Yes, the studies I have read have said that Glycine can protect against certain cancers as you have shown. Pancreatic cancer is the nastiest of the nastiest cancers. My father-in-law has it and it is essentially a death sentence. I’m glad glycine protects against it!
I love GLYNAC. Glycine improves my sleep and NAC improves my mood. It’s a supplement that generally makes me happier and if it can help me live longer, all the better.
I’ve been on the same boat for a while. Didn’t feel the love when taking glynac (way overrated in my opinion) and ditched then about 10 days ago. I’ll try to stick with the ones I see a clear positive effect (and not just some research somewhere shows that xyz substance increased lifespan of fruit flies lol).
Melatonin alone, or glycine alone, reduce colorectal tumors. Combining them has no effect.
Melatonin and glycine alone significantly reduced the tumor volume by 63.2% (p = 0.002) and 43% (p = 0.044) over time, respectively, while tumor volume increased by 8.7% in the controls. Moreover, treatment with melatonin and glycine alone reduced the tumor proliferation index. Most interestingly, the combination therapy did not have any influence on the above-mentioned tumor parameters.
Looks like melatonin would be the better sleep agent.
Glycine and aging: Evidence and mechanisms (2023):
GNMT enzyme plays a key role. It clears methionine (potentially mimicking restriction) and makes sarcosine (declines with age and activates cellular cleanup).
GNMT also links to lifespan via insulin/IGF, autophagy, and spermidine.
GNMT: Glycine N-methyltransferase (GNMT) is an enzyme and a crucial regulator of cellular SAM & SAH via methionine metabolism
https://sciencedirect.com/science/article/pii/S1568163723000818
It is interesting that mTOR inhibition is life extending (in animal models), and that glycine is life extending (in animal model) despite being mTOR activating.
Many hallmarks of aging, yes.
But how to avoid offsetting of benefits?
Glycine actually is a pretty good sweetener for coffee and tea
Thanks @Jonas , very helpful review.
It is interesting that mTOR inhibition is life extending (in animal models), and that glycine is life extending (in animal model) despite being mTOR activating.
Makes you wonder if glycine’s mTORC1 activation might mask its true life-extension potential and that rapamycin+glycine might be synergistic for that same reason.
I’m not particularly knowledgeable re the exact mechanism by which rapamycin inhibits mTORC1, but to a first approximation, it seems to work similarly to a noncompetitive/insurmountable antagonist. This is especially with regard to 4E-BP1 phosphorylation, which requires mTORC1 dimerization.
Whereas relatively short exposure to FKBP12-rapamycin did not affect the structural integrity of mTORC1, extended incubations resulted in a drastic reduction in the total number of intact mTORC1 particles. Many smaller fragments appeared in the background, suggesting that FKBP12-rapamycin may cause disassembly of mTORC1. Once initiated, this dissociation appears to be swift, as we were unable to detect intermediates with defined structures during the course of the reaction. After 1 hr incubation, virtually no intact mTORC1 particles could be detected, and the sample contained only smaller fragments, likely representing free mTOR or its sub-complexes, and undefined aggregates (Figure 4B). [ref]
Also some evidence for glycine activating mTORC1 in primary cells (hepatocytes). [ref]
These are close to physiologically relevant extracellular glycine concentrations, since in fasting healthy subjects, extracellular glycine in skeletal muscle is about 0.3 mM, and in transplanted liver it’s about 0.2 mM. Seems much more tightly regulated in brain (about 0.5uM), probably due to its role as a neurotransmitter (co-agonist at the NMDA receptor).
It can have 2 different implications:
The only way would be test this 2 compounds on mice / C Elegans or other animals
Maybe the mechanism to how it works causes a net benefit to lifespan despite mTOR activation? In which case rapamycin + glycine would work better than either by itself.
Not a fan of glycine. I’ll stick with RAPA.
I don’t take Glycine on Rapa days. Unfortunately my Marine Collagen Peptides contain almost 2 g of Glycine, so have to skip those too.
Glycine is Not a mTORC1 Activator
Show me the papers.
I can find no evidence that glycine supplementation would affect the efficacy of rapamycin.
