None listed
Conditions
Brief summary
Older people are more likely to lose than gain weight and weight loss is a strong predictor of poor outcomes in older people. Weight lost in older people predominantly comprises muscle and insufficient protein intake is likely to exacerbate muscle loss by limiting muscle anabolism. When severe, muscle loss leads to sarcopenia or cachexia, which are strongly associated with adverse outcomes. Protein-enriched supplements are often used to preserve and restore skeletal muscle mass in the elderly population. The rationale for using protein supplements in older people is strengthened by evidence that ageing has a minimal effect on the capacity to synthesize muscle protein acutely after protein ingestion. Accordingly if older people can ingest enough protein it is likely to have beneficial effects on muscle mass. Muscle protein deposition and anabolic effects are greater when amino acid concentrations are higher, however, there are limits to the amount of protein that can be chronically ingested, particularly by older people, due to factors such as cost, palatability and suppression of energy intake at subsequent meals. Furthermore, in young adults, the onset of satiety after ingestion of more rapidly digested and absorbed proteins is earlier, and its duration shorter than with ‘slower’ proteins. Administration of more rapidly absorbed proteins to under-nourished older people may, therefore, have the advantages of not only enhancing muscle protein synthesis, but also of minimising the duration of any potentially appetite suppressant effects. An effective way to increase muscle protein deposition, by accelerating the absorption of proteins, may be to hydrolyse them, ie digest proteins in their component amino acids. In healthy older people, for example, administration of partially hydrolysed casein resulted in earlier and higher peak amino acids (particularly essential amino acids, e.g. ~3-fold increase in peak plasma leucine concentration) than administration of the same amounts of un-hydrolysed casein (~2-fold increase). Insights into the digestion and absorption kinetics of dietary protein-derived amino acids after protein ingestion can successfully be obtained by using cow milk protein with intrinsically labelled amino acids (L-[1-13C]-phenylalanine and L-[1-13C]-leucine), which are measured in muscle biopsies after administration to calculate fractional synthetic rates of the muscle. Aim: To determine the acute effects of hydrolysis of protein on protein absorption and digestion kinetics of milk protein, administered directly into the small intestine. Hypothesis: In older subjects the plasma amino acid concentrations will peak more rapidly and the muscle protein deposition will be higher after ingestion of the completely digested protein (free amino acids) when compared with the intact intrinsically-labelled milk protein.
Interventions
The study will involve 20 healthy older men (age: greater than 65y, BMI 22-30kg/m2). Recruitment will be by (i) advertisement and (ii) from databases of our previous studies. Subjects will attend the Discipline of Medicine, Royal Adelaide Hospital, for an initial screening visit where inclusion and exclusion criteria will be evaluated, and the following baseline measurements will be obtained: body composition (DEXA), and biochemistry screen. Subjects will be asked to refrain from exercise and co
The study will involve 20 healthy older men (age: greater than 65y, BMI 22-30kg/m2). Recruitment will be by (i) advertisement and (ii) from databases of our previous studies. Subjects will attend the Discipline of Medicine, Royal Adelaide Hospital, for an initial screening visit where inclusion and exclusion criteria will be evaluated, and the following baseline measurements will be obtained: body composition (DEXA), and biochemistry screen. Subjects will be asked to refrain from exercise and complete a food diary to determine their energy and protein intake during the 2 days before the study day. Subjects will be studied on 1 study day to determine the effects of intraduodenal (ID) administration (at a rate of 4mL/min; 240mL over 60min) of i) milk protein intrinsically labelled with L-[1-13C]-phenylalanine and L-[1-13C]-leucine (25g, 100kcal, 1.7 kcal/min), or ii) amino acid mixture matching (isocaloric) the milk protein including L-[1-13C]-phenylalanine and L-[1-13C]-leucine; on absorption and digestion kinetics; muscle protein fractional synthetic rates; antropyloroduodenal (ADP) pressures and; appetite and gastrointestinal symptoms, in a randomized, double-blind, parallel study design, with 10 subjects in each group. Subjects will be provided with a standardized evening meal to consume on the night before the study, and will be instructed to fast overnight from solids and liquids and to refrain from strenuous physical activity until they attend the laboratory at 0800am. On arrival, a Teflon catheter will be inserted in an antecubital vein for stable isotope infusion. A second Teflon catheter will be inserted in an antecubital vein of the contralateral arm for blood sampling. The plasma phenylalanine pools will be primed with a single intravenous dose containing L-[ring-2 H5 ]-phenylalanine (2.2 micromol/kg), L-[3,5-D2]-tyrosine (0.674 micromol/kg), and L-[1-13C]-leucine (4.391 micromol/kg) after which continuous intravenous infusion with the same tracers will be started for the rest of the study day until t=360min (L-[ring-2 H5 ]phenylalanine: 0.055 micromol/kg/min; L-[3,5-D2]-tyrosine: 0.017 micromol/kg/min; L-[1-13C]-leucine: 0.110 micromol/kg/min). A small-diameter, manometric catheter will be inserted into the stomach through an anesthetized nostril and allowed to pass into the duodenum by peristalsis. The correct positioning of the catheter will be maintained by continuous measurement of the transmucosal potential difference (TMPD). The intraduodenal protein infusion will start at t=0, ~120min after commencement of the intravenous infusion, once baseline ADP motility has been recorded for ~15min. During the 60min ‘protein’ infusion, ADP motility will be measured continuously (0-60min). Blood samples will be drawn, visual analog scale (VAS) questionnaires to assess perceptions of appetite and gastrointestinal symptoms will be completed, at -150, -60, -30, 0, 15, 30, 45, 60, 90, 120, 150, 180, 240, 300, 360 min. Muscle biopsies (~55mg) will be collected from the middle region of the vastus lateralis muscle at 0 and 180 min. After completion of a meal, subjects will be allowed to leave the laboratory.
Sponsors
Stijn Soenen
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Prevention
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
Male
Age
65 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Body Mass Index (BMI): 22-30 kg/m2 Weight stable (<5% fluctuation in body weight in previous 3 months) Age >65
Exclusion criteria
smokers of cigarettes/cigars/marijuana; intake of >2 standard drinks on >5 days per week; intake of >4 cups of caffeinated drinks per day; intake of any illicit substance; vegetarians; lactose intolerance; Use of prescribed or non-prescribed medications (including vitamins and herbal supplements) which may effect gastrointestinal function or appetite - if subjects are willing, and able, to stop using medications, vitamins and/or supplements which affect gastrointestinal or energy metabolism during the study a washout period of at least 14 days prior to the first test day will apply; food allergy(s), diabetes mellitus (fasting glucose >6.9 mmol/L), epilepsy, or gallbladder, pancreatic, cardiovascular or respiratory diseases; significant gastrointestinal symptoms, disease or surgery (apart from uncomplicated appendectomy), as determined by a questionnaire; impaired cognitive function (score <25 on Mini-Mental State Examination); depression (a score >11 on the Geriatric Depression Questionnaire); any other illness deemed significant by the investigator (including chronic illnesses not explicitly listed above); low ferritin levels (<20ug/l) and plasma Hb levels (<130g/l), or blood donated in the 12 weeks prior to taking part in the study, in line with current Australian Red Cross Guidelines; individuals who are found to be unable to comprehend the study protocol.
Outcome results
None listed