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Review

Potential Relevance of Bioactive Peptides in Sports Nutrition

1
Centre for Sports Science and University Sports, Institute for Nutrition, Exercise and Health, University of Vienna, Auf der Schmelz, 61150 Vienna, Austria
2
Department for Nutritional Science, Institute for Nutrition, Exercise and Health, University of Vienna, 61150 Vienna, Austria
3
Department of Sport and Sport Science, University of Freiburg, 79102 Freiburg, Germany
4
Praxisklinik Rennbahn, CH-4132 Muttenz, Switzerland
*
Author to whom correspondence should be addressed.
Academic Editor: Aloys Berg
Nutrients 2021, 13(11), 3997; https://doi.org/10.3390/nu13113997
Received: 11 August 2021 / Revised: 27 October 2021 / Accepted: 4 November 2021 / Published: 10 November 2021
(This article belongs to the Special Issue Nutrients Supporting an Active Lifestyle)

Abstract

Bioactive peptides are physiologically active peptides mostly derived from proteins following gastrointestinal digestion, fermentation or hydrolysis by proteolytic enzymes. It has been shown that bioactive peptides can be resorbed in their intact form and have repeatedly been shown to have a positive effect on health-related parameters such as hypertension, dyslipoproteinemia, inflammation and oxidative stress. In recent years, there has been increasing evidence that biologically active peptides could also play an important role in sports nutrition. Current studies have shown that bioactive peptides could have a positive impact on changes in body composition and muscular performance, reduce muscle damage following exercise and induce beneficial adaptions within the connective tissue. In the following overview, potential mechanisms as well as possible limitations regarding the sports-related effect of bioactive peptides and their potential mechanisms are presented and discussed. In addition, practical applications will be discussed on how bioactive peptides can be integrated into a nutritional approach in sports to enhance athletic performance as well as prevent injuries and improve the rehabilitation process.
Keywords: muscular performance; connective tissue; muscle recovery; body composition; endurance muscular performance; connective tissue; muscle recovery; body composition; endurance

1. Introduction

The importance of a sports specific diet that is tailored to the type of sports and the associated energy requirements during exercise is largely undisputed. Dietary management helps to maintain an optimal health status of athletes during training and competition but can also prevent injuries, enhance performance and improve regeneration [1,2]. The increasing knowledge about the importance of sport specific adaptations allows individual nutrition recommendations depending on the requirement profile. Robust evidence in the field of sports nutrition is found, e.g., carbohydrates in endurance sports and proteins in strength sports [1,2,3]. In addition to the amount and quality of macronutrients, aspects such as timing and periodization of proteins and carbohydrates are increasingly being researched [4,5,6,7]. One aspect of maximizing physical performance relative to body weight is improving body composition. Body composition plays a very important role in many types of sports, such as endurance sports, aesthetic sports and disciplines with weight classes [8]. It is well known that diet, together with an adequate physical stimulus, is an important component in promoting changes in body composition, such as increasing muscle mass or decreasing fat mass [9]. Nutritive components may improve the metabolism, structure and function of muscles and connective tissue via various signaling pathways [10]. The importance of the connective tissues is increasingly being recognized as structural adaptations within connective tissues, particularly in the area of myotendinous junctions, can help to improve performance and prevent injuries [11].
In general, the effects of proteins of different sources, amino acid compositions and individual amino acids have been the focus of sports specific research for many years. More recently, also studies related to bioactive peptides have yielded interesting and promising results. Bioactive peptides are physiologically active molecules mostly derived from proteins following hydrolysis. The effects of bioactive peptides appear to be due to random interactions with receptors or endogenous proteins such as mammalian target of rapamycin (mTOR), glycogen synthase or glucose transporter type 4 (GLUT-4) that exceed the effects of individual amino acids [12,13,14,15]. Bioactive peptides have repeatedly been shown to have a beneficial influence on health-related parameters such as hypertension, dyslipoproteinemia, inflammation and oxidative stress. In recent years, increasing evidence suggests that biologically active peptides could also play an important role in sports nutrition [16]. Several studies have already shown positive effects after administration of bioactive peptides on relevant, sports-specific aspects such as performance, regeneration and structural adaptations [16]. Currently, much of the existing knowledge is based on cell culture and animal studies but also on human interventional studies, e.g., with hydrolyzed protein.
The findings on bioactive peptides and their synergistic effect in combination with physical exercise can be beneficial not only for high-performance athletes. Strategies from sport and nutrition could also help to maintain and improve health and well-being for the general population. In this context, the aim is to preserve or even improve relevant aspects related to aging such as muscle mass, functional capacity, mitochondrial function or adaptations within connective tissues [17,18,19,20,21]. Therefore, bioactive peptides could represent another potentially specific and promising strategy to address different aspects of aging.
In the following sections, studies related to the effects of bioactive peptides on sports specific outcomes will be presented. These sports specific outcomes will be subdivided into results related to body composition, endurance performance and regeneration following muscle damage.

2. Methods

The current literature search was completed at the following electronic databases: Pubmed, ScienceDirect, Scopus and Web of Science. The literature review was performed from articles published up to February 2021. The search string contained the following two segments: the first segment encompassed synonyms of peptides and the second segment included synonyms related to sport performance. All segments were combined using the Boolean operator “AND” and all synonyms within each segment connected with “OR”. The respective MeSHterms were used for each keyword. Due to the limited studies available, both in vitro and in vivo studies were considered relevant.

3. Effect on Body Composition

An optimal composition of muscle and fat mass is crucial for many athletes in various sports. It is now well established that nutritional stimuli (e.g., protein intake and amino acid composition), beyond just caloric intake, can support improvements in body composition in terms of an increase in muscle mass and a decrease in fat mass [9,22]. Muscular hypertrophy is particularly important for athletes in the context of increasing muscular strength. Evidence that protein supplementation promotes fat-free mass and muscular strength has been shown in a recent meta-analysis by Morton et al. [23]. Regarding the effects of bioactive peptides, an increase in fat-free mass was observed in non-athletic populations when collagen peptides compared to placebo were taken in combination with 12 weeks of resistance training in young men [24,25], elderly sarcopenic men [26] and premenopausal women [27]. The positive influence of bioactive peptides on muscular hypertrophy could also lead to effects on muscular strength [16]. Benefits on muscle strength were observed in studies with collagen peptides in relation to hand strength in older women [27] and isokinetic quadriceps strength in older men compared to placebo [26]. In other studies with collagen peptides, a descriptive increase in muscle strength were observed in younger as well as older men after 8 and 12 weeks of resistance training compared to placebo, however, these improvements were not statistically significant [24,25,28].
With respect to muscle mass, an upregulation of anabolic signaling is necessary to induce muscular hypertrophy [29]. The stimulation of the mTOR signaling pathway via amino acids such as leucine is one mechanism known to increase muscular protein synthesis [30,31]. In addition, small peptides such as the dipeptide hydroxyproline-glycine have also been shown to activate this signaling pathway in vitro, thereby enhancing hypertrophy in myotubes [32]. Since dipeptides could also be detected in the blood and thus seem to be bioavailable after ingestion of collagen peptides [33], the effect of collagen peptides on body composition is an interesting field of research. Remarkably, collagen peptides have an incomplete amino acid spectrum and low leucine content. Therefore, one might expect a small anabolic effect [34]. However, the positive effect of collagen peptides on body composition could possibly be explained by the signaling effect of bioactive peptides.
Besides collagen peptides, there are many peptides from other sources that would also be potential candidates. While the effects of whey protein on lean mass are well described [35], bioactive peptides in whey hydrolysate have received little attention. Besides the high biological value and high content of leucine [31,36,37,38], the bioactive peptides in whey hydrolysate could play a role in the observed anabolic effects. Based on the observations in rats that the dipeptide leucine-valine increased the expression of mTOR, it may well be that dipeptides in whey hydrolysate have similar anabolic effects to leucine as a single amino acid [12]. The extent of the influence of bioactive peptides in whey hydrolysate is difficult to determine; two studies found no benefits from supplementation in combination with a resistance training of whey hydrolysate compared to whey protein in young men [39,40].

