The DOI matches its Crossref record; 34 of the 35 references it cites were found in a registry or an index.
The effect of higher protein dosing in critically ill patients with high nutritional risk (EFFORT Protein): an international, multicentre, pragmatic, registry-based randomised trial
Abstract
Background On the basis of low-quality evidence, international critical care nutrition guidelines recommend a wide range of protein doses. The effect of delivering high-dose protein during critical illness is unknown. We aimed to test the hypothesis that a higher dose of protein provided to critically ill patients would improve their clinical outcomes. Methods This international, investigator-initiated, pragmatic, registry-based, single-blinded, randomised trial was undertaken in 85 intensive care units (ICUs) across 16 countries. We enrolled nutritionally high-risk adults (≥18 years) undergoing mechanical ventilation to compare prescribing high-dose protein (≥2·2 g/kg per day) with usual dose protein (≤1·2 g/kg per day) started within 96 h of ICU admission and continued for up to 28 days or death or transition to oral feeding. Participants were randomly allocated (1:1) to high-dose protein or usual dose protein, stratified by site. As site personnel were involved in both prescribing and delivering protein dose, it was not possible to blind clinicians, but patients were not made aware of the treatment assignment. The primary efficacy outcome was time-to-discharge-alive from hospital up to 60 days after ICU admission and the secondary outcome was 60-day morality. Patients were analysed in the group to which they were randomly assigned regardless of study compliance, although patients who dropped out of the study before receiving the study intervention were excluded. This study is registered with ClinicalTrials.gov, NCT03160547. Findings Between Jan 17, 2018, and Dec 3, 2021, 1329 patients were randomised and 1301 (97·9%) were included in the analysis (645 in the high-dose protein group and 656 in usual dose group). By 60 days after randomisation, the cumulative incidence of alive hospital discharge was 46·1% (95 CI 42·0%-50·1%) in the high-dose compared with 50·2% (46·0%-54·3%) in the usual dose protein group (hazard ratio 0·91, 95% CI 0·77-1·07; p=0·27). The 60-day mortality rate was 34·6% (222 of 642) in the high dose protein group compared with 32·1% (208 of 648) in the usual dose protein group (relative risk 1·08, 95% CI 0·92-1·26). There appeared to be a subgroup effect with higher protein provision being particularly harmful in patients with acute kidney injury and higher organ failure scores at baseline. Interpretation Delivery of higher doses of protein to mechanically ventilated critically ill patients did not improve the time-to-discharge-alive from hospital and might have worsened outcomes for patients with acute kidney injury and high organ failure scores. Funding None.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“but demonstrated higher mortality in patients with renal failure.145”
From Malnutrition and Cachexia in Inpatients With Acute Cardiac Conditions: A Scientific Statement From the American Heart Association (2026) · cites this paper as [145]
In the citing paper
“The recruited patients' energy intake was very variable, although similar in the groups (around 14 kcal/kg/d) receiving high and low-dose proteins.”
From ESPEN practical and partially revised guideline: Clinical nutrition in the intensive care unit (2023) · cites this paper as [60]
In the citing paper
“Recently [60], a comparison between 1.6 ± 0.5 g/kg/d compared with 0.9 ± 0.3 g/kg/d administered protein did not find any significant difference in outcomes, but an increased mortality in patients with acute kidney injury randomized to high protein intakes.”
From ESPEN practical and partially revised guideline: Clinical nutrition in the intensive care unit (2023) · cites this paper as [60]
Citations
Cites
A Proportional Hazards Model for the Subdistribution of a Competing Risk
Fine, J. P., & Gray, R. J. (1999) · Journal of the American Statistical Association · doi:10.1080/01621459.1999.10474144 · Cited by 14,290
Vincent, J. L., Moreno, R., Takala, J., Willatts, S., De Mendonça, A., Bruining, H., Reinhart, C. K., Suter, P. M., & Thijs, L. G. (1996) · Intensive Care Medicine · doi:10.1007/bf01709751 · Cited by 11,674
A global clinical measure of fitness and frailty in elderly people
Rockwood, K. (2005) · Canadian Medical Association Journal · doi:10.1503/cmaj.050051 · Cited by 8,968
Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury
Mehta, R. L., Kellum, J. A., Shah, S. V., Molitoris, B. A., Ronco, C., Warnock, D. G., Levin, A., & the Acute Kidney Injury Network (2007) · Critical Care · doi:10.1186/cc5713 · Cited by 7,046
A Class of $K$-Sample Tests for Comparing the Cumulative Incidence of a Competing Risk
Gray, R. J. (1988) · The Annals of Statistics · doi:10.1214/aos/1176350951 · Cited by 4,957
McClave, S. A., Taylor, B. E., Martindale, R. G., Warren, M. M., Johnson, D. R., Braunschweig, C., McCarthy, M. S., Davanos, E., Rice, T. W., Cresci, G. A., et al. (2016) · Journal of Parenteral and Enteral Nutrition · doi:10.1177/0148607115621863 · Cited by 3,982
Self-citationESPEN guideline on clinical nutrition in the intensive care unit.
