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Glutamine and muscle wasting

Glutamine and muscle wasting

Exercising as an anti-depressant treatment improves myscle immunity and prevents Glutamine and muscle wasting enteroinvasion during parenteral nutrition. It Glutamine and muscle wasting as a buffer and aasting excess muuscle into other amino acids, amino sugars and urea. The chaperone balance hypothesis: the importance of the extracellular to intracellular HSP70 ratio to inflammation-driven type 2 diabetes, the effect of exercise, and the implications for clinical management. Download the app. Article PubMed PubMed Central Google Scholar Rose WC.

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L-Glutamine Benefits

Glutamine plays a key role in several essential metabolic processes and Metabolic disorders and fat metabolism an important modulator of the heat shock protein HSP ajd, a crucial mechanism to maintain wastijg homeostasis and to promote cell resistance to injury and death.

This review summarized the effects of free l -glutamine or muecle dipeptide l -alanyl- l -glutamine upon muscle injury and inflammation, as well as muscle recovery from resistance training. The kDa HSP HSP70 expression is enhanced by glutamine, via the hexosamine biosynthetic pathway, which inhibits the NF-κB pathway regenerating and recovering myofibers through the regulation of the early inflammatory response to muscle injury, which may be impaired by local and systemic inflammatory injury due to reduced intracellular levels waating HSP Studies Glutamins that chronic oral administration wastibg free l wastibg or the dipeptide can attenuate the injury muscls inflammation induced by intense aerobic and Glutamine and muscle wasting exercise.

However, the effects Skin nourishing ingredients muscle recovery from resistance training are unclear. Wasing G. Candow, Scott C. Forbes, Fat loss mindset secrets Paul Faulkner.

Musclee C. Refalo, Eric R. Helms, … Jackson Wawting. Mishti Wastibg, Robert J. Naughton, … Liam Corr. Glutamine is a versatile amino acid, abundant in the plasma and skeletal muscle, accounting for most Skin nourishing ingredients the intramuscular free amino Glutaine content.

It is Gluyamine from glutamate and ammonia by the enzyme glutamine synthetase, and is stored and released predominantly by the skeletal muscle [ 1 ]. This amino acid is also synthesized by adipocytes, liver, and GGlutamine, and after its release into the bloodstream, glutamine is transported to be metabolized nad several tissues [ 2 ].

As a precursor for Gputamine and pyrimidines, glutamine enables the synthesis of DNA and Muxcle, Glutamine and muscle wasting Gluta,ine synthesis and DNA repair of nucleotide and nucleic acids [ Elevate workout reaction time45 mscle.

This amino acid is also used as the main oxidative fuel to replenish intermediates of the tricarboxylic acid cycle in rapidly dividing cells [ aand ], such as enterocytes and colonocytes Gltuamine 6 ], fibroblasts, Glutajine immune cells such as lymphocytes [ 78 ], macrophages, and neutrophils [ 9 Natural metabolic boosters, 10 wasitng, 11 musce, 12 ].

The members an the solute carrier SLC 38 gene family are the principal transporters of glutamine in mammalian cells, allowing the extremely rapid cellular turnover rates Glutaminr glutamine flux [ 1314 ] and the redox aasting [ Glutamin ].

Glutamine is the major inter-organ nitrogen transporter and regulator of acid-base balance. In the kidneys, Glutamine and muscle wasting is used nad the muuscle epithelial cells providing NH3 for urea synthesis and elimination of muscoe excess wastinh [ 116 ].

The skeletal muscle amino acid metabolism generates glutamine to detoxify the ammonia produced [ 17 Glutamine and muscle wasting, Monitoring blood sugar levels ].

Additionally, glutamine contributes to the intermediary metabolism [ 19 ] in the synthesis of amino sugars and proteins [ 202122 ], promotes insulin secretion from pancreatic beta cells, wastinv is Glutaamine precursor of key molecules such as myscle excitatory neurotransmitter glutamate, the inhibitory neurotransmitter γ-aminobutyrate GABAand the antioxidant glutathione GSH anx 1Coconut Oil for Petswawting ], considered a powerful marker Skin nourishing ingredients the cellular redox potential [ Glutammine26 ].

It ad also wastinf demonstrated that glutamine enhances the Electrolyte Levels junction protein abundance, maintaining the integrity Hydration for outdoor workouts the Nutritional support for joint health in athletes mucosal barrier wastimg improving its function wasitng 27Gkutamine ].

Recently, glutamine was amd to reduce the intestinal catabolism of amino acids, which may improve their bioavailability in the musccle circulation [ 29 ].

Notwithstanding, glutamine adn also a potent inducer of the heat wazting protein Glutaamine response to wqsting homeostasis, Glutaminw repair from injury and mhscle death [ 30 musclle, 31 ].

Annd being originally classified as a waating amino acid [ 32 ] in healthy individuals [ Glutajine ], abundant Gltuamine suggests that Citrus aurantium for digestion is essential in specific stress situations such as severe Ideal body composition, trauma, and overtraining [ 93435GlutwmineSkin nourishing ingredients, 37 amd, 38 ].

In hypercatabolic states, when the elevated demand exceeds the Glutakine to produce adequate amounts of this amino acid Glutamihe 394041 ], the impairment of immune function may occur [ 3742 ].

Due to the important pleiotropic roles in metabolism muzcle tissue homeostasis, glutamine is one of the most studied amino acids Oral medication for diabetes prevention exercise immunology [ 33 ]. Given the Guarana Capsules for Focus consumption of free glutamine by intestinal cells, musle dipeptides have been studied as an alternative for transposing the intestinal Glutamne and increasing the bioavailability of this amino wastig to cells of the immune system.

Conversely, the effects wastinh these supplements on muscle recovery musle resistance wastihg are poorly elucidated.