4. Effects on Endurance Performance

Apart from changes in body composition and biomechanical mechanisms, metabolic factors such as improvements in fat oxidation, glucose availability and consumption, as well as muscle glycogen replenishment, play a crucial role in endurance performance [41]. Whether or how bioactive peptides or proteins can enhance these effects is not well understood and their influence on endurance performance is still controversial [16].
To date, few studies have investigated the influence of protein hydrolysates or small peptides on endurance performance. Most recently, it has been shown that collagen peptide supplementation in women can support the effects on endurance performance during concurrent training. A total of 12 weeks of concurrent training resulted in a significant improvement in running distance in a one hour time trial compared to the placebo group. This improvement could not only be explained by metabolic improvements. The significant increase in fat-free mass and strength observed in subjects receiving the collagen peptides [42] may also suggest that biomechanical improvements, leading to enhanced muscle work efficiency, could also be involved in enhancing endurance performance. In another study, Hansen and colleagues observed a performance benefit from supplementation with whey hydrolysate plus carbohydrates compared to carbohydrates alone during a one-week training camp [43]. A performance enhancing effect could also be observed with casein hydrolysate in combination with carbohydrates compared to carbohydrates alone. The improvement in performance occurred in the last third of the 60 km cycling time trial [44]. This could potentially be explained by the results of Oosthuyse et al. [45], who found an increase in fat oxidation following casein ingestion. This effect could lead to a saving of carbohydrate stores and had a positive effect on performance in the time trial compared to the placebo. In the study, performance was not significantly improved by carbohydrate alone or carbohydrate plus whey hydrolysate compared to placebo [45].
Possible explanations for an improved endurance performance include an increased glycogen uptake and storage in muscle cells. For example, isoleucine-valine, a peptide from hydrolyzed whey protein, has been shown to stimulate glucose uptake in vitro [13] and to increase muscle glycogen content after exercise in rats [12]. Observations in mice could show that hydrolyzed whey protein leads to an activation of glycogen synthase [14]. In rats, an increased translocation of GLUT-4 transporters from the cytoplasm into the cell membrane in an insulin-independent manner was demonstrated [15]. In addition, it was also shown that whey hydrolysate further increased the uptake of glucose into skeletal muscle cells compared to whey protein [14,15]. In summary, in rodents, whey hydrolysate in combination with glucose appears to raise skeletal glycogen stores more than glucose and whey protein or glucose alone [46]. However, this effect could not always be confirmed in human studies. Thus, in humans, the administration of hydrolysates from casein, whey or wheat plus carbohydrates showed no advantages with regard to carbohydrate uptake or metabolism compared to a comparable dose of carbohydrates [47,48,49].
Another way in which athletic performance can be optimized by nutrition is by influencing endothelial function. In this context, nitrate supplementation is already used by some athletes, but also other food components such as omega-3 fatty acids or some secondary plant products also have a beneficial effect on endothelial function, thus improving muscle perfusion [50,51,52]. Bioactive peptides from various sources, such as whey [53,54,55,56], plants [57] or eggs [58], could be a promising research subject for acute effects on performance during high intense or prolonged exercise. It is already known that peptides from these sources can improve endothelial function by suppressing the angiotensin converting enzyme (ACE). Thus, it is possible that specific bioactive peptides can be used to acutely influence performance. However, there are still many open questions and, therefore, the influence of different bioactive peptides on biomechanical and metabolic factors following endurance or concurrent training needs to be investigated in further studies.

5. Effects on Muscle Damage

Performing unaccustomed exercise has repeatedly been shown to result in exercise-induced skeletal muscle damage (EIMD) [59,60]. Especially eccentric muscle work (e.g., the lengthening of a contracting muscle) seems to facilitate structural damage including Z disk streaming and disrupted sarcomeres, and thus impairments within the excitation-contraction coupling system [61,62]. Previous findings demonstrated that besides the involvement of muscle tissue, connective tissue can also be affected by excessive mechanical loading [63,64]. As a consequence, this may lead to extracellular matrix (ECM) disruption [63,64].
Signs of EIMD are temporary but typically persist for up to several days after cessation of exercise. Frequently reported consequences include muscle soreness, decrements in force-generating capacity as well as elevated levels of specific biomarkers (e.g., creatine kinase (CK), lactate dehydrogenase or myoglobin) [65]. The fact that severe EIMD might compromise athletic performance for several days [66,67] highlights the need for new strategies which could help to attenuate EIMD [68]. Besides approaches in the field of pharmacological and physical therapy [69], nutritional strategies, especially the intake of bioactive peptides [70], have recently gained increasing attention [68].
Until now, several investigations have been conducted with peptides and hydrolysates on muscular performance following exercise to volitional fatigue. In 2010, Buckley and colleagues [71] performed a randomized, placebo-controlled trial and examined the effects of whey hydrolysate on muscle soreness, serum CK activity and TNF-alpha concentrations following unaccustomed eccentric exercise. The results demonstrated that hydrolyzed whey facilitated a rapid regeneration of force capacity, assessed via maximal isometric contractions, which was significantly enhanced compared to the control group [71]. Interestingly, the authors did not report any group differences in muscle soreness and found no evidence for changes in CK or TNF-alpha. In a recent study, Brown and colleagues [72] investigated the effects of whey protein hydrolysate on EIMD and recovery following exhaustive repeated-sprint exercises in females. To assess changes over time, biomarkers of EIMD were assessed up to three days following cessation of exercise. The findings demonstrated that the supplementation with whey hydrolysate led to lower CK levels at 48h and attenuated the decline in muscle function (evidenced by an improved reactive strength index and higher flexibility). These positive short-term effects of hydrolysates are in accordance with the findings from further studies [43,73], although some researchers reported contradictory results [74].
Regarding longitudinal trials, Lollo et al. [75] investigated the effects of whey hydrolysate supplementation during a 12-week soccer-specific intervention on performance and recovery. The results supported the findings of acute trials and demonstrated that whey hydrolysate supplementation significantly attenuated markers of muscle damage such as CK (−42% reduction) and lactate dehydrogenase (−30% reduction) compared to control.
Besides whey peptides, collagen peptides have also been investigated regarding muscular recovery. A previously published randomized-controlled trial by Clifford and co-workers [70] investigated the effects of collagen peptides on muscle function and muscle damage. To quantify muscle function and damage, the authors implemented maximal voluntary contractions as well as countermovement jumps. Muscle soreness was assessed via a visual analogue scale. The results from this trial revealed that explosive force production was more rapidly restored in the collagen peptide group compared to the control group. Additionally, evidence for attenuated muscle soreness following strenuous exercise was observed with the ingestion of collagen peptides. Furthermore, positive effects on an accelerated muscle recovery were also seen following the ingestion of isolated soy protein [76].
In general, however, it needs to be mentioned that evidence is rather scarce on whether peptides or protein hydrolysates facilitate muscle recovery and decrease muscle damage following intensive exercise. It should be particularly emphasized that all studies did not directly assess the specific peptide composition in their supplements, which limits the conclusions about the direct effects of bioactive peptides on muscle damage. The fact that some studies report beneficial effects is encouraging but warrants more research with a more specific look on the bioactivity of individual peptides.

5.1. Effects on Protein Synthesis

Following high-intensity and strenuous exercise, it is generally accepted that both muscle protein synthesis as well as degradation are increased. When the stimulation of muscle protein synthesis is greater compared to protein breakdown, muscle net balance is increased. This can be further improved by the addition of exogenous amino acids, which provide the induction of an anabolic environment and thus facilitate tissue remodeling [77]. Bioactive peptides are increasingly considered as a crucial factor for regulating muscle protein turnover. In previous in vitro trials, it has been demonstrated that the collagen derived dipeptide hydroxyprolyl-glycine (Hyp-Gly) induces myotube hypertrophy by activating anabolic signaling pathways such as PI3K/Akt/mTOR [32]. Therefore, Hyp-Gly potentially could facilitate an accelerated recovery of the contractile machinery, allowing an accelerated force recovery following EIMD. This evidence, however, relies on findings from in vitro studies and needs to be confirmed by future in vivo trials.

5.2. Effects on Inflammation

Acute exercise-induces muscle trauma initiates a sequence of cellular processes including a robust inflammatory response [78,79]. Depending on the type of exercise, elevated levels of inflammatory markers can be found for up to several days [80,81]. Despite the fact that an adequate level of inflammation is pivotal for adequate wound healing [82] and satellite cell response [83], a chronic pro-inflammatory status impairs muscle regeneration [84] and induce lysis of muscle membranes [80]. Consequently, it might be assumed that specific nutritional requirements might help to maintain an optimal inflammation level within the muscle following EIMD.
To date, much of the current evidence on the anti-inflammatory potential of bioactive peptides is based on mammalian cell culture experiments [85]. Previous trials that have focused on casein derived peptides found that tripeptides with the sequence Val-Pro-Pro demonstrate a robust anti-inflammatory potential by inhibiting the nuclear factor kappa B pathway [86]. Similarly, Jiehui and colleagues (2014) found that the peptide Gln-Glu-Pro-Val-Leu (also obtained from casein) seemed to be involved in nitric oxide release and augmenting the production of anti-inflammatory cytokines such as IL-4 and IL-10 [87]. A recent animal experiment investigated the effects of a specific dipeptide (L-alanyl-L-glutamine) in male Wistar rats. The findings indicated that this dipeptide induced cytoprotective effects being mediated by heat shock protein-70 (HSP 70) responses. Additionally, plasma levels of CK, TNF-alpha and lactate dehydrogenase were decreased which might be associated with enhanced muscle cell protection and attenuated inflammation following exercise [88]. Despite the evidence in animals, research in humans is still scarce and it is unknown whether these anti-inflammatory effects in in vitro and animal experiments can contribute to a better muscle recovery after EIMD in humans.

