Effects of Whey and Collagen Protein Blend on Protein Synthesis Rates
Condition: Muscle Protein Synthesis
Study type: Interventional

Summary: 
      Rationale: Protein ingestion stimulates muscle protein synthesis and augments the muscle
      protein synthetic response to a single exercise session. In support, protein supplementation
      has been shown to augment the gains in muscle mass and strength following resistance exercise
      training. The force generated by contracting muscle is transferred through a network of
      connective tissue proteins towards the bone. Consequently, remodeling of skeletal muscle
      connective tissue represents an essential component of skeletal muscle adaptation to
      exercise. The anabolic effect of a protein supplement is mainly determined by the plasma
      amino acid response after ingestion. Although whey protein is considered the preferred
      protein source to maximize myofibrillar protein synthesis rates, it contains insufficient
      glycine and proline to support the post-exercise increase in connective tissue protein
      synthesis rates. In contrast, collagen protein is rich in glycine and proline and has,
      therefore, been proposed as a preferred protein source to support connective tissue
      remodeling. Hence, the combined ingestion of whey plus collagen protein may therefore be
      preferred to stimulate both myofibrillar and collagen protein synthesis rates in skeletal
      muscle tissue. The most ideal protein supplement for stimulating both myofibrillar and
      collagen protein synthesis is one that gives a rapid initial rise in plasma amino acid
      concentrations including leucine, proline and glycine concentrations. However, the effect a
      blend of whey and collagen protein on myofibrillar and connective tissue protein synthesis
      rates is unknown.

      Objective: To assess the effect of a whey and collagen protein blend versus a placebo on
      myofibrillar and connective tissue protein synthesis rates in muscle obtained during recovery
      from exercise and rest in vivo in humans.

      Study design: Double-blind, parallel-group, placebo-controlled intervention study.

      Study population: 28 healthy recreationally active males (18-35 y; BMI: 18.5-30 kg/m2).

      Intervention: Participants will perform unilateral resistance exercise followed by the
      ingestion of either a blend of 25 g whey and 5 g collagen protein or a non-caloric placebo
      (flavored water). Continuous intravenous stable isotope amino acid tracer infusions will be
      applied, and plasma and muscle samples will be collected in order to assess protein synthesis
      rates in muscle tissue.
    

Detailed description: 
      This study utilizes a double-blind, parallel-group, placebo-controlled intervention with two
      groups. In total, up to 38 healthy recreationally active male subjects (age: 18-35 y) will be
      included in the study, while 28 subjects need to finish the experimental test day. Subjects
      will perform a single unilateral resistance exercise session (leg press and leg extension)
      and will be randomly assigned to consume a beverage containing either a blend of 25 g whey
      and 5 g collagen protein or a placebo with non-nitrogenous, non-caloric flavored water. Blood
      and muscle biopsies will be collected while a primed continuous infusion of L-[ring-13C6]
      phenylalanine infusion will be administered. The duration of the entire study will be
      approximately 24 months. This period includes screening, testing and data analysis of all 28
      subjects. Subject testing will be done after approximately 12 months.

      Subjects will participate in one screening session. During this session, the study procedures
      will be explained again verbally and any remaining questions by the subject will be answered.
      Thereafter, the informed consent form will be signed. Subjects will be asked to fill in a
      medical questionnaire to gather information about their general health, medical history, use
      of medication and sports activities. Body height , body weight and body composition will be
      measured. The BIA is a simple and non-invasive procedure. Finally, subjects will be
      familiarized and tested for strength on the exercise machines (leg-press and leg-extension).
      Subjects will be instructed on proper single legged weight-lifting technique on each exercise
      machine (leg-press and leg-extension) and complete a standardized testing protocol to
      determine a measurement of maximal strength (1RM) on each exercise machine. The testing
      protocol requires that the subjects complete sets on each exercise machine increasing in
      weight until volitional fatigue occurs. The heaviest weight that could have been lifted with
      good execution of the exercise will be taken as the 1RM. Following the determination of 1RM,
      subjects will be scheduled for their experimental testing day.

      All subjects will consume a standardized dinner the evening before each test day. The
      subjects will receive the meal after the screening test in a thermal bag. The subjects will
      be instructed to store the meal in a freezer until preparation and to prepare the meal
      themselves according to the instructions on the label. All subjects will be instructed to
      refrain from any sort of heavy physical exercise and alcohol intake 2 days before the test
      day. In addition, subjects will be asked to record their food intake and physical activity
      for 48 h before the start of the test day in a diary that will be provided during the
      screening.

      Each subject will participate only in 1 experimental test day, which lasts ~9 h. The protocol
      is designed to assess the post-exercise plasma amino acid responses, myofibrillar and
      connective tissue protein synthesis.

      A general overview of the study protocol is shown in Figure 1. At 7:45 am, following an
      overnight fast, subjects will arrive at the laboratory by car or public transportation.
      Subjects will rest in a supine position and a Teflon catheter will be inserted in a heated
      dorsal hand vein and placed in a hot-box (60°C) for arterialized blood sampling. In the
      contralateral arm, another Teflon catheter will be inserted for stable isotope infusion. A
      basal arterialized venous blood sample will be collected (t = -210 min), after which a single
      intravenous dose of L-[ring-13C6] phenylalanine (Cambridge Isotopes, Andover, MA) will be
      administered. Thereafter, a continuous infusion of L-[ring-13C6] phenylalanine will be
      started (t = -210 min) using a calibrated space plus infusomat pump (Braun, Melsungen,
      Germany), running for 510 min. A muscle biopsy from the upper leg that will not perform the
      unilateral exercise session will be collected at t = -180 min as a reference to assess
      post-absorptive muscle protein synthesis rates. After the first muscle biopsy was performed,
      muscle thickness of the rectus femoris muscle will be measured via ultrasound. Arterialized
      venous blood samples will be collected at t = -210, -180, -120, -60 and 0 min. At t = -45
      min, a unilateral exercise, that consists of 4 sets of 8 repetitions on the leg press and leg
      extension machine at 80% 1RM 8 reps and last set until failure, will be performed. At t = 0
      min muscle biopsies will be collected from the vastus lateralis muscle of both the rested and
      exercised leg. Immediately following blood collection (t = 0 min), subjects will ingest a
      test drink containing a blend of 25 g whey and 5 g collagen protein (PRO) or a non-caloric
      placebo (CON). Following ingestion of the test drink, arterialized venous blood samples will
      be collected at t = 30, 60, 90, 120, 180, 240 and 300 min. Furthermore, an additional muscle
      sample will be collected from the rested and exercised leg at t = 300 min.
    

Intervention name(s): Whey/collagen protein blend; Resistance exercise
Intervention type(s): Dietary Supplement; Behavioral
Intervention description(s): Ingestion of 30g of protein dissolved in 300ml water consumed after an exercise session; A single resistance exercise session of the leg press and leg extension exercise
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Double-blind, parallel-group, placebo-controlled intervention study
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Basic Science