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Duchenne muscular dystrophy (DMD) is a severe neuromuscular disease due to loss of dystrophin, leading to progressive muscle wasting and physical inactivity. In this pilot study, we studied the effect of daily supplementation of the anabolic substrate beta-hydroxy-beta-methylbutyrate (HMB) on whole body protein and amino acid kinetics using novel isotope methods and daily activity in a canine model of DMD. Six DMD dogs were administered 3 g daily of HMB or placebo for 28 days according to a randomized, placebo-controlled, double-blinded crossover design. We measured pre- and post-intervention daily activity, biochemistry markers, and whole-body amino acid kinetics. We tracked daily activity with an activity monitoring device and measured plasma creatine kinase and standard clinical biochemistry panels to monitor muscle and organ function. To calculate whole body and intracellular amino acid production, we administered in the postabsorptive state an IV stable isotope solution containing 20 amino acid tracers. We collected blood before and six times after until two hours post tracer pulse administration and measured amino acid enrichments and concentrations by LC–MS/MS, subsequently followed by (non) compartmental modeling of the decay enrichment curves. Results were expressed as mean with 95% CI. Whole body production, plasma concentrations, and intra-/extracellular compartmental analyses of various amino acids were attenuated in HMB-dosed DMD dogs. Specifically, the plasma concentration of hydroxyproline (marker of collagen breakdown) was significantly higher in the placebo group compared to the HMB group. The intra- and extracellular pool sizes and flux between the two compartments of hydroxyproline was reduced in HMB treated dogs. DMD dogs treated with HMB as compared to placebo had a respective 40% increase in exertional (play) (951 [827, 1075] versus 569 [491, 647]; p < 0.0001) and 10.5% increase in non-exertional (active) activity (15,366 [14742, 15990] versus 13,806 [13148,14466]; p = 0.0016). In addition, a 6% reduction was found in rest time after HMB supplementation compared to placebo (23,857 [23,130, 24,584], versus 25,363 [24500, 26225]; p = 0.0122). Creatine kinase was not statistically different between groups. We did not observe any adverse clinical or biochemical-related effects of HMB dosing. Daily HMB supplementation in DMD dogs can safely and positively influence protein and amino acid metabolism and improve overall daily activity. [ABSTRACT FROM AUTHOR]

Human sepsis is characterized by increased protein breakdown and changes in arginine and citrulline metabolism. However, it is unclear whether this is caused by changes in transorgan metabolism. We therefore studied the changes in protein and arginine-related metabolism on the whole body (Wb) and transorgan levels in a Pseudomonas aeruginosa-induced pig sepsis model. We studied 22 conscious pigs for 18 h during sepsis induced by infusing live bacteria (Pseudomonas aeruginosa) or after placebo infusion (Control). We used stable isotope tracers to measure Wb and skeletal muscle protein synthesis and breakdown, as well as Wb, splanchnic, skeletal muscle, hepatic, and portal-drained viscera (PDV) arginine and citrulline disposal and production rates. During sepsis, arginine Wb production (P = 0.0146), skeletal muscle release (P = 0.0035), and liver arginine uptake were elevated (P = 0.0031). Wb de novo arginine synthesis, citrulline production, and transorgan PDV release of citrulline, glutamine, and arginine did not differ between Sepsis and Control pigs. However, Wb (P < 0.0001) and muscle (P < 0.001) protein breakdown were increased, suggesting that the enhanced arginine production is predominantly derived from muscle breakdown in sepsis. In conclusion, live bacterium sepsis increases muscle arginine release and liver uptake, mirroring previous pig endotoxemia studies. In contrast to observations in humans, acute live bacterium sepsis in pigs does not change citrulline production or arterial arginine concentration. We therefore conclude that the arginine dysregulation observed in human sepsis is possibly initiated by enhanced protein catabolism and splanchnic arginine catabolism, whereas decreased arterial arginine concentration and citrulline metabolism may require more time to fully manifest in patients. NEW & NOTEWORTHY: Our work highlights that arginine availability may be largely determined by muscle breakdown and hepatic extraction in early sepsis, while citrulline production appears maintained. Additionally, our work highlights a novel ANCOVA approach for transorgan analysis to control for inherent variation in transorgan data and increase statistical sensitivity. [ABSTRACT FROM AUTHOR]

To better understand working memory (WM) deficits in Mild Cognitive Impairment (MCI), we examined information precision and associative binding in WM in 21 participants with MCI, compared to 16 healthy controls, using an item-location delayed reproduction task. WM, along with other executive functions (i.e. Trail Making Task (TMT) and Stroop task), were measured before and after a 2-h nap. The napping manipulation was intended as an exploratory element to this study exploring potential impacts of napping on executive functions. Compared to healthy participants, participants with MCI exhibited inferior performance not only in identifying encoded WM items but also on item-location associative binding and location precision even when only one item was involved. We also found changes on TMT and Stroop tasks in MCI, reflecting inferior attention and inhibitory control. Post-napping performance improved in most of these WM and other executive measures, both in MCI and their healthy peers. Our study shows that associative binding and WM precision can reliably differentiate MCIs from their healthy peers. Additionally, most measures showed no differential effect of group pre- and post-napping. These findings may contribute to better understanding cognitive deficits in MCI therefore improving the diagnosis of MCI. [ABSTRACT FROM AUTHOR]

