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Glycine, should we be taking it?

scientists reverse aging in human cell lines and give theory of aging

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#61 Skyguy2005

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Posted 27 July 2015 - 02:38 AM

 

http://www.sciencedi...304416580901415

 

This study concluded not all amino acids inhibit autophagy equally. I couldn't get the full test. I am not clear how many were tested. Neither glycine nor methionine were mentioned.  Of course "isolated rat hepatocytes" might not be a good indicator for an entire human.

 

Does amino acid restriction (all amino acids, not just methionine) not increase autophagy? I saw a study where all amino acids inhibit autophagy (even glycine). Given the prominent role of autophagy, proteasome, and protein tidying-up does this not implicate *protein* restriction, especially methionine and cysteine, as the best strategy to inhbit aging? 

 

I'll try and get this study again. Thanks for the replies btw.

 

 

I found it hard to interpret the results. What do all the +s and -s mean?



#62 Skyguy2005

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Posted 27 July 2015 - 02:49 AM

 

What precisely can the extension of life be due to if it is not protein restriction and hence autophagy/proteasome related? It certainly cannot be to do with the protein nature, or ratio, of almonds/beef. They contain about the same amount of protein (although perhaps almonds contain more calories per protein content)

 

Not all protein is created equal.  They're all made out of amino acids, but the amino acids are present in different ratios in different proteins, and different amino acids have different effects on health and lifespan.  So in fact, the nature of the protein is very important.  The message of this thread is that sufficient amounts of Gly are a way to get the effects of Met restriction.  We know that Met restriction increases lifespan in experimental animals, but it's hard to restrict Met and eat a normal diet.  Much easier to supplement Gly.

 

 

Methionine restriction seems promising.

 

Glycine addition is less convincing to me, I'm trying to find more studies supporting it. Autophagy and proteasome, protein degradation etc. seems so important that I'd like to know what its effects are on that mechanism.

 

Caloric restriction, isocaloric (equal) amounts of everything being restricted, is due to autophagy though in large part. This by definition does not involve changing the ratio of Met/Gly or anything like that. But it extends lifespan!

 

I've seen some evidence that the lifespan of the controls in the Met/Gly study wasn't that long. However, there does seem to be something in it as several studes link it to longevity. It seems boring saying "more studies are needed". Ho hum.
 



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#63 Phoenicis

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Posted 27 July 2015 - 10:02 AM

Regarding your question about the difference between restricting methioine and other amino acids; this study shows more benefits for methioine restriction over other AAs:

Personally, I am sceptical that caloric restriction sans protein restriction would work in humans. The first study emphasizes the strong impact that protein has on humans vesus mice:

I have also found some interesting new information on folate, but in order to not derail this thread any further I'll start a new topic soon! I do agree that evidence for glycine could be better, but the pace of research can be quite slow. We did mangage to dig up a good amount of information in this thread and I do see improvements in my health after taking glycine regularly. Until new studies are published I'm not sure there's much more to analyze?


Edited by Phoenicis, 27 July 2015 - 10:18 AM.

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#64 david ellis

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Posted 28 July 2015 - 09:09 PM

Glycine - should we be taking it?   I found another reason for taking it.   Glycine supports correction of Metabolic syndrome.

 

 

 

 

 

 

 

 

 

 

 

 

   

 

 


Edited by david ellis, 28 July 2015 - 09:10 PM.

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#65 Darryl

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Posted 28 July 2015 - 10:24 PM

Glycine - should we be taking it?   I found another reason for taking it.   Glycine supports correction of Metabolic syndrome.

 

There's certainly enough material touching on glycine and elements of metabolic syndrome to merit its own study category. Some appeared in my prior post under inflammation.

 

Muller, WA et al. 1975. Effect of alanine and glycine on glucagon secretion in postabsorptive and fasting obese manThe Journal of Clinical Endocrinology & Metabolism40(3), 418-425.

El Hafidi M et al. 2004. Glycine intake decreases plasma free fatty acids, adipose cell size, and blood pressure in sucrose-fed ratsAmerican Journal of Physiology-Regulatory, Integrative and Comparative Physiology287(6), R1387-R1393.

Gameiro A et al. 2005. The neurotransmitters glycine and GABA stimulate glucagon‐like peptide‐1 release from the GLUTag cell lineThe Journal of physiology569(3), 761-772.

Alarcon-Aguilar FJ et al. 2008. Glycine regulates the production of pro-inflammatory cytokines in lean and monosodium glutamate-obese mice.European journal of pharmacology599(1), 152-158.

Cruz M et al. 2008. Glycine treatment decreases proinflammatory cytokines and increases interferon-γ in patients with Type 2 diabetesJournal of endocrinological investigation31(8), 694-699.

Garcia-Macedo R et al. 2008. Glycine increases mRNA adiponectin and diminishes pro-inflammatory adipokines expression in 3T3-L1 cellsEuropean journal of pharmacology587(1), 317-321.

Almanza-Perez JC. 2010. Glycine regulates inflammatory markers modifying the energetic balance through PPAR and UCP-2Biomedicine & Pharmacotherapy64(8), 534-540.

Bruns H et al. 2011. Glycine and taurine equally prevent fatty livers from Kupffer cell‐dependent injury: an in vivo microscopy studyMicrocirculation18(3), 205-213.

