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CompletedNCT03293004CollagenUpdated Aug 21, 2018

Collagen Vitamin C Dose Response Performance

An interventional study of Hydrolyzed collagen and Vitamin C in Healthy Volunteers, sponsored by University of California, Davis. Completed at 1 site in United States. Open to male participants aged 18 Years to 25 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2018-08-21.

Sponsored by University of California, Davis · Not applicable, Interventional, and Treatment

Phase
Not applicable
Study type
Interventional
Enrollment
23
Allocation
Randomized
Ages
18 Years to 25 Years
Sex
Male
01

Study 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.

Read the 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.

02

Conditions studied

  • Healthy Volunteers

Keywords

  • collagen
  • tendon
  • procollagen type I N-terminal
  • athletes
  • vitamin C
  • hydrolyzed collagen
03

In context

Lead sponsor

University of California, Davis is the lead sponsor of 810 studies on the registry; 142 are open to participants now.

Of its 67 completed or terminated interventional studies of FDA-regulated products, 43 (64%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 25 Years
Sexes eligible
Male
Accepts healthy volunteers
Yes

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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

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.
05

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Crossover assignment
Masking
Double (Participant, Investigator)
Enrollment
23 participants (actual)

Study arms

  • Experimental
    Hydrolyzed collagen

    First, we aim to determine the optimal amount of hydrolyzed collagen with a constant dose of vitamin C in humans to increase a marker of collagen synthesis (PINP). In a randomized, double-blinded, crossover design subjects consume a nutritional supplement with varying doses of hydrolyzed collagen (control (0 g), 5 10, 20 and 30 g hydrolyzed collagen) with a constant dose of vitamin C (50 mg). Each intervention will be separated by a 6-day wash out. Subjects will be asked to consume the supplement 1 hour before 6-min of jump rope exercise. Following completion of exercise, subjects will remain in the lab in a rested state for the subsequent 4 hours. After 4 hours and 24 hours blood samples will be collected. Blood samples will be used for PINP analysis.

    Dietary Supplement: Hydrolyzed collagen

  • Experimental
    Vitamin C

    Second, we aim to determine the optimal amount of vitamin C with the determined optimal dose of hydrolyzed collagen in humans to increase a marker of collagen synthesis (PINP). In a randomized, double-blinded, crossover design subjects consume a nutritional supplement with varying doses of vitamin C (0 (control), 50, 250 and 500 mg) with an optimized dose of hydrolyzed collagen as determined from the first arm. Each intervention will be separated by a 6-day wash out. Subjects will be asked to consume the supplement 1 hour before 6-min of jump rope exercise. Following completion of exercise, subjects will remain in the lab in a rested state for the subsequent 4 hours. After 4 hours and 24 hours blood samples will be collected. Blood samples will be used for PINP analysis.

    Dietary Supplement: Vitamin C

  • Experimental
    Optimized Collagen and Vitamin C supplement

    The findings from the first 2 arms of the study will be used to inform a training-based study aimed to determine whether exercise together with this optimal dose of hydrolyzed collagen and vitamin C is sufficient to improve rate of force development (RFD) and performance. A gummy food will be developed with the optimized dose of hydrolyzed collagen and vitamin C as well as a placebo. In a randomized, double-blinded, parallel design with subjects undertake a 3 week exercise protocol. The supplement will be ingested 1 hour prior to each exercise session (Monday/Wednesday/Friday). Exercise testing to assess rate of force development (RFD) will take place at the end of each week (Fridays) and these outcomes will be the basis for determining the effects of the nutrition intervention on performance.

    Dietary Supplement: Optimized Hydrolyzed Collagen and Vitamin C

  • Placebo comparator
    Gummy Placebo

    A gummy food will be developed with the optimized dose of hydrolyzed collagen and vitamin C as well as a placebo. In a randomized, double-blinded, parallel design with subjects undertake a 3 week exercise protocol. The supplement or placebo will be ingested 1 hour prior to each exercise session (Monday/Wednesday/Friday). Exercise testing to assess rate of force development (RFD) will take place at the end of each week (Fridays) and these outcomes will be the basis for determining the effects of the nutrition intervention on performance.

    Dietary Supplement: Gummy Placebo

Interventions

  • Dietary supplementHydrolyzed collagen

    Escalating dose of Hydrolyzed collagen

  • Dietary supplementVitamin C

    Escalating dose of Vitamin C

  • Dietary supplementOptimized Hydrolyzed Collagen and Vitamin C

    combination of optimized doses of Hydrolyzed Collagen and Vitamin C

  • Dietary supplementGummy Placebo

    Gummy placebo

06

What researchers measure

Primary outcomes

  1. PINP Levels

    To determine optimal dose of supplemental hydrolyzed collagen and vitamin C required to maximally elevate PINP levels (a marker of collagen synthesis) in healthy athletes.

    Time frame: 9 weeks

  2. Rate of force development (RFD)

    a measure of explosive strength

    Time frame: 3 weeks

07

Study locations

1 site
  • University of California Davis
    Davis, California 95616, United States
08

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

09

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reached

Ran from Sep 2017 to primary completion in May 2018, 8 months.

How these figures are worked out, and which studies are left out of them.

Registered
Sep 15, 2017
First posted
Sep 26, 2017
StartActual
Sep 13, 2017
Primary completionActual
May 24, 2018
CompletionActual
May 24, 2018
Last update
Aug 21, 2018
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Aug 21, 2018, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT03293004
Responsible party
Sponsor
First posted
Sep 26, 2017
Start date
Sep 13, 2017
Primary completion
May 24, 2018
Completion
May 24, 2018
Last update
Aug 21, 2018

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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Studies of the drugs tested here: Collagen · Ascorbic Acid

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