Singer, P., Blaser, A. R., Berger, M. M., Alhazzani, W., Calder, P. C., Casaer, M. P., Hiesmayr, M., Mayer, K., Montejo, J. C., Pichard, C., et al. (2019) · Clinical Nutrition · doi:10.1016/j.clnu.2018.08.037 · Cited by 2,904
Quality of life and pharmacoeconomics in clinical trials
Pater, J. L. (1996) · Controlled Clinical Trials · doi:10.1016/s0197-2456(97)82191-5 · Cited by 2,410
Acute skeletal muscle wasting in critical illness
Puthucheary, Z. A., Rawal, J., McPhail, M., Connolly, B., Ratnayake, G., Chan, P., Hopkinson, N. S., Padhke, R., Dew, T., Sidhu, P. S., et al. (2013) · JAMA · doi:10.1001/jama.2013.278481 · Cited by 2,103
SARC-F: A simple questionnaire to rapidly diagnose sarcopenia
Malmstrom, T. K., & Morley, J. E. (2013) · Journal of the American Medical Directors Association · doi:10.1016/j.jamda.2013.05.018 · Cited by 1,319
Flagged first, then by citations
1 of the 35 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Items 101–200 of 401
Protective nutrition strategy in the acute phase of critical illness: why, what and how to protect
Wang, Y., Li, Y., Li, N., Li, Y., Li, H., & Zhang, D. (2025) · Frontiers in Nutrition · doi:10.3389/fnut.2025.1555311 · Cited by 8
Yoshida, M., Yamamoto, R., Izumino, H., Matsushima, S., Takatani, Y., Hatakeyama, J., Nakanishi, N., Watanabe, S., Taguchi, A., Kano, K., et al. (2025) · Clinical Nutrition · doi:10.1016/j.clnu.2025.07.021 · Cited by 8
Shaping the future of muscle health: A clinical nutrition perspective and research agenda
van Zanten, A. R. H., Deutz, N. E. P., Pršo, A.-M. L., Prado, C. M. M., Schooneman, M. G., Soeters, M. R., de van der Schueren, M. A. E., Weijs, P. J. M., & Jager‐Wittenaar, H. (2026) · Clinical Nutrition · doi:10.1016/j.clnu.2026.106652 · Cited by 6
Summers, M. J., Bels, J. L. M., Karahalios, A., Gunaratne, R. K., Presneill, J., Plummer, M. P., Lee, Z., Heyland, D. K., Mesotten, D., Stoppe, C., et al. (2026) · Clinical Nutrition · doi:10.1016/j.clnu.2026.106665 · Cited by 9
Self-citationCallahan, J.-C., Parot‐Schinkel, E., Asfar, P., Ehrmann, S., Tirot, P., & Guitton, C. (2024) · BMJ Open · doi:10.1136/bmjopen-2023-080003 · Cited by 7
Pelekhaty, S. L., Gessler, J., Dante, S. A., Rector, N., Galvagno, S. M., Stachnik, S., Rabin, J., & Tabatabai, A. (2024) · Nutrition in Clinical Practice · doi:10.1002/ncp.11132 · Cited by 6
Wittholz, K., Bongetti, A. J., Fetterplace, K., Caldow, M. K., Karahalios, A., Souza, D. P. D., Doomun, S. N. E., Rooyackers, O., Koopman, R., Lynch, G. S., et al. (2024) · Journal of Parenteral and Enteral Nutrition · doi:10.1002/jpen.2622 · Cited by 6
Amino acids and the kidney; friends or foes?
Redaelli, M. B., Landoni, G., Monti, G., & Bellomo, R. (2024) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0000000000001083 · Cited by 6
“The role of urea and the duration of amino acid administration could be among the key factors that explain the different findings between nutritional studies involving high-protein regimens [16,17] and those involving short-term intravenous amino acids administration”
Leitliniengerechte Therapie der Sepsis
Schmoch, T., Weigand, M. A., & Brenner, T. (2023) · Die Anaesthesiologie · doi:10.1007/s00101-023-01354-5 · Cited by 7
Gusdon, A., Savarraj, J. P. J., Feng, D., Starkman, A., Li, G., Bodanapally, U. K., Zimmerman, W., Ryan, A. S., Choi, H., & Badjatia, N. (2024) · Scientific Reports · doi:10.1038/s41598-024-64666-5 · Cited by 7
“However, the recent EFFORT Protein trial found no significant survival benefit of a high protein diet alone with an increased risk of acute kidney injury (AKI) in at risk patients 8 .”
BackgroundReta-Pérez, O., Colmenero, M., Hernández-Socorro, C. R., Saavedra, P., Maichle, S., Portugal-Rodríguez, E., Cerezo-Arias, M., Sanchez-Ales, L., Martínez-Carmona, J. F., Mateu‐Campos, L., et al. (2024) · Nutrients · doi:10.3390/nu16091366 · Cited by 7
“…it has recently been reported that the administration of higher doses of protein in mechanically ventilated ICU patients did not improve the time to hospital discharge and, moreover, could worsen outcomes, particularly in patients with acute kidney injury and elevated organ failure scores [26–29].”