Blancas-Flores G et al 2012. Glycine suppresses TNF-alpha-induced activation of NF-κB in differentiated 3T3-L1 adipocytesEuropean journal of pharmacology689(1), 270-277.

 

Wu HW et al. 2012. Effects of glycine on phagocytosis and secretion by Kupffer cells in vitroWorld journal of gastroenterology: WJG18(20), 2576.

Díaz-Flores M et al. 2013. Oral supplementation with glycine reduces oxidative stress in patients with metabolic syndrome, improving their systolic blood pressureCanadian journal of physiology and pharmacology91(10), 855-860.

Li C et al. 2013. Regulation of glucagon secretion in normal and diabetic human islets by γ-hydroxybutyrate and glycineJournal of Biological Chemistry288(6), 3938-3951.

Lustgarten MS et al. 2013. Serum glycine is associated with regional body fat and insulin resistance in functionally-limited older adultsPloS one8(12), e84034.

Noe SA et al. 2013. Effect of glycine on protein oxidation and advanced glycation end products formationJournal of Experimental & Clinical Medicine5(3), 109-114.

Ruiz-Ramirez A et al. 2014. Glycine restores glutathione and protects against oxidative stress in vascular tissue from sucrose-fed ratsClinical Science126(1), 19-29.

Tastesen HS. 2014. Scallop protein with endogenous high taurine and glycine content prevents high-fat, high-sucrose-induced obesity and improves plasma lipid profile in male C57BL/6J miceAmino acids46(7), 1659-1671.

McCarty MF & DiNicolantonio JJ. 2014. The cardiometabolic benefits of glycine: Is glycine an ‘antidote’to dietary fructose?Open Heart1(1), e000103.

 

Kupffer cells are the liver's innate immune system, and their inflammatory cytokine and superoxide production is implicated in much of the injury of non-alcoholic fatty liver disease and hepatic fibrosis.

Adiponectin is the adipose secreted hormone that improves insulin sensitivity, reduces gluconeogenesis and inflammation, and speeds glucose & triglyceride clearance when body fat is low.  

Glucagon like peptide-1 is the intestinal enteroendocrine secreted hormone that promotes beta cell mass, insulin secretion and sensitivity, and increases satiety/decreases food intake.


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#66 Phoenicis

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Posted 29 July 2015 - 04:01 AM

Thanks again Darryl, you truly are a research prodigy, those are some very interesting studies. Just when I thought we were running out of cool studies on glycine to read.

 

Here's a link to thenew thread on folate, MR and Metformin if anyone is interested: http://www.longecity...life-extension/


Edited by Phoenicis, 29 July 2015 - 04:03 AM.


#67 david ellis

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Posted 29 July 2015 - 07:44 PM

Darryl, I pick up a leaf, you pick up trees. Thanks for your post.


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#68 Phoenicis

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Posted 10 August 2015 - 01:51 PM

PPAR-alpha agonists upregulate arginine, glycine and serine de novo synthesis:


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#69 Castiel

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Posted 23 August 2015 - 05:52 AM

glycine stimulates production of Growth Hormone.... Having more Growth Hormone is always a bad thing in my book.. So no thanks! 

In rodents, as mentioned by others previously on this thread, glycine supplementation appears to function as a calorie restriction mimetic and lengthens lifespan by 30%.

 

Of course, randomly adding growth hormone for no reason is not good.   But if the body is rejuvenating and increasing its own production as a result, than it is not bad, especially if we see that other lifeforms gain life-extension and disease resistance as well.

 

 

 

All or most of the SENS types of damage would still be there, and would still need to be fixed. 

 

This assumes that it would not be reverted.   It is said that there are quality control mechanisms for mitochondria, human neurons can keep their high energy requirements that necessitate lots of it from high functioning mitochondria up to the age of 122.   Older animals can keep neurons working for centuries, and in them there is no evidence of mitosens solutions evolving, afaik(e.g. bowhead whale), if there is evidence of such that would change my viewpoint.   What that means is that either existing mechanisms, upregulation of existing mechanisms, or similar quality control mechanisms are sufficient to indefinitely maintain mitochondria quality.   Any age related accumulation of mutations could very well simply be due to age related dysfunction of quality control mechanisms.

 

Molecular garbage that leads to diseases like Alzheimers and other neurodegenerative conditions have been vinculated to deficiency of garbage export mechanisms via the glymphatic system of the brain.   Even a partially functioning glymphatic system enables at least 122 years(lifespan over 40 years over what most humans reach) of dementia free brain.   A fully rejuvenated glymphatic system might keep things going indefinitely in the brain.   Cells can even export organelles,  it remains to be seen whether the accumulation of molecular garbage elsewhere is due to failure to recycle or failure to export, the rest of the body has the lymphatic system and it ages too.    In any case it is in the brain where cells are amongst the most metabolically demanding(generating lots of garbage) and where cells do not divide(which dilutes garbage) that one would expect garbage to be a problem, yet as said even with aging garbage removal system the brain can last for over 122 years dementia free in some.   That is what is easiest is the export of garbage out, like we do in our society, much easier than recycling it all, any accumulation that occurs might very well simply be the result of aging garbage exporting mechanisms.

 

Nuclear mutations are a non-issue.  Parent to child about 50 mutations pass on, some of the fastest reproducing cells(think it was blood stem cells) have only about 400 mutations in a centenarian negligible for a genome Billions of bases wide.   And also iirc, sperm producing stem cells are also quite rapidly reproducing, and while there is increased disease chance in offspring, perfectly healthy perfectly young offspring is possible from very old men.