Background This narrative review describes foundational and emerging evidence of how dietary protein intakes may influence muscle-related attributes of older adults. Methods PubMed was used to identify pertinent research. Results Among medically stable older adults, protein intakes below the recommended dietary allowance (RDA) (0.8 g/kg body weight [BW]/d) exacerbate age-related reductions in muscle size, quality, and function. Dietary patterns with total protein intakes at or moderately above the RDA, including one or preferably more meals containing sufficient dietary protein to maximize protein anabolism, promote muscle size and function. Some observational studies suggest protein intakes from 1.0 to 1.6 g/kg BW/d may promote greater muscle strength and function more so than muscle size. Experimental findings from randomized controlled feeding trials indicate protein intakes greater than the RDA (averaging ~1.3 g/kg BW/d) do not influence indices of lean body mass or muscle and physical functions with non-stressed conditions, but positively influence changes in lean body mass with purposeful catabolic (energy restriction) or anabolic (resistance exercise training) stressors. Among older adults with diagnosed medical conditions or acute illness, specialized protein or amino acid supplements that stimulate muscle protein synthesis and improve protein nutritional status may attenuate the loss of muscle mass and function and improve survival of malnourished patients. Observational studies favor animal versus plant protein sources for sarcopenia-related parameters. Conclusions Quantity, quality, and patterning of dietary protein consumed by older adults with varied metabolic states, and hormonal and health status influence the nutritional needs and therapeutic use of protein to support muscle size and function. [ABSTRACT FROM AUTHOR]

With prolonged pandemic conditions, and emerging evidence but persisting low awareness of the importance of nutritional derangements, ESPEN has promoted in close collaboration with World Health Organization-Europe a call for papers on all aspects relating COVID-19 and nutrition as well as nutritional care, in the Society Journals Clinical Nutrition and Clinical Nutrition ESPEN. Although more COVID-related papers are being submitted and continue to be evaluated, ESPEN and WHO present the current editorial to summarize the many published findings supporting major interactions between nutritional status and COVID-19. These include 1) high risk of developing the disease and high risk of severe disease in the presence of pre-existing undernutrition (malnutrition) including micronutrient deficiencies; 2) high risk of developing malnutrition during the course of COVID-19, with substantial impact on long-term sequelae and risk of long COVID; 3) persons with obesity are also prone to develop or worsen malnutrition and its negative consequences during the course of COVID-19; 4) malnutrition screening and implementation of nutritional care may improve disease outcomes; 5) social and public health determinants contribute to the interaction between nutritional status and COVID-19, including negative impact of lockdown and social limitations on nutrition quality and nutritional status. We believe the evidence supports the need to consider COVID-19 as (also) a case of malnutrition-enhanced disease and disease-related malnutrition, with added risk for persons both with and without obesity. Similarities with many other disease conditions further support recommendations to implement standard nutritional screening and care in COVID-19 patients, and they underscore the relevance of appropriate nutritional and lifestyle prevention policies to limit infection risk and mitigate the negative health impact of acute pandemic bouts. [ABSTRACT FROM AUTHOR]

Background There is growing interest in the supplementation of arginine (Arg) and citrulline (Cit) in obesity due to their potential anti-obesogenic and anti-inflammatory properties. However, there is no consensus on the metabolic changes in Arg kinetics in obesity. Objectives This exploratory cross-sectional study aimed to investigate the association between obesity, sex, and sex-by-obesity interaction on whole-body Arg kinetics in a large group of human subjects. Methods We studied 83 nonobese [BMI (kg/m2) <30] and 80 morbidly obese (BMI >30) middle-aged individuals (40% males) enrolled in the MEDIT (Metabolism of Disease with Isotope Tracers) trial. After body-composition measurement by DXA, we collected arterial(ized) blood samples for amino acid (AA) concentrations, markers of inflammation [high-sensitivity C-reactive protein (hs-CRP)], liver function, and glucose in a postabsorptive state. We administered a pulse of AA stable tracers and measured whole-body production (WBP) of Arg, Cit, ornithine (Orn), phenylalanine, and tyrosine, and calculated their clearance (disposal capacity) and metabolite interconversions [markers for NO and de novo Arg production, systemic Arg hydrolysis, and whole-body protein breakdown (wbPB)]. We measured plasma enrichments by LC-MS/MS and statistics by Fisher's exact test or analysis of (co)variance. Significance was set at P  < 0.05. Results Obese individuals were normoglycemic and characterized by low-grade inflammation (P  < 0.0001) and greater wbPB (P  = 0.0298). We found lower plasma Cit concentration (P  < 0.0001) in the obese group but no differences in the WBP of Arg, Cit, and Orn. Furthermore, we observed overproduction of NO (P  < 0.0001) in obesity but lower de novo Arg production (P  = 0.0007). The WBP of Arg was lower in females for almost all Arg-related AAs, except for plasma Cit and NO production. Conclusions Alterations in Arg metabolism are present in morbid obesity. Further studies are needed to investigate if these changes could be related to factors such as increased Arg requirement in obesity or metabolic adaptation. [ABSTRACT FROM AUTHOR]