5.3. Effects on Oxidative Stress

Previous research has shown that several peptides demonstrate a high antioxidative capacity. Without adequate clearance of reactive oxygen species (ROS) by antioxidants, ROS are capable of damaging virtually all major cellular constituents [89]. Although physiological levels of ROS play an important role as regulatory mediators in intramuscular signaling processes [90], disproportionate amounts have been discussed to be involved in prolonged inflammation and exaggerated muscle damage following exercise [91].
In terms of bioactive peptides, previous trials have again primarily focused on peptides derived from milk products. In a study by Suetsuna and colleagues (2000), casein peptides with the sequence Tyr-Phe-Tyr-Pro-Glu-Leu have been demonstrated to have free radical scavenging effects [92]. Within their study, the authors sequentially removed amino acids from the peptide and found that the highest antioxidant capacity can be achieved with the dipeptide Glu-Leu [92]. Also with casein, Kitts [93] has shown that phosphopeptides are able to demonstrate free radical quenching activity.
Similar to casein peptides, several other peptides have shown to possess antioxidant potential [94] including whey [95], collagen [96] or soy [97,98]. Nevertheless, it is currently not known exactly to what extent this antioxidant capacity contributes to changes in EIMD in humans.
In summary, previous findings revealed that various peptides demonstrate distinct effects on muscle damage via optimizing the inflammatory response, myofibrillar re-structuring or minimizing oxidative stress. Nevertheless, current evidence is still far from being conclusive and further in vivo trials in humans are necessary to elucidate potential benefits of bioactive peptides on muscle damage.

6. Effects on Connective Tissue

Connective tissue is essential for the execution of human movements and therefore, the properties and the function of connective tissue is an important determinant for athletic performance [99,100]. Intense and/or unaccustomed prolonged physical exercise induces enhanced stress and strain which could result in tendinopathy and functional joint pains among athletes [101]. Connective tissue needs to adapt its structure and composition permanently to the physical requirements, in order to optimally support athletic performance, to cope with enhanced loading and to prevent degeneration [102]. Exercise-induced adaptions as well as nutrition seems to influence connective tissue. More specifically, its alterations of material and morphological adaptions after supplementation of biologically active peptides have gained increasing attention in the scientific community [103].
The structure of its extracellular matrix (ECM) and specifically its protein composition defines mechanical properties of connective tissue [104]. Since collagen is the most abundant matrix molecule [102,104] research of connective tissue adaptions has focused on its synthesis in fibroblasts [105].

6.1. Effects on Tendon Properties

The ordered assembly in fibrils contributes to the characteristic elastic behavior of tendons and allows efficient storing and returning of energy during tensile loads [106]. Reinforcement of the ECM by an elevated synthesis rate in tenocytes increases its ability to tolerate higher stress levels [107]. Intact and healthy tendons improve athletic performances such as running economy [100] and decrease the risk of injury [107].
To date, multiple trials have investigated the stimulating effects of bioactive peptides on collagen synthesis in tendons. Schunck and Oesser (2013) reported a pronounced stimulatory effect on RNA expression and biosynthesis of matrix molecules after adding collagen hydrolysates to primary fibroblasts in vitro. These findings were confirmed by an in vivo animal study, which revealed that collagen peptides supplemented to rabbits over a time period of 56 days increased collagen fibril diameter and possibly improved mechanical properties of the Achilles tendon [108]. The authors contributed this effect to the high concentration of glycine within the supplement [109,110]. Alongside single amino acids, the authors suspected a promoting effect of the tri-peptide glycine-proline-arginine (Gly-Pro-Arg). It shows various functions in the human body; for instance, antiaggregatory effect has been shown in platelets [111]. Moreover, gelatin supplementation led to increased levels of collagen synthesis markers in blood after rope skipping exercises [112]. Since gelatin per se does not contain collagen peptides, conclusions from these results on biologically active peptides remain speculative. However, their formation during digestive degradation processes could potentially contribute to the stimulating effect.
On the one hand, there is not enough evidence highlighting the effects of a supplementation with collagen peptides on tendon adaptions in humans, due to a lack of studies in vivo. On the other hand, a beneficial influence of collagen peptide supplementation is conceivable, since a stimulating effect of collagen peptides on tendon fibroblasts is indicated in vitro [113] and it shows a promoting effect on tendon adaptions in animals [108] as well as increased collagen synthesis after gelatin intake in humans [112]. Further research is needed for practical recommendations.
Supplementation with proteins containing high concentrations of leucine and other essential amino acids (EAA) is currently a major field of myofibrillar protein synthesis research [23]. Its impact on tendinous adaptions has also gained interest. In an animal study, Barbosa and colleagues (2012) revealed a stimulating effect of a leucine-rich diet on collagen content and biomechanical adaptions of the deep digital flexor tendon in malnourished rats conducting aerobic physical exercise [114]. In humans, a 12-weeks high-intensity resistance training in combination with supplementation of high-leucine whey hydrolysate led to an augmented cross-sectional area of the proximal patellar tendon [115]. This might demonstrate an advantageous impact of a supplementation with EAA rich peptides on exercise induced adaptions in healthy tendons. It has to be mentioned that no specific peptides have been identified in these studies.
Due to the pronounced and repetitive loading of tendons in sports, tendinopathy is a severe issue among athletes [101]. Among other therapies, peptide intake was subject of research about tendon healing. The results of a study by Praet and colleagues (2019) indicate a beneficial effect of exercise combined with collagen hydrolysate supplementation on tendon healing in subjects with Achilles’ tendinopathy. The authors attribute it to the high glycine uptake of 1.1g per day. Glycine was related to improved matrix organization strength and tenocyte remodeling by modulation of TNF-alpha, matrix metalloproteases and collagen precursors [116,117]. In Achilles tendinopathic patients with extracorporeal shockwave therapy, a positive influence of a supplement containing arginine and collagen could be demonstrated [118]. These results indicate a beneficial effect of single amino acids and maybe specific peptides on tendon healing therapy [119]. Further research is needed to characterize the role of biologically active peptides in detail and to detect potential mechanisms.

6.2. Effects on Cartilage and Functional Joint Pain

Athletes show an increased risk of articular cartilage lesions leading to functional joint pain [120]. One therapeutic attempt includes the treatment and prevention of degenerative articular processes by stimulation of collagen synthesis with biologically active peptides [103].
In vitro, cultured chondrocytes showed stimulation of proteoglycans as well as type II collagen and increased protease activity [121,122]. Several studies showed beneficial effects of collagen peptide supplementation on pain and joint mobility of athletic subjects suffering from functional joint pains, in vivo [123,124]. According to the authors, the stimulatory effect of collagen peptides on ECM-protein synthesis could likely explain these results. Although the exact mechanism remains unclear, specific biologically active signaling peptides derived from hydrolyzed collagen such as hydroxyproline-proline-glycine (Hyp-Pro-Gly) and hydroxyproline-glycine (Hyp-Gly) are suspected to trigger those reactions [32,124,125,126].
Research indicates that a supplementation with whey hydrolysate might stimulate collagen synthesis [114]. Thus, the potential influence of whey hydrolysate supplementation on cartilage regeneration and recovery of functional joint pains should be discussed. However, because of a lack of studies, statements about the effects of a whey hydrolysate supplementation on articular cartilage remain speculative.

7. Practical Applications

The primary goal in competitive sport is to increase and optimize athletic performance. For this purpose, the training process is often intensified in regular phases of the yearly competition cycle, which substantially increases the mechanical and metabolic stress acting on the athlete [127]. In order to optimally prepare for these high-intensity phases, both stringent exercise routines as well as dietary strategies have been incorporated into training management in elite sport [77,128,129]. In particular, certain peptides as well as hydrolyzed proteins have been demonstrated to have beneficial effects with regard to myotendinous adaptations and an accelerated recovery.
Indeed, previous in vitro and in vivo studies have confirmed that several bioactive peptides elicit strongly upregulating effects on muscle protein synthesis [32] or increase muscular strength [26] and recovery [70]. This is of special interest for sports, where large forces against an object or opponent (e.g., combat sports) are needed. Interestingly, recent discussions in the scientific community address the fact that these peptides may also be helpful for reducing injuries and accelerating return-to-sport [130]. Besides positive effects on strength and recovery, recent investigations found that hydrolyzed proteins might also influence endurance performance and metabolism [42,43,45]. Hansen et al. (2015), for example, revealed that whey hydrolysate in combination with carbohydrate enhanced running performance and facilitated recovery from strenuous training compared to carbohydrate alone [43]. These findings indicate that it might also be advantageous to incorporate nutritional interventions with certain peptides into sports with endurance aspects. In this context, it needs to be mentioned that evidence is still scarce and also contradictory findings exist in the current literature [131].

