Oral Glutamine Research Articles

Use of oral glutamine in radiation-induced adverse effects in patients with thoracic and upper aerodigestive malignancies: Results of a prospective observational study.

Cancer growth in host tissues features glutamine (gln) depletion over time, decreasing epithelial cells' optimal functioning. In addition, radiotherapy (RT) and/or chemotherapy (CT) cause damage to normal tissues, probably enhanced by this depletion. The present study prospectively examined the effect of gln supplementation on 72 patients with thoracic and upper aerodigestive malignancies (T&UAM) treated with sequential or concurrent RT-CT or RT alone. All patients received prophylactic gln powder 15 g bid for the full duration of treatment. The severity of acute radiation toxicities was graded according to the RT Oncology Group/European Organization for Research and Treatment of Cancer criteria. Primary endpoints were the incidence of grade >2 toxicities, weight loss and requirement for analgesics, and the secondary endpoint was the association of the length of irradiated esophagus from treatment planning with the use of opioids. The incidence of adverse effects was as follows: Grade >2 stomatitis, 25.0%; esophagitis, 60.5%; dysphagia, 54.2%; pain, 25.4%; mycosis, 40.8%. Stomatitis grade >2 was more frequent in patients with head and neck tumors (P<0.001) and in those with prior surgery (P<0.001). Esophagitis (P=0.020) and dysphagia (P=0.008) grade >2 were more frequent in patients with concurrent RT-CT. Regarding analgesics, 9.9% of patients received no pain treatment, 56.3% received simple analgesic therapy and 33.8% opioids. Patients on opioid therapy had a greater mean length of irradiated esophagus (P=0.024) or length >12 cm (P=0.018). In 54.2% of patients, weight loss was observed, particularly with concurrent RT-CT (P=0.007). Thus, the use of oral gln may have an important role in reducing acute radiation toxicities and weight loss, and in lowering the requirement for analgesics in patients with T&UAM. Further randomized trials are required to identify the appropriate gln dose, duration of treatment and precise radiation dosimetric parameters in this group of patients. The present clinical trial was retrospectively registered in the ClinicalTrials.gov Protocol Registration and Results System (registration no. NCT05054517/22-09-2021).

Glutamine for prevention and alleviation of radiation-induced oral mucositis in patients with head and neck squamous cell cancer: Systematic review and meta-analysis of controlled trials.

We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) that investigated glutamine efficacy in preventing and alleviating radiation-induced oral mucositis (OM) among patients with head and neck (H&N) cancer. We screened five databases from inception till February 4, 2021 and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We included 11 RCTs, comprising 922 patients (458 and 464 patients were assigned to glutamine and control group, respectively). The incidence and onset of radiation-induced OM of any grade did not substantially differ between both groups. However, glutamine substantially reduced the severity of radiation-induced OM, as reflected by the reduced incidence of severe OM and reduced mean maximal OM grade score. Additionally, glutamine significantly decreased the rates of analgesic opioid use, nasogastric tube feeding, and therapy interruptions. Oral glutamine supplementation demonstrated various therapeutic benefits in preventing and ameliorating radiation-induced OM among patients with H&N cancer.

Formulation and in vivo study of the solid effervescent system as a new strategy for oral glutamine delivery

Glutamine (GLN) used as a dietary supplement is practically insoluble in water, which reduces its bioavailability after oral administration. Here, effervescent GLN (EBGLN) was prepared by comminution with an effervescent base (EB) that enhances its water solubility. EB (80 mg/mL) composed of citric acid, tartaric acid, and sodium bicarbonate was used in the ratio 1:2:3. This formulation was characterized in the liquid state (solubility studies, pH, effervescence time, GLN content) and solid-state (size analysis, residual moisture, flow properties studies, differential scanning calorimetry, thermogravimetric analysis, powder x-ray diffraction, and Fourier transformed infrared Raman spectroscopy). In vivo studies were performed with adult overnight fasted (15 h) rats. The rats were euthanized 30, 60, and 120 min after the oral administration (gavage) of water (vehicle of GLN), EB (vehicle of EBGLN), GLN (glutamine dissolved in water), or EBGLN (GLN dissolved in EB). Blood was collected and the plasma concentrations (nmol/mL) of GLN, glutamic acid, alanine, aspartic acid, asparagine, histidine, serine, arginine, tyrosine, tryptophan, methionine, phenylalanine, valine, leucine, and isoleucine were obtained by high-performance liquid chromatography (HPLC) analysis. Physicochemical characterizations indicated that EBGLN was present as a physical mixture with lower crystallinity and higher solubility when compared with pure GLN. In vivo experiments demonstrated improved oral GLN bioavailability from EBGLN (500 mg/kg - 30 min and 60 min). Therefore, the solid effervescent system represents a new strategy for oral glutamine delivery with potential clinical relevance.