BackgroundNutrition therapy for critically ill patients - Five key problems
Kreymann, K. G., & de Heer, G. (2025) · Clinical Nutrition · doi:10.1016/j.clnu.2025.01.004 · Cited by 6
Chong, S. H., Huang, Y., Heng, M. S., Chong, E. S. T., Lim, C. D. Q., Wong, K. W., Chan, H. N., Heyland, D. K., Stoppe, C., Compher, C. W., et al. (2025) · Nutrition Reviews · doi:10.1093/nutrit/nuaf042 · Cited by 5
Self-citationEnergy Expenditure in Critically Ill Obese Patients—A Prospective Observational Study
de Heer, G., Burdelski, C. M., Ammon, C., Doliwa, A. L., Hilbert, P., Kluge, S., & Grensemann, J. (2025) · Nutrients · doi:10.3390/nu17132060 · Cited by 5
“…of illness to shorten patients’ time in a catabolic state, but it has been shown that high protein doses may be harmful, particularly in patients with organ failure [34] and a post hoc analysis of this study including obese patients did not find a benefit for the high protein group either [27].”
Targeting Dio3 to enhance mitophagy and ameliorate skeletal muscle wasting in sepsis
Wang, G., Chen, M., Zhang, Y., Wang, D., Gao, T., Duan, J., Lu, H., Cheng, M., Xu, Y., Li, X., et al. (2025) · Redox Biology · doi:10.1016/j.redox.2025.103751 · Cited by 6
“Although this approach has been recommended by nutritional societies, recent studies have demonstrated its ineffective-ness [5].”
Wu, T., Wei, Y.-Q., Xiong, J., Wu, J.-B., Lin, X., Zhuang, Y., Luo, C., Xu, M., Chen, X., Lin, Z., et al. (2025) · Critical Care · doi:10.1186/s13054-025-05660-9 · Cited by 5
“Most previous trials evaluated combined exercise and nutrition programs versus usual care, making it difficult to isolate their individual or additive effects [11, 12].”
Gut-to-brain signaling restricts dietary protein intake during recovery from catabolic states
Jaschke, N., Luchsinger, J. R., Chen, Z., Wulfmeyer, V. C., de la Rosa, X., Hahn, O., Zhang, C., Bachtel, N. D., Cullen, J. L., Rachner, T. D., et al. (2025) · Cell · doi:10.1016/j.cell.2025.10.005 · Cited by 8
Xu, J., Zhang, J., Yang, L., Han, Z., & Yue, M. (2025) · European journal of medical research · doi:10.1186/s40001-025-03340-6 · Cited by 5
The intensity of organ support: Restrictive or aggressive therapy for critically ill patients
Li, H., Li, Y., Fu, Y., Zhang, X., & Zhang, D. (2023) · Journal of Intensive Medicine · doi:10.1016/j.jointm.2023.04.002 · Cited by 5
Heuts, S., de Heer, P., Gabrio, A., Bels, J. L. M., Lee, Z., Stoppe, C., van Kuijk, S. M. J., Beishuizen, A., de Bie-Dekker, A., Fraipont, V., et al. (2023) · Clinical Nutrition ESPEN · doi:10.1016/j.clnesp.2023.10.040 · Cited by 5
Self-citationProtein provision during critical illness
Stoppe, C., & Hartl, W. H. (2024) · The Lancet · doi:10.1016/s0140-6736(24)01499-5 · Cited by 5
Self-citationWang, Y., Li, Y., Zhang, Y., Wang, H., Li, Y., Zhang, L., Zhang, C., Gao, M. Q., Li, H., & Zhang, D. (2024) · Frontiers in Nutrition · doi:10.3389/fnut.2024.1469870 · Cited by 5
Zaloumis, S. G., Summers, M. J., Presneill, J., Bellomo, R., Chapple, L. S., Chapman, M. J., Deane, A. M., Ferrie, S., French, C., Hurford, S., et al. (2025) · Trials · doi:10.1186/s13063-025-08759-0 · Cited by 5
“The revised primary outcome of the EFFORT Protein trial was “time to discharge alive from hospital up to 60 days after ICU admission” and there was no evidence of a between group difference [16].”
Nutrition Optimization Among Critically Ill Patients in the Cardiac Intensive Care Unit
Allaparthi, S., Bode, A., Bury, C., & Vest, A. R. (2025) · Current Cardiology Reports · doi:10.1007/s11886-025-02208-9 · Cited by 7
“Furthermore, this study suggested higher mortality with greater protein provision among patients with renal failure [56].”
Three main components of initial enteral support for neurological patients in critical illness
Ershov, V. I., & Новикова, Т. В. (2023) · Russian Journal of Anesthesiology and Reanimatology · doi:10.17116/anaesthesiology202306184 · Cited by 5
Current concepts on feeding the critically ill patient: a narrative review
Adolph, M., van Zanten, A. R. H., Berger, M. M., Petros, S., Hiesmayr, M., Weimann, A., Martignoni, M. E., Feil, K., Hirschberger, S., Haller, V., et al. (2026) · Critical Care · doi:10.1186/s13054-026-06123-5 · Cited by 4
“Taken together, recent trials support caution with early high-dose protein provision and suggest that moderate protein doses, approximately 1.0–1.2 g/kg/day in many ICU populations, may be a pragmatic and safer target until more precise phenotype-guided strategies have been validated [2, 3, 25].”
