nutrients

Systematic Review
Nutritional Strategies in the Rehabilitation of Musculoskeletal
Injuries in Athletes: A Systematic Integrative Review
John E. Giraldo-Vallejo 1,2 , Miguel Á. Cardona-Guzmán 1 , Ericka J. Rodríguez-Alcivar 1 , Jana Kočí 2,3 ,
Jorge L. Petro 2,4 , Richard B. Kreider 5 , Roberto Cannataro 2,6 and Diego A. Bonilla 1,2,3,7, *

1 Grupo de Investigación NUTRAL, Facultad de Ciencias de Nutrición y Alimentos, Universidad CES,

Medellín 050021, Colombia
2 Research Division, Dynamical Business & Science Society—DBSS International SAS, Bogotá 110311, Colombia
3 Department of Education, Faculty of Education, Charles University, 11636 Prague, Czech Republic
4 Research Group in Physical Activity, Sports and Health Sciences (GICAFS), Universidad de Córdoba,
Montería 230002, Colombia
5 Exercise & Sport Nutrition Laboratory, Human Clinical Research Facility, Texas A&M University,
College Station, TX 77843, USA
6 Galascreen Laboratories, Department of Pharmacy, Health, and Nutritional Sciences, University of Calabria,
87036 Rende, Italy
7 Sport Genomics Research Group, Department of Genetics, Physical Anthropology and Animal Physiology,
Faculty of Science and Technology, University of the Basque Country (UPV/EHU), 48940 Leioa, Spain
* Correspondence: dabonilla@dbss.pro; Tel.: +57-320-335-2050

Abstract: It is estimated that three to five million sports injuries occur worldwide each year. The
highest incidence is reported during competition periods with mainly affectation of the musculoskele-
tal tissue. For appropriate nutritional management and correct use of nutritional supplements, it
is important to individualize based on clinical effects and know the adaptive response during the
rehabilitation phase after a sports injury in athletes. Therefore, the aim of this PRISMA in Exercise,
Rehabilitation, Sport Medicine and Sports Science PERSiST-based systematic integrative review was
to perform an update on nutritional strategies during the rehabilitation phase of musculoskeletal
Citation: Giraldo-Vallejo, J.E.;
injuries in elite athletes. After searching the following databases: PubMed/Medline, Scopus, PEDro,
Cardona-Guzmán, M.Á.;
Rodríguez-Alcivar, E.J.; Kočí, J.; Petro,
and Google Scholar, a total of 18 studies met the inclusion criteria (Price Index: 66.6%). The risk
J.L.; Kreider, R.B.; Cannataro, R.; of bias assessment for randomized controlled trials was performed using the RoB 2.0 tool while
Bonilla, D.A. Nutritional Strategies in review articles were evaluated using the AMSTAR 2.0 items. Based on the main findings of the
the Rehabilitation of Musculoskeletal selected studies, nutritional strategies that benefit the rehabilitation process in injured athletes include
Injuries in Athletes: A Systematic balanced energy intake, and a high-protein and carbohydrate-rich diet. Supportive supervision
Integrative Review. Nutrients 2023, should be provided to avoid low energy availability. The potential of supplementation with collagen,
15, 819. https://doi.org/10.3390/ creatine monohydrate, omega-3 (fish oils), and vitamin D requires further research although the
nu15040819 effects are quite promising. It is worth noting the lack of clinical research in injured athletes and
Academic Editor: Louise Deldicque the higher number of reviews in the last 10 years. After analyzing the current quantitative and
non-quantitative evidence, we encourage researchers to conduct further clinical research studies
Received: 23 December 2022
evaluating doses of the discussed nutrients during the rehabilitation process to confirm findings, but
Revised: 30 January 2023
also follow international guidelines at the time to review scientific literature.
Accepted: 1 February 2023
Published: 5 February 2023
Keywords: sports injury; musculoskeletal pain; nutrients; dietary supplements; sports nutrition;
sports nutritional physiological phenomena; athletic injuries

Copyright: © 2023 by the authors.

Licensee MDPI, Basel, Switzerland.
This article is an open access article 1. Introduction
distributed under the terms and Currently, elite athletes are subjected to a grueling competitive calendar [1] which
conditions of the Creative Commons
is generally associated with a higher training volume and competition load [2]. The
Attribution (CC BY) license (https://
consequence of this competitive model is not only reduced performance, as has been
creativecommons.org/licenses/by/
reported in several sports [3–6], but also an increase in the occurrence of lesions. In recent
4.0/).

Nutrients 2023, 15, 819. https://doi.org/10.3390/nu15040819 https://www.mdpi.com/journal/nutrients

Nutrients 2023, 15, 819 2 of 25

years, studies on injury prevention [7] along with the technologies and strategies to prevent
them have increased exponentially; however, the incidence of sport-related injuries has
remained constant [8]. An injury episode can be expressed as the number of injuries that
the athlete may suffer per 1000 h of exposure to the risk of injury, both in training and
in competition. It is estimated that an average of 3 to 5 million sports injuries occur in
a year [9], with the prevalence being higher during competitions (72.2%) than during
training (21.8%) [10]. For instance, Dupont et al. [11] reported a 6.2 times higher injury
rate in soccer players who played two games a week compared to those who played
only one, with the majority of injuries (76%) caused by overuse. In general, the injury
rate in soccer is mostly significant during games/matches (9.5 to 48.7 injuries/1000 h in
competitive male youth players, 2.5 to 8.7 injuries/1000 h in male professional players,
and 12.5 to 30.3 injuries/1000 h in female players) [12]. Importantly, it has been reported
that approximately 81 per 1000 elite athletes suffered an injury during competition at
World Championships with a 40.9% prevalence of musculoskeletal injuries [13]. Similarly,
a college basketball player has a rate of 9.9 injuries per 1000 h of competitive games,
while only 4.3 injuries are sustained per 1000 h of training [14]. In the National Basketball
Association professional league, the exposure rate per player is 3.26 injuries per 1000 h of
competitive play, with the prevalence being higher in the first month of the league [15].
The number of musculoskeletal injuries and illnesses suffered by athletes during a
season has recently been related to sporting success, showing that the lower the number
of sporting injuries, the higher the performance [16]. In particular, soft tissue injuries
involving muscle, tendons, and ligaments are very common at all levels of sport [17]. The
most frequent injuries are muscle (especially in the hamstring muscles [18]), ligament (i.e.,
anterior cruciate ligament rupture [19]), and joint (i.e., ankle sprain [8]) injuries. In fact, up
to 80% of injuries generally affect the musculoskeletal tissue. For instance, deltoid muscle
injuries per year are between 12 and 19% in baseball players and between 23 and 38% in
swimmers [20]. In marathon runners, the incidence of training-related lower limb muscle
injuries is estimated to be between 19 and 58% [21]. In tennis, about 3.49 injuries/1000 h
have been reported frequently in joints (29.5%), tendinopathies (22.1%), ankle (20%), and
wrist (15.8%) [22].
Generally, two stages of management can be considered in the rehabilitation process
from a sport injury [23]. The first stage corresponds to the phase of immobilization, atrophy,
and subsequent tissue repair. This stage can last for several days or months depending on
the severity of the injury. Normally, it is a period that leads to deconditioning due to the
lack of movement of the affected body section. This might evoke significant loss of muscle
mass as well as functional alterations of the musculoskeletal and connective tissues [24].
Some nutritional strategies are suggested to contribute to the protection/repair of muscle
tissue and modulation of the immune system by controlling catabolic and inflammation
processes through the regulation of reactive oxygen species (ROS) production and catabolic
pathways [17,25,26]. However, to date, the effect of these nutrients on the rehabilitation
of elite athletes is unclear or even ambiguous in certain contexts [27]. The second stage
corresponds to the readaptation to training and improvement of the psychological profile
(i.e., emotional level) of the athlete. Some authors refer to this as the reathletization
phase [28]. We have recently highlighted the compensatory neural changes (e.g., brain
cortical changes) and the cognitive load that might affect recovery and relapse after a
musculoskeletal injury [29]. Since early mobilization and stimulation of the affected tissue
(i.e., low-intensity pulsed ultrasound, neuromuscular electric stimulation) has been shown
to have a positive effect on collagen reorganization and general connective tissue repair,
it is recommended to start with a controlled loading program as soon as pain or injury
permits [6]. It is worth noting that medical personnel, physiotherapists, and athletic trainers
should respect the natural healing process of the human body and ensure a balance between
workload and rest time to avoid longer lasting tissue damage [30,31].
To facilitate the recovery of physical-related parameters, a multidisciplinary team of
sports practitioners is needed to cover the energetic, nutritional, and psychological among
Nutrients 2023, 15, 819 3 of 25

