LONGECITY

I started taking Glycine as a potential way to mitigate glyphosate, but would like to know opinions on this.

Could Glyphosate be mistaken in our bodies for Glycine, (Dr. Stephanie Seneff, Dr. Anthony Samsel) resulting in erroneous protein folding, leading to production problems of any protein involving Glycine such as collagen, trypsin, myosin, CYP, etc, leading to diseases like chronic joint pain, leaky gut, peristalsis/dysbiosis, SIBO, Autism, autoimmunity, cancer, Parkinsons, Alzheimers, Diabetes, Obesity, infertility, etc.???

And then, if their is a chance that Glyphosate could be doing this, I'd ask the opinions regarding using Glycine supplementation to help mitigate this, as recommended by Dr. Dietrich Klinghardt. The ide being that a saturation of Glycine would reduce the rate of Glyphosate incorporation into proteins.

I have started taking Glycine anyway, after learning numerous other benefits.

Thanks.

Oxid Med Cell Longev. 2018 Feb 21;2018:2101562. 

 

 

Glycine supplementation extends lifespan of male and female mice

 

First published: 27 March 2019

 

https://doi.org/10.1111/acel.12953

 

 

Abstract

Diets low in methionine extend lifespan of rodents, though through unknown mechanisms. Glycine can mitigate methionine toxicity, and a small prior study has suggested that supplemental glycine could extend lifespan of Fischer 344 rats. We therefore evaluated the effects of an 8% glycine diet on lifespan and pathology of genetically heterogeneous mice in the context of the Interventions Testing Program. Elevated glycine led to a small (4%–6%) but statistically significant lifespan increase, as well as an increase in maximum lifespan, in both males (p = 0.002) and females (p < 0.001). Pooling across sex, glycine increased lifespan at each of the three independent sites, with significance at p = 0.01, 0.053, and 0.03, respectively. Glycine‐supplemented females were lighter than controls, but there was no effect on weight in males. End‐of‐life necropsies suggested that glycine‐treated mice were less likely than controls to die of pulmonary adenocarcinoma (p = 0.03). Of the 40 varieties of incidental pathology evaluated in these mice, none were increased to a significant degree by the glycine‐supplemented diet. In parallel analyses of the same cohort, we found no benefits from TM5441 (an inhibitor of PAI‐1, the primary inhibitor of tissue and urokinase plasminogen activators), inulin (a source of soluble fiber), or aspirin at either of two doses. Our glycine results strengthen the idea that modulation of dietary amino acid levels can increase healthy lifespan in mice, and provide a foundation for further investigation of dietary effects on aging and late‐life diseases.

Excellent citation Phoebus.It shows a decent, but still underwhelming lifespan effect, and adds to prior evidence that Glycine is a good thing.  However, I'm starting to become skeptical of some of these studies that show such marginal effects.  After all, couldn't it just as easily be a crowding out effect, where eating so much more glycine precludes eating some other more damaging protein, or another damaging protein is interfered with.  Or any number of other effects.  Just getting a bit jaded I guess, and wanting to see real progress and real insights.

Aside from that, the study also shows aspirin as a control that provides no lifespan effect.  Isn't that a result at odds with previous studies?  Or does aspirin only confer a benefit so far in Planarians, for example. 

Does this study actually tell us anything important?

By the day I'm becoming more and more opposed to trivial things like playing with metabolism, CR schemes and various single-molecule interventions.  These things translate very badly, if at all.  It's not just that we need more radical interventions.  It's also the huge opportunity cost of funding and paying attention to these very marginal effects in mice.

By the day I'm becoming more and more opposed to trivial things like playing with metabolism, CR schemes and various single-molecule interventions.  These things translate very badly, if at all.  It's not just that we need more radical interventions.  It's also the huge opportunity cost of funding and paying attention to these very marginal effects in mice.

What is your alternative approach?

Excellent citation Phoebus.It shows a decent, but still underwhelming lifespan effect, and adds to prior evidence that Glycine is a good thing.  However, I'm starting to become skeptical of some of these studies that show such marginal effects.  After all, couldn't it just as easily be a crowding out effect, where eating so much more glycine precludes eating some other more damaging protein, or another damaging protein is interfered with.  Or any number of other effects.  Just getting a bit jaded I guess, and wanting to see real progress and real insights.