InfluentialNutrition Therapy in Critically Ill Adults
Patel, J. J., & McClave, S. A. (2026) · New England Journal of Medicine · doi:10.1056/nejmra2506111 · Cited by 4
Self-citationLooking to the future: Agendas, directions, and resources for nutrition research
Heitman, K. N., Hubbard, J. L., Easter, L. H., & Kilkus, J. M. (2024) · Nutrition in Clinical Practice · doi:10.1002/ncp.11154 · Cited by 4
Lee, G. H., Kim, Y., Park, S. H., Park, S., Lim, S. Y., & Choi, S. A. (2024) · Frontiers in Nutrition · doi:10.3389/fnut.2024.1367727 · Cited by 4
High vs low protein intake in chronic critical illness: A systematic review and meta-analysis
Castro, S., Tomé, A., Granja, C., Macedo, A., & Binnie, A. (2024) · Clinical Nutrition ESPEN · doi:10.1016/j.clnesp.2024.12.003 · Cited by 4
Concurrent nutrition and physical rehabilitation interventions for patients with critical illness
González-Seguel, F., Mayer, K. P., & Stapleton, R. D. (2024) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0000000000001099 · Cited by 4
“…recent 17 & & & The EFFORT-Protein (Effect of Higher Dosing in Critically Ill Patients) trial compared high-dose enteral protein ( (cid:4) 2.2 g/kg per day) with usual dose ( (cid:5) 1.2 g/kg per day) using the pre-ICU actual dry weight, starting within 96 h after ICU admission ( n ¼ 1301) [17 & ].”
InfluentialNutrition Therapy in Critically Ill Patients with Obesity: An Observational Study
Delgado, J. C. L., Sanchez-Ales, L., Lasierra, J. L. F., Marco, E. M., Bordejé, M.-L., Portugal-Rodríguez, E., Lorencio, C., Vera, P., Aldunate-Calvo, S., Llorente-Ruiz, B., et al. (2025) · Nutrients · doi:10.3390/nu17040732 · Cited by 6
“Recent trials evaluating the use of protein intakes above recommendations (i.e., >1.5 g/Kg/d) reported negative results [29].”
InfluentialPotential Benefits of Medical Nutrition Therapy for Timely Ventilator Weaning in the Critically Ill
Rosa, S. D., Rauseo, M., Umbrello, M., Lassola, S., & Battaglini, D. (2025) · Anesthesiology · doi:10.1097/aln.0000000000005557 · Cited by 6
Nutritional Parameters Associated With Hospital Mortality in Patients With Acute Kidney Injury
Martín-del-Campo, F., Sotelo-Anaya, R., Castro-Mata, P. C., García-García, G., Gallardo-González, A. M., Gómez-Fregoso, J. A., Rodríguez-García, F. G., Luquin-Arellano, V. H., Abundis-Mora, G. J., Alcantar-Vallin, L., et al. (2025) · Journal of Renal Nutrition · doi:10.1053/j.jrn.2025.07.003 · Cited by 5
Nutrition in critical illness—research is worth the EFFORT
Ridley, E. J., & Chapple, L. S. (2023) · The Lancet · doi:10.1016/s0140-6736(23)00091-0 · Cited by 4
Raina, R., Suchan, A., Soundararajan, A., Brown, A., Davenport, A., Shih, W. V., Nada, A., Irving, S. Y., Mannemuddhu, S. S., Vitale, V. S., et al. (2023) · Nutrition · doi:10.1016/j.nut.2023.112272 · Cited by 4
Gehri, L., Schmidbauer, M. L., Putz, T., Ratkovic, L., Maskos, A., Zeisberger, C., Zibold, J., Dimitriadis, K. A., & on behalf of the IGNITE Study Group (2024) · Journal of Clinical Medicine · doi:10.3390/jcm13020447 · Cited by 4
“While guidelines do specify concrete target values, well-defined targets, timing, and the effect of a high protein intake on outcomes are subject to recent debates [34–36].”
BackgroundNew randomized controlled trials on micronutrients in critical care nutrition: A narrative review
Halim, Z., Huang, Y., Lee, Z., & Lew, C. C. H. (2024) · Nutrition in Clinical Practice · doi:10.1002/ncp.11195 · Cited by 7
Self-citationPatients’ Experience of Nutrition Therapy During Critical Illness and Recovery
Hardy, G., Marshall, A. P., Gantner, D. C., & Ridley, E. J. (2024) · Critical Care Clinics · doi:10.1016/j.ccc.2024.09.004 · Cited by 5
Yasuda, H., Horikoshi, Y., Kamoshita, S., Kuroda, A., & Moriya, T. (2023) · Nutrients · doi:10.3390/nu16010057 · Cited by 4
“In critically ill patients, nutritional deficiency can increase mortality [1,2], and nutritional excess can increase infection complications and kidney injury [3,4].”
BackgroundArabi, Y. M., Al‐Dorzi, H. M., Aldibasi, O. S., Sadat, M., Jose, J., Muharib, D., Algethamy, H. M., Al-Fares, A. A., Al-Hameed, F. M., Mady, A. M., et al. (2024) · Trials · doi:10.1186/s13063-024-08105-w · Cited by 4
“In addition, an unplanned interim analysis was carried out on June 7, 2023, in response to the publication of the EFFORT-protein trial (high versus moderate protein), which found no difference in the primary outcome but a worse outcome in subgroups of patients with AKI and high SOFA [47].”
MethodDietary protein in the ICU in relation to health outcomes
Bear, D. E., Summers, M. J., & Chapple, L. S. (2024) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0000000000001066 · Cited by 4
Self-citationEFFORT Protein trial: questions remain.
