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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Muscle fiber-type specific expression of UCP3-protein is reported here for the firts time, using immunofluorescence microscopy
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Abstract: INTRODUCTION: Early protein and energy feeding in critically ill patients is heavily debated and early protein feeding hardly studied.
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BACKGROUND: Findings on the association between early high protein provision and mortality in ICU patients are inconsistent. The relation between early high protein provision and mortality in patients receiving CRRT remains unclear. The aim was to study the association between early high protein provision and hospital and ICU mortality and consistency in subgroups.METHODS: A retrospective cohort study was conducted in 2618 ICU patients with a feeding tube and mechanically ventilated ≥48 h (2003-2016). The association between early high protein provision (≥1.2 g/kg/day at day 4 vs. <1.2 g/kg/day) and hospital and ICU mortality was assessed for the total group, for patients receiving CRRT, and for non-septic and septic patients, by Cox proportional hazards analysis. Adjustments were made for APACHE II score, energy provision, BMI, and age.RESULTS: Mean protein provision at day 4 was 0.96 ± 0.48 g/kg/day. A significant association between early high protein provision and lower hospital mortality was found in the total group (HR 0.48, 95% CI 0.39-0.60, p = <0.001), CRRT-receiving patients (HR 0.62, 95% CI 0.39-0.99, p = 0.045) and non-septic patients (HR 0.56, 95% CI 0.44-0.71, p = <0.001). However, no association was found in septic patients (HR 0.71, 95% CI 0.39-1.29, p = 0.264). These associations were very similar for ICU mortality. In a sensitivity analysis for patients receiving a relative energy provision >50%, results remained robust in all groups except for patients receiving CRRT.CONCLUSIONS: Early high protein provision is associated with lower hospital and ICU mortality in ICU patients, including CRRT-receiving patients. There was no association for septic patients.
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BackgroundIncreased protein provision might ameliorate muscle wasting and improve long-term outcomes in critically ill patients. The aim of the PRECISe trial was to assess whether higher enteral protein provision (ie, 2·0 g/kg per day) would improve health-related quality of life and functional outcomes in critically ill patients who were mechanically ventilated compared with standard enteral protein provision (ie, 1·3 g/kg per day).MethodsThe PRECISe trial was an investigator-initiated, double-blinded, multicentre, parallel-group, randomised controlled trial in five Dutch hospitals and five Belgian hospitals. Inclusion criteria were initiation of invasive mechanical ventilation within 24 h of intensive care unit (ICU) admission and an expected duration of invasive ventilation of 3 days or longer. Exclusion criteria were contraindications for enteral nutrition, moribund condition, BMI less than 18 kg/m2, kidney failure with a no dialysis code, or hepatic encephalopathy. Patients were randomly assigned to one of four randomisation labels, corresponding with two study groups (ie, standard or high protein; two labels per group) in a 1:1:1:1 ratio through an interactive web-response system. Randomisation was done via random permuted-block randomisation in varying block sizes of eight and 12, stratified by centre. Participants, care providers, investigators, outcome assessors, data analysts, and the independent data safety monitoring board were all blinded to group allocation. Patients received isocaloric enteral feeds that contained 1·3 kcal/mL and 0·06 g of protein/mL (ie, standard protein) or 1·3 kcal/mL and 0·10 g of protein/mL (ie, high protein). The study-nutrition intervention was limited to the time period during the patient's ICU stay in which they required enteral feeding, with a maximum of 90 days. The primary outcome was EuroQoL 5-Dimension 5-level (EQ-5D-5L) health utility score at 30 days, 90 days, and 180 days after randomisation, adjusted for baseline EQ-5D-5L health utility score. This trial was registered with ClinicalTrials.gov (NCT04633421) and is closed to new participants.FindingsBetween Nov 19, 2020, and April 14, 2023, 935 patients were randomly assigned. 335 (35·8%) of 935 patients were female and 600 (64·2%) were male. 465 (49·7%) of 935 were assigned to the standard protein group and 470 (50·3%) were assigned to the high protein group. 430 (92·5%) of 465 patients in the standard protein group and 419 (89·1%) of 470 patients in the high protein group were assessed for the primary outcome. The primary outcome, EQ-5D-5L health utility score during 180 days after randomisation (assessed at 30 days, 90 days, and 180 days), was lower in patients allocated to the high protein group than in those allocated to the standard protein group, with a mean difference of –0·05 (95% CI –0·10 to –0·01; p=0·031). Regarding safety outcomes, the probability of mortality during the entire follow-up was 0·38 (SE 0·02) in the standard protein group and 0·42 (0·02) in the high protein group (hazard ratio 1·14, 95% CI 0·92 to 1·40; p=0·22). There was a higher incidence of symptoms of gastrointestinal intolerance in patients in the high protein group (odds ratio 1·76, 95% CI 1·06 to 2·92; p=0·030). Incidence of other adverse events did not differ between groups.InterpretationHigh enteral protein provision compared with standard enteral protein provision resulted in worse health-related quality of life in critically ill patients and did not improve functional outcomes during 180 days after ICU admission.
