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Nutritional Support for Exercise-Induced

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Article · November 2015

DOI: 10.1007/s40279-015-0398-4

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 Sports Med
DOI 10.1007/s40279-015-0398-4

1 REVIEW ARTICLE

2 Nutritional Support for Exercise-Induced Injuries

3 Kevin D. Tipton1

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4
5

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Ó The Author(s) 2015. This article is published with open access at Springerlink.com

6 Abstract Nutrition is one method to counter the negative minimally processed foods or ingredients made from whole 35
7 impact of an exercise-induced injury. Deficiencies of foods. The diet composition should be carefully assessed 36
8 energy, protein and other nutrients should be avoided. and changes considered as the injury heals and activity 37
9 Claims for the effectiveness of many other nutrients fol- patterns change. 38
10
11
12
lowing injuries are rampant, but the evidence is equivocal.
The results of an exercise-induced injury may vary widely
depending on the nature of the injury and severity. Injuries
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1 Introduction
39

40
13 typically result in cessation, or at least a reduction, in
14 participation in sport and decreased physical activity. Limb Injuries are an inescapable aspect of exercising and par- 41
15 immobility may be necessary with some injuries, con- ticipation in sport. The particular results of an exercise- 42
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16 tributing to reduced activity and training. Following an induced injury may vary widely depending on the nature 43
17 injury, an inflammatory response is initiated and while and severity of the injury. Injuries typically result in ces- 44
18 excess inflammation may be harmful, given the importance sation, or at least a reduction, in participation in sport and 45
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19 of the inflammatory process for wound healing, attempting decreased physical activity. More severe injuries may 46
20 to drastically reduce inflammation may not be ideal for result in immobilization of a limb. Recent evidence sug- 47
21 optimal recovery. Injuries severe enough for immobiliza- gests that half of the total number of injuries can be con- 48
22 tion of a limb result in loss of muscle mass and reduced sidered severe, leading to an average of [3 weeks without 49
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23 muscle strength and function. Loss of muscle results from training or competing [1]. Thus, interventions that can 50
24 reductions in basal muscle protein synthesis and the increase the rate of healing and decrease the time to return 51
25 resistance of muscle to anabolic stimulation. Energy bal- to play are important. Among other options used by 52
26 ance is critical. Higher protein intakes (2–2.5 g/kg/day) trainers, physicians and athletes, nutritional support may 53
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27 seem to be warranted during immobilization. At the very help enhance recovery. A great deal of material has been 54
28 least, care should be taken not to reduce the absolute written on the topic of nutrition for exercise-induced 55
29 amount of protein intake when energy intake is reduced. injuries [2–4], but very little stems from studies directly 56
30 There is promising, albeit preliminary, evidence for the use examining these issues. The aim of this review is to 57
31 of omega-3 fatty acids and creatine to counter muscle loss examine and update the evidence for nutritional strategies 58
32 and enhance hypertrophy, respectively. The overriding to support the enhancement of recovery and return to 59
33 nutritional recommendation for injured exercisers should training and competition. Given the relative dearth of direct 60
34 be to consume a well-balanced diet based on whole, information on nutrition for exercise-induced injuries, an 61
attempt also will be made to glean what insight is possible 62
from other models, including trauma, wound healing, 63
A1 & Kevin D. Tipton immobilization and bed rest studies. 64
A2 k.d.tipton@stir.ac.uk
Most injuries severe enough to result in immobilization 65
A3 1
Health and Exercise Sciences Research Group, University of and/or reduced physical activity may be considered to have 66
A4 Stirling, Cottrell Building, Stirling FK9 4LA, Scotland, UK two main stages. Both stages may be influenced by 67

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 K. D. Tipton

68 nutrition. The first stage is the healing and recovery phase. 3 Injuries Involving Immobilization and/ 117
69 Immediately after an injury, wound healing begins. It is a or Reduced Activity 118
70 complex process involving three, overlapping phases:
71 inflammation, proliferation and remodelling. Bone repair is Injuries severe enough to result in immobilization of a limb 119
72 similar to, but slightly different from, soft tissue repair [2]. and/or bed rest leading to drastically reduced levels of 120
73 This healing stage may involve reduced activity or even physical activity have obvious negative ramifications. 121
74 complete immobility of a limb lasting from only a few days Disuse of a limb results in loss of muscle mass and reduced 122
75 up to several months depending on the nature and severity muscle strength and function [6, 21–24]. Moreover, 123
76 of the injury [5]. The second stage to consider follows the immobilization is detrimental for tendon structure and 124
77 return to activity. Rehabilitation and increased activity, function [25]. Substantial muscle loss has been reported in 125
78 overall and for an immobilized limb, are typical of this as little as 5 days of disuse [24]. Earlier we reported that 126
79 stage. This second stage is much more clearly demarcated metabolic measurements in muscle suggest that muscle 127
80 for injuries involving immobilization, but the transition tissue is lost with only 36 h of inactivity [26]. Moreover, 128
81 between stages is less clear for other injuries. Typically, Reich et al. [27] reported altered gene expression with 48 h 129