Schuetz, P. (2023) · The Lancet · doi:10.1016/s0140-6736(23)01255-2 · Cited by 2
Early administration of high protein for critically ill patients with acute kidney injury?
Al‐Dorzi, H. M., & Arabi, Y. M. (2023) · Critical Care · doi:10.1186/s13054-023-04764-4 · Cited by 4
“Worse outcomes were observed in the pre-specified subgroup of patients with AKI [4].”
BackgroundResultLv, C., Zhou, L., Zhou, Y., Lew, C. C. H., Lee, Z., Hasan, M. S., Li, B., Liu, Y., Lin, J., Mao, W., et al. (2024) · Burns & Trauma · doi:10.1093/burnst/tkae027 · Cited by 4
“In a recent large trial, a high-protein strategy was associated with worse outcomes for patients with AKI in a subgroup analysis [12].”
BackgroundResultInfluentialSelf-citationThe History of Critical Care Nutrition
Martindale, R. G., Hurt, R. T., Mundi, M. S., & McClave, S. A. (2024) · Critical Care Clinics · doi:10.1016/j.ccc.2024.09.001 · Cited by 2
Kubesch, N. J., Gaitonde, S., Petriti, U., Bakker, E., Basu, S., Birks, L. E., Aubrun, E., de Vries, S. T., & Schneider, R. (2024) · Clinical and Translational Science · doi:10.1111/cts.70072 · Cited by 3
“15 This may indicate, for instance, a potential lack of registries in these regions, a lack of possibilities to link data sources, less reliable health registers, less recognition for the registries' potential value, or differences in data protection laws, in cultural perceptions of health systems…”
Hepduman, D., & Sungurtekin, H. (2025) · Clinical Science of Nutrition · doi:10.62210/clinscinutr.2025.103 · Cited by 3
Elkalawy, H., Sekhar, P., Fayad, M., Barrima, M. A. E., & Abdullah, M. (2025) · Acute and Critical Care · doi:10.4266/acc.001025 · Cited by 4
Oral nutritional management in short bowel syndrome
Verbiest, A., Meyere, L. D., Pauwels, N., Overloop, Y., & Vanuytsel, T. (2025) · Best Practice & Research Clinical Gastroenterology · doi:10.1016/j.bpg.2025.102082 · Cited by 3
Feeding the injured brain: nutrients, dose, timing, and monitoring
Arabi, Y. M., Stoppe, C., Casaer, M. P., Ridley, E. J., Reignier, J., Al‐Dorzi, H. M., Annoni, F., & Preiser, J. (2026) · Intensive Care Medicine · doi:10.1007/s00134-026-08324-6 · Cited by 3
Self-citationSchleef, M., Mayet, V., Gouge, A. L., Badie, J. C., Chauvelot, L., Devaquet, J., Jaber, S., Jabot, J., Lambiotte, F., Madeux, B., et al. (2026) · Intensive Care Medicine · doi:10.1007/s00134-026-08369-7 · Cited by 3
“Moreover, in a recent international randomized trial in critically ill patients, high-protein feeding (2.2 g/kg/d) did not decrease the time to hospital discharge alive and possibly worsened outcomes in predefined subgroups of patients with AKI or high organ-failure scores [15].”
InfluentialYoshida, M., Yamamoto, R., Sagawa, M., Toshima, G., Ukita, S., Higashibeppu, N., Tatsumi, H., Matsuo, Y., Yoneda, R., Ishihara, E., et al. (2026) · Clinical Nutrition ESPEN · doi:10.1016/j.clnesp.2026.103301 · Cited by 3
Nutrition support in the ICU: current evidence and evolving standards
Peake, S., Ridley, E. J., & Reignier, J. (2026) · Intensive Care Medicine · doi:10.1007/s00134-026-08474-7 · Cited by 3
“International surveys and large pragmatic trials on calo-rie and protein delivery in the ICU show that usual practice is to initiate enteral nutrition within 24–48 h of ICU admission [2–7, 12, 13].”
JPEN Journal Club 80. Prespecified outcomes
Koretz, R. L. (2023) · Journal of Parenteral and Enteral Nutrition · doi:10.1002/jpen.2567 · Cited by 3
Huang, L., Shi, F., Hu, D., & Kang, D. (2024) · Medicine · doi:10.1097/md.0000000000037375 · Cited by 3
“Notably, studies such as the Heyland study [8] and Professor Kistler’s CAPLA randomized clinical trial [9] exemplify the impact of IIRs/IITs, being published in prestigious journals such as Lancet and Nature Medicine , respectively.”
BackgroundKatsumata, Y., Yatabe, T., Kuroiwa, H., Iwata, H., Oda, S., & Kawano, T. (2024) · Annals of Nutrition and Metabolism · doi:10.1159/000540301 · Cited by 4
“A recent RCT [20] showed that high doses of protein (2.2 g/kg/day) initiated within 96 h of ICU admission might worsen outcomes in patients with acute kidney injury and high organ failure scores in mechanically ventilated critically ill patients.”
