The critical care community still has mixed feelings when considering the optimal nutrition of intensive care unit (ICU) patients, which is understandable as randomized controlled trials have not been very helpful in improving clinical practice. There have been no randomized controlled trials (RCTs) to contribute to the discussion, especially concerning the role of enterally fed protein in optimal critical care. Recent studies on the route of feeding have shown that enteral nutrition (EN) is not necessarily superior to parenteral nutrition (PN) [1, 2]. There appears to be a strong consensus, with backup from a meta-analysis, on the preferential use of EN over PN [3]. The infection rate was especially used as an argument; however, this is not substantiated in recent trials [1, 2]. We have to consider how applicable this current knowledge is to all ICU patients. Early EN is still the preferred way of feeding [3]. Starting feeding early may improve the outcome of ICU patients. RCTs have all investigated (supplemental parenteral) energy delivery [4]. Only two trials have ‘considered’ protein: the PERMIT trial [5] (protein supplemented, equal level) and EAT-ICU trial [6] (protein supplemented, higher level). Early energy delivery should be applied cautiously since it appears to be related to worse outcome in ICU patients [7, 8, 9]. Therefore, and from the perspective of clinical practice, the Swiss Supplemental PN (SPN) trial appears to provide the most logical design [10]—start with early EN and evaluate on day 3 what the level of energy delivery is; when delivery levels are low (< 60%) start supplementation PN. In clinical practice in our ICU the enteral feeding levels are high enough to avoid PN supplementation, which therefore restricts the specific indication to use PN. The focus of this research has been caloric delivery. There are more than enough observational data to support that higher protein delivery is associated with improved outcome in ICU patients [7, 8, 9]. These observational studies clearly show the benefit of higher protein delivery. However, they are considered relatively weak evidence since illness is considered a confounding factor in the relationship between delivery and outcome for which we cannot completely adjust. Randomized trials have not been conducted, although two trials with randomized high(er) amino acid infusion are available and somewhat contradicting [11, 12]. As with the studies on caloric delivery, the studies on protein have been hampered by insufficient knowledge on energy and protein metabolism under these (patho)physiological circumstances in the ICU patient [7, 8, 9]. Therefore, mechanistic studies on the protein physiology in ICU patients is an essential and current development. The Swedish group of Wernerman and Rooyackers has provided crucial information on the topic. They showed that it was possible to change protein balance during the early phase of admission to the ICU from negative to positive by a short-term (3-h) high-level (1 g/kg/day) amino acid (AA) infusion [13]. This observation was very important to help understand the physiology since it showed that, under these circumstances of critical illness, some basic principles of nutrition still perform well. In the December 2017 issue of Critical Care, Sundstrom et al. showed that the effect of supplemental AA infusion at 3 h is still present at 24 h [14]. Why is this so important to know? We know from extensive studies in sports and the elderly that protein synthesis can be stimulated by bolus protein feeding; however, we know relatively little about the effects of continuous (low dose per time unit) feeding. While the absolute levels of protein balance still have to be considered with caution (e.g., choice of tracer), and we are not completely sure where the protein is going, we now know this positive effect on protein balance is lasting. The next challenge is to reconnect this physiological information with the outcome of ICU patients. We have shown that muscle (protein) mass at admission to the ICU is relevant for the outcome of ICU patients [15]. We do not know if we can change muscle mass and outcome of ICU patients with protein nutrition. The study by Sundstrom et al. [14] is very promising for protein balance, but will that be enough to change outcome? And, if so, is that true for all patients—does one size fit all? The ICU patient group is heterogeneous. Earlier, we found high protein delivery to be associated with lower mortality, except for sepsis patients and patients with early caloric overfeeding [7]. The EAT-ICU trial did not find an effect of early goal-directed feeding on physical component score at 6 months or on mortality [6]. Goal-directed feeding included feeding energy based on indirect calorimetry and protein up to 1.5 g/kg/day from day 1. Feeding calories up to the measured caloric target from day 1 may be equal to caloric overfeeding [7]. The 47% of patients with sepsis in the EAT-ICU trial might also not benefit from the higher protein feeding [7]. Therefore, the effects of protein and energy cannot be assessed individually from this trial. Ferrie et al. showed interesting differences in muscle mass and function between an AA infusion rate of 0.8 and 1.2 g/kg/day [12], but not all patients are equal—one size does not fit all! Those patients with a low protein reserve (low muscle mass) may be at highest risk in the ICU and may benefit more from intervention with early protein nutrition. We have to await further studies, including randomized studies and post-hoc observational studies, to further develop this area of interest. The studies trying to understand the mechanism behind the physiological effect are important as well; we might come nearer to the truth of what works and what does not work in ICU nutrition.