 

Aside from that, the study also shows aspirin as a control that provides no lifespan effect.  Isn't that a result at odds with previous studies?  Or does aspirin only confer a benefit so far in Planarians, for example. 

 

Does this study actually tell us anything important?

 

By the day I'm becoming more and more opposed to trivial things like playing with metabolism, CR schemes and various single-molecule interventions.  These things translate very badly, if at all.  It's not just that we need more radical interventions.  It's also the huge opportunity cost of funding and paying attention to these very marginal effects in mice.

Maybe the animals in those studies are very well kept. I'm not well kept, I'm unkempt from living near a big road and sometimes eating O6 foods due to social pressure. I take it buy Cycle. Cycle mitoQ, cycle melatonin, I even took four bottles of C60oo... What do we know

Surprised i haven't seen this before but it is really interesting. Sorry if its been posted before i only had a quick look though the previous posts.

https://academic.oup...4/3/847/4431102

"Glutathione deficiency in elderly humans occurs because of a marked reduction in synthesis. Dietary supplementation with the glutathione precursors cysteine and glycine fully restores glutathione synthesis and concentrations and lowers levels of oxidative stress and oxidant damages. These findings suggest a practical and effective approach to decreasing oxidative stress in aging."

Glutothione in red blood cells was dramatically increased and levels of oxidants such as lipid peroxides were brought down impressively.

Unless i calculated wrong, it takes around 8 grams of glycine (also cysteine, didnt look into how much) to get these effects.

Glycine really does seem to be quite a fascinating substance for anti-aging. Considering that it appears to be a rate limiting factor for glutathione AND collagen synthesis, has the potential to extend lifespan and lowers oxidative stress in the elderly.  .

Definitely going to start mixing some in with the collagen i already take, around 8g .

on examine.com they say abput glycine "It can play both stimulatory and depressant roles in the brain"

what does that exactly mean? do they mean it causes depression? or they mean something completely different?

on examine.com they say abput glycine "It can play both stimulatory and depressant roles in the brain"

what does that exactly mean? do they mean it causes depression? or they mean something completely different?

They probably mean it in a general sense. Like inhibitory versus disinhibitory or relaxing versus stimulating  (and not necessarily  a "this feels good" relaxation or stimulation). Or maybe they just mean to say on the neurological level brain cells or brain systems get stimulated or inhibited by glycine (and the perceived effects might be whatever).

I've used glycine for several years now and in my experience it's true that it can promote sleep but also wakefulness and decrease the fatigued feeling one might get near the end of the day. I think Taurine is the most extreme example of a simple compound that both is obviously relaxing and obviously stimulating --- but glycine is much more subtle I'd say in these two regards. This might be a personal thing but Benzodiazepines does this for me as well, to a rather high degree, especially higher doses I tend to get quite agitated and feel great interest in doing things. (I do not recommend anyone use benzodiazepines without a doctor involved or for longer than is medically necessary.)

I've used glycine so frequently for so long I can't really comment too much on how it feels, but I'd say it probably makes me sleep better at night and make me feel a little less fatigued during the day. How do I know? Well I don't take that many supplements, I think this is probably the case with magnesium as well which I used to take for a very long time but recently I improved my diet and so I only take Mg for the relaxing effects if I feel very tense etc. Only thing I added at the same time as glycine (several grams a day) is magnesium, but like I said I mostly stopped taking that. Also when I first began taking glycine it did produce an acute relaxing effect that was rather impressive, but that disappeared, maybe it was just temporary tension I had at the time making the action obvious, or placebo.

So in short I think glycine has some positive effects on mood/endurance/sleep, and thankfully it's a rather subtle effect in the long run. Whereas I don't know if I'd enjoy taking Taurine again for any amount of period because it's so obvious it does something paradoxically stimulating and inhibitory at the same time, and I find that somewhat annoying (again that probably is something you'd get over taking it for long enough which I havent really done with that compound).

