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Glycine Is Directly Anabolic AND Anticatabolic For The Muscle

Discussion in 'Scientific Studies' started by haidut, Dec 8, 2017.

  1. haidut

    haidut Member

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    I posted a few interesting studies about glycine in the past. Among the interesting properties are lowering cortisol, increasing DHT synthesis, improving insulin sensitivity, and serving as a biomarker of stress.
    Glycine Powerfully Lowers Cortisol
    Glycine Strongly Upregulates 5-alpha Reductase (5-ar) Activity
    Taurine/glycine Ratio As A Biomarker Of Stress

    The anticortisol and androgenic properties of glycine make it a prime candidate for building lean muscle tissue, and while the bodybuilding community is more interested in AAS, the livestock industry is constantly searching for new ways to increase muscle growth in animals without using steroids. As a result of this pursuit for anabolic substances, a group of scientists published a study a few years ago showing that a HED of 6g-7g of glycine fully restores the anabolic effects of leucine under conditions of increased inflammation for the organism.
    Glycine restores the anabolic response to leucine in a mouse model of acute inflammation. - PubMed - NCBI

    It is well-known that anabolic effects of protein greatly diminish an even completely disappear with aging, and inflammation is probably a large factor in that. As a result, most people over 30 have some degree of sarcopenia (muscle wasting). The above study is interesting but was considered not very relevant to people because it was assumed that glycine played only a peripheral role and the anabolic effects were actually due to leucine. In addition, a state of chronic inflammation is (wrongly) believed to affect only a small percentage of people.
    This new study below goes a step further and shows that glycine is actually directly anabolic and anticatabolic itself, and at quite reasonable doses/concentrations. The human doses needed to achieve the concentrations mentioned in the study are in the range of 1.5g-6g daily. It is noteworthy that the lowest concentration (equivalent to about 1.5g daily human dose) of glycine actually had the strongest boosting effect on mTOR. So if a person is not in state of severe inflammation, it may be that this meager dose of glycine is all that is needed to restore anabolic state and prevent further catabolism. Russian studies from the 1960s, which were recently replicated in the US, found that glycine exerts an anti-inflammatory effects at any dose. So, even lower doses than 1.5g daily may be sufficient to exert this positive effect on muscle tissue.
    Hey @AretnaP, @Jsaute21, @dand - you may find this very interesting.

    http://jn.nutrition.org/content/146/12/2461.long

    "...The accretion of muscle protein is dependent on the balance between protein synthesis and degradation (2325). Alterations in protein turnover are associated with the development of skeletal muscle hypertrophy or atrophy in humans and animals (26, 27). Data from clinical trials and animal models indicate that supplementation of amino acids could stimulate protein synthesis (28, 29) or decrease protein breakdown (3032) in skeletal muscle, thus contributing to enhanced protein accretion in cells. Our recent studies (19) showed that glycine, one of the most abundant free amino acids in the plasma of pigs (33), promotes skeletal muscle growth in young pigs, suggesting a crucial role of glycine in nutrition and metabolism. However, little is known about the effects of glycine on protein turnover in skeletal muscle or the underlying mechanisms."

    "...Our data presented here support the idea that PI3K/Akt is the central hub of glycine-mediated protein turnover in a C2C12 cell model. Specifically, glycine exposure resulted in mTORC1 activation, which was associated with a decreased protein level of p-AMPK, a negative regulator of mTORC1 signaling. This result is in agreement with previous studies showing that the AMPK activator AICAR inhibited the activation of mTORC1 and its downstream targets (34, 35)."

    "...It should be noted that glycine activated mTORC1 and its downstream target P70S6K without affecting the protein abundance of p-4E-BP1 in C2C12 cells. This effect was unexpected, and the reason for this observation is currently unknown."