other demands of the injured elite athletes. Our group has emphasized that adopting a sys-
temic (integrative and multifactorial), evolutionary (intuitive), and adaptive (ever-changing
based on individualization) perspective or ‘Bio-Logic approach’ [32] would enhance our
understanding of the flow of information through interactions between system components
and their regulatory aspects for a given phenotype and the allostatic load. Indeed, the
allostatic load (as the cost a biological system must pay in order to reset physiological
parameters [e.g., injury recovery] during the adaptation [33]) has been proposed as a
promising and underutilized measure that might be useful to assess the spinal cord injury
time course [34]. Importantly, nutrition is one of the many factors that might impact the
allostatic load and, thereby, it might influence the musculoskeletal tissue overload and
repair. Therefore, a special nutritional intervention throughout the rehabilitation process
is warranted to ensure integral recovery while accelerating tissue regeneration [24]. In
this regard, it should be noted that tissue repair is a high energy-consuming process (i.e.,
protein synthesis, cytoskeleton remodeling, etc.). As a result, the energetic and protein defi-
ciency might hamper proper healing and increase the inflammatory response which would
decrease the rate of tissue recovery while increase injury relapse [23]. In this sense, the aim
of this systematic integrative review was to update the effective nutritional strategies that
benefit the rehabilitation of musculoskeletal injuries in elite athletes.

2. Methods
This study employed the five stages developed by Whittemore and Knafl [35] as the
established guidelines of the integrative review. This allows for the combination of past
empirical or theoretical literature to provide a more comprehensive understanding of a
particular phenomenon or healthcare problem, which has a greater impact to establish
evidence-based recommendations. The aim was to synthesize the occurrence of literature
regarding nutrition interventions for the injured athlete. Similar to previously published
articles [36], the review methodology was enhanced by optimizing the stages of literature
search, data evaluation, and data analysis in order to systematize the review process and
improve the scientific soundness according to recommendations given by Hopia et al. [37]
and the PRISMA in Exercise, Rehabilitation, Sport Medicine and Sports Science (PERSiST)
guidelines [38]. The protocol of this review was published and freely accessible at Figshare
to avoid unnecessary duplication (DOI: 10.6084/m9.figshare.21399696).

2.1. Eligibility Criteria

The inclusion criteria for this review were as follows: (1) Empirical or theoretical
articles (quantitative, qualitative, mixed method studies, and systematic reviews) that
assessed or included elite/high-performance male and female athletes over 18 years of age.
Only review articles that evaluated the use of nutrients in the rehabilitation phase after
a musculoskeletal sports injury were reported or discussed; (2) studies were published
between 2012 and 2022; (3) articles were written in the English and Spanish language;
(4) available in full text; and (5) focused solely on the assessment of nutritional (energy
intake, macronutrient distribution, micronutrients, etc.) or supplementation strategies
during the rehabilitation process in injured athletes. On the other hand, the exclusion
criteria consisted of articles that: (1) Included children, older adults, physically active peo-
ple, amateur or recreational population and non-conventional athletes; (2) commentaries,
dissertations, theses, editorials, letters to the editor, and books; (3) interventions where the
dosage and timing of intake of nutrients and sports supplements were not specified; and
(4) articles that did not analyze the relationship between nutrition and musculoskeletal
sports injuries (e.g., concussions).

2.2. Information Sources

The following academic databases were selected to examine the literature: PubMed/
Medline, Scopus, PEDro, and Google Scholar.
Nutrients 2023, 15, 819 4 of 25

2.3. Search Strategy

The patient, intervention, comparison, and outcome (PICO) strategy was utilized for
structuring the research question: P (athletes aged >18 years old) I (nutritional intervention)
C (placebo, or non-exposed control group [pre-post]) O (musculoskeletal recovery- or
rehabilitation-related outcomes) [39]. The authors followed the identical string in searching
the databases to ensure consistency with the data search, as follows: (i) Pubmed/MedLine,
(Nutrition OR supplementation) AND sports AND inju*, and “sports injuries” OR “ath-
letic injuries” OR “sport injury rehabilitation” AND (nutrition OR dietary supplements);
(ii) Scopus, “sports injuries” OR “athletic injuries” OR “sport injury rehabilitation” AND
(nutrition OR dietary supplements). In addition, further papers were hand searched (e.g.,
snowballing) in the databases. The data search in PEDro and Google Scholar was performed
using free language terms, such as nutrition, supplementation, and musculoskeletal injuries.

2.4. Selection Process

After executing Boolean algorithms, filters were used in the different databases to
select potentially eligible articles. Four authors independently evaluated the databases
for articles that met the inclusion criteria (J.E.G-V., M.A.C-G., E.J.R-A., and D.A.B.). Dis-
crepancies were identified and resolved through discussion (with a fourth author where
necessary). Those publications that met all the requirements went on to the next phase of
data analysis and synthesis. The database search took place during June and October 2022
to capture relevant articles for the review, although an updated search was conducted prior
to manuscript submission.

2.5. Data Collection Process and Items

A table to synthesize results and findings was built with the following data: (i) General
information on the study (title, author, year, and type of study); (ii) description of the study
population; (iii) study aim and methodology; (iv) characteristics of the nutritional and/or
supplementation strategy (timing and dosage); and (v) main findings of the study.

2.6. Study Risk of Bias Assessment

Risk of bias assessment for randomized clinical studies was performed using the
Cochrane RoB 2.0 tool (RoB2 Development Group, University of Bristol, Bristol, UK) [40].
Five bias domains (randomization process, deviations from intended interventions, miss-
ing outcome data, outcome measurement, and selection of the reported outcomes) were
evaluated [41]. The overall assessment of the risk of bias for each outcome was presented
as: ‘Low risk’, ‘some concerns’, or ‘high risk’ of bias. We used the AMSTAR 2.0 checklist in
order to assess the methodological quality of the selected review articles [42]. The 16 items
presented to determine the classification of the systematic review as ‘reliable’ or ‘not very
valid’ were considered [43].

3. Results
3.1. Study Selection
After running the search algorithms with Boolean operators and free language terms,
3736 references were obtained. Filtering by date, type of article, language, and availability
of full text resulted in 1065 potentially eligible studies. It should be noted that +100 clinical
trials were published between 1992 and 2012. However, after screening the abstracts and full
texts of these articles and analyzing strict compliance with inclusion criteria, 1045 articles
were excluded. A total of 18 studies met the requirements of this integrative systematic
review (Price Index: 66.6%). Figure 1 shows a flow diagram of the literature search.

3.2. Risk of Bias within Studies

Compared to review articles, fewer clinical trials have been carried out in the last
10 years. The methodological quality of the five randomized clinical trials included in this
integrative systematic review is shown in Figure 2.
Nutrients 2023, 15, 819
atic review (Price Index: 66.6%). Figure 1 shows a flow diagram of the literature search.
5 of 29

full texts of these articles and analyzing strict compliance with inclusion criteria, 1045 ar-
Nutrients 2023, 15, 819 5 of 25
ticles were excluded. A total of 18 studies met the requirements of this integrative system-
atic review (Price Index: 66.6%). Figure 1 shows a flow diagram of the literature search.

Figure 1. PRISMA flow diagram.

3.2. Risk of Bias within Studies

Compared to review articles, fewer clinical trials have been carried out in the last 10
years. The methodological quality of the five randomized clinical trials included in this
integrative systematic review is shown in Figure 2.
Figure 1. PRISMA flow diagram.
Figure 1. PRISMA flow diagram.

3.2. Risk of Bias within Studies

Compared to review articles, fewer clinical trials have been carried out in the last 10
years. The methodological quality of the five randomized clinical trials included in this
integrative systematic review is shown in Figure 2.

