Intermittent feeding and circadian rhythm in critical illness

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.Imre W.K. Kouw, Leonie K. Heilbronn, and Arthur R.H. van Zante

The use of doubly labeled milk protein to measure postprandial muscle protein synthesis rates in vivo in humans

We aimed to determine the impact of precursor pool dilution on the assessment of postprandial myofibrillar protein synthesis rates (MPS). A Holstein dairy cow was infused with large amounts of L-[1-13C]phenylalanine and L-[1-13C]leucine and the milk was collected and fractionated. The enrichment levels in the casein were 38.7 and 9.3 MPE, respectively. In a subsequent human experiment, 11 older men (age: 71+/-1 y, BMI: 26+/-0.1 kgm-2) received a primed constant infusion of L-[ring-2H5]phenylalanine and L-[1-13C]leucine. Blood and muscle samples were collected before and after the ingestion of 20 g doubly-labeled casein to assess postprandial MPS based on the 1.) constant tracer infusion of L-[ring-2H5]phenylalanine, 2.) ingestion of intrinsically L-[1-13C]phenylalanine labeled casein, 3.) constant infusion of L-[1-13C]leucine in combination with the ingestion of intrinsically L-[1-13C]leucine labeled casein. Postprandial MPS was increased (P0.05). Our findings confirm that the postprandial MPS assessed using the primed continuous tracer infusion approach may differ if tracer steady-state conditions in the precursor pools are perturbed. The use of intrinsically doubly-labeled protein provides a method to study the metabolic fate of the ingested protein and the subsequent postprandial MPS response

No differences in muscle protein synthesis rates following ingestion of wheat protein, milk protein, and their protein blend in healthy, young males

Plant-derived proteins have been suggested to have less anabolic properties when compared with animal-derived proteins. Whether blends of plant- and animal-derived proteins can compensate for their lesser anabolic potential has not been assessed. The present study compares post-prandial muscle protein synthesis rates following the ingestion of milk protein with wheat protein or a blend of wheat plus milk protein in healthy, young males. In a randomised, double-blind, parallel-group design, 36 males (23 (sd 3) years) received a primed continuous L-[ring-C-13(6)]-phenylalanine infusion after which they ingested 30 g milk protein (MILK), 30 g wheat protein (WHEAT) or a 30 g blend combining 15 g wheat plus 15 g milk protein (WHEAT+MILK). Blood and muscle biopsies were collected frequently for 5 h to assess post-prandial plasma amino acid profiles and subsequent myofibrillar protein synthesis rates. Ingestion of protein increased myofibrillar protein synthesis rates in all treatments (P < 0 center dot 001). Post-prandial myofibrillar protein synthesis rates did not differ between MILK v. WHEAT (0 center dot 053 (sd 0 center dot 013) v. 0 center dot 056 (sd 0 center dot 012) %center dot h(-1), respectively; t test P = 0 center dot 56) or between MILK v. WHEAT+MILK (0 center dot 053 (sd 0 center dot 013) v. 0 center dot 059 (sd 0 center dot 025) %center dot h(-1), respectively; t test P = 0 center dot 46). In conclusion, ingestion of 30 g milk protein, 30 g wheat protein or a blend of 15 g wheat plus 15 g milk protein increases muscle protein synthesis rates in young males. Furthermore, muscle protein synthesis rates following the ingestion of 30 g milk protein do not differ from rates observed after ingesting 30 g wheat protein or a blend with 15 g milk plus 15 g wheat protein in healthy, young males

Exercise Plus Presleep Protein Ingestion Increases Overnight Muscle Connective Tissue Protein Synthesis Rates in Healthy Older Men

Protein ingestion and exercise stimulate myofibrillar protein synthesis rates. When combined, exercise further increases the postprandial rise in myofibrillar protein synthesis rates. It remains unclear whether protein ingestion with or without exercise also stimulates muscle connective tissue protein synthesis rates. The authors assessed the impact of presleep protein ingestion on overnight muscle connective tissue protein synthesis rates at rest and during recovery from resistance-type exercise in older men. Thirty-six healthy, older men were randomly assigned to ingest 40 g intrinsically L-[1-C-13]-phenylalanine and L-[1-C-13]-leucinelabeled casein protein (PRO, n = 12) or a nonprotein placebo (PLA, n = 12) before going to sleep. A third group performed a single bout of resistance-type exercise in the evening before ingesting 40 g intrinsically-labeled casein protein prior to sleep (EX+PRO, n = 12). Continuous intravenous infusions of L-[ring-H-2(5)]-phenylalanine and L-[1-C-13]-leucine were applied with blood and muscle tissue samples collected throughout overnight sleep. Presleep protein ingestion did not increase muscle connective tissue protein synthesis rates (0.049 +/- 0.013 vs. 0.060 +/- 0.024%/hr in PLA and PRO, respectively; p = .73). Exercise plus protein ingestion resulted in greater overnight muscle connective tissue protein synthesis rates (0.095 +/- 0.022%/hr) when compared with PLA and PRO (p &lt; .01). Exercise increased the incorporation of dietary protein-derived amino acids into muscle connective tissue protein (0.036 +/- 0.013 vs. 0.054 +/- 0.009 mole percent excess in PRO vs. EX+PRO, respectively; p &lt; .01). In conclusion, resistance-type exercise plus presleep protein ingestion increases overnight muscle connective tissue protein synthesis rates in older men. Exercise enhances the utilization of dietary protein-derived amino acids as precursors for de novo muscle connective tissue protein synthesis during overnight sleep.</p

