Randomized Controlled-Feeding Study of Dietary Emulsifier Carboxymethylcellulose Reveals Detrimental Impacts on the Gut Microbiota and Metabolome.

BACKGROUND & AIMS: Epidemiologic and murine studies suggest that dietary emulsifiers promote development of diseases associated with microbiota dysbiosis. Although the detrimental impact of these compounds on the intestinal microbiota and intestinal health have been demonstrated in animal and in vitro models, impact of these food additives in healthy humans remains poorly characterized. METHODS: To examine this notion in humans, we performed a double-blind controlled-feeding study of the ubiquitous synthetic emulsifier carboxymethylcellulose (CMC) in which healthy adults consumed only emulsifier-free diets (n = 9) or an identical diet enriched with 15 g per day of CMC (n = 7) for 11 days. RESULTS: Relative to control subjects, CMC consumption modestly increased postprandial abdominal discomfort and perturbed gut microbiota composition in a way that reduced its diversity. Moreover, CMC-fed subjects exhibited changes in the fecal metabolome, particularly reductions in short-chain fatty acids and free amino acids. Furthermore, we identified 2 subjects consuming CMC who exhibited increased microbiota encroachment into the normally sterile inner mucus layer, a central feature of gut inflammation, as well as stark alterations in microbiota composition. CONCLUSIONS: These results support the notion that the broad use of CMC in processed foods may be contributing to increased prevalence of an array of chronic inflammatory diseases by altering the gut microbiome and metabolome (ClinicalTrials.gov, number NCT03440229).

A Randomized Trial Comparing the Specific Carbohydrate Diet to a Mediterranean Diet in Adults With Crohn's Disease.

BACKGROUND & AIMS: This study compared the effectiveness of the Specific Carbohydrate Diet (SCD) to the Mediterranean diet (MD) as treatment for Crohn's disease (CD) with mild to moderate symptoms. METHODS: Adult patients with CD and with mild-to-moderate symptoms were randomly assigned 1:1 to consume the MD or SCD for 12 weeks. For the first 6 weeks, participants received prepared meals and snacks according to their assigned diet. After 6 weeks, participants were instructed to follow the diet independently. The primary outcome was symptomatic remission at week 6. Key secondary outcomes at week 6 included fecal calprotectin (FC) response (FC <250 µg/g and reduction by >50% among those with baseline FC >250 µg/g) and C-reactive protein (CRP) response (high-sensitivity CRP <5 mg/L and >50% reduction from baseline among those with high-sensitivity CRP >5 mg/L). RESULTS: The study randomized 194 patients, and 191 were included in the efficacy analyses. The percentage of participants who achieved symptomatic remission at week 6 was not superior with the SCD (SCD, 46.5%; MD, 43.5%; P = .77). FC response was achieved in 8 of 23 participants (34.8%) with the SCD and in 4 of 13 participants (30.8%) with the MD (P = .83). CRP response was achieved in 2 of 37 participants (5.4%) with the SCD and in 1 of 28 participants (3.6%) with the MD (P = .68). CONCLUSIONS: The SCD was not superior to the MD to achieve symptomatic remission, FC response, and CRP response. CRP response was uncommon. Given these results, the greater ease of following the MD and other health benefits associated with the MD, the MD may be preferred to the SCD for most patients with CD with mild to moderate symptoms. ClinicalTrials.gov Identifier: NCT03058679.

The Influence of Timing in Critical Care Nutrition.

Proper timing of critical care nutrition has long been a matter of controversy. Critical illness waxes and wanes in stages, creating a dynamic flux in energy needs that we have only begun to examine. Furthermore, response to nutrition support likely differs greatly at the level of the individual patient in regard to genetic status, disease stage, comorbidities, and more. We review the observational and randomized literature concerning timing in nutrition support, discuss mechanisms of harm in feeding critically ill patients, and highlight the role of precision nutrition for moving the literature beyond the realm of blunt population averages into one that accounts for the patient-specific complexities of critical illness and host genetics.

Influence of Corticosteroid Use on Short- and Long-Term Outcomes of Biologic Therapy for Inflammatory Bowel Diseases.