Effectiveness of glutamine in the management of oral mucositis in cancer patients: a meta-analysis of randomized controlled trials.

The aim of this meta-analysis was to evaluate the effectiveness of glutamine for preventing or treating moderate-to-severe oral mucositis induced by chemotherapy or radiation therapy in patients with cancer. PubMed, Cochrane Library, and Embase were searched for eligible randomized controlled trials (RCTs) up to June 2020. The outcomes analyzed were oral mucositis (at all levels of severity). Data were pooled using the random-effects model and are expressed as risk ratios (RRs) and corresponding 95% confidence intervals (CIs). Heterogeneity was assessed and quantified using I2. Sixteen RCTs were included in this review. In this meta-analysis, compared with placebo, glutamine significantly reduced the incidence of grade 3 and 4 oral mucositis induced by chemotherapy or radiation therapy (RR, 0.53; 95% CI, 0.32-0.88). In subgroup analysis, oral glutamine administration (RR, 0.56; 95% CI, 0.34-0.92) and a medium or low daily dose of glutamine (RR, 0.58; 95% CI, 0.44-0.77; RR, 0.53; 95% CI, 0.28-0.94; respectively) decreased risk. Glutamine caused a borderline significant reduction in the risk of grade 3 and 4 oral mucositis induced by radiotherapy (RR, 0.75; 95% CI, 0.58-0.99) and especially in its prevention (RR, 0.51; 95% CI, 0.28-0.94). Glutamine significantly reduces the risk of oral mucositis during chemotherapy or radiation therapy. Furthermore, large prospective trials are required to support these findings.

Oral glutamine inhibits tumor growth of gastric cancer bearing mice by improving immune function and activating apoptosis pathway

Gastric cancer is one of the most common cancers in the world. It has been shown that exogenous glutamine (GLN) can inhibit the growth of tumor in vivo, but the relationship between GLN and gastric cancer has not been studied. The gastric cancer bearing mouse model was constructed and taken GLN orally at the same time, and the results found that oral GLN (1 or 2 g/kg/d) significantly inhibited the growth rate of tumor and reduce the weight of tumor tissues. Immunohistochemistry showed that oral GLN significantly reduced the PCNA index, which further proved that GLN could inhibit the growth of tumor cells. At the same time, TUNEL assay showed that oral GLN significantly enhanced the apoptosis levels of tumor cells. In addition, GLN reduced GSH levels in tumor tissues, but increased the levels of GSH in plasma, improved the T-lymphocyte transformation rate and NK cell activity, significantly inhibited the secretion of TNF-α and promoted the secretion of IL-2, thus regulating the immune function in vivo. Further detection of apoptosis pathway showed that oral GLN significantly enhanced the expression of pro-apoptotic factor Bad and inhibited the expression of Bcl-2. Meanwhile, GLN significantly increased the activities of Caspase-3, Caspase-8, caspase-9 and PARP. GSH activator NAC had a similar effect to GLN, which could improve the immune function and activate apoptosis pathway, while GSH inhibitor BSO significantly blocked the regulation of GLN, destroyed the immune balance and inhibited apoptosis, but IL-2 significantly blocked the anti-apoptotic effect of BSO. Therefore, oral GLN can improve immune function and activate apoptosis pathway through GSH, and then inhibit the growth of tumor in vivo.