DOCUMENT
Purpose of reviewSkeletal muscle mass with aging, during critical care, and following critical care is a determinant of quality of life and survival. In this review, we discuss the mechanisms that underpin skeletal muscle atrophy and recommendations to offset skeletal muscle atrophy with aging and during, as well as following, critical care.Recent findingsAnabolic resistance is responsible, in part, for skeletal muscle atrophy with aging, muscle disuse, and during disease states. Anabolic resistance describes the reduced stimulation of muscle protein synthesis to a given dose of protein/amino acids and contributes to declines in skeletal muscle mass. Physical inactivity induces: anabolic resistance (that is likely exacerbated with aging), insulin resistance, systemic inflammation, decreased satellite cell content, and decreased capillary density. Critical illness results in rapid skeletal muscle atrophy that is a result of both anabolic resistance and enhanced skeletal muscle breakdown.SummaryInsofar as atrophic loss of skeletal muscle mass is concerned, anabolic resistance is a principal determinant of age-induced losses and appears to be a contributor to critical illness-induced skeletal muscle atrophy. Older individuals should perform exercise using both heavy and light loads three times per week, ingest at least 1.2 g of protein/kg/day, evenly distribute their meals into protein boluses of 0.40 g/kg, and consume protein within 2 h of retiring for sleep. During critical care, early, frequent, and multimodal physical therapies in combination with early, enteral, hypocaloric energy (ﰅ10–15kcal/kg/day), and high-protein (>1.2 g/kg/day) provision is recommended.
DOCUMENT
Background: A protein intake of 30‐40 g per meal is suggested to maximally stimulate muscle protein synthesis in older adults and could therefore contribute to the prevention of sarcopenia. Protein intake at breakfast and lunch is often low and offers a great opportunity to improve daily protein intake. Protein, however, is known for its satiating effects. Therefore, we explored the association between the amount of protein intake at breakfast and lunch and total daily protein intake in older adults.Methods: Protein intake was assessed by a 3‐day food record in 498 community dwelling older adults (≥55 years) participating different lifestyle interventions. Linear mixed model analysis was used to examine the association between protein intake at breakfast or lunch and total daily protein intake, adjusted for sex, age, body mass index, smoking status, study and total energy intake.Results: After adjustment for potential confounders, a 10 g higher protein intake at breakfast was associated with a 3.2 g higher total daily protein intake (P = 0.008) for males and a 4.9 g (P < 0.001) higher total daily protein intake for females. A 10 g higher protein intake at lunch was associated with a 3.7 g higher total daily protein intake (P < 0.001) for males, and a 5.8 g higher total daily protein intake (P < 0.001) for females.Conclusions: A higher protein intake at breakfast and lunch is associated with a higher total daily protein intake in community dwelling older adults. Stimulating a higher protein intake at breakfast and lunch might represent a promising nutritional strategy to optimise the amount of protein per meal without compromising total daily protein intake.
DOCUMENT
Om inzicht te krijgen in spierveroudering is genexpressie gemeten in vastus lateralis biopten van jonge en oude mannen en vrouwen. We vonden dat tijdens het ouder worden bij beide geslachten dezelfde categorieën genen in spieren worden aan- en uitgeschakeld (“gereguleerd”); de mate van deze zogenaamde differentiële expressie was echter geslachtsspecifiek. Bij mannen was oxidatieve fosforylering het meest in het oog springende proces, en bij vrouwen was dit celgroei gemedieerd door AKT-signalering. De conclusie is dat dezelfde processen zijn geassocieerd met skeletspierveroudering bij mannen en vrouwen, maar dat de differentiële expressie van die processen geslachtsspecifiek is.
MULTIFILE
Introduction: A protein intake of 25–30 g per meal is suggested to maximally stimulate muscle protein synthesis in older adults in order to prevent sarcopenia. Protein intake at breakfast is often low and therefore breakfast offers the potential for protein suppletion. Since protein is known for its satiating effects, we explored the association between the amount of protein intake at breakfast and total daily protein intake in older adults. Methods: Baseline protein intake was assessed by a 3-day dietary record in 507 community dwelling older adults of 55 years and older participating in lifestyle interventions at the Amsterdam Nutritional Assessment Center. Multiple linear regression analysis was used to examine the association between protein intake at breakfast (in g) and total daily protein intake (in g, and g/kg body weight), adjusted for energy intake (kcal/d), sex, age and BMI. Interactions were tested for sex, age and BMI but were not significant (p>0.80). Results: Mean age was 67.6 ± (SD) 7.3 years, 42% was female, and mean BMI was 30.0 ± 5.6 kg/m2. Total daily protein intake was 81 ± 24 g which equals 0.96 ± 0.3 g/kg and 17.6 ± 3.7 percent of total energy intake. Protein intake at breakfast was 14 ± 7 g. A 10 g higher protein intake at breakfast was associated with a 6.7 g (SE = 1.0; P<0.001) and a 0.06 g/kg (SE = 0.01; P<0.001) higher total daily protein intake after adjustment for confounders. Key conclusions: A higher protein intake at breakfast does not compromise total daily protein intake in community dwelling older adults.