These days I just pour some powder into a glass of water, probably been taking 10+ grams for several weeks now, can't say there's any bad effects, , I don't know, hard to say. One reason I did stop taking Mg as supplement is because I was a little worried I was making myself too much on the "depressed" side, too tired or relaxed and so on, which maybe was the case for a while or maybe not, but that's certainly  a real possibility with Magnesium (glycine probably not so much I'm guessing). I used to only take maybe 5grams a day, or less, now I think I'd rather take a bit more like 10 grams or more, after listening to some supplement crank talk about this, and it seems reasonable to want to balance out the diet with some glycine if you eat a lot of meat, fish, or most other protein rich foods of the modern world, and not any of the more glycine rich foods people used to eat for most of human evolution (bone broth, boil all the cadaver remains and eat the amino acid soup, for tens of thousands of years or who knows how long people have been cooking meat)

I was looking into skin barrier stuff and found this. (in rats)

https://www.ncbi.nlm...pubmed/25498544

"These results suggested that the administration of PO and OG improved skin barrier dysfunction and altered muscle-related gene expression."

Unsure if glycine would have similar benefits, but i think there is likely more benefits to consuming both glycine and collagen.

Surprised i haven't seen this before but it is really interesting. Sorry if its been posted before i only had a quick look though the previous posts.

https://academic.oup...4/3/847/4431102

Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation

"Glutathione deficiency in elderly humans occurs because of a marked reduction in synthesis. Dietary supplementation with the glutathione precursors cysteine and glycine fully restores glutathione synthesis and concentrations and lowers levels of oxidative stress and oxidant damages. These findings suggest a practical and effective approach to decreasing oxidative stress in aging."

 

Glutothione in red blood cells was dramatically increased and levels of oxidants such as lipid peroxides were brought down impressively.

Unless i calculated wrong, it takes around 8 grams of glycine (also cysteine, didnt look into how much) to get these effects.

 

Glycine really does seem to be quite a fascinating substance for anti-aging. Considering that it appears to be a rate limiting factor for glutathione AND collagen synthesis, has the potential to extend lifespan and lowers oxidative stress in the elderly.  .

Definitely going to start mixing some in with the collagen i already take, around 8g .

This is an interesting paper. I've been taking ~15g glycine per day and ~2g NAC per day for a while, mainly for glutathione status.

This paper suggests 8g/day of glycine and 10.5g/day of NAC. The dosage of NAC seems excessive, although the patients were elderly, as opposed to the paper I point out below, which used 1.8g/day of NAC for 4 weeks as a treatment for hypertension in middle aged patients (but also increased the GSH:GSSG ratio significantly 

https://www.ncbi.nlm...pubmed/26447155

 ABSTRACT

Background: Elevated total plasma homocysteine (tHcy) is considered to be an independent cardiovascular disease risk factor, although tHcy lowering by B-vitamins improves only certain clinical endpoints. N-acetylcysteine (NAC), a thiol-containing antioxidant, acutely lowers tHcy and possibly also blood pressure. However, to our knowledge, at present no conclusive long-term evaluation exists that controls for factors such as hyperlipidemia, smoking, medication, and disease stage, all of which affect the thiol redox state, including tHcy. Objective: We reanalyzed 2 double-blind, placebo-controlled trials in unmedicated middle-aged men, one in a hyperlipidemic group (HYL group; n = 40) and one in a normolipidemic group (NOL group; n = 42), each stratified for smokers and nonsmokers.

Design: We evaluated the effect of 4 wk of oral NAC (1.8 g/d) on tHcy (primary endpoint), plasma thiol (cysteine), and intracellular glutathione concentrations as well as on blood pressure. The HYL group had total cholesterol .220 mg/dL or triglycerides .150 mg/dL.

Results: NAC treatment significantly (P = 0.001, multivariate analysis of variance for repeated measures) lowered postabsorptive plasma concentrations of tHcy by 211.7% 6 3.0% (placebo: 4.1% 6 3.6%) while increasing those of cysteine by 28.1% 6 5.7% (placebo: 4.0% 6 3.4%) with no significant impact of hyperlipidemia or smoking. Moreover, NAC significantly decreased systolic (P = 0.003) and diastolic (P = 0.017) blood pressure within all subjects with a significant reduction in diastolic pressure in the HYL group (P = 0.008) but not in the NOL group. An explorative stepwise multiple regression analysis identified 1) post-treatment cysteine as well as 2) pretreatment tHcy and 3) albumin plasma concentrations as being significant contributors to tHcy reduction.