A prospective randomized controlled study to evaluate the role of oral glutamine in chemo-radiation induced oral mucositis among carcinoma of oropharynx and larynx patients

A prospective randomized controlled study to evaluate the role of oral glutamine in chemo-radiation induced oral mucositis among carcinoma of oropharynx and larynx patients

Use of immunonutriente to treat a diarrheic episode in a dog

Diarrhea is considered a very common sign in the pet clinic, and the use of immunomodulatory nutrients in the treatment of this condition is considered a new therapeutic modality increasingly used by veterinarians. Dietary supplementation of probiotics, prebiotics, and L-glutamine has shown beneficial effects in the control and treatment of diarrhea in humans. Due to the few descriptions of the use of immunonutrients in the veterinary literature, this study aimed to report the case of a female Poodle dog, aged 13 years, with diarrhea, submitted to oral glutamine treatment for 5 days, which resulted in the complete remission of the diarrheal episode.

Effects of Oral Glutamine Supplementation on Early Postnatal Muscle Morphology in Low and Normal Birth Weight Piglets.

Simple SummaryThe lower survival rate and diminished overall growth and performance of low birth weight piglets is an economic and ethical issue in pig production. Adapted nutrition can help to compensate growth retardation, in particular, if nutrients in milk are not sufficient for newborn piglets. This study investigated the effects of oral glutamine supplementation during the first days after birth on skeletal muscle morphology of piglets with low or normal birth weight. The results indicated that glutamine supplementation changed the intramuscular amino acid concentration in the short term and influenced the muscle fiber size and abundance of myosin heavy chain isoforms within longissimus and semitendinosus muscle in neonatal piglets. Furthermore, differences in muscle fiber size and intramuscular lipid deposition were observed between low and normal birth weight piglets that disappeared in older piglets, independent of supplementation. The results indicated a delayed muscle development in low birth weight piglets. This delay can partly be compensated during growth by adequate nutrition.Adapted nutrition can improve the growth of low birth weight (LBW) piglets. Since maternal milk is thought to provide insufficient glutamine (Gln) for LBW piglets, the current study investigated the influence of Gln supplementation during the early suckling period on development and lipid deposition in skeletal muscle. The weight differences between LBW and normal birth weight (NBW) littermates persisted from birth to slaughter (p < 0.001). However, intramuscular Gln and Ala concentrations were altered in piglets according to the supplementation (p < 0.01). There were larger muscle fibers (p = 0.048) in Gln-supplemented piglets. Capillarization or nuclei number per muscle fiber was not influenced by birth weight (BiW) or Gln supplementation. Abundance of myosin heavy chain (MYH) isoforms was slightly altered by Gln supplementation. LBW piglets had more lipid droplets than NBW piglets at day 5 of life in both muscles (p < 0.01). The differences decreased with age. Adipocyte development increased with age, but was not influenced by BiW or supplementation. The results indicate that BiW differences were accompanied by differences in lipid deposition and muscle fiber structure, suggesting a delayed development in LBW piglets. Supplementation with Gln may support piglets to overcome those disadvantages.

A systematic review of interventions to mitigate radiotherapy-induced oral mucositis in head and neck cancer patients

BackgroundOral mucositis is a debilitating consequence of radiotherapy in patients with head and neck cancers. Radiation-induced oral mucositis (RIOM) can cause pain and weight loss, reduce quality of life and affect treatment outcomes.MethodsA systematic review was undertaken to identify and examine the efficacy of low-cost interventions to mitigate RIOM and to develop clinical guidelines based on the evidence.ResultsThe author identified three interventions: benzydamine hydrochloride mouth rinse (BHM), honey and oral glutamine (OG). The search identified twenty-four studies in total. Four studies examined BHM; all findings were favourable, although only one had moderate methodological quality, and the rest were low. The product was poorly tolerated by some participants in one study. Twelve studies examined honey. Eleven of these had favourable results; two studies had moderate methodological quality, and the rest were low. Eight studies examined OG. Six of these had favourable results; two studies had moderate methodological quality, and the rest were low.ConclusionThe author cannot recommend BHM to mitigate RIOM due to the overall low quality of the studies and poor tolerance to the product. The author cannot recommend honey to mitigate RIOM due to weak evidence supporting the intervention. The author can recommend OG to mitigate RIOM. There is a need for high-quality studies with a consensus of the methodology to reduce heterogeneity and examination of the cost-effectiveness of the interventions.

Efficacy Oral Glutamine to Prevent Oral Mucositis and Reduce Hospital Costs During Chemotherapy in Children with Acute Lymphoblastic Leukemia.