8. Conclusions

In summary, various findings point towards potential beneficial effects of specific bioactive peptides on exercise performance as well as recovery and tissue repair. Although these preliminary findings are promising, further studies are warranted before definitive conclusions can be drawn. In particular, studies with specific or known peptide sequences are lacking in order to be able to evaluate the effects of specific peptides. This highlights the need for further research on the modes of action both in vitro and in vivo. Based on the present narrative review, future studies need to focus on (i) the effects of bioactive peptides on biomechanical as well as metabolic responses in humans and (ii) elaborating the underlying physiological mechanisms of various peptides. Lastly, (iii) the investigation of potential effects in different sport populations are necessary in order to evaluate potential field of applications. Moreover, the majority of existing studies examined the effects of hydrolyzed proteins but not of individual bioactive peptide forms.

Author Contributions

Conceptualization, D.K., J.K., S.J. and C.C.; methodology, D.K., J.K., S.J. and C.C.; formal analysis, D.K., J.K., S.J. and C.C.; investigation, D.K., J.K., S.J. and C.C.; resources, D.K., J.K., S.J. and C.C.; data curation, D.K., J.K., S.J. and C.C.; writing—original draft preparation, J.K., S.J.; writing—review and editing, D.K., C.C.; supervision, D.K., C.C.; project administration, D.K.; All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Acknowledgments

