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haidut

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Lung and brain (glioblastoma) cancer are among the deadliest. The 5 year survival rates of both are below 20%. So, any progress in treating those cancer types would be a huge leap forward for oncology. As the study says, there is a growing realization that cancers are highly metabolically deranged and that goes beyond the Warburg effect. The study found that increased catabolism of the amino acid glycine (and thus lower levels) leads to tumor formation and aggressive phenotype. Inhibiting the enzyme that degrades glycine was highly therapeutic. The same effect can be achieved by supplying extra glycine. As Peat said "that kind of chemotherapy [glycine] can be pleasant".
Gelatin, stress, longevity
"...When cells are stressed, they form extra collagen, but they can also dissolve it, to allow for tissue remodeling and growth. Invasive cancers over-produce this kind of enzyme, destroying the extracellular matrix which is needed for normal cellular differentiation and function. When collagen is broken down, it releases factors that promote wound healing and suppress tumor invasiveness. (Pasco, et al., 2003) Glycine itself is one of the factors promoting wound healing and tumor inhibition. It has a wide range of antitumor actions, including the inhibition of new blood vessel formation (angiogenesis), and it has shown protective activity in liver cancer and melanoma. Since glycine is non-toxic (if the kidneys are working, since any amino acid will contribute to the production of ammonia), this kind of chemotherapy can be pleasant."

The fact that this approach worked in two very different cancer types, which oncology considered completely unrelated, suggests that it is a general features of cancer cells and can be exploited against any tumor type, as Peat suggests above and the second study acknowledges.


SHMT2 drives glioma cell survival in ischaemia but imposes a dependence on glycine clearance
http://www.cell.com/molecular-therapy-family/nucleic-acids/fulltext/S2162-2531(17)30262-7
https://medicalxpress.com/news/2015-04-biologists-brain-tumor-weakness.html
"...Biologists at MIT and the Whitehead Institute for Biomedical Research have discovered a vulnerability of brain cancer cells that could be exploited to develop more-effective drugs against brain tumors. The study, led by researchers from the Whitehead Institute and MIT's Koch Institute for Integrative Cancer Research, found that a subset of glioblastoma tumor cells is dependent on a particular enzyme that breaks down the amino acid glycine. Without this enzyme, toxic metabolic byproducts build up inside the tumor cells, and they die. Blocking this enzyme in glioblastoma cells could offer a new way to combat such tumors, says Dohoon Kim, a postdoc at the Whitehead Institute and lead author of the study, which appears in the April 8 online edition of Nature."

https://medicalxpress.com/news/2018-03-rna-based-therapeutic-inhibits-metabolic-pathway.html
"...The discovery of elevated expression of normal or mutant forms of metabolic enzymes in a variety of cancers has created great interest in cancer metabolism, explains Uttam Surana from the Institute of Molecular and Cell Biology, and Dave Wee from the Institute of High Performance Computing. Targeting TIC metabolism is emerging as a promising strategy to thwart the progression of various cancers. Previous studies have shown that TIC of non-small cell lung carcinoma (NSCLC) tumors contain high levels of glycine decarboxylase (GLDC), an enzyme that breaks down the amino-acid glycine. Overexpression of GLDC stimulates the generation of tumors and the proliferation of TIC, and high GLDC levels are associated with poor survival rates in NSCLC patients. No therapeutic agents have been developed against GLDC until now. Surana and Wee identified short synthetic RNA sequences (steric hindrance antisense oligonucleotides, or shAONs) that suppressed the production GLDC protein in human lung cancer cells, hindering their proliferation and preventing tumor formation."
 

Vinero

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Do you take glycine yourself? What do you think about the recent worry on the forum that glycine supplements might be contaminated with lead?
 

Koveras

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Lung and brain (glioblastoma) cancer are among the deadliest. The 5 year survival rates of both are below 20%. So, any progress in treating those cancer types would be a huge leap forward for oncology. As the study says, there is a growing realization that cancers are highly metabolically deranged and that goes beyond the Warburg effect. The study found that increased catabolism of the amino acid glycine (and thus lower levels) leads to tumor formation and aggressive phenotype. Inhibiting the enzyme that degrades glycine was highly therapeutic. The same effect can be achieved by supplying extra glycine. As Peat said "that kind of chemotherapy [glycine] can be pleasant".
Gelatin, stress, longevity
"...When cells are stressed, they form extra collagen, but they can also dissolve it, to allow for tissue remodeling and growth. Invasive cancers over-produce this kind of enzyme, destroying the extracellular matrix which is needed for normal cellular differentiation and function. When collagen is broken down, it releases factors that promote wound healing and suppress tumor invasiveness. (Pasco, et al., 2003) Glycine itself is one of the factors promoting wound healing and tumor inhibition. It has a wide range of antitumor actions, including the inhibition of new blood vessel formation (angiogenesis), and it has shown protective activity in liver cancer and melanoma. Since glycine is non-toxic (if the kidneys are working, since any amino acid will contribute to the production of ammonia), this kind of chemotherapy can be pleasant."