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formed on this topic is notable to date. Only one retrospective cross-sectional study that
evaluated injured Australian and international athletes was included [44].
Nutrients 2023, 15, 819 6 of 25

Table 1. Quality assessment checklist for included review articles.

Papadopoulou Burton Turnagol Khatri Smith-Ryan Papadopoulou Quintero Kahn Pyne et al.
Close et al. Tipton Wall et al.
AMSTAR QUESTIONS et al. 2022 et al. 2022 et al. 2022 et al. 2021 et al. 2020 et al. 2020 et al. 2018 et al. 2015 2014
2019 [13] 2015 [17] 2015 [52]
[10] [45] [46] [47] [48] [49] [50] [51] [53]
Did the research questions and inclusion
criteria for the review include the Yes Yes Yes Yes No Yes Yes Yes Yes Yes Yes Yes
components of PICO?
Did the report of the review contain an
explicit statement that the review methods
were established prior to the conduct of the No Yes No Medium No No No Medium No No No No
review and did the report justify any
significant deviations from the protocol?
Did the review authors explain their selection
of the study designs for inclusion in No Yes No Yes No No No Yes No No No No
the review?
Did the review authors use a comprehensive
No Medium No Medium No No No Medium No No No No
literature search strategy?
Did the review authors perform study
No Yes No Yes No No No No No No No No
selection in duplicate?
Did the review authors perform data
No Yes No Yes No No No No No No No No
extraction in duplicate?
Did the review authors provide a list of
No Yes No Yes No No No Yes No No No No
excluded studies and justify the exclusions?
Did the review authors describe the included
No No No Medium No No No No No No No No
studies in adequate detail?
Did the review authors use a satisfactory
technique for assessing the risk of bias (RoB)
No 0 No Yes No No No 0 No No No No
in individual studies that were included in
the review?
Did the review authors report on the sources
of funding for the studies included in No No No Yes No No No No No No No No
the review?
If meta-analysis was performed did the
review authors use appropriate methods for 0 0 0 0 0 0 0 0 0 0 0 0
statistical combination of results?
If meta-analysis was performed, did the
review authors assess the potential impact of
0 0 0 0 0 0 0 0 0 0 0 0
RoB in individual studies on the results of the
meta-analysis or other evidence synthesis?
Did the review authors account for RoB in
individual studies when
No No No Yes No No No No No No No No
interpreting/discussing the results of
the review?
Nutrients 2023, 15, 819 7 of 25

Table 1. Cont.

Papadopoulou Burton Turnagol Khatri Smith-Ryan Papadopoulou Quintero Kahn Pyne et al.
Close et al. Tipton Wall et al.
AMSTAR QUESTIONS et al. 2022 et al. 2022 et al. 2022 et al. 2021 et al. 2020 et al. 2020 et al. 2018 et al. 2015 2014
2019 [13] 2015 [17] 2015 [52]
[10] [45] [46] [47] [48] [49] [50] [51] [53]
Did the review authors provide a satisfactory
explanation for, and discussion of, any
Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes
heterogeneity observed in the results of
the review?
If they performed quantitative synthesis did
the review authors carry out an adequate
investigation of publication bias (small study 0 0 0 0 0 0 0 0 0 0 0 0
bias) and discuss its likely impact on the
results of the review?
Did the review authors report any potential
sources of conflict of interest, including any
Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes
funding they received for conducting
the review?

Table 2. Synthesis of the selected articles for the integrative review.

Participants
Type of Study Aim Methodology Dosage and Timing Main Findings Reference
(M; F)
n = 45 (32 M; 13 F) Muscle strengthening exercises, A muscle rehabilitation
To determine the effect of a
high-performance athletes. proprioception, and running. program with or without
muscle 2–3-week rehabilitation
Athletes were randomly leucine favored the
program following ACL
Rugby (n = 17), Soccer (n = 10), assigned to receive L-leucine 330 mg of L-leucine per capsule improvement of muscle quality. Laboute
reconstruction and the
RCT/Quantitative Analysis Handball (n = 5), Judo (n = 4), (n = 22) or placebo (n = 23). four times per day (1.2 g However, leucine et al. (2013)
influence of L-leucine
Basketball (n = 3), Tennis Thigh perimeter, isokinetic leucine daily). supplementation favored the [54]
supplementation on muscle
(n = 2), Climbing (n = 1), strength, single-leg long jump, recovery of the injured muscle
strength in athletes undergoing
Motocross (n = 1), Kitesurf and body fat (based on and a reduction of 1.28% in
sports reathletization.
(n = 1). skinfolds) were measured. body fat.

• High protein diet (1.6 to

To summarize the physiological 2.5 g/kg/day) with a
basis of muscle atrophy/disuse high leucine content Specific nutritional compounds,
and discuss nutritional (2.5–3 g). Consume 4–6 such as Ω3, high protein diet
74 references Expert view and meals daily with 20–35 g
Narrative intervention strategies to limit (including leucine), CrM, and
(from year of publication non-structured analysis of the per meal. Wall et al. (2015) [52]
Review/Qualitative Analysis muscle tissue loss during HMB may assist in maintaining
to 2015). scientific literature. • 1.5 g of HMB two times
recovery from injury (including muscle protein synthesis rates
non-immobilization- per day. during a period of injury.
induced disuse). • 4 g of Ω3 per day.
• 20 g of CrM per day
(high or loading dose).
Nutrients 2023, 15, 819 8 of 25

Table 2. Cont.

Participants
Type of Study Aim Methodology Dosage and Timing Main Findings Reference
(M; F)
Athletes were assigned to
n = 30 (30 M; 0 F) To examine the effectiveness
receive glucosamine (n = 15) or Glucosamine sulfate
Athletes who underwent of glucosamine sulfate
placebo (n = 15) during 8 weeks. 1000 mg of glucosamine sulfate supplementation did not Eraslan and Ulkar (2015)
RCT/Quantitative Analysis arthroscopic ACL administration on the
Knee pain (VAS), functional per day for 8 weeks. positively affect the [55]
reconstruction (73% were rehabilitation outcomes of ACL
status, and isokinetic strength rehabilitation outcomes.
soccer players). reconstructed male athletes.
were measured.
Athletes with musculoskeletal
injuries have significantly
To translate the knowledge 4000 IU of Vitamin D per day or lower vitamin D levels relative
74 references Expert view and
Narrative regarding the role of vitamin D 50,000 IU per week for 8 weeks to athletes without injuries. Kahn et al. (2015) [51]
(from year of publication non-structured analysis of the
Review/Qualitative Analysis in athletic injuries to sports (to correct deficiency Treatment of vitamin D
to 2015). scientific literature.
physical therapy practice. during rehabilitation). deficiency would lead to a
decrease in the recurrence
of musculoskeletal injuries.

To examine and update the • High protein diet (2 to The best recommendation
evidence for nutritional 2.5 g/kg/day). would be to adopt a ‘first, do
strategies to support the • 10–20 g of EAA two no harm’ approach. The basis
136 references enhancement of recovery and Expert view and times per day.
Narrative Review/Qualitative of nutritional strategy for an
(from year of publication return to training and non-structured analysis of the • Fish oil (Ω3). Tipton (2015) [17]
Analysis injured athlete should be a
to 2015). competition (focus on the first scientific literature. • CrM. well-balanced diet based on
stage of injury, i.e., wound • Micronutrients (vitamin whole foods from nature that
healing and reduced activity A, vitamin C, vitamin D, are minimally processed.
or immobilization). Zn, etc.).

Twelve weeks of vitamin D3

n = 21 (21 M; 0 F) supplementation appears to be
Athletes received vitamin D for
Swiss elite wheelchair indoor sufficient to reach an optimal
To investigate the effect of 12 weeks after detecting
athletes with a spinal cord vitamin D status in indoor
vitamin D supplementation on insufficiency at baseline. 6000 IU of vitamin D3
injury. wheelchair athletes. The real
RCT/Quantitative Analysis muscle strength and Muscle strength, power, and (cholecalciferol) daily over Flueck et al. (2016) [56]
effect of vitamin D
performance in indoor the extremity function and 12 weeks.
Wheelchair rugby (n = 15), supplementation on upper
wheelchair athletes. symptoms (DASH
basketball (n = 4), or table body exercise performance in
questionnaire) were measured.
tennis (n = 2). athletes with a spinal cord
injury still remains unclear.
Nutrients 2023, 15, 819 9 of 25

Table 2. Cont.