BACKGROUND: Corticosteroids (CS) are widely used to treat Crohn's disease (CD) and ulcerative colitis (UC), but are not recommended as maintenance therapy. Biologic drugs are widely used as an alternative to or in conjunction with CS to induce and maintain remission. This meta-analysis tested the hypothesis that CS use is associated with differential response to biologics. METHODS: We identified published placebo-controlled clinical trials of biologic drugs approved for the treatment of CD or UC. Pooled estimates of the risk difference (RD) and 95% confidence intervals were derived from random effects models for induction of response and remission and maintenance of remission comparing biologic with CS versus biologic alone. Heterogeneity of response was estimated using I2. RESULTS: Fifteen studies met the inclusion criteria. Pooled estimates of the RD and I2 comparing biologic plus CS versus biologic alone were as follows: induction of UC response 0.15 (0.05, 0.25), I2 = 57.29% and CD response 0.02 (- 0.03, 0.06), I2 = 0.01%; induction of UC remission 0.03 (- 0.01, 0.08), I2 = 0.00% and CD remission 0.08(0.02, 0.14), I2 = 7.81%; and maintenance of UC remission - 0.06 (- 0.13, 0.01), I2 = 0.00% and CD remission - 0.06 (- 0.14, 0.03), I2 = 11.24%. Patients in the placebo arm of CD trials who were receiving CS were less likely to achieve remission during the induction phase (pooled RD - 0.05 (- 0.09, - 0.00), I2 = 0.00%). CONCLUSIONS: In this meta-analysis of placebo-controlled trials, CS use was associated with higher biologic response rates for UC and remission rates for CD during the induction phase, but were not associated with improved maintenance of remission.

Dietary Guidance From the International Organization for the Study of Inflammatory Bowel Diseases.

Recent evidence points to a plausible role of diet and the microbiome in the pathogenesis of both Crohn's disease (CD) and Ulcerative Colitis (UC). Dietary therapies based on exclusion of table foods and replacement with nutritional formulas and/or a combination of nutritional formulas and specific table foods may induce remission in CD. In UC, specific dietary components have also been associated with flare of disease. While evidence of varying quality has identified potential harmful or beneficial dietary components, physicians and patients at the present time do not have guidance as to which foods are safe, may be protective or deleterious for these diseases. The current document has been compiled by the nutrition cluster of the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) based on the best current evidence to provide expert opinion regarding specific dietary components, food groups and food additives that may be prudent to increase or decrease in the diet of patients with inflammatory bowel diseases to control and prevent relapse of inflammatory bowel diseases.

Combination of High-Calorie Delivery and Organ Failure Increases Mortality Among Patients With Acute Respiratory Distress Syndrome.

OBJECTIVES: Among critically ill patients, the benefits of nutrition support may vary depending on severity of organ dysfunction. The objective of the current article was to explore the relationship between organ failure and calories exposure with hospital mortality during the first week of acute respiratory distress syndrome. DESIGN: Retrospective observational study. SETTING: Single-center ICU. PATIENTS: Adults admitted to the ICU with a diagnosis of acute respiratory distress syndrome. INTERVENTIONS: Calorie delivery from enteral nutrition, parenteral nutrition, propofol, and dextrose containing fluids were collected for 7 days following intubation. Sequential Organ Failure Assessment score was calculated at ICU admit and for the same 7 days to describe organ dysfunction; four different Sequential Organ Failure Assessment variables were created 1) Sequential Organ Failure Assessment at ICU admit, 2) average Sequential Organ Failure Assessment for the first 7 days following intubation, 3) the highest Sequential Organ Failure Assessment for the first 7 days following intubation, and 4) change in Sequential Organ Failure Assessment from intubation to 7 days later. MEASUREMENTS AND MAIN RESULTS: A total of 298 patients were included. Sequential Organ Failure Assessment at ICU admit, average Sequential Organ Failure Assessment for the first 7 days following intubation, highest Sequential Organ Failure Assessment for the first 7 days following intubation, change in Sequential Organ Failure Assessment from intubation to 7 days later, and calorie delivery the first 7 days following intubation were all associated with increased likelihood of mortality. Compared with patients with low organ failure and low-calorie delivery, those with high-calorie delivery and low organ failure, low-calorie delivery and high organ failure, and the combination of both high organ failure with high-calorie delivery were associated with an incremental increase in the likelihood or mortality. CONCLUSIONS: Organ failure appears to modify the relationship between calorie exposure and ICU outcome. Additional research is needed to identify appropriate thresholds for safe calorie exposure with increased organ failure.