Thus, the aim of this Glytamine was to summarize the evidence regarding the effects of free l muacle or the dipeptide l -alanyl- l G,utamine upon muscle injury and inflammation, as well as on muscle recovery from resistance training. Muscle contractions wating mechanical loading Gluatmine microtrauma in muscle fibers, resulting in the rupture of the extracellular matrix, basal an, and Glutamihe, in addition to the alteration of calcium homeostasis, which promotes changes in the cell membrane structure and permeability [ 4849 ].

Following structural damage and functional impairment of the Glutaminf tissue, wasitng rupture and extravasation of intracellular proteins such as myoglobin, creatine Glytamine CKand lactate dehydrogenase Lowering AC levelsinto the extracellular medium, trigger the local inflammatory response [ 4750Glutanine52 ].

Hence, ahd stress muzcle in the skeletal muscle Glutakine triggered by damage to protein structure and might be further increased by the secondary induced damage in addition wastimg inflammatory processes [ 49 ]. The local inflammatory response involves muscle protein Glutamkne systems that are orchestrated by a anr of signalling pathways, wastinng or suppressed by hormones and cytokines [ 50 musclw, 53 ].

Protein degradation in muscle tissue is accompanied by a systemic acute phase response that may vary according to the type of exercise and its frequency, duration, and intensity [ 54 ]. Local inflammation is characterized by an increased number of infiltrating and resident immune cells, such as mast cells [ 55 ], neutrophils and T regulatory lymphocytes [ 56 ], eosinophils [ 57 ], and CD8 T lymphocytes [ 58 ] at the injury site, thereby releasing pro-inflammatory effectors.

Macrophages are the predominant leucocytes observed during the regeneration phase of the stretch-injured skeletal muscle, exerting specific roles throughout the whole process.

Briefly, exercise-induced inflammatory processes include the release of cytokines and chemokines driving a rapid influx of neutrophils, followed by the differentiation of monocytes into macrophages that promote the phagocytosis of necrotic muscle debris.

These cells switch then into anti-inflammatory macrophages and proliferate during the regeneration process of the damaged skeletal muscle [ 60 ].

During local inflammation occurs the synthesis and release of molecules such as monocyte chemotactic protein MCP -1, chemokine derived from macrophage MDCtumour necrosis factor TNF -α, interleukin IL -8, vascular endothelial growth factor VEGFleukaemia inhibitory factor LIFfractalkine, and urokinase plasminogen activator uPA [ 5361 ].

Most of these proteins act as chemotactic factors at the site of inflammation, promoting the initial recruitment of satellite cells, neutrophils, monocytes, and, later, lymphocytes for tissue repair [ 5262636465 ].

Eccentric exercise is acknowledged for the generation of a local inflammatory response in the skeletal muscle with the timing and peak of neutrophil infiltration linked to the magnitude of muscle function decrements [ 6667 ]. Intense exercise stimulates a well-defined systemic cytokine response, associated with the exercise-induced metabolic stress responses [ 6869 ].

The systemic response initiates with a rapid increase of pro-inflammatory components IL-6, IL-8which in turn generates an anti-inflammatory feedback by increasing the release of interleukin IL and interleukin IL -1 receptor antagonist [ 70 ]. The resolution of inflammation characterizes a shift from a pro-inflammatory state to the anti-inflammatory phase, followed by repair and regeneration of injured tissues, processes markedly played by macrophages that include angiogenesis, matrix remodelling, and establishment of homeostasis [ 71 ].

This process is vital for the recovery of injured muscle; however, continuous muscle injury triggers a chronic inflammatory response, which can aggravate the underlying lesions by degrading intact proteins, implying reduced performance and compromised health [ 527273 ].

Systemic inflammation is associated with reduced rates of protein synthesis in addition to an enhanced protein breakdown [ 74 ]. In this regard, pro-inflammatory cytokines may account for the loss of muscle mass by activating catabolic and downregulating the anabolic pathways [ 75 ].

Intense training with continuous rest deprivation increases the release of pro-inflammatory indicators, which may induce fatigue and overtraining syndrome in athletes [ 53 ]. The effects exerted by pro-inflammatory cytokines on muscle mass are partially mediated by the induction of the transcription factor NF-κB signalling [ 487677 ].

In a single bout of intense resistance exercise and in an acute bout of treadmill run, NF-κB activity is increased in the skeletal muscle of humans and rats, respectively [ 7879 ], in addition to an increase in genic expression of the interleukins IL-6, IL-8, IL-1β, and IL and of TNF-α, MCP-1, LIF, and TG-β [ 53 ].

It has been proposed that cytokines e. IL, IL, and IL may have anabolic effects and modify the contractile function of the skeletal muscle. Cytokine secretion by the skeletal muscle involves several intracellular factors such as MCP-1, heat shock factor HSF -1, and histone deacetylases, besides nuclear factor of activated T cells and NF-κB [ 5361768081 ].

The NF-κB signalling pathway acts as the central regulator of the stress-induced mechanical, oxidative, and inflammatory responses [ 5277 ]. However, its persistent activation, as well as increased synthesis of inflammatory molecules, may excessively recruit immune cells, consequently promoting additional tissue damage [ 73 ].

Under these conditions, protective systems such as HSP are activated against excessive inflammatory damage induced by exercise, in order to restore homeostasis and ensure cell survival [ 3031 ]. One of the most basic mechanisms of cellular defence includes the expression of HSP to neutralize harmful agents and events, induce cell protection and tolerance to injury, and warrant maximum cell survival in the skeletal muscle [ 82 ].

HSP is a highly conserved family of stress-inducible proteins, essential for cellular homeostasis, protecting against a variety of stress stimulus [ 8384 ], injury, and death and modulating the early inflammatory response to muscle injury [ 3031 ].