Objective:To investigate the use of glutamine administered orally during Methotrexate chemotherapy to prevent oral mucositis and reduce hospital costs in children with acute lymphoblastic leukemia (ALL). Methods:Twenty-four children received oral glutamine (400 mg/kg body weight per day) and twenty four received placebo on days of chemotherapy administration and for at least 14 additional days. Oral mucositis was graded daily at each day of treatment till completion of therapy. The study groups were compared for the oral mucositis development using the WHO scale. Results:Oral mucositis occurred in 4.2 % of the glutamine group and 62.5% in the placebo group. The use of glutamine was directly associated with prevention of oral mucositis than placebo (OR 0,026; 95% CI: 0,003-0,228). The duration of length hospital stay was lower in the glutamine group than in the placebo group ((8 vs 12 days); p = 0,005). Hospital cost per day for glutamine group was 40 USD per day while placebo group was 48 USD per day. Conclusions:There was significant difference in the prevention of oral mucositis by oral glutamine vs placebo. The hospital cost for glutamine supplementation was lower than control group.

Glutamine for Amelioration of Radiation and Chemotherapy Associated Mucositis during Cancer Therapy.

Glutamine is a major dietary amino acid that is both a fuel and nitrogen donor for healing tissues damaged by chemotherapy and radiation. Evidence supports the benefit of oral (enteral) glutamine to reduce symptoms and improve and/or maintain quality of life of cancer patients. Benefits include not only better nutrition, but also decreased mucosal damage (mucositis, stomatitis, pharyngitis, esophagitis, and enteritis). Glutamine supplementation in a high protein diet (10 grams/day) + disaccharides, such as sucrose and/or trehalose, is a combination that increases glutamine uptake by mucosal cells. This increased topical effect can reduce painful mucosal symptoms and ulceration associated with chemotherapy and radiation in the head and neck region, esophagus, stomach and small intestine. Topical and oral glutamine seem to be the preferred routes for this amino acid to promote mucosal healing during and after cancer treatment.

Effects of Micronutrients or Conditional Amino Acids on COVID-19-Related Outcomes: An Evidence Analysis Center Scoping Review

Recent narrative reviews have described the potential efficacy of providing individuals infected with coronavirus disease 2019 (COVID-19) with additional micronutrients to reduce disease severity. Although there are compelling reasons why providing additional micronutrients or conditional amino acids may affect COVID-19-related outcomes, evidence is lacking. The objective of this scoping review is to explore and describe the literature examining the effect of providing additional micronutrients or conditional amino acids (glutamine, arginine) in adults with conditions or infections similar to COVID-19 infection on COVID-19-related health outcomes. A literature search of the MEDLINE database and hand search of Cochrane Database of systematic reviews retrieved 1,423 unique studies, and 8 studies were included in this scoping review. Four studies examined a target population with ventilator-related pneumonia and acute respiratory distress syndrome, and the other 4 studies included patients who were at risk for ventilator-associated pneumonia. Interventions included intravenous ascorbic acid, intramuscular cholecalciferol, enteral and intramuscular vitamin E, enteral zinc sulfate, and oral and parenteral glutamine. In 6 of the 8 included studies, baseline status of the nutrient of interest was not reported and, thus, it is uncertain how outcomes may vary in the context of nutrient deficiency or insufficiency compared with sufficiency. In the absence of direct evidence examining efficacy of providing additional micronutrients or conditional amino acids to standard care, registered dietitian nutritionists must rely on clinical expertise and indirect evidence to guide medical nutrition therapy for patients infected with COVID-19.