Open Access Funding by the University of Vienna.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Jäger, R.; Kerksick, C.M.; Campbell, B.I.; Cribb, P.J.; Wells, S.D.; Skwiat, T.M.; Purpura, M.; Ziegenfuss, T.N.; Ferrando, A.A.; Arent, S.M.; et al. International Society of Sports Nutrition Position Stand: Protein and exercise. J. Int. Soc. Sports Nutr. 2017, 14, 20. [Google Scholar] [CrossRef][Green Version]
  2. Kerksick, C.M.; Wilborn, C.D.; Roberts, M.D.; Smith-Ryan, A.; Kleiner, S.M.; Jäger, R.; Collins, R.; Cooke, M.; Davis, J.N.; Galvan, E.; et al. ISSN exercise & sports nutrition review update: Research & recommendations. J. Int. Soc. Sports Nutr. 2018, 15, 38. [Google Scholar] [CrossRef][Green Version]
  3. Thomas, D.T.; Erdman, K.A.; Burke, L.M. Position of the Academy of Nutrition and Dietetics, Dietitians of Canada, and the American College of Sports Medicine: Nutrition and Athletic Performance. J. Acad. Nutr. Diet. 2016, 116, 501–528. [Google Scholar] [CrossRef]
  4. Stellingwerff, T.; Morton, J.P.; Burke, L.M. A Framework for Periodized Nutrition for Athletics. Int. J. Sport Nutr. Exerc. Metab. 2019, 29, 141–151. [Google Scholar] [CrossRef] [PubMed][Green Version]
  5. Marquet, L.-A.; Brisswalter, J.; Louis, J.; Tiollier, E.; Burke, L.M.; Hawley, J.; Hausswirth, C. Enhanced Endurance Performance by Periodization of Carbohydrate Intake. Med. Sci. Sports Exerc. 2016, 48, 663–672. [Google Scholar] [CrossRef]
  6. Marquet, L.-A.; Hausswirth, C.; Molle, O.; Hawley, J.A.; Burke, L.M.; Tiollier, E.; Brisswalter, J. Periodization of Carbohydrate Intake: Short-Term Effect on Performance. Nutrients 2016, 8, 755. [Google Scholar] [CrossRef] [PubMed][Green Version]
  7. Kerksick, C.M.; Arent, S.; Schoenfeld, B.J.; Stout, J.R.; Campbell, B.; Wilborn, C.D.; Taylor, L.; Kalman, D.; Smith-Ryan, A.E.; Kreider, R.; et al. International society of sports nutrition position stand: Nutrient timing. J. Int. Soc. Sports Nutr. 2017, 14, 1–21. [Google Scholar] [CrossRef] [PubMed]
  8. Sundgot-Borgen, J.; Garthe, I. Elite athletes in aesthetic and Olympic weight-class sports and the challenge of body weight and body compositions. J. Sports Sci. 2011, 29, S101–S114. [Google Scholar] [CrossRef] [PubMed]
  9. Aragon, A.A.; Schoenfeld, B.J.; Wildman, R.; Kleiner, S.; Van Dusseldorp, T.; Taylor, L.; Earnest, C.P.; Arciero, P.J.; Wilborn, C.; Kalman, D.S.; et al. International society of sports nutrition position stand: Diets and body composition. J. Int. Soc. Sports Nutr. 2017, 14, 1–19. [Google Scholar] [CrossRef][Green Version]
  10. Stellingwerff, T.; Bovim, I.M.; Whitfield, J. Contemporary Nutrition Interventions to Optimize Performance in Middle-Distance Runners. Int. J. Sport Nutr. Exerc. Metab. 2019, 29, 106–116. [Google Scholar] [CrossRef]
  11. Kovács, B.; Kóbor, I.; Gyimes, Z.; Sebestyén, Ö.; Tihanyi, J. Lower leg muscle–tendon unit characteristics are related to marathon running performance. Sci. Rep. 2020, 10, 1–8. [Google Scholar] [CrossRef]
  12. Moura, C.S.; Lollo, P.C.B.; Neder Morato, P.; Risso, E.M.; Amaya-Farfán, J. Bioactivity of food peptides: Biological response of rats to bovine milk whey peptides following acute exercise. Food Nutr. Res. 2017, 61, 1290740. [Google Scholar] [CrossRef][Green Version]
  13. Morifuji, M.; Koga, J.; Kawanaka, K.; Higuchi, M. Branched-Chain Amino Acid-Containing Dipeptides, Identified from Whey Protein Hydrolysates, Stimulate Glucose Uptake Rate in L6 Myotubes and Isolated Skeletal Muscles. J. Nutr. Sci. Vitaminol. 2009, 55, 81–86. [Google Scholar] [CrossRef][Green Version]
  14. Kanda, A.; Morifuji, M.; Fukasawa, T.; Koga, J.; Kanegae, M.; Kawanaka, K.; Higuchi, M. Dietary Whey Protein Hydrolysates Increase Skeletal Muscle Glycogen Levels via Activation of Glycogen Synthase in Mice. J. Agric. Food Chem. 2012, 60, 11403–11408. [Google Scholar] [CrossRef] [PubMed]
  15. Neder Morato, P.; Lollo, P.C.B.; Moura, C.S.; Batista, T.; Camargo, R.L.; Carneiro, E.M.; Amaya-Farfan, J. Whey Protein Hydrolysate Increases Translocation of GLUT-4 to the Plasma Membrane Independent of Insulin in Wistar Rats. PLoS ONE 2013, 8, e71134. [Google Scholar] [CrossRef][Green Version]
  16. Kohl, J.J.; König, S.; Centner, D.C. Applications in Nutrition. In Biologically Active Peptides, 1st ed.; Toldra, F.W.J., Ed.; Academic Press Elsevier: London, UK, 2021; pp. 525–550. [Google Scholar]
  17. Moreira, O.C.; Estébanez, B.; Martínez-Florez, S.; De Paz, J.A.; Cuevas, M.J.; González-Gallego, J. Mitochondrial Function and Mitophagy in the Elderly: Effects of Exercise. Oxidative Med. Cell. Longev. 2017, 2017, 1–13. [Google Scholar] [CrossRef]
  18. Kulkarni, S.S.; Salehzadeh, F.; Fritz, T.; Zierath, J.; Krook, A.; Osler, M.E. Mitochondrial regulators of fatty acid metabolism reflect metabolic dysfunction in type 2 diabetes mellitus. Metabolism 2012, 61, 175–185. [Google Scholar] [CrossRef] [PubMed][Green Version]
  19. Gan, Z.; Fu, T.; Kelly, D.P.; Vega, R.B. Skeletal muscle mitochondrial remodeling in exercise and diseases. Cell Res. 2018, 28, 969–980. [Google Scholar] [CrossRef] [PubMed]
  20. Svensson, R.B.; Heinemeier, K.M.; Couppé, C.; Kjaer, M.; Magnusson, S.P. Effect of aging and exercise on the tendon. J. Appl. Physiol. 2016, 121, 1353–1362. [Google Scholar] [CrossRef]
  21. Distefano, G.; Goodpaster, B.H. Effects of Exercise and Aging on Skeletal Muscle. Cold Spring Harb. Perspect. Med. 2018, 8, a029785. [Google Scholar] [CrossRef][Green Version]
  22. Lim, M.; Pan, B.; Toh, D.; Sutanto, C.; Kim, J. Animal Protein versus Plant Protein in Supporting Lean Mass and Muscle Strength: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Nutrients 2021, 13, 661. [Google Scholar] [CrossRef] [PubMed]
  23. Morton, R.W.; Murphy, K.T.; McKellar, S.R.; Schoenfeld, B.J.; Henselmans, M.; Helms, E.; Aragon, A.A.; Devries, M.C.; Banfield, L.; Krieger, J.W.; et al. A systematic review, meta-analysis and meta-regression of the effect of protein supplementation on resistance training-induced gains in muscle mass and strength in healthy adults. Br. J. Sports Med. 2018, 52, 376–384. [Google Scholar] [CrossRef] [PubMed]
  24. Kirmse, M.; Oertzen-Hagemann, V.; De Marées, M.; Bloch, W.; Platen, P. Prolonged Collagen Peptide Supplementation and Resistance Exercise Training Affects Body Composition in Recreationally Active Men. Nutrients 2019, 11, 1154. [Google Scholar] [CrossRef] [PubMed][Green Version]
  25. Oertzen-Hagemann, V.; Kirmse, M.; Eggers, B.; Pfeiffer, K.; Marcus, K.; De Marées, M.; Platen, P. Effects of 12 Weeks of Hypertrophy Resistance Exercise Training Combined with Collagen Peptide Supplementation on the Skeletal Muscle Proteome in Recreationally Active Men. Nutrients 2019, 11, 1072. [Google Scholar] [CrossRef] [PubMed][Green Version]
  26. Zdzieblik, D.; Oesser, S.; Baumstark, M.W.; Gollhofer, A.; König, D. Collagen peptide supplementation in combination with resistance training improves body composition and increases muscle strength in elderly sarcopenic men: A randomised controlled trial. Br. J. Nutr. 2015, 114, 1237–1245. [Google Scholar] [CrossRef][Green Version]
  27. Jendricke, P.; Centner, C.; Zdzieblik, D.; Gollhofer, A.; König, D. Specific Collagen Peptides in Combination with Resistance Training Improve Body Composition and Regional Muscle Strength in Premenopausal Women: A Randomized Controlled Trial. Nutrients 2019, 11, 892. [Google Scholar] [CrossRef][Green Version]
  28. Centner, C.; Zdzieblik, D.; Roberts, L.; Gollhofer, A.; König, D. Effects of Blood Flow Restriction Training with Protein Supplementation on Muscle Mass and Strength in Older Men. J. Sports Sci. Med. 2019, 18, 471–478. [Google Scholar]
  29. Gonzalez, A.M.; Hoffman, J.R.; Stout, J.R.; Fukuda, D.; Willoughby, D.S. Intramuscular Anabolic Signaling and Endocrine Response Following Resistance Exercise: Implications for Muscle Hypertrophy. Sports Med. 2016, 46, 671–685. [Google Scholar] [CrossRef]
  30. Kim, Y. Effects of Exercise Training Alone on Depot-Specific Body Fat Stores in Youth: Review of Recent Literature. Pediatr. Exerc. Sci. 2018, 30, 58–68. [Google Scholar] [CrossRef]
  31. Dickinson, J.M.; Fry, C.S.; Drummond, M.J.; Gundermann, D.M.; Walker, D.K.; Glynn, E.L.; Timmerman, K.L.; Dhanani, S.; Volpi, E.; Rasmussen, B. Mammalian Target of Rapamycin Complex 1 Activation Is Required for the Stimulation of Human Skeletal Muscle Protein Synthesis by Essential Amino Acids. J. Nutr. 2011, 141, 856–862. [Google Scholar] [CrossRef][Green Version]