 

Cell depletion would also be addressed in most of the body by restoring telomere length to stem cell pools and rejuvenating niches.   In the brain it is said that in healthy old adults there is no cell loss in some of the examined areas, only in diseased old adults does it occur, and the thought that we all lost cells is said to be the result of averaging diseased with nondiseased aging populations.

 

 

 

 

This ignores the fact that predation and infection is rampant in nature, thus animals have never needed any help in order to die. .... Thus the idea of an evolved aging program is completely at odds with what we observe in nature. 

http://io9.com/are-l...tion-1710634703

It has been seen that aging populations can outcompete immortal populations in evolutionary simulations.

 

 

The reality is that we've observed populations which have indeed bred like mad and collapsed their food supply, the species later suffering catastrophic collapse itself if not going extinct.   Predation is nice, but tell me who is going to be more likely to succumb to it, the young? the less fit? or the fittest?   The reality is that the fittest prey or predator will be unlikely to succumb to predation or disease barring aging all the others will be much likelier to succumb first, this will lead to a loss of genetic diversity compromising population fitness, and for the same reasons things like incest avoidance exist, a process like aging is necessary to keep populations at viable size and preserve genetic diversity.


Edited by Castiel, 23 August 2015 - 05:53 AM.

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#70 wolfeye

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Posted 30 August 2015 - 05:57 PM

erg-log  speculates in using L-glycine alpha-ketoglutarate

 

http://www.ergo-log....supplement.html


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#71 resting

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Posted 07 September 2015 - 08:46 PM

I do not know if this has been flagged but seems interesting.

 

Intravascular Absorption of Glycine Irrigating Solution during Shoulder Arthroscopy: A Case Report and Follow-up Study

 

http://anesthesiolog...ticleid=1948943

 

 


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#72 niner

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Posted 07 September 2015 - 09:44 PM

Intravascular Absorption of Glycine Irrigating Solution during Shoulder Arthroscopy: A Case Report and Follow-up Study
http://anesthesiolog...ticleid=1948943

This is pretty different than what we're doing.  Here they used 18 liters(!) of 1.5% glycine solution as a surgical irrigant.  The patient had a significant amount of glycine in their system, but it looks like the problem was all the water that came along with it, because they were seriously hyponatremic.  None of that can happen if you're just taking glycine orally.



#73 resting

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Posted 07 September 2015 - 09:47 PM

Looks like Vitamin C can enhance absorption.

 

http://static-conten...0803333/001.png


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#74 Phoenicis

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Posted 11 September 2015 - 01:09 PM

I just wanted to say that I am seeing really great benefits from taking 10g glycine/day. I have seen improvements to my psoriais and my skin overall. The effect is very noticeable and I'm glad I gave this a try.

 

One thing I'm still wondering about is the long term impact that large doses of glycine (10-20g) / day would have on the liver and kindneys. I am also taking metformin (1g), nicotinamide (1-1.5g) and concerta (28mg) daily, so I hope I'm not overloading my system?

 

Here's some interesting recent studies I came accross:

 

 


Edited by Phoenicis, 11 September 2015 - 01:17 PM.

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#75 docmaas

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Posted 15 September 2015 - 12:58 AM

I did a little blood sugar check today with glycine.  I had a fair amount of watermelon only this morning.  My fasting blood glucose was 123.  About 30 minutes after eating the watermelon it had risen to 143.  At that time I took 5-7 gms of glycine in carbonated water with lime flavoring.  From that point on I measured blood glucose about every 30 minutes until it bottomed out and started to rise again. Here are the numbers:

 

8:22 a.m.  fasting 123

12:03 p.m.  143  (30-45 minutes after eating watermelon)

12:29 p.m.  136

1:06 p.m. 114

1:34 p.m.  97

2:01 p.m. 93

2:29 p.m. 85

3:00 p.m. 89

3:30 p.m. 95

4:15 p.m. 90  (ate some meat and a vegetables 3-4 tsp max)

5:53 p.m. 100 (no additional food)

 

When I return home next week I will repeat this beginning with 24hr fasting numbers for 3-4 hours followed by a fixed amount of some kind of measurable carbs.  I may add some taurine to the mix as well.  I'm also seriously considering getting some benagene and trying that as well.  I did a significant amount of research on it today including locating the 1968 Japanese study which I will post on the "wow" benagene thread hopefully tonight but if not, not until next week.

 

This experiment is a more methodical observation of my experience with glycine over the last couple of weeks.  Taking it causes very quick drops in blood sugar but over a duration of 2-3 hours the impact fades.  I generally take 15-20 gms a day and am eating significantly more carbs than I have allowed myself prior to starting glycine.  I've continued my exercise regimen mostly with 2-2 mile open water ocean swims.  I'm also taking mitoq and niagen daily and vitamin D, A and baby aspirin at night.


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#76 Logic

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Posted 15 September 2015 - 04:41 PM

Any consensus on optimal dosage?


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#77 docmaas

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Posted 15 September 2015 - 05:25 PM

I came to the 5gm per dose from a trial I read iirc.  I tend to go bigger if the carb load is larger.  From what research is available I think there is no danger from up to 20gm/day and perhaps much higher. 