Conclusions: Four weeks of oral NAC treatment significantly decreased plasma tHcy concentrations, irrespective of lipid or smoking status, and lowered systolic blood pressure in both normolipidemic and hyperlipidemic men, with significant diastolic blood pressure reductions in the HYL group only. Increased oral intake of cysteine may therefore be considered for primary or secondary prevention of vascular events with regard to the 2 independent risk factors of hyperhomocysteinemia and arterial hypertension.

It seems clear that cysteine is the limiting factor in glutathione synthesis (especially considering that it exists in MUCH lower concentrations than glycine in the blood). However given that we know that glycine (despite it's abundance in the blood), is insufficient in humans for collagen synthesis, it may also be a limiting factor for making glutathione in some circumstances, i.e. when there are demands for it elsewhere. Here is a good example, where children experiencing catch-up growth after malnutrition no longer had enough glycine for glutathione synthesis:

https://www.academia...emental_Glycine

Conclusion: it is advisable for take both NAC and Glycine. NAC for glutathione and Glycine for collagen, and glutathione in some demanding circumstances. 

I take them in the day, once I've broken my fast. On workout days I tend o use Whey instead of NAC (also a good source of cysteine), but without the direct anti-oxidative effects that might (if taken close to a workout) impede the damage required for muscle development.

What about all that fuzz about NAC destroying BBB and lining of the gut?

https://www.ncbi.nlm...ubmed/24898644/

https://www.ncbi.nlm...les/PMC3261620/

One of those uses N-acetylcholine, not cysteine. Still concerning though.

What about all that fuzz about NAC destroying BBB and lining of the gut?

https://www.ncbi.nlm...ubmed/24898644/

https://www.ncbi.nlm...les/PMC3261620/

One of those uses N-acetylcholine, not cysteine. Still concerning though.

What about all that fuzz about NAC destroying BBB and lining of the gut?

https://www.ncbi.nlm...ubmed/24898644/

https://www.ncbi.nlm...les/PMC3261620/

Cheers, I stopped looking at that second paper after the typo. Good to know.

Just in case you have not seen the last blog by Josh Mitteldorf on mitochondrial health which includes glycine:

http://joshmitteldor...d-mitochondria/

 

"Glycine

The theory in the Japanese paper is that glycine treats the downstream symptom of epigenetic reprogramming in the mitochondria.  In other words, glycine does not stop the detrimental epigenetic changes in mitochondria that come with age, however one of the most important of these changes results in a glycine shortage in the mitochondria.  Hence, glycine supplementation effectively attacks the problem at an intermediate stage.

Could a molecule as simple (non-specific) as glycine be an anti-aging compound?  Glycine comes to us with a sketchy but promising history.  In one rat study, a hefty dose of glycine increased lifespan by 27% longer than controls.  “Hefty” is the human equivalent of ~3 ounces per day.  I’m tentatively filing this study in the “too good to be true” drawer, because it appeared only as a conference abstract 5 years ago and has never been fleshed out with a peer-reviewed full text.

A shortage of protein has a powerful anti-aging effect across many species.  And a shortage of one critical amino acid–methionine–is sufficient to trigger this response.  This may be because methionine is the “start codon”; every gene begins with a methionine, and a severe shortage of methionine can slow down all protein synthesis.  

Directly engineering a shortage of methionine in the human body is just too difficult to manage, because too many protein foods have methionine, and we’re too fond of protein.  (Animal proteins are consistently loaded with methionine, whereas some vegetable sources have less.)  In studies of lab animals, a methionine shortage is engineered by using fully artificial protein sources, constituted from individual amino acids.  People would never want to live this way on synthetic food, even if we could afford it; but using glycine to create a methionine shortage sounds more palatable.  Glycine plays a role in breaking down methionine in the liver, and if the glycine level is jacked up super-high, it is (theoretically) possible to force this reaction so far as to create a methionine shortage.

For some of us, methionine restriction holds up the tantalizing prospect of gaining benefits of dietary restriction while allowing us to eat to satiety.  But the idea remains untested in humans.  Protein deficiency can lead to loss of strength and endurance and the ability to concentrate–even as it increases life expectancy.  Depression is another risk.  Rats that have tried methionine restriction are not recommending it for humans; in fact, they quickly come to crave methionine; they recognize methionine-deficient foods and shun them.

