Role of ketones, ketogenic diets and intermittent fasting in ICU

Gunst, Jan; Casaer, Michaël P; Langouche, Lies; Berghe, Greet Van den

doi:10.1097/mcc.0000000000000841

Cited by 14 publications

(27 citation statements)

References 52 publications

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“…Increasing evidence suggests a potentially protective effect of enhancing ketone availability during critical illness [ 1 ]. Whereas ketone bodies may serve as vital and more energy-efficient energy substrate than glucose or fatty acids, ketones may also exert signaling functions leading to anti-inflammatory effects and activation of recovery processes such as muscle regeneration and autophagy [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

“…In line with this, studies performed in animal models of sepsis and brain injury have demonstrated protective effects of providing ketones or ketogenic diets [ 3 , 4 ]. However, human evidence remains scarce, with only a few small randomized controlled trials (RCTs) suggesting improved blood glucose control by ketone supplementation or ketogenic diets [ 1 ].…”

Section: Introductionmentioning

confidence: 99%

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Impact of tight glucose control on circulating 3-hydroxybutyrate in critically ill patients

et al. 2021

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Background Recent evidence suggests a potentially protective effect of increasing ketone body availability via accepting low macronutrient intake early after onset of critical illness. The impact of blood glucose control with insulin on circulating ketones is unclear. Whereas lowering blood glucose may activate ketogenesis, high insulin concentrations may have the opposite effect. We hypothesized that the previously reported protective effects of tight glucose control in critically ill patients receiving early parenteral nutrition may have been mediated in part by activation of ketogenesis. Methods This is a secondary analysis of 3 randomized controlled trials on tight versus liberal blood glucose control in the intensive care unit, including 700 critically ill children and 2748 critically ill adults. All patients received early parenteral nutrition as part of the contemporary standard of care. Before studying a potential mediator role of circulating ketones in improving outcome, we performed a time course analysis to investigate whether tight glucose control significantly affected ketogenesis and to identify a day of maximal effect, if any. We quantified plasma/serum 3-hydroxybutyrate concentrations from intensive care unit admission until day 3 in 2 matched subsets of 100 critically ill children and 100 critically ill adults. Univariable differences between groups were investigated by Kruskal-Wallis test. Differences in 3-hydroxybutyrate concentrations between study days were investigated by Wilcoxon signed-rank test. Results In critically ill children and adults receiving early parenteral nutrition, tight glucose control, as compared with liberal glucose control, lowered mean morning blood glucose on days 1–3 (P < 0.0001) via infusing insulin at a higher dose (P < 0.0001). Throughout the study period, caloric intake was not different between groups. In both children and adults, tight glucose control did not affect 3-hydroxybutyrate concentrations, which were suppressed on ICU days 1–3 and significantly lower than the ICU admission values for both groups (P < 0.0001). Conclusion Tight versus liberal glucose control in the context of early parenteral nutrition did not affect 3-hydroxybutyrate concentrations in critically ill patients. Hence, the protective effects of tight glucose control in this context cannot be attributed to increased ketone body availability.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Impact of tight glucose control on circulating 3-hydroxybutyrate in critically ill patients

et al. 2021

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“…Hence, efficacy and safety remain to be studied. Apart from intermittent feeding strategies, ketogenic diets or ketone supplementation could be beneficial [ 85 ]. Although ketogenic diets have been used in selected patients including patients with refractory status epilepticus, the efficacy and safety of ketogenic diets or ketone supplements for general critically ill patients remain to be studied [ 85 ].…”

Section: Introductionmentioning

confidence: 99%

Toward nutrition improving outcome of critically ill patients: How to interpret recent feeding RCTs?