 

I think that a low dose lozenge could be designed so that a diabetic could more or less keep the amount of glycine available according to what they are consuming.  It seems to be both load and time constrained but keeping a close eye on blood glucose will allow one to keep the levels low enough < 130-140 to avoid the permanent damage that comes with glycation.  I personally try to stay below 140 but do occasionally exceed that level.  I ususally take 5-6 gms with every sit down meal.

 

I don't think glycine used in this way is yet a widespread technique.  There is research to support it but most researchers don't have a lot of patients and most practitioners don't have time to keep up with all the viable possibilities.  It seems to work so well though that I expect it will grow in popularity.

 

The best aspect for me is a very minimal gastric distress impact.  In fact I think I'm pretty much over what there was after just a couple of weeks and worst of it was simply an almost immediate need to hit the head but only once.  

 

I carry 1gm caps with me for when I need to get a dose while away from home.

 

Mike


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#78 aza

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Posted 16 September 2015 - 03:17 PM

this seems to be interesting http://www.cell.com/...77?showall=true

Serine, but Not Glycine, Supports One-Carbon Metabolism and Proliferation of Cancer Cells

"Although serine and glycine can be interconverted and either might be used for nucleotide synthesis and one-carbon metabolism, we show that exogenous glycine cannot replace serine to support cancer cell proliferation. Cancer cells selectively consumed exogenous serine, which was converted to intracellular glycine and one-carbon units for building nucleotides. Restriction of exogenous glycine or depletion of the glycine cleavage system did not impede proliferation. In the absence of serine, uptake of exogenous glycine was unable to support nucleotide synthesis. Indeed, higher concentrations of glycine inhibited proliferation. Under these conditions, glycine was converted to serine, a reaction that would deplete the one-carbon pool. Providing one-carbon units by adding formate rescued nucleotide synthesis and growth of glycine-fed cells. We conclude that nucleotide synthesis and cancer cell proliferation are supported by serine—rather than glycine—consumption."

 


Edited by aza, 16 September 2015 - 03:18 PM.

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#79 niner

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Posted 17 September 2015 - 03:45 AM

this seems to be interesting http://www.cell.com/...77?showall=true

Serine, but Not Glycine, Supports One-Carbon Metabolism and Proliferation of Cancer Cells

"Although serine and glycine can be interconverted and either might be used for nucleotide synthesis and one-carbon metabolism, we show that exogenous glycine cannot replace serine to support cancer cell proliferation. Cancer cells selectively consumed exogenous serine, which was converted to intracellular glycine and one-carbon units for building nucleotides. Restriction of exogenous glycine or depletion of the glycine cleavage system did not impede proliferation. In the absence of serine, uptake of exogenous glycine was unable to support nucleotide synthesis. Indeed, higher concentrations of glycine inhibited proliferation. Under these conditions, glycine was converted to serine, a reaction that would deplete the one-carbon pool. Providing one-carbon units by adding formate rescued nucleotide synthesis and growth of glycine-fed cells. We conclude that nucleotide synthesis and cancer cell proliferation are supported by serine—rather than glycine—consumption."

 

I'm very glad to hear that.  I was concerned, as there seems to be a need for both gly and ser to produce 1 carbon units in cancer cells, in order to keep up with all the synthetic needs that fast-growing cells have.  With people looking at enzymes in the glycine synthetic pathway as drug targets, I was beginning to wonder if eating gobs of exogenous Gly was such a great idea. 


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#80 docmaas

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Posted 20 September 2015 - 10:28 PM

regarding glucagon and ketones.  I've been consuming up to 20gm of glycine/day in an effort to reduce my blood glucose.  It works very well.  Interestingly as a part of this effort I have been freely consuming carbs but occasionally I have detected a slight ketone odor when urinating.  I found this strange since my carb consumption is higher than it has been for some time but from what this says it may be that if the carbs are on the low side the excess glucagon may be causing the ketone formation.  

 

I don't know if this is a reasonable guess or not and I guess I could test for it with ketone stix but it seemed like this might be a possibility.  

 

Mike

 

I think I may have found some information that explains the decrease in IGF-1 levels in Brind, J. et al. (2011)'s glycine supplemented rats. It appears that glycine stimulates glucogen production, but this effect is opoposed by also ingesting glucose:

  • Gannon, M. et al. (2002). The metabolic response to ingested glycine. Am J Clin Nutr. vol. 76 no. 6 1302-1307

It should also be noted that Brind, J et al. (2011) noted decreases in glucose and insulin, wheras Gannon, M. et al. (2002) found that glycine supplementation increased insulin modestly, but not glucose. Glycine also delayed increases in insulin after glucose administration and modestly lowered the overall amount of insulin. Gannon, M. et al (2002) note that glycine accelarated glucose clearance.

 

This study is very interesting:

  • McCarty, MF. (1999).Vegan proteins may reduce risk ofcancer, obesity, and cardiovasculardisease by promoting increased glucagon activity. Medical Hypotheses(1999)53(6), 459–485

McCarty, MF. (1999). argues that increased glucagon production has insulin sensitizing properties. Essentally he argues that glucagon has the following impact on the liver:

  1. increased CaMP activity and PKA
  2. suppression of anabolic activities
  3. increased fatty acid oxidation, ketone production
  4. upregulation of IGFBP-1, which sequesters unbound insulin like growth factor (IGF-1) and blocks its activity.

