Impact of Fat Co-ingestion With Protein on the Post-prandial Anabolic Response in Elderly Men
Condition: Sarcopenia
MeSH terms: Sarcopenia
Study type: Interventional

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): PRO+FAT; PRO
Intervention type(s): Dietary Supplement; Dietary Supplement
Other intervention name(s): 20 g of casein + 26.7 g Anhydrous Milk Fat; 20 g of casein
Intervention MeSH terms: Caseins
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Prevention