These proteins are named according to the molecular weight as follows: HSP90, HSP70, HSP60, and HSP27, and the upregulation under stress conditions provides cytoprotection by re-establishing protein homeostasis against several stressors, including exercise [ 85 ].

Under normal physiological conditions, HSP acts as a chaperone protein helping the protein folding mainly unfolded, misfolded, and partially folded new peptide chains and translocation into the endoplasmic reticulum lumen [ 86 ].

When the body is under excessive stress, these proteins exert a protective role by lessening oxidative action of the reactive oxygen species ROS and a wide range of metabolic stress, including structural and functional myodamage [ 8788 ]. Despite the fact that exercise is a potent inductor of the HSP response [ 89 ], local and systemic inflammatory lesion leads to a reduction in intracellular HSP70 levels, which may impair tissue readjustment [ 308990 ].

Modifications in gene expression occur to yield an increase in the content of HSP [ 3031 ], proteins that act as molecular chaperones, being crucial in helping the cellular remodelling processes of denatured proteins, independent of the training response [ 8991 ]. A reduction in pro-inflammatory cytokine release has been observed following the initiation of a heat shock response [ 85 ], and this process may be related to the binding of HSP to the heat shock element HSE found in the promoters of cytokine genes e.

IL-1β [ 9293 ]. During stress, the latent monomer of heat shock factor HSF -1 is rapidly converted to a trimeric form active in the nucleus to bind to the promoters of HSF-responsive heat shock genes and activate their transcription [ 9495 ].

HSF-1 has been demonstrated to perform this function by repressing the transcription of cytokine genes, including TNF-α and IL-1β, antagonizing the acute phase response [ 9296 ]. Because IL-1β immediately responds to a wide diversity of pro-inflammatory insults and affects the function of many targets, it is essential to limit the potentially harmful aspects of inflammation by negatively regulating IL-1β expression [ 92 ].

HSP27 and HSP70 are considered the most robust and recognized induced chaperones; both play important cytoprotective roles acting at multiple apoptotic pathway control points to ensure that stress-induced injury does not inappropriately trigger cell death, thus disabling apoptosis [ 97 ].

The induction of HSP is characterized by low transient regulation of most cellular proteins and the expression of the kDa protein family HSP A kDa stress-inducible Hsp72, a prominent member of the HSP70 family, is one of the largest inducible HSP isoforms interacting with other proteins in a way dependent of ATP and has been extensively studied in the mammalian skeletal muscle [ 31 ].

The Hsp72 expression is more abundant in slow-oxidative than fast-glycolytic skeletal muscle fibres, and the expression is elevated by the increased contractile activity of the muscles with exercise, as well as heat stress [ 98 ].

HSP70 has been involved in the regulation steps of skeletal muscle plasticity [ 303199], apoptosis, and cell death, affecting protein refolding processes, signalling for ubiquitin degradation, and translocation of proteins [ ]. Both exhaustive endurance exercise and resistance exercise with maximal eccentric repetitions have been shown to increase the level of Hsp72 expression [ ].

In general, HSP70 is induced by diversified stimuli such as hypoxia, acidosis, increased muscle temperature, and ischaemia-reperfusion, most of them are by-products of resistance exercise associated with elevated levels of metabolic stress [ 3089 ].

Conversely, in exercise, HSP facilitates mitochondrial biogenesis, despite regulating the signalling pathways associated with apoptosis [ 49].

HSP70 is also involved in the control of the primary response to muscle injury [ 30 ] and inhibition of the NF-κB signalling pathway by modulating the inflammatory response and attenuating pro-inflammatory cytokine release [, ]. The chaperone equilibrium hypothesis proposes that NF-κB activation may decrease intracellular levels of HSP70, releasing extracellular HSP70 as a pro-inflammatory component, which may be linked to reduced oxidative stress in target cells.

Nonetheless, when extracellular HSP70 is continuously elevated, it stimulates inflammation, oxidative stress, reduced expression of HSF-1, and possibly reduced intracellular HSP70 [ 91 ]. Stress conditions promoting instability and denaturation of proteins induce the release of HSF-1, which the activity is associated with the expression of HSP70 in the myocardium, skeletal muscle, and human leucocytes [ 76].

Evidence suggests that the increased HSP expression on the leucocyte surface after acute intense training signals excessive stress [ ].

In general, the expression of HSP70 has become a major interest of studies because of its role in modulating inflammatory immune response and cytoprotection under stress conditions in a wide diversity of experimental injury models [ 73]. In this sense, the effect of glutamine as a potential therapeutic element has been observed.

Glutamine improves HSP70 and HSP27 expression [ 4344] and acts not only as a modulator of the heat shock response but also as a competent inducer of HSF-1 expression, activating its transcription [ 93, ].

The hexosamine biosynthetic pathway HBP has been shown to induce HSP70 expression, and glutamine is an essential substrate for this pathway. Its activity is enhanced by glutamine via O-glycosylation, leading to the translocation and transcriptional stimulation of key transcription factors HSF-1 and Sp1 required for maximal HSP70 induction [ ].

The expression of the HSF-1, HSP70, and HSP27 all depend on Sp1 for optimal transcriptional activity [ ]. Considering the effect of glutamine on Sp1 and in the modulation of the HSP response [ 93,], this amino acid has been considered an important therapeutic element [ 33 ].

Hence, glutamine could be used to induce a beneficial stress response and prevent tissue damage under disturbing conditions Fig. Moreover, HSP synthesis has shown to be dependent on adequate concentrations of glutamine [ 93 ].

Glutamine modulates the exercise-induced heat shock and inflammatory responses. The heat shock response is induced by stress signals produced during exercise. HSP70 and HSP27 are upregulated under stress conditions providing cytoprotection by remodeling misfolded and unfolded proteins and limiting damage induced by reactive oxygen species ROS and inflammatory stimulus.

