Intermittent feeding and circadian rhythm in critical illness

Imre W K Kouw, Leonie K Heilbronn, Arthur R H van Zanten, Imre W K Kouw, Leonie K Heilbronn, Arthur R H van Zanten

Abstract

Purpose of review: Circadian rhythms, i.e., periodic oscillations in internal biological processes, modulate metabolic processes such as hormonal signalling, nutrient absorption, and xenobiotic detoxification. Meal timing is a strong entraining cue for peripheral clocks in various organs, and eating out of circadian phases can impair glucose, gastrointestinal, and muscle metabolism. Sleep/wake cycles and circadian rhythms are extremely disrupted during critical illness. Timing of nutritional support may help preserve circadian rhythms and improve post-Intensive Care Unit (ICU) recovery. This review summarises circadian disruptors during ICU admission and evaluates the potential benefits of intermittent feeding on metabolism and circadian rhythms.

Recent findings: Rhythmic expression of core clock genes becomes rapidly disturbed during critical illness and remains disturbed for weeks. Intermittent, bolus, and cyclic enteral feeding have been directly compared to routine continuous feeding, yet no benefits on glycaemic control, gastrointestinal tolerance, and muscle mass have been observed and impacts of circadian clocks remain untested.

Summary: Aligning timing of nutritional intake, physical activity, and/or medication with circadian rhythms are potential strategies to reset peripheral circadian rhythms and may enhance ICU recovery but is not proven beneficial yet. Therefore, selecting intermittent feeding over continuous feeding must be balanced against the pros and cons of clinical practice.

Conflict of interest statement

There are no conflicts of interest.

Author contribution: I.W.K.K., L.K.H., and A.R.H.V.Z. were responsible for conceptualisation, data curation, and original draft writing and review and editing of the final manuscript.

Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.

Figures

Box 1
Box 1
no caption available
FIGURE 1
FIGURE 1
Clinical and environmental factors in the ICU that impact circadian rhythms.

References

    1. Rousseau AF, Prescott HC, Brett SJ, et al. . Long-term outcomes after critical illness: recent insights. Crit Care 2021; 25:108.
    1. Regmi P, Heilbronn LK. Time-restricted eating: benefits, mechanisms, and challenges in translation. iScience 2020; 23:101161.
    2. This review provides an overview on the effect of meal timing on circadian rhythmns and summarises the mechanisms of action on the proposed metabolic health benefits of time-restricted eating in preclinical models and humans.

    1. Daou M, Telias I, Younes M, et al. . Abnormal sleep, circadian rhythm disruption, and delirium in the ICU: are they related? Front Neurol 2020; 11:549908.
    2. Review on the physiological consequences of poor sleep quality circadian dysrhythmia, delirium and critical illness.

    1. Kreymann KG, Berger MM, Deutz NE, et al. . ESPEN guidelines on enteral nutrition: intensive care. Clin Nutr 2006; 25:210–223.
    1. McClave SA, Taylor BE, Martindale RG, et al. . Guidelines for the provision and assessment of nutrition support therapy in the adult critically ill patient: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.). J Parenter Enteral Nutr 2016; 40:159–211.
    1. Parr EB, Heilbronn LK, Hawley JA. A time to eat and a time to exercise. Exerc Sport Sci Rev 2020; 48:4–10.
    2. Perspective paper summarising the effects of time-restricted eating and exercise training on metabolic health.