    "...In addition, glycine repressed mRNA levels of atrogin-1 and MuRF1, 2 critical genes involved in proteasome degradation of intracellular proteins (13, 15). Our results are in agreement with a previous study that showed that BCAA administration attenuates atrogin-1 and MuRF1 mRNA levels and prevented a decrease in soleus muscle weight in growing rats (39). Importantly, we showed that the effect of glycine on mRNA expression of MuRF1 is dependent on PI3K/Akt signaling, because the repressing effect was abrogated by the PI3K/Akt inhibitor LY294002 (Figure 4). Consistent with the activation of mTORC1 signaling and inhibition of the expression of key genes involved in protein degradation, the addition of glycine to the culture medium led to an increase in the rate of protein synthesis and a decrease in the rate of protein degradation (Tables 1 and 2), which are required for cell proliferation. Considering the positive relation between the upregulated genes involved in ubiquitin-mediated protein breakdown and the development of muscle atrophy (14), our results indicate that glycine supplementation might be a potential nutritional strategy to prevent or treat the muscle wasting that is often observed in various disorders, such as metabolic diseases and severe infections. In vivo studies are warranted to test this hypothesis."

    "...In conclusion, the results of the present study showed that glycine, as a functional amino acid, plays a previously unrecognized, important role in regulating protein turnover via PI3K/Akt-dependent activation of mTORC1 and inhibition of proteolysis signaling in C2C12 cells. These findings provide a biochemical mechanism for dietary glycine supplementation to promote lean tissue growth in young pigs and possibly other mammals with a deficiency of glycine."
     
  2. AretnaP

    AretnaP Member

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    Good finding. Glycine is almost like nature's aspirin (both exist in nature, but glycine can be found in greater abundance), anti-inflammatory, anti-excitotoxic, pro-longevity.
     
  3. Koveras

    Koveras Member

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    A few more for everyone - endotoxin/LPS/TLR4 seems to be behind some of the aforementioned chronic inflammation and anabolic/leucine resistance in aged muscle.


    Am J Physiol Regul Integr Comp Physiol. 2016 Aug 1;311(2):R365-73. doi: 10.1152/ajpregu.00043.2016. Epub 2016 May 25.
    Glycine enhances muscle protein mass associated with maintaining Akt-mTOR-FOXO1 signaling and suppressing TLR4 and NOD2 signaling in piglets challenged with LPS.
    Liu Y1, Wang X2, Wu H2, Chen S2, Zhu H2, Zhang J2, Hou Y2, Hu CA3, Zhang G4.
    Pro-inflammatory cytokines play a critical role in the pathophysiology of muscle atrophy. We hypothesized that glycine exerted an anti-inflammatory effect and alleviated lipopolysaccharide (LPS)-induced muscle atrophy in piglets. Pigs were assigned to four treatments including the following: 1) nonchallenged control, 2) LPS-challenged control, 3) LPS+1.0% glycine, and 4) LPS+2.0% glycine. After receiving the control, 1.0 or 2.0% glycine-supplemented diets, piglets were treated with either saline or LPS. At 4 h after treatment with saline or LPS, blood and muscle samples were harvested. We found that 1.0 or 2.0% glycine increased protein/DNA ratio, protein content, and RNA/DNA ratio in gastrocnemius or longissimus dorsi (LD) muscles. Glycine also resulted in decreased mRNA expression of muscle atrophy F-box (MAFbx) and muscle RING finger 1 (MuRF1) in gastrocnemius muscle. In addition, glycine restored the phosphorylation of Akt, mammalian target of rapamycin (mTOR), eukaryotic initiation factor 4E binding protein 1 (4E-BP1), and Forkhead Box O 1 (FOXO1) in gastrocnemius or LD muscles. Furthermore, glycine resulted in decreased plasma tumor necrosis factor-α (TNF-α) concentration and muscle TNF-α mRNA abundance. Moreover, glycine resulted in decreased mRNA expresson of Toll-like receptor 4 (TLR4), nucleotide-binding oligomerization domain protein 2 (NOD2), and their respective downstream molecules in gastrocnemius or LD muscles. These results indicate glycine enhances muscle protein mass under an inflammatory condition. The beneficial roles of glycine on the muscle are closely associated with maintaining Akt-mTOR-FOXO1 signaling and suppressing the activation of TLR4 and/or NOD2 signaling pathways.

