Leucine Co-ingestion and Myofibrillar Protein Synthesis in Older Adults
Condition: Aging; Sarcopenia
MeSH terms: Sarcopenia
Study type: Interventional

Summary: 
      The loss of muscle mass with aging is associated with a dysregulation of muscle protein
      synthesis (MPS) that is generally characterized by a suppressed MPS response to protein
      ingestion. This 'anabolic resistance' to protein feeding can be overcome with the ingestion
      of larger protein servings (~0.4g/kg/meal, equivalent to ~ 30 - 40g/meal); however, older
      adults would likely find it challenging to consume such quantities of protein on a per meal
      basis.

      The amino acid leucine has a unique role as a key 'activator' of MPS. Some research shows
      that increasing the leucine content of a suboptimal dose of a protein supplement can enhance
      the MPS response in older adults. However it is currently unknown whether the co-ingestion of
      leucine with normal, mixed meals can increase MPS. Furthermore, it has been suggested that
      leucine supplementation may only benefit older adults consuming suboptimal daily protein
      intakes. Therefore, the purpose of the current study is to examine the impact of leucine
      co-ingestion with mixed macronutrient meals on the myofibrillar protein synthetic response in
      older men consuming daily protein intakes at or below the current recommendations. A further
      objective is to determine whether the myofibrillar protein synthetic response to a session of
      resistance exercise is enhanced by leucine supplementation with meals. The investigators
      hypothesize that, in both the exercised and non-exercised condition, leucine co-ingestion at
      meals will enhance integrative myofibrillar protein synthesis in older adults consuming lower
      daily protein intakes, but will not augment MPS in those consuming higher daily protein. The
      investigators further hypothesize that the influence of leucine supplementation on MPS will
      be greater in the exercise condition than the non-exercise condition.
    

Detailed description: 
      At baseline, participants will be asked to wear a pedometer and to complete a physical
      activity and a weighed food record for 3 days. Resting energy expenditure (indirect
      calorimetry), body weight and body composition (DEXA) will be assessed in the fasted state. A
      strength test will be conducted to determine 1 repetition maximum (1-RM) and the maximum load
      that each participant can lift for 15 - 24 repetitions using a seated leg extension machine.
      Participants will then be randomized to one of two groups matched for age, activity level and
      BMI: higher (1.2 g/kg/d) or lower daily protein (0.8 g/kg/d). Participants will then commence
      a 9 day controlled diet (day -3 to 6) designed to meet energy requirements for weight
      maintenance and to provide a daily protein intake according to each participant's group
      allocation (i.e. 0.8 or 1.2 g/kg/d).

      All participants will be provided with flavored, supplemental beverages (Infinit Nutrition,
      Windsor, Ontario) and will be instructed to consume one beverage half way through each meal
      from day 0 - 5. Individual servings of the supplement will be packaged into a ziplocked pouch
      by Infinit Nutrition in power form. Participants will be required to add water to the power
      at home. During day 0 - 2 (unsupplemented period) the beverage will be a placebo
      (maltodextrin and sucrose), and during day 3 - 5 (leucine supplementation period) the
      beverage will contain crystalline leucine (5 g) with sucrose for flavour. The beverages will
      be provided in a single-blind manner, energy-matched and will be similar in odour, color, and
      taste. Participants will also be blinded to their group allocation.

      Aminoacidemia, insulinemia and glycaemia will be determined in response to breakfast, lunch
      and dinner ingestion during the unsupplemented (day 2) and leucine supplemented (day 5)
      periods. During each of these blood sampling trials blood samples will be obtained
      immediately before and 20, 40, 60, 90, 120, 180, 240 min following the ingestion of each meal
      (total of 25 x 4ml blood samples per participant per trial).

      Integrative MPS will be measured in the exercised and non-exercised leg over the
      unsupplemented (day 0 - 3) period and leucine supplemented (day 3 - 6) period using orally
      ingested deuterated water (D20) and muscle biopsies obtained from the vastus lateralis on
      days 0, 3 and 6. Participants will report to the laboratory in the fasted state on day 0 and,
      following a muscle biopsy from the vastus lateralis and saliva sample, participants will
      consume a single 100 ml oral bolus of D20 at approximately 0900. Immediately following the
      D20 bolus participants will perform a bout of unilateral leg extension exercise (3 sets to
      volitional failure at the maximum load they can lift for 15-24 repetitions (~40-50% 1-RM)).
      On day 3 participants will perform an identical resistance exercise session with the
      exception that repetitions will be clamped at the number achieved on day 0. Following both
      exercise sessions participants will consume their individualized breakfast (with the placebo
      beverage on day 0 and with the leucine beverage on day 3) in the laboratory before returning
      home. Bilateral muscle biopsies will be obtained prior to the exercise on day 3 (end of
      unsupplemented period) and on day 6 (end of leucine supplemented period). Total body water
      deuterium enrichment can be used as a surrogate for plasma alanine labelling and will be
      determined from saliva swabs collected by the participant every morning at 0900. Participants
      will be instructed to not eat or drink anything for 30 min before saliva sampling and samples
      will be stored in the participant's freezer before their next visit to the laboratory.
    

Intervention name(s): Leucine; Placebo
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): 5 g leucine with sucrose and maltodextrin; 5 g glycine with sucrose and maltodextrin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Prevention
Keywords: Leucine; Protein; Diet; Muscle protein synthesis