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82 complete recovery and return to full function and training of muscle disuse. Thus, even injuries that result in only 130
83 takes longer than the immobilization period [6]. Full short-term muscle disuse may have negative metabolic 131

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84 recovery from some injuries may take even up to several consequences. Clearly, nutritional measures that may 132
85 years [7–9]. Thus, nutritional support may be crucial to influence the response of muscle and tendon to injury-in- 133
86 lessen the length of time and reduce the negative aspects of duced immobilization and inactivity can help an exerciser 134
87 reduced activity and immobilization, as well as to support return to full activity and training more quickly. 135
88 the return to activity and training. Given that nutritional The metabolic mechanism for changes in muscle mass is 136
89 recommendations for increasing muscle size and strength net muscle protein balance (NBAL), i.e. the balance 137
90
91
92
during rehabilitation would be similar to other muscle
growth situations [10–14], the focus of this review pri-
marily will be on the first stage of injury, i.e. wound
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between the rate of muscle protein synthesis (MPS) and
breakdown (MPB). In particular, muscle size and strength
are lost when there is negative balance between myofib-
138
139
140
93 healing and reduced activity or immobilization. The bulk rillar MPS and MPB. Muscle is lost over any given period 141
94 of this review will address injuries requiring immobiliza- of time when periods of negative NBAL are greater than 142
95 tion and reduced physical activity, but there will also be periods of positive NBAL. During muscle disuse, the basal, 143
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96 discussion of nutrition for other injuries. i.e. resting and fasted, rate of MPS is decreased [21, 23, 144
28]. The influence of MPB on NBAL during muscle disuse 145
is less clear. The measurement of MPB in humans is dif- 146
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97 2 Inflammation ficult, and indirect measures are often necessary to attempt 147
to assess changes in MPB that may contribute to muscle 148
98 During the first stage following an injury, an inflammatory loss. After 14 days of strict bed rest, dynamic measurement 149
99 response is initiated. The inflammatory response initiates of MPB using stable isotopic tracers showed that MPB was 150
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100 activation of many processes that are crucial for optimal decreased, albeit to a lesser extent than MPS [21]. Thus, 151
101 healing [15, 16]. This inflammation may last for a few after 14 days the decrease in MPS was greater than that of 152
102 hours up to several days depending on the type and severity MPB leading to negative NBAL and muscle loss during 153
103 of the injury [17]. An oft-cited aim of post-injury nutrition disuse. There is now preliminary and indirect evidence that 154
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104 is to reduce, or even abolish, the inflammatory response. MPB may be increased during the first few days of 155
105 Excess inflammation is, of course, counterproductive for immobility [24, 29, 30]. These data suggest that it is pos- 156
106 healing. However, given the importance of the inflamma- sible that a transient increase in MPB contributes to muscle 157
107 tory process for wound healing [17], a drastic reduction of loss early after a limb is immobilized, but increases in these 158
108 inflammation may not be ideal for optimal recovery. Most indirect, static markers of MPB do not persist for longer 159
109 exercise-induced injuries, particularly in otherwise healthy periods, e.g. 14 days [31, 32]. Moreover, there is con- 160
110 exercisers and athletes, would not be severe enough for vincing evidence that static, indirect markers of MPB do 161
111 uncontrolled inflammation to be an issue [17]. Thus, not represent the dynamic muscle metabolism [33]. Thus, 162
112 nutritional interventions intended to reduce inflammation solid conclusions regarding the importance of MPB for 163
113 [18–20] may be contra-indicated. Therefore, careful con- muscle loss during limb immobility are lacking. Never- 164
114 sideration of the appropriate approach to managing theless, it seems clear that decreased MPS is the major 165
115 inflammation is important for optimal recovery from metabolic mechanism behind negative NBAL and muscle 166
116 injury. disuse atrophy [28]. 167