The fact that this approach worked in two very different cancer types, which oncology considered completely unrelated, suggests that it is a general features of cancer cells and can be exploited against any tumor type, as Peat suggests above and the second study acknowledges.


SHMT2 drives glioma cell survival in ischaemia but imposes a dependence on glycine clearance
http://www.cell.com/molecular-therapy-family/nucleic-acids/fulltext/S2162-2531(17)30262-7
https://medicalxpress.com/news/2015-04-biologists-brain-tumor-weakness.html
"...Biologists at MIT and the Whitehead Institute for Biomedical Research have discovered a vulnerability of brain cancer cells that could be exploited to develop more-effective drugs against brain tumors. The study, led by researchers from the Whitehead Institute and MIT's Koch Institute for Integrative Cancer Research, found that a subset of glioblastoma tumor cells is dependent on a particular enzyme that breaks down the amino acid glycine. Without this enzyme, toxic metabolic byproducts build up inside the tumor cells, and they die. Blocking this enzyme in glioblastoma cells could offer a new way to combat such tumors, says Dohoon Kim, a postdoc at the Whitehead Institute and lead author of the study, which appears in the April 8 online edition of Nature."

https://medicalxpress.com/news/2018-03-rna-based-therapeutic-inhibits-metabolic-pathway.html
"...The discovery of elevated expression of normal or mutant forms of metabolic enzymes in a variety of cancers has created great interest in cancer metabolism, explains Uttam Surana from the Institute of Molecular and Cell Biology, and Dave Wee from the Institute of High Performance Computing. Targeting TIC metabolism is emerging as a promising strategy to thwart the progression of various cancers. Previous studies have shown that TIC of non-small cell lung carcinoma (NSCLC) tumors contain high levels of glycine decarboxylase (GLDC), an enzyme that breaks down the amino-acid glycine. Overexpression of GLDC stimulates the generation of tumors and the proliferation of TIC, and high GLDC levels are associated with poor survival rates in NSCLC patients. No therapeutic agents have been developed against GLDC until now. Surana and Wee identified short synthetic RNA sequences (steric hindrance antisense oligonucleotides, or shAONs) that suppressed the production GLDC protein in human lung cancer cells, hindering their proliferation and preventing tumor formation."

Hopefully they don't take the advice to restrict glycine then (unless there is something unique going on here...)

Amino acids in diet could be key to starving cancer

Modulating the therapeutic response of tumours to dietary serine and glycine starvation

"The non-essential amino acids serine and glycine are used in multiple anabolic processes that support cancer cell growth and proliferation (reviewed in ref. 1). While some cancer cells upregulate de novo serine synthesis2,3,4, many others rely on exogenous serine for optimal growth5,6,7. Restriction of dietary serine and glycine can reduce tumour growth in xenograft and allograft models7,8. Here we show that this observation translates into more clinically relevant autochthonous tumours in genetically engineered mouse models of intestinal cancer (driven by Apc inactivation) or lymphoma (driven by Myc activation). The increased survival following dietary restriction of serine and glycine in these models was further improved by antagonizing the anti-oxidant response. Disruption of mitochondrial oxidative phosphorylation (using biguanides) led to a complex response that could improve or impede the anti-tumour effect of serine and glycine starvation. Notably, Kras-driven mouse models of pancreatic and intestinal cancers were less responsive to depletion of serine and glycine, reflecting an ability of activated Kras to increase the expression of enzymes that are part of the serine synthesis pathway and thus promote de novo serine synthesis."​
 

haidut

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Do you take glycine yourself? What do you think about the recent worry on the forum that glycine supplements might be contaminated with lead?

I use gelatin every once in a while, usually after a night of drinking to soothe the gut and improve barrier healing. The few isolated glycine products I tried did not give me bad symptoms but I find gelatin is more convenient and available everywhere.
 

haidut

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Hopefully they don't take the advice to restrict glycine then (unless there is something unique going on here...)

