Brook · Clinical nutrition (Edinburgh, Scotland) 2021 · randomized trial · n=8

A collagen hydrolysate/milk protein-blend stimulates muscle anabolism equivalently to an isoenergetic milk protein-blend containing a greater quantity of essential amino acids in older men.

Cited 12 times in the scientific literature.

Level 2 - randomized trial

Individual randomized trial

PubMed 33487503 · doi:10.1016/j.clnu.2021.01.002 · record verified 2026-08-29

What was done

Eight healthy older men (age 71 ± 1 years, BMI 27 ± 1 kg/m²) participated in a randomized trial comparing two isoenergetic oral nutritional supplements providing 20 g of protein: a collagen protein hydrolysate plus milk protein blend (CP+MP; Fresubin 3.2 kcal DRINK, 125 ml) versus a non-blended milk protein source (MP, 200 ml) containing higher essential amino acids (EAA). Vastus lateralis (VL) muscle protein synthesis (MPS) and plasma amino acids were measured using stable isotope-tracer mass spectrometry, and anabolic signaling was assessed via immunoblotting from muscle biopsies taken at baseline and 2 and 4 hours post-feeding. Measures were evaluated at rest after feeding (FED) and after feeding combined with unilateral leg resistance exercise (FED-EX; 6 × 8 reps at 75% 1-RM). Plasma insulin was measured via ELISA.

What was found

MP resulted in a greater increase in plasma leucine (mean 152 ± 6 μM vs 113 ± 4 μM, P < 0.001) and total EAA (mean 917 ± 25 μM vs 786 ± 15 μM, P < 0.01) compared to CP+MP. CP+MP increased plasma glycine (peak 385 ± 57 μM, P < 0.05), proline (peak 323 ± 29 μM, P < 0.01), and non-essential amino acids (peak 1621 ± 107 μM, P < 0.01), whereas MP showed no increase. Peak plasma insulin was greater with CP+MP (58 ± 10 mU/mL) than MP (42 ± 6 mU/mL, P < 0.01). Despite these differences, MPS increases were equivalent between CP+MP and MP under FED (MP: 0.039 ± 0.005%/h to 0.081 ± 0.014%/h, P < 0.05; CP+MP: 0.042 ± 0.004%/h to 0.085 ± 0.007%/h, P < 0.05) and FED-EX (MP: 0.039 ± 0.005%/h to 0.093 ± 0.013%/h, P < 0.01; CP+MP: 0.042 ± 0.004%/h to 0.105 ± 0.015%/h, P < 0.01) conditions. Muscle p-mTOR fold-change increased more with CP+MP during FED (P < 0.05), and p-eEF2 fold-change decreased more with CP+MP during FED-EX (P < 0.05); otherwise anabolic signaling was indistinguishable.

Why it matters

This study shows that blending collagen hydrolysate with milk protein can stimulate acute postprandial muscle protein synthesis to the same extent as pure milk protein in older men, despite providing lower essential amino acid and leucine content.

Limits

The study had a very small sample size (n = 8) and included only healthy older men, limiting generalizability to women, sarcopenic patients, or clinical populations. It measured only acute 4-hour fractional synthetic rates and signaling pathways rather than long-term gains in muscle mass, strength, or physical function.

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