There are other amino acids that might have a significantly greater impact.
From what I can deduce from the paper it might be better to avoid amino acids as much as possible on the day you take rapamycin.
I can find no literature that glycine is a significant mTORC1 activator.
leucine is the primary priming activator of mTORC1
According to the study, glycine serves as a “priming” amino acid, making mTORC1 more sensitive to the activation of other amino acids, such as leucine. But glycine didn’t seem to activate mTORC1 directly on its own.
“Individual amino acids have little effect on mTORC1 activity”
“Here we demonstrate that activation of mTORC1 by amino acids includes two discrete and separable steps: priming and activation. Sensitizing mTORC1 activation by priming amino acids is a prerequisite for subsequent stimulation of mTORC1 by activating amino acids. Priming is achieved by a group of amino acids that includes l-asparagine, l-glutamine, l-threonine, l-arginine, l-glycine, l-proline, l-serine, l-alanine, and l-glutamic acid. The group of activating amino acids is dominated by l-leucine”
Bottom line: Out of an abundance of caution, I will forego supplementing with amino acids including glycine on the days I take rapamycin. The interaction of amino acids and rapamycin are not well studied.
I agree. I don’t take anything besides metformin on my rapa day. I need to let my body have a break anyway.
Spermidine, if you take it, should be taken on Rapa day as it enhances the autophagic effects. I still have some I bought that I mix with EVOO and black pepper.
Correction. Sorry to mislead.
The combination did not potentiate the intervention, but still had an effect, similar to glycine alone.
3.3. Change in Tumor Volume
We observed an 8.7% (−17.5; 40.9) increased tumor volume in the control group and a 63.2% (−3.1; 71.1) decreased tumor volume in melatonin, 43% (−12.6; 70.1) in glycine, and 47.7% (−116.9; 60.6) in combined supplementation with melatonin and glycine at day 8 vs. day 14.
That is a decrease in tumor volume of
63.2% for melatonin,
43% for glycine; and
47.7% for the combo.
The effect was on the 14th day.
Am I missing something? It looks like it is better to just take the melatonin.
What was the dose of Melatonin per kg of weight?
No disagreement here. I opined as much, in the post above.
Looks like melatonin would be the better sleep agent.
But this is a one-dimensional benefit shown in Wistar rats. Glycine has other benefits shown in human trials. There is the benefit to glycated hemoglobin shown in human patients in my post 14 above.
Díaz-Flores et al administered 15-g glycine daily (5 g, 3 times daily) to patients with metabolic syndrome. Despite fasting glucose rising significantly from 101 mg/dL to 114 mg/dL (P =0.001), glycated hemoglobin fell from 7.81% to 6.45% (P =0.0001);
5-g glycine 4 times daily for 6 months in an uncontrolled clinical trial, glycated hemoglobin fell from 9.6% to 6.9% (P <0.05);
Glycine supplementation was also associated with significant reductions in systolic blood pressure
The reduction in effect on tumors occurred when the melatonin was combined with glycine in water (dose was also in water, for melatonin and glycine, singly). I am wondering if this reduced effect will also occur, when melatonin and glycine are dosed separately (glycine during the day, and melatonin before bed), considering that the half life of glycine is 4 hours, max.
In any case, even if the effect on tumors is reduced, there is still a reduction - 47.7%. But that comes with other benefits of glycine.
Rats received 1.5 mL of milk (3.5% fat) containing either melatonin (100 mg/kg of rat body weight; Sigma-Aldrich, St. Louis, MO, USA) or the corresponding amount of microcrystalline cellulose (placebo; from Sigma-Aldrich, St. Louis, MO, USA) daily via gavage.
Divided by 12.3, that is a hefty 480 mg of melatonin for a 60kg individual. Not a dangerous dose (John Hemming’s experience bears that out). But a bit difficult to comply with, for me. In the 90s, I took 6 mg of melatonin before bed, and was groggy the whole morning.
Huge dose! To avoid being groggy in the morning, I take only 3mg at bedtime.
The combo beat glycine, did not beat melatonin. If this is what you are talking about.
