a review." Oxidative medicine and cellular longevity 2017 (2017).
Meléndez-Hevia, Enrique, et al. "A weak link in metabolism: the metabolic capacity for glycine biosynthesis does not satisfy the need for collagen synthesis." Journal of biosciences 34 (2009): 853-872.
Tan, Chengquan, et al. "A review of the amino acid metabolism in placental function response to fetal loss and low birth weight in pigs." Journal of Animal Science and Biotechnology 13.1 (2022): 28.
Wang, W., Wu, Z., Dai, Z., Yang, Y., Wang, J., & Wu, G. (2013). Glycine metabolism in animals and humans: implications for nutrition and health. Amino Acids, 45(3), 463-477.
Cysteine
Rushworth, G. F., & Megson, I. L. (2014). Existing and potential therapeutic uses for N-acetylcysteine: The need for conversion to intracellular glutathione for antioxidant benefits. Pharmacology & Therapeutics, 141(2), 150-159.
Samuni, Yuval, et al. "The chemistry and biological activities of N-acetylcysteine." Biochimica et Biophysica Acta (BBA)-General Subjects 1830.8 (2013): 4117-4129.
Zafarullah, M., Li, W. Q., Sylvester, J., & Ahmad, M. (2003). Molecular mechanisms of N-acetylcysteine actions. Cellular and Molecular Life Sciences CMLS, 60(1), 6-20.
Lifespan references
Acosta-Rodríguez, Victoria, et al. "Circadian alignment of early onset caloric restriction promotes longevity in male C57BL/6J mice." Science 376.6598 (2022): 1192-1202.
Martin-Montalvo, Alejandro, et al. "Metformin improves healthspan and lifespan in mice." Nature communications 4.1 (2013): 2192.
Konopka, Adam R., et al. "Metformin inhibits mitochondrial adaptations to aerobic exercise training in older adults." Aging cell 18.1 (2019): e12880.
Strong, Randy, et al. "Rapamycin‐mediated mouse lifespan extension: late‐life dosage regimes with sex‐specific effects." Aging Cell 19.11 (2020): e13269.
Janes, Matthew R., and David A. Fruman. "Immune regulation by rapamycin: moving beyond T cells." Science signaling 2.67 (2009): pe25-pe25.
Su, Yuan, et al. "Alpha-ketoglutarate extends Drosophila lifespan by inhibiting mTOR and activating AMPK." Aging (Albany NY) 11.12 (2019): 4183.
Wink, Lily, Richard A. Miller, and Gonzalo G. Garcia. "Rapamycin, Acarbose and 17α-estradiol share common mechanisms regulating the MAPK pathways involved in intracellular signaling and inflammation." Immunity & Ageing 19.1 (2022): 1-20.
I love the depth of research in this post, but I had difficulty tracing references to specific claims. I'm curious -- why not just hyperlink in the text to the references themselves?
I'd also like to take a closer look at the paper on the human trial conducted at the Baylor College of Medicine.
Yeah that's a good point and thanks for stopping by. I found that having hyperlinks or in text citations come at the expense of readability and flow. and given that this is a substack article, what I did was to include a few in text citations, and put the main references at the top as the first comment which is what the bulk of the article is based on. I was hoping this would strike a balance but looks like that wasn't the case! let me know if you're able to find the references in the comments :)
It would definitely be more helpful to have hyperlinks or use Substack's footnotes feature, as that would enable to the reader to see exactly which study is connected to which claim.
Fascinating; so glad to find this as I've been looking for a piece that brings it all together.
Question: what is your opinion on Glynac-ET?
NAC Ethyl Ester has been shown to be far more bioavailable than NAC; readily crosses the BBB; easily enters/transported by RBCs, and as an ester is readily received by all cells/organs.
Thx for stopping by David. Indeed NAC in ethyl ester form has much higher bioavailability. So it's the form I'd prefer. However, it's still not very widespread and hence the costs are also higher. https://VisViva.health looks promising but isn't live yet.
As for glycine, it is already 95% bioavailable so there's no added benefit from producing an ethyl ester form.
Thinking on this more: I do wonder sometimes: if the BBB is preventing most of the NAC from crossing into the brain, maybe it's doing its job? Maybe my body knows better? Maybe circumventing that protection entails all kinds of long-term risks we don't know about? This would argue for using the non-ester NAC form. What do you think?
