Sarcopenia Clinical Trial
Official title:
Impact of Fat Co-ingestion With Protein on the Post-prandial Anabolic Response in Elderly Men (Pro-Fat Study)
Rationale: The progressive loss of skeletal muscle mass with aging, or sarcopenia, has a
major impact on our healthcare system due to increased morbidity and greater need for
hospitalization and/or institutionalization. One way to prevent skeletal muscle loss is to
improve dietary intake of the elderly. It has already been shown that ingestion of dietary
protein stimulates muscle protein synthesis and inhibits muscle protein breakdown, resulting
in an overall positive net protein balance. However, the impact of fat (as part of the meal)
on dietary protein-induced muscle protein synthesis remains largely unknown. Based on
previous studies by other research groups, we hypothesize that fat further stimulates the
muscle anabolic response to protein ingestion.
Objective: The primary objective of this study is to investigate the effect of a single
meal-like amount of protein with or without fat on postprandial muscle protein synthesis
rates in healthy elderly men. Furthermore, as a secondary objective, we will assess
digestion and absorption kinetics.
Study design: double-blind randomized intervention study Study population: 24 healthy
elderly men (55-85 y) Intervention: one group (n=12) will consume a test beverage of 350 mL
containing 20 g of intrinsically labeled casein, and the other group (n=12) will consume a
beverage of the same volume containing 20 g of casein plus 20 g of fat.
Main study parameters/endpoints: Primary endpoint: muscle protein synthesis rates. Secondary
endpoint: digestion and absorption kinetics.
The progressive loss of skeletal muscle mass with aging, or sarcopenia, has a major impact
on our healthcare system due to increased morbidity and greater need for hospitalization
and/or institutionalization. The age-related loss of skeletal muscle mass is facilitated by
a combination of factors, which include a less than optimal diet and a sedentary lifestyle.
These factors contribute to a disruption in the regulation of skeletal muscle protein
turnover, leading to an imbalance between muscle protein synthesis (MPS) and degradation.
One way to overcome this problem is to improve dietary intake of the elderly. It has been
well established that nutrient intake greatly affects protein turnover in skeletal muscle
tissue.
Ingestion of dietary protein stimulates MPS rates and inhibits muscle protein breakdown
rates, resulting in an overall positive net protein balance in both the young and elderly.
However, it is not clear what the impact is of co-ingestion of other macronutrients on
digestion and absorption kinetics or MPS rates in the healthy young or the elderly. We have
recently conducted a study to examine the impact of carbohydrate co-ingestion on
postprandial MPS in the healthy young and old. Indeed, preliminary results show that
carbohydrate co-ingestion stimulates protein synthesis.
Interestingly, very little is known about the impact of fat co-ingestion with protein on the
stimulation of post-prandial MPS rates. What is noteworthy is that Elliot et al.
investigated the effect of whole milk ingestion on net muscle protein balance after
resistance exercise using an arteriovenous balance approach. Ingestion of whole milk
(containing 50 en% fats) stimulated the post-exercise net uptake of phenylalanine and
threonine to a greater extent than ingestion of fat-free milk (containing 6 en% fat).
Although, amino acid uptake is indicative of 'muscle anabolism', it is not a direct measure
of MPS so no firm conclusions can be deduce from this work. Furthermore, milk also contains
a certain amount of carbohydrates (fat-free milk 55 en% and whole milk 30 en%), which does
not allow for direct assessment of fat co-ingestion per se.
Certainly, other studies have investigated the effect of long term fatty acid intake, using
direct incorporation methods, on the MPS rates. For example, long term omega-3
polyunsaturated fatty acid (n-3 PUFA) supplementation increased feeding-mediated MPS rates
in young, middle-aged, and older adults. The mechanism(s) underpinning the enhanced effect
of n-3 PUFA supplementation on post-prandial MPS rates to dietary protein are not well
defined. It has been speculated that the enhanced feeding-effect of n-3 PUFA on postprandial
MPS rates is due to remodeling of the sarcolemma to include a greater n-3 PUFA content, and
ultimately enhances insulin's action on muscle protein metabolism. This is clearly a long
term effect, but what about the acute effects of fat co-ingestion on postprandial MPS rates?
Katsanos et al. found that elevated plasma fatty acid concentrations did not interfere with
the post-prandial stimulation of MPS. However, subjects ingested a single bolus of essential
amino acids while receiving fatty acid infusion, which clearly does not reflect a 'real
world' setting. In the end, there is reason to believe that the presence of fat in a meal
further stimulates the muscle anabolic response to meal ingestion. However, fat intake may
also modulate gastric emptying and dietary protein digestion and absorption kinetics. To
date, the acute (not long-term supplementation) impact of fat in a meal on post-prandial
muscle protein anabolism and digestion and absorption kinetics remains completely
unexplored, and thus we can only speculate on the impact that fat co-ingestion has on
postprandial MPS rates.
In the present study we will investigate the effect of a single meal-like amount of protein
with or without fat on postprandial MPS in healthy elderly men. Furthermore, we will assess
digestion and absorption kinetics. The use of intrinsically labeled casein will allows us
determine de novo MPS from amino acids that come available through the test beverage.
;
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Prevention
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