Guidelines for the Provision and Assessment of Nutrition Support Therapy in the Pediatric Critically Ill Patient: Society of Critical Care Medicine and American Society for Parenteral and Enteral Nutrition.

This document represents the first collaboration between two organizations, American Society of Parenteral and Enteral Nutrition and the Society of Critical Care Medicine, to describe best practices in nutrition therapy in critically ill children. The target of these guidelines is intended to be the pediatric (> 1 mo and < 18 yr) critically ill patient expected to require a length of stay greater than 2 or 3 days in a PICU admitting medical, surgical, and cardiac patients. In total, 2,032 citations were scanned for relevance. The PubMed/Medline search resulted in 960 citations for clinical trials and 925 citations for cohort studies. The EMBASE search for clinical trials culled 1,661 citations. In total, the search for clinical trials yielded 1,107 citations, whereas the cohort search yielded 925. After careful review, 16 randomized controlled trials and 37 cohort studies appeared to answer one of the eight preidentified question groups for this guideline. We used the Grading of Recommendations, Assessment, Development and Evaluation criteria to adjust the evidence grade based on assessment of the quality of study design and execution. These guidelines are not intended for neonates or adult patients. The guidelines reiterate the importance of nutritional assessment, particularly the detection of malnourished patients who are most vulnerable and therefore potentially may benefit from timely intervention. There is a need for renewed focus on accurate estimation of energy needs and attention to optimizing protein intake. Indirect calorimetry, where feasible, and cautious use of estimating equations and increased surveillance for unintended caloric underfeeding and overfeeding are recommended. Optimal protein intake and its correlation with clinical outcomes are areas of great interest. The optimal route and timing of nutrient delivery is an area of intense debate and investigations. Enteral nutrition remains the preferred route for nutrient delivery. Several strategies to optimize enteral nutrition during critical illness have emerged. The role of supplemental parenteral nutrition has been highlighted, and a delayed approach appears to be beneficial. Immunonutrition cannot be currently recommended. Overall, the pediatric critical care population is heterogeneous, and a nuanced approach to individualizing nutrition support with the aim of improving clinical outcomes is necessary.

Guidelines for parenteral nutrition in preterm infants: The American Society for Parenteral and Enteral Nutrition.

BACKGROUND: Parenteral nutrition (PN) is prescribed for preterm infants until nutrition needs are met via the enteral route, but unanswered questions remain regarding PN best practices in this population. METHODS: An interdisciplinary committee was assembled to answer 12 questions concerning the provision of PN to preterm infants. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) process was used. Questions addressed parenteral macronutrient doses, lipid injectable emulsion (ILE) composition, and clinically relevant outcomes, including PNALD, early childhood growth, and neurodevelopment. Preterm infants with congenital gastrointestinal disorders or infants already diagnosed with necrotizing enterocolitis or PN-associated liver disease (PNALD) at study entry were excluded. RESULTS: The committee reviewed 2460 citations published between 2001 and 2023 and evaluated 57 clinical trials. For most questions, quality of evidence was very low. Most analyses yielded no significant differences between comparison groups. A multicomponent oil ILE was associated with a reduction in stage 3 or higher retinopathy of prematurity (ROP) compared to an ILE containing 100% soybean oil. For all other questions, expert opinion was provided. CONCLUSION: Most clinical outcomes were not significantly different between comparison groups when evaluating timing of PN initiation, amino acid dose, and ILE composition. Future clinical trials should standardize outcome definitions to permit statistical conflation of data, thereby permitting more evidence based recommendations in future guidelines. This guideline has been approved by the ASPEN 2022-2023 Board of Directors.

Current practices in nutrition therapy in cardiac surgery patients: An international multicenter observational study.

