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Whey protein but not collagen peptides stimulate acute and longer-term muscle protein synthesis with and without resistance exercise in healthy older women: a randomized controlled trial

Sara Y. Oikawa, Michael J. Kamal, Erin K. Webb, Chris McGlory, Steven K. Baker, Stuart M. Phillips
The American Journal of Clinical Nutrition 2020 111(3):708–718

Bibliography

PubMed
PMID 31919527
PubMed Central
PMC7049536
DOI
10.1093/ajcn/nqz332
Funding
Supported by Canadian Institutes of Health Research grant 399384 (to SMP).
Competing interests
SMP reports having received competitive research funding, travel expenses, and honoraria for speaking from the US National Dairy Council and the Dairy Farmers of Canada. All other authors report no conflicts of interest. Additional per subsequent corrigendum (Am J Clin Nutr 2020;112(6):1656; PMID 33301004): Dr. Stuart Phillips reports personal fees from Enhanced Recovery and equity from Exerkine, outside the submitted work. In addition, Dr. Phillips has a patent 3,052,324 issued to Exerkine, and a patent 16/182,891 pending to Exerkine. Biohack Blueprint assessment: The senior author has substantial and repeated funding relationships with the dairy industry, which is the commercial beneficiary of a finding favourable to whey protein. This is directly relevant to interpretation of the paper's conclusion and was expanded in a formal corrigendum after publication.

Study snapshot

DesignRandomised, double-blind, parallel-group controlled trial using [¹³C₆]-phenylalanine infusion for acute muscle protein synthesis and D₂O oral tracer for longer-term integrated MPS
ModelHealthy postmenopausal women aged 60–80 (mean 69 ± 3), non-diabetic, non-smoking, 3500–10,000 steps/day
Samplen=22 randomised (11 per group); n=15 with usable myofibrillar MPS data due to laboratory equipment malfunction (8 whey, 7 collagen); n=22 with collagen protein synthesis data
Intervention30 g whey protein isolate (Fonterra) twice daily versus 30 g hydrolysed collagen (Gelita Bodybalance) twice daily for 6 days, on top of a controlled 1.6 g/kg/day protein diet. Two bouts of unilateral leg resistance exercise (~60% 1RM) during the 6-day period allowed within-person comparison of feeding (rest leg) vs feeding-plus-exercise (exercise leg).
Duration6 days total supplementation; acute MPS measured 0–4 h post-feeding on day 0; integrated MPS measured across days 0–6
EndpointsPrimary: acute fractional synthetic rate of myofibrillar muscle protein synthesis (%/h) and longer-term integrated MPS (%/d), in rested and exercised legs; Secondary: intramuscular collagen protein synthesis; Plasma amino acid concentration-time curves; mTOR pathway phosphorylation (4EBP1, AKT, mTOR, p70S6K, S6) by Western blot

What the study showed, in plain terms

Researchers gave 22 healthy older women a controlled diet plus a 30 g protein drink twice a day for six days — either whey protein or an equivalent amount of hydrolysed collagen. During the six days, each woman did resistance exercise on one leg only, twice, so that the exercised leg and the rested leg in the same person could be compared. They used two stable-isotope tracer techniques to measure how fast the muscles in each leg were building new protein: one for the acute response after a single meal, and one for the cumulative response across the whole six days.

Whey protein clearly stimulated muscle protein building — acutely after ingestion, and cumulatively across the six-day window — in both the rested leg and the exercised leg. The exercised leg responded even more strongly than the rested leg. Collagen, by contrast, did not raise the muscle protein building rate above baseline in the rested leg, and only produced a small increase in the exercised leg. Across every comparison, whey produced significantly more muscle protein synthesis than collagen.

Interestingly, collagen also did not stimulate intramuscular collagen protein synthesis specifically — despite being rich in the exact amino acids (glycine, proline) that intramuscular collagen is built from. Exercise did stimulate collagen protein synthesis in both groups, but the type of protein supplement did not matter for that outcome. The message is straightforward: for older women trying to build or preserve muscle, whey protein is the better supplement choice, and even the best protein supplement is more effective when combined with resistance exercise.

Key findings

  • Acute myofibrillar MPS: whey increased MPS by 0.017 ± 0.008 %/h in the rested leg and 0.032 ± 0.012 %/h in the exercised leg (both p<0.01 vs baseline). Collagen produced no significant rise in the rested leg and only a 0.012 ± 0.013 %/h rise in the exercised leg.
  • Acute MPS was significantly greater in whey than collagen in both rested and exercised legs (p=0.02).
  • Integrated 6-day MPS: whey increased MPS by 0.063 ± 0.059 %/d in the rested leg and 0.173 ± 0.104 %/d in the exercised leg (both p<0.0001 vs baseline). Collagen produced no significant increase above baseline in either leg.
  • Integrated MPS was significantly greater with whey than collagen in both conditions (p<0.0001).
  • Plasma leucine peak: 645 ± 206 μM after whey versus 223 ± 117 μM after collagen (p<0.001). Leucine AUC significantly higher after whey (p=0.012).
  • Plasma essential amino acid AUC and Cmax significantly higher after whey than collagen (both p=0.003).
  • Intramuscular collagen protein synthesis increased with resistance exercise (p=0.01) but did not differ between supplement groups (p=0.154).
  • mTOR pathway phosphorylation (4EBP1, AKT, mTOR, p70S6K, S6) at 4 hours post-feeding did not differ between supplement groups.

What this study can and cannot tell us

  • Small sample. The primary MPS analysis is based on n=15 (8 whey, 7 collagen) due to a laboratory equipment malfunction that lost samples from 7 randomised participants. This substantially reduces statistical power and increases the influence of individual variation.
  • Short duration (6 days). The trial cannot address whether longer-term collagen supplementation might produce cumulative effects via slower or indirect pathways not captured by 6-day integrated MPS.
  • Single-sex (women), single-age-band (60–80), single-ethnicity healthy cohort. Findings may not generalise to older men, frail older adults, or those with metabolic or catabolic conditions.
  • MPS is a mechanistic endpoint, not a functional one. The paper does not measure muscle mass, strength, or physical function directly — those endpoints require longer trials (see Zdzieblik 2021 in this corpus, which shows a functional effect of collagen despite this trial showing no acute MPS effect). The apparent contradiction may reflect different mechanisms operating over different timescales.
  • Anabolic signalling (mTOR pathway) was measured only at 4 h post-feeding. Peak phosphorylation may have occurred earlier and been missed.
  • The dose used (60 g/day = 30 g × 2) is at the high end of typical clinical supplementation and may not represent effects at lower doses.
  • Whey protein content was 46% EAA and delivered ~5.5× more leucine per serving than collagen. Because the mechanism the paper measures (MPS via mTOR/leucine signalling) is specifically sensitive to leucine, the outcome partly reflects the difference in leucine content rather than being a fair test of "protein quality" for all muscle-relevant purposes.
  • Senior author has substantial dairy industry funding relationships, which are directly relevant to a study concluding in favour of a dairy protein. The formal COI was expanded post-publication via corrigendum.
  • Only one specific collagen hydrolysate was tested (Bodybalance). Different collagen preparations may not behave identically.

Related papers in the corpus

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The Influence of Specific Bioactive Collagen Peptides on Body Composition and Muscle Strength in Middle-Aged, Untrained Men: A Randomized Controlled Trial
Denise Zdzieblik et al. · International Journal of Environmental Research and Public Health · 2021

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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