Participants
Type of Study Aim Methodology Dosage and Timing Main Findings Reference
(M; F)

• Avoid chronic low

energy availability
(<30 kcal per kg of FFM
per day). The nutritional strategies
• High protein diet discussed in this review can be
To identify nutritional
(2.3 g/kg/day). implemented to decrease risk,
strategies to assist with the
89 references Expert view and • 10–20 g of EAA two marked loss of muscle mass
Narrative Review/Qualitative most common injuries and
(from year of publication non-structured analysis of the times per day. due to disuse, and recovery Close et al. (2019) [13]
Analysis consideration of the change in
to 2019).
energy requirements during the
scientific literature. • 5 g of Ω3 per day time in the injured athlete.
(2 weeks). Supportive supervision should
injury period.
• 20 g of CrM per day be provided to avoid low
(divided in four doses). energy availability.
• 2000–4000 UI of vitamin
D per day.
• ~1300 mg of Ca per day.

• High protein diet (1.6 to

2.5 g/kg/day) with A high protein diet is
An overview of the nutritional Semi-structured literature
20–35 g per meal (10 g of recommended to maintain
strategies and search in PubMed, Science
80 references EAA). muscle mass. An adequate
Narrative Review/Qualitative recommendations after a Direct, Scielo, Embase, and
(from year of publication to • 3–5 mg of CoQ10 per supply of antioxidant Quintero et al. (2018) [50]
Analysis muscular sports injury, Google Scholar databases using
2018). day. compounds and the use of
emphasizing on specific search terms (MeSH
• ≥1010 CFU of probiotics might accelerate the
muscle recovery. and DeCS).
Lactobacillus acidophilus or muscle recovery process.
Bifidobacterium longum.

Athletes were assigned to

The results of this study
receive CrM (n = 9) or placebo
To investigate the effect of indicate that CrM
n = 18 (n = 9) during 6 weeks as part
creatine (Cr) supplementation supplementation combined
(10 M; 8 F) of the conservative treatment of 20 g of CrM for 5 days (loading
on regeneration periods in with therapeutic strategy
RCT/Quantitative Analysis Injured adolescent male and the tendinopathy. Segmental phase) followed by 5 g daily for Juhasz et al. (2018) [57]
tendon overuse injury effectively supports the
female competitive lean mass, ankle plantar flexion 37 days (maintenance phase).
rehabilitation of adolescent rehabilitation of tendon
fin swimmers. peak torque, pain intensity, and
fin swimmers. overuse injury of adolescent
muscle damage
fin swimmers.
were measured.

• Ensure sufficient energy. Given the metabolic demand of

• High protein diet tissue/wound recovery
To provide a narrative (1.6 g/kg/day) with processes, staying as close to
synthesis of the scientific 20–30 g per meal of
316 references Expert group statement with energy balance as possible and
Narrative Review/Qualitative background related to selected leucine-rich protein
(from year of publication non-structured analysis of the thus avoiding drastic Collins et al. (2020) [58]
Analysis topics (Expert Group Topic 7: (≥2.5 g) throughout the
to 2020). scientific literature. reductions in energy intake, is
Nutrition for Injury) within an day including pre-sleep. perhaps the most
elite sports setting. • Avoid deficiencies in Ca, crucial nutritional aspect
Zn, Cu, Mn, vitamin D, during rehabilitation.
and vitamin C.
Nutrients 2023, 15, 819 10 of 25

Table 2. Cont.

Participants
Type of Study Aim Methodology Dosage and Timing Main Findings Reference
(M; F)

• Adequate energy intake. Adequate intake of

• High protein diet macronutrients can support
(2 g/kg/day) with anabolism in athletes. Dietary
To define the proper nutrition 20–30 g per meal of
77 references Expert view and protocols should consider
Narrative Review/Qualitative for athletes in order to hasten leucine-rich protein
(from year of publication non-structured analysis of the doses, timing, rehabilitation Papadopoulou et al. (2020) [49]
Analysis their return to the sport after (≥2.5 g) every 2–4 h.
to 2020). scientific literature. time, type, and quality of
surgery or injury. • 10–20 g of EAA. nutrients, as well as the type of
• Fish oil (Ω3) and CrM. injury, and the injured
• Avoid deficiencies in body part.
vitamins D and K.

• High protein diet (at

least 1.6 and closer to
2–3 g/kg/day) of The athlete’s energy
leucine-rich protein requirements should be
To provide an evidence-based, (≈3 g) per serving. identified to avoid energy
practical guide for athletes with • 20 g of CrM per day deficit. Higher protein intakes,
106 references Expert view and (divided in four doses)
Narrative Review/Qualitative injuries treated surgically or with special attention to evenly Smith-Ryan et al. (2020)
(from year of publication non-structured analysis of the for 5 days and then 3–5 g
Analysis conservatively, along with distributed consumption [48]
to 2020). scientific literature. daily.
healing and throughout the day, will
rehabilitation considerations. • EAA ingestion minimize loss of muscle mass
immediately before and strength during times
surgery or therapy. of immobilization.
• ≥1010 CFU of
Lactobacillus acidophilus or
Bifidobacterium longum.

Structured literature search in Strong evidence of COL use in

48 references To evaluate the effect of COL
Systematic Review/Qualitative PubMed, Web of Science, and 5–15 g of COL at least 1 h prior improving joint pain and
(from year of publication and exercise on joint function Khatri et al. (2021) [47]
Analysis CINAHL. Fifteen references to exercise for over 3 months. functionality (15 g/day may be
to 2020). and athletic recovery.
met the inclusion criteria. a more effective dose).
HMB supplementation might
Athletes were assigned to
n = 8 (4 M; 4 F) To analyze the effect of 4 weeks enhance muscle power in
receive HMB (n = 4) or placebo
Federated athletes (including of physical rehabilitation with athletes with patellar
(n = 4) during 4 weeks. Body 3 g of HMB per day 60 min Sánchez-Gómez et al. (2022)
RCT/Quantitative Analysis basketball, volleyball, handball, HMB supplementation in tendinopathy. It seems to
composition, perceived pain, before exercise. [59]
and athletics) with athletes diagnosed with optimize adaptions during the
and muscular function
patellar tendinopathy. patellar tendinopathy. non-invasive treatment of
were measured.
the injury.
Nutrients 2023, 15, 819 11 of 25

Table 2. Cont.

Participants
Type of Study Aim Methodology Dosage and Timing Main Findings Reference
(M; F)

• Adequate energy intake

(25–30 kcal/kg/day). Diets that include high quality
• Adequate intake of nutrients, rich in macro, micro,
To define the proper nutritional
carbohydrates and and bioactive compounds are
77 references elements tailored by athletes’ Expert view and
Narrative Review/Qualitative especially proteins (type, recommended. Biomedical
(from year of publication needs in order to facilitate their non-structured analysis of the Papadopoulou et al. (2022) [10]
Analysis frequency, and amount). indices and vitamin and
to 2022). fast return to sports after scientific literature.
• CrM, Fish oil (Ω3), mineral levels should be
surgery or injury.
curcumin, bromelain. evaluated and monitored to
• Avoid deficiencies in avoid deficiencies.
vitamins and minerals.

• Maintain energy
availability (45 kcal per
kg of FFM per day). It is important to provide
• High protein diet (2 to athletes with an adequate
To present various nutritional
2.3 g/kg/day) with amount of macro- and
182 references strategies for reducing the risk Expert view and
Narrative Review/Qualitative 20–25 g per meal of micro-nutrients and nutritional
(from year of publication of injury and improving the non-structured analysis of the Turnagöl et al. (2022) [46]
Analysis leucine-rich protein (3 g). supplements to meet the
to 2022). treatment and rehabilitation scientific literature.
• 15 g of COL 60 min demands of the catabolic state
process in combat sports.
before an exercise and contribute to the
rehabilitation program. injury-healing process.
• CrM, Ω3, vitamin D, and
Ca.