While reductions in IGF-1 sounds good, inductions of CaMP and PKA would seem bad, since Cheng, C. et al. (2014) seem to show that the beneficial effects of prolonged fasting on stem cell regeneration are blocked by PKA, as well as IGF-1. Nonetheless increased glucagen could explain why Brind, J. et al. (2011)'s glycine supplemented rats had low IGF-1 levels.

 

The question that remains for me is how much glycine is best for making MR more efficient, while not stimulating GH and PKA excessively? It also appears that glucose should be avoided, as this would according to Gannon, M. et al. (2002) attenuate glucogen production.

 


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#81 docmaas

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Posted 20 September 2015 - 10:37 PM

I believe Larrgus is referring to Dr. Joel Brind:  http://www.proglyta.com/blog/

 

I just encountered him last night.  He seems to be on the leading edge of commercializing glycine.  However, he is very open about saying there is no need to buy either of his formulations and that glycine can be bought as a pure protein or as gelatin as well as in his products which I find commendable.  He also not a physician but a biochemist.

 

Mike 

If you are interested go to youtube and search for glycine and inflammation. There is a 3 part video of a doctor who talks about

glycine, methionine and inflammation. According to him 8 grams is the best dose and he said that the reason for too much inflammation

is because people lack glycine because they do not eat whole meat anymore only the muscle but no cartilage and because of this they lack

glycine. He also talks about glycine and heart diseases. It sounds as if glycine is a miracle substance which fixes all kinds of issues caused

by inflammation.

 



#82 docmaas

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Posted 21 September 2015 - 12:19 AM

Thanks to both of you and again to you Niner for the comment on the  surgical irrigation.  I had also encountered this article and at least one other on the same phenomenon.  I believe that glycine solution is no longer used for a surgical irrigant.

 

Mike

 

this seems to be interesting http://www.cell.com/...77?showall=true

Serine, but Not Glycine, Supports One-Carbon Metabolism and Proliferation of Cancer Cells

"Although serine and glycine can be interconverted and either might be used for nucleotide synthesis and one-carbon metabolism, we show that exogenous glycine cannot replace serine to support cancer cell proliferation. Cancer cells selectively consumed exogenous serine, which was converted to intracellular glycine and one-carbon units for building nucleotides. Restriction of exogenous glycine or depletion of the glycine cleavage system did not impede proliferation. In the absence of serine, uptake of exogenous glycine was unable to support nucleotide synthesis. Indeed, higher concentrations of glycine inhibited proliferation. Under these conditions, glycine was converted to serine, a reaction that would deplete the one-carbon pool. Providing one-carbon units by adding formate rescued nucleotide synthesis and growth of glycine-fed cells. We conclude that nucleotide synthesis and cancer cell proliferation are supported by serine—rather than glycine—consumption."

 

I'm very glad to hear that.  I was concerned, as there seems to be a need for both gly and ser to produce 1 carbon units in cancer cells, in order to keep up with all the synthetic needs that fast-growing cells have.  With people looking at enzymes in the glycine synthetic pathway as drug targets, I was beginning to wonder if eating gobs of exogenous Gly was such a great idea. 

 

 



#83 docmaas

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Posted 21 September 2015 - 07:22 AM

Glycine, the apple and the pear?

 

subcutaneous thigh fat correlates positively with glycine levels while IM thigh fat and abdominal adiposity correlate negatively.   Seems to be confirming the apple and pear body types but there is a lot more confirmation of metabolite and metabolic syndrome alignment.  

 

This is a metabolic profile study of metabolites: 

The objectives of the current study were to characterize the association between mid-thigh intermuscular and subcutaneous adipose tissue (IMAT, SCAT, respectively) and, abdominal adiposity with the serum metabolite profile, to identify significant metabolites as further associated with the homeostasis model assessment of insulin resistance (HOMA-IR), and, to develop a HOMA-IR associated metabolite predictor set representative of regional adiposity, in 73 functionally-limited (short physical performance battery ≤10; SPPB) older adults (age range, 70–85 y).

 

Found here: http://www.plosone.o...resentation=PDF

 

 

Stepwise Regression Identifies Glycine as a HOMA-IR Associated Predictor of IMAT and Abdominal Adiposity To determine a HOMA-IR associated metabolite predictor set representative of IMAT and abdominal adiposity, multivariateadjusted stepwise regression was used (Table 5). Although sex, age and total fat were found to explain 36.0% of the variability inherent in IMAT, the combination of glycine and 2-hydroxyisobutyrate were found to explain an additional 15%, for a total adjusted R2 of 51%. Similarly, although the combination of sex, age and total fat explained 33.4% of the variation inherent in abdominal adiposity, glycine was found to explain an additional 8%, for a total R2 of 41.4%. It is important to note that use of stepwise regression identified glycine as a negative predictor of both IMAT and abdominal adiposity. Furthermore, because glycine was the only metabolite significantly positively associated with thigh subcutaneous adipose tissue, stepwise regression for SCAT was not determined. To assess internal validity of the results obtained from stepwise regression bootstrapping was performed. 200 bootstrap samples were created, and the variables that were found to be significant in the stepwise models were forced in. The median R2 across the bootstrap replicates for the IMAT and abdominal adiposity models was found to be 0.55 (95% CI 0.38, 0.68) and 0.45 (95% CI 0.27, 0.57), respectively, which is similar to the model performance found in the stepwise models. Bootstrapbased 95% CI for the metabolites identified using stepwise regression are shown in Table 5

 

And a bit further on:  

 

Multivariable-adjusted stepwise regression identified glycine as a HOMA-IR associated predictor of both IMAT and abdominal adiposity. In addition, glycine was the only metabolite to reach statistical significance in its association with SCAT, thereby identifying glycine as a HOMA-IR associated marker of multiple adipose-containing compartments. Because glycine has previously been shown to reduce plasma insulin and fat mass in rodents [33,34], future studies aimed at testing the hypothesis that glycine supplementation may reduce fat mass and improve insulin sensitivity in glycine-deficient functionally-limited older adults are of interest.

