Comprehensive metabolic amino acid flux analysis in critically ill patients

Deutz, N.E.P.; Singer, Pierre; Wierzchowska-McNew, Raven; Viana, Marina Verçoza; Bendavid, Itai; Pantet, Olivier; Thaden, John J.; Have, Gabriella A.M. Ten; Engelen, M.P.; Berger, Mette M.

doi:10.1016/j.clnu.2021.03.015

Cited by 23 publications

(46 citation statements)

References 63 publications

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“…At baseline there are major differences in plasma amino acid concentrations compared to healthy volunteers [26]. Also, whole body production is substantially higher, which is consistent with previous observations that show that metabolism is upregulated in critically ill patients, most likely in relation to the elevated inflammatory response [27].…”

Section: Protein Metabolismsupporting

confidence: 89%

“…Nitrogen balance can be measured in clinical practice, but it is not a precise method, especially due to the estimation of non-urinary nitrogen excretion [42]. At baseline we could only observe minor differences in plasma amino acid concentrations compared to healthy volunteers [26,43], with only a few amino acids being below the reference ranges. Protein breakdown was elevated in both groups at baseline, being significantly higher than in healthy subjects, as was whole-body production in all patients, consistent with previous observations that show that metabolism is upregulated in critically ill patients, most likely in relation to the elevated inflammatory response [26,27].…”

Section: Protein Metabolismmentioning

confidence: 76%

“…There seems to be a positive correlation between muscle wasting, inflammation, and organ failure burden [5]. Protein breakdown was measured by the stable isotope pulse method which is a validated and precise method [26], however, it is not easily measured at the bedside. Nitrogen balance can be measured in clinical practice, but it is not a precise method, especially due to the estimation of non-urinary nitrogen excretion [42].…”

Section: Protein Metabolismmentioning

confidence: 99%

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Impact of β−hydroxy-β−methylbutyrate (HMB) on muscle loss and protein metabolism in critically ill patients: A RCT

et al. 2021

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Purpose: Muscle wasting deteriorates life quality after critical illness and increases mortality. Wasting starts upon admission to intensive care unit (ICU). We aimed to determine whether bÀhydroxy-bÀmethylbutyrate (HMB), a metabolite of leucine, can attenuate this process.Methods: Prospective randomized, placebo-controlled double blind trial. Inclusion criteria: ICU patients depending on mechanical ventilation on day 3 having a functional gastrointestinal tract. They were randomized to HMB (3 g/day) or placebo (maltodextrin) from day 4 on for 30 days. Primary outcome: magnitude of loss of skeletal muscle area (SMA) of the quadriceps femoris measured by ultrasound at days 4 and 15. Secondary outcomes: body composition, change in protein metabolism assessed by amino acids tracer pulse, and global health at 60 days. Data are mean [95% CI]. Statistics by ANCOVA with correction for confounders sex, age and/or BMI. Results: Thirty patients completed the trial, aged 65 [59, 71] years, SAPS2 score 48 [43, 52] and SOFA 8.5 [7.4, 9.7]. The loss of total SMA was 11% between days 4 and 15 (p < 0.001), but not different between the groups (p ¼ 0.86). In the HMB group, net protein breakdown (D Estimate HMB-Placebo: À153 [-242, À63]; p ¼ 0.0021) and production of several amino acid was significantly reduced, while phase angle increased more (0.66 [0.09, 1.24]; p ¼ 0.0247), and SF-12 global health improved more 53.19], p ¼ 0.04). Conclusion: HMB treatment did not significantly reduce muscle wasting over 10 days of observation (primary endpoint), but resulted in significantly improved amino acid metabolism, reduced net protein breakdown, a higher phase angle and better global health. Clinicaltrials.gov identifier: NCT03628365.