Certain nutritional
supplements might have pain
Structured literature search in
To evaluate current research on COL, hydrolyzed COL, amino relieving, anti-inflammatory,
155 references Medline, Cinahl, Amed,
Scoping Review/Qualitative the use of nutritional acids, vitamin C, glucosamine, and structural tendon effects
(from year of publication EMBase, SPORTDiscus, and Burton et al. (2022) [45]
Analysis supplements for treating HMB, Ω3, antioxidants, and that augment the positive
to 2022). Cochrane. Sixteen references
tendon injuries. CrM have been studied. functional outcomes gained
met the inclusion criteria.
from progressive
exercise rehabilitation.
Online questionnaire for
historical records and a
Nutritional strategies to
n = 133 (77 M; 56) To identify nutrition-related qualified dietitian collected
support injury prevention
International level Australian factors associated with a information regarding habitual
Cross-sectional should focus on energy
rowers from seniors (n = 115) history of rib stress injuries in Ca intake. Body composition NA Lundy B et al. 2022 [44]
Study/Quantitative Analysis availability and its contribution
and under 23-year-old levels elite rowers (including the and BMD were measured with
to health and function,
(n = 18). injury time course). DXA. A sub-group of
including menstrual status.
participants (n = 68) were
assessed for vitamins D and K.
Ω3: Omega-3 fatty acids; ACL: Anterior cruciate ligament; BCAA: Branched chain amino acids; BMD: Bone mineral density; Ca: Calcium; CFU: Colony-forming units; COL: Collagen
peptides and specific gelatin products; CoQ10: Coenzyme Q10 (ubiquinone); CrM: Creatine monohydrate; Cu: Copper; DASH: Disabilities of the Arm, Shoulder and Hand; EAA:
Essential amino acids; FFM: Fat-free mass; HMB: β-hydroxi-β-methylbutyrate; IU: International units; Mn: Manganese; RCT: Randomized controlled trial; DXA: Dual-energy X-ray
absorptiometry; VAS: Visual analogue scale; Zn: Zinc.
Nutrients 2023, 15, 819 12 of 25

4. Discussion
Sports injuries represent a major economic expense with more than USD 9 billion
spent annually on injury recovery and rehabilitation in young adult athletes (17 to 44 years
old) [48]. Traditionally, rehabilitation management of sports injuries has been approached
from the area of physiotherapy and sports medicine by means of mechanical activities
(such as local cold, heat, massage, extracorporeal shock waves, isometric exercises, etc.),
anti-inflammatory drugs (paracetamol, non-steroidal anti-inflammatory drugs [NSAIDs],
ibuprofen, diclofenac, betamethasone, and muscle relaxants) and surgical interventions [60].
However, sports nutrition and supplementation play an important role as non-pharmacological
strategies during the different stages of inflammation and healing of musculoskeletal in-
juries in the athlete. Considering the volume of evidence analyzed in this study, nutritional
strategies have been shown to be effective in optimizing the management of inflammation,
injury-generated oxidative stress and, in general, the process of musculoskeletal tissue
repair [48,61]. In general, study findings agree on the importance of monitoring energy
availability and dietary protein intake since they play a fundamental role in the recovery
process during sports injury. Nevertheless, in light of the current evidence it is not possible
to draw definitive conclusions and recommend supplementation with other nutrients (e.g.,
collagen, Omega-3 fatty acids, creatine, vitamin D, β-hydroxy-β-methylbutyrate [HMB],
glucosamine, probiotics, and other micronutrients [Ca and Zn]) given the few number of
controlled clinical trials. This has been frequently stated in recent review articles [50,62].
The following sections of this integrative systematic review describe in detail the advances
of the last years regarding nutritional strategies that deserve attention and may be applied
during the rehabilitation process of musculoskeletal injuries in the elite athlete.

4.1. Energy Availability

Nutrition practitioners should provide supportive supervision of energy intake by
the injured athlete (as close as possible to energy balance or even slightly superior). Even
though the period of injury or immobilization may entail a decrease in physical activity, it
has been reported that energy expenditure may be higher (≈20%) during the early phases,
especially in severe injuries [23,48]. It should be highlighted that the process of muscle
protein synthesis (MPS) is high energy-demanding, ranging from ≈485 kcal/day in a
muscular young man to ≈120 kcal/day in an active elderly woman [24]. Some studies have
concluded that an energy deficit of 20% can lead to a decrease in MPS of about 19% [30].
Moreover, genome and cytoskeleton remodeling are another energetically costly function
of any cell [63,64]. Therefore, drastic decreases in energy intake can accelerate muscle mass
loss by decreasing MPS and facilitating muscle protein breakdown (MPB), which hinders
the rehabilitation process. Complementarily, it should be considered that excess energy
results in an increase in adipose tissue and systemic inflammation, which aggravates the
loss of muscle mass [31]. This higher energy cost has been recently referred to as the
‘allostasis and stress-induced energy expenditure’ and, therefore, is part of the allostatic
overload that takes place during the musculoskeletal injury [65].
Energy availability (EA) is defined as the amount of energy available to maintain
metabolic function after subtracting the exercise energy expenditure (EEE) from energy
intake (EI) [66]. The assessment of EA is used as a diagnostic tool for the management of rel-
ative energy deficiency in sport (RED-S) and it is expressed as: EA = EI − EEE/FFM [67–69].
There is evidence that to have a healthy physiological function in athletes engaged in prepa-
ration or competition activities, it is determined that EA should be ≈45 kcal/kg FFM per
day [69]. An insufficient energy intake might evoke in EA below the previous recommended
value which is known as low energy availability (LEA). This can seriously compromise
the body functions required to maintain optimal health and physical performance. In fact,
health alterations may occur after only 5 days of LEA in women [70]. It is worth noting that
most of the included articles in this integrative review agree with this recommendation to
sports practitioners: Avoid EA values <30 kcal/kg FFM/day [10,13,44,46,48,49,58]. LEA
may cause strong alterations in the endocrine system [66] which encompass disruption of
Nutrients 2023, 15, 819 13 of 25

the hypothalamic-pituitary-gonadal axis, thyroid, appetite-regulating and sex hormones

(testosterone and progesterone) [71], decreased insulin and insulin-like growth factor 1
(IGF-1), increased growth hormone (GH) resistance and cortisol elevations. Furthermore,
profound alterations have been reported on bone health [72], metabolic profile, and car-
diovascular, gastrointestinal, immune, and psychological function in addition to eating
disorders and decreased athletic performance [67,69,73]. This low energy scenario not
only increases the risk of musculoskeletal injuries, but also hampers the natural healing
process of rehabilitation. LEA prevention during injury recovery in elite athletes requires
a commitment between the athlete and sports practitioners [69] with special attention to
the education component to raise awareness of unwanted effects [74]. In this sense, tools
that have not yet been validated have been designed to help in the prevention and early
detection of LEA for the prevention of long-term sequelae [75].

