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Glycine Reduces NAFLD by modulating fatty acid oxidation, glutathione synthesis, and the gut microbiome - 2020

Lokzo

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Amino acids alleviate liver disease​

Glycine is known to be reduced in patients with nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), diseases with no approved treatments. Rom et al. found that glycine biosynthetic genes showed reduced expression in humans and mice with NAFLD. Conversely, both genetic and dietary reduction of glycine worsened symptoms in the model, suggesting a potential causative role for glycine in NAFLD onset. Administration of glycine or a Gly-Gly-L-Leu tripeptide improved symptoms in a mouse model of NASH by enhancing fatty acid oxidation and glutathione synthesis and modulated the gut microbiome through a potentially indirect effect, indicating the potential of the approach as a treatment.

Abstract​

Nonalcoholic fatty liver disease (NAFLD) including nonalcoholic steatohepatitis (NASH) has reached epidemic proportions with no pharmacological therapy approved. Lower circulating glycine is consistently reported in patients with NAFLD, but the causes for reduced glycine, its role as a causative factor, and its therapeutic potential remain unclear. We performed transcriptomics in livers from humans and mice with NAFLD and found suppression of glycine biosynthetic genes, primarily alanine-glyoxylate aminotransferase 1 (AGXT1). Genetic (Agxt1−/− mice) and dietary approaches to limit glycine availability resulted in exacerbated diet-induced hyperlipidemia and steatohepatitis, with suppressed mitochondrial/peroxisomal fatty acid β-oxidation (FAO) and enhanced inflammation as the underlying pathways. We explored glycine-based compounds with dual lipid/glucose-lowering properties as potential therapies for NAFLD and identified a tripeptide (Gly-Gly-L-Leu, DT-109) that improved body composition and lowered circulating glucose, lipids, transaminases, proinflammatory cytokines, and steatohepatitis in mice with established NASH induced by a high-fat, cholesterol, and fructose diet. We applied metagenomics, transcriptomics, and metabolomics to explore the underlying mechanisms. The bacterial genus Clostridium sensu stricto was markedly increased in mice with NASH and decreased after DT-109 treatment. DT-109 induced hepatic FAO pathways, lowered lipotoxicity, and stimulated de novo glutathione synthesis. In turn, inflammatory infiltration and hepatic fibrosis were attenuated via suppression of NF-κB target genes and TGFβ/SMAD signaling. Unlike its effects on the gut microbiome, DT-109 stimulated FAO and glutathione synthesis independent of NASH. In conclusion, impaired glycine metabolism may play a causative role in NAFLD. Glycine-based treatment attenuates experimental NAFLD by stimulating hepatic FAO and glutathione synthesis, thus warranting clinical evaluation.

Glycine-based treatment ameliorates NAFLD by modulating fatty acid oxidation, glutathione synthesis, and the gut microbiome | Science Translational Medicine
 

Perry Staltic

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Glycine also - supposedly - helps detox the body of glyphosate, which is a glycine analogue.
 

Birdie

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I've found using glycine can activate IBS.
 

Kray

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Any supplement that isn’t tolerated could cause IBS.
Got it. Had never heard that was a known issue with glycine in particular; in fact, I had thought it was known to be helpful in IBS. Pretty sure my doc had me take it years ago when I had symptoms of same.

Thanks for your quick response!
 

Perry Staltic

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Got it. Had never heard that was a known issue with glycine in particular; in fact, I had thought it was known to be helpful in IBS or intestinal issues in general.

Could be the dose. Too much of anything can cause problems
 

Kray

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Got it. Had never heard that was a known issue with glycine in particular; in fact, I had thought it was known to be helpful in IBS. Pretty sure my doc had me take it years ago when I had symptoms of same.

Could be the dose. Too much of anything can cause problems
True- more is not always better, a hard thing to learn in our culture! Love your name!
 

Mauritio

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That is no good! Any documentation to support?
I've had similar results . Also got minor allergic symptoms from the glycine powders . I think I've tried 3 different vendors , one with from a lab with the highest purity I could find , and even that one gave allergy symptoms .
I've read chamomile tea is high in glycine.
 
Last edited:

Kray

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I've had similar results . Also got minor allergic symptoms from the glycine powders . I think I've tried 3 different vendors , one with from a lab wor the highest purity I could find , and even that one gave allergy symptoms .
I've read chamomile tea is high in glycine.
What kind of (allergy) symptoms should one be looking for?
 

Kray

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Dark circles under eyes and light swelling of the upper eyelid are the most obvious.
Seems like dark circles is a common symptom of many sensitivities. Probably good to keep to food sources if there's any question. Also seems like some here on the forum have problems even with collagen or gelatin supplements; not sure if this would point to a particular amino acid, or more the concentrated form of them altogether.
 

Mauritio

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Seems like dark circles is a common symptom of many sensitivities. Probably good to keep to food sources if there's any question. Also seems like some here on the forum have problems even with collagen or gelatin supplements; not sure if this would point to a particular amino acid, or more the concentrated form of them altogether.
Yeah I also cant eat pure gelatin. I think it gives me endotoxin symptoms , could be feeding the wrong bacteria or there's too much histamine in there .
 

tankasnowgod

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I've found using glycine can activate IBS.

Glycine can stimulate the "Bile Acid Receptor." Overall, a good thing, but yes, too much bile will cause GI distress, usually diarrhea. Taurine can have some similar issues (usually at lower doses).

I think it's wise to add glycine slowly, although recently when I added glycine back, I added much higher doses at first..... I ramped up to 50+ grams a day by accident, and yet, no GI issues. Good to know, but I scaled it back, mainly because I didn't want to tear through my glycine supplement that quick.

Having said that, there's always the potential issue of some contaminant with a supplement, and that can cause issues too.
 

Birdie

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That is no good! Any documentation to support?
Not sure what you mean by documentation. I kept notes but are you asking for my notes? I'm not in the Ray Peat category, remembering all the details. ;)

I'd read a lot back when I'd tried glycine. Something about the process of separating out or synthesizing glycine was the lightbulb event for me.

Still, I was wanting to use glycine, for some forgotten benefit, but every time, even adding a 1/4 teaspoon to a smoothie, I would experience and IBS attack. I use about 2 teaspoons of gelatin now..

I just wanted to put that out in case it might help somebody with IBS and experiencing attacks like I did.
 

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