Effects of glutamine supplementation on critically ill patients: Focus on efficacy and safety. An overview of systematic reviews

Apostolopoulou, Aikaterini; Haidich, Anna‐Bettina; Kofina, Konstantinia; Manzanares, William; Bouras, Emmanouil; Tsaousi, Georgia; Stoppe, Christian; Dardavessis, Theodore; Chourdakis, Michael

doi:10.1016/j.nut.2020.110960

Cited by 8 publications

(8 citation statements)

References 37 publications

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“…Increased glutamine levels in glaucoma may be a consequence of trying to keep glutamate (Glu) concentration unchanged. As glutamine is considered generally safe and is used for cryopreservation of tissues/cells (20,21), an increase in [glutamine] to keep glutamate concentration low (and constant) could be a mechanism to prevent excitotoxic damage caused by accumulation of the amino acid. In paired values in a non-human primate glaucoma model, the concentration of glutamate in the AH before and after the onset of glaucoma was not significantly different.…”

Section: Discussionmentioning

confidence: 99%

Targeted Metabolomics Shows That the Level of Glutamine, Kynurenine, Acyl-Carnitines and Lysophosphatidylcholines Is Significantly Increased in the Aqueous Humor of Glaucoma Patients

Lillo

Marín²,

Serrano-Marín³

et al. 2022

Front. Med.

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The composition of the aqueous humor of patients with glaucoma is relevant to understand the underlying causes of the pathology. Information on the concentration of metabolites and small molecules in the aqueous humor of healthy subjects is limited. Among the causes of the limitations is the lack of healthy controls since, until recently, they were not surgically intervened; therefore, the aqueous humor of patients operated for cataract was used as a reference. Sixteen aqueous humor samples from healthy subjects undergoing refractive surgery and eight samples from glaucoma patients were used to assess the concentration of 188 compounds using chromatography and mass spectrometry. The concentration of 80 of the 188 was found to be reliable, allowing comparison of data from the two groups (glaucoma and control). The pattern found in the controls is similar to, but not the same as, that reported using samples from “controls” undergoing cataract surgery. Comparing data from glaucoma patients and healthy subjects, 57 of the 80 compounds were significantly (p < 0.05) altered in the aqueous humor. Kynurenine and glutamine, but not glutamate, were significantly increased in the glaucoma samples. Furthermore, 10 compounds were selected considering a statistical score of p < 0.0001 and the degree of change of more than double or less than half. The level of C10 (decanoyl)-carnitine decreased, while the concentration of spermidine and various acyl-carnitines and lysophosphatidylcholines increased in glaucoma. Principal component analysis showed complete segregation of controls and cases using the data for the 10 selected compounds. The receiver operating characteristic curve these 10 compounds and for glutamine allowed finding cut-off values and significant sensitivity and specificity scores. The concentration of small metabolites in the aqueous humor of glaucoma patients is altered even when they take medication and are well controlled. The imbalance affects membrane components, especially those of the mitochondria, suggesting that mitochondrial abnormalities are a cause or consequence of glaucoma. The increase in glutamine in glaucoma is also relevant because it could be a means of keeping the concentration of glutamate under control, thus avoiding its potential to induce the death of neurons and retinal cells. Equally notable was the increase in kynurenine, which is essential in the metabolism of nicotine adenine dinucleotides.

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Section: Discussionmentioning

confidence: 99%

Targeted Metabolomics Shows That the Level of Glutamine, Kynurenine, Acyl-Carnitines and Lysophosphatidylcholines Is Significantly Increased in the Aqueous Humor of Glaucoma Patients

Lillo

Marín²,

Serrano-Marín³

et al. 2022

Front. Med.