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Section: Protein Metabolismsupporting

confidence: 89%

Section: Protein Metabolismmentioning

confidence: 76%

Section: Protein Metabolismmentioning

confidence: 99%

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Impact of β−hydroxy-β−methylbutyrate (HMB) on muscle loss and protein metabolism in critically ill patients: A RCT

et al. 2021

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“…However, in order to develop new food interventions in critical illness, insight in whole body BCAA production and disposal rates are of importance. For instance, BCAA production rates are elevated in critical illness by increased protein breakdown [13]. This information (and not BCAA concentration levels) support hypotheses like: extra BCAA supplementation can bring the patients in a more anabolic state.…”

Section: Critical Illnessmentioning

confidence: 76%

“…With this approach, BCAA, BCKA, and HMB whole body production, interconversion, and disposal rates can be measured simultaneously. Comprehensive metabolic flux analysis may be able to identify whether distinct metabolic signatures are present in specific patient populations [13,14].…”

Section: New Flux Measurement Approachmentioning

confidence: 99%

In-vivo production of branched-chain amino acids, branched-chain keto acids, and β-hydroxy β-methylbutyric acid

Have¹,

Engelen²,

Deutz³

2021

Current Opinion in Clinical Nutrition &Amp; Metabolic Care

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Purpose of reviewThe branched-chain amino acids (BCAA), branched-chain keto acids (BCKA), and b-hydroxy bmethylbutyric acid (HMB) have regained interest as food ingredients in health and disease. To support nutritional strategies, it is critical to gain insight into the whole body and transorgan kinetics of these components. We, therefore, reviewed the most recent literature in this field on in vivo analysis of BCAA, BCKA, and HMB kinetics in health and disease. Recent findingsWith a new comprehensive metabolic flux analysis BCAA, BCKA, and HMB whole body production, interconversion and disposal rates can be measured simultaneously. Recent studies have provided us with a better understanding of whole-body and transorgan kinetics under postabsorptive, postprandial, hibernating, and lactating conditions. In human pathophysiological conditions like COPD, obesity, and diabetes, the added value of BCAA kinetic measurements over the commonly used concentration measurements only, is discussed.

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Alanine, a potential amino acid biomarker of pediatric sepsis: a pilot study in PICU

Liu,

Xu,

et al. 2024

Amino Acids

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Sepsis is characterized by a metabolic disorder of amino acid occurs in the early stage; however, the profile of serum amino acids and their alterations associated with the onset of sepsis remain unclear. Thus, our objective is to identify the specific kinds of amino acids as diagnostic biomarkers in pediatric patients with sepsis. Serum samples were collected from patients with sepsis admitted to the pediatric intensive care unit (PICU) between January 2019 and December 2019 on the 1st, 3rd and 7th day following admission. Demographic and laboratory variables were also retrieved from the medical records specified times. Serum amino acid concentrations were detected by UPLC-MS/MS system. PLS-DA (VIP > 1.0) and Kruskal-Wallis test (p < 0.05) were employed to identify potential biomarkers. Spearman’s rank correlation analysis was conducted to find the potential association between amino acid levels and clinical features. The diagnostic utility for pediatric sepsis was assessed using receiver operating characteristic (ROC) curve analysis. Most of amino acid contents in serum were significantly decreased in patients with sepsis, but approached normal levels by the seventh day post-diagnosis. Threonine (THR), lysine (LYS), valine (VAL) and alanine (ALA) emerged as potential biomarkers related for sepsis occurrence, though they were not associated with PELOD/PELOD-2 scores. Moreover, alterations in serum THR, LYS and ALA were linked to complications of brain injury, and serum ALA levels were also related to sepsis-associated acute kidney injury. Further analysis revealed that ALA was significantly correlated with the Glasgow score, serum lactate and glucose levels, C-reactive protein (CRP), and other indicators for liver or kidney dysfunction. Notably, the area under the ROC curve (AUC) for ALA in distinguishing sepsis from healthy controls was 0.977 (95% CI: 0.925-1.000). The serum amino acid profile of children with sepsis is significantly altered compared to that of healthy controls. Notably, ALA shows promise as a potential biomarker for the early diagnosis in septic children.

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Comprehensive metabolic amino acid flux analysis in critically ill patients

Cited by 23 publications

References 63 publications

Impact of β−hydroxy-β−methylbutyrate (HMB) on muscle loss and protein metabolism in critically ill patients: A RCT

Impact of β−hydroxy-β−methylbutyrate (HMB) on muscle loss and protein metabolism in critically ill patients: A RCT

In-vivo production of branched-chain amino acids, branched-chain keto acids, and β-hydroxy β-methylbutyric acid

Alanine, a potential amino acid biomarker of pediatric sepsis: a pilot study in PICU

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