BACKGROUND: Cardiac surgery patients with a prolonged stay in the intensive care unit (ICU) are at high risk for acquired malnutrition. Medical nutrition therapy practices for cardiac surgery patients are unknown. The objective of this study is to describe the current nutrition practices in critically ill cardiac surgery patients worldwide. METHODS: We conducted a prospective observational study in 13 international ICUs involving mechanically ventilated cardiac surgery patients with an ICU stay of at least 72 h. Collected data included the energy and protein prescription, type of and time to the initiation of nutrition, and actual quantity of energy and protein delivered (maximum: 12 days). RESULTS: Among 237 enrolled patients, enteral nutrition (EN) was started, on average, 45 h after ICU admission (range, 0-277 h; site average, 53 [range, 10-79 h]). EN was prescribed for 187 (79%) patients and combined EN and parenteral nutrition in 33 (14%). Overall, patients received 44.2% (0.0%-117.2%) of the prescribed energy and 39.7% (0.0%-122.8%) of the prescribed protein. At a site level, the average nutrition adequacy was 47.5% (30.5%-78.6%) for energy and 43.6% (21.7%-76.6%) for protein received from all nutrition sources. CONCLUSION: Critically ill cardiac surgery patients with prolonged ICU stay experience significant delays in starting EN and receive low levels of energy and protein. There exists tremendous variability in site performance, whereas achieving optimal nutrition performance is doable.

Guidelines for the provision of nutrition support therapy in the adult critically ill patient: The American Society for Parenteral and Enteral Nutrition.

BACKGROUND: This guideline updates recommendations from the 2016 American Society for Parenteral and Enteral Nutrition (ASPEN)/Society of Critical Care Medicine (SCCM) critical care nutrition guideline for five foundational questions central to critical care nutrition support. METHODS: The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) process was used to develop and summarize evidence for clinical practice recommendations. Clinical outcomes were assessed for (1) higher vs lower energy dose, (2) higher vs lower protein dose, (3) exclusive isocaloric parenteral nutrition (PN) vs enteral nutrition (EN), (4) supplemental PN (SPN) plus EN vs EN alone, (5A) mixed-oil lipid injectable emulsions (ILEs) vs soybean oil, and (5B) fish oil (FO)-containing ILE vs non-FO ILE. To assess safety, weight-based energy intake and protein were plotted against hospital mortality. RESULTS: Between January 1, 2001, and July 15, 2020, 2320 citations were identified and data were abstracted from 36 trials including 20,578 participants. Patients receiving FO had decreased pneumonia rates of uncertain clinical significance. Otherwise, there were no differences for any outcome in any question. Owing to a lack of certainty regarding harm, the energy prescription recommendation was decreased to 12-25 kcal/kg/day. CONCLUSION: No differences in clinical outcomes were identified among numerous nutrition interventions, including higher energy or protein intake, isocaloric PN or EN, SPN, or different ILEs. As more consistent critical care nutrition support data become available, more precise recommendations will be possible. In the meantime, clinical judgment and close monitoring are needed. This paper was approved by the ASPEN Board of Directors.

Nutritional screening tool for critically ill children: a systematic review.

CONTEXT: Nutritional screening tools (NSTs) are used to identify patients who are at risk of nutritional status (NS) deterioration and associated clinical outcomes. Several NSTs have been developed for hospitalized children; however, none of these were specifically developed for Pediatric Intensive Care Unit (PICU) patients. OBJECTIVE: A systematic review of studies describing the development, application, and validation of NSTs in hospitalized children was conducted to critically appraise their role in PICU patients. DATA SOURCES: PubMed, Embase, Web of Science, Scopus, SciELO, LILACS, and Google Scholar were searched from inception to December 11, 2020. DATA EXTRACTION: The review included 103 studies that applied NSTs at hospital admission. The NST characteristics collected included the aims, clinical setting, variables, and outcomes. The suitability of the NSTs in PICU patients was assessed based on a list of variables deemed relevant for this population. DATA ANALYSIS: From 19 NSTs identified, 13 aimed to predict NS deterioration. Five NSTs were applied in PICU patients, but none was validated for this population. NSTs did not include clinical, NS, laboratory, or dietary variables that were deemed relevant for the PICU population. CONCLUSION: None of the available NSTs were found to be suitable for critically ill children, so a new NST should be developed for this population. AQ6. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42020167898.

New implementations for the ASPEN clinical guidelines and a call for protocol review on the nutrition guidelines for adult head and neck cancer.

The current article details new upgrades to the guideline methodology, including the publication of "a priori" protocols, methods for assuring agreement between reviewers, adoption of Covidence software for tracking reasons for article exclusion, the establishment of a separate bias panel to improve study quality assessment, an algorithm for study design inclusion, and Delphi technique implementation for the management and external validation of expert opinion. These methodologic additions will provide greater transparency and accountability for the choices made during the guideline development process.

Overview of Study Designs: A Deep Dive Into Research Quality Assessment.