    1. Bohe J, Low JF, Wolfe RR, et al. . Latency and duration of stimulation of human muscle protein synthesis during continuous infusion of amino acids. J Physiol 2001; 532 (Pt 2):575–579.
    1. Gazzaneo MC, Suryawan A, Orellana RA, et al. . Intermittent bolus feeding has a greater stimulatory effect on protein synthesis in skeletal muscle than continuous feeding in neonatal pigs. J Nutr 2011; 141:2152–2158.
    1. Evans DC, Forbes R, Jones C, et al. . Continuous versus bolus tube feeds: Does the modality affect glycemic variability, tube feeding volume, caloric intake, or insulin utilization? Int J Crit Illn Inj Sci 2016; 6:9–15.
    1. Chowdhury AH, Murray K, Hoad CL, et al. . Effects of bolus and continuous nasogastric feeding on gastric emptying, small bowel water content, superior mesenteric artery blood flow, and plasma hormone concentrations in healthy adults: a randomized crossover study. Ann Surg 2016; 263:450–457.
    1. Dirks ML, Smeets JSJ, Holwerda AM, et al. . Dietary feeding pattern does not modulate the loss of muscle mass or the decline in metabolic health during short-term bed rest. Am J Physiol Endocrinol Metab 2019; 316:E536–E545.
    1. Pletschette Z, Preiser JC. Continuous versus intermittent feeding of the critically ill: have we made progress? Curr Opin Crit Care 2020; 26:341–345.
    1. Puthucheary Z, Gunst J. Are periods of feeding and fasting protective during critical illness? Curr Opin Clin Nutr Metab Care 2021; 24:183–188.
    1. Di Girolamo FG, Situlin R, Fiotti N, et al. . Intermittent vs. continuous enteral feeding to prevent catabolism in acutely ill adult and pediatric patients. Curr Opin Clin Nutr Metab Care 2017; 20:390–395.
    1. Bear DE, Hart N, Puthucheary Z. Continuous or intermittent feeding: pros and cons. Curr Opin Crit Care 2018; 24:256–261.
    1. Van Dyck L, Casaer MP. Intermittent or continuous feeding: any difference during the first week? Curr Opin Crit Care 2019; 25:356–362.
    1. Patel JJ, Rosenthal MD, Heyland DK. Intermittent versus continuous feeding in critically ill adults. Curr Opin Clin Nutr Metab Care 2018; 21:116–120.
    1. Zheng X, Sehgal A. AKT and TOR signaling set the pace of the circadian pacemaker. Curr Biol 2010; 20:1203–1208.
    1. Crosby P, Hamnett R, Putker M, et al. . Insulin/IGF-1 drives PERIOD synthesis to entrain circadian rhythms with feeding time. Cell 2019; 177:896–909 e20.
    1. Tuvia N, Pivovarova-Ramich O, Murahovschi V, et al. . Insulin directly regulates the circadian clock in adipose tissue. Diabetes 2021; 70:1985–1999.
    2. One of the first human studies to show insulin as the primary mechanism of feeding-induced entrainment of peripheral circadian clocks in adipose tissue (through transcriptional changes in PER leading to the phase shift of circadian oscillations).

    1. Lamia KA, Sachdeva UM, DiTacchio L, et al. . AMPK regulates the circadian clock by cryptochrome phosphorylation and degradation. Science 2009; 326:437–440.
    1. Ramsey KM, Yoshino J, Brace CS, et al. . Circadian clock feedback cycle through NAMPT-mediated NAD+ biosynthesis. Science 2009; 324:651–654.
    1. Nakahata Y, Sahar S, Astarita G, et al. . Circadian control of the NAD+ salvage pathway by CLOCK-SIRT1. Science 2009; 324:654–657.
    1. Zeb F, Wu X, Chen L, et al. . Effect of time-restricted feeding on metabolic risk and circadian rhythm associated with gut microbiome in healthy males. Br J Nutr 2020; 123:1216–1226.
    2. This study is one of the first to demonstrate that time-restricted eating increases gut microbiome diversity and alters Sirt1 and clock genes Bmal1 and Clock mRNA expression in humans.

    1. Mindikoglu AL, Abdulsada MM, Jain A, et al. . Intermittent fasting from dawn to sunset for 30 consecutive days is associated with anticancer proteomic signature and upregulates key regulatory proteins of glucose and lipid metabolism, circadian clock, DNA repair, cytoskeleton remodeling, immune system and cognitive function in healthy subjects. J Proteomics 2020; 217:103645.
    2. This is the first human serum proteomics study assessing the effect of 30-day intermittent fasting with simultaneous assessment of clinical metabolic parameters, serum biomarkers, and faecal microbiota.