InfluentialLi, J. Q., Sun, T., Zuo, J. T., Yao, X., Cai, L. N., Zheng, H. Y., & Ye, X. H. (2024) · Journal of Advanced Nursing · doi:10.1111/jan.16384 · Cited by 4
Empfehlungen und Innovationen in der Ernährungsmedizin für kritisch Kranke
Vögelin, C., Koch, J., Marx, G., & Hill, A. (2025) · AINS - Anästhesiologie · Intensivmedizin · Notfallmedizin · Schmerztherapie · doi:10.1055/a-2292-8916 · Cited by 3
Davies, C., Johansson, L., Brett, S. J., Cole, E., & The MODET Investigators (2025) · Journal of the Intensive Care Society · doi:10.1177/17511437251349679 · Cited by 3
“Similarly, the findings from the EFFORT protein trial 40 and the PRECISe trial 41 recently concluded that higher protein intake may not be as beneficial as once thought.”
Lumlertgul, N., Wannakittirat, A., Kung, J. Y. C., Srisawat, N., Collister, D., See, E. J., Pannu, N., Mehta, R. L., Soranno, D. E., Ostermann, M., et al. (2025) · BMC Medicine · doi:10.1186/s12916-025-04202-y · Cited by 3
Wang, J.-K., Chen, Y., Zhao, Z., Lian, G., Peng, L., Zhou, X., Sha, S., Qiao, W., Tian, H., Li, L., et al. (2024) · International Journal of Surgery · doi:10.1097/js9.0000000000001818 · Cited by 4
Stewart, B. T., Pham, T. N., Cancio, L. C., O’Keefe, G. E., Nordlund, M. J., Day, A. G., & Heyland, D. K. (2024) · The Journal of Trauma: Injury, Infection, and Critical Care · doi:10.1097/ta.0000000000004432 · Cited by 3
Self-citationRaphaeli, O., Singer, P., Robinson, E., Statlender, L., & Kagan, I. (2024) · Nutrients · doi:10.3390/nu16193258 · Cited by 5
“Interestingly, patients with co-morbidities such as pulmonary or cardiac diseases had better survival when receiving high protein support.”
BackgroundResultWhy One-Size-Fits-All Doesn’t Work in Intensive Care Unit Nutrition?
Bear, D. E., Lambell, K., & Stoppe, C. (2024) · Critical Care Clinics · doi:10.1016/j.ccc.2024.09.008 · Cited by 3
Self-citationElliott, E. C., Trujillo-Rivera, E. A., Dughly, O., Dean, T., Harrar, D. B., Bell, M. J., & Wai, K. (2024) · Pediatric Critical Care Medicine · doi:10.1097/pcc.0000000000003641 · Cited by 3
Acute management of sepsis beyond 24 hours
Premachandra, A., & Heming, N. (2024) · Seminars in Respiratory and Critical Care Medicine · doi:10.1055/s-0044-1787991 · Cited by 2
Wang, C.-Y., Wang, T.-J., Wu, Y.-C., & Hsu, C.-Y. (2024) · Acute and Critical Care · doi:10.4266/acc.2024.00843 · Cited by 2
“In-triguingly, higher protein doses not only failed to decrease 60-day mortality, but might have worsened outcomes for patients with acute kidney injury [49].”
Nutritional support for intensive care patients: the role of lipid component
Пасечник, И. Н., Talyzin, P. A., & Skobelev, E. I. (2024) · Russian Journal of Anesthesiology and Reanimatology · doi:10.17116/anaesthesiology202403158 · Cited by 2
SARCOPENIA AND GASTROINTESTINAL CANCER: NUTRITIONAL APPROACH FOCUSING ON CURCUMIN SUPPLEMENTATION
de ALMEIDA, P. S., Barão, K., & Forones, N. M. (2025) · Arquivos de Gastroenterologia · doi:10.1590/s0004-2803.24612024-068 · Cited by 2
“The authors suggest that further clinical studies are still needed involving burned, polytraumatized, obese, and post-surgical patients, who may benefit from high doses of protein (60) .”
Does nutrition therapy alter the pathophysiology of severe acute pancreatitis?
Gao, L., Xu, Y., & Ke, L. (2025) · Current Opinion in Critical Care · doi:10.1097/mcc.0000000000001284 · Cited by 2
Mundi, M. S., Mechanick, J. I., Patel, J. J., Newberry, C. A., Sankararaman, S., Rosenthal, M. D., Elfadil, O. M., Bering, J., Katz, J., Stoppe, C., et al. (2025) · Journal of Parenteral and Enteral Nutrition · doi:10.1002/jpen.2790 · Cited by 3
Self-citationToloi, J. M., Laranja, A. C. G., Toledo, D. O., Treml, R. E., Malbouisson, L. M. S., Manzanares, W., & Silva, J. M. (2025) · Nutrients · doi:10.3390/nu17172742 · Cited by 4
“Notably, while the prescribed doses in trials such as the PRECISe [26] and EFFORT [25] trials exceeded 2 g/kg/day, actual protein intake in these studies (e.g., 1.6 g/kg/day in EFFORT) was similar to the achieved intake in our study, reinforcing the practical challenge of reaching target doses in…”
InfluentialAugmented Enteral Protein in Critical Illness—Reply
Summers, M. J., Chapple, L. S., Deane, A. M., & TARGET Protein Investigators (2025) · JAMA · doi:10.1001/jama.2025.13868 · Cited by 2
Chaparro, C. J., Maluf, V. A. B., Pabion, C., Stern, F., Moullet, C., Kiszio, B., Pugliese, M., Ramelet, A., Morice, C., Valla, F. V., et al. (2025) · Clinical Nutrition · doi:10.1016/j.clnu.2025.09.023 · Cited by 2
Optimizing protein in critical illness: Is g/fat-free mass the key?