On the other hand, there are other diverse benefits documented for glycine supplementation, beginning with better sleep, insulin sensitivity and cancer resistance.  A minimum of 3 or 4 grams is required to have any effect.  You can buy it in powder form by the pound.  From Finland, here’s Valdu Heiskanen’s comprehensive page on glycine."

A bit old thread but feel the following extensive recent review might be relevant to be posted here. You might possibly have a comment or experience in using Glycine in conjunction with NAC? (the paper cites clinical results in humans, see Sect. 3.4).

"The restriction of calories, branched-chain amino acids, and methionine have all been shown to extend lifespan in model organisms. Recently, glycine was found to boost longevity in genetically heterogenous mice. This simple amino acid similarly extends lifespan in rats and improves health in mammalian models of age-related disease. While compelling data indicate that glycine is a pro-longevity molecule, divergent mechanisms may underlie its effects on aging. Glycine is abundant in collagen, a building block for glutathione, a precursor to creatine, and an acceptor for the enzyme glycine N-methyltransferase (GNMT). A review of the literature strongly implicates GNMT, which clears methionine from the body by taking a methyl group from S-adenosyl-L-methionine and methylating glycine to form sarcosine. In flies, Gnmt is required for reduced insulin/insulin-like growth factor 1 signaling and dietary restriction to fully extend lifespan. The geroprotector spermidine requires Gnmt to upregulate autophagy genes and boost longevity. Moreover, the overexpression of Gnmt is sufficient to extend lifespan and reduce methionine levels. Sarcosine, or methylglycine, declines with age in multiple species and is capable of inducing autophagy both in vitro and in vivo. Taken all together, existing evidence suggests that glycine prolongs life by mimicking methionine restriction and activating autophagy." (abstract)

"...Supplementation with both glycine (100 mg/kg/day) and N-acetylcysteine (100 mg/kg/day) – two building blocks of glutathione – was recently shown to improve biomarkers relevant to several hallmarks of aging in a cohort of 24 older adults. As an example relevant to the hallmark chronic inflammation, this supplementation regimen decreased levels of pro-inflammatory cytokines in plasma ..." (from Sect 3.4)

Glycine and aging: Evidence and mechanisms. Ageing Research Reviews. 2023;87:101922.

https://www.scienced...000818?via=ihub

Great feedback Kevnzworld. Thank you. Recollect you on this Forum since the time I began following it.

Functional decline of physiological systems during ageing leads to age-related diseases. Dietary glycine increases healthy lifespan in model organisms and might decrease inflammation in humans, suggesting its geroprotective potential. This review summarises the evidence of glycine administration on the characteristics of eleven physiological systems in adult humans. Databases were searched using key search terms: ‘glycine’, ‘adult’, ‘supplementation’/ ‘administration’/ ‘ingestion’/ ‘treatment’. Glycine was administered to healthy and diseased populations (18 and 34 studies) for up to 14 days and 4 months, respectively. The nervous system demonstrated the most positive effects, including improved psychiatric symptoms from longer-term glycine administration in psychiatric populations. While longer-term glycine administration improved sleep in healthy populations, these studies had small sample sizes with a high risk of bias. Larger and long-term studies with more robust study designs in healthy populations to examine the effects of glycine administration on preventing, delaying or reversing the ageing process are warranted.

 Screenshot 2023-11-17 101108.png   223.76KB   0 downloads

Soh J, Raventhiran S, Lee JH, et al. The effect of glycine administration on the characteristics of physiological systems in human adults: A systematic review. GeroScience. Published online October 18, 2023.
https://link.springe...357-023-00970-8

Another reason to consider glycine supplementation: osteoarthritis (OA)

Surely because I am older that many of you here and my knees hurts sometime. OA is so common, so typical of aging. The Aging enemy is always there, its not forgiving and not forgetting you .......

Paz-Lugo P de, Lupiáñez JA, Meléndez-Hevia E. High glycine concentration increases collagen synthesis by articular chondrocytes in vitro: acute glycine deficiency could be an important cause of osteoarthritis. Amino Acids. 2018;50(10):1357.