Comprehensive metabolic flux analysis to explain skeletal muscle weakness in COPD

Engelen, M.P.; Jonker, Renate; Thaden, John J.; Have, Gabriella A.M. Ten; Jeon, M.S.; Dasarathy, Srinivasan; Deutz, Nicolaas E. P.

doi:10.1016/j.clnu.2020.01.010

Cited by 21 publications

(21 citation statements)

References 49 publications

(66 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…5), reflecting the impact of HMB on metabolism. An association between protein metabolism and muscle strength was found in patients with advanced cancer and patients with Chronic Obstructive Pulmonary Disease [44,45]. The alterations in protein metabolism probably precedes measurable changes in muscle mass.…”

Section: Protein Metabolismmentioning

confidence: 97%

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

et al. 2021

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Protein Metabolismmentioning

confidence: 97%

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

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…Although control subjects fulfilled all required inclusion and exclusion criteria, they also had early characteristics of metabolic syndrome. The elevated BMI and sedentary lifestyle of both the control and COPD groups have been observed in our previous studies (COPD [33] as well as in cancer [34]) due to the US population in general getting more obese, independent of the presence of disease [34]. Therefore, we think that our randomly selected control group provides a good representation of the current older population without COPD.…”

Section: Demographics Body Composition and Muscle Function And Postmentioning

confidence: 89%

Risk Factors for Postural and Functional Balance Impairment in Patients with Chronic Obstructive Pulmonary Disease

Park

Deutz

Cruthirds

et al. 2020

JCM

View full text Add to dashboard Cite

Reduced balance function has been observed during balance challenging conditions in the chronic obstructive pulmonary disease (COPD) population and is associated with an increased risk of falls. This study aimed to examine postural balance during quiet standing with eyes open and functional balance in a heterogeneous group of COPD and non-COPD (control) subjects, and to identify risk factors underlying balance impairment using a large panel of methods. In COPD and control subjects, who were mostly overweight and sedentary, postural and functional balance were assessed using center-of-pressure displacement in anterior-posterior (AP) and medio-lateral (ML) directions, and the Berg Balance Scale (BBS), respectively. COPD showed 23% greater AP sway velocity (p = 0.049). The presence of oxygen therapy, fat mass, reduced neurocognitive function, and the presence of (pre)diabetes explained 71% of the variation in postural balance in COPD. Transcutaneous oxygen saturation, a history of exacerbation, and gait speed explained 83% of the variation in functional balance in COPD. Neurocognitive dysfunction was the main risk factor for postural balance impairment in the control group. This suggests that specific phenotypes of COPD patients can be identified based on their type of balance impairment.

show abstract

“…NO has been shown to modulate synthesis of monoamine neurotransmitters (norepinephrine, serotonin, dopamine) as well as influence the hypothalamus–pituitary–adrenal axis [ 99 ]. Our previous work comparing COPD patients to healthy controls found alterations in the arginine pathway [ 31 , 33 ] and a higher NO production [ 31 ]. Our present data in CD only identified an increase in clearance of citrulline and ornithine, suggesting arginine metabolism and metabolites may not be underlying contributors to depression in COPD.…”

Section: Discussionmentioning

confidence: 99%

Disturbances in branched-chain amino acid profile and poor daily functioning in mildly depressed chronic obstructive pulmonary disease patients

et al. 2021

View full text Add to dashboard Cite

Background Depression is one of the most common and untreated comorbidities in chronic obstructive pulmonary disease (COPD), and is associated with poor health outcomes (e.g. increased hospitalization/exacerbation rates). Although metabolic disturbances have been suggested in depressed non-diseased conditions, comprehensive metabolic phenotyping has never been conducted in those with COPD. We examined whether depressed COPD patients have certain clinical/functional features and exhibit a specific amino acid phenotype which may guide the development of targeted (nutritional) therapies. Methods Seventy-eight outpatients with moderate to severe COPD (GOLD II–IV) were stratified based on presence of depression using a validated questionnaire. Lung function, disease history, habitual physical activity and protein intake, body composition, cognitive and physical performance, and quality of life were measured. Comprehensive metabolic flux analysis was conducted by pulse stable amino acid isotope administration. We obtained blood samples to measure postabsorptive kinetics (production and clearance rates) and plasma concentrations of amino acids by LC–MS/MS. Data are expressed as mean [95% CI]. Stats were done by graphpad Prism 9.1.0. ɑ < 0.05. Results The COPD depressed (CD, n = 27) patients on average had mild depression, were obese (BMI: 31.7 [28.4, 34.9] kg/m2), and were characterized by shorter 6-min walk distance (P = 0.055), physical inactivity (P = 0.03), and poor quality of life (P = 0.01) compared to the non-depressed COPD (CN, n = 51) group. Lung function, disease history, body composition, cognitive performance, and daily protein intake were not different between the groups. In the CD group, plasma branched chain amino acid concentration (BCAA) was lower (P = 0.02), whereas leucine (P = 0.01) and phenylalanine (P = 0.003) clearance rates were higher. Reduced values were found for tyrosine plasma concentration (P = 0.005) even after adjustment for the large neutral amino acid concentration (= sum BCAA, tyrosine, phenylalanine and tryptophan) as a marker of dopamine synthesis (P = 0.048). Conclusion Mild depression in COPD is associated with poor daily performance and quality of life, and a set of metabolic changes in depressed COPD that include perturbation of large neutral amino acids, specifically the BCAAs. Trial registration clinicaltrials.gov: NCT01787682, 11 February 2013—Retrospectively registered; NCT02770092, 12 May 2016—Retrospectively registered; NCT02780219, 23 May 2016—Retrospectively registered; NCT03796455, 8 January 2019—Retrospectively registered.

show abstract

Comprehensive metabolic flux analysis to explain skeletal muscle weakness in COPD

Cited by 21 publications

References 49 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

Risk Factors for Postural and Functional Balance Impairment in Patients with Chronic Obstructive Pulmonary Disease

Disturbances in branched-chain amino acid profile and poor daily functioning in mildly depressed chronic obstructive pulmonary disease patients

Contact Info

Product

Resources

About