David - that's possible and there are simply no research to compare. however, there are promising research on using combinations of amino acids to treat Alzheimer's. The efficacy and safety appears strong. My opinion is that helpful molecules will remain helpful after crossing the BBB. Harmful molecules likewise will remain harmful in the brain.
Second, ethyl ester isn't anything new. Baby aspirin is one of the first ethyl ester form drugs that reached the mass market. The safety profile of ethyl ester of a variety of compounds is well established.
Of course, it may be prudent to wait for more data on ethyl ester form of NAC if you're concerned.
One thing I've been wondering Henry; I take a lot of whey/casein/collagen and so have a good amount of glycine in me at any time. If I take N-Acetyl L-Cysteine will that combine with the Glycine? Or do they have to be taken simultaneously? Thanks!
It depends. There's very little glycine in whey but collagen has up to 1/3 in glycine. So if you take 15g of collagen that could give you around 5g of glycine.
If you weigh 50kg that would be enough. Otherwise, you may top up on glycine to make up for the difference.
I have been following the 100mg/kg/day of glycine and 100mg/kg/day of N-acetyl cysteine daily protocol, but splitting the protocol into two daily doses.
Two questions:
1. Is dividing the protocol into two-doses recommended or sub-optimal?
2. Are the doses taken on an empty stomach or with food? I have read somewhere that taking with a protein source diminishes the effect.
Hi Michael - apologies for the slow response, thx for stopping by.
1. From the mice trial which saw a 25% increase in lifespan, GlyNAC was part of their regular food intake fed throughout the day. From this we might speculate that two doses is better than one. And a continuous slow release would be even better. Slow release has also been shown to reverse epigenetic age by 7 years in Brian Kennedy's human RCT, albeit for Ca-AKG, not GlyNAC but these may be useful clues to guide us.
2. With or without food. Hard to say which is optimal but as per the above, the effect is there even when taken with food. Taking NAC without food has been shown to increase gastrointestinal side effects.
I am on my third month of the protocol and replicating the original Baylor study as much as possible. I have recently learned the Baylor subjects were taking two doses per day - which is exactly how I have been dosing. Additionally, I learned GlyNAC is best two hours after eating as the presence of protein negatively impacts the uptake of the GlyNAC.
While my results are purely anecdotal, I have noticed a marked improvement cognitively and feel significantly more energetic. I plan to perform some blood testing in a month to gain further data concerning the impacts.
That's fantastic to hear. thanks also for sharing the two-dose regimen used in the trial. I'd be very interested in your blood test results if you're open to sharing them.
I weigh 174 lbs or 78.3 kg resulting in 7.8 grams/day. Do I start with that dosage or start lower and increase with tolerance. I have a NAC - sulfur sensitivity issue and have blood pressure problems with glycine.
Fred, NAC does have sulfur in its structure, and some folks can be sensitive to sulfur-containing compounds. There's some evidence showing that glycine might lower blood pressure, but it can vary from person to person. Given your NAC-sulfur sensitivity and blood pressure issues with glycine, I would strongly recommend consulting with a healthcare professional before trying any dosage.
You note: "many people make the mistake of supplementing glutathione directly, which may not be as effective as supplementing its precursors: glycine and NAC (GlyNAC)."
1) What is the data comparing direct supplementation vs pre-cursor supplementation?
2) The studies you cite about 80 year olds -- are those about taking the precursors, or the final compound?
The statement about direct supplementation vs. precursor supplementation is based on the observation that oral glutathione supplementation might not be as effective in raising intracellular glutathione levels. This is due to poor absorption and rapid breakdown of glutathione in the gastrointestinal tract. Supplementing with precursors, like glycine and NAC, has been shown to be more effective in supporting the body's natural production of glutathione.
The studies I mentioned involving 80-year-olds focus on taking the precursors, glycine and NAC (GlyNAC), not the final compound (glutathione). The Baylor College of Medicine's human trial specifically examined the effects of GlyNAC supplementation on various biomarkers and real-life performance differences in both elderly and young participants.
@stargazer36. this is an emerging area of research but currently the consensus is that glycine and NAC have been found to help stabilize mood. However, when a person is accustomed to experiencing intense emotional highs and lows, achieving a more stabilized mood might feel unusually flat or dull. The absence of emotional intensity as a loss of vitality or a decrease in mood quality, when it may actually be a more balanced emotional state. I've included more details on each below:
Glycine can have calming effects on the brain. It acts as an inhibitory neurotransmitter in the central nervous system, particularly in the spinal cord, brainstem, and retina. Glycine is also a co-agonist of NMDA receptors, which are involved in memory and learning. Normally, glycine's action would be expected to stabilize mood rather than disrupt it.