Life presents a web of interconnected causes and effects, transforming the simple art of observation into a deceptively complex affair. Study designs were created to address this complexity, though no study design is ideal. The current paper reviews the major study designs, providing tips to research-consuming clinicians for spotting lapses in validity through the introduction of confounding, selection, and information biases. This article touches on randomized control trials, post hoc analyses, randomized crossover trials, quasi-experimental trials, cohort studies, case-control studies, cross-sectional studies, case series, case reports, and expert opinion. The purpose of this review is to move the reader beyond the tidy realm of simple rules and bias forms into the nuanced mire that is research quality assessment.

Impact of MnSOD and GPx1 Genotype at Different Levels of Enteral Nutrition Exposure on Oxidative Stress and Mortality: A Post hoc Analysis From the FeDOx Trial.

BACKGROUND: Converting nutrition support to energy results in mitochondrial free radical production, possibly increasing oxidative stress. Highly prevalent single nucleotide variants (SNV) exist for the genes encoding antioxidant enzymes responsible for the detoxification of reactive oxygen species. Our objective was to explore the interaction between nutrition support and genetic SNV's for two anti-oxidant proteins (rs4880 SNV for manganese superoxide dismutase and rs1050450 SNV for glutathione peroxidase 1) on oxidative stress and secondarily on intensive care unit (ICU) mortality. METHODS: We performed a post-hoc analysis on 34 mechanically ventilated sepsis patients from a randomized control feeding trial. Participants were dichotomized into those who carried both the rs4880 and the rs1050450 at-risk alleles (Risk Group) versus all others (Nonrisk Group). We explored the interaction between genotype and percent time spent in the upper median of energy exposure on oxidative stress and ICU mortality. RESULTS: Adjusting for confounders, the slope of log F2-isoprostane levels across percentage of days spent in the upper median of daily kilocalories per kilogram (kcal/kg) was 0.01 higher in the Risk Group compared to the Non-Risk Group (p=0.01). Every 1 percent increase in days spent in the upper median of daily kcal/kg was associated with an adjusted 10.3 percent increased odds of ICU mortality amongst participants in the Risk Group (odds ratio [OR]=1.103, p=0.06) but was highly insignificant in the Nonrisk group (OR=0.991, P=0.79). CONCLUSION: Nutrition support may lead to increased oxidative stress and worse clinical outcomes in a large percent of ICU patients with an at-risk genotype.

Clinical Nutrition Research and the COVID-19 Pandemic: A Scoping Review of the ASPEN COVID-19 Task Force on Nutrition Research.

The purpose of this scoping review by the American Society for Parenteral and Enteral Nutrition (ASPEN) Coronavirus Disease 2019 (COVID-19) Nutrition Task Force was to examine nutrition research applicable to the COVID-19 pandemic. The rapid pace of emerging scientific information has prompted this activity to discover research/knowledge gaps. This methodology adhered with recommendations from the Joanna Briggs Institute. There were 2301 citations imported. Of these, there were 439 articles fully abstracted, with 23 main topic areas identified across 24 article types and sourced across 61 countries and 51 specialties in 8 settings and among 14 populations. Epidemiological/mechanistic relationships between nutrition and COVID-19 were reviewed and results mapped to the Population, Intervention, Comparator, Outcome, and Time (PICO-T) questions. The aggregated data were analyzed by clinical stage: pre-COVID-19, acute COVID-19, and chronic/post-COVID-19. Research gaps were discovered for all PICO-T questions. Nutrition topics meriting urgent research included food insecurity/societal infrastructure and transcultural factors (pre-COVID-19); cardiometabolic-based chronic disease, pediatrics, nutrition support, and hospital infrastructure (acute COVID-19); registered dietitian nutritionist counseling (chronic/post-COVID-19); and malnutrition and management (all stages). The paucity of randomized controlled trials (RCTs) was particularly glaring. Knowledge gaps were discovered for PICO-T questions on pediatrics, micronutrients, bariatric surgery, and transcultural factors (pre-COVID-19); enteral nutrition, protein-energy requirements, and glycemic control with nutrition (acute COVID-19); and home enteral and parenteral nutrition support (chronic/post-COVID-19). In conclusion, multiple critical areas for urgent nutrition research were identified, particularly using RCT design, to improve nutrition care for patients before, during, and after COVID-19.

Tutorial: A Step-by-Step Guide (Version 2.0) for Measuring Abdominal Circumference and Skeletal Muscle From a Single Cross-Sectional Computed-Tomography Image Using the National Institutes of Health ImageJ.