In patients with malnutrition there is an increased long-term risk for mortality beyond the preciding hospital stay. We investigated the effects of postdischarge nutritional support in the outpatient setting on all-cause mortality in the populaton of malnourished medical patients in a systematic review of randomized controlled trials. We searched MEDLINE and EMBASE, from inception to December 21, 2022. Randomized-controlled trials investigating nutritional support in medical patients following hospital discharge vs. control group (usual care, placebo and no nutritional support) were included. Data were independently extracted by two authors and were pooled using random effects model. Our primary outcome was all cause-mortality up to 12-months (end of intervention) of hospital discharge. We included 14 randomized-controlled trials with a total of 2438 participants and mostly moderate trial quality. Compared to the control group, patients receiving outpatient nutritional support had lower mortality (13 trials, odds ratio [OR] 0.63, 95% confidence interval [CI] 0.48 to 0.84, p = 0.001, I2 = 1%). Nutritional support was also associated with a significant increase in the mean daily intake of energy (568 kcal, 95% CI 24 to 1,113, p = 0.04), proteins (24 g, 95% CI 7 to 41), p = 0.005) and body weight (1.1 kg, 95% CI 0.6 to 1.7), p < 0.001). No differences were found on hospital readmissions and handgrip strength. This meta-analysis of randomized-controlled trials with mostly moderate trial quality suggests that nutritional support in the outpatient setting significantly increases nutritional intake as well as body weight, and importantly improves survival. Further large-scale and high-quality intervention trials are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

In 1982 and 2011, Clinical Science published papers that used infusion of stable isotope-labeled amino acids to assess skeletal muscle protein synthesis in the fasted and fed state and before and after a period of increased intake of omega-3 fatty acids, respectively; both of these papers have been highly cited. An overview of the study designs, key findings and novel features, and a consideration of the lasting impact of these two papers is presented. The earlier paper introduced stable isotope tracer approaches in humans that showed consuming a meal will increase whole body oxidation, synthesis, and breakdown of protein, but that protein synthesis is greater than breakdown resulting in net accumulation of protein. The paper also demonstrated that consuming a meal promotes net protein synthesis in skeletal muscle. The later paper introduced the concept that omega-3 polyunsaturated fatty acids are able to improve anabolism by reporting that 8 weeks consumption of high-dose omega-3 fatty acids by healthy young and middle-aged adults increased skeletal muscle protein synthesis during a hyperaminoacidemic–hyperinsulinemic clamp compared with what was seen during the clamp at study entry. Omega-3 fatty acids also increased the phosphorylation of important signaling proteins in muscle, including mammalian target of rapamycin, p70s6k, and Akt, during the clamp. These two papers remain relevant because they offer experimental approaches to study human (patho)physiology in different contexts, they present novel insights into the impact of nutritional state (feeding) and specific nutrients (omega-3 fatty acids) on muscle protein synthesis, and they suggest ways to explore the potential of interventions to help prevent and reverse the age-, disease-, and disuse-associated decline in muscle mass. [ABSTRACT FROM AUTHOR]