  32. Kitakaze, T.; Sakamoto, T.; Kitano, T.; Inoue, N.; Sugihara, F.; Harada, N.; Yamaji, R. The collagen derived dipeptide hydroxyprolyl-glycine promotes C2C12 myoblast differentiation and myotube hypertrophy. Biochem. Biophys. Res. Commun. 2016, 478, 1292–1297. [Google Scholar] [CrossRef]
  33. Sugihara, F.; Inoue, N.; Kuwamori, M.; Taniguchi, M. Quantification of hydroxyprolyl-glycine (Hyp-Gly) in human blood after ingestion of collagen hydrolysate. J. Biosci. Bioeng. 2012, 113, 202–203. [Google Scholar] [CrossRef]
  34. Phillips, S.M. Current Concepts and Unresolved Questions in Dietary Protein Requirements and Supplements in Adults. Front. Nutr. 2017, 4, 13. [Google Scholar] [CrossRef][Green Version]
  35. Naclerio, F.; Larumbe-Zabala, E. Effects of Whey Protein Alone or as Part of a Multi-ingredient Formulation on Strength, Fat-Free Mass, or Lean Body Mass in Resistance-Trained Individuals: A Meta-analysis. Sports Med. 2015, 46, 125–137. [Google Scholar] [CrossRef]
  36. Devries, M.C.; McGlory, C.; Bolster, D.R.; Kamil, A.; Rahn, M.; Harkness, L.; Baker, S.K.; Phillips, S. Protein leucine content is a determinant of shorter- and longer-term muscle protein synthetic responses at rest and following resistance exercise in healthy older women: A randomized, controlled trial. Am. J. Clin. Nutr. 2018, 107, 217–226. [Google Scholar] [CrossRef]
  37. Churchward-Venne, A.T.; Breen, L.; Di Donato, D.M.; Hector, A.J.; Mitchell, C.J.; Moore, D.R.; Stellingwerff, T.; Breuille, D.; Offord, E.A.; Baker, S.K.; et al. Leucine supplementation of a low-protein mixed macronutrient beverage enhances myofibrillar protein synthesis in young men: A double-blind, randomized trial. Am. J. Clin. Nutr. 2014, 99, 276–286. [Google Scholar] [CrossRef] [PubMed][Green Version]
  38. Churchward-Venne, T.A.; Burd, N.A.; Mitchell, C.J.; West, D.W.D.; Philp, A.; Marcotte, G.R.; Baker, S.K.; Baar, K.; Phillips, S.M. Supplementation of a suboptimal protein dose with leucine or essential amino acids: Effects on myofibrillar protein synthesis at rest and following resistance exercise in men. J. Physiol. 2012, 590, 2751–2765. [Google Scholar] [CrossRef] [PubMed]
  39. Mobley, C.B.; Haun, C.T.; Roberson, P.A.; Mumford, P.W.; Romero, M.A.; Kephart, W.C.; Anderson, R.G.; Vann, C.G.; Osburn, S.C.; Pledge, C.D.; et al. Effects of Whey, Soy or Leucine Supplementation with 12 Weeks of Resistance Training on Strength, Body Composition, and Skeletal Muscle and Adipose Tissue Histological Attributes in College-Aged Males. Nutrients 2017, 9, 972. [Google Scholar] [CrossRef]
  40. Lockwood, C.; Roberts, M.D.; Dalbo, V.J.; Smith-Ryan, A.E.; Kendall, K.; Moon, J.R.; Stout, J.R. Effects of Hydrolyzed Whey versus Other Whey Protein Supplements on the Physiological Response to 8 Weeks of Resistance Exercise in College-Aged Males. J. Am. Coll. Nutr. 2016, 36, 16–27. [Google Scholar] [CrossRef] [PubMed]
  41. Hearris, M.A.; Hammond, K.M.; Fell, J.M.; Morton, J.P. Regulation of Muscle Glycogen Metabolism during Exercise: Implications for Endurance Performance and Training Adaptations. Nutrients 2018, 10, 298. [Google Scholar] [CrossRef][Green Version]
  42. Jendricke, P.; Kohl, J.; Centner, C.; Gollhofer, A.; König, D. Influence of Specific Collagen Peptides and Concurrent Training on Cardiometabolic Parameters and Performance Indices in Women: A Randomized Controlled Trial. Front. Nutr. 2020, 7, 580918. [Google Scholar] [CrossRef] [PubMed]
  43. Hansen, M.; Bangsbo, J.; Jensen, J.; Bibby, B.M.; Madsen, K. Effect of Whey Protein Hydrolysate on Performance and Recovery of Top-Class Orienteering Runners. Int. J. Sport Nutr. Exerc. Metab. 2015, 25, 97–109. [Google Scholar] [CrossRef] [PubMed]
  44. Saunders, M.J.; Moore, R.W.; Kies, A.K.; Luden, N.D.; Pratt, C.A. Carbohydrate and protein hydrolysate coingestions improvement of late-exercise time-trial performance. Int. J. Sport Nutr. Exerc. Metab. 2009, 19, 136–149. [Google Scholar] [CrossRef] [PubMed]
  45. Oosthuyse, T.; Carstens, M.; Millen, A. Whey or Casein Hydrolysate with Carbohydrate for Metabolism and Performance in Cycling. Int. J. Sports Med. 2015, 36, 636–646. [Google Scholar] [CrossRef] [PubMed]
  46. Morifuji, M.; Kanda, A.; Koga, J.; Kawanaka, K.; Higuchi, M. Post-exercise carbohydrate plus whey protein hydrolysates supplementation increases skeletal muscle glycogen level in rats. Amino Acids 2010, 38, 1109–1115. [Google Scholar] [CrossRef] [PubMed]
  47. Van Hall, G.; Shirreffs, S.M.; Calbet, J.A.L. Muscle glycogen resynthesis during recovery from cycle exercise: No effect of additional protein ingestion. J. Appl. Physiol. 2000, 88, 1631–1636. [Google Scholar] [CrossRef][Green Version]
  48. Van Loon, L.J.; Saris, W.H.; Kruijshoop, M.; Wagenmakers, A. Maximizing postexercise muscle glycogen synthesis: Carbohydrate supplementation and the application of amino acid or protein hydrolysate mixtures. Am. J. Clin. Nutr. 2000, 72, 106–111. [Google Scholar] [CrossRef]
  49. Cogan, K.E.; Evans, M.; Iuliano, E.; Melvin, A.; Susta, D.; Neff, K.; De Vito, G.; Egan, B. Co-ingestion of protein or a protein hydrolysate with carbohydrate enhances anabolic signaling, but not glycogen resynthesis, following recovery from prolonged aerobic exercise in trained cyclists. Graefe’s Arch. Clin. Exp. Ophthalmol. 2018, 118, 349–359. [Google Scholar] [CrossRef]
  50. Żebrowska, A.; Mizia-Stec, K.; Mizia, M.; Gąsior, Z.; Poprzęcki, S. Omega-3 fatty acids supplementation improves endothelial function and maximal oxygen uptake in endurance-trained athletes. Eur. J. Sport Sci. 2015, 15, 305–314. [Google Scholar] [CrossRef]
  51. Martini, D.; Marino, M.; Angelino, D.; Del Bo’, C.; Del Rio, D.; Riso, P.; Porrini, M. Role of berries in vascular function: A systematic review of human intervention studies. Nutr. Rev. 2019, 78, 189–206. [Google Scholar] [CrossRef]
  52. Bowtell, J.; Kelly, V. Fruit-Derived Polyphenol Supplementation for Athlete Recovery and Performance. Sports Med. 2019, 49, 3–23. [Google Scholar] [CrossRef][Green Version]
  53. Ballard, K.D.; Bruno, R.S.; Seip, R.L.; Quann, E.E.; Volk, B.M.; Freidenreich, D.J.; Kawiecki, D.M.; Kupchak, B.R.; Chung, M.-Y.; Kraemer, W.J.; et al. Acute ingestion of a novel whey-derived peptide improves vascular endothelial responses in healthy individuals: A randomized, placebo controlled trial. Nutr. J. 2009, 8, 34. [Google Scholar] [CrossRef][Green Version]
  54. Ballard, K.D.; Kupchak, B.R.; Volk, B.M.; Mah, E.; Shkreta, A.; Liptak, C.; Ptolemy, A.S.; Kellogg, M.; Bruno, R.; Seip, R.L.; et al. Acute effects of ingestion of a novel whey-derived extract on vascular endothelial function in overweight, middle-aged men and women. Br. J. Nutr. 2013, 109, 882–893. [Google Scholar] [CrossRef][Green Version]
  55. Martin, M.; Hagemann, D.; Nguyen, T.T.; Schwarz, L.; Khedr, S.; Moskopp, M.L.; Henle, T.; Deussen, A. Plasma concentrations and ACE-inhibitory effects of tryptophan-containing peptides from whey protein hydrolysate in healthy volunteers. Eur. J. Nutr. 2019, 59, 1135–1147. [Google Scholar] [CrossRef] [PubMed]
  56. De Oliveira, G.V.; Souza, M.; Cordeiro, E.M.; Conte-Junior, C.; Alvares, T.S. Effects of fish protein hydrolysate ingestion on endothelial function compared to whey protein hydrolysate in humans. Int. J. Food Sci. Nutr. 2019, 71, 242–248. [Google Scholar] [CrossRef] [PubMed]
  57. Daskaya-Dikmen, C.; Yucetepe, A.; Karbancioglu-Guler, F.; Daskaya, H.; Ozcelik, B. Angiotensin-I-Converting Enzyme (ACE)-Inhibitory Peptides from Plants. Nutrients 2017, 9, 316. [Google Scholar] [CrossRef] [PubMed]
  58. Liu, Y.-F.; Oey, I.; Bremer, P.; Carne, A.; Silcock, P. Bioactive peptides derived from egg proteins: A review. Crit. Rev. Food Sci. Nutr. 2018, 58, 2508–2530. [Google Scholar] [CrossRef]
  59. Ebbeling, C.B.; Clarkson, P.M. Exercise-Induced Muscle Damage and Adaptation. Sports Med. 1989, 7, 207–234. [Google Scholar] [CrossRef]
  60. Clarkson, P.M.; Hubal, M. Exercise-Induced Muscle Damage in Humans. Am. J. Phys. Med. Rehabil. 2002, 81, S52–S69. [Google Scholar] [CrossRef]
  61. Proske, U.; Morgan, D.L. Muscle damage from eccentric exercise: Mechanism, mechanical signs, adaptation and clinical applications. J. Physiol. 2001, 537, 333–345. [Google Scholar] [CrossRef]
  62. Morgan, D.L.; Allen, D.G. Early events in stretch-induced muscle damage. J. Appl. Physiol. 1999, 87, 2007–2015. [Google Scholar] [CrossRef] [PubMed][Green Version]
