Protein supplementation has shown to improve muscle mass in older adults. However, its effect may be influenced by supplementation dose, frequency and timing. This systematic review aimed to assess the effect of dose, frequency and timing of protein supplementation on muscle mass in older adults. Five databases were systematically searched from inception to 14 March 2023, for randomised controlled trials investigating the effect of protein supplementation on muscle mass in adults aged ≥65 years. Random effects meta-analyses were performed, stratified by population. Subgroups were created for dose (≥30 g, <30 g/day), frequency (once, twice, three times/day) and timing of supplementation (at breakfast, breakfast and lunch, breakfast and dinner, all meals, between meals). Heterogeneity within and between subgroups was assessed using I 2 and Cochran Q statistics respectively. Thirty-eight articles were included describing community-dwelling (28 articles, n=3204, 74.6±3.4 years, 62.8 % female), hospitalised (8 articles, n=590, 77.0±3.7 years, 50.3 % female) and institutionalised populations (2 articles, n=156, 85.7±1.2 years, 71.2 % female). Protein supplementation showed a positive effect on muscle mass in community-dwelling older adults (standardised mean difference 0.116; 95 % confidence interval 0.032–0.200 kg, p=0.007, I 2=15.3 %) but the effect did not differ between subgroups of dose, frequency and timing (Q=0.056, 0.569 and 3.084 respectively, p>0.05). Data including hospitalised and institutionalised populations were limited. Protein supplementation improves muscle mass in community-dwelling older adults, but its dose, frequency or timing does not significantly influence the effect.
Background & aims: Optimal nutritional support during the acute phase of critical illness remains controversial. We hypothesized that patients with low skeletal muscle area and -density may specifically benefit from early high protein intake. Aim of the present study was to determine the association between early protein intake (day 2–4) and mortality in critically ill intensive care unit (ICU) patients with normal skeletal muscle area, low skeletal muscle area, or combined low skeletal muscle area and -density. Methods: Retrospective database study in mechanically ventilated, adult critically ill patients with an abdominal CT-scan suitable for skeletal muscle assessment around ICU admission, admitted from January 2004 to January 2016 (n = 739). Patients received protocolized nutrition with protein target 1.2–1.5 g/kg/day. Skeletal muscle area and -density were assessed on abdominal CT-scans at the 3rd lumbar vertebra level using previously defined cut-offs. Results: Of 739 included patients (mean age 58 years, 483 male (65%), APACHE II score 23), 294 (40%) were admitted with normal skeletal muscle area and 445 (60%) with low skeletal muscle area. Two hundred (45% of the low skeletal muscle area group) had combined low skeletal muscle area and -density. In the normal skeletal muscle area group, no significant associations were found. In the low skeletal muscle area group, higher early protein intake was associated with lower 60-day mortality (adjusted hazard ratio (HR) per 0.1 g/kg/day 0.82, 95%CI 0.73–0.94) and lower 6-month mortality (HR 0.88, 95%CI 0.79–0.98). Similar associations were found in the combined low skeletal muscle area and -density subgroup (HR 0.76, 95%CI 0.64–0.90 for 60-day mortality and HR 0.80, 95%CI 0.68–0.93 for 6-month mortality). Conclusions: Early high protein intake is associated with lower mortality in critically ill patients with low skeletal muscle area and -density, but not in patients with normal skeletal muscle area on admission. These findings may be a further step to personalized nutrition, although randomized studies are needed to assess causality.
Skeletal muscle-related symptoms are common in both acute coronavirus disease (Covid)-19 and post-acute sequelae of Covid-19 (PASC). In this narrative review, we discuss cellular and molecular pathways that are affected and consider these in regard to skeletal muscle involvement in other conditions, such as acute respiratory distress syndrome, critical illness myopathy, and post-viral fatigue syndrome. Patients with severe Covid-19 and PASC suffer from skeletal muscle weakness and exercise intolerance. Histological sections present muscle fibre atrophy, metabolic alterations, and immune cell infiltration. Contributing factors to weakness and fatigue in patients with severe Covid-19 include systemic inflammation, disuse, hypoxaemia, and malnutrition. These factors also contribute to post-intensive care unit (ICU) syndrome and ICU-acquired weakness and likely explain a substantial part of Covid-19-acquired weakness. The skeletal muscle weakness and exercise intolerance associated with PASC are more obscure. Direct severe acute respiratory syndrome coronavirus (SARS-CoV)-2 viral infiltration into skeletal muscle or an aberrant immune system likely contribute. Similarities between skeletal muscle alterations in PASC and chronic fatigue syndrome deserve further study. Both SARS-CoV-2-specific factors and generic consequences of acute disease likely underlie the observed skeletal muscle alterations in both acute Covid-19 and PASC.