Amino acids in diet could be key to starving cancer

Modulating the therapeutic response of tumours to dietary serine and glycine starvation

"The non-essential amino acids serine and glycine are used in multiple anabolic processes that support cancer cell growth and proliferation (reviewed in ref. 1). While some cancer cells upregulate de novo serine synthesis2,3,4, many others rely on exogenous serine for optimal growth5,6,7. Restriction of dietary serine and glycine can reduce tumour growth in xenograft and allograft models7,8. Here we show that this observation translates into more clinically relevant autochthonous tumours in genetically engineered mouse models of intestinal cancer (driven by Apc inactivation) or lymphoma (driven by Myc activation). The increased survival following dietary restriction of serine and glycine in these models was further improved by antagonizing the anti-oxidant response. Disruption of mitochondrial oxidative phosphorylation (using biguanides) led to a complex response that could improve or impede the anti-tumour effect of serine and glycine starvation. Notably, Kras-driven mouse models of pancreatic and intestinal cancers were less responsive to depletion of serine and glycine, reflecting an ability of activated Kras to increase the expression of enzymes that are part of the serine synthesis pathway and thus promote de novo serine synthesis."​

I know, right? I wonder how that glycine/serine restriction was accomplished. Maybe if they used a drug of some sort it has other effects they neglected to mention.
 

yerrag

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I use gelatin every once in a while, usually after a night of drinking to soothe the gut and improve barrier healing. The few isolated glycine products I tried did not give me bad symptoms but I find gelatin is more convenient and available everywhere.
I have been using gelatin as well, more of the hydrolysate than the gelling gelatin of Great Lakes. I haven't used used the amino acid glycine mainly because Ray Peat discourages the use of isolated amino acids. I've also begun to buy more meats that are rich in gelatin such as oxtail, ox legs, ox tripe, pork legs, pork ears and nape.

But I've began to question whether getting processed gelatin from Great Lakes and its kind is such a good idea. Primarily it's due to there being no assurance that the supply of raw materials is free from contamination with glyphosate, the result of using GMO-based feeds. And glyphosate substituting glycine in the gelatin taken has consequences, as brought up by a thread or two in this forum.

I'm now reconsidering the use of glycine as a result. Do you think the glycine we can get from say Bulksupplements is purified enough that it doesn't contain glyphosate?

If the answer is no, I would end up back to relying on getting glycine from food, although that would be more time-consuming. Even then, there is no assurance the food isn't glyphosate contaminated unless I become a farmer.
 

haidut

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I have been using gelatin as well, more of the hydrolysate than the gelling gelatin of Great Lakes. I haven't used used the amino acid glycine mainly because Ray Peat discourages the use of isolated amino acids. I've also begun to buy more meats that are rich in gelatin such as oxtail, ox legs, ox tripe, pork legs, pork ears and nape.

But I've began to question whether getting processed gelatin from Great Lakes and its kind is such a good idea. Primarily it's due to there being no assurance that the supply of raw materials is free from contamination with glyphosate, the result of using GMO-based feeds. And glyphosate substituting glycine in the gelatin taken has consequences, as brought up by a thread or two in this forum.

I'm now reconsidering the use of glycine as a result. Do you think the glycine we can get from say Bulksupplements is purified enough that it doesn't contain glyphosate?

If the answer is no, I would end up back to relying on getting glycine from food, although that would be more time-consuming. Even then, there is no assurance the food isn't glyphosate contaminated unless I become a farmer.

I can't say either way without testing it. But I had good experiences with glycine from several vendors and got tested for lead and other heavy metals months down the road (for unrelated reasons) and my numbers were fine.
 

yerrag

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I can't say either way without testing it. But I had good experiences with glycine from several vendors and got tested for lead and other heavy metals months down the road (for unrelated reasons) and my numbers were fine.
It's good to know you experienced nosigns of heavy metal toxicity from using glycine. Is there any way glyphosate toxicity could be determined?
 

Nicole W.

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I have been using gelatin as well, more of the hydrolysate than the gelling gelatin of Great Lakes. I haven't used used the amino acid glycine mainly because Ray Peat discourages the use of isolated amino acids. I've also begun to buy more meats that are rich in gelatin such as oxtail, ox legs, ox tripe, pork legs, pork ears and nape.

But I've began to question whether getting processed gelatin from Great Lakes and its kind is such a good idea. Primarily it's due to there being no assurance that the supply of raw materials is free from contamination with glyphosate, the result of using GMO-based feeds. And glyphosate substituting glycine in the gelatin taken has consequences, as brought up by a thread or two in this forum.

I'm now reconsidering the use of glycine as a result. Do you think the glycine we can get from say Bulksupplements is purified enough that it doesn't contain glyphosate?