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PURPOSE OF REVIEW: Protein delivery in the critically ill still is a highly debated issue. Here, we discuss only the most recent updates in the literature concerning protein nutrition of the critically ill.RECENT FINDINGS: Up to now, there are no randomized controlled trials (RCTs) published on enteral provision of protein that were randomized for protein level of intake. In the past year, there have been two new observational studies published, one of which in critically ill children. Also, two randomized controlled trials with high parenteral amino acid provision have been published. The overall view on nutrition support has not been changed convincingly by these studies. Recent findings have confirmed that protein and amino acid provision are highly important for outcome in critically ill patients. For the first time, a randomized study confirmed this, however, only on the short term. The other RCT confirmed that an extreme dosing of amino acids is not related to improvement in outcome. One observational study showed that the effect of protein on outcome should be adjusted for energy intake and vice versa, showing that adequate protein is related to improved outcome and adequate energy provision is not. The other observational study confirmed importance of protein in paediatric ICU but also gained some insight into improvement of protein delivery by postpyloric feeding and usefulness of a dedicated dietitian in the ICU.SUMMARY: We will continue to improve protein delivery to critically ill patients; however, the quest for evidence and feeding guidelines still remains.
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Even in a less eventful year, it’s no easy feat: working to make our food supply healthy and sustainable. But 2020 brought a spate of new challenges. It was the year of Brexit, Black Lives Matter, and the COVID-19 pandemic. A year of hope and loss and solidarity, of masks and worries and Zoom calls. Of infection sweeping through the meatpacking industry and sometimes, of empty supermarket shelves. It was also the year that brought us the glimmering realisation that everything could be different. When so much has changed – how we work, who we spend time with, how far we venture from home – what all might be possible for food and for farming? In Flevo Campus’s latest collection of essays, thirteen journalists, scholars, and thought leaders from the US, the Netherlands, and the UK share insight into the question: How can we build resilience into our food supply – and grow more resilient ourselves? Every year, Flevo Campus publishes the best work on feeding the cities of today and tomorrow. This year’s edition includes essays by Stephen Satterfield, Charles C. Mann, Herman Lelieveldt, Hester Dibbits, Kelly Streekstra, Sigrid Wertheim-Heck, Anke Brons, Joris Lohman, Sebastiaan Aalst, Marian Stuiver, Frank Verhoeven, Emily Whyman, and Lenno Munnikes.
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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.
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Using either freshly pulped or preserved seaweed biomass for the extraction of protein can have a great effect on the amount of protein that can be extracted. In this study, the effect of four preservation techniques (frozen, freeze-dried, and air-dried at 40 and 70 °C) on the protein extractability, measured as Kjeldahl nitrogen, of four seaweed species, Chondrus crispus (Rhodophyceae), Ascophyllum nodosum, Saccharina latissima (both Phaeophyceae) and Ulva lactuca (Chlorophyceae), was tested and compared with extracting freshly pulped biomass. The effect of preservation is species dependent: in all four seaweed species, a differenttreatment resulted in the highest protein extractability. The pellet (i.e., the non-dissolved biomass after extraction) was also analyzed as in most cases the largest part of the initial protein ended up in the pellet and not in the supernatant. Of the four species tested, freeze-dried A. nodosum yielded the highest overall protein extractability of 59.6% with a significantly increased protein content compared with the sample before extraction. For C. crispus extracting biomass air-dried at 40 °C gave the best results with a protein extractability of 50.4%. Preservation had little effect on the protein extraction for S. latissima; only air-drying at 70 °C decreased the yield significantly. Over 70% of the initial protein ended up in the pellet for all U. lactuca extractions while increasing the protein content significantly. Extracting freshly pulped U. lactuca resulted in a 78% increase in protein content in the pellet while still containing 84.5% of the total initial total protein. These results show the importance of the right choice when selecting a preservation method and seaweed species for protein extraction. Besides the extracted protein fraction, the remainingpellet also has the potential as a source with an increased protein content.
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From PLoS website: In general, dietary antigens are tolerated by the gut associated immune system. Impairment of this so-called oral tolerance is a serious health risk. We have previously shown that activation of the ligand-dependent transcription factor aryl hydrocarbon receptor (AhR) by the environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) affects both oral tolerance and food allergy. In this study, we determine whether a common plant-derived, dietary AhR-ligand modulates oral tolerance as well. We therefore fed mice with indole-3-carbinole (I3C), an AhR ligand that is abundant in cruciferous plants. We show that several I3C metabolites were detectable in the serum after feeding, including the high-affinity ligand 3,3´-diindolylmethane (DIM). I3C feeding robustly induced the AhR-target gene CYP4501A1 in the intestine; I3C feeding also induced the aldh1 gene, whose product catalyzes the formation of retinoic acid (RA), an inducer of regulatory T cells. We then measured parameters indicating oral tolerance and severity of peanut-induced food allergy. In contrast to the tolerance-breaking effect of TCDD, feeding mice with chow containing 2 g/kg I3C lowered the serum anti-ovalbumin IgG1 response in an experimental oral tolerance protocol. Moreover, I3C feeding attenuated symptoms of peanut allergy. In conclusion, the dietary compound I3C can positively influence a vital immune function of the gut.
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