Collagen Vitamin C Dose Response Performance

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.

Inclusion Criteria:

- Collegiate level male athletes between 18 - 25 years of age

- Currently registered/participating as an intercollegiate athlete

- < 3 musculoskeletal injuries in the past year

- No health or dietary restriction that would be affected by the supplementation
protocol.

Exclusion Criteria:

- History of more than 3 musculoskeletal injuries within the past 12 months.

- Health, dietary restriction or diet that would be affected by the supplementation
protocol.

- Then initial phases of this study will be performed in males since collagen synthesis
varies significantly throughout the menstrual cycle in females. Since collagen in the
main outcome measure for this study this natural variation would confound the initial
phase of the work. Provided this work proves successful then we will aim to perform
similar studies in females.