The latent heat shock factor HSF -1 monomer is converted to a trimeric active form in the nucleus during stress to bind to the promoters of heat shock genes and activate transcription. HSP70 also regulates the primary response to muscle lesion and inhibits the NF-κB signalling pathway by modulating the inflammatory response and attenuating pro-inflammatory cytokines release.

Glutamine improves HSP70 and HSP27 expression and acts not only as a modulator of the heat shock response but also as a competent inducer of HSF-1 expression, activating its transcription.

: Glutamine and muscle wasting

Regenerating muscle Sorry, a shareable link is not currently available for this article. Article CAS Google Scholar Darmaun D, Manary M, Matthews D A method for measuring both glutamine and glutamate levels and stable isotope enrichments. Lacey JM, Wilmore DW. It has been suggested that the effects of glutamine are mixed, and studies fail to demonstrate positive benefits on buffering capacity, time to exhaustion, protein balance, and other ergogenic effects regarding muscle recovery from exercise [ ]. Matthews D, Motil K, Rohrbaugh D, Burke J, Young V, Bier D Measurement of leucine metabolism in man from a primed, continuous infusion of L-[1- 13 C]leucine.
Oral L-glutamine pretreatment attenuates skeletal muscle atrophy induced by h fasting in mice Preedy Department of Biomedical Sciences, University of Westminster, London, United Kingdom Vinood B. Due to the important pleiotropic roles in metabolism and tissue homeostasis, glutamine is one of the most studied amino acids in exercise immunology [ 33 ]. Simar D, Malatesta D, Badiou S, Dupuy AM, Caillaud C. Glutamine is the major inter-organ nitrogen transporter and regulator of acid-base balance. L-alanylglutamine inhibits signaling proteins that activate protein degradation, but does not affect proteins that activate protein synthesis after an acute resistance exercise.
Glutamine protects against muscle injuries and aging

Using in vitro and in vivo state-of-the-art methodologies the researchers showed that muscle injury, ischemia and aged-related muscle wasting are conditions characterized by reduced glutamine. One reason for this is the loss of glutamine production by the muscle itself because of its damage.

Berardi explains, "Using genetic tools and pharmacological drugs inhibiting GLUD1, an enzyme that metabolizes glutamine, we could prevent the post-injury drop in glutamine. This resulted in the overproduction of glutamine by inflammatory cells , named macrophages, reaching the muscle after damage.

The newly produced glutamine could be used by muscle stem cells to quickly regenerate the damaged muscle tissue. We found the same thing in acute as well as chronic degenerative conditions, such as aging, leading to a faster muscle functional recovery. This study reveals glutamine as a sensor molecule whose levels in the muscle tissue control a regenerative program and suggests that GLUD1 is a therapeutic target that could enable opportunities for muscle regeneration after acute injury or chronic degenerative conditions such as aging.

Mazzone emphasizes the potential of their discovery: "This provides hope for the treatment of degenerative muscle conditions, including trauma, ischemia and aging.

The latter in particular represents an important challenge for healthcare with an increasing average age of the global population, accompanied by aged-related sarcopenia. In a joined effort with VIB Discovery Sciences and the Centre for Drug Design and Discovery, we are currently developing and testing more selective GLUD1 inhibitors for chronic muscle wasting conditions including muscular dystrophy.

More information: Min Shang et al. Macrophage-derived glutamine boosts satellite cells and muscle regeneration, Nature DOI: html This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission.

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An observer blinded to the group allocations performed the tissue analysis and scored the severity of organ injury.

The severity of liver injuries observed in the tissue sections was scored as follows: 0, minimal or no evidence of injury; 1, mild injury consisting of cytoplasmic vacuolation and focal nuclear pyknosis; 2, moderate to severe injury with extensive nuclear pyknosis, cytoplasmic hypereosinophilia, and loss of intercellular borders; and 3, severe necrosis with disintegration of the hepatic cords, hemorrhage, and neutrophil infiltration Ke et al.

All evaluations were performed on five fields per section and five sections per organ by a blinding observer. The collected data were analyzed using SPSS for Windows v The continuous variables have been expressed in Mean ± SD, and an independent t -test was employed to analyze and compare the tissue injury score between prevention and treatment group.

The analysis of variance ANOVA was applied to examine the differences of CK-MM and blood cell count between three groups. The significance level for all statistical comparisons was set as α less than or equal to 0.

The skeletal muscle damage biomarker CK-MM was analyzed. The data showed that timing of the oral intake affects the reduction of serum CK-MM level. The CK-MM level of untreated vehicle group was elevated after exhaustive exercise and reached its highest point at 24 h after exercise Figure 1. The serum CK-MM level of the prevention group was elevated at 12 h.

The treatment group exhibited almost no elevation. FIGURE 1. The comparison of CK-MM levels between groups. The CK-MM levels of treatment group were lower than those in prevention group at 12 and 24 hs. Complete blood count analysis was performed at various time points after exercise treatment.

Hematocrit showed a similar trend to RBC. The average HCT was significantly higher in the treatment group 12 h after exercise and reached a maximum difference at 24 h. We also observed that PLT improved to a similar extent as RBC did.

The average PLT was considerably higher in the treatment group after exercise 12 h and had a maximum improvement at 24 h.

The average PLT of the treatment group in p24 was In this part, we found that oral intake of glutamine elevated RBC, HCT, and PLT amounts only in the treatment group.

FIGURE 2. The comparison of blood count levels between groups. Treatment group had higher RBC A , HCT B and PLT C values than those in prevention group at 24 hs. The HE staining results indicated tissue injuries in the cardiac muscles Figure 3A , kidneys Figure 3B , and liver Figure 3C in the prevention group, with average respective scores of 1.