    1. Mason IC, Qian J, Adler GK, et al. . Impact of circadian disruption on glucose metabolism: implications for type 2 diabetes. Diabetologia 2020; 63:462–472.
    1. Zhao L, Hutchison AT, Wittert GA, et al. . Intermittent fasting does not uniformly impact genes involved in circadian regulation in women with obesity. Obesity 2020; 28 Suppl 1:S63–S67.
    2. This is one of the few human studies to examine the impact of intermittent fasting on peripheral clocks by analysing clock gene expression in human muscle and adipose fat tissue biopsies following an 8-week intermittent fasting intervention in 37 women with obesity.

    1. Acuna-Fernandez C, Marin JS, Diaz-Casado ME, et al. . Daily changes in the expression of clock genes in sepsis and their relation with sepsis outcome and urinary excretion of 6-sulfatoximelatonin. Shock 2020; 53:550–559.
    1. Diaz E, Diaz I, Del Busto C, et al. . Clock genes disruption in the intensive care unit. J Intensive Care Med 2019; 885066619876572.
    1. Davidson S, Villarroel M, Harford M, et al. . Day-to-day progression of vital-sign circadian rhythms in the intensive care unit. Crit Care 2021; 25:156.
    1. Okutan B, Kjer CKW, Poulsen LM, et al. . Sleep-wake rhythms determined by actigraphy during in-hospital stay following discharge from an intensive care unit. Acta Anaesthesiol Scand 2021; 65:801–808.
    2. Prospective cohort study that quantified sleep-wake patterns using accelerometry in ICU patients in the first week after ICU discharge.

    1. Yang PL, Ward TM, Burr RL, et al. . Sleep and circadian rhythms in survivors of acute respiratory failure. Front Neurol 2020; 11:94.
    1. 2020; Maas MB, Iwanaszko M, Lizza BD, et al. . Circadian gene expression rhythms during critical illness. crit care med. 48:e1294–e1299.
    1. Diaz E, Diaz I, Del Busto C, et al. . Clock genes disruption in the intensive care unit. J Intensive Care Med 2020; 35:1497–1504.
    1. Coiffard B, Diallo AB, Culver A, et al. . Circadian rhythm disruption and sepsis in severe trauma patients. Shock 2019; 52:29–36.
    1. Hughes ME, Abruzzi KC, Allada R, et al. . Guidelines for genome-scale analysis of biological rhythms. J Biol Rhythms 2017; 32:380–393.
    1. Maas MB, Lizza BD, Kim M, et al. . Stress-induced behavioral quiescence and abnormal rest-activity rhythms during critical illness. Crit Care Med 2020; 48:862–871.
    2. Large observational study in 112 critically ill patients quantifying rest-activity rhythms compared with 101 control patients (age-matched community-dwelling volunteers, hospital bedrest volunteers, and sleep deprived volunteers) using 24 h accelerometry.

    1. Maas MB, Lizza BD, Abbott SM, et al. . Factors disrupting melatonin secretion rhythms during critical illness. Crit Care Med 2020; 48:854–861.
    2. Large observational study observing melatonin rhythms in 112 ICU patients for 24-48 h within the first day of ICU admission in combination with the assessment of environmental entrainers including light intensity, nutritional intake, physical activity levels, medication, encephalopathy, and multiple organ system function.

    1. McNelly AS, Bear DE, Connolly BA, et al. . Effect of intermittent or continuous feed on muscle wasting in critical illness: A phase II clinical trial. Chest 2020.
    1. Dong J, Liu R, Li L, et al. . [Effects of intermittent feeding and continuous feeding on muscle atrophy and nutritional status in critically ill patients]. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2021; 33:844–848.
    1. Ren CJ, Yao B, Tuo M, et al. . Comparison of sequential feeding and continuous feeding on the blood glucose of critically ill patients: a noninferiority randomized controlled trial. Chin Med J (Engl) 2021; 134:1695–1700.
    1. Sjulin TJ, Strilka RJ, Huprikar NA, et al. . Intermittent gastric feeds lower insulin requirements without worsening dysglycemia: a pilot randomized crossover trial. Int J Crit Illn Inj Sci 2020; 10:200–205.
    1. Seyyedi J, Rooddehghan Z, Mohammadi M, et al. . Comparison of the effect of enteral feeding through the bolus and continuous methods on serum phosphorus and glucose levels in patients with mechanical ventilation: a randomized clinical trial. J Nutr Metab 2020; 2020:6428418.
    1. Zhu W, Jiang Y, Li J. Intermittent versus continuous tube feeding in patients with hemorrhagic stroke: a randomized controlled clinical trial. Eur J Clin Nutr 2020; 74:1420–1427.
    1. Satinsky I, Richtarova J. Intermittent feeding in intensive care – the theory and practice. Rozhl Chir 2021; 100:66–73.
    1. Ma Y, Cheng J, Liu L, et al. . Intermittent versus continuous enteral nutrition on feeding intolerance in critically ill adults: a meta-analysis of randomized controlled trials. Int J Nurs Stud 2021; 113:103783.
    2. Latest meta-analysis on the effects of intermittent versus continuous enteral feeding on feeding intolerance in critically ill adults.