    J Cell Physiol. 2005 Apr;203(1):144-55.
    Endotoxin disrupts the leucine-signaling pathway involving phosphorylation of mTOR, 4E-BP1, and S6K1 in skeletal muscle.
    Lang CH1, Frost RA.
    Endotoxin (i.e., lipopolysaccharide, LPS) impairs skeletal muscle protein synthesis. Although this impairment is not acutely associated with a decreased plasma concentration of total amino acids, LPS may blunt the anabolic response to amino acids. To examine this hypothesis, rats were injected intraperitoneally with LPS or saline (Sal) and 4 h thereafter were orally administered either leucine (Leu) or Sal. The gastrocnemius was removed 20 min later to assess signaling components important in the translational control of protein synthesis. In the Sal-Leu group phosphorylation of 4E-BP1 in muscle was markedly increased, compared to values from time-matched saline-treated control rats. This change was associated with a redistribution of eukaryotic initiation factor (eIF) 4E from the inactive eIF4E x 4E-BP1 complex to the active eIF4E x eIF4G complex. In LPS-treated rats, the Leu-induced phosphorylation of 4E-BP1 and changes in eIF4E distribution were partially or completely abrogated. LPS also antagonized the Leu-induced increase in phosphorylation of S6K1, ribosomal protein S6 and mTOR. Neither LPS nor leu altered the total amount or phosphorylation of TSC2 in muscle. The ability of LPS to blunt the anabolic effects of Leu could not be attributed to differences in the plasma concentrations of insulin or Leu between groups. Furthermore, the replacement of plasma insulin-like growth factor (IGF)-I in LPS-treated rats to basal levels also did not ameliorate the defect in leucine-induced phosphorylation of S6K1 or S6, although it did reverse the LPS-induced decrease in the constitutive phosphorylation of mTOR, S6 and 4E-BP1. Pretreatment with the glucocorticoid receptor antagonist RU486 was unable to prevent the LPS-induced leucine resistance. In contrast, to the abovementioned results with leucine, LPS did not prevent the ability of pharmacological levels of IGF-I to phosphorylate 4E-BP1, S6K1, mTOR or alter the availability of eIF4E. Hence, LPS working via a glucocorticoid-independent mechanism produces a leucine resistance in skeletal muscle that might be expected to impair the ability of this amino acid to stimulate translation initiation and protein

    J Gerontol A Biol Sci Med Sci. 2015 Feb;70(2):232-46. doi: 10.1093/gerona/glu067. Epub 2014 May 20.
    Elevated muscle TLR4 expression and metabolic endotoxemia in human aging.
    Ghosh S1, Lertwattanarak R2, Garduño Jde J2, Galeana JJ2, Li J3, Zamarripa F3, Lancaster JL3, Mohan S4, Hussey S1, Musi N5.
    Aging is associated with alterations in glucose metabolism and sarcopenia that jointly contribute to a higher risk of developing type 2 diabetes. Because aging is considered as a state of low-grade inflammation, in this study we examined whether older, healthy (lean, community-dwelling) participants have altered signaling flux through toll-like receptor 4 (TLR4), a key mediator of innate and adaptive immune responses. We also examined whether a 4-month aerobic exercise program would have an anti-inflammatory effect by reducing TLR4 expression and signaling. At baseline, muscle TLR4, nuclear factor κB p50 and nuclear factor κB p65 protein content, and c-Jun N-terminal kinase phosphorylation were significantly elevated in older versus young participants. The plasma concentration of the TLR4 agonist lipopolysaccharide and its binding protein also were significantly elevated in older participants, indicative of metabolic endotoxemia, which is a recently described phenomenon of increased plasma endotoxin level in metabolic disease. These alterations in older participants were accompanied by decreased insulin sensitivity, quadriceps muscle volume, and muscle strength. The exercise training program increased insulin sensitivity, without affecting quadriceps muscle volume or strength. Muscle TLR4, nuclear factor κB, and c-Jun N-terminal kinase, and plasma lipopolysaccharide and lipopolysaccharide binding protein were not changed by exercise. In conclusion, insulin resistance and sarcopenia of aging are associated with increased TLR4 expression/signaling, which may be secondary to metabolic endotoxemia.
     
