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.
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BackgroundICU patients lose muscle mass rapidly and maintenance of muscle mass may contribute to improved survival rates and quality of life. Protein provision may be beneficial for preservation of muscle mass and other clinical outcomes, including survival. Current protein recommendations are expert-based and range from 1.2 to 2.0 g/kg. Thus, we performed a systematic review and meta-analysis on protein provision and all clinically relevant outcomes recorded in the available literature.MethodsWe conducted a systematic review and meta-analyses, including studies of all designs except case control and case studies, with patients aged ≥18 years with an ICU stay of ≥2 days and a mean protein provision group of ≥1.2 g/kg as compared to <1.2 g/kg with a difference of ≥0.2 g/kg between protein provision groups. All clinically relevant outcomes were studied. Meta-analyses were performed for all clinically relevant outcomes that were recorded in ≥3 included studies.ResultsA total of 29 studies published between 2012 and 2022 were included. Outcomes reported in the included studies were ICU, hospital, 28-day, 30-day, 42-day, 60-day, 90-day and 6-month mortality, ICU and hospital length of stay, duration of mechanical ventilation, vomiting, diarrhea, gastric residual volume, pneumonia, overall infections, nitrogen balance, changes in muscle mass, destination at hospital discharge, physical performance and psychological status. Meta-analyses showed differences between groups in favour of high protein provision for 60-day mortality, nitrogen balance and changes in muscle mass.ConclusionHigh protein provision of more than 1.2 g/kg in critically ill patients seemed to improve nitrogen balance and changes in muscle mass on the short-term and likely 60-day mortality. Data on long-term effects on quality of life are urgently needed.
MULTIFILE
BackgroundIncreased physical activity and dietary protein intake are promising interventions to prevent or treat the age-related decline in physical performance in older adults. There are well-controlled exercise as well as dietary intervention studies that show beneficial effects on physical performance in older adults. In practice, however, weekly group based exercise or nutritional programs may not be as effective. To optimise these exercise programs for community dwelling older adults, a digitally supported and personalised home-based exercise training program has been designed aiming to improve physical performance in older adults. In addition, a protein intervention in combination with the training program may further improve physical performance in older adults.MethodsThe VITAMIN study will be a cluster randomised controlled trial with three parallel arms. In total, 240 community dwelling older adults (≥ 55 years) participating in weekly group exercise are randomly allocated into: 1) regular weekly exercise program (Control group, n = 80), 2) digitally supported personalised home-based exercise training program group (VITA group, n = 80) and 3) digitally supported personalised home-based exercise training program group plus dietary protein counselling (VITA-Pro group, n = 80). The VITAMIN study aims to evaluate effectiveness of the digitally supported personalised home-based exercise training program as well as the additional value of dietary protein on physical performance after 6 months. In addition, a 12 month follow-up measurement will assess the retaining effect of the interventions. Primary outcome is physical performance measured by the Modified Physical Performance Test (M-PPT) and relevant secondary and observational outcomes include habitual physical activity and dietary intake, body composition, cognitive performance, quality of life, compliance and tablet usage. Data will be analysed by Linear Mixed Models.DiscussionTo our knowledge, the VITAMIN study is the first study that investigates the impact of home-based exercise, protein intake as well as use of persuasive technology in the population of community dwelling older adults.Trial registrationNL56094.029.16 / NTR (TC = 5888; registered 03–06-2016).
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While the creation of an energy deficit (ED) is required for weight loss, it is well documented that actual weight loss is generally lower than what expected based on the initially imposed ED, a result of adaptive mechanisms that are oppose to initial ED to result in energy balance at a lower set-point. In addition to leading to plateauing weight loss, these adaptive responses have also been implicated in weight regain and weight cycling (add consequences). Adaptions occur both on the intake side, leading to a hyperphagic state in which food intake is favored (elevated levels of hunger, appetite, cravings etc.), as well as on the expenditure side, as adaptive thermogenesis reduces energy expenditure through compensatory reductions in resting metabolic rate (RMR), non-exercise activity expenditure (NEAT) and the thermic effect of food (TEF). Two strategies that have been utilized to improve weight loss outcomes include increasing dietary protein content and increasing energy flux during weight loss. Preliminary data from our group and others demonstrate that both approaches - especially when combined - have the capacity to reduce the hyperphagic response and attenuate reductions in energy expenditure, thereby minimizing the adaptive mechanisms implicated in plateauing weight loss, weight regain and weight cycling. Past research has largely focused on one specific component of energy balance (e.g. hunger or RMR) rather than assessing the impact of these strategies on all components of energy balance. Given that all components of energy balance are strongly connected with each other and therefore can potentially negate beneficial impacts on one specific component, the primary objective of this application is to use a comprehensive approach that integrates all components of energy balance to quantify the changes in response to a high protein and high energy flux, alone and in combination, during weight loss (Fig 1). Our central hypothesis is that a combination of high protein intake and high energy flux will be most effective at minimizing both metabolic and behavioral adaptations in several components of energy balance such that the hyperphagic state and adaptive thermogenesis are attenuated to lead to superior weight loss results and long-term weight maintenance.