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168 Another metabolic contributor to muscle loss with following injury. The rationale for the use of many nutri- 218
169 immobility is the resistance of MPS to anabolic stimula- ents has been touted, yet direct evidence is largely lacking. 219
170 tion. Both bed rest [34] and limb immobilization [23, 35] Only a few studies actually have directly investigated these 220
171 models demonstrate that muscle exhibits ‘anabolic resis- issues [2, 3]. A complete consideration of all nutrients 221
172 tance’ with disuse. The response of MPS to hyper- claimed to confer benefits during muscle loss is beyond the 222
173 aminoacidaemia from amino acid infusion [23], essential scope of this review. Thus, the discussion will focus on the 223
174 amino acid (EAA) ingestion [34], and protein ingestion rationale and evidence for the use of the more prominently 224
175 [35] is reduced following a period of disuse. Moreover, evaluated nutrients. 225
176 complete muscle disuse is not necessary to stimulate some The single most important nutritional consideration 226
177 level of anabolic resistance. Simply reducing muscle during reduced muscle activity and/or immobility is to 227
178 activity for 14 days is enough to reduce the response of avoid nutrient deficiencies. Deficiencies of energy, vita- 228
179 MPS to ingested protein [36]. The mechanisms for this lack mins, minerals and macronutrients—particularly protein— 229
180 of response to hyperaminoacidaemia are undoubtedly will impair wound healing and exacerbate loss of muscle 230
181 multifactorial and have yet to be definitively determined. and tendon mass and function. Whereas healthy exercisers 231

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182 Possible mediators of anabolic resistance with muscle and athletes are unlikely to suffer from malnourishment, 232
183 disuse include impaired protein digestion and amino acid choices made during recovery from an injury need to be 233

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184 absorption [37, 38], altered microvascular perfusion and carefully considered to optimize recovery and return to 234
185 amino acid uptake into muscle [34, 39, 40], and impaired training. 235
186 intracellular molecular anabolic signalling [23, 34, 41].
187 Despite the lack of certainty concerning mechanisms, it is 4.1 Energy 236
188 clear that a reduction in the ability of muscle to respond to
189 stimulation from hyperaminoacidaemia is a major factor Energy intake is a critical component of any nutrition plan 237
190
191
192
leading to muscle atrophy with disuse or even reduced
activity.
Muscle loss is not the only negative consequence of
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for optimal recovery from an injury resulting in immobi-
lization and reduced activity. However, recommendations
for energy intake may not be as obvious as many would
238
239
240
193 inactivity in muscle tissue. Muscle mitochondrial oxidative believe. Whereas energy intake during short periods of 241
194 function and metabolic flexibility are impaired with muscle inactivity tends to be greater than expenditure, during 242
195 disuse. Downregulation of mitochondrial protein tran- prolonged periods of reduced activity, spontaneous energy 243
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196 scription, decreases in translational signalling pathways intake matches energy expenditure [45]. Given that energy 244
197 involved in mitochondrial biogenesis, and declines in expenditure almost certainly will be reduced with a 245
198 mitochondrial enzyme activities all result from immobi- reduction in training and activity, a conscious decision to 246
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199 lization [31]. Some of these changes occur as early as 48 h drastically reduce energy intake is the intuitive choice. If 247
200 following initiation of inactivity. Nearly all aspects of the injured limb is involved in ambulation, energy expen- 248
201 mitochondrial function are impacted [31]. It is well-known diture may be expected to decline even more, both by 249
202 that muscle disuse leads to depressed insulin sensitivity necessity and voluntarily due to a reluctance to ambulate 250
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203 [42, 43]. Moreover, simply reducing activity of muscle for [46, 47]. Of course, the amount of alternative training and/ 251
204 2 weeks may lead to decreased insulin sensitivity of mus- or physical activity will be a determinant of total energy 252
205 cle [28]. Reduced glucose transport protein 4 (GLUT4) expenditure during immobilization. Finally, another, less 253
206 content in immobilized muscle likely contributes to the obvious, contributor to lower energy expenditure is a 254
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207 deleterious impact on glucose metabolism [44]. These decrease in protein turnover [21]. Thus, to avoid increased 255
208 adverse changes to muscle oxidative and metabolic func- body fat and total mass, most injured athletes, unsurpris- 256
209 tion during immobilization are more evidence of the ingly, will first choose a decrease in energy intake. 257
210 potential for the damaging impact of reduced muscle The magnitude of any decrease in energy expenditure 258
211 activity or immobilization following exercise-induced following an injury with muscle immobilization is likely 259
212 injuries. not as great as was first thought. During the healing pro- 260
cess, energy expenditure is increased, particularly if the 261
injury is severe [48]. Energy expenditure may be increased 262
213 4 Nutrition Support for Injuries Involving by 15 % up to 50 %, depending on the type and severity of 263
214 Immobilization and/or Reduced Activity the injury. Thus, whereas reduced physical activity and 264
training may result in reduced total energy expenditure, the 265
215 There are many nutrients and nutritional strategies that overall reduction may be less than appears obvious. 266
216 have been proposed to help ameliorate the detrimental Moreover, the energy cost of ambulation may need to be 267
217 impact of muscle immobilization and/or decreased activity considered. If an athlete must use crutches, the energy 268