et al. 2023

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Although numerous observational studies associated underfeeding with poor outcome, recent randomized controlled trials (RCTs) have shown that early full nutritional support does not benefit critically ill patients and may induce dose-dependent harm. Some researchers have suggested that the absence of benefit in RCTs may be attributed to overrepresentation of patients deemed at low nutritional risk, or to a too low amino acid versus non-protein energy dose in the nutritional formula. However, these hypotheses have not been confirmed by strong evidence. RCTs have not revealed any subgroup benefiting from early full nutritional support, nor benefit from increased amino acid doses or from indirect calorimetry-based energy dosing targeted at 100% of energy expenditure. Mechanistic studies attributed the absence of benefit of early feeding to anabolic resistance and futile catabolism of extra provided amino acids, and to feeding-induced suppression of recovery-enhancing pathways such as autophagy and ketogenesis, which opened perspectives for fasting-mimicking diets and ketone supplementation. Yet, the presence or absence of an anabolic response to feeding cannot be predicted or monitored and likely differs over time and among patients. In the absence of such monitor, the value of indirect calorimetry seems obscure, especially in the acute phase of illness. Until now, large feeding RCTs have focused on interventions that were initiated in the first week of critical illness. There are no large RCTs that investigated the impact of different feeding strategies initiated after the acute phase and continued after discharge from the intensive care unit in patients recovering from critical illness.

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“…One indirect calorimetry study found that AKI patients, both septic and nonseptic, were not given enough lipid to support measured lipid oxidation rates, while carbohydrates were given more than actual glucose oxidation rates [99]. Thus, alternative approaches could include limiting the glycemic load or changing the delivery of feeds to allow for adequate periods of fasting capable of enhancing FAO, ketogenesis and autophagy [100 ▪ ].…”

Section: Introductionmentioning

confidence: 99%

“…Prior work has extensively examined the timing of feeding initiation in ICU patients, however an organized approach to comparing an intermittent versus continuous feeding protocol and by extension the importance of fasting periods in critically ill patients has yet to be undertaken. Several small noninferiority RCTs reported favorably on clinical endpoints such as gastrointestinal distress and aspiration pneumonia for those receiving intermittent feeds compared to those continuously fed [100 ▪ ,101 ▪ ]. However, the small sample sizes, lack of harder endpoints, inconsistent reporting on metabolic variables, and heterogeneity in feed and insulin administration protocols limit our ability to make broader conclusions about the effect of fasting duration on optimizing metabolism to survive critical illnesses such as sepsis.…”

Section: Introductionmentioning

confidence: 99%

When a calorie isn’t just a calorie: a revised look at nutrition in critically ill patients with sepsis and acute kidney injury

Nadamuni¹,

Venable²,

Huen

2022

Current Opinion in Nephrology &Amp; Hypertension

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Purpose of reviewTo discuss how nutritional management could be optimized to promote protective metabolism in sepsis and associated acute kidney injury.Recent findingsRecent evidence suggests that sepsis is a metabolically distinct critical illness and that certain metabolic alterations, such as activation of fasting metabolism, may be protective in bacterial sepsis. These findings may explain the lack of survival benefit in recent randomized controlled trials of nutrition therapy for critical illness. These trials are limited by cohort heterogeneity, combining both septic and nonseptic critical illness, and the use of inaccurate caloric estimates to determine energy requirements. These energy estimates are also unable to provide information on specific substrate preferences or the capacity for substrate utilization. As a result, high protein feeding beyond the capacity for protein synthesis could cause harm in septic patients. Excess glucose and insulin exposures suppress fatty acid oxidation, ketogenesis and autophagy, of which emerging evidence suggest are protective against sepsis associated organ damage such as acute kidney injury.SummaryDistinguishing pathogenic and protective sepsis-related metabolic changes are critical to enhancing and individualizing nutrition management for critically ill patients.

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Role of ketones, ketogenic diets and intermittent fasting in ICU

Cited by 14 publications

References 52 publications

Impact of tight glucose control on circulating 3-hydroxybutyrate in critically ill patients

Impact of tight glucose control on circulating 3-hydroxybutyrate in critically ill patients

Toward nutrition improving outcome of critically ill patients: How to interpret recent feeding RCTs?

When a calorie isn’t just a calorie: a revised look at nutrition in critically ill patients with sepsis and acute kidney injury

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