NAC is recognized for its role as a precursor to the antioxidant glutathione and as a modulator of glutamate levels in the brain. Glutamate is the primary excitatory neurotransmitter, and its dysregulation is linked to mood disorders. NAC's ability to modulate glutamate and increase glutathione could potentially have mood-stabilizing effects.
References
Kumar, Premranjan, et al. "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." Clinical and translational medicine 11.3 (2021): e372.
Kumar, Premranjan, Ob W. Osahon, and Rajagopal V. Sekhar. "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." Nutrients 14.5 (2022): 1114.
Kumar, Premranjan, et al. "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." The Journals of Gerontology: Series A 78.1 (2023): 75-89.
López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013). The hallmarks of aging. Cell, 153(6), 1194-1217.
Elorinne, Anna-Liisa, et al. "Food and nutrient intake and nutritional status of Finnish vegans and non-vegetarians." PloS one 11.2 (2016): e0148235.
Hoffman, Jay R., and Michael J. Falvo. "Protein–which is best?." Journal of sports science & medicine 3.3 (2004): 118.
Rushton, D. Hugh. "Nutritional factors and hair loss." Clinical and experimental dermatology 27.5 (2002): 396-404.
Hao, Jiaqing, et al. "Consumption of fish oil high-fat diet induces murine hair loss via epidermal fatty acid binding protein in skin macrophages." Cell Reports 41.11 (2022): 111804.
Meldrum, B. S. (2000). Glutamate as a neurotransmitter in the brain: review of physiology and pathology. The Journal of nutrition, 130(4S Suppl), 1007S-15S.
Salminen, A., Kaarniranta, K., Kauppinen, A., & Ojala, J. (2021). Age-related changes in AMPK activation: role for AMPK phosphatases and inhibitory phosphorylation by upstream signaling pathways. Ageing Research Reviews, 66, 101249.
Sekhar, R. V., Patel, S. G., Guthikonda, A. P., Reid, M., Balasubramanyam, A., Taffet, G. E., & Jahoor, F. (2011). Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation. The American Journal of Clinical Nutrition, 94(3), 847-853.
Sekhar, R. V., McKay, S. V., Patel, S. G., Guthikonda, A. P., Reddy, V. T., Balasubramanyam, A., & Jahoor, F. (2020). Glutathione synthesis is diminished in patients with uncontrolled diabetes and restored by dietary supplementation with cysteine and glycine. Diabetes Care, 34(1), 162-167.
Sadowska-Bartosz, I., & Bartosz, G. (2014). Effect of antioxidants supplementation on aging and longevity. BioMed research international, 2014.
Wu, G., Fang, Y. Z., Yang, S., Lupton, J. R., & Turner, N. D. (2004). Glutathione metabolism and its implications for health. The Journal of Nutrition, 134(3), 489-492.
Varani, James, et al. "Decreased collagen production in chronologically aged skin: roles of age-dependent alteration in fibroblast function and defective mechanical stimulation." The American journal of pathology 168.6 (2006): 1861-1868.
Glycine
Razak, Meerza Abdul, et al. "Multifarious beneficial effect of nonessential amino acid, glycine: a review." Oxidative medicine and cellular longevity 2017 (2017).
Meléndez-Hevia, Enrique, et al. "A weak link in metabolism: the metabolic capacity for glycine biosynthesis does not satisfy the need for collagen synthesis." Journal of biosciences 34 (2009): 853-872.
Tan, Chengquan, et al. "A review of the amino acid metabolism in placental function response to fetal loss and low birth weight in pigs." Journal of Animal Science and Biotechnology 13.1 (2022): 28.
Wang, W., Wu, Z., Dai, Z., Yang, Y., Wang, J., & Wu, G. (2013). Glycine metabolism in animals and humans: implications for nutrition and health. Amino Acids, 45(3), 463-477.
Cysteine
Rushworth, G. F., & Megson, I. L. (2014). Existing and potential therapeutic uses for N-acetylcysteine: The need for conversion to intracellular glutathione for antioxidant benefits. Pharmacology & Therapeutics, 141(2), 150-159.
Samuni, Yuval, et al. "The chemistry and biological activities of N-acetylcysteine." Biochimica et Biophysica Acta (BBA)-General Subjects 1830.8 (2013): 4117-4129.