  63. Stauber, W.T.; Clarkson, P.M.; Fritz, V.K.; Evans, W.J. Extracellular matrix disruption and pain after eccentric muscle action. J. Appl. Physiol. 1990, 69, 868–874. [Google Scholar] [CrossRef]
  64. Armstrong, P.R.B.; Warren, G.L.; Warren, J.A. Mechanisms of Exercise-Induced Muscle Fibre Injury. Sports Med. 1991, 12, 184–207. [Google Scholar] [CrossRef] [PubMed]
  65. Byrne, C.; Twist, C.; Eston, R. Neuromuscular Function after Exercise-Induced Muscle Damage. Sports Med. 2004, 34, 49–69. [Google Scholar] [CrossRef] [PubMed]
  66. Sieljacks, P.; Matzon, A.; Wernbom, M.; Ringgaard, S.; Vissing, K.; Overgaard, K. Muscle damage and repeated bout effect following blood flow restricted exercise. Graefe Arch. Clin. Exp. Ophthalmol. 2016, 116, 513–525. [Google Scholar] [CrossRef] [PubMed]
  67. Doma, K.; Leicht, A.; Sinclair, W.; Schumann, M.; Damas, F.; Burt, D.; Woods, C. Impact of Exercise-Induced Muscle Damage on Performance Test Outcomes in Elite Female Basketball Players. J. Strength Cond. Res. 2018, 32, 1731–1738. [Google Scholar] [CrossRef][Green Version]
  68. Harty, P.S.; Cottet, M.L.; Malloy, J.K.; Kerksick, C.M. Nutritional and Supplementation Strategies to Prevent and Attenuate Exercise-Induced Muscle Damage: A Brief Review. Sports Med. Open 2019, 5, 1–17. [Google Scholar] [CrossRef]
  69. Dupuy, O.; Douzi, W.; Theurot, D.; Bosquet, L.; Dugue, B. An Evidence-Based Approach for Choosing Post-exercise Recovery Techniques to Reduce Markers of Muscle Damage, Soreness, Fatigue, and Inflammation: A Systematic Review with Meta-Analysis. Front. Physiol. 2018, 9, 403. [Google Scholar] [CrossRef]
  70. Clifford, T.; Ventress, M.; Allerton, D.; Stansfield, S.; Tang, J.; Fraser, W.D.; Vanhoecke, B.; Prawitt, J.; Stevenson, E. The effects of collagen peptides on muscle damage, inflammation and bone turnover following exercise: A randomized, controlled trial. Amino Acids 2019, 51, 691–704. [Google Scholar] [CrossRef][Green Version]
  71. Buckley, J.D.; Thomson, R.; Coates, A.M.; Howe, P.; DeNichilo, M.O.; Rowney, M.K. Supplementation with a whey protein hydrolysate enhances recovery of muscle force-generating capacity following eccentric exercise. J. Sci. Med. Sport 2010, 13, 178–181. [Google Scholar] [CrossRef]
  72. Brown, M.; Stevenson, E.J.; Howatson, G. Whey protein hydrolysate supplementation accelerates recovery from exercise-induced muscle damage in females. Appl. Physiol. Nutr. Metab. 2018, 43, 324–330. [Google Scholar] [CrossRef] [PubMed]
  73. Cooke, M.B.; Rybalka, E.; Stathis, C.G.; Cribb, P.J.; Hayes, A. Whey protein isolate attenuates strength decline after eccentrically-induced muscle damage in healthy individuals. J. Int. Soc. Sports Nutr. 2010, 7, 30. [Google Scholar] [CrossRef] [PubMed][Green Version]
  74. Gee, I.T.; Woolrich, T.J.; Smith, M.F. Effectiveness of Whey Protein Hydrolysate and Milk-Based Formulated Drinks on Recovery of Strength and Power Following Acute Resistance Exercise. J. Hum. Kinet. 2019, 68, 193–202. [Google Scholar] [CrossRef] [PubMed][Green Version]
  75. Lollo, P.; Amaya-Farfan, J.; Faria, I.; Salgado, J.; Chacon-Mikahil, M.P.T.; da Cruz, A.G.; Oliveira, C.; Montagner, P.; Arruda, M. Hydrolysed whey protein reduces muscle damage markers in Brazilian elite soccer players compared with whey protein and maltodextrin. A twelve-week in-championship intervention. Int. Dairy J. 2014, 34, 19–24. [Google Scholar] [CrossRef]
  76. Shenoy, S.; Dhawan, M.; Sandhu, J.S. Four Weeks of Supplementation with Isolated Soy Protein Attenuates Exercise-Induced Muscle Damage and Enhances Muscle Recovery in Well Trained Athletes: A Randomized Trial. Asian J. Sports Med. 2016, 7, e33528. [Google Scholar] [CrossRef][Green Version]
  77. Moore, D.R. Maximizing Post-exercise Anabolism: The Case for Relative Protein Intakes. Front. Nutr. 2019, 6, 6. [Google Scholar] [CrossRef]
  78. Fielding, R.A.; Violan, M.A.; Svetkey, L.; Abad, L.W.; Manfredi, T.J.; Cosmas, A.; Bean, J. Effects of prior exercise on eccentric exercise-induced neutrophilia and enzyme release. Med. Sci. Sports Exerc. 2000, 32, 359–364. [Google Scholar] [CrossRef]
  79. Tidball, J.G. Inflammatory cell response to acute muscle injury. Med. Sci. Sports Exerc. 1995, 27, 1022–1032. [Google Scholar] [CrossRef]
  80. Tidball, J.G. Inflammatory processes in muscle injury and repair. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2005, 288, R345–R353. [Google Scholar] [CrossRef] [PubMed][Green Version]
  81. Cerqueira, É.; Marinho, D.A.; Neiva, H.P.; Lourenço, O. Inflammatory Effects of High and Moderate Intensity Exercise—A Systematic Review. Front. Physiol. 2020, 10, 1550. [Google Scholar] [CrossRef]
  82. Lin, E.; Kotani, J.G.; Lowry, S.F. Nutritional modulation of immunity and the inflammatory response. Nutrients 1998, 14, 545–550. [Google Scholar] [CrossRef]
  83. Hawke, T.; Garry, D.J. Myogenic satellite cells: Physiology to molecular biology. J. Appl. Physiol. 2001, 91, 534–551. [Google Scholar] [CrossRef] [PubMed]
  84. Perandini, L.A.; Chimin, P.; Lutkemeyer, D.D.S.; Câmara, N.O.S. Chronic inflammation in skeletal muscle impairs satellite cells function during regeneration: Can physical exercise restore the satellite cell niche? FEBS J. 2018, 285, 1973–1984. [Google Scholar] [CrossRef] [PubMed][Green Version]
  85. Guha, S.; Majumder, K. Structural-features of food-derived bioactive peptides with anti-inflammatory activity: A brief review. J. Food Biochem. 2018, 43, e12531. [Google Scholar] [CrossRef] [PubMed]
  86. Chakrabarti, S.; Wu, J. Milk-Derived Tripeptides IPP (Ile-Pro-Pro) and VPP (Val-Pro-Pro) Promote Adipocyte Differentiation and Inhibit Inflammation in 3T3-F442A Cells. PLoS ONE 2015, 10, e0117492. [Google Scholar] [CrossRef] [PubMed][Green Version]
  87. Jiehui, Z.; Liuliu, M.; Haihong, X.; Yang, G.; Yingkai, J.; Lun, Z.; Li, D.X.A.; Dongsheng, Z.; Shaohui, Z. Immunomodulating effects of casein-derived peptides QEPVL and QEPV on lymphocytes in vitro and in vivo. Food Funct. 2014, 5, 2061–2069. [Google Scholar] [CrossRef]
  88. Raizel, R.; Leite, J.S.M.; Hypólito, T.M.; Coqueiro, A.Y.; Newsholme, P.; Cruzat, V.F.; Tirapegui, J. Determination of the anti-inflammatory and cytoprotective effects of l-glutamine and l-alanine, or dipeptide, supplementation in rats submitted to resistance exercise. Br. J. Nutr. 2016, 116, 470–479. [Google Scholar] [CrossRef][Green Version]
  89. Dröge, W. Free Radicals in the Physiological Control of Cell Function. Physiol. Rev. 2002, 82, 47–95. [Google Scholar] [CrossRef]
  90. Powers, S.K.; Ji, L.L.; Kavazis, A.N.; Jackson, M.J. Reactive Oxygen Species: Impact on Skeletal Muscle. Compr. Physiol. 2011, 1, 941–969. [Google Scholar] [CrossRef][Green Version]
  91. Aoi, W.; Naito, Y.; Takanami, Y.; Kawai, Y.; Sakuma, K.; Ichikawa, H.; Yoshida, N.; Yoshikawa, T. Oxidative stress and delayed-onset muscle damage after exercise. Free. Radic. Biol. Med. 2004, 37, 480–487. [Google Scholar] [CrossRef]
  92. Suetsuna, K.; Ukeda, H.; Ochi, H. Isolation and characterization of free radical scavenging activities peptides derived from casein. J. Nutr. Biochem. 2000, 11, 128–131. [Google Scholar] [CrossRef]
  93. Kitts, D. Antioxidant properties of casein-phosphopeptides. Trends Food Sci. Technol. 2005, 16, 549–554. [Google Scholar] [CrossRef]
  94. Power, O.; Jakeman, P.; Fitzgerald, R.J. Antioxidative peptides: Enzymatic production, in vitro and in vivo antioxidant activity and potential applications of milk-derived antioxidative peptides. Amino Acids 2013, 44, 797–820. [Google Scholar] [CrossRef] [PubMed]
  95. Hernández-Ledesma, B.; Dávalos, A.; Bartolomé, A.B.; Amigo, L. Preparation of Antioxidant Enzymatic Hydrolysates from α-Lactalbumin and β-Lactoglobulin. Identification of Active Peptides by HPLC-MS/MS. J. Agric. Food Chem. 2005, 53, 588–593. [Google Scholar] [CrossRef]
  96. Barzideh, Z.; Latiff, A.A.; Gan, C.-Y.; Abedin, Z.; Alias, A.K. ACE Inhibitory and Antioxidant Activities of Collagen Hydrolysates from the Ribbon Jellyfish (Chrysaora sp.). Food Technol. Biotechnol. 2014, 52, 495–504. [Google Scholar] [CrossRef]
  97. Park, S.Y.; Lee, J.-S.; Baek, H.-H.; Lee, H.G. Purification and characterization of antioxidant peptides from soy protein hydrolysate. J. Food Biochem. 2010, 34, 120–132. [Google Scholar] [CrossRef]
  98. Ma, H.; Liu, R.; Zhao, Z.; Zhang, Z.; Cao, Y.; Ma, Y.; Guo, Y.; Xu, L. A Novel Peptide from Soybean Protein Isolate Significantly Enhances Resistance of the Organism under Oxidative Stress. PLoS ONE 2016, 11, e0159938. [Google Scholar] [CrossRef] [PubMed]