Impact of the Macronutrient Composition of a Nutritional Supplement on Muscle Protein Synthesis Rates in Older Men: A Randomized, Double Blind, Controlled Trial

CONTEXT: An impaired muscle protein synthetic response to feeding likely contributes to muscle loss with aging. There are few data available on the effect of the macronutrient composition of clinical supplements on the postprandial muscle protein synthetic response in older subjects. OBJECTIVE: To determine the impact of the macronutrient composition of a nutritional supplement on the postprandial muscle protein synthetic response in older men. METHODS: A total of 45 non-sarcopenic older men (age: 69+/-1 y; BMI: 25.7+/-0.3 kg/m2) were randomly assigned to ingest 21 g of leucine-enriched whey protein with carbohydrate (9 g) and fat (3 g) (Pro-En), an isonitrogenous amount of 21 g of leucine-enriched whey protein without carbohydrate and fat (Pro), or an isocaloric mixture (628 kJ) containing carbohydrate and fat only (En). Stable isotope tracer methodology was applied to assess basal as well as postprandial muscle protein synthesis rates in the three groups. RESULTS: Ingestion of protein in the Pro-En and Pro groups significantly increased muscle protein synthesis rates when compared with basal rates (from 0.032+/-0.003 to 0.053+/-0.004 and 0.040+/-0.003 to 0.049+/-0.003 %/h, respectively; P<0.05), whereas ingestion of carbohydrate and fat did not increase muscle protein synthesis rates in the En group (from 0.039+/-0.004 to 0.040+/-0.003 %/h; P=0.60). Despite the greater postprandial rise in circulating insulin concentration in the Pro-En group, no significant differences were observed in postprandial muscle protein synthesis rates between the Pro-En and Pro groups (P=0.32). Postprandial muscle protein synthesis rates were higher in the Pro-En vs En group (P=0.01). CONCLUSION: The ingestion of a nutritional supplement containing 21 g of leucine-enriched whey protein significantly raises muscle protein synthesis rates in non-sarcopenic older men, but co-ingestion of carbohydrate and fat does not modulate the postprandial muscle protein synthetic response to protein ingestion in older men

Ingestion of Free Amino Acids Compared with an Equivalent Amount of Intact Protein Results in More Rapid Amino Acid Absorption and Greater Postprandial Plasma Amino Acid Availability Without Affecting Muscle Protein Synthesis Rates in Young Adults in a Double-Blind Randomized Trial

Background: The rate of protein digestion and amino acid absorption determines the postprandial rise in circulating amino acids and modulates postprandial muscle protein synthesis rates.Objective: We sought to compare protein digestion, amino acid absorption kinetics, and the postprandial muscle protein synthetic response following ingestion of intact milk protein or an equivalent amount of free amino acids.Methods: Twenty-four healthy, young participants (mean +/- SD age: 22 +/- 3 y and BMI 23 +/- 2 kg/m(2); sex: 12 male and 12 female participants) received a primed continuous infusion of L-[ring-H-2(5)]-phenylalanine and L-[ring-3,5-H-2(2)]-tyrosine, after which they ingested either 30 g intrinsically L-[1-C-13]-phenylalanine-labeled milk protein or an equivalent amount of free amino acids labeled with L-[1-C-13]-phenylalanine. Blood samples and muscle biopsies were obtained to assess protein digestion and amino acid absorption kinetics (secondary outcome), whole-body protein net balance (secondary outcome), and mixed muscle protein synthesis rates (primary outcome) throughout the 6-h postprandial period.Results: Postprandial plasma amino acid concentrations increased after ingestion of intact milk protein and free amino acids (both P < 0.001), with a greater increase following ingestion of the free amino acids than following ingestion of intact milk protein (P-time x treatment < 0.001). Exogenous phenylalanine release into plasma, assessed over the 6-h postprandial period, was greater with free amino acid ingestion (76 +/- 9%) than with milk protein treatment (59 +/- 10%; P < 0.001). Ingestion of free amino acids and intact milk protein increased mixed muscle protein synthesis rates (P-time < 0.001), with no differences between treatments (from 0.037 +/- 0.015%/h to 0.053 +/- 0.014%/h and 0.039 +/- 0.016%/h to 0.051 +/- 0.010%/h, respectively; P-time x treatment = 0.629).Conclusions: Ingestion of a bolus of free amino acids leads to more rapid amino acid absorption and greater postprandial plasma amino acid availability than ingestion of an equivalent amount of intact milk protein. Ingestion of free amino acids may be preferred over ingestion of intact protein in conditions where protein digestion and amino acid absorption are compromised