Zafarullah, M., Li, W. Q., Sylvester, J., & Ahmad, M. (2003). Molecular mechanisms of N-acetylcysteine actions. Cellular and Molecular Life Sciences CMLS, 60(1), 6-20.
Lifespan references
Acosta-Rodríguez, Victoria, et al. "Circadian alignment of early onset caloric restriction promotes longevity in male C57BL/6J mice." Science 376.6598 (2022): 1192-1202.
Martin-Montalvo, Alejandro, et al. "Metformin improves healthspan and lifespan in mice." Nature communications 4.1 (2013): 2192.
Konopka, Adam R., et al. "Metformin inhibits mitochondrial adaptations to aerobic exercise training in older adults." Aging cell 18.1 (2019): e12880.
Strong, Randy, et al. "Rapamycin‐mediated mouse lifespan extension: late‐life dosage regimes with sex‐specific effects." Aging Cell 19.11 (2020): e13269.
Janes, Matthew R., and David A. Fruman. "Immune regulation by rapamycin: moving beyond T cells." Science signaling 2.67 (2009): pe25-pe25.
Su, Yuan, et al. "Alpha-ketoglutarate extends Drosophila lifespan by inhibiting mTOR and activating AMPK." Aging (Albany NY) 11.12 (2019): 4183.
Wink, Lily, Richard A. Miller, and Gonzalo G. Garcia. "Rapamycin, Acarbose and 17α-estradiol share common mechanisms regulating the MAPK pathways involved in intracellular signaling and inflammation." Immunity & Ageing 19.1 (2022): 1-20.
thanks, lots in the works so stay tuned
I love the depth of research in this post, but I had difficulty tracing references to specific claims. I'm curious -- why not just hyperlink in the text to the references themselves?
I'd also like to take a closer look at the paper on the human trial conducted at the Baylor College of Medicine.
Thanks (:
Yeah that's a good point and thanks for stopping by. I found that having hyperlinks or in text citations come at the expense of readability and flow. and given that this is a substack article, what I did was to include a few in text citations, and put the main references at the top as the first comment which is what the bulk of the article is based on. I was hoping this would strike a balance but looks like that wasn't the case! let me know if you're able to find the references in the comments :)
It would definitely be more helpful to have hyperlinks or use Substack's footnotes feature, as that would enable to the reader to see exactly which study is connected to which claim.
I'll give footnotes a shot. thanks Maxim
Fascinating; so glad to find this as I've been looking for a piece that brings it all together.
Question: what is your opinion on Glynac-ET?
NAC Ethyl Ester has been shown to be far more bioavailable than NAC; readily crosses the BBB; easily enters/transported by RBCs, and as an ester is readily received by all cells/organs.
Thx for stopping by David. Indeed NAC in ethyl ester form has much higher bioavailability. So it's the form I'd prefer. However, it's still not very widespread and hence the costs are also higher. https://VisViva.health looks promising but isn't live yet.
As for glycine, it is already 95% bioavailable so there's no added benefit from producing an ethyl ester form.
Yes, very true. Also of interest: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8773164/
Thinking on this more: I do wonder sometimes: if the BBB is preventing most of the NAC from crossing into the brain, maybe it's doing its job? Maybe my body knows better? Maybe circumventing that protection entails all kinds of long-term risks we don't know about? This would argue for using the non-ester NAC form. What do you think?
David - that's possible and there are simply no research to compare. however, there are promising research on using combinations of amino acids to treat Alzheimer's. The efficacy and safety appears strong. My opinion is that helpful molecules will remain helpful after crossing the BBB. Harmful molecules likewise will remain harmful in the brain.
Second, ethyl ester isn't anything new. Baby aspirin is one of the first ethyl ester form drugs that reached the mass market. The safety profile of ethyl ester of a variety of compounds is well established.
Of course, it may be prudent to wait for more data on ethyl ester form of NAC if you're concerned.
One thing I've been wondering Henry; I take a lot of whey/casein/collagen and so have a good amount of glycine in me at any time. If I take N-Acetyl L-Cysteine will that combine with the Glycine? Or do they have to be taken simultaneously? Thanks!
It depends. There's very little glycine in whey but collagen has up to 1/3 in glycine. So if you take 15g of collagen that could give you around 5g of glycine.
If you weigh 50kg that would be enough. Otherwise, you may top up on glycine to make up for the difference.
Hope that helps.
I have been following the 100mg/kg/day of glycine and 100mg/kg/day of N-acetyl cysteine daily protocol, but splitting the protocol into two daily doses.