  99. Stafylidis, S.; Arampatzis, A. Muscle—Tendon unit mechanical and morphological properties and sprint performance. J. Sports Sci. 2007, 25, 1035–1046. [Google Scholar] [CrossRef]
  100. Albracht, K.; Arampatzis, A. Exercise-induced changes in triceps surae tendon stiffness and muscle strength affect running economy in humans. Graefe Arch. Clin. Exp. Ophthalmol. 2013, 113, 1605–1615. [Google Scholar] [CrossRef] [PubMed]
  101. Lopes, A.D.; Hespanhol, L.C.; Yeung, S.S.; Costa, L.O.P. What Are the Main Running-Related Musculoskeletal Injuries? A Systematic Review. Sports Med. 2012, 42, 891–905. [Google Scholar] [CrossRef]
  102. Kjaer, M. Role of Extracellular Matrix in Adaptation of Tendon and Skeletal Muscle to Mechanical Loading. Physiol. Rev. 2004, 84, 649–698. [Google Scholar] [CrossRef] [PubMed]
  103. Alcock, R.D.; Shaw, G.C.; Tee, N.; Burke, L.M. Plasma Amino Acid Concentrations After the Ingestion of Dairy and Collagen Proteins, in Healthy Active Males. Front. Nutr. 2019, 6, 163. [Google Scholar] [CrossRef] [PubMed][Green Version]
  104. McKee, T.J.; Perlman, G.; Morris, M.; Komarova, S.V. Extracellular matrix composition of connective tissues: A systematic review and meta-analysis. Sci. Rep. 2019, 9, 10542. [Google Scholar] [CrossRef] [PubMed][Green Version]
  105. Kjaer, M.; Langberg, H.; Heinemeier, K.; Bayer, M.L.; Hansen, M.; Holm, L.; Doessing, S.; Kongsgaard, M.; Krogsgaard, M.R.; Magnusson, S.P. From mechanical loading to collagen synthesis, structural changes and function in human tendon. Scand. J. Med. Sci. Sports 2009, 19, 500–510. [Google Scholar] [CrossRef] [PubMed]
  106. Kannus, P. Structure of the tendon connective tissue. Scand. J. Med. Sci. Sports 2000, 10, 312–320. [Google Scholar] [CrossRef]
  107. Galloway, M.T.; Lalley, A.L.; Shearn, J.T. The Role of Mechanical Loading in Tendon Development, Maintenance, Injury, and Repair. J. Bone Jt. Surg. Am. 2013, 95, 1620–1628. [Google Scholar] [CrossRef]
  108. Minaguchi, J.; Koyama, Y.-I.; Meguri, N.; Hosaka, Y.; Ueda, H.; Kusubata, M.; Hirota, A.; Irie, S.; Mafune, N.; Takehana, K. Effects of Ingestion of Collagen Peptide on Collagen Fibrils and Glycosaminoglycans in Achilles Tendon. J. Nutr. Sci. Vitaminol. 2005, 51, 169–174. [Google Scholar] [CrossRef][Green Version]
  109. Yin, M.; Rusyn, I.; Schoonhoven, R.; Graves, L.M.; Rusyn, E.V.; Li, X.; Li, F.; Cox, A.D.; Harding, T.W.; Bunzendahl, H.; et al. Inhibition of chronic rejection of aortic allografts by dietary glycine. Transplantation 2000, 69, 773–781. [Google Scholar] [CrossRef]
  110. Yin, M.; Ikejima, K.E.; Arteel, G.; Seabra, V.; Bradford, B.U.; Kono, H.; Rusyn, I.; Thurman, R.G. Glycine accelerates recovery from alcohol-induced liver injury. J. Pharmacol. Exp. Ther. 1998, 286, 1014–1019. [Google Scholar]
  111. Nonaka, I.; Katsuda, S.-I.; Ohmori, T.; Shigehisa, T.; Nakagami, T.; Maruyama, S. In Vitro and in Vivo Anti-platelet Effects of Enzymatic Hydrolysates of Collagen and Collagen-related Peptides. Biosci. Biotechnol. Biochem. 1997, 61, 772–775. [Google Scholar] [CrossRef]
  112. Shaw, G.; Lee-Barthel, A.; Ross, M.L.; Wang, B.; Baar, K. Vitamin C–enriched gelatin supplementation before intermittent activity augments collagen synthesis. Am. J. Clin. Nutr. 2016, 105, 136–143. [Google Scholar] [CrossRef] [PubMed][Green Version]
  113. Schunck, M.; Oesser, S. Specific collagen peptides benefit the biosynthesis of matrix molecules of tendons and ligaments. J. Int. Soc. Sports Nutr. 2013, 10, P23. [Google Scholar] [CrossRef][Green Version]
  114. Barbosa, A.W.C.; Benevides, G.P.; Alferes, L.M.T.; Salomão, E.M.; Gomes-Marcondes, M.C.C.; Gomes, L. A leucine-rich diet and exercise affect the biomechanical characteristics of the digital flexor tendon in rats after nutritional recovery. Amino Acids 2010, 42, 329–336. [Google Scholar] [CrossRef] [PubMed]
  115. Farup, J.; Rahbek, S.K.; Vendelbo, M.H.; Matzon, A.; Hindhede, J.; Bejder, A.; Ringgard, S.; Vissing, K. Whey protein hydrolysate augments tendon and muscle hypertrophy independent of resistance exercise contraction mode. Scand. J. Med. Sci. Sports 2013, 24, 788–798. [Google Scholar] [CrossRef] [PubMed]
  116. Praet, S.F.; Purdam, C.R.; Welvaert, M.; Vlahovich, N.; Lovell, G.; Burke, L.M.; Gaida, J.E.; Manzanero, S.; Hughes, D.; Waddington, G. Oral Supplementation of Specific Collagen Peptides Combined with Calf-Strengthening Exercises Enhances Function and Reduces Pain in Achilles Tendinopathy Patients. Nutrients 2019, 11, 76. [Google Scholar] [CrossRef] [PubMed][Green Version]
  117. Vieira, C.P.; De Oliveira, L.P.; Guerra, F.D.R.; Almeida, M.D.S.D.; Marcondes, M.C.C.G.; Pimentel, E.R. Glycine Improves Biochemical and Biomechanical Properties Following Inflammation of the Achilles Tendon. Anat. Rec. Adv. Integr. Anat. Evol. Biol. 2015, 298, 538–545. [Google Scholar] [CrossRef] [PubMed]
  118. Notarnicola, A.; Pesce, V.; Vicenti, G.; Tafuri, S.; Forcignanò, M.; Moretti, B. SWAAT Study: Extracorporeal Shock Wave Therapy and Arginine Supplementation and Other Nutraceuticals for Insertional Achilles Tendinopathy. Adv. Ther. 2012, 29, 799–814. [Google Scholar] [CrossRef]
  119. Baar, K. Stress Relaxation and Targeted Nutrition to Treat Patellar Tendinopathy. Int. J. Sport Nutr. Exerc. Metab. 2019, 4, 1–5. [Google Scholar] [CrossRef] [PubMed][Green Version]
  120. McAdams, T.R.; Mithoefer, K.; Scopp, J.M.; Mandelbaum, B.R. Review: Articular Cartilage Injury in Athletes. Cartilage 2010, 1, 165–179. [Google Scholar] [CrossRef][Green Version]
  121. Jennings, L.; Wu, L.; King, K.B.; Hämmerle, H.; Cs-Szabo, G.; Mollenhauer, J. The Effects of Collagen Fragments on the Extracellular Matrix Metabolism of Bovine and Human Chondrocytes. Connect. Tissue Res. 2001, 42, 71–86. [Google Scholar] [CrossRef]
  122. Fichter, M.; Körner, U.; Schömburg, J.; Jennings, L.; Cole, A.A.; Mollenhauer, J. Collagen degradation products modulate matrix metalloproteinase expression in cultured articular chondrocytes. J. Orthop. Res. 2006, 24, 63–70. [Google Scholar] [CrossRef] [PubMed]
  123. Dressler, P.; Gehring, D.; Zdzieblik, D.; Oesser, S.; Gollhofer, A.; König, D. Improvement of Functional Ankle Properties Following Supplementation with Specific Collagen Peptides in Athletes with Chronic Ankle Instability. J. Sports Sci. Med. 2018, 17, 298–304. [Google Scholar] [CrossRef] [PubMed][Green Version]
  124. Zdzieblik, D.; Oesser, S.; Gollhofer, A.; König, D. Improvement of activity-related knee joint discomfort following supplementation of specific collagen peptides. Appl. Physiol. Nutr. Metab. 2017, 42, 588–595. [Google Scholar] [CrossRef][Green Version]
  125. Walrand, S.; Chiotelli, E.; Noirt, F.; Mwewa, S.; Lassel, T. Consumption of a Functional Fermented Milk Containing Collagen Hydrolysate Improves the Concentration of Collagen-Specific Amino Acids in Plasma. J. Agric. Food Chem. 2008, 56, 7790–7795. [Google Scholar] [CrossRef]
  126. Watanabe-Kamiyama, M.; Shimizu, M.; Kamiyama, S.; Taguchi, Y.; Sone, H.; Morimatsu, F.; Shirakawa, H.; Furukawa, Y.; Komai, M. Absorption and Effectiveness of Orally Administered Low Molecular Weight Collagen Hydrolysate in Rats. J. Agric. Food Chem. 2010, 58, 835–841. [Google Scholar] [CrossRef]
  127. Campbell, S.C.; Wisniewski, P.J. Chapter 13—Nutritional Recommendations for Athletes. In Nutrition in the Prevention and Treatment of Disease, 4th ed.; Coulston, A.M., Boushey, C.J., Ferruzzi, M.G., Delahanty, L.M., Eds.; Academic Press: Cambridge, MA, USA, 2017; pp. 255–271. [Google Scholar] [CrossRef]
  128. Cintineo, H.P.; Arent, M.A.; Antonio, J.; Arent, S.M. Effects of Protein Supplementation on Performance and Recovery in Resistance and Endurance Training. Front. Nutr. 2018, 5, 83. [Google Scholar] [CrossRef]
  129. Drummond, M.J.; Rasmussen, B. Leucine-enriched nutrients and the regulation of mammalian target of rapamycin signalling and human skeletal muscle protein synthesis. Curr. Opin. Clin. Nutr. Metab. Care 2008, 11, 222–226. [Google Scholar] [CrossRef]
  130. Baar, K. Minimizing Injury and Maximizing Return to Play: Lessons from Engineered Ligaments. Sports Med. 2017, 47, 5–11. [Google Scholar] [CrossRef][Green Version]
  131. McLellan, T.M.; Pasiakos, S.M.; Lieberman, H.R. Effects of Protein in Combination with Carbohydrate Supplements on Acute or Repeat Endurance Exercise Performance: A Systematic Review. Sports Med. 2013, 44, 535–550. [Google Scholar] [CrossRef]
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