Nakamura, K., Nakano, H., & Kanda, N. (2025) · Clinical Nutrition · doi:10.1016/j.clnu.2025.10.022 · Cited by 2
Tweel, L. E., Brody, R. A., Samavat, H., Day, A. G., Jiang, X., Byham-Gray, L. D., Patel, J. J., Compher, C. W., & Heyland, D. K. (2025) · Journal of Parenteral and Enteral Nutrition · doi:10.1002/jpen.70033 · Cited by 3
“12,15,18,19 Nutrition risk scores were calculated using the modified Nutrition Risk in the Critically Ill (mNUTRIC) tool, along with Strength, Assistance in walking, Rising from a chair, Climbing stairs, and Falls (SARC ‐”
InfluentialSelf-citationGopal, A. B., Mahadevaiah, T., Chun, A., Giles, L. C., Merlin, T., & Murthy, T. A. (2025) · Journal of Parenteral and Enteral Nutrition · doi:10.1002/jpen.70034 · Cited by 2
Gustafson, O. D., Dalton, R., Thurley, N., Pattison, N. A., Bedford, J., Watkinson, P., & Vollam, S. (2025) · Critical Care · doi:10.1186/s13054-025-05755-3 · Cited by 2
Domingues, C. R., Rodeia, S., Francisco, A. R., Santos, L., Cerca, C., Costa, M., Pinto, V., Fortuna, P., Brito-Costa, A., & Bento, L. F. N. (2025) · Intensive Care Medicine Experimental · doi:10.1186/s40635-025-00823-y · Cited by 3
Hu, Y., Xu, T., Wei, J., Zhu, P., Shi, D., & Liu, J. (2025) · International Urology and Nephrology · doi:10.1007/s11255-025-04958-5 · Cited by 3
“Specifically, 7 of the 14 analyzed trials conducted primary analyses on an ITT basis [16, 17, 20–22, 25, 27] and 6 trials employed a modified ITT approach [15, 18, 23, 24, 26, 28], while 1 trial reported results based on a per-protocol analysis [19].”
Proteins in artificial nutrition: toward an individualized and phase-specific prescription
Schüetz, P., Carrera-Gil, F., & Wunderle, C. (2026) · Clinical Nutrition · doi:10.1016/j.clnu.2026.106577 · Cited by 2
Molfino, A., Imbimbo, G., Rothenberg, E. M., Bosaeus, I. G., Jager‐Wittenaar, H., Schneider, S. M., Biolo, G., Cederholm, T., Arends, J., & Muscaritoli, M. (2026) · Clinical Nutrition · doi:10.1016/j.clnu.2026.106595 · Cited by 2
“These observations are in line with several clinical trials on critically ill patients showing limited benefits from full-replacement nutritional intervention [18 – 20].”
Suzuki, G., Iwanami, Y., NAKAZAWA, M., Yoshioka, S., Furuta, M., Nakanishi, M., Kanayama, H., Ishikawa, K., Nishioka, S., Kobori, T., et al. (2026) · Trials · doi:10.1186/s13063-026-09584-9 · Cited by 2
“Recent randomized controlled trials (RCTs) have reported that protein delivery exceeding 1.2 g/kg/day, when administered as a stand-alone inter - vention, does not significantly improve patient-centered outcomes [12] and may even be harmful in certain clinical contexts [5, 13].”
InfluentialDu, Q., Congcong, Q., Guochen, L., Qianyu, B., Batejin, Shuanglin, Z., Bagena, B., Meiyu, B., Yimin, Z., Meiling, S., et al. (2026) · Frontiers in Medicine · doi:10.3389/fmed.2026.1770345 · Cited by 4
“Overall, assessment and monitoring of protein requirements in critically ill patients should move from fixed-formula approaches toward dynamic strategies that integrate guideline ranges, nitrogen balance, body composition monitoring, organ function, and disease phenotype (2, 22, 24, 25).”
Nutrition support for patients on mechanical circulatory support
Dresen, E., Modir, R., & Stoppe, C. (2023) · Current Opinion in Anaesthesiology · doi:10.1097/aco.0000000000001323 · Cited by 2
Self-citationNutritional management in critically ill patients with COVID-19: a retrospective multicentre study
Danel, J. K., Taborek, M., Nowotarska, A., Winiarska, K., Dylczyk-Sommer, A., Szczeklik, W., Białka, S., Czarnik, T., Sołek-Pastuszka, J., & Krzych, Ł. J. (2024) · Anaesthesiology Intensive Therapy · doi:10.5114/ait.2024.138559 · Cited by 2
Year in Review 2023: Noteworthy Literature in Cardiothoracic Critical Care
Alber, S. M., Tanabe, K. J., Hennigan, A., Tregear, H., & Gilliland, S. (2024) · Seminars in Cardiothoracic and Vascular Anesthesia · doi:10.1177/10892532241249582 · Cited by 2
“13,14 In the Effect of Higher Protein Dosing in Critically Ill Patients (EFFORT Protein Trial), Heyland et al undertook a large, international, pragmatic, single-blinded, registry based randomized control trial across 85 ICUs in 15 countries.”