4.2. Loss of Muscle Mass and Protein Intake

Whereas an increase in mechanical stress stimulates an anabolic response with conse-
quent muscle hypertrophy, situations of immobilization or disuse generate the opposite
effect by increasing anabolic resistance resulting in muscle atrophy [76]. It has been esti-
mated that during immobilization ≈0.5–0.6% of muscle mass is lost per day. Therefore,
this worrisome loss of muscle mass is accompanied by an even greater loss of strength [1].
As a result, not only muscle structural atrophy, but also neuromuscular degeneration may
occur [2]. These periods of immobilization are also associated with a loss of bone mineral
density in most parts of the body [3], which increases the risk of fractures especially in
the elderly or in subjects that due to nutritional deficiencies and high loads generate sig-
nificant bone demineralization (cases that may occur in athletes with eating disorders or
who undergo very strict weight loss regimens with high training loads). In addition, the
cardiovascular and cardiorespiratory systems are largely affected by this immobilization
condition. Of note, a daily loss of 0.99 and 1.6% in maximal oxygen consumption (VO2max )
and cardiac output, respectively, after only 2 weeks of bed rest have been reported [4].
Interestingly, the longitudinal Dallas Bedrest and Training study showed that VO2max
decreased more after 3 weeks of bedrest than during 30 years of aging [5]. It is important to
point out that due to the loss of muscle mass and physical inactivity, periods of disuse also
induce an alteration of the metabolic state, favoring an increase in insulin resistance [6].
In relation to the loss of muscle mass, it is known that the net protein balance is the
difference between MPS and MPB [11,16]. Therefore, a MPB greater than MPS would
induce a decrease in muscle mass, especially if a LEA is present. Different studies have
shown that in the first days of injury, the MPB is transiently elevated [7,8,14]. This transient
increase could be the cause of the high loss of muscle mass that occurs in the first days after
injury. However, it is currently considered that the energy-related decrease in MPS is the
main cause of the disuse in muscle atrophy observed for periods of more than 2 weeks [14].
Another factor contributing to the loss of muscle mass during the immobilization period
is the previously mentioned anabolic resistance, which is defined as the inability of an
anabolic stimulus (e.g., protein, hormonal stimulation, and/or muscle tension) to stimulate
SPM caused by aging, periods of inactivity, or during critical illnesses [15]. In this regard,
Wall et al. [14] showed how SPM, in response to 20 g protein intake, was ≈31% lower after
immobilization which indicates a decrease in tissue sensitivity to amino acids. Moreover,
this might be explained by the energy crisis and intrinsic restrictions in the injured tissue
which disrupt both extra- and intracellular energy production pathways and cytoskeleton
organization during the allodynamic response [65].
Although the cellular mechanisms inherent in the process of immobilization-induced
atrophy are unclear, the following are postulated: (i) The reduction in myogenic capacity
(i.e., decreased satellite cell content and functionality) [1]; (ii) the mitochondrial dysfunc-
tion with consequent increase in free radicals and increased inflammatory response [3];
and (iii) an imbalance in the protein synthesis/degradation balance due to an inhibi-
tion of anabolic signaling pathways (i.e., PI3K/PDK/PKB/mTORC1) and activation of
Nutrients 2023, 15, 819 14 of 25

proteolytic pathways (i.e., ubiquitin-proteosome, calpain and caspase system, cellular

autophagy, etc.) [11]. Therefore, periods of absence of stimulation have important conse-
quences at a multisystemic level, as evidenced in older adults. Reducing daily physical
activity generates considerable changes, such as 14% reduction in energy expenditure,
lower insulin sensitivity (−43%), decreased lipid metabolism, increased visceral fat, de-
creased cardiorespiratory capacity, increased inflammatory markers, and a decrease in
postprandial protein synthesis (26%) and leg muscle mass (−3.9%) [16]. Other studies
conducted during controlled periods of immobilization in young subjects have shown a
reduction in the expression and concentration of the glucose transporter in muscle (SLC2A4,
also known as GLUT-4), resulting in reduced glucose tolerance [19].
Considering all of the above, a fundamental nutrient for injury recovery in athletes is
dietary protein [77]. Inadequate protein intake will lead to increased loss of muscle mass,
decreased tissue repair and healing, inflammation and impaired healing, all of which are
MPS-dependent processes. At the same time, the anabolic resistance produced during the
immobilization process generates an increase in the requirements of this macronutrient. In
this regard, in vitro research [76] has demonstrated the action of amino acids on satellite
cell dynamics, revealing that protein supplementation appears to accelerate satellite cell
responses after acute muscle damage. This may be important in muscle remodeling and
injury recovery processes. On the other hand, studies in humans suggest that dietary
protein may have an important effect on the activity of satellite cells after exercise in
untrained people, where there is greater muscle damage after exercise [76]. Additionally,
as a protective measure, it has been shown that the inclusion of protein intake prior to sleep
may be another strategy to improve muscle mass retention during periods of injury, as
has been shown in studies with energy restriction [78]. Regarding protein intake, there are
three fundamental factors: The quantity, the quality of the protein (source), and the time
and frequency of consumption, all considering the total energy intake of the individual. In
energy-restricted feeding programs, it has been observed that a higher protein intake leads
to a lower loss of muscle mass. For example, Mettler et al. [79] conducted a 2-week study
where participants were subjected to a 40% energy restriction and divided into two groups:
One group was given 1 g of protein per kg/day, while the other was given 2.3 g/kg/day.
The subjects in the group that consumed less protein reported a muscle mass loss of 1.6 kg
compared to 0.3 kg in the group that consumed a higher protein diet. Most of the reviewed
articles included in this integrative review recommend a high protein diet (from 1.6 to
3 g/kg/day) with 20–30 g of leucine-rich protein (≈3 g) per meal throughout the day
(including pre-sleep intake). This dosage per meal (0.3 g of protein per kg per meal) has
been shown to be effective in increasing MPS in young [19] and older adults [80]. It needs
to be noted that a uniform distribution of proteins over a 24-h period is more favorable
than when quantities are distributed unevenly [81]. Indeed, Mamerow et al. [82] showed
that a homogeneous distribution of protein consumption increases MPS by more than 25%
compared to a distribution where protein is mainly concentrated in the evening meal [82].
Based on this physiological response, it seems that the injured athlete will also benefit from
eating 4–6 protein meals throughout the day to prevent loss of muscle mass [83]. Pre-sleep
casein protein ingestion seems to be an effective strategy to boost the muscle adaptive
response during a resistance exercise program [84], but more research is needed in exercise
rehabilitation programs.

4.3. Tissue Repair and Inflammation

4.3.1. Creatine Monohydrate
The most widely studied and safest nutritional supplement is creatine, especially in
the form of creatine monohydrate (CrM) [85]. Its administration results in increases in
the total musculoskeletal creatine pool by around 25% (up to ≈37% if accompanied with
physical exercise) [86] which benefits the athlete’s recovery time and improves athletic
performance (increased strength, muscle mass, and power) [87]. It has been reported that
the increase in muscle creatine after CrM supplementation might optimize the function
Nutrients 2023, 15, 819 15 of 25

of the creatine kinase/phosphocreatine system and subsequently benefit energy- and

mechanical-dependent processes in different tissues [88,89].
Potential effects of CrM consumption as a therapeutic nutritional agent in clinical
conditions have been suggested for some chronic and traumatic diseases (acute injuries,
spinal cord injury, postoperative orthopedic recovery, muscular dystrophy, immobility, and
atrophy due to muscle disuse, among others) [90]. Furthermore, CrM supplementation
could help in maintaining or improving clinical outcomes by improving physiological
adaptations during rehabilitation processes in patients with substantially reduced skeletal
muscle contractile capacity [91], as in the case of sports injuries. Periods of extreme inac-
tivity, such as periods of immobilization, have shown not only a loss of muscle mass and
strength, but also a 24% decrease in muscle creatine stores [92]. Consequently, maintaining
or increasing muscle creatine levels during periods of inactivity or recovery from injury
may offer benefits [93]. Indeed, several studies have evaluated the potential effects of
CrM supplementation during periods of immobilization [94] revealing: (i) Maintenance of
muscle mass or cross-sectional area, muscle strength, and endurance; (ii) maintenance or in-
crease in total muscle creatine concentration; (iii) maintenance of GLUT-4 concentration [95];
(iv) increased muscle glycogen; and (v) increased expression of growth factors (IGF-1) and
myogenic regulatory factors [88,93]. However, it is difficult to draw definitive conclusions
due to heterogeneity in study designs (e.g., duration, immobilized limb, experience level of
participants, etc.). For example, Johnson et al. [96] showed how CrM supplementation re-
duced muscle mass loss in immobilized arms; however, another study failed to demonstrate
the same effect in lower limbs after a short-term protocol of CrM supplementation [97]. A
clinical intervention during a period of 10 weeks of rehabilitation, showed that CrM intake
favors the increase in muscle mass after immobilization-induced loss [98]. In particular, it
seems that CrM supplementation may be effective, not over short but longer periods of
time, although the overall impact on reducing muscle loss is inconclusive [83]. Recently, a
randomized controlled clinical trial conducted by Juhasz et al. (2018) [57] concluded that
CrM supplementation (20 g for 5 days followed by 5 g for the rest of the study) combined
with therapeutic strategy effectively supports the rehabilitation of tendon overuse injury of
adolescent fin swimmers. A recent systematic review that evaluated pre- and post-surgical
nutrition for preservation of muscle mass, strength, and functionality also concluded that
CrM supplementation merits consideration in the general population [99]. In agreement
with the collective body of evidence reviewed in this systematic integrative review, we
adhere to this recommendation considering the very good safety profile of CrM at doses of
0.1 g/kg/day. Notwithstanding, the few clinical studies on the effects of CrM within elite
athletic population warrant more research as concluded by Mistry et al. (2022) in a recent
systematic review [100].

