Table 5.

Collagen-derived proteins: effects on muscle in relation to age, exercise, energy restriction and source.

Reference	Study Design	Protein Composition	Measurements	Key Outcomes
Oikawa et al., 2020 [27]	Double-blind, parallel group, randomised controlled trial (RCT) within-subject design (unilateral leg—rest, contralateral leg—resistance exercise (RE)) 22 healthy older female (F) (n = 11/group, 69 ± 3 years, mean ± standard deviation (SD)) Randomised to collagen protein or whey protein 2 ×/d for 6 d and unilateral RE twice during 6 d period	Collagen protein—30 g amino acids (AA) of hydrolysed collagen protein Whey protein—30 g AA of whey protein isolate (breakdown of AA composition within each supplement can be found in original article)	Myofibrillar and collagen protein synthesis, cell signalling, baseline body composition and strength	Plasma leucine concentrations increased above baseline post whey protein, but not collagen peptide supplementation Myofibrillar muscle protein synthesis (MPS) increased at rest and post-RE following whey protein, but only increased post-RE following collagen peptide supplementation Collagen peptide supplementation did not influence integrated myofibrillar MPS Rates of integrated myofibrillar MPS significantly greater in whey protein than collagen peptide supplementation
Kirmse et al., 2019 [128] (uses data set from Oertzen-Hagemann et al., 2019)	Randomised, double-blind, placebo-controlled design 57 moderately trained males (M) (24 ± 3 years, mean ± SD) were randomised to full-body resistance exercise training (RET) 3 ×/week for 12 weeks and collagen peptide (n = 29) or placebo (n = 28) Supplements taken daily for 12 weeks	Hydrolysed collagen peptide—15 g/d Placebo—15 g/d noncaloric silicon dioxide	Body composition, muscle thickness, strength, muscle fibre cross sectional area (CSA), dietary analysis	Strength and type II CSA increased in both groups Fat free mass (FFM) significantly increased in the collagen peptide group, not placebo Body fat mass (FM) did not change in the collagen peptide group but increase in the placebo group No difference in macronutrient intake between groups Protein intake was 1.81 ± 0.42 and 1.74 ± 0.5 g/kg/d in collagen and placebo groups, respectively
Zdzieblik et al., 2015 [26]	Randomised, double-blind, placebo-controlled design 53 older (72.2 ± 4.68 years, mean ± SD) sarcopenic M randomised to full body RET 3 ×/week for 12 weeks and collagen peptide (n = 26) or placebo (n = 27) Supplements taken daily for 12 weeks	Collagen peptide—15 g/d Placebo—15 g/d silicon dioxide (breakdown of AA composition within collagen peptide supplement can be found in original article)	Body composition, strength, dietary analysis	Increase in FFM and strength greater in collagen peptide versus placebo group Decrease in FM was greater in collagen peptide versus placebo group No difference in dietary intake between groups pre or post intervention and neither were protein deficient
Jendricke et al., 2019 [135]	Randomised, double-blind, placebo-controlled design 77 premenopausal untrained F were randomised to full body RET 3 ×/week for 12 weeks and collagen peptide (n = 40, 38.3 ± 8.7 years) or placebo (n = 37, 41.6 ± 6.9 years) (mean ± SD) Supplements taken daily for 12 weeks	Collagen peptide—15 g/d Placebo—15 g/d noncaloric silicon dioxide	Body composition, strength	Increase in FFM and hand grip strength was higher in collagen peptide versus placebo group Decrease in percentage body fat was greater in collagen peptide versus placebo group
Oertzen-Hagemann et al., 2019 [28]	Randomised, double-blind, placebo-controlled design 25 M (24.2 ± 2.6 years, mean ± SD) were randomised to full body RET 3 ×/week for 12 weeks and collagen peptide (n = 12) or placebo (n = 13) Supplements taken daily for 12 weeks	Hydrolysed collagen peptide—15 g/d Placebo—15 g/d noncaloric silicon dioxide	Body composition, strength, proteome	Collagen peptide is bioactive, demonstrated by increased circulating levels of hydroxyproline 2 h following collagen peptide ingestion Body mass and FFM higher in collagen peptide group versus placebo 221 higher abundant proteins identified in collagen peptide group versus on 44 in placebo (proteomic analysis) Upregulated proteins in the collagen peptide group mostly associated with protein metabolism of contractile fibres
Hays et al., 2009 [127]	Double-blind, randomised, cross-over design 9 healthy F (71 ± 1 years, mean ± standard error of the mean (SEM)) completed 2 × 15 d trials (7 d wash-out period in between) Each trial consisted of consuming 0.8 g protein/kg body weight/d with either whey protein or collagen peptide intended to provide ~0.4 g/kg body weight/d	Hydrolysed collagen peptide—~0.4 g/kg body weight/d Whey protein—~0.4 g/kg body weight/d	Body composition, nitrogen balance, dietary analysis	Body weight decreased after whey but not collagen protein intake Nitrogen excretion was higher during whey versus collagen protein intake No difference in macronutrient intake between collagen peptide and whey protein groups (protein intake was 0.82 ± 0.04 g/kg/d)