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269 expenditure for ambulation is increased two- to threefold 4.2 Protein and Amino Acids 322
270 [47]. Therefore, the total energy expenditure may not
271 decrease as much as may be at first thought, particularly if The macronutrient most prominently associated with 323
272 the athlete does not voluntarily restrict movement during nutrition support for injuries involving immobility is pro- 324
273 recovery. tein. Given a reduction in overall energy intake, if protein 325
274 An effort to attain energy balance during recovery from intake is kept proportional, an absolute reduction in protein 326
275 injury is critical. If restriction of energy intake is too sev- intake is likely. Clearly, insufficient protein intake will 327
276 ere, recovery almost certainly will be slowed due to neg- impede wound healing and increase inflammation to pos- 328
277 ative metabolic consequences. Negative energy balance sibly deleterious levels [59, 60]. Given that muscle loss 329
278 will interfere with wound healing [48] and exacerbate results from decreased synthesis of myofibrillar proteins 330
279 muscle loss [49, 50]. MPS is an energetically expensive [23], and that the healing processes are heavily reliant on 331
280 process. It has been estimated that a well-muscled male synthesis of collagen and other proteins [15], the impor- 332
281 expends *500 kcal a day on MPS even without the con- tance of protein should be obvious. Moreover, the reduc- 333
282 sideration of physical activity [51]. MPS and associated tion in protein intake, per se, may have a detrimental 334

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283 synthetic intracellular signalling proteins are downregu- impact on muscle metabolism—even if the overall intake 335
284 lated by *20–30 % during even a moderate energy deficit remains at or near the recommended dietary allowance 336

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285 [52, 53]. Given that decreased synthesis of myofibrillar (0.8 g protein/day/kg BM). This disruption may be par- 337
286 proteins is the major metabolic contributor to muscle loss, ticularly evident if habitual protein intake is high, e.g. 338
287 if sustained, this energy deficit will result in accelerated [1.5 g protein/day/kg BM. A drastic decrease in protein 339
288 loss of muscle mass [49]. Moreover, impaired MPS and intake results in negative nitrogen balance [61]. During 340
289 negative energy balance, per se, will slow wound healing. negative energy balance, this loss of nitrogen is almost 341
290 Much care should be taken to ensure that sufficient energy certainly from muscle [52]. We recently demonstrated that 342
291
292
293
is consumed during recovery from an injury.
Whereas, negative energy balance is clearly to be
avoided, a large positive energy balance also is undesirable
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athletes consuming relatively high protein intakes (*2.3 g
protein/day/kg BM) had reduced muscle loss during peri-
ods of negative energy balance compared with athletes
343
344
345
294 for optimal healing and recovery. Positive energy balance with lower protein intakes (*1.0 g/day/kg BM) [50]. 346
295 results in increased lean body mass (BM) in healthy Thus, it may be that relatively high protein intakes, i.e. 347
296 humans [54]. Thus, it may be appealing to suggest a pos- [2.0 g protein/day/kg BM, are necessary to prevent mus- 348
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297 itive energy balance during immobilization, even consid- cle loss. However, it should be considered that no direct 349
298 ering a small increase in body fat. However, there is comparison of 1.6 g/day/kg BM to the higher protein 350
299 evidence that a positive energy balance actually accelerates intake during energy restriction was made [50]. Conse- 351
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300 muscle loss during inactivity, most likely via activation of quently, it is not clear if the preservation of muscle in our 352
301 systemic inflammation [55]. However, these data stem study was due to increasing the protein intake from 353
302 from a bed rest study, and it is not clear how much sys- habitual (*1.6 g/day/kg BM) to higher intakes in the high 354
303 temic inflammation is increased with limb immobility. protein group or reducing from habitual to the lower 355
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304 Moreover, excess energy with reduced activity leads to amount of protein in the low-protein group. Moreover, 356
305 decreased insulin sensitivity and alterations in muscle and during bed rest, increasing protein intake from 1.0 to 1.6 g 357
306 adipose metabolism [56]. Therefore, careful assessment of protein/day/kg BM failed to attenuate muscle loss [62]. A 358
307 energy balance via techniques such as indirect calorimetry potential contributor to the difference between these stud- 359
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308 during both the period of inactivity and rehabilitation may ies is that the participants in the bed rest study were female 360
309 be well worthwhile. It also is possible that energy, per se, [62]. The influence of sex on the response of muscle to 361
310 may not be the most important factor to consider. The disuse and protein ingestion remains to be elucidated. 362
311 macronutrient composition of the energy may be an oper- Nevertheless, it seems clear that appropriate evaluation of 363
312 ative factor. Recent evidence suggests that oversupply of habitual protein intake that helps inform recommendations 364
313 lipids decreases insulin sensitivity and impairs the response for protein intake after injury should be made. 365
314 of MPS to amino acids [57]. Thus, both energy and Other factors in relation to protein should be considered 366
315 macronutrient intake must be considered very carefully. If in addition to the absolute amount of protein intake. The 367
316 reduced energy intake is warranted, factors promoting pattern of protein intake in terms of timing and amount in 368
317 satiety despite a reduced energy intake, including protein each meal is an important factor. The importance of protein 369
318 dose and type, plus low energy density choices such as intake stems from the resulting hyperaminoacidaemia and 370
319 vegetables need to be considered [58]. Energy balance increased MPS [63, 64]. In healthy, active muscle 371
320 should be the aim during reduced inactivity and/or immo- *20–25 g (0.25–0.30 g/kg BM) in one dose of protein 372
321 bilization due to injury. maximizes the response of MPS in both resting and 373