Taste disorder’s management: a systematic review

Taste disorder is a frequent drug-induced or disease-related oral trouble. Various pharmacological, surgical, or physical treatments have previously been proposed for taste function recovery. The aim of the present systematic review was to assess the effects of palliative and curative interventions on taste recovery in light of recent literature. In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, a search of the literature published up to June 2019 was conducted using MEDLINE via PubMed, EMBASE, and The US National Institutes of Health Trials Register (PROSPERO registration reference: CRD 42019139315). The methodological quality of the included trials was rated with the "Delphi list For Quality Assessment of Randomized Clinical Trials" and the Newcastle-Ottawa scale. From the 1842 titles first identified, 28 articles met the inclusion criteria. Interventions included zinc (aspartate, sulfate, gluconate, acetate, picolinate, and Polaprezinc®), esomeprazole, L-thyroxin, bethanechol, oral glutamine, delta-9-tetrahydrocannabinol, alpha-lipoic acid, Ginkgo biloba, artificial saliva, pilocarpine, local anesthesia, and improved oral hygiene. The quality of evidence ranged from poor to high. Improving oral hygiene may promote taste ability. Zinc may prevent and alleviate taste disorder in patients undergoing head and neck radiotherapy. The systematic review provided evidence about the clinical efficacy of oral procedures, zinc supplementation, and palliative cares in dysgeusic patients. Further research is needed to find effective treatments with low adverse effects.

Glycine Enhances Satellite Cell Proliferation, Cell Transplantation, and Oligonucleotide Efficacy in Dystrophic Muscle.

The need to distribute therapy evenly systemically throughout the large muscle volume within the body makes Duchenne muscular dystrophy (DMD) therapy a challenge. Cell and exon-skipping therapies are promising but have limited effects, and thus enhancing their therapeutic potency is of paramount importance to increase the accessibility of these therapies to DMD patients. In this study, we demonstrate that co-administered glycine improves phosphorodiamidate morpholino oligomer (PMO) potency in mdx mice with marked functional improvement and an up to 50-fold increase of dystrophin in abdominal muscles compared to PMO in saline. Glycine boosts satellite cell proliferation and muscle regeneration by increasing activation of mammalian target of rapamycin complex 1 (mTORC1) and replenishing the one-carbon unit pool. The expanded regenerating myofiber population then results in increased PMO uptake. Glycine also augments the transplantation efficiency of exogenous satellite cells and primary myoblasts in mdx mice. Our data provide evidence that glycine enhances satellite cell proliferation, cell transplantation, and oligonucleotide efficacy in mdx mice, and thus it has therapeutic utility for cell therapy and drug delivery in muscle-wasting diseases.

Effect of glutamine supplement on chemo-radiation induced mucositis in head and neck cancer patients: a prospective study

Background: Radiotherapy is one of the primary modalities of cancer treatment but may associated with short and long-term toxicities. Oral mucositis is frequently encountered in head and neck cancer resulting in unplanned treatment breaks. Few studies emphasized that use of oral glutamine may significantly reduce oral mucositis and other acute toxicities. This study aims to assess the effects of glutamine on oral mucositis in head and neck cancer patients receiving chemo-radiation.Methods: It is a prospective study carried out in sixty-four head and neck cancer patients attending radiotherapy department for chemo-radiation from January 2018 to May 2019. Patients were randomly assigned into two arms containing 32 subjects in each. All the patients in arm-A were taking oral glutamine supplement of 15 mg once daily, two hours prior to radiation and arm-B serve as the control group. Dose of radiation fixed at 66 Gy in 33 fractions over a period of 7 weeks along with an infusion of weekly cisplatin (40 mg/m2). Patients were evaluated regarding onset, severity and the recovery period of mucositis.Results: Oral mucositis appeared at around 5th week in arm-A and 3rd week in arm-B (p&lt;0.0001). Number of patients with mucositis is significantly less in arm-A (75%, 24 out of 32) as compared to arm-B (96.8%) (p=0.0310). The time required for healing of mucositis is significantly less than 1 week in arm-A compared to ~2 weeks in the arm-B (p&lt;0.0001).Conclusions: Oral glutamine when given prior to radiation results in delayed onset of oral mucositis with decreased severity and an early healing period.

Oral glutamine supplementation increases seizure severity in a rodent model of mesial temporal lobe epilepsy

