The purpose of this systematic review was to examine the effects of COL on exercise performance, recovery, and rehabilitation in the elderly, and elite and recreational athletes. The most prominent effects of COL were observed on joint function and recovery from joint injuries.
Effects of collagen supplementation on joint function and recovery from joint injuries
All five studies reported beneficial effects of COL in reducing joint pain, improving joint function, increasing the length of pain-free strenuous exertion, and reducing the need for alternative therapies, especially when combined with an exercise rehabilitation programme (Table 1). Both Clark and colleagues (2008) (10 g/day COL) and Zdzieblik et al. (2017) (5 g/day COL) observed that COL led to a decrease in activity-related joint discomfort and use of alternative therapies to manage pain (PLA alternative therapy use 3.25-fold higher than COL in the former study and COL resulted in a 59% decrease of therapies in the latter). Interestingly, even though Zdzieblik et al. (2017) supplemented for 12 weeks, it was still effective in alleviating joint symptoms. This is in contrast to Clark and colleagues (2008), who did not see a statistically significant improvement until the final visit at 24 weeks, implying that it may take ≥ 3 months to realise the benefits of COL. These results also suggest that 5 g/day COL may be as effective as 10 g/day COL in alleviating pain during activity for athletes, in the absence of a degenerative joint disease. A possible explanation for the reduction in joint pain may be that COL increases type I, II, IV collagen, proteoglycan, and elastin synthesis in the articular cartilage, possibly reducing tissue damage and decreasing pain (Oesser and Seifert 2003; Schunck and Oesser 2013). Collagen peptide supplementation may also aid formation of ECM molecules leading to increased firmness of the connective tissue, and downregulation of matrix metalloproteinases that degrade ECM collagen proteins (Schunck and Oesser 2013). Moreover, collagen peptides may possess anti-inflammatory properties, as glycine can inhibit pro-inflammatory cytokine release (e.g. interleukin-6; Hartog et al. 2013). However, more human studies are required to better understand the regulatory mechanisms of COL.
Young athletes had improved ankle function with COL, citing a lower feeling of the ankle ‘giving away’ and a decrease in reoccurrence of ankle injuries after suffering from chronic ankle instability (possibly having clinical applicability; Dressler et al. 2018). Nevertheless, the baseline CAIT scores were lower for COL than PLA, which may have led to difference in ankle function improvements in the target group. Similarly, Praet and colleagues (2019) coupled COL with an eccentric bi-daily calf strengthening and a return-to-running exercise protocol in athletes suffering from Achilles tendinopathy. The participants were able to return to running after the treatment but did not reach pre-injury levels within the duration of the study. The COL used contained 22% glycine, which is known to enhance collagen matrix organisation strength, reduce inflammation and influence tenocyte metabolism in tendons (Vieira et al. 2018). The eccentric training protocol used may have also improved the tendon structure and reduced neovascularization (associated with tendinosis; Ohberg and Alfredson 2004). Indeed, eccentric training can elicit a transformation in the ECM composition of skeletal muscles through the remodelling of endomysial type IV collagen (Mackey et al. 2004).
In a study by Lugo et al. (2013), UC-II derived from chicken sternum increased pain-free exercise duration (2.8 min vs 1.4 min, COL vs baseline) and improved knee extension range of motion (81.0 ± 1.3° vs 73.2 ± 1.9°, COL vs baseline). However, no significant changes were observed in either exercise duration or knee extension range with PLA. The beneficial effects of COL in this study could be due to the activated T regulatory cells specific to UC-II. Type II collagen releases anti-inflammatory cytokines (interleukin-10 and transforming growth factor-β) that have the potential to counter the pro-inflammatory cascade associated with strenuous physical exertion, creating a shift towards ECM replenishment by the chondrocytes (Lugo et al. 2013). Therefore, supplementing even 40 mg/day of UC-II may have the potential to improve joint functionality and range of motion. Overall, COL, coupled with a rehabilitative exercise protocol, may accelerate recovery from joint injuries and improve joint function, possibly via its anti-inflammatory properties, or effects on ECM regeneration, and collagen synthesis in cartilage and tendons.
