I'm glad you're thinking this through with me. I agree, there are many important issues to sort through. The report you cited above contains many fascinating details; I don't see anything that is negative about glyNAC.
For general interest, I have been taking 7 grams of NAC and about 50 grams of glycine daily for a few months now, so far all positive (mood, cognition, GERD, weight, energy, IBS/endotoxin reactions, loss of sugar craving, remarkable return to normal 180/120 down to 120/80 of blood pressure and I've let go of three blood pressure medications). I also have begun to measure glutathione ratios and fating amino acids in the neurology clinic.
Some observations:
1) I think the forum generally agrees glycine is a good thing, some think best with collagen.
2) I agree with some postings here that we don't know whether NAC adds anything to glycine, and I don't know whether NAC is any different from cysteine and whether effects would be different in different situations. You need two substances to patent and so there is some pressure to study glyNAC rather tha one or the other substance alone.
3) I don't think either substance or the combintation does much below the age of 45-50 for the general population. The effects above that age are very different, since they have a stress condition called "age", and many younger patients with chronic conditions (GERD, migraine, anxiety) may have abnormal glycine, cystine, GSH, or GSSH levels or ratios.
4) Probably most people here would agree that the literature supports extension of life with methionine restriction. While both are sulfur-containing aas, methionine participates in methylation reactions (not Peaty) and cysteine suppresses methionine.
5) The literature is confusing, but it appears to me that oxidized glutathione is acutely suppressed then upregulated during stress (fasting, alcoholism, leaky gut in Ehlers-Danlos, stressful exercise) as part of the stress reaction and that methionine then locks in the structure of the stress response.
6) If there is insufficient cysteine for these stress cycles, the reduced cysteine will fall, as will glutamate, in chronic illness.
7) So can we just feed glycine? Maybe, but you need enough glutathione to put the glycine bricks in place. If total glutathione levels are low, you can't hang on to glycine sufficiently to repair.
8) Stress reactions are asymmetric. There is a brief stress, then the body responds with structures that persist longer than the stress, in anticipation of a possible stress repeat- the body learns. In Selye's sequence, the hands are cold, the blood pressure rises, the blood clots, the thyroid stops, dthe thymus shrinks, and aminos are released from skin and muscle under catabolic signaling. Stress raises amino acids in the serum and reduces them in the skin and muscle. Stores are build again more slowly, through diet and Peaty hormonal sequences. We store most of our glycine in our skin, which functions as as stress pump, buffering stress by releasing glycine and reduced cysteine. At the end of the acute stress response we slowly build these stores back again, partly through diet and partly through synthesis.
9) The core idea of aging as system and energy biology (as opposed to simple oxidation, telomeres, or genetic accumulation of errors) is that the walls built largely from glycine need energy to replace and maintain them at all levels of biology; very roughly speaking, glycine is the bricks, glutathione repairs the energy generators to lift the bricks, and without glutathione you can't keep up the brick repairs. The body lays down structure and locks its knees to keep from falling down (fat, arthritis, sclerosis, amyloid) using methylation reactions.
10) I agree that a little methyl sink is a good idea, and that it is helpful to avoid methionine. Cysteine supplementation, I think, allows you to not hang onto methionine.
For general interest, I have been taking 7 grams of NAC and about 50 grams of glycine daily for a few months now, so far all positive (mood, cognition, GERD, weight, energy, IBS/endotoxin reactions, loss of sugar craving, remarkable return to normal 180/120 down to 120/80 of blood pressure and I've let go of three blood pressure medications). I also have begun to measure glutathione ratios and fating amino acids in the neurology clinic.
Some observations:
1) I think the forum generally agrees glycine is a good thing, some think best with collagen.
2) I agree with some postings here that we don't know whether NAC adds anything to glycine, and I don't know whether NAC is any different from cysteine and whether effects would be different in different situations. You need two substances to patent and so there is some pressure to study glyNAC rather tha one or the other substance alone.
3) I don't think either substance or the combintation does much below the age of 45-50 for the general population. The effects above that age are very different, since they have a stress condition called "age", and many younger patients with chronic conditions (GERD, migraine, anxiety) may have abnormal glycine, cystine, GSH, or GSSH levels or ratios.
4) Probably most people here would agree that the literature supports extension of life with methionine restriction. While both are sulfur-containing aas, methionine participates in methylation reactions (not Peaty) and cysteine suppresses methionine.
5) The literature is confusing, but it appears to me that oxidized glutathione is acutely suppressed then upregulated during stress (fasting, alcoholism, leaky gut in Ehlers-Danlos, stressful exercise) as part of the stress reaction and that methionine then locks in the structure of the stress response.
6) If there is insufficient cysteine for these stress cycles, the reduced cysteine will fall, as will glutamate, in chronic illness.
7) So can we just feed glycine? Maybe, but you need enough glutathione to put the glycine bricks in place. If total glutathione levels are low, you can't hang on to glycine sufficiently to repair.
8) Stress reactions are asymmetric. There is a brief stress, then the body responds with structures that persist longer than the stress, in anticipation of a possible stress repeat- the body learns. In Selye's sequence, the hands are cold, the blood pressure rises, the blood clots, the thyroid stops, dthe thymus shrinks, and aminos are released from skin and muscle under catabolic signaling. Stress raises amino acids in the serum and reduces them in the skin and muscle. Stores are build again more slowly, through diet and Peaty hormonal sequences. We store most of our glycine in our skin, which functions as as stress pump, buffering stress by releasing glycine and reduced cysteine. At the end of the acute stress response we slowly build these stores back again, partly through diet and partly through synthesis.
9) The core idea of aging as system and energy biology (as opposed to simple oxidation, telomeres, or genetic accumulation of errors) is that the walls built largely from glycine need energy to replace and maintain them at all levels of biology; very roughly speaking, glycine is the bricks, glutathione repairs the energy generators to lift the bricks, and without glutathione you can't keep up the brick repairs. The body lays down structure and locks its knees to keep from falling down (fat, arthritis, sclerosis, amyloid) using methylation reactions.
10) I agree that a little methyl sink is a good idea, and that it is helpful to avoid methionine. Cysteine supplementation, I think, allows you to not hang onto methionine.
