Tier 3 — preclinical

Vitamin C–Enriched Gelatin Supplementation before Intermittent Activity Augments Collagen Synthesis

Gregory Shaw, Ann Lee-Barthel, Megan L.R. Ross, Bing Wang, Keith Baar
American Journal of Clinical Nutrition 2017 105(1):136-143

Bibliography

PubMed
PMID 27852613
PubMed Central
PMC5183725
DOI
10.3945/ajcn.116.138594
Funding
Supported by a National Institute on Aging project grant (R01AG045375 to K. Baar); University of California, Davis College of Biological Sciences (to K. Baar); and an Australian Institute of Sport sport nutrition research grant (to G. Shaw). None of the funders had a role in the design, implementation, analysis, or interpretation of the data.
Competing interests
The authors reported no conflicts of interest related to the study.

Study snapshot

DesignRandomised, double-blinded, crossover trial in humans, with an accompanying ex vivo engineered-ligament bioassay
ModelHealthy, recreationally active young men
Samplen=8 (crossover design; all subjects completed all three treatment arms). Serum from 4 of the 8 subjects was additionally used in the engineered-ligament bioassay.
InterventionVitamin C-enriched gelatin (0, 5 or 15 g, with 48 mg vitamin C), consumed 1 hour before each of four bouts of 6 minutes of rope-skipping exercise over 3 days (3 sessions/day, ≥6 hours apart), in a randomised crossover design with a 4-day washout between treatments
Duration72 hours (acute supplementation-and-exercise protocol per treatment arm, with blood sampling out to 72 hours post-exercise)
EndpointsCirculating glycine, proline, hydroxyproline and hydroxylysine (HPLC amino acid analysis); Serum N-terminal propeptide of collagen I (PINP), a biomarker of collagen synthesis; Collagen content and tensile mechanics of engineered ligaments treated with post-supplementation serum (ex vivo bioassay)

What the study showed, in plain terms

This is a small mechanistic study, not a clinical trial of a commercial collagen peptide product — it is included here because it offers a plausible biological explanation for why timing a collagen-rich supplement around exercise might matter.

Eight young men consumed 0, 5 or 15 g of vitamin C-enriched gelatin an hour before short bouts of rope-skipping, repeated several times over three days. The amino acids that make up collagen (glycine, proline, hydroxyproline, hydroxylysine) rose in the blood in a dose-dependent way, peaking about an hour after the drink.

In a laboratory bioassay, serum collected after the 15 g dose supported measurably more collagen production and stronger tissue when used to grow engineered ligaments, and blood markers of collagen synthesis roughly doubled after exercise in the 15 g group compared with placebo. This is best read as mechanistic support for exercise timing around collagen/gelatin intake, not as evidence for any specific collagen peptide product's clinical effects.

Key findings

  • Collagen-associated amino acids (glycine, proline, hydroxyproline, hydroxylysine) rose in a dose-dependent manner, peaking 1 hour after ingestion of the supplement.
  • Engineered ligaments treated with serum collected 1 hour after gelatin ingestion showed dose-dependent increases in collagen content and mechanical strength (maximal tensile load, modulus, ultimate tensile strength) compared with pre-supplementation serum.
  • Subjects who consumed 15 g gelatin 1 hour before exercise showed roughly double the serum PINP (a marker of collagen synthesis) at 4 hours post-exercise compared with placebo, an effect maintained through 72 hours.
  • The branched-chain amino acid leucine, not enriched in collagen, showed no differences between treatment groups, consistent with the effect being specific to collagen-derived amino acids rather than general protein intake.

What this study can and cannot tell us

  • Very small human cohort (n=8), typical of an exploratory mechanistic study but underpowered for definitive clinical conclusions.
  • Primary outcomes are surrogate/mechanistic biomarkers (circulating amino acids, serum PINP, engineered-ligament tissue culture) rather than a clinical outcome such as pain, injury rate or function.
  • PINP in blood is generally considered a marker of bone collagen turnover rather than tendon, ligament or cartilage synthesis specifically, so the in vivo result may primarily reflect bone rather than connective tissue elsewhere in the body — the authors are explicit about this uncertainty.
  • Tests plain gelatin (a food-grade collagen derivative) plus vitamin C, not a standardised hydrolysed collagen peptide supplement, and only in the context of a specific acute exercise-timing protocol.

Related papers in the corpus

Tier 4
Effect of Vitamin C and Its Derivatives on Collagen Synthesis and Cross-Linking by Normal Human Fibroblasts
N. Boyera et al. · International Journal of Cosmetic Science · 1998

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Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability Dr. Abdulla Mostafa, PhDCellular Senescence, Neurological, Mitochondrial & Brain-Ageing Biology