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“…Although glutamine is not considered an essential amino acid since it is produced mainly in skeletal muscle, it can become conditionally essential in critical conditions such as a catabolic state [15]. Glutamine supplementation has been recommended in critically ill patients staying in the ICU for a long time whose muscle mass decreases rapidly [21, 24]. Although glutamine improves some fatigue markers, it does not increase physical performance [25], and the available evidence is not strong enough to recommend it in sports nutrition [20].…”

Section: Discussionmentioning

confidence: 99%

“…Side effects attributable to glutamine supplementation have not been reported thus far [23,24]. Nevertheless, in our study, one patient (Patient 9) had an epileptic status without stroke-like episodes, but this event is considered to be related to the natural history of MELAS syndrome, and one patient (Patient 8) with 12 g/day glutamine showed a mild elevation of transaminase levels that returned to normal values with 18 g/day and therefore is assumed not to be related to the glutamine dosage.…”

Section: Discussionmentioning

confidence: 99%

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High‐dose oral glutamine supplementation reduces elevated glutamate levels in cerebrospinal fluid in patients with mitochondrial encephalomyopathy, lactic acidosis and stroke‐like episodes syndrome

Guerrero-Molina¹,

Morales-Conejo

Delmiro

et al. 2022

Euro J of Neurology

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Background and Purpose: Mitochondrial encephalomyopathy, lactic acidosis and strokelike episodes (MELAS) syndrome is a genetically heterogeneous disorder caused by mitochondrial DNA mutations. There are no disease-modifying therapies, and treatment remains mainly supportive. It has been shown previously that patients with MELAS syndrome have significantly increased cerebrospinal fluid (CSF) glutamate and significantly decreased CSF glutamine levels compared to controls. Glutamine has many metabolic fates in neurons and astrocytes, and the glutamate-glutamine cycle couples with many metabolic pathways depending on cellular requirements. The aim was to compare CSF glutamate and glutamine levels before and after dietary glutamine supplementation. It is postulated that high-dose oral glutamine supplementation could reduce the increase in glutamate levels.Method: This open-label, single-cohort study determined the safety and changes in glutamate and glutamine levels in CSF after 12 weeks of oral glutamine supplementation.Results: Nine adult patients with MELAS syndrome (66.7% females, mean age 35.8 ± 3.2 years) were included. After glutamine supplementation, CSF glutamate levels were significantly reduced (9.77 ± 1.21 vs. 18.48 ± 1.34 μmol/l, p < 0.001) and CSF glutamine levels were significantly increased (433.66 ± 15.31 vs. 336.31 ± 12.92 μmol/l, p = 0.002). A side effect observed in four of nine patients was a mild sensation of satiety.One patient developed mild and transient elevation of transaminases, and another patient was admitted for an epileptic status without stroke-like episode.Discussion: This study demonstrates that high-dose oral glutamine supplementation significantly reduces CSF glutamate and increases CSF glutamine levels in patients with MELAS syndrome. These findings may have potential therapeutic implications in these patients.

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“…18 Besides, the effect of autophagy explains that preserving (or minimizing) early nutrition may be more beneficial to critically ill patients. 19 Recent observational studies have revealed 20,21 that providing nutritional support rich in glutamine, either alone 22 or combined with probiotics 23 or alanine, 24 can reduce hospitalization time and infection of moderate to severe traumatic brain injury. In the CALORIES 25 and NUTRIREA-2 6 trials, lower calories and protein intake during the first week of ICU stay exhibited better clinical outcomes.…”

Section: Discussionmentioning

confidence: 99%

Low-Protein, Hypocaloric Nutrition with Glutamine versus Full-Feeding in the Acute Phase in ICU Patients with Severe Traumatic Brain Injury

Xiong

Qian

2021

NDT

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Effects of glutamine supplementation on critically ill patients: Focus on efficacy and safety. An overview of systematic reviews

Cited by 8 publications

References 37 publications

Targeted Metabolomics Shows That the Level of Glutamine, Kynurenine, Acyl-Carnitines and Lysophosphatidylcholines Is Significantly Increased in the Aqueous Humor of Glaucoma Patients

Targeted Metabolomics Shows That the Level of Glutamine, Kynurenine, Acyl-Carnitines and Lysophosphatidylcholines Is Significantly Increased in the Aqueous Humor of Glaucoma Patients

High‐dose oral glutamine supplementation reduces elevated glutamate levels in cerebrospinal fluid in patients with mitochondrial encephalomyopathy, lactic acidosis and stroke‐like episodes syndrome

Low-Protein, Hypocaloric Nutrition with Glutamine versus Full-Feeding in the Acute Phase in ICU Patients with Severe Traumatic Brain Injury

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