Background There has been growing interest in studying postprandial glucose responses using continuous glucose monitoring (CGM) in nondiabetic individuals. Accurate measurement of glucose responses to meals can facilitate applications such as precision nutrition and early detection of diabetes. Objectives We aimed to quantify the discordance between simultaneous postprandial glucose measurements made using plasma and CGM. Methods We studied 10 nondiabetic older adults who randomly consumed 9 predefined meals of varying macronutrient compositions. Glucose was measured for 8 h after the meal by the CGM, blood samples for plasma collection were taken regularly, and plasma glucose was quantified using gold-standard laboratory measurement and a fingerstick blood glucose meter. The primary outcome measured was the mean absolute relative difference (MARD) of CGM and fingerstick measurements relative to the gold standard. Secondary outcomes were Bland–Altman statistics, Clarke Error Grid, and time in range metrics. Additional subgroup analyses were performed by stratifying the postprandial glucose measurements based on the macronutrient composition of the meals. Results When compared against the gold-standard postprandial glucose measurements, the fingerstick meter was more accurate (MARD: 8.0%; 95% CI: 7.6%, 8.6%) than the CGM (MARD: 13.7%; 95% CI: 13.1%, 14.3%; P  < 0.0001). After the meals, Bland–Altman analysis demonstrated that the CGM underestimated the 8-h gold-standard glucose rise by 12.8 mg/dL on average (P  < 0.0001), whereas the fingerstick meter did so by 5.5 mg/dL on average (P  < 0.0001). The CGM underestimated the time spent in the 70–180 mg/dL range (P  = 0.002) and overestimated the time spent <70 mg/dL (P  < 0.0001) compared with the other 2 methods. Conclusions We discovered discordance between gold standard, fingerstick, and CGM in measuring plasma glucose concentrations after a meal. Consequently, emerging applications of CGM in healthy individuals, such as precision nutrition and diabetes onset prediction, may need to account for these discordances. This trial was registered at clinicaltrials.gov as NCT04928872. [ABSTRACT FROM AUTHOR]

Background Disturbances in protein metabolism and impaired muscle health have been observed in chronic obstructive pulmonary disease (COPD). The ω-3 (n–3) PUFAs EPA and DHA are known for their anti-inflammatory and muscle health-enhancing properties. Objectives We examined whether daily EPA + DHA supplementation can improve daily protein homeostasis in patients with COPD by reducing postabsorptive whole-body protein breakdown (PB) and enhancing the anabolic response to feeding in a dose-dependent way. Methods Normal-weight participants with moderate to severe COPD (n  = 32) received daily for 4 wk, according to a randomized double-blind placebo controlled 3-group design, a high dose (3.5 g, n  = 10) of EPA + DHA, a low dose (2.0 g, n  = 10) of EPA + DHA, or placebo (olive oil, n  = 12) via gel capsules. At pre- and postintervention, stable isotope tracers were infused to assess postabsorptive netPB [postabsorptive PB – protein synthesis (PS)] and the anabolic response (prandial netPS = prandial PS-PB) to a protein meal. In addition, muscle mass and function were measured. Results Plasma phosphatidylcholine EPA and DHA concentrations were higher after 4 wk of supplementation in both EPA + DHA groups (P  < 0.004), and there was a trend toward higher values for plasma EPA after the high compared with the low dose of EPA + DHA (P  = 0.065). Postabsorptive PB was lower after 4 wk of the high dose of EPA + DHA, whereas netPB was lower independent of the dose of EPA + DHA (low dose, P  = 0.037; high dose, P  = 0.026). Prandial netPS was increased only after the high dose of EPA + DHA (P  = 0.03). Extremity lean mass but not muscle function was increased, independent of the EPA + DHA dose (P  < 0.05). Conclusions Daily n–3 PUFA supplementation for 4 wk induces a shift toward a positive daily protein homeostasis in patients with COPD in part in a dose-dependent way. Daily doses up to 3.5 g EPA and DHA are still well tolerated and lead to protein gain in these patients. This trial was registered at clinicaltrials.gov as NCT01624792. [ABSTRACT FROM AUTHOR]

Background: Small‐ and large‐intestinal perturbations have been described as prevalent extracardiac systemic manifestations in congestive heart failure (CHF), but alterations in protein digestion and absorption and plasma short‐chain fatty acid (SCFA) concentrations and the potential link with other systemic effects (muscle and cognitive health) have not been investigated in CHF. Methods: We analyzed protein digestion and absorption with dual stable tracer method in 14 clinically stable, noncachectic CHF outpatients (mean left ventricular ejection fraction: 35.5% [95% CI, 30.9%–40.1%]) and 15 controls. Small‐intestinal non–carrier‐mediated permeability and active carrier‐mediated glucose transport were quantified by sugar permeability test. Plasma SCFA (acetate, propionate, butyrate, isovalerate, valerate) concentrations were measured as intestinal microbial metabolites. Muscle function was assessed by isokinetic dynamometry, cognition by a battery of tests, and well‐being by questionnaire. Results: Protein digestion and absorption were impaired by 29.2% (P =.001) and active glucose transport by 38.4% (P =.010) in CHF. Non–carrier‐mediated permeability was not altered. Whereas plasma propionate, butyrate, and isovalerate concentrations were lower in CHF (P <.05), acetate and valerate concentrations did not differ. Overall, intestinal dysfunction was associated with impaired leg muscle quality, emotional distress, and cognitive dysfunction (P <.05). Conclusions: We identified impaired protein digestion and absorption and altered SCFA concentrations as additional intestinal dysfunctions in CHF that are linked to reduced muscle and cognitive health and well‐being. More research is needed to implement strategies to improve intestinal function in CHF and to investigate the mechanisms underlying its link with other systemic manifestations. [ABSTRACT FROM AUTHOR]