4.3.2. Omega-3 Fatty Acids

Inflammation is part of the natural tissue recovery process; therefore, a drastic reduc-
tion (using drugs or other substances) or an excess of acute inflammation could result in
an inadequate physiological response and lead to a suboptimal recovery. Under normal
conditions, muscle injuries generate a complex and coordinated inflammatory response that
is characterized by: (i) The activation of both endothelial cells in the vessels supplying the
muscle and cells residing in the muscle tissue, such as satellite cells, fibroblasts, and leuko-
cytes (macrophages, CD8+ T lymphocytes, mast cells, eosinophils and, later, regulatory
CD4+ CD25+ FOXP3+ T lymphocytes; and (ii) the recruitment and subsequent infiltration
into the injured muscle of various leukocytes, especially neutrophils and monocytes (which
differentiate into macrophages) [101–104].
This acute response initially generates pain, swelling, and loss of function [101].
Therefore, the use of anti-inflammatory strategies that include long-chain fatty acids of the
omega-3 family might be useful for short periods of time. Eicosapentaenoic acid (EPA) and
docosahexaenoic acid (DHA) [105–107] have been shown to decrease the concentrations of
some inflammatory markers, pain intensity, and the use of NSAIDs in some inflammatory
Nutrients 2023, 15, 819 16 of 25

diseases [105]. Moreover, other molecules derived from both EPA (e.g., resolvins E) and
DHA (e.g., resolvins D, maresins, and protectins) have been shown to induce the resolution
of inflammation [108]. Finally, these molecules as well as EPA and DHA are known
to directly or indirectly affect transcription factors that regulate the expression of genes
encoding inflammatory proteins (e.g., cytokines, chemokines, enzymes, and adhesion
molecules) [13].
Clinical trials on the role of omega-3 fatty acids in sports-induced inflammation have
focused primarily on exercise-induced muscle damage and its respective consequences
(i.e., soreness, muscle swelling, loss of strength, and decreased range of motion) [106].
However, the evidence is not consistent and does not allow for extracting clear recom-
mendations regarding amounts and timing due to conflicting results and methodological
limitations [22,109]. In fact, in relation to its role in sports injuries, most research has focused
on traumatic brain injury and suggests that DHA may have positive effects [22,25]. On the
other hand, it has been described that the acute inflammation generated by a muscle injury
is a necessary physiological response and, therefore, its reduction or blockage compromises
the process of repair and regeneration of muscle tissue [101–103]. As a result, it has been
suggested that a high intake of EPA and DHA could have negative effects in the first days
post-injury [110].
On the other hand, it is known that arachidonic acid not only originates from eicosanoids
that participate in the initial inflammatory response, but also gives rise to lipoxins that
along with resolvins, protectins, and maresins (derived from EPA and DHA) act as me-
diators of the resolution of inflammation [10,49]. This suggests that perhaps the ratio of
arachidonic acid to the sum [EPA+DHA] is as or more relevant than total omega-3 intake.
However, arachidonic acid is not the most abundant omega-6 fatty acid in typical diets
of industrialized countries [10], but is a linoleic acid. This latter function reduces the
conversion of α-linolenic acid of the omega-3 family to EPA and DHA, thus competing with
cell membrane phospholipids [49,61]. Therefore, considering the lack of clear evidence to
establish guidelines for the intake of these fatty acids in athletes, when the aim is to prevent
or assist in the treatment of muscle injury, it is considered more prudent to recommend
that the athlete’s diet has a low omega-6/omega-3 ratio.

4.3.3. Collagen Peptides and Specific Gelatin Products

Tendon injuries are quite frequent in athletes, and their origin is multifactorial. One
randomized, double-blind, crossover study showed that the combination of jumping exer-
cise together with gelatin and vitamin C supplementation (15 g gelatin + 50 mg vitamin C)
increased in vitro collagen production and a two-fold increase in amino terminal propep-
tide of type I collagen in blood, which is indicative of increased collagen synthesis [111].
This suggests that the inclusion of collagen peptides and specific-gelatin products in com-
bination with an intermittent exercise program may enhance collagen synthesis, which
could play a beneficial role in injury prevention and tissue repair. In this sense, research has
shown that supplementation with hydrolyzed collagen (≈10 g per day) can increase carti-
lage thickness in patients with osteoarthritis [112] and decrease knee pain in athletes [113].
Indeed, the recent systematic review performed by Kahtri et al. (2021) [47] concluded that
‘collagen peptides and specific gelatin products have strong evidence in improving joint
pain and functionality (especially at doses of 15 g/day)’. The data presented suggest a bene-
fit of gelatin along with vitamin C and/or hydrolyzed collagen supplements; therefore, it is
expected that future clinical studies need to confirm this recommendation in injury-related
specific conditions [93].

4.3.4. HMB
β-hydroxy-β-methylbutyrate (HMB) is a leucine-derived metabolite marketed as a
supplement to increase MPS and decrease MPB [93]. Different mechanisms have been
proposed to justify its anti-catabolic action including activation of the PI3K/Akt/PDK/IGF-
1/mTORC1 signaling pathway [114]. However, the same benefit can be obtained with
Nutrients 2023, 15, 819 17 of 25

the ingestion of leucine or whey protein [115]. The effects of this substance on muscle
mass gain and muscle damage are unclear in trained athletes [116,117]. In fact, there is
controversy in the literature due to the different study designs, the lack of transparency,
and even the possible conflict of interest in some studies [93]. Despite the above, HMB
is recommended by some of the reviews evaluated [45,52], which highlight that it can
be useful in rehabilitation characterized by periods of extreme inactivity. For instance,
Deutz et al. [118] showed improved lean mass preservation in older adults ingesting HMB
during 10 days of bed rest. However, only one pilot study with eight federated athletes
diagnosed with patellar tendinopathy has shown positive effects with doses of ≈3 g/day
before the exercise rehabilitation program [59]. Based on the accumulated evidence, unlike
other supplements, such as CrM, HMB cannot be confidently recommended to injured
athletes since the effects may not be more effective than following current protein intake
recommendations [93,107].

4.3.5. Vitamin D
There is a growing body of literature highlighting the importance of vitamin D, beyond
its classically described effects on phosphorus and calcium metabolism in bone [119–121].
Importantly, a high prevalence of vitamin D deficiency in the athlete population has been
highlighted and, given the important role it plays in the adaptive processes to intense
exercise [93], it is necessary to monitor and maintain adequate levels in preparation and
competition phases. Regarding the relationship between vitamin D and muscle perfor-
mance, it is known that vitamin D binds to vitamin D receptors in muscle tissue to regulate
gene expression in muscle fibers (especially type II). A study in 22 judo athletes with
vitamin D deficiency showed an improvement in isokinetic dynamometry in quadriceps
and hamstring strength tests with daily intake of 150,000 IU of vitamin D3 for 8 days [122].
Regarding athletic injuries, low serum 25-hydroxyvitamin D levels have been asso-
ciated with increased risk of stress fracture by 3.6 times in Finnish military recruits [123].
Similarly, vitamin D insufficiency results in 1.86 times the risk of lower extremity mus-
cle strain and 3.86 times the risk of hamstring injury in athletes in the National Football
League [124]. It should be noted that vitamin D insufficiency is established at <80 nmol/L
while deficiency is at <50 nmol/L [44]. It has also been documented that supplementation
with 800 IU of vitamin D3 in addition to 2 g/day of calcium reduced stress fractures in
female recruits by 20% [125]. In a study of National Football League players, it was found
that those with at least one muscle injury had significantly lower vitamin D levels than
those with no injuries during the season [126]. Complementarily, serum 25-hydroxyvitamin
D levels after vitamin D supplementation not only increases but has a significantly negative
correlation with selected biomarkers of skeletal muscle damage and post-exercise levels of
pro-inflammatory cytokines [127].
In addition to the association with risk of injury, vitamin D may also influence recovery
after some types of surgery. Barker et al. [128] observed that subjects with low vitamin
D levels had delayed strength recovery after anterior cruciate ligament surgery. Since
low levels are associated with risk of injury (e.g., stress fractures, muscle injuries, and
upper respiratory tract infections) [129], vitamin D supplementation in athletes with low
serum 25-hydroxyvitamin D concentrations would be indicated as an adjuvant strategy to
decrease the rate of injury. In athletes with spinal cord injury, benefits of oral vitamin D
supplementation (6000 IU/day) for 12 weeks to correct deficiencies have been reported in
Swiss para-athletes [56]. Despite the above-mentioned research, contradictory results have
been found that do not allow for a clear conclusion due, to a large extent, to the diversity in
the designs of these investigations (e.g., differences in baseline 25-hydroxyvitamin D levels,
supplementation protocol, number of participants, etc.) [130]. Therefore, more studies
with solid intervention designs are needed to evaluate vitamin D supplementation in the
recovery process after a sports injury [131].
Nutrients 2023, 15, 819 18 of 25