If the answer is no, I would end up back to relying on getting glycine from food, although that would be more time-consuming. Even then, there is no assurance the food isn't glyphosate contaminated unless I become a farmer.
It says on the Great Lakes website that they routinely test for the presence of glyphosate and include the data found from the third party who tests showing that its lower than detectable limits. What gave you the impression that this is not true? Have you spoken to them directly?
 

yerrag

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It says on the Great Lakes website that they routinely test for the presence of glyphosate and include the data found from the third party who tests showing that its lower than detectable limits. What gave you the impression that this is not true? Have you spoken to them directly?
You're assuming I have read Great Lakes' website and am aware of their statement in this regard. But thanks for pointing it out as it makes me feel a whole lot better about using their products.

Nonetheless, I still would prefer to use a product that is labeled "Glyphosate-Free" emphatically, as the spread of the use of GMO-based seems to go unimpeded, and sooner or later the supply of glyphosate-free raw materials would be restricted. The cost-competitive nature of businesses render it necessary to source lower cost raw materials, and GMO-based feeds are certainly appearing to be more cost-competitive. This makes it more and more difficult to avoid glyphosate contamination in gelatin products.
 

haidut

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It's good to know you experienced nosigns of heavy metal toxicity from using glycine. Is there any way glyphosate toxicity could be determined?

Not sure, but I think it can be tested for in the blood.
 

Nicole W.

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You're assuming I have read Great Lakes' website and am aware of their statement in this regard. But thanks for pointing it out as it makes me feel a whole lot better about using their products.

Nonetheless, I still would prefer to use a product that is labeled "Glyphosate-Free" emphatically, as the spread of the use of GMO-based seems to go unimpeded, and sooner or later the supply of glyphosate-free raw materials would be restricted. The cost-competitive nature of businesses render it necessary to source lower cost raw materials, and GMO-based feeds are certainly appearing to be more cost-competitive. This makes it more and more difficult to avoid glyphosate contamination in gelatin products.
I agree and that is always in the back of my mind. There are other gelatin/collagen hydrolysate brands I’ve thought of trying but none of them provide the data from third party testing and that’s where they lose me. Just because its organic and made in the USA is not enough of a reassurance. Even with the data, I still worry a bit. With any processed food or supplement you never really know.
 

haidut

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Sure enough, there is a test, but it's urine:

Glyphosate Test

It should be enough, as glyphosate gets excreted promptly and elevated if someone has glyphosate toxicity it should show up on the urine test. I think there is also a blood test but only a few labs offer it. Google for "glyphosate blood test".
 

yerrag

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Perhaps there is, but top search results of Google don't seem to come up positive for a blood test. But the urine test should be fine. I prefer not being poked, and that is just good news.
 

Koveras

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I know, right? I wonder how that glycine/serine restriction was accomplished. Maybe if they used a drug of some sort it has other effects they neglected to mention.

"Diets. From weaning, mice received ‘normal chow’ (Rat and Mouse Breeder and Grower, 801730, Special Diet Services, SDS, UK) and water ad libitum. On normal chow, dietary amino acids are derived from whole proteins contained in the raw ingredients (wheat, wheatfeed, barley, de-hulled extracted toasted soya, maize and fish meal), with a small amount of purified lysine added as a supplement. Two sets of experimental diets were used, both based on Baker Purified Amino Acid Diet38 from TestDiet (Richmond, IN): ‘Diet 1-Control’ contained all essential amino acids plus serine, glycine, glutamine, arginine, cystine, and tyrosine; ‘Diet 1-SG-free’ was the same as Diet 1-Control, but without serine and glycine, with the other amino acid levels increased proportionally to achieve the same total amino acid content. These ‘Diet 1’ formulations were used previously7. ‘Diet 2-Control’ contained all essential amino acids plus serine, glycine, glutamine, arginine, cystine, tyrosine, alanine, proline, glutamate and asparagine; ‘Diet 2-SG-free’ was the same as Diet 2-Control, but without serine and glycine, with the other amino acid levels increased proportionally to achieve the same total amino acid content. ‘Diet 2’ formulations were used for the Eμ-Myc;Tigar experiment (Fig. 2f). All other cohorts received the previously published Diet 1 formulations."

I wonder if the "serine and glycine free" diet happened to be a glyphosate free (or reduced) diet.
 

Koveras

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I know, right? I wonder how that glycine/serine restriction was accomplished. Maybe if they used a drug of some sort it has other effects they neglected to mention.

Looks like serine is more problematic, and whether glycine can be an issue depends on methyl donor availability

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

Previous work has shown that some cancer cells are highly dependent on serine/glycine uptake for proliferation. 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.
 

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