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374 exercised muscle [64, 65]. However, given the onset of Furthermore, supplementation of branched-chain amino 427
375 anabolic resistance with immobility and reduced activity acids attenuated the nitrogen loss during bed rest, but did 428
376 [23, 34, 35], it is likely that the amount of protein in each not impact MPS [84]. However, it is possible that leucine 429
377 dose necessary to maximally stimulate MPS in immobi- may be more effective by overcoming the resistance of 430
378 lized muscle will be increased [66]. Moreover, the overall muscle to anabolic stimulation. MPS was measured in the 431
379 response of MPS throughout the day is optimized when this fasting state in the bed rest study [84], so there was no 432
380 amount of protein is spread equally over the day [67, 68]. assessment of the impact of leucine on anabolic resistance. 433
381 This evenly spaced protein intake pattern is markedly dif- In older humans, increasing the amount of leucine restored 434
382 ferent from the pattern habitually used by most athletes the response of MPS to protein ingestion [85, 86]. More- 435
383 [69, 70]. Thus, whereas the impact of meal pattern on the over, leucine ingestion increases the utilization of ingested 436
384 response of MPS during reduced activity is unknown, it amino acids for MPS [87]. Thus, leucine could play an 437
385 seems prudent to recommend that athletes should plan their important role in situations with limited energy and protein 438
386 meal pattern to optimize MPS and ameliorate the loss of intake, such as with injuries. Nevertheless, to date no study 439
387 muscle protein. has directly investigated the response of muscle to leucine 440

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388 The response of MPS to protein ingestion stems from (or branched-chain amino acid) ingestion during a period 441
389 the EAA content of the protein i.e. nonessential amino of muscle disuse following an injury in humans. There are 442

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390 acids are not necessary for maximal stimulation of MPS also potential negative effects with use of high-dose leu- 443
391 [71, 72]. Thus, EAA supplementation has been recom- cine supplementation. Thus, caution is warranted prior to 444
392 mended for amelioration of muscle loss during muscle making recommendations for leucine supplementation 445
393 disuse following injury. During prolonged bed rest [73] and during muscle disuse. Clearly, the evidence is intriguing 446
394 joint immobilization [74], EAA supplementation has been and this intervention should be attempted in future studies. 447
395 shown to reduce the loss of muscle mass and strength.
396
397
398
However, the dose of EAA may be critical. Smaller doses
of EAA failed to prevent muscle loss during bed rest [75].
The volunteers in that study were in negative energy bal-
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4.3 Other Nutrients