The treatment group had less tissue injury in the cardiac muscles Figure 3D , kidneys Figure 3E , and liver Figure 3F , with average respective scores of 0 Figure 3G , 1.

These data of histological examination indicated that the treatment group had a more substantial reduction in damage, especially cardiac and renal damage, compared with the prevention group Figure 3. FIGURE 3. The histological finding and tissue injury score between prevention and treatment group.

The histological examination of prevention A—C and treatment group D—F. The prevention group had higher tissue injury score on the Heart G and kidney H than those in treatment group. There was no significant difference between groups on the liver I.

We found that glutamine can reduce skeletal muscle damage caused by exhaustive exercise, and the treatment group had a greater reduction in damage than the prevention group did Figure 1. We also found that oral intake of glutamine elevated RBC, HCT, and PLT amounts only in the treatment group Figure 2.

A histological examination indicated that the treatment group had a more substantial reduction in damage, especially cardiac and renal damage, compared with the prevention group Figure 3.

The results of this study indicated that the effect of supplementing L-glutamine after exercise was more satisfactory than that before exercise. The tissue section results demonstrated that glutamine not only protected muscles under exhaustive exercise but also prevented damage to specific organs.

After exhaustive exercise, because of the continued contraction of skeleton muscles and enhanced circulation stress, both skeletal and cardiac muscles are damaged. Markers of skeletal and cardiac muscle damage, such as serum biomarker CK-MM, indicated damage after exercise, and the damage could also be found in histopathology examinations Amelink et al.

Studies have demonstrated that supplementation with glutamine has beneficial effects on reducing the parameters of muscle damage and inflammation in exercise rats Bowtell et al. Similarly, in our study, the serum CK-MM level of the untreated vehicle group was elevated after exhaustive exercise and reached its highest point at 24 h after exercise Figure 1.

Decreased glutamine concentrations typically correlate with the severity of the underlying disease process, with large amounts of glutamine catabolized in muscle at the time of damage. Concentrations only gradually recover in the later stage of healing Durkalec-Michalski et al.

During exhaustive exercise, the protein metabolism of muscles increases. At this time, glutamine can assist in gluconeogenesis, generating glucose to be used by the muscles, promoting energy metabolism and antioxidant capacity, reducing organ damage, and contributing to the synthesis and repair of muscle tissue.

Under exhaustive exercise, glutamine in the body is used in substantial quantities, resulting in a decreased glutamine concentrations Afonso et al. We further found that the intake timing will notably affect the beneficial effect of glutamine for exhaustive exercise.

This might cause by a short half-life of glutamine. Glutamine was more effective when taken orally after rather than before exhaustive exercise. We also found that the RBC level increased substantially upon the post-exercise intake of glutamine Figure 2.

Previous researchers have demonstrated that glutamine is an essential source for glutathione synthesis in human erythrocytes Whillier et al.

During exhaustive exercise, because of elevated oxidative stress and overloaded cardiac output, RBC becomes oxidative damaged Smith, No study has discussed whether glutamine mitigates oxidative damage on RBC or enhances the regeneration of RBC after exhaustive exercise.

We found that the RBC level increase and accordingly glutamine might enhance the regeneration of RBC upon oral intake after exercise Figure 2.

The differences between the prevention and treatment groups were not only with respect to RBC concentration, but also regarding tissue damage for histological examinations. The treatment group showed more considerable damage reduction in the cardiac muscle and kidneys than the prevention group showed.

Figures 3G, H The primary cause for this difference in damage reduction might be the maldigestion of glutamine during exercise. Eating before exhaustive exercise often causes maldigestion; furthermore, body temperature increases during exercise until rest.

Research has demonstrated that in a hot environment, intestinal permeability is reduced by glutamine supplementation Pugh et al. Therefore, glutamine intake is more beneficial after rather than before exhaustive exercise. Relative to the prevention group, the treatment group had a more considerable reduction in the damage to their cardiac muscles and kidneys.

Our results revealed that the timing of glutamine oral intake influences outcomes, such as improved organs protection and elevated RBC concentration in blood.

Although the conditions of sports practice in humans are far different from those that can be applied in laboratory rats, these results might suggest athletes take supplements at the proper timing after exhaustive exercise.

Daily supplementation of L-glutamine can reduce the skeletal muscle damage caused by exhaustive exercise and that the timing of the oral intake affects the reduction. Glutamine as a treatment more considerably reduced damage than it had as a prophylactic.

We also observed that the oral intake of glutamine could elevate RBC, HCT, and PLT only after exhaustive exercise. It seems like the proper timing for taking glutamine supplements is after exercise. However, the further clinical trial is needed in the future study.

The animal study was reviewed and approved by the Institutional Animal Care and Use Committee of Tzu Chi University IACUC No: C-CL: Conceptualization, and prepared the original draft.

C-YK: Designed the animal study, analyzed the data, and wrote the original draft. W-TW: Performed the histological examination, supervised the study and data collection. R-PL: Conceptualization, supervised the study, completed the final manuscript.

All authors contributed to the article and approved the submitted version. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers.

Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. Afonso, J. The effectiveness of post-exercise stretching in short-term and delayed recovery of strength, range of motion and delayed onset muscle soreness: A systematic review and meta-analysis of randomized controlled trials.

