Protein Nutrition in Crohn’s disease
Research type
Research Study
Full title
Investigating protein nutrition in paediatric Crohn’s disease.
IRAS ID
297431
Contact name
Gordon Moran
Contact email
Sponsor organisation
University of Nottingham
Duration of Study in the UK
2 years, 0 months, 1 days
Research summary
Up to 60% of adult Crohn’s disease (CD) patients have clinical evidence of low muscle mass even when in clinical remission(1) indicating the poorly reversible nature of this chronic phenomenon. Muscle mass is maintained through the daily balance of muscle protein synthesis (MPS) and muscle protein breakdown (MPB), with the essential amino acid (EAA) components of a meal and muscle contraction being the primary stimulators of MPS. Patients with active CD show a significant decrease in the expression of muscle proteins in hypertrophic signalling pathways (Akt, P70S6K1) with no change in the expression of atrophic signalling (MAFbx, MuRF1)(2).
The majority (20-85%) of Inflammatory Bowel Disease patients suffer from nutritional deficiencies with protein-calorie malnutrition common when in an active phase of the disease(3) and micronutrient deficiencies a recognisable problem in remission(4). In CD, up to 75% of hospitalized patients are malnourished and as many as 50% are in negative nitrogen balance(5). Adult patients with active CD ingest considerably less daily protein intake than age- BMI- matched healthy controls [CD, 70.3 g ± 6.1; HV, 92.6 g ± 7.8, p = 0.03](6). Similar observations may be true for children with inactive CD where protein intake is lower with 79 ± 5g/day reported in CD and 90 ± 10g/day reported in HV(7) though these findings were not statistically significant.
Apart from decreased ingestion, malabsorption may be a contributing factor to malnourishment in CD. Intestinal motility, measured using cine-MRI, is reduced in active CD, possibly further decreasing intestinal digestion and absorption of dietary peptides (8). In male paediatric patients with long term CD, muscle metabolism is perturbed by a negative branched chain amino acid balance in the forearm (7). CD may have a significant effect on protein digestion and absorption, and blunt the MPS response to feeding, leading to a chronic muscle mass reduction that may persist even when in remission.The essential amino acid (EAA) components of a protein-meal are crucial for the stimulation of muscle protein synthesis (MPS) and we have shown of all the EAA, leucine plays a key role in driving MPS. Low serum levels EAA/leucine have been reported in adult CD (9) but their role in the aetiology of sarcopenia in paediatric CD is unknown. Further, how CD affects the protein digestion/absorption and how this contributes to low EAA/leucine remains unclear.
Recent advances in stable isotope tracer techniques now enable a more accurate determination of protein digestibility (10). By following the appearance of intrinsically labelled AAs into the blood upon digestion of the intrinsically labelled protein, alongside the appearance of label-free AAs, protein digestibility can be accurately determined (11).REC name
South Central - Hampshire A Research Ethics Committee
REC reference
21/SC/0285
Date of REC Opinion
10 Nov 2021
REC opinion
Further Information Favourable Opinion