There is a theoretical rationale for the efficacy for

448

449
399 ance. So, it is unclear if the smaller dose of EAA may have increased consumption of a variety of nutrients other than 450
400 been more effective during energy balance. Moreover, protein and amino acids during immobilization or reduced 451
401 unlike many other proposed interventions, there has been activity following injury. These nutrients include, but are 452
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402 direct measurement of muscle loss with EAA supplemen- not limited to, creatine, omega-3 fatty acids, and antioxi- 453
403 tation following an injury. Dreyer et al. [76] demonstrated dants. Again it must be emphasized that deficiencies of 454
404 that 20 g of EAA ingested twice daily between meals for these nutrients, and others, will impair wound healing and 455
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405 1 week prior and 2 weeks following total knee arthroplasty slow recovery. However, evidence that supplementation of 456
406 enhanced recovery in older patients. Of course, it is not nutrients on top of an ample supply will enhance recovery 457
407 certain that injured athletes would experience a similar from injury is scarce. 458
408 response to EAA ingestion after injury. Thus, whereas Creatine supplementation is widely used to enhance 459
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409 there is not a complete lack of equivocation, there is at least muscle gains during resistance exercise training [88]. 460
410 some evidence of efficacy of EAA supplementation during Furthermore, creatine supplementation has been shown to 461
411 immobilization. Moreover, it is not clear if EAA supple- counteract disorders of muscle [89]. However, the evidence 462
412 mentation is more effective than consuming whole proteins for use of creatine to counter muscle loss during immo- 463
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413 containing the same amount of EAA. Given the cost (and bility is less clear. Creatine supplementation during 464
414 taste) of EAA supplements, intact proteins may be 2 weeks of lower-limb immobility in otherwise healthy 465
415 preferred. volunteers did not lessen the loss of muscle mass or 466
416 The potential for EAA supplementation to ameliorate strength in healthy volunteers during 2 weeks of casting 467
417 muscle loss during disuse may be attributed to the bran- [90]. Moreover, muscle strength was not improved by 468
418 ched-chain amino acid leucine, as it has long been known creatine supplementation following total knee arthroplasty 469
419 to increase protein synthesis in rodent and cell models [77, [91]. On the other hand, muscle atrophy in immobilized 470
420 78]. Moreover, recent evidence suggests that leucine arm muscle was decreased with creatine supplementation 471
421 ingestion increases MPS in healthy humans [79]. Thus, the [92]. Thus, it could be that arm and leg muscles respond 472
422 use of leucine to ameliorate muscle loss is often touted differently to creatine supplementation during immobility. 473
423 [80]. However, the impact of leucine on human MPS and Moreover, creatine supplementation did prevent a decrease 474
424 muscle loss during disuse is less clear. Leucine has been in GLUT4 content during immobilization but increased it 475
425 shown to restore impaired MPS in rats [81, 82] and ame- to a greater extent than placebo during rehabilitation [44]. 476
426 liorates muscle loss in rats during immobilization [83]. Thus, despite questions about the impact on muscle 477

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478 atrophy, creatine may have a positive impact on the muscle associated with hydroxyproline synthesis necessary for 531
479 oxidative impairments observed during muscle disuse [31, collagen formation. For most micronutrients the story is 532
480 42–44]. During rehabilitation after immobility, creatine similar, i.e. deficiencies should be avoided, but supple- 533
481 supplementation resulted in an increased rate of muscle mentation above sufficiency does not appear warranted. 534
482 growth and strength gains compared with placebo [90]. Sufficient calcium and vitamin D during healing from 535
483 Thus, the efficacy of creatine supplementation for aug- fractures is important for optimal bone formation. More- 536
484 mentation of muscle hypertrophy seems to be a consistent over, there is an association of low vitamin D status with 537
485 finding, but results of investigations on creatine and muscle impaired recovery from knee surgery [102]. However, 538
486 atrophy are more equivocal. there is no clear evidence for the necessity of supranormal 539
487 Omega-3 fatty acids (n-3FA) also have received con- micronutrient intakes during recovery from injury [59]. 540
488 siderable attention in the context of nutritional support for Oxidative damage is often a concern immediately fol- 541
489 injuries. In many cases, this attention is related to the anti- lowing an injury. Oxidative damage is thought to be a 542
490 inflammatory and immunomodulatory properties of n-3FA contributing factor for muscle loss, primarily by increasing 543
491 [93, 94]. High levels of n-3FA are found in many foods, MPB [103]. Thus, antioxidant compounds, including 544

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492 particularly some cold-water dwelling fish (e.g. mackerel, n-3FA, have been commonly recommended to improve 545
493 salmon). Thus, fish oil supplementation is often touted for healing and recovery [60, 103]. Antioxidant supplementa- 546