Effects of collagen supplementation on body composition
Out of the four studies assessing changes in body composition and muscle strength, Zdzieblik et al. (2015) found COL complemented with a guided resistance training programme induced significant changes in elderly sarcopenic men (class I or II). There was an increase of over 5 kg of FFM and a decrease of 6 kg in FM with COL. Whereas in PLA, FFM increased by 3 kg and FM decreased by 4 kg, likely due to the resistance training programme (Zdzieblik et al. 2015). Though changes were seen in both groups, the effects were more noticeable in the COL group (r 0.72; p < 0.001 vs r 0.55; p < 0.003, correlation coefficient COL vs PLA). In addition, the outcomes were not as pronounced in pre-menopausal women, with only a 1.8% increase in FFM (Jendricke et al. 2019) or in recreationally active young with two studies noting a 2 kg increase in FFM (Oertzen-Hagemann et al. 2019; Kirmse et al. 2019). Kirmse et al. (2019) and Jendricke et al. (2019) both observed a significant increase in FFM with COL, with the latter observing a decrease in FM in pre-menopausal women (− 1.5 ± 1.7 kg COL vs + 0.7 ± 1.6 kg in PLA). The changes in FFM are possibly attributed to an increase in surrounding connective tissue, as there was no difference in fibre cross-sectional area (fCSA) hypertrophy in either group (Kirmse et al. 2019). Previous studies have also observed an increase in ECM synthesis in connective tissue with COL supplementation (Schunck and Oesser 2013). For changes in FM, COL has shown to reduce body weight gain and adipocyte enlargement (Chiang et al. 2016). However, the BF losses reported in elderly sarcopenic men was likely to be higher, as participants had ~ 30% BF (Zdzieblik et al. 2015), whereas participants in Kirmse et al. (2019) had ~ 11% BF at baseline.
Using skeletal muscle proteomics, Oertzen-Hagemann et al. (2019) observed that COL induced a higher increase in proteins (such as myosin proteins, actin-binding proteins and tropomyosins) related to resistance training adaptations, likely due to the high hydroxyproline-peptide concentration in collagen peptide supplements as observed previously (Kitakaze et al. 2016). Furthermore, a higher increase in myotilin, a muscle Z-disk protein, which is an important marker for myofibril remodelling post-exercise, was observed in the COL group. The higher upregulation of proteins with resistance training and COL indicates a deeper effect on skeletal muscle proteomes as compared to resistance training solely. Adaptations in the ECM seemed to have occurred largely due to the resistance training programme and may have been independent of COL as similar proteins affecting the ECM were upregulated in PLA (Kjaer et al. 2006).
Collagen supplementation combined with resistance training elicited moderate improvements in body composition. The increase in FFM is purportedly due to COL’s effect on the surrounding connective tissue, and not myofibrillar protein, as there were no changes observed in fCSA hypertrophy.
Effects of collagen supplementation on muscle soreness and recovery from exercise
To date, two studies have investigated the impact of COL on muscle soreness and recovery from strenuous exercise (Lopez et al. 2015; Clifford et al. 2019). Collagen peptides derived from chicken sternal cartilage seemed to attenuate decrements in bench-press performance, improve recovery (8.3 vs 7.3 points, COL vs PLA on a perceived recovery scale), and reduce symptoms of delayed onset of muscle soreness (58 vs 72%, decrease in performance COL vs PLA; Lopez et al. 2015). Plasma biomarkers for muscle damage and inflammation were also lower in the COL group. A higher tolerance for repeated high-intensity resistance exercise protocol in the intervention group was observed, demonstrating that COL may accelerate the protective adaptation of the ‘repeated bout effect’, allowing for enhanced musculoskeletal recovery by possible ECM remodelling (Lopez et al. 2015). In contrast, Clifford et al. (2019) found no influence of COL on markers of inflammation and bone collagen synthesis, although COL was found to reduce muscle soreness by around 4.1–5.4 mm post-exercise on a visual analogue scale. As the study assessed inflammation and bone collagen turnover through blood samples, the mechanisms behind the positive changes observed could not be thoroughly explained. A larger sample size using muscle biopsies and additional biomarkers for connective tissue turnover is required in future studies to get a greater understanding of how COL might influence recovery.
Previously, COL has reduced joint and muscle pain in recreational athletes (Clark et al. 2008; Zdzieblik et al. 2017) and aided recovery in active individuals (Lopez et al. 2015). Recently, a study found that whey protein can stimulate collagen synthesis in muscle after resistance training (Holm et al. 2017). Though collagen has a different amino acid profile from whey protein, it will be interesting to gain an understanding into the adaptations occurring with COL.