ABSTRACT Background: Glutamine synthetase (GS) is the only enzyme known to synthesize significant amounts of glutamine in mammals, and loss of GS in the hippocampus has been implicated in the pathophysiology of medication refractory mesial temporal lobe epilepsy (MTLE). Moreover, loss-of-function mutations of the GS gene causes severe epileptic encephalopathy, and supplementation with glutamine has been shown to normalize EEG and possibly improve the outcome in these patients. Here we examined whether oral glutamine supplementation is an effective treatment for MTLE by assessing the frequency and severity of seizures after supplementation in a translationally relevant model of the disease. Methods: Male Sprague Dawley rats (380–400 g) were allowed to drink unlimited amounts of glutamine in water (3.6% w/v; n = 8) or pure water (n = 8) for several weeks. Ten days after the start of glutamine supplementation, GS was chronically inhibited in the hippocampus to induce MTLE. Continuous video-intracranial EEG was collected for 21 days to determine the frequency and severity of seizures. Results: While there was no change in seizure frequency between the groups, the proportion of convulsive seizures was significantly higher in glutamine treated animals during the first three days of GS inhibition. Conclusion: The results suggest that oral glutamine supplementation transiently increases seizure severity in the initial stages of an epilepsy model, indicating a potential role of the amino acid in seizure propagation and epileptogenesis.

Oral glutamine challenge is a marker of altered ammonia metabolism and predicts the risk of hepatic encephalopathy.

The current therapies for hepatic encephalopathy (HE) are not completely effective in all patients, probably due to the physiopathological heterogeneity and the different conditions underlying the bout of HE. We hypothesized that oral glutamine challenge (OGC) is able to predict the risk of HE through the identification of various features and types of HE. We included 238 cirrhotic patients (198 without and 40 with a previous HE episode) that underwent OGC, obtaining baseline and 60minutes post-load ammonia levels. Combined evaluation of baseline hyperammonemia (>78mcg/dL) and impaired OGC (Δ >32mcg/dL) defined low-, intermediate- and high-risk groups. Patients were censored at HE, liver transplantation and death or 6years of follow-up. The 28.3% (56/198) of the main cohort suffered from HE during the follow-up. In the competing risk analysis, both intermediate- (subhazard ratio (sHR) 2.01 (95% CI 1.00-4.14); P=.048) and high-risk groups (sHR 4.67 (95% CI 2.19-9.98); P=.0001) were associated with the first HE episode, together with age and albumin. Similar results were found for repeated HE events. The cumulative incidence for HE of the high-risk group was two and four times greater than the intermediate- and low-risk groups, respectively. The HE grade was also higher in individuals with the greatest risk (P=.035). The most common precipitant factor was diuretics in the high-risk group, while infections and electrolyte imbalance predominated in the rest of patients. Oral glutamine challenge identified patients at risk of HE and defined specific features of the episodes. This tool could be useful in the decision-making process for the adequate management of HE.

Oral glutamine supplementation attenuates inflammation and oxidative stress-mediated skeletal muscle protein content degradation in immobilized rats: Role of 70 kDa heat shock protein

Skeletal muscle disuse results in myofibrillar atrophy and protein degradation, via inflammatory and oxidative stress-mediated NF-kB signaling pathway activation. Nutritional interventions, such as l-glutamine (GLN) supplementation have shown antioxidant properties and cytoprotective effects through the modulation on the 70-kDa heat shock protein (HSP70) expression. However, these GLN-mediated effects on cell signaling pathways and biochemical mechanisms that control the myofibrillar protein content degradation in muscle disuse situations are poorly known yet. This study investigated the effects of oral GLN plus l-alanine (ALA; GLN ​+ ​ALA-solution) supplementation, either in their free or dipeptide (L-alanyl-l-glutamine-DIP) form, on GLN-glutathione (GSH) axis and cytoprotection mediated by HSP70 protein expression in the slow-twitch soleus and fast-twitch gastrocnemius skeletal muscle of rats submitted to 14-days of hindlimb immobilization-induced disuse muscle atrophy. Forty-eight Wistar rats were distributed into 6 groups: hindlimb immobilized (IMOB group) and hindlimb immobilized orally supplemented with either GLN (1 g kg−1) plus ALA (0.61 g kg−1) ​(GLN ​+ ​ALA-IMOB group) or 1.49 ​g ​kg−1 of DIP (DIP-IMOB group) and; no-immobilized (CTRL) and no-immobilized supplemented GLN ​+ ​ALA and DIP baselines groups. All animals, including CTRL and IMOB rats (water), were supplemented via intragastric gavage for 14 days, concomitantly to immobilization period. Plasma and muscle GLN levels, lipid (thiobarbituric acid reactive substances-TBARS) and protein (carbonyl) peroxidation, erythrocyte concentration of reduced GSH and GSH disulfide (GSSG), plasma and muscle pro-inflammatory TNF-α levels, muscle IKKα/β-NF-kB signaling pathway and, the myofibrillar protein content (MPC) were measured. The MPC was significantly lower in IMOB rats, compared to CTRL, GLN ​+ ​ALA, and DIP animals (p ​< ​0.05). This finding was associated with reduced plasma and muscle GLN concentration, equally in IMOB animals. Conversely, both GLN ​+ ​ALA and DIP supplementation restored plasma and muscle GLN levels, which equilibrated GSH and intracellular redox status (GSSG/GSH ratio) in erythrocytes and skeletal muscle even as, increased muscle HSP70 protein expression; attenuating oxidative stress and TNF-α-mediated NF-kB pathway activation, fact that reverberated on reduction of MPC degradation in GLN ​+ ​ALA-IMOB and DIP-IMOB animals (p ​< ​0.05). In conclusion, the findings shown herein support the oral GLN ​+ ​ALA and DIP supplementations as a therapeutic and effective nutritional alternative to attenuate the deleterious effects of the skeletal muscle protein degradation induced by muscle disuse.