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494 reduction of inflammation. Supplementation with n-3FA tion in rodent models results in decreased oxidative stress, 547
495 certainly may be important if inflammation is excessive or but equivocal results in terms of muscle loss with immo- 548
496 prolonged [93]. However, as mentioned previously, careful bility [103]. In high doses, there does seem to be some 549
497 consideration of the use of anti-inflammatory nutrients or impact of antioxidant supplementation on muscle loss in 550
498 drugs is necessary given the importance of the inflamma- rodents. However, equivalent doses likely would be prob- 551
499 tory response for wound healing [18–20]. There is evidence lematic and potentially toxic if taken by humans [103]. 552
500
501
502
of impaired wound healing with n-3FA supplementation
[95, 96]. Thus, an automatic recommendation of n-3FA
supplementation for all injuries does not seem wise.
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Lower doses that might be better tolerated tend not to be as
effective. In one human study, vitamin C and E supple-
mentation failed to influence recovery of muscle dysfunc-
553
554
555
503 Another potential property of n-3FA that may have tion following knee surgery [104]. However, vitamin C 556
504 relevance for injuries resulting in immobilization or status prior to supplementation was correlated with 557
505 reduced activity has recently been investigated. Rats fed improvements in muscle function. Thus, taken together, 558
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506 high amounts of fish oil during hind limb immobilization these results suggest that sufficient antioxidant intake is 559
507 demonstrated less muscle loss than those rats on high corn important for optimal recovery, but supplementation on top 560
508 oil diets [97]. Moreover, 8 weeks of fish oil supplementa- of sufficiency is unnecessary if nutrient status is adequate. 561
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509 tion increased the response of MPS to hyperaminoaci-

510 daemia and hyperinsulinaemia in both older [98] and
511 younger volunteers [99]. The efficacy for fish oil in this 5 Nutrition Support for Other Injuries 562
512 context is thought to be due to changes in the muscle
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513 membrane lipid composition in relation to intracellular Not all injuries require limb immobilization. So, even if 563
514 anabolic signalling [98–100]. This preliminary evidence training is curtailed or reduced, muscle loss may be less 564
515 suggests that fish oil supplementation could play a role in and the metabolic consequences might not be as severe. 565
516 the amelioration of muscle loss with disuse. Then again, There is also evidence that some injuries might have par- 566
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517 high fish oil diets inhibited recovery of muscle mass during ticular nutritional requirements. Thus, a brief discussion of 567
518 recovery from hind limb suspension in rodents [101]. what little is known about nutrition to support a few 568
519 Taken together, it seems that whereas high fish oil (n-3FA) selected types of injuries seems warranted. 569
520 consumption may ameliorate muscle loss during a cata-
521 bolic situation, it does not seem to be effective to enhance 5.1 Concussion/Traumatic Brain Injuries 570
522 muscle hypertrophy. Moreover, the appropriate dose for
523 injured humans has not been established. Thus, wholesale Traumatic brain injuries (TBI) in athletes are attracting an 571
524 recommendations for fish oil supplementation during increasing amount of attention and scrutiny. In contact 572
525 immobilization must be considered premature and caution sports, such as rugby and American football, these injuries 573
526 is warranted. are increasingly common. TBI also are common in other 574
527 There is a clear association of many micronutrients, contact sports and in military personnel. Diagnosis of TBI 575
528 such as zinc, vitamin C, vitamin A (and others), with is being treated much more seriously than in earlier times. 576
529 various aspects of wound healing and recovery from injury, Moreover, increasing awareness of long-term conse- 577
530 including muscle disuse. For example, vitamin C is quences of TBI, particularly if there are repetitive 578

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579 incidences, is forthcoming. Significant brain abnormalities contribution of the n-3FA, other nutrients, or the lifestyle 632
580 were reported in a group of retired American football intervention to the improvement in cognitive function 633
581 players [105]. In addition, retired American football play- cannot be definitively identified. A follow-up, double- 634
582 ers over the age of 50 with a history of repetitive TBI blind, placebo-controlled study determined that nutritional 635
583 demonstrated rates of cognitive impairment five times that supplementation, including n-3FA, resulted in improved 636
584 of retirees without a history of TBI [106]. The pathogenic neuropsychological function in healthy volunteers [117]. 637
585 process leading to these problems is related to the sec- Again, determination of the precise role of n-3FA in this 638
586 ondary phase of recovery following TBI, which includes improvement is not possible given the large number of 639
587 processes such as neuroinflammation, increased excitatory nutrients consumed in the supplement. Therefore, whereas 640
588 amino acids, free radicals and ion imbalances that lead to preclinical and preliminary data on the impact of n-3FA for 641
589 axonal and neuronal damage [107]. However, there still are recovery from TBI are promising, solid recommendations 642
590 no approved therapies to treat TBI or the underlying pro- to include n-3FA in a treatment regimen cannot be made, at 643
591 cesses of TBI and enhance recovery from TBI [107]. Thus, least until the results of the ongoing clinical trials are 644
592 it seems clear that a nutritional intervention that could reported. 645