BackgroundHaste makes waste: Early nutrition prescription for critically ill patients
Chen, S., & Chang, Z. (2024) · Aging Medicine · doi:10.1002/agm2.12337 · Cited by 2
“22 The results showed that providing larger doses of protein did not improve survival to discharge in critically ill patients with acute kidney injury and high organ failure scores and may lead to adverse outcomes.”
BackgroundErnährung auf der Intensivstation
Hill, A., & Meyer, M.-T. (2024) · intensiv · doi:10.1055/a-2346-7627 · Cited by 2
Which Outcomes Should We be Using in Critical Care Nutrition Trials?
Watson, N., Nazeer, S., & Puthucheary, Z. (2024) · Critical Care Clinics · doi:10.1016/j.ccc.2024.09.005 · Cited by 2
Weakness acquired in the cardiac intensive care unit: still the elephant in the room?
Aerde, N. V., & Hermans, G. (2024) · European Heart Journal Acute Cardiovascular Care · doi:10.1093/ehjacc/zuae146 · Cited by 2
Levodopa and nutrition support: A case report of Parkinsonism‐hyperpyrexia syndrome
Burslem, R., Ramos, L., Chou, C., Szlufman, C., & Ziegler, J. (2025) · Nutrition in Clinical Practice · doi:10.1002/ncp.11297 · Cited by 2
“22,23 As such, in patients who are critically ill receiving levodopa, clinicians could consider lower protein doses to reduce the risk of PHS.”
Kristof, A. S., Hong, M., Boufaied, N., Tousson-Abouelazm, N., Dandamudi, S., Joung, K.-B., Hatzakorzian, R., Port, M., Campisi, G., Piccirillo, C. A., et al. (2025) · American Journal of Clinical Nutrition · doi:10.1016/j.ajcnut.2025.05.025 · Cited by 3
Self-citationHigh protein intake: Effect of level versus feeding site
Bistrian, B. R. (2023) · Journal of Parenteral and Enteral Nutrition · doi:10.1002/jpen.2529 · Cited by 2
Year 2023 in review - Critical care nephrology
Chvojka, J., & Matějovič, M. (2023) · Anesteziologie a intenzivní medicína · doi:10.36290/aim.2023.056 · Cited by 2
Pelekhaty, S. L., Peiffer, M., Leibowitz, J. L., & Tabatabai, A. (2023) · Journal of Parenteral and Enteral Nutrition · doi:10.1002/jpen.2596 · Cited by 2
Con - The Harms of Overfeeding Early in Critical Illness
Gessouroun, A., & DiNizo, D. (2023) · Journal of Cardiothoracic and Vascular Anesthesia · doi:10.1053/j.jvca.2023.10.009 · Cited by 2
van Ruijven, I. M., Brunsveld‐Reinders, A. H., Stapel, S. N., & Weijs, P. J. M. (2023) · Clinical Nutrition · doi:10.1016/j.clnu.2023.11.035 · Cited by 2
Deane, A. M., & Casaer, M. P. (2024) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0000000000001016 · Cited by 2
Metadata
- Authors
- Heyland, D. K., Patel, J., Compher, C., Rice, T. W., Bear, D. E., Lee, Z.-Y., González, V. C., O'Reilly, K., Regala, R., Wedemire, C., Ibarra-Estrada, M., Stoppe, C., Ortiz-Reyes, L., Jiang, X., & Day, A. G.
- Affiliations
- Queen's University (CA)
- Medical College of Wisconsin (US)
- Hospital of the University of Pennsylvania (US)
- Vanderbilt University Medical Center (US)
- Guy's and St Thomas' NHS Foundation Trust (GB)
- University of Malaya (MY)
- Fundacion Allende (AR)
- King's College Hospital NHS Foundation Trust (GB)
- Legacy Salmon Creek Medical Center (US)
- Universidad de Guadalajara (MX)
- Universitätsklinikum Würzburg (DE)
- Corresponding author
- Heyland, Daren K
- ORCID
- Venue
- The Lancet
- Publisher
- Elsevier BV
- Published
- 2023-02
- Volume
- 401
- Issue
- 10376
- Pages
- 568-576
- ISSN
- 0099-5355 (ISSN-L)
- 0140-6736
- OpenAlex
- W4318022770
- Cited by
- 401
- References
- 35
- Citations by year
- 2026: 118 · 2025: 114 · 2024: 113 · 2023: 56
- FWCI
- 70.39
- Type
- journal article
- Language
- en
- Update notices
- erratum (2023-03-25)
- Open access
- closed
- Licence
- Locations
- The Lancet (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Society for Parenteral and Enteral Nutrition
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Clinical Nutrition and Gastroenterology
- Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Sepsis Diagnosis and Treatment
- Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Intensive Care Unit Cognitive Disorders
- Keywords
- critically ill patients, intensive care nutrition, protein supplementation, nutritional risk, mechanical ventilation, 60-day mortality, hospital discharge, ICU length of stay, mechanical circulatory support, sepsis, acute kidney injury, acute respiratory failure, acute coronary syndrome, acute stroke, acute heart failure, acute liver failure, acute neurological injury, acute pancreatitis
- MeSH terms
- Adult, Critical Care, Hospitalization, Humans, Intensive Care Units, Registries, Respiration, Artificial, Critical Illness
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
