Collagen Vitamin C Dose Response Performance
Condition: Healthy Volunteers
Study type: Interventional

Summary: 
      Previous work has shown that gelatin supplementation could increase collagen synthesis in
      humans. In this study subjects consume placebo, 5 or 15 g of gelatin with a standard amount
      of vitamin C (48 mg) 1 hour before 6 minutes of jump rope exercise. The feeding and exercise
      intervention was repeated every 6 hours while the subjects were awake for three days and the
      amount of the amino terminal procollagen I peptide (PINP) was determined; a marker of
      collagen synthesis, in the blood. Consistent with the hypothesis that gelatin increases
      collagen synthesis in humans; the amount of PINP in the 15 g gelatin group was significantly
      higher than either the placebo or the 5 g groups. These data conclusively demonstrate that
      gelatin supplementation can increase exercise-induced collagen synthesis in humans.
      Hydrolyzed collagen has a similar amino acid profile, in particular with high concentrations
      of glycine, proline, hydroxyproline, and arginine. Thus the current study aims to precisely
      map out the dose response relationship of hydrolyzed collagen and vitamin C on PINP and to
      determine the optimal dose to achieve maximal increased in PINP levels.
    

Detailed description: 
      In preliminary work investigating the physiological determinants of maximal performance in
      throwing events, researchers found that the best predictor of elite performance was the rate
      of force development (RFD; Force (N) x time (sec)) when performing and isometric squat.
      Therefore, it is not surprising that in order to maximize performance, athletes train to
      optimize RFD.

      RFD is determined by three factors:

        1. Neural activation of the muscles

        2. Type of motor protein (fast or slow myosin)

        3. Force transfer Interestingly, performance in power movements (that are highly dependent
           on RFD) like vertical jump is closely related to tendon stiffness and inversely related
           to muscle size. This indicates that force transfer, in the form of tendon stiffness,
           plays an important role in performance and can explain a large amount of variance in
           determining an athlete's ability to rapidly develop force during a dynamic movement.

      The stiffness of a tendon is determined by the amount and cross-linking of collagen within
      the tissue. Acute exercise is known to increase collagen synthesis as well as the expression
      of the primary enzyme involved in collagen cross-linking, lysyl oxidase. The result is a
      denser and stiffer tissue after training. Even though the relationship between exercise and
      collagen synthesis is known, whether this measure of performance can be improved with
      nutritional interventions has not been determined.

      A recent study looking at amino acid levels following consumption of increasing doses of
      gelatin (derivative of collagen) in human subjects has shown that the key primary and trace
      amino acids found in collagen increase in human serum after consuming gelatin. Further, the
      peak of these amino acids occurs 60 minutes after consuming the gelatin supplement.
      Therefore, consuming a collagen supplement 1 hour before an exercise intervention should
      maximize delivery of amino acids to bone and other connective tissues.

      To determine whether the gelatin supplement could increase collagen synthesis in humans,
      subjects consumed placebo, 5 or 15 g of gelatin with a standard amount of vitamin C (48 mg) 1
      hour before 6 minutes of jump rope exercise. The feeding and exercise intervention was
      repeated every 6 hours while the subjects were awake for three days and the amount of the
      amino terminal procollagen I peptide (PINP) was determined; a marker of collagen synthesis,
      in the blood. Consistent with the hypothesis that gelatin increases collagen synthesis in
      humans; the amount of PINP in the 15 g gelatin group was significantly higher than either the
      placebo or the 5 g groups. These data conclusively demonstrate that gelatin supplementation
      can increase exercise-induced collagen synthesis in humans.

      Similarly, supplementation with collagen hydrolysate has previously been shown to improve
      cartilage function in a randomized clinical trial in patients with osteoarthritis [9].
      McAlindon and colleagues showed that consuming 10 g of collagen hydrolysate per day resulted
      in an increase in gadolinium enhanced MRI of collagen [9]. This finding suggests that the
      hydrolyzed collagen increased cartilage formation. In agreement with this finding, a 24-week
      randomized clinical trial in athletes showed that 10 g of GELITA® collagen hydrolysate
      significantly decreased knee pain. Mouse studies using C14 labeled hydrolyzed collagen
      hydrolysate demonstrated that >95% of the hydrolyzed collagen was absorbed in the first 12
      hours after feeding. Interestingly, even though tracer from a separate C14 labeled proline
      could be incorporated into skin collagen at the same rate as tracer from hydrolyzed collagen,
      tracer from the hydrolyzed collagen was incorporated into the collagen of cartilage and
      muscle two-fold more than the tracer from proline. These data suggest that musculoskeletal
      collagen synthesis is greater in response to gelatin or hydrolyzed collagen than to the
      individual amino acids.

      Even though the blood measure of PINP levels likely reflects bone collagen synthesis, using
      an engineered ligament model, a similar response has been demonstrated in tendons/ligaments
      treated with serum from people 1 hour after supplementation with gelatin. This work has shown
      that in the presence of serum isolated from the 5 and 15 grams of gelatin groups a step-wise
      increase in the collagen content of the ligaments. From this work, it can be ascertained that
      PINP can be used dependably as an indirect marker of collagen synthesis and that the changes
      observed in bone (blood levels) reflect what is occurring in other connective tissues as
      well.

      The current study aims to precisely map out the dose response relationship of hydrolyzed
      collagen and vitamin C on PINP and to determine the optimal dose to achieve maximal increased
      in PINP levels. Secondly, whether this optimal dose of hydrolyzed collagen and vitamin C,
      taken before training is sufficient to improve RFD and performance will be determined. To
      achieve this goal, subjects will first consume increasing doses of hydrolyzed collagen (0
      (control), 5, 10, 20 and 30 g) alongside a constant amount of vitamin C (50 mg). Once the
      optimal dose of hydrolyzed collagen is determined this dose will be administered with
      increasing doses of vitamin C (0 (control), 50, 250, 500 mg) to determine the optimal dose of
      vitamin C to maximize PINP levels. Both hydrolyzed collagen and vitamin C supplementation
      will be given 1 hour before 6 minutes of jump rope exercise.

      After the optimal doses of hydrolyzed collagen and vitamin C are determined, the effects of
      the optimal dose of hydrolyzed collagen and vitamin C on performance will be assessed.
      Subjects will undergo an explosive/power-based exercise training program three days a week
      (Monday/Wednesday/Friday) for three weeks. The hydrolyzed collagen and vitamin C will be
      ingested 1 hour before each training session. Baseline exercise testing will take place at
      week 0, then exercise testing will occur on Friday of each week (week 1, 2 and 3). Subjects
      will undergo a series of tests to determine the RFD in the isometric squat, and
      countermovement and squat jump height.
    

Intervention name(s): Hydrolyzed collagen; Vitamin C; Optimized Hydrolyzed Collagen and Vitamin C; Gummy Placebo
Intervention type(s): Dietary Supplement; Dietary Supplement; Dietary Supplement; Dietary Supplement
Intervention description(s): Escalating dose of Hydrolyzed collagen; Escalating dose of Vitamin C; combination of optimized doses of Hydrolyzed Collagen and Vitamin C; Gummy placebo
Intervention MeSH terms: Vitamins; Ascorbic Acid
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: A double blinded cross over design where subject are randomized to consume all 5 intervention doses.
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: collagen; tendon; procollagen type I N-terminal; athletes; vitamin C; hydrolyzed collagen