Two questions:
1. Is dividing the protocol into two-doses recommended or sub-optimal?
2. Are the doses taken on an empty stomach or with food? I have read somewhere that taking with a protein source diminishes the effect.
Hi Michael - apologies for the slow response, thx for stopping by.
1. From the mice trial which saw a 25% increase in lifespan, GlyNAC was part of their regular food intake fed throughout the day. From this we might speculate that two doses is better than one. And a continuous slow release would be even better. Slow release has also been shown to reverse epigenetic age by 7 years in Brian Kennedy's human RCT, albeit for Ca-AKG, not GlyNAC but these may be useful clues to guide us.
2. With or without food. Hard to say which is optimal but as per the above, the effect is there even when taken with food. Taking NAC without food has been shown to increase gastrointestinal side effects.
hope this helps!
Henry, thank you for the response.
I am on my third month of the protocol and replicating the original Baylor study as much as possible. I have recently learned the Baylor subjects were taking two doses per day - which is exactly how I have been dosing. Additionally, I learned GlyNAC is best two hours after eating as the presence of protein negatively impacts the uptake of the GlyNAC.
While my results are purely anecdotal, I have noticed a marked improvement cognitively and feel significantly more energetic. I plan to perform some blood testing in a month to gain further data concerning the impacts.
That's fantastic to hear. thanks also for sharing the two-dose regimen used in the trial. I'd be very interested in your blood test results if you're open to sharing them.
Absolutely!
Excellent and well written article. thank you!
good review :-) and thank you for adding the reference list
thx for stopping by Michael. I've also subscribed to forever healthy and your twitter.
I weigh 174 lbs or 78.3 kg resulting in 7.8 grams/day. Do I start with that dosage or start lower and increase with tolerance. I have a NAC - sulfur sensitivity issue and have blood pressure problems with glycine.
Fred, NAC does have sulfur in its structure, and some folks can be sensitive to sulfur-containing compounds. There's some evidence showing that glycine might lower blood pressure, but it can vary from person to person. Given your NAC-sulfur sensitivity and blood pressure issues with glycine, I would strongly recommend consulting with a healthcare professional before trying any dosage.
Two questions:
You note: "many people make the mistake of supplementing glutathione directly, which may not be as effective as supplementing its precursors: glycine and NAC (GlyNAC)."
1) What is the data comparing direct supplementation vs pre-cursor supplementation?
2) The studies you cite about 80 year olds -- are those about taking the precursors, or the final compound?
Great questions!
The statement about direct supplementation vs. precursor supplementation is based on the observation that oral glutathione supplementation might not be as effective in raising intracellular glutathione levels. This is due to poor absorption and rapid breakdown of glutathione in the gastrointestinal tract. Supplementing with precursors, like glycine and NAC, has been shown to be more effective in supporting the body's natural production of glutathione.
The studies I mentioned involving 80-year-olds focus on taking the precursors, glycine and NAC (GlyNAC), not the final compound (glutathione). The Baylor College of Medicine's human trial specifically examined the effects of GlyNAC supplementation on various biomarkers and real-life performance differences in both elderly and young participants.
Apr 30 update: More in-text citations have been added.
Interesting. So the 100mg/kg/day of NAC and glycine would equal ~ 8 grams each per day for a 175lb adult? That's not just a little bit.
That's correct. They treated different dosages in their follow-up RCT in 2023 and found that only 5g and above had a statistically significant effect.
Could supplementing with glycine and NAC be causing a drop in mood?
@stargazer36. this is an emerging area of research but currently the consensus is that glycine and NAC have been found to help stabilize mood. However, when a person is accustomed to experiencing intense emotional highs and lows, achieving a more stabilized mood might feel unusually flat or dull. The absence of emotional intensity as a loss of vitality or a decrease in mood quality, when it may actually be a more balanced emotional state. I've included more details on each below:
Glycine can have calming effects on the brain. It acts as an inhibitory neurotransmitter in the central nervous system, particularly in the spinal cord, brainstem, and retina. Glycine is also a co-agonist of NMDA receptors, which are involved in memory and learning. Normally, glycine's action would be expected to stabilize mood rather than disrupt it.
NAC is recognized for its role as a precursor to the antioxidant glutathione and as a modulator of glutamate levels in the brain. Glutamate is the primary excitatory neurotransmitter, and its dysregulation is linked to mood disorders. NAC's ability to modulate glutamate and increase glutathione could potentially have mood-stabilizing effects.
Hope this helps.