DOCUMENT
Introduction: A protein intake of 25–30 g per meal is suggested to maximally stimulate muscle protein synthesis in older adults in order to prevent sarcopenia. Protein intake at breakfast is often low and therefore breakfast offers the potential for protein suppletion. Since protein is known for its satiating effects, we explored the association between the amount of protein intake at breakfast and total daily protein intake in older adults. Methods: Baseline protein intake was assessed by a 3-day dietary record in 507 community dwelling older adults of 55 years and older participating in lifestyle interventions at the Amsterdam Nutritional Assessment Center. Multiple linear regression analysis was used to examine the association between protein intake at breakfast (in g) and total daily protein intake (in g, and g/kg body weight), adjusted for energy intake (kcal/d), sex, age and BMI. Interactions were tested for sex, age and BMI but were not significant (p>0.80). Results: Mean age was 67.6 ± (SD) 7.3 years, 42% was female, and mean BMI was 30.0 ± 5.6 kg/m2. Total daily protein intake was 81 ± 24 g which equals 0.96 ± 0.3 g/kg and 17.6 ± 3.7 percent of total energy intake. Protein intake at breakfast was 14 ± 7 g. A 10 g higher protein intake at breakfast was associated with a 6.7 g (SE = 1.0; P<0.001) and a 0.06 g/kg (SE = 0.01; P<0.001) higher total daily protein intake after adjustment for confounders. Key conclusions: A higher protein intake at breakfast does not compromise total daily protein intake in community dwelling older adults.
DOCUMENT
The International Protein Summit in 2016 brought experts in clinical nutrition and protein metabolism together from around the globe to determine the impact of high-dose protein administration on clinical outcomes and address barriers to its delivery in the critically ill patient. It has been suggested that high doses of protein in the range of 1.2-2.5 g/kg/d may be required in the setting of the intensive care unit (ICU) to optimize nutrition therapy and reduce mortality. While incapable of blunting the catabolic response, protein doses in this range may be needed to best stimulate new protein synthesis and preserve muscle mass. Quality of protein (determined by source, content and ratio of amino acids, and digestibility) affects nutrient sensing pathways such as the mammalian target of rapamycin. Achieving protein goals the first week following admission to the ICU should take precedence over meeting energy goals. High-protein hypocaloric (providing 80%-90% of caloric requirements) feeding may evolve as the best strategy during the initial phase of critical illness to avoid overfeeding, improve insulin sensitivity, and maintain body protein homeostasis, especially in the patient at high nutrition risk. This article provides a set of recommendations based on assessment of the current literature to guide healthcare professionals in clinical practice at this time, as well as a list of potential topics to guide investigators for purposes of research in the future.
DOCUMENT
Evaluating protein kinetics in the critically ill population remains a very difficult task. Heterogeneity in the intensive care unit (ICU) population and wide spectrum of disease processes creates complexity in assessing protein kinetics. Traditionally, protein has been delivered in the context of total energy. Focus on energy delivery has recently come into question, as the importance of supplemental protein in patient outcomes has been shown in several recent trials. The ICU patient is prone to catabolism, immobilization, and impaired immunity, which is a perfect storm for massive loss of lean body tissue with a unidirectional flow of amino acids from muscle to immune tissue for immunoglobulin production, as well as liver for gluconeogenesis and acute phase protein synthesis. The understanding of protein metabolism in the ICU has been recently expanded with the discovery of how the mammalian target of rapamycin complex 1 is regulated. The concept of "anabolic resistance" and identifying the quantity of protein required to overcome this resistance is gaining support among critical care nutrition circles. It appears that a minimum of at least 1.2 g/kg/d with levels up to 2.0 g/kg/d of protein or amino acids appears safe for delivery in the ICU setting and may yield a better clinical outcome.
DOCUMENT
The results of this study indicate that whole body metabolic and cardiovascular responses to 140 min of either steady state or variable intensity exercise at the same average intensity are similar, despite differences in skeletal muscle carbohydrate metabolism and recruitment
DOCUMENT
We tested the hypothesis that in human ageing a decreased intramuscular acylcarnitine status is associated with (pre-)frailty, reduced physical performance and altered mitochondrial function. Results showed that intramuscular total carnitine levels and acetylcarnitine levels were lower in (pre-)frail old females compared to fit old females and young females, whereas no differences were observed in males. The low intramuscular acetylcarnitine levels in females correlated with low physical performance, even after correction for muscle mass (%), and were accompanied with lowered expression of genes involved in mitochondrial energy production and functionality. We concluded that in (pre-)frail old females, intramuscular total carnitine levels and acetylcarnitine levels are decreased, and this decrease is associated with reduced physical performance and low expression of a wide range of genes critical for mitochondrial function. The results stress the importance of taking sex differences into account in ageing research.
MULTIFILE