 

There is much more along the same lines.

 

Mike


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#84 docmaas

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Posted 24 September 2015 - 07:33 AM

33% life extension for rats fed 8%-12% glycine!

http://www.fasebj.or...Abstracts/528.2

 

Tantalizing but haven't found the original paper.  The principal author, Joe Brind, has a blog though:  http://www.proglyta.com/blog/

 

Mike


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#85 tunt01

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Posted 24 September 2015 - 09:13 PM

33% life extension for rats fed 8%-12% glycine!

http://www.fasebj.or...Abstracts/528.2

 

Tantalizing but haven't found the original paper.  The principal author, Joe Brind, has a blog though:  http://www.proglyta.com/blog/

 

Mike

 

Interesting.  That's a helluva lot of glycine.

 

It says 88 weeks on an F344 mouse for control.  That seems low to me.  Here is another F344 study w/ Metformin and CR for comparison.

 

88 / 52 = 1.6923 yrs   CONTROL (GLYCINE STUDY)

113 / 52 = 2.1731 yrs (GLYCINE)

796.4 / 365 = 2.1819 yrs CONTROL (CR/MET STUDY)

866.5 / 365 = 2.374 yrs  CR (CR/MET STUDY)

814.5 / 365 = 2.2315 yrs MET (CR/MET STUDY)

 

Maybe he did something to the controls and then got an average result from Glycine?  Or maybe just the methionine content was so detrimental/high ?  I'm not sure what a normal methionine as % of caloric intake for a mouse, or if that is even comparable to a human.


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#86 docmaas

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Posted 24 September 2015 - 09:32 PM

Thanks for pulling in that additional data.  Could be lab conditions or a bad batch of mice or bad protocol.  Who knows?  I've written to Brind on his blog to see if I can get the whole document.    I'll post further info if I get it.

 

I've been reading his series on glycine and inflammation.  I don't know nearly enough to comment on how reasonable his ideas are but I am getting a clearer picture of the methionine/homocysteine/methylation process.  

 

He seems to have a somewhat unorthodox view of what causes what and gives  the current understanding of in vogue alternative medicine (Yasko et al) methylation issues short shrift. Given the huge amount of interest and effort and the paucity of reports of success around methylation he may be on to something.

 

Mike

 

33% life extension for rats fed 8%-12% glycine!

http://www.fasebj.or...Abstracts/528.2

 

Tantalizing but haven't found the original paper.  The principal author, Joe Brind, has a blog though:  http://www.proglyta.com/blog/

 

Mike

 

Interesting.  That's a helluva lot of glycine.

 

It says 88 weeks on an F344 mouse for control.  That seems low to me.  Here is another F344 study w/ Metformin and CR for comparison.

 

88 / 52 = 1.6923 yrs   CONTROL (GLYCINE STUDY)

113 / 52 = 2.1731 yrs (GLYCINE)

796.4 / 365 = 2.1819 yrs CONTROL (CR/MET STUDY)

866.5 / 365 = 2.374 yrs  CR (CR/MET STUDY)

814.5 / 365 = 2.2315 yrs MET (CR/MET STUDY)

 

Maybe he did something to the controls and then got an average result from Glycine?  Or maybe just the methionine content was so detrimental/high ?  I'm not sure what a normal methionine as % of caloric intake for a mouse, or if that is even comparable to a human.

 

 



#87 docmaas

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Posted 24 September 2015 - 11:40 PM

More Glycine supplementation experiment results.  Mostly using this model:  http://ajcn.nutritio.../76/6/1302.full  (Note these are all non diabetic subjects so there are no elevated glucose measurements and the peak in blood glucose occurs earlier and the return to normal is faster.)  The patterns are similar to my experience just offset and faster.  Interestingly my peak with 3 tsp (@15 g) of glycine was more similar to that seen in this study.  hard to draw and hard and fast conclusions on a single event though.

 

I've been approaching the use of glycine as a daily/ad hoc blood sugar lowering agent.  Most of the research seems to be oriented around longer periods and focuses on lowering hba1c through a fixed amount of glycine per day usually dosed tid rather than the peaks and valleys of daily carbohydrate intake.  I want to know if I can eat some ice cream or cookies with contemporaneous glycine dosing and avoid going into a high blood glucose state where glycation becomes an issue.  I think the most damage from t2 diabetes comes from glycation and if one can keep blood sugar low enough (<130-140) to largely avoid glycation the disease itself is much less threatening.  

 

I've been doing glycine for about 2.5 weeks.  I've found that when I do check blood sugar and find it high that a quick 5 grams or so of glycine brings it down within 30-60 minutes or so.   See my watermelon post above. 