Effects of collagen supplementation on collagen synthesis and muscle protein synthesis
Four studies assessed the effects of COL on collagen synthesis and muscle protein synthesis. Shaw et al. (2017) found that collagen synthesis increased and remained elevated for 72 h, with 15 g/day COL enriched with vitamin C as compared to a 5 g/day dose and PLA. The amino acid content of blood peaked 1 h after 15 g COL consumption (increase of 376 mmol/L in glycine, and 162 mmol/L of proline vs baseline) and 30 min after 5 g COL, providing important information regarding exercise timing in accordance with the collagen dose. The 15 g/day COL augmented collagen synthesis in the recovery period after exercise as seen by the increase in bone collagen synthesis markers (PINP) (153% increase in PINP with 15 g COL, vs 59.2% increase with 5 g COL and 53.9% increase with PLA). This indicates that the improved collagen synthesis with 15 g/day COL coupled with an intermittent exercise protocol, consumed 60 min prior to exercise, may improve tissue repair and help prevent injuries.
In addition, the presence of vitamin C promotes hydroxyproline formation (Pinnell et al. 1987) and cultivates collagen cross-linking (Levene et al. 1972), making it essential for collagen synthesis.
Interestingly, only Shaw et al. (2017) found that bone collagen synthesis markers (PINP) increased significantly with COL (15 g dose only) whereas, Clifford et al. (2019) and Lis and Baar (2019) did not observe any changes in PINP following 20 g/day COL and varied doses (15 g gelatine enriched with vitamin C, 15 g hydrolysed collagen and a 15 g gummy containing 7.5 g gelatine and 7.5 g hydrolysed collagen), respectively. Lis and Baar (2019) suggested that they did not see significant changes due to high variability of the PINP testing kit used. The addition of vitamin C may interfere with the Enzyme-Linked Immunosorbent Assay (ELISA) kit used in this study, which is in contrast to Shaw and colleagues results (2017). This could be due to the difference in collagen supplements (gelatine and hydrolysed collagen) and the blood clotting time (20 min) used by Lis and Baar (2019), whereas Shaw et al. (2017) used only gelatine and a 2-h clotting time. Heat and a longer waiting period may degrade vitamin C, reducing the variability of the ELISA reaction. Hence, a more reliable outcome measure (possibly mass spectrometry), and setting testing protocols for vitamin C inclusion, are needed to conclude which form of COL may be most effective.
Two studies compared the effect that COL has on MPS (i) 30 g/day whey protein vs 30 g/day COL (Oikawa et al. 2020a) and (ii) 60 g/day lactalbumin vs 60 g/day COL (Oikawa et al. 2020b), finding a greater increase in MPS with whey protein (0.173 ± 0.104% whey protein vs 0.020 ± 0.034% COL, after exercise) and with lactalbumin (13 ± 5% higher than COL). Though the supplements were isonitrogenous, the plasma leucine concentration was 87% higher with lactalbumin and 5.5 times higher in whey protein than COL, which is the likely reason for the increased MPS (Devries et al. 2018). Indeed, lactalbumin and whey protein may be considered higher quality proteins due to AA profile (high amounts of leucine and tryptophan), digestibility and bioavailability, earning each a Protein Digestibility-Corrected Amino Acid Score of 1. Whereas, COL has a PDCAAS score of 0, as it lacks the essential AA tryptophan (Phillips 2017). Protein quality may impact skeletal muscle adaptations and recovery, hence lactalbumin might be better suited for supplementation following exercise if the main priority is hypertrophy. Interestingly, whey protein induced a higher MPS response at rest and with exercise acutely and up to 4 h later, whereas COL only elevated MPS levels acutely with exercise (Oikawa et al. 2020a). Intriguingly, Oikawa et al. (2020a) found no differences for muscle collagen protein synthesis following participants consuming either COL or whey protein, with a significant increase found as a result of exercise. Potentially indicating that total protein and amino acid profile may be more influential than type of protein on MPS and muscle collagen protein synthesis. However, further studies like these are necessary to assess different protein sources, doses, and exercise forms in a variety of populations to test their efficacy.