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L-glutamine and recovery Addition of glutamine Circuit training routines Skin nourishing ingredients amino ad and wasfing does not Glutamin anabolism in young human males following exercise. Skin nourishing ingredients references. Supplementing with L-glutamine allows your muscles Skin nourishing ingredients fight and mudcle a bit further. Krause M, Heck TG, Bittencourt A, et al. Diabetes mellitus, a disease affecting a quarter of a billion people worldwide [4]can cause skeletal muscle damage and atrophy via diabetic neuropathy and by the more direct effects of high glucose and low insulin [3] on muscle cell metabolism. Read on to find out if glutamine can benefit bodybuilders and other athletes!
Glutamine and Myostatin Expression in Muscle Wasting

Conclusion: The therapeutic effect of L-glutamine after exhaustive exercise was more effective than preventive before exercise. Acute muscle damage often occurs after exhaustive exercise and also causes levels of lactatic acid, creatine kinase CK , aspartate aminotransferase AST , alanine aminotransferase ALT , and lactate dehydrogenase in serum to increase Baumert et al.

Exercise, especially exhaustive exercise, defined as exercise till unable to move, causes an inflammatory response and damage to multiple organs, including skeletal muscles, the respiratory system, the liver, and the kidneys Ke et al.

During exhaustive exercise, inflammatory responses such as leukocyte aggregation can be identified in muscle tissue Peake et al. Muscle damage can occur when weaker sarcomeres are destroyed during muscle contraction or when a coupling mechanism stimulated through muscle excitation leads to excessive muscle lengthening Negro et al.

In addition, protein catabolism is greater than protein anabolism during exhaustive exercise. In the metabolic pathway of protein catabolism, the nitrogen-containing pathway must first undergo transamination Gleeson, ; Coqueiro et al. Glutamine in the muscle is converted into glutamic acid to facilitate transamination, and the glutamine concentration in the body thus decreases after exhaustive exercise Trivedi et al.

Therefore, a moderate amount of glutamine supplementation may assist in reducing muscle damage resulting from exhaustive exercise Gleeson, Glutamine is not only nutritious but also able to regulate other bioactivities in the body. The animal study indicates that oral supplementation with L-glutamine and alanine in the free form can effectively maintain glutamine stores, leading to lower levels of proinflammatory biomarkers such as TNF-a, IL-1β and IL-6 Cruzat et al.

Additionally, the study shows that these supplementations can also have beneficial effects on biomarkers of muscle damage and inflammation such as muscle glycogen and plasma creatine kinase isozyme CK after a period of training.

The study also found that while glutamine and alanine supplementation improved some fatigue markers, it did not improve exercise performance Coqueiro et al. Moreover, glutamine affects many bioactivities in the digestive system and the immune system in the human body. In the digestive system, glutamine supplements can accelerate rapidly dividing cells and reduce splanchnic bed damage in the intestines, liver, and pancreas Coqueiro et al.

In the immune system, glutamine downregulates lymphocyte count, macrophage count, and the expression of proinflammatory cytokines, such as interlukin-1 IL-1 , IL-2, Interferon-gamma Amin et al. Glutamine supplementation for human exercise was demonstrated to effectively reduce tissue and organ damage and promote glycogen synthesis, providing nutritional support for the immune system, and preventing infection Bowtell et al.

Muscle metabolism parameters such as creatine kinase isozyme MM CK-MM were used as an indicator for muscle damage. The serum level of CK-MM typically increases after exercise Banfi et al. During exercise, local hypoxia in skeletal muscles, accumulation of metabolites, and an increase in free radicals cause cell membrane damage and increased permeability.

At this time, CK-MM in muscle cells penetrates the cell membrane and enters the blood, which is the same process that leads to an increase of CK-MM after exhaustive exercise Koch et al.

Platelet count also decreases after exercise and this decrease might be related to exercise-based cardiac rehabilitation that decreases mortality in patients with coronary artery disease Anz et al.

Researchers also have reported that supplementation after exercise exerts many beneficial effects; especially in muscle recovery and connective tissue damage Grassi et al.

Although studies have demonstrated that glutamine has beneficial effects for exercise, a crucial factor remains unclear. Researchers have been focused on the effect of glutamine on immunoregulation and muscle damage during exercise, and no other organ pathology observation for the use of glutamine has been undertaken.

Furthermore, no study has discussed whether various intake timings affect glutamine bioactivity in exhaustive exercise. If glutamine supplementation has a treatment effect after exercise, then glutamine supplementation may be has a preventive effect before exercise.

Nevertheless, there is no research show which is better to have glutamine supplementation before or after exercise. Thus, the purpose of this study was to examine the differential effect of glutamine supplementation before and after exercise to identify the optimal timing of glutamine supplementation.

We hypothesize that glutamine supplementation before exercise may have a similar effect to after exercise. Besides, glutamine regulates not only the immune cells but also other tissues or blood cells, such as RBC and platelets. In this study, animal experimentation was conducted to explore the difference in the effect of L-glutamine supplementation at different times i.

The Sprague—Dawley rat model was applied. The eighteen experimental animals were randomly divided into three groups, namely, the vehicle group no glutamine treatment , the prevention group administered glutamine before exhaustive exercise , and the treatment group administered glutamine after exercise.

The three groups engaged in the same exercise program. Blood samples were collected at different times, and CK-MM was tested to assess muscle tissue damage. After the experiment, heart, kidney, and liver tissue sections were dissected to measure tissue damage. The animal study was performed according to institutional protocols of the Institutional Animal Care and Use Committee of Tzu Chi University IACUC No: Experimental rats, with body weights between and g, were ordered from LASCO animal center Taipei, Taiwan.

The rats were housed in a controlled environment of 22°C ± 1°C with a 12 h light-dark cycle. Food pellets and water were provided ad libitum. Before the beginning of the day experiment, the rats were trained to exercise on a treadmill.

After 14 days, the rats were transitioned to exercising on a treadmill and underwent exhaustive exercise. The rats were randomly grouped into a vehicle group, treatment group, and prevention group.

The vehicle group received 0. The actual mean dose of L-glutamine administered was between 0. The prevention group received the same single-dose glutamine 1 hour before the exercise.