    1. Flower L, Haines RW, McNelly A, et al. . Effect of intermittent or continuous feeding and amino acid concentration on urea-to-creatinine ratio in critical illness. J Parenter Enteral Nutr 2021.
    2. Sub study on one of the largest multicentre RCT that compared 10 days of intermittent feeding with continuous feeding on muscle mass changes. This secondary analysis assessed urea-to-creatinine ratio trajectory, as a marker of muscle wasting, during intermittent vs continuous feeding.

    1. Abe T, Kazama R, Okauchi H, et al. . Food deprivation during active phase induces skeletal muscle atrophy via IGF-1 reduction in mice. Arch Biochem Biophys 2019; 677:108160.
    1. Lundell LS, Parr EB, Devlin BL, et al. . Time-restricted feeding alters lipid and amino acid metabolite rhythmicity without perturbing clock gene expression. Nat Commun 2020; 11:4643.
    2. One of the few diet-controlled human studies that investigated the effect of 5 days of time-restricted eating on clock gene expression in vivo in skeletal muscle.

    1. Jamshed H, Beyl RA, Della Manna DL, et al. . Early time-restricted feeding improves 24-h glucose levels and affects markers of the circadian clock, aging, and autophagy in humans. Nutrients 2019; 11:1234.
    1. Jakubowicz D, Landau Z, Tsameret S, et al. . Reduction in glycated hemoglobin and daily insulin dose alongside circadian clock upregulation in patients with type 2 diabetes consuming a three-meal diet: a randomized clinical trial. Diabetes Care 2019.
    1. Davis R, Bonham MP, Nguo K, et al. . Glycaemic response at night is improved after eating a high protein meal compared with a standard meal: a cross-over study. Clin Nutr 2020; 39:1510–1516.
    1. Parr EB, Devlin BL, Radford BE, et al. . A delayed morning and earlier evening time-restricted feeding protocol for improving glycemic control and dietary adherence in men with overweight/obesity: a randomized controlled trial. Nutrients 2020; 12:505.
    1. Plummer MP, Bellomo R, Cousins CE, et al. . Dysglycaemia in the critically ill and the interaction of chronic and acute glycaemia with mortality. Intensive Care Med 2014; 40:973–980.
    1. Investigators N-SS, Finfer S, Chittock DR, et al. . Intensive versus conventional glucose control in critically ill patients. N Engl J Med 2009; 360:1283–1297.
    1. Van Dyck L, Vanhorebeek I, Wilmer A, et al. . Towards a fasting-mimicking diet for critically ill patients: the pilot randomized crossover ICU-FM-1 study. Crit Care 2020; 24:249.
    2. This pilot study in critically ill patients shows that 24-h macronutrient restriction can initiate a metabolic fasting response.

    1. Held NM, Wefers J, van Weeghel M, et al. . Skeletal muscle in healthy humans exhibits a day-night rhythm in lipid metabolism. Mol Metab 2020; 37:100989.
    2. Clinical study in humans showing that skeletal muscle lipid content and composition displays day-night rhythmicity in healthy, lean volunteers.

    1. van Moorsel D, Hansen J, Havekes B, et al. . Demonstration of a day-night rhythm in human skeletal muscle oxidative capacity. Mol Metab 2016; 5:635–645.

Source: PubMed

3
Abonnieren