  4. OP
    haidut

    haidut Member

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    So...naltrexone or another TLR4 antagonist could be synergistic with glycine? I saw a few studies saying emodin (another TLR4 antagonist) is anabolic for bone and muscle so it matches with the studies you posted.
     
  5. robknob

    robknob Member

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    Interesting studies all, another good reason to eat meat. I wonder why cows milk is so low in glycine seeing as it is otherwise extremely anabolic...
    I agree with your premise regarding chronic inflammation but in the real world having glycine + LPS would probably send two very different signals, possibly inhibiting the immune response in a dangerous way, better to stop the LPS at its source before signaling for anabolism for you old folks out there.
     
  6. Koveras

    Koveras Member

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    I agree that stopping LPS at the source is a good strategy but I would be surprised if glycine was anti-inflammatory in a negative or dangerous fashion

    • "Glycine protects against shock caused by hemorrhage, endotoxin and sepsis, prevents ischemia/reperfusion and cold storage/reperfusion injury to a variety of tissues and organs including liver, kidney, heart, intestine and skeletal muscle, and diminishes liver and renal injury caused by hepatic and renal toxicants and drugs. Glycine also protects against peptidoglycan polysaccharide-induced arthritis and inhibits gastric secretion and protects the gastric mucosa against chemically and stress-induced ulcers."
    • "Dietary glycine improved survival rates and liver function in endotoxemic mice by regulating the production of proinflammatory or anti-inflammatory cytokines in liver. It attenuated liver injury by deactivating KCs through inhibiting TNF-alpha secretion and increasing IL-10 production.”
    • " Interestingly, dietary glycine largely prevented inflammation and injury in the lung following endotoxin.”
     
  7. Lucenzo01

    Lucenzo01 Member

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    Thanks Haidut. I still don't know why I react in such a weird way to glycine and it's a pain the ass after reading all its benefits.
     
  8. milk_lover

    milk_lover Member

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    What brand are you using? Pure Bulk glycine doesn't give me bad symptoms.
     
  9. Nathan777

    Nathan777 Member

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    So for supplementation is it recommended to take pure glycine, or collagen/gelatin supplementation along with muscle meats as RP suggests should work just as well (or better)?
     
  10. Waynish

    Waynish Member

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    I keep hearing this... Where is aspirin found in nature?
     
  11. Nathan777

    Nathan777 Member

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  12. robknob

    robknob Member

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    Hmm I stand corrected... now that I think about it, glycine is definitely not anabolic by itself, so it wouldn't be sending signals like I was thinking. Leucine on the other hand would be sending those signals so that'd be interesting to compare the two.
     
  13. OP
    haidut

    haidut Member

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    Are you sure? Look at the original post and the underlined quote in red. Glycine (by itself) increased protein synthesis and reduced its degradation.
     
  14. REOSIRENS

    REOSIRENS Member

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    Glycine is really great... I am already fit ...but whenever I take calcium carbonate with glycine I get buff really fast...it burns fat so easily and without exercise...
     
  15. Jeemmy

    Jeemmy Member

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    That sounds so good, how much do you take?
     
  16. robknob

    robknob Member

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    I see what you're saying, but many amino acids upregulate mTOR. Sensing of amino acids is the basic cell stimulus for growth, so glycine is not unique in this way and is not on the level of bcaas as you would know. Besides, how long could protein synthesis be maintained with just glycine? The EAAs would likely be exhausted very quickly if only glycine is provided.

    My point was just that it's interesting that glycine appears to be an immune factor as well as an anabolic factor, which are circuits that are generally opposed to each other. Maybe it is the versatility of glycines simple structure.
     
  17. Antonello

    Antonello Member

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    can we consider supplement magnesium glycinate a good source for get glycine?
     
  18. OP
    haidut

    haidut Member

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    Yes, as it is mostly glycine. The elemental magnesium in the glycinate salt is somewhere around 10% so the rest is glycine.
     
  19. Kunder

    Kunder Member

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    Most of my amino acid supplements have an L - in the name. My glycine doesn’t even though it is the same manufacturer.

    What gives?
     
  20. OP
    haidut

    haidut Member

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