During this period, polyethylene catheters PE were inserted into the right femoral artery to collect blood samples Ke et al. The femoral artery catheter was also connected to an electrophysiological amplifier Gould Instruments, Cleveland, OH, United States to monitor arterial pressure and heart rate.

The surgical incision was less than 0. After the surgery, the animals were placed in a metabolic cage and awakened soon thereafter. The rats were allowed free access to food and water.

Maximum running times were attained for each rat, and the maximum running time was 30 min. Exhaustion was defined in accordance per previous studies Ke et al.

Specifically, exhaustion was concluded to have occurred when the rat was unable to maintain pace with the treadmill and when the rat lay flat on the treadmill and remained on the grid at the back of the treadmill for a period of 30 s despite being gently pushed with sticks or breathed upon.

The blood samples were collected before exercise, 12 h and 24 h after exercise. These samples were placed into heparinized tubes and measured immediately for blood cell counts Sysmex K, NY, United States.

The samples were then centrifuged at 3, × g for 10 min. After centrifugation, supernatant was collected and the level of CK-MM was measured within 1 hour by using an automatic biochemical analyzer COBAS INTEGRA , Roche Diagnostics, Basel, Switzerland. Euthanasia was conducted 24 h after treatments.

The rats were deeply anesthetized using isoflurane inhalation and then blood withdrawal was performed for euthanasia. The heart, kidneys, and liver were removed immediately.

An observer blinded to the group allocations performed the tissue analysis and scored the severity of organ injury. The severity of liver injuries observed in the tissue sections was scored as follows: 0, minimal or no evidence of injury; 1, mild injury consisting of cytoplasmic vacuolation and focal nuclear pyknosis; 2, moderate to severe injury with extensive nuclear pyknosis, cytoplasmic hypereosinophilia, and loss of intercellular borders; and 3, severe necrosis with disintegration of the hepatic cords, hemorrhage, and neutrophil infiltration Ke et al.

All evaluations were performed on five fields per section and five sections per organ by a blinding observer. The collected data were analyzed using SPSS for Windows v The continuous variables have been expressed in Mean ± SD, and an independent t -test was employed to analyze and compare the tissue injury score between prevention and treatment group.

The analysis of variance ANOVA was applied to examine the differences of CK-MM and blood cell count between three groups. The significance level for all statistical comparisons was set as α less than or equal to 0. The skeletal muscle damage biomarker CK-MM was analyzed. The data showed that timing of the oral intake affects the reduction of serum CK-MM level.

The CK-MM level of untreated vehicle group was elevated after exhaustive exercise and reached its highest point at 24 h after exercise Figure 1.

The serum CK-MM level of the prevention group was elevated at 12 h. The treatment group exhibited almost no elevation. FIGURE 1. The comparison of CK-MM levels between groups. The CK-MM levels of treatment group were lower than those in prevention group at 12 and 24 hs.

Complete blood count analysis was performed at various time points after exercise treatment. Hematocrit showed a similar trend to RBC. The average HCT was significantly higher in the treatment group 12 h after exercise and reached a maximum difference at 24 h.

We also observed that PLT improved to a similar extent as RBC did. The average PLT was considerably higher in the treatment group after exercise 12 h and had a maximum improvement at 24 h. The average PLT of the treatment group in p24 was In this part, we found that oral intake of glutamine elevated RBC, HCT, and PLT amounts only in the treatment group.

FIGURE 2. The comparison of blood count levels between groups. Treatment group had higher RBC A , HCT B and PLT C values than those in prevention group at 24 hs. The HE staining results indicated tissue injuries in the cardiac muscles Figure 3A , kidneys Figure 3B , and liver Figure 3C in the prevention group, with average respective scores of 1.

The treatment group had less tissue injury in the cardiac muscles Figure 3D , kidneys Figure 3E , and liver Figure 3F , with average respective scores of 0 Figure 3G , 1.

These data of histological examination indicated that the treatment group had a more substantial reduction in damage, especially cardiac and renal damage, compared with the prevention group Figure 3. FIGURE 3. The histological finding and tissue injury score between prevention and treatment group.

The histological examination of prevention A—C and treatment group D—F. The prevention group had higher tissue injury score on the Heart G and kidney H than those in treatment group. There was no significant difference between groups on the liver I. We found that glutamine can reduce skeletal muscle damage caused by exhaustive exercise, and the treatment group had a greater reduction in damage than the prevention group did Figure 1.

We also found that oral intake of glutamine elevated RBC, HCT, and PLT amounts only in the treatment group Figure 2. A histological examination indicated that the treatment group had a more substantial reduction in damage, especially cardiac and renal damage, compared with the prevention group Figure 3.

The results of this study indicated that the effect of supplementing L-glutamine after exercise was more satisfactory than that before exercise. The tissue section results demonstrated that glutamine not only protected muscles under exhaustive exercise but also prevented damage to specific organs.

After exhaustive exercise, because of the continued contraction of skeleton muscles and enhanced circulation stress, both skeletal and cardiac muscles are damaged. Markers of skeletal and cardiac muscle damage, such as serum biomarker CK-MM, indicated damage after exercise, and the damage could also be found in histopathology examinations Amelink et al.

Studies have demonstrated that supplementation with glutamine has beneficial effects on reducing the parameters of muscle damage and inflammation in exercise rats Bowtell et al.

Similarly, in our study, the serum CK-MM level of the untreated vehicle group was elevated after exhaustive exercise and reached its highest point at 24 h after exercise Figure 1. Decreased glutamine concentrations typically correlate with the severity of the underlying disease process, with large amounts of glutamine catabolized in muscle at the time of damage.