 

In the three sessions below I took varying amounts of glycine (4.68 g /tsp) with 6 usp tsp (@25 g) of sucrose and measured the blood sugar before and during the next few hours until blood sugar fell below 100.  I did this in the morning after consuming two cups of black coffee.  The fasting blood sugar is recorded before consuming the glycine/sucrose blend.  I simply measured out the sugar and glycine dissolved them in warm water and drank them quickly.

 

I did not do a sucrose only control as I felt it unnecessary and don't need to experience high blood glucose any more than I already do.

 

Additional Glycine appears to lower the peak and reduce the total time of elevated glucose.  I calculated the total time as the sum of the differences between glucose and 100 (arbitrary floor) until glucose fell to < 100

 

9/22/2015 glucose with glycine

6 tsp sugar 1 tsp glycine

fasting 91

MIN GLUCOSE

10 102

20 120

30 129

40 136

50 136

60 151

70 147

80 137

90 143

100 132

110 121

120 114

150 97

180 88

TOTAL TIME Glucose > 100 = 367

 

9/23/2015 glucose with glycine

6 tsp sugar 2 tsp glycine

fasting 97

MIN GLUCOSE

10 109

20 106

30 110

40 137

50 126

60 146

70 142

80 133

90 131

110 113

130 106

150 96

TOTAL TIME Glucose > 100 = 278

 

9/24/2015 glucose with glycine

6 tsp sugar 3 tsp glycine

fasting 100

MIN GLUCOSE

10 92

20 115

30 141

40 140

50 136

60 137

70 137 

80 124

90 112

110 103

130 101

150 95

TOTAL TIME Glucose > 100 = 250


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#88 resveratrol_guy

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Posted 05 October 2015 - 05:09 AM

9/22/2015 glucose with glycine

6 tsp sugar 1 tsp glycine

fasting 91

MIN GLUCOSE

10 102


150 97

180 88

TOTAL TIME Glucose > 100 = 367

 

9/23/2015 glucose with glycine

6 tsp sugar 2 tsp glycine

fasting 97

MIN GLUCOSE

10 109


150 96

TOTAL TIME Glucose > 100 = 278

 

9/24/2015 glucose with glycine

6 tsp sugar 3 tsp glycine

fasting 100

MIN GLUCOSE

10 92


150 95

TOTAL TIME Glucose > 100 = 250

 

Thanks for this meticulous data. It really seems as though the time required to return to 95-97 does not vary with the glycine dose, given a constant dose of sugar. So it sort of sounds to me as though glycine is acting more as a fixed-threshold signalling molecule than an ordinary amino acid, as one would normally expect highly bioavailable amino acids to raise insulin in a manner monotonic with the amount ingested, just as it would with protein powder. In that case, presumably, consuming more protein would cause plasma glucose to drop faster due to a higher insulin spike. But because that didn't happen here in any obvious way, I would say that your insulin response to the various doses of glycine was essentially constant.

 

I realize it sounds totally nuts to think of protein building blocks as metabolic signalling molecules analogous to various stem cell activators, but your data only adds to all of the animal studies above which suggest that this may be the case. But that's the whole point: it's nuts. As in, glycine says: "OMG there's no big game to hunt! We're stuck here picking nuts from the trees all day just to stay alive. We need to turn on the starvation defense mechanisms, e.g. SIRT1 etc. Throttle down the sex drive because there's not enough protein to produce offspring;" whereas methionine consuption signals exactly the opposite.

 

Why else would neurons and so many other cells have receptors for this isolated amino acid? Looking at it another way, I think there's a good chance that rat success implies human success because presumably these receptors go way way back in evolutionary history; after all, glycine is about as simple as it gets in biology.

 

I'm also pleased at the relatively dose-agnostic nature of your results, as it means that I can expect more benefits from less (8g?) glycine per day. That's really important to me because I'm trying to restrict protein to the maximum extent possible, largely because I believe niner's conjecture that equilibrium considerations would imply that low protein consumption would stimulate the recycling of junk protein via autophagy. (No wonder the Alzheimer's rate in France is so high. They eat meat and cheese like there's no tomorrow. The cheese protects their arteries and prevents cardiovascular failures on account of vitamin K2, while at the same time suppressing neuronal autophagy, allowing brain plaques to accrue unabated on account of the high methionine content.)

 

For similar reasons, I would also expect methionine restriction to upregulate macroautophagy, i.e. intercellular junk protein depletion via microglia (in the brain) or macrophages (elsewhere).  (Alpha-synuclein clearance comes to mind, but I don't know enough about that to comment.) That would be really exciting because it's these intercellular junk proteins which tend to be the heaviest and thus the most resistent to degradation, e.g. phosphotau aggregates weighing 100+ KDa. But I have no evidence that this is in fact the case. :(


Edited by resveratrol_guy, 05 October 2015 - 05:15 AM.

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#89 Darryl

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Posted 05 October 2015 - 05:30 AM

Caldow MK et al. 2015. Glycine supplementation during calorie restriction accelerates fat loss and protects against further muscle loss in obese miceClinical Nutritionhttp://dx.doi.org/10...lnu.2015.08.013

 

Calorie restriction (CR) reduces co-morbidities associated with obesity, but also reduces lean mass thereby predisposing people to weight regain. Since we demonstrated that glycine supplementation can reduce inflammation and muscle wasting, we hypothesized that glycine supplementation during CR would preserve muscle mass in mice.