4.4. Future Directions

In general, nutritional recommendations for rehabilitation and return to competition
are similar to those made for muscle gain [18], which may be due to the increased need
for energy and higher protein intake in order to avoid loss of muscle mass [19]. However,
despite current knowledge in sports nutrition, there is insufficient clinical information on
the use of certain nutrients in the injured athlete [17]. Importantly, the effects on improving
musculoskeletal and tendon/ligament tissue function in the injured athlete requires further
research. For this reason, it is important to develop future studies to evaluate the clinical
effects of these nutrients during the injury rehabilitation program in the athletic population.
One of the factors contributing to muscle atrophy induced by physical inactivity or
immobilization is ROS production [132]. This seems to be due to its interference with the
MPS process by hindering translation initiation [133]. In addition, it has been observed
that these ROS can activate different proteolytic systems, such as autophagy, calpain, or
the ubiquitin proteasome system, which increases proteolysis and susceptibility to amino
acid oxidation [132]. The use of antioxidants can be effective in decreasing immobilization-
induced muscle atrophy, albeit, this is currently a controversial issue. In recent years,
evidence is accumulating on the role of ROS as cellular signaling and their involvement in
exercise adaptation processes (e.g., mitochondrial dynamics/biogenesis, insulin sensitivity,
muscle hypertrophy, antioxidant enzyme expression, etc.) [134–137]. Therefore, it has
been reported that high doses of antioxidant supplements can block the exercise-induced
adaptive response of muscle tissue [138]. For example, Barker et al. [139] showed how
vitamin C and vitamin E intake can negatively influence the recovery of muscle function
after knee surgery, although in this study, adequate prior vitamin C status was correlated
with better muscle function. These data suggest that a correct antioxidant status is nec-
essary to maintain physiological ROS ranges and, therefore, permissive to all adaptive
processes. An interesting point to note is that there is no data that high intakes of fruits and
vegetables (sources of antioxidants) attenuate adaptations to exercise; therefore, it would
be appropriate to recommend that athletes consume a quality diet and avoid mega doses of
antioxidant supplements and micronutrients [140]. Recommendations for injured athletes
comprise the intake of antioxidants and micronutrients through a varied and balanced
diet, rich in protein, fiber, fruits, and vegetables, which might support the maintenance
of antioxidant status. Future intervention studies should provide more evidence on the
need for antioxidant supplementation on recovery after injury, considering aspects, such as
dose and type of antioxidant used. For example, curcumin and derivates (curcuminoids)
are mentioned in the UEFA expert group statement as a potential strategy to combat the
acute inflammatory process during the injury rehabilitation program; however, they also
highlight the fact that it requires corroboration in relevant human studies to recommend
its use [58]. Doses used at the time of supplementation are generally safe up to about
5 g/day [93] although some side effects, such as nausea, diarrhea, headache, and yellow
stools have been reported [141]. Finally, in view of its possible role as a neuroprotective
agent with analgesic effects [142], it has been suggested that melatonin supplementation
before physical exercise could be a strategy in the rehabilitation of spinal cord injuries [143].
Melatonin has good tolerability after short-term use and, thereby, is a good candidate
molecule to perform clinical trials in injured athletes.

5. Limitations and Strengths

This review should be read in light of various limitations/strengths. First, it focused
on outcomes related to the treatment or intervention of serious and non-serious injuries
reported within each study. While partial generalizability may take place, it is worth noting
that we did not fully cover prevention of injuries, injury-associated risk factors, nor other
types of injuries (e.g., traumatic brain injury). Even though it is beyond the scope of this
work, sports practitioners are encouraged to facilitate nutritional post-exercise recovery [84]
and follow injury prevention programs based on international consensus [144] along with
the findings of this comprehensive review of the literature. It is the first time that scientific
Nutrients 2023, 15, 819 19 of 25

evidence on this topic is analyzed under a systematized methodology that included quality
and risk of bias assessment. Finally, conclusions and recommendations given in this
systematic integrative review should be discussed carefully in other populations (e.g.,
physically active individuals) in contrast to athletes.

6. Conclusions
Nutritional strategies that would most likely benefit the rehabilitation process in
injured athletes include energy availability, and high protein and carbohydrate diets.
Importantly, supportive supervision should be provided to avoid LEA. Considering the
current evidence, it is not possible to draw definitive conclusions on supplementation
with other nutrients, such as collagen, Omega-3 fatty acids, creatine, vitamin D, HMB,
glucosamine, and other micronutrients given the few numbers of controlled clinical trials.
After analyzing the full body of evidence, study findings agree on the importance of
monitoring energy availability and the high protein intake; however, there is a notable
lack of clinical research evaluating nutritional supplements in injured athletes. It should
be noted that a higher number of literature review articles has been published in the last
10 years compared to clinical studies. While a low-to-moderate risk of bias was detected
in the selected clinical trials, a low quality and high risk of bias were common among the
review articles (mainly narrative). Therefore, researchers are encouraged to conduct further
experimental studies evaluating the discussed nutrients and to follow international review
guidelines at the time of reviewing literature to enhance quality and transparency.

Author Contributions: Conceptualization, J.E.G.-V., M.Á.C.-G., E.J.R.-A. and D.A.B.; methodology,

D.A.B. and J.L.P.; validation, D.A.B.; data extraction, J.E.G.-V., M.Á.C.-G., E.J.R.-A. and D.A.B.;
writing—original draft preparation, J.E.G.-V., M.Á.C.-G., E.J.R.-A., J.L.P. and D.A.B.; writing—review
and editing, D.A.B., R.C., J.K., J.L.P. and R.B.K.; supervision, D.A.B. All authors have read and
agreed to the published version of the manuscript. D.A.B. serves as science product manager for
MTX Corporation® , a company that produces, distributes, sells, and conducts research on dietary
supplements (including creatine) in Europe, has acted as a scientific consultant for MET-Rx and
Healthy Sports in Colombia, and has received honoraria for speaking about creatine at international
conferences. R.B.K. has conducted industry-sponsored research, received financial support for
presenting about dietary supplements at industry-sponsored scientific conferences, and has served as
an expert witness on cases related to exercise physiology and nutrition. Additionally, R.B.K. serves
as chair of the “Creatine for Health” scientific advisory board for Alzchem Group AG, while D.A.B.
serves as member of this board. The other authors declare that they have no competing interests.
Funding: The APC was partially funded by the Galascreen Laboratories, Research Division at DBSS
International SAS, and CESNUTRAL (Acta0037Proy151TG).
Institutional Review Board Statement: Not applicable.
Informed Consent Statement: Not applicable.
Data Availability Statement: Not applicable.
Acknowledgments: We would like to thank the external researchers that evaluated the first version
of the drafted manuscript as part of the thesis activities required by the Master of Science in Sports
Nutrition degree program at Universidad CES.
Conflicts of Interest: D.A.B. serves as science product manager for MTX Corporation® , a company
that produces, distributes, sells, and conducts research on dietary supplements (including creatine)
in Europe, has acted as a scientific consultant for MET-Rx and Healthy Sports in Colombia, and has
received honoraria for speaking about creatine at international conferences. R.B.K. has conducted
industry-sponsored research, received financial support for presenting about dietary supplements at
industry-sponsored scientific conferences, and has served as an expert witness on cases related to
exercise physiology and nutrition. Additionally, R.B.K. serves as chair of the “Creatine for Health”
scientific advisory board for Alzchem Group AG, while D.A.B. serves as member of this board. The
other authors declare that they have no competing interests.
Nutrients 2023, 15, 819 20 of 25

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