Concentrations only gradually recover in the later stage of healing Durkalec-Michalski et al. During exhaustive exercise, the protein metabolism of muscles increases. At this time, glutamine can assist in gluconeogenesis, generating glucose to be used by the muscles, promoting energy metabolism and antioxidant capacity, reducing organ damage, and contributing to the synthesis and repair of muscle tissue.

Under exhaustive exercise, glutamine in the body is used in substantial quantities, resulting in a decreased glutamine concentrations Afonso et al.

We further found that the intake timing will notably affect the beneficial effect of glutamine for exhaustive exercise.

This might cause by a short half-life of glutamine. Glutamine was more effective when taken orally after rather than before exhaustive exercise. We also found that the RBC level increased substantially upon the post-exercise intake of glutamine Figure 2.

Previous researchers have demonstrated that glutamine is an essential source for glutathione synthesis in human erythrocytes Whillier et al. During exhaustive exercise, because of elevated oxidative stress and overloaded cardiac output, RBC becomes oxidative damaged Smith, No study has discussed whether glutamine mitigates oxidative damage on RBC or enhances the regeneration of RBC after exhaustive exercise.

We found that the RBC level increase and accordingly glutamine might enhance the regeneration of RBC upon oral intake after exercise Figure 2. The differences between the prevention and treatment groups were not only with respect to RBC concentration, but also regarding tissue damage for histological examinations.

The treatment group showed more considerable damage reduction in the cardiac muscle and kidneys than the prevention group showed. Figures 3G, H The primary cause for this difference in damage reduction might be the maldigestion of glutamine during exercise. Eating before exhaustive exercise often causes maldigestion; furthermore, body temperature increases during exercise until rest.

Research has demonstrated that in a hot environment, intestinal permeability is reduced by glutamine supplementation Pugh et al. Therefore, glutamine intake is more beneficial after rather than before exhaustive exercise.

Relative to the prevention group, the treatment group had a more considerable reduction in the damage to their cardiac muscles and kidneys.

Our results revealed that the timing of glutamine oral intake influences outcomes, such as improved organs protection and elevated RBC concentration in blood. Although the conditions of sports practice in humans are far different from those that can be applied in laboratory rats, these results might suggest athletes take supplements at the proper timing after exhaustive exercise.

Daily supplementation of L-glutamine can reduce the skeletal muscle damage caused by exhaustive exercise and that the timing of the oral intake affects the reduction.

Glutamine as a treatment more considerably reduced damage than it had as a prophylactic. We also observed that the oral intake of glutamine could elevate RBC, HCT, and PLT only after exhaustive exercise. It seems like the proper timing for taking glutamine supplements is after exercise.

However, the further clinical trial is needed in the future study. In vitro otherwise known as isolated cells in glass tubes studies, glutamine has been shown to increase muscle anabolism muscle growth when consumed in excess and catabolism muscle loss when not consumed to create a deficit.

The problem with in-vitro is that because these cells are separate from the rest of the body, many mechanisms are not able to happen, making the results not always the same between test tubes and actual people. This difference is proven in other human studies that have shown a failure to induce muscle protein synthesis when dosed the exact same scaling up of course as the vitro studies.

In other small studies also in vitro , it has been reported that glutamine lessens the rate of leucine oxidation, simply meaning it allows more leucine to go towards muscle growth. This might explain the results of other studies that have come before it.

Those participating in hours of endurance exercise without a chance to refuel may be able to achieve more benefits from glutamine in the form of faster recovery or less muscle catabolism dosed at anywhere between grams. Not because more glutamine will provide additional benefits, but because hours of physical activity might actually lower glutamine levels in the body below optimal, causing slower recovery or muscle loss.

This means any recovery or muscle loss prevention will come from returning glutamine stores in the body to their normal levels. This might help us understand why glutamine is less likely to benefit bodybuilding or intense but short training as it will not deplete glutamine stores enough to negatively affect recovery or muscle loss.

Others that might suffer from lower glutamine levels that potentially could benefit the same way as long-distance endurance athletes include individuals who eat a very low amount of protein in their diet, as well as vegans. Beyond exercise-related benefits though, glutamine has proven benefits in the realm of immune health and intestinal health.

Without getting too scientific which has already happened a bit too much in this article already , glutamine is required to produce a protein needed by white blood cells. This protein known as cytokines, and when increased in the body will actually help you fight off bacterial disease and possibly even help with healing wounds.

As for your intestines, the small intestine in particular requires more glutamine than any other part of your body. Simply put, glutamine helps maintain the integrity of the intestinal walls, lowering its permeability sometimes called a leaky gut.

So what does this all mean? Well unfortunately for those of us hoping to use it for increased recovery from weight lifting or increasing muscle protein synthesis, the studies are mixed.

In vitro studies have shown slight benefits, but when converted to actual human subjects these benefits seem to disappear. For those who are deficient in glutamine, such as vegans, individuals eating a very low protein diet or after a very long endurance workout, supplemental glutamine can help restore glutamine stores in their body to baseline.

This will provide them with an anti-catabolism effect of their muscle mass and increased recovery, but only back to the level of healthy individuals. It is naturally found in your body and has no negative side effects up to around 50 grams way more than you would ever need to take.

Who knows, we may find out eventually that it actually does benefit healthy individuals who lift weights once bigger studies have been conducted, but until then, it is important to remain sceptical about any claims made about glutamine in regards to its bodybuilding benefits.

Our articles should be used for informational and educational purposes only and are not intended to be taken as medical advice.

Glutamine and muscle wasting October 29, Glutaminne VIB the Flanders Institute Glutamine and muscle wasting Biotechnology. A team headed by Prof. Massimiliano Mazzone VIB-KU Leuven Center for Cancer Biologyin collaboration with Dr. Emanuele Berardi and Dr.

Author: Brakus

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