 
High-fat fed male C57BL/6 mice underwent 20 days CR (40% reduced calories) supplemented with glycine (1 g/kg/day; n = 15, GLY) or l-alanine (n = 15, ALA). Body composition and glucose tolerance were assessed and hindlimb skeletal muscles and epididymal fat were collected.
 
Eight weeks of a high-fat diet (HFD) induced obesity and glucose intolerance. CR caused rapid weight loss (ALA: 20%, GLY: 21%, P < 0.01), reduced whole-body fat mass (ALA: 41%, GLY: 49% P < 0.01), and restored glucose tolerance to control values in ALA and GLY groups. GLY treated mice lost more whole-body fat mass (14%, p < 0.05) and epididymal fat mass (26%, P < 0.05), less lean mass (27%, P < 0.05), and had better preserved quadriceps muscle mass (4%, P < 0.01) than ALA treated mice after 20 d CR. Compared to the HFD group, pro-inflammatory genes were lower (P < 0.05), metabolic genes higher (P < 0.05) and S6 protein phosphorylation lower after CR, but not different between ALA and GLY groups. There were significant correlations between %initial fat mass (pre CR) and the mRNA expression of genes involved in inflammation (r = 0.51 to 0.68, P < 0.05), protein breakdown (r = −0.66 to −0.37, P < 0.05) and metabolism (r = −0.59 to −0.47, P < 0.05) after CR.
 
Taken together, these findings suggest that glycine supplementation during CR may be beneficial for preserving muscle mass and stimulating loss of adipose tissue.

 


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#90 docmaas

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Posted 05 October 2015 - 05:43 PM

I think that since doing these tests I've noticed a tendency for the rise in blood glucose to continue after the cessation of the tests back to higher levels than the initial "fasting" level.  This may imply that the glycine has been inactivated or removed over time.  The fact that the initial peak does decline with higher doses may be an indication that there are both time dependent and dose dependent limits.  I guess the next experiment might be to add subsequent ingestions of glycine to see if 1) further decrease occurs and or 2) if the subsequent peak can be reduced over time by subsequent consumption of glycine.   

 

I think I earlier mentioned that slow dissolving lozenges of glycine or a time release version might make it even more useful for diabetics.

 

My curiosity is piqued by your French hypothesis.  Unfortunately I am not well informed on most of what you bring up.  Hopefully others will comment.

 

9/22/2015 glucose with glycine

6 tsp sugar 1 tsp glycine

fasting 91

MIN GLUCOSE

10 102


150 97

180 88

TOTAL TIME Glucose > 100 = 367

 

9/23/2015 glucose with glycine

6 tsp sugar 2 tsp glycine

fasting 97

MIN GLUCOSE

10 109


150 96

TOTAL TIME Glucose > 100 = 278

 

9/24/2015 glucose with glycine

6 tsp sugar 3 tsp glycine

fasting 100

MIN GLUCOSE

10 92


150 95

TOTAL TIME Glucose > 100 = 250

 

Thanks for this meticulous data. It really seems as though the time required to return to 95-97 does not vary with the glycine dose, given a constant dose of sugar. So it sort of sounds to me as though glycine is acting more as a fixed-threshold signalling molecule than an ordinary amino acid, as one would normally expect highly bioavailable amino acids to raise insulin in a manner monotonic with the amount ingested, just as it would with protein powder. In that case, presumably, consuming more protein would cause plasma glucose to drop faster due to a higher insulin spike. But because that didn't happen here in any obvious way, I would say that your insulin response to the various doses of glycine was essentially constant.

 

I realize it sounds totally nuts to think of protein building blocks as metabolic signalling molecules analogous to various stem cell activators, but your data only adds to all of the animal studies above which suggest that this may be the case. But that's the whole point: it's nuts. As in, glycine says: "OMG there's no big game to hunt! We're stuck here picking nuts from the trees all day just to stay alive. We need to turn on the starvation defense mechanisms, e.g. SIRT1 etc. Throttle down the sex drive because there's not enough protein to produce offspring;" whereas methionine consuption signals exactly the opposite.

 

Why else would neurons and so many other cells have receptors for this isolated amino acid? Looking at it another way, I think there's a good chance that rat success implies human success because presumably these receptors go way way back in evolutionary history; after all, glycine is about as simple as it gets in biology.

 

I'm also pleased at the relatively dose-agnostic nature of your results, as it means that I can expect more benefits from less (8g?) glycine per day. That's really important to me because I'm trying to restrict protein to the maximum extent possible, largely because I believe niner's conjecture that equilibrium considerations would imply that low protein consumption would stimulate the recycling of junk protein via autophagy. (No wonder the Alzheimer's rate in France is so high. They eat meat and cheese like there's no tomorrow. The cheese protects their arteries and prevents cardiovascular failures on account of vitamin K2, while at the same time suppressing neuronal autophagy, allowing brain plaques to accrue unabated on account of the high methionine content.)

 

For similar reasons, I would also expect methionine restriction to upregulate macroautophagy, i.e. intercellular junk protein depletion via microglia (in the brain) or macrophages (elsewhere).  (Alpha-synuclein clearance comes to mind, but I don't know enough about that to comment.) That would be really exciting because it's these intercellular junk proteins which tend to be the heaviest and thus the most resistent to degradation, e.g. phosphotau aggregates weighing 100+ KDa. But I have no evidence that this is in fact the case. :(

 

 






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