Systematic review of natural and miscellaneous agents for the management of oral mucositis in cancer patients and clinical practice guidelines-part 1: vitamins, minerals, and nutritional supplements.

To update the clinical practice guidelines for the use of natural and miscellaneous agents for the prevention and/or treatment of oral mucositis (OM). A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer / International Society of Oral Oncology (MASCC/ISOO). The body of evidence for each intervention, in each cancer treatment setting, was assigned an evidence level. The findings were added to the database used to develop the 2014 MASCC/ISOO clinical practice guidelines. Based on the evidence level, the following guidelines were determined: Recommendation, Suggestion, and No Guideline Possible. A total of 78 papers were identified within the scope of this section, out of which 29 were included in this part, and were analyzed with 27 previously reviewed studies. A new Suggestion was made for oral glutamine for the prevention of OM in head and neck (H&N) cancer patients receiving radiotherapy with concomitant chemotherapy. The previous Recommendation against the use of parenteral glutamine for the prevention of OM in hematopoietic stem cell transplantation (HSCT) patients was re-established. A previous Suggestion for zinc to prevent OM in H&N cancer patients treated with radiotherapy or chemo-radiotherapy was reversed to No Guideline Possible. No guideline was possible for other interventions. Of the vitamins, minerals, and nutritional supplements studied for the management of OM, the evidence supports a Recommendation against parenteral glutamine in HSCT patients and a Suggestion in favor of oral glutamine in H&N cancer patients for the management of OM.

Effect of Oral Branched-Chain Amino Acids and Glutamine Supplementation on Skeletal Muscle Atrophy After Total Gastrectomy in Rat Model

BackgroundSarcopenia is closely related to short-term outcomes of surgery and long-term prognosis. After gastrectomy, a decrease in muscle strength occurs because of insufficient nutrient intake and disturbed digestive function. Branched-chain amino acids (BCAAs) and glutamine (Gln) play vital roles in the signaling pathways regulating protein synthesis and protein degradation. In this study, we investigated the effects of BCAA and Gln supplementation alone or in combination on skeletal muscle atrophy after total gastrectomy in a rat model. MethodsMale Wistar rats were divided into five groups: (1) sham operation (n = 8); (2) total gastrectomized rats (TG [control group], n = 16); (3) TG with BCAA (TG-B, n = 16); (4) TG with Gln (TG-G, n = 16); and (5) TG with BCAA and Gln (TG-BG, n = 16). In all groups, body weight, muscle weight, and marker for muscle metabolism were examined. ResultsWeight gain was significantly greater in the TG-BG group (130.5%) than in the TG group (108.1%) at 15 wk (P < 0.05). The gastrocnemius muscle weight was significantly higher for TG-BG (2.84 g) than for TG (2.44 g) at 15 wk (P < 0.05). Western blotting indicated that atrogin-1 and MuRF1 levels were lower in the TG-BG group than in the TG group but were not suppressed in the TG-B or TG-G group. ConclusionsIn a rodent sarcopenia model induced by TG, the administration of BCAA in combination with Gln more effectively inhibited muscle atrophy than the administration of BCAA or Gln alone.