BACKGROUND: In patients with acute and chronic illness, depleted skeletal muscle (SM) mass, also referred to as sarcopenia, is a condition associated with an underlying disease process and adverse outcomes. Because of software upgrades and errors related to installation, clarifications and a revised tutorial were needed for calculating SM cross-sectional area (CSA) using the National Institutes of Health (NIH) ImageJ. METHODS: A pilot study was conducted to determine the usability of the tutorial version 2.0. Eight adults (≥18 years of age) who had no previous experience or background in body composition or computed-tomography imaging and owned a personal laptop computer (Mac or PC) were included in the pilot study. Participants were tested on the completion of 4 tasks: (1) installation of software, (2) updating the software, (3) following revised tutorial (version 2.0), and (4) transferring information from the software to a spreadsheet for calculation of SM CSA. RESULTS: All participants completed the tutorial and all assigned tasks, 4/4 (100%). However, 38% (3/8) of the participants made errors while cutting and pasting values from the ImageJ results box to a spreadsheet for calculating SM CSA. CONCLUSION: The tutorial version 2.0 was easy to follow and provided sufficient information for adults to install, update, and perform the steps of body composition for the NIH ImageJ software without major issues. Care should be taken when cutting and pasting results from the software as well as when using the Microsoft Excel spreadsheet for calculating SM CSA.

American Society for Parenteral and Enteral Nutrition Clinical Guidelines: The Validity of Body Composition Assessment in Clinical Populations.

On behalf of the American Society for Parenteral and Enteral Nutrition (ASPEN), a systematic review was conducted to evaluate the best available evidence regarding the validity of relevant body composition methods (eg, dual energy X-ray absorptiometry [DXA], ultrasound [US], and bioelectrical impedance analysis [BIA]) in clinical populations. The guidelines targeted adults >18 years of age with a potentially inflammatory condition or pathological end point associated with a specific disease or clinical condition. In total, 7375 studies were retrieved, and 15 DXA, 7 US, and 23 BIA studies provided applicable data. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses was used to assess the diagnostic accuracy of the test method against a "gold standard" reference. The Grading of Recommendations, Assessment, Development and Evaluation criteria were used to separate the evaluation of the body of evidence from the recommendations. Based on a limited number of studies and expert opinion, DXA is recommended for the assessment of fat mass in patients with a variety of disease states; however, the validity of DXA for lean mass assessment in any clinical population remains unknown. No recommendations can be made at this time to support the use of US or BIA in the clinical setting, as data to support its validity in any specific patient population are limited in scope or by the proprietary nature of manufacture-specific BIA regression models to procure body composition data, respectively. Directions for future research are provided. These clinical guidelines were approved by the ASPEN Board of Directors.

Real-Time Energy Exposure Is Associated With Increased Oxidative Stress Among Feeding-Tolerant Critically Ill Patients: Results From the FEDOX Trial.

BACKGROUND: Prospective randomized controlled trials (PRCTs) that found harm in patients receiving higher levels of energy exposure have been largely ignored, in part because of the lack of a known mechanism of harm. OBJECTIVE: The current 7-day pilot study is a PRCT and post hoc analysis designed to explore the relationship between energy exposure and oxidative stress (as plasma total F2-isoprostanes) in mechanically ventilated intensive care unit patients with systemic inflammatory response syndrome. METHODS: Thirty-five participants were randomized to receive either 100% or 40% of their estimated energy needs. Our intent-to-treat model found no differences in F2-isoprostanes between groups. A post hoc analysis revealed that on days when participants were in the highest tertile of daily kcal/kg, the real-time energy flow rate within 2 hours of the blood draw was predictive of increased oxidative stress. On these days, participants in the second or third vs the first tertile of real-time energy flow rate experienced a 41.8% (P = .006) or 26.5% (P = .001) increase in F2-isoprostane levels, respectively. This was confirmed through a within-group subanalysis restricted to participants with measurements on both sides of the median of real-time energy flow rate that found a 28.2% F2-isoprostane increase on days in the upper vs lower median of flow rate (P = .002). CONCLUSION: The benefits of feeding may be more nuanced than previously suspected. Our findings imply a potential mechanism of harm in meeting the current recommendations for nutrition support in the critically ill that warrants further investigation.