Oikawa et al., 2018 [77]	Double-blind, parallel group, RCT 16 M (69 ± 3 years) and 15 F (68 ± 4 years) were randomised to collagen peptide (n = 15) or whey protein (n = 16) and completed 4 phases: 1. 1-week energy balance 2. 1-week energy restriction (−500 kcal/d) and protein supplementation (1.6.g protein/kg/d with 45 ± 9% from whey protein (30 g 2 ×/d) or collagen peptide (30 g 2 ×/d)) 3. 2-week energy restriction with step reduction (≤750 steps/d) 4. 1-week habitual activity (continuing the high protein supplementation protocol) (mean ± SD)	Hydrolysed collagen peptide—30 g Whey protein isolate—30 g (breakdown of AA composition within each supplement can be found in original article)	Myofibrillar MPS, body composition, fascicle CSA, inflammation, insulin sensitivity	Protein supplementation (whey protein or collagen peptide) did not prevent leg LM loss during energy restriction and energy restriction with step reduction Whey protein, but not collagen peptide, augmented lean body mass, leg LM and MPS during habitual activity MPS remained suppressed during the energy restriction with step reduction and habitual activity phases in the collagen peptide group
Impey et al., 2018 [129]	Repeated-measures, counterbalanced design 7–9 d wash-out period 8 recreational M cyclists (25 ± 3 years, mean ± SD) completed an exercise trial in conditions of reduced carbohydrate with hydrolysed collagen or whey protein consumed before, during and after exercise	Hydrolysed collagen blend—22 g (66 g total) taken pre, during and post-exercise Whey protein—22 g (66 g total) taken pre, during and post-exercise	Cell signalling, muscle mitochondria markers	No effect of hydrolysed collagen (or whey protein) on markers of muscle mitochondrial adaptations Hydrolysed collagen supplementation increased anabolic signalling but to a lesser extent than whey protein
Clifford et al., 2019 [29]	Double-blind, placebo-controlled, independent group design 24 recreationally active M were randomised to collagen peptide (n = 12, 24.1 ± 4.3 years) or placebo (n = 12, 24.8 ± 4.8 years) supplementation 7 d before and 2 d after exercise (mean ± SD)	Collagen peptide—20 g/d Isoenergetic and isovolumic placebo—20 g/d	Muscle function, dietary analysis	Countermovement jump recovered quicker following collagen peptide supplementation (versus placebo) No difference in macronutrient intake between groups throughout the study Protein intake was 1.26 ± 0.46 and 1.18 ± 0.27 g/kg/bm−1 for collagen peptide and placebo groups, respectively.
Rindom et al., 2016 [132]	Double-blind, randomised, cross-over design 12 young M (24.6 ± 2.1 years, mean ± SD) completed 1 week of intense full-body RET (4 RET sessions) whilst consuming collagen protein or whey protein, followed by 3 weeks recovery, then completed another 1-week period of intense RET whilst consuming collagen or whey protein (opposite to the type ingested during the first week)	Collagen protein—20 g/d Whey protein—20 g/d During the intense RET period, all volunteers received 1.4 g protein/kg bodyweight in addition to the study supplement (i.e., whey/collagen protein)	Muscle function	48 h after the final exercise bout, maximal voluntary contraction had returned to baseline in both groups. No difference was noted between whey or collagen protein groups at any timepoint 48 h after the final exercise bout, counter movement jump (CMJ) height had returned to baseline in the collagen protein, but not whey protein, supplemented group 3 h after the final exercise bout, whey protein supplemented group displayed attenuated losses in CMJ compared to collagen protein
Oikawa et al., 2019 [130]	Double-blind, randomised, cross-over design 4 d wash-out 11 endurance trained adults (M n = 5, F n = 6, 24 ± 4 years, mean ± SD) engaged in daily high-intensity interval training with hydrolysed collagen or α-lactalbumin supplementation for 3 d	Hydrolysed collagen peptides—60 g/d α-lactalbumin—60 g/d (breakdown of AA composition within each supplement can be found in original article)	Myofibrillar and sarcoplasmic MPS, dietary analysis	Plasma leucine and tryptophan concentrations were greater following α-lactalbumin compared to hydrolysed collagen supplementation Exercise-induced increased in myofibrillar and sarcoplasmic MPS were greater with α-lactalbumin compared to hydrolysed collagen supplementation No differences in macronutrient intake between groups
Centner et al., 2019 [137]	Prospective, randomised, placebo-controlled design Older M randomised to 8 weeks blood flow resistance (BFR) training with collagen hydrolysate (n = 11, 61.7 ± 5.5 years) or 8 weeks BFR training with placebo (n = 11, 56.6 ± 6.1 years) or no training with collagen hydrolysate (control) (n = 8, 62.5 ± 10.5 years) (mean ± SD)	Collagen hydrolysate—15 g/d Placebo—silicon dioxide—15 g/d	CSA and muscle function	Muscle CSA increase in BFR-collagen hydrolysate (+6.7% ± 3.2%) and BFR-placebo (+5.7% ± 2.7%) but not in control 1-repition maximum strength increased in BRF-collagen hydrolysate (+10.2% ± 24.8%), and BFR-placebo (+4.8% ± 11.4%) but not control, relative to pre-study levels

Abbreviations: AA, amino acid; BFR, blood flow restriction; counter movement jump, CMJ; CSA, cross-sectional area; F, females; FFM, fat-free mass; FM, fat mass; M, males; MPS, muscle protein synthesis; RCT, randomised controlled trial; RE, resistance exercise; RET, resistance exercise training; SD, standard deviation; SEM, standard error of the mean.