I alternate thru taurine and glycine @ bedtime and morning/daytime. In evening its taken with a small dose of tryptophan and 5mg time released melatonin. By alternating the taurine and glycine it seems to help keep the beneficial effect on sleep. As taurine also has a strong agonist affinity for the gly receptors IMO its best to separate to prevent competitiveness. But as a general guide I find taurine more fitying @bedtime and glycine during active hours but they both work at bedtime IME.
There is an interesting effect on why it seems glycine can both inhibit and stimulate cancer proliferation. By supplementation of glycine you downregulate the cellular Serine hydroxymethyltransferase 2 (SHMT2). SHMT2 is a bidirectional pathway of serine-glycine. It can sythesizs glycine from serine or vise-vera. If you do a quick search of SHMT2 and cancer you will see a ton of research all pointing to its upregulation as directly increasing cancer cell proliferation. In a few of the studies they suppress SHMT2 or use KO mice and glycine does not reverse this suppression.
At the same time we have research clearly indicating supplemental glycine added to pre-exsisting cancer cells can increase proliferation. The answer could be thru mtorc1 activation. Glycine does in fact activate/stimulate cellular MTORC1/AKT which certainly has been shown to increase cancer cell proliferation. A search of “glycine and mtor” will net you numerous research supporting this effect. But what is interesting is stimulation of AMPK inhibits this glycine intitated mtorc1 activation. The one study I took notes of used ALCAR but take your pick. Further Rapa would certainly abolish this mtor activation. Point being it should not stimulate mtorc1 given those parameters of activated AMPK. But as cancers are run away proliferation your typical BCAA etc are all going to feed the furnace as is glucose which tends to so significantly.
Research also indicated that when you have NAFLD or what they are now more specifically named “Metabolic dysfunction-associated steatotic liver disease” (MASLD). The liver actually creates even greater glycine deficiency by the reverse SHMT2 pathway. Causing serine synthesis from glycine breakdown. Limited glycine availability in steatotic livers impaires glutathione synthesis. Glycine supplemetation prevents this reverse SHMT2 depleting activity.
Of interest doxycycline and sertraline (zoloft) both downregulate SHMT2 and have been used in research as targets in cancer treatement and in combo with radiotherapy.
Looking at this together it would seem to support use of glycine to ensure glutathione levels. The issue of increasing malignancy cell proliferation seems to be countered by any AMPK activating compounds. Given most on here are thru .ifestyle or supplementation/medication activating AMPK the MTORC1 stimulating effect is negated. Rapa itself does this directly in a more powerful way.
Not sure if I am a proponent of the massive dosages some have mentioned here (30+ grams) with further research into the effects of the metabolites from its catabolization and any possible toxicity etc . Have not looked into this at all. My dosing has always been >10g/d.
One last thing I consider in the benefit category of glycine that I rately see mentioned is its an intracellular osmolyte. Taking a bolus of glycine has the effect of increasing intracellular hydration/volume, something that can be in deficit as we age and our thrist mechanism becomes blunted and kidneys age. Beyond helping mantain healthy osomtic volume, it’s bolus can create a temporary spike in inteacellular volume/pressure…a “swell” effect that can further stimulate positive effects in the mitochondria and cyto. Bad things start to happenn to cells and their mitochondria that are in chronic dehydration causing the cells to use sodium influx to balance osmotic pressure.
I first learned about glycines intracellular hydrating effects as a young kid on the farm. When we had baby farm animals sheep goat calf pigglet get scours or that had troubled birth or for whatever reason had gotten off tit and dehydrated we used a substance called Re-Sorb. It was full of the typicals you expect in rehydration drenchs (drinks) sodium chloride, potasium, asorbic acid (a separate packet with glucose (dextrose)) but it also had a very sizable amount of glycine over 6 grams. Well the other ingredients were easily explained by my grandfather and father but it took our vet on one of his visits to explain the glycine (pre-internet days). Its one of a group of osomtic amino acids glycine, taurine, alanine, proline. I ended up formulating a hydration drink for workouts long cardio and long hot days hunmping it on the farm. The drinks are slightly different for each but the base osmotic aminos are the same. But in researching for those I learned how they function as intracellular osmolytes and their benfits from that focus. Lets just say gatoraide and 99% sport drinks can be way better. Consider this info was known and practiced in the livestock industry in at least the early 80s.