F
593 ameliorate the consequences of TBI and improve cognitive
594 and neuromuscular function would be valuable for active 5.2 Muscle Tissue Injuries 646

OO
595 and retired athletes.
596 Nutritional treatments for TBI-related problems centre Common exercise-induced injuries include those with 647
597 around antioxidants and anti-inflammatory agents. Virtu- damaged muscle and other soft tissues. These injuries 648
598 ally all of the research to date is based on rodent models. likely will not necessarily result in immobilization of the 649
599 One study showed that rats eating a diet supplemented with limb, but will require a reduction in activity of the injured 650
600 curcumin, an anti-inflammatory compound, had decreased limb—if for no other reason than that the injury is painful. 651
601
602
603
levels of factors found to increase following TBI. These
factors include oxidized proteins, normalized brain-derived
neurotrophic factor (BDNF), and molecules in the patho-
PR
A common model used to examine muscle injuries is an
eccentric exercise model. In this model, the volunteers
perform a number of eccentric—force production during
652
653
654
604 genic pathway downstream of BDNF [108]. Moreover, muscle lengthening—contractions. Loss of muscle func- 655
605 cognitive function was improved in the rats consuming tion, increases in blood proteins associated with muscle 656
606 supplemental curcumin. The efficacy of n-3FA for ame- damage, and increased pain result from these types of sit- 657
D
607 lioration of TBI-related damage also has been investigated. uations [118–121]. Several methods have been used to 658
608 Animal studies consistently demonstrated that both pro- perform the eccentric contractions, including eccentric 659
609 phylactic and therapeutic use of n-3FA decreases axonal resistance exercise, dynamometers, stepping down from a 660
SE

610 and neuronal damage, inflammation, and apoptosis and bench or block and downhill running [119]. Many inves- 661
611 normalizes BDNF and neurotransmitter levels [109–113]. tigations have focused on nutrients that may be useful in 662
612 Moreover, these changes lead to improved cognitive recovery from these intense exercise situations. 663
613 function. Thus, there seems to be promising evidence of the Many nutrients have been touted to alleviate symptoms 664
VI

614 efficacy of curcumin and, especially, n-3FA for recovery associated with muscular injuries using these eccentric 665
615 from TBI in rodents. However, it is not clear if the efficacy exercise models. A complete examination of this literature 666
616 of n-3FA for TBI in rodents can be generalized to humans. is beyond the scope of this review. Interested readers are 667
617 The promising nature of data generated from animal referred to recent reviews [118, 121–124]. Overall, the 668
RE

618 studies suggests that n-3FA may be an effective nutrient to nutrients most often associated with alleviation of pain and 669
619 counter the negative long-term effects of TBI. To date, no increased recovery from eccentric exercise include protein 670
620 study has been published examining this question in and amino acids, anti-inflammatory compounds and 671
621 humans. However, clinical trials are under way after the antioxidants. The available information does not readily 672
622 US Institute of Medicine recommended further investiga- lend itself to a solid conclusion for any of these nutritional 673
623 tion in 2011. There have been a small number of case countermeasures to the deleterious effects of muscle injury. 674
624 studies suggesting that high-dose n-3FA may improve Moreover, it is not certain that this eccentric exercise 675
625 acute outcomes after TBI [114, 115]. Moreover, an open- model is an appropriate way to evaluate soft tissue injuries 676
626 design study demonstrated that a nutritional intervention, in exercisers. Nonetheless, many studies have attempted to 677
627 including n-3FA, improved cognitive function in retired assess nutritional interventions to enhance recovery after 678
628 American football players with a history of TBI [116]. exercise-induced muscle damage and many recommenda- 679
629 However, the players in this study participated in lifestyle tions are commonly made. 680
630 interventions in addition to consuming a supplement that Protein and amino acids probably have been the most 681
631 contained n-3FA and several other ingredients. Thus, the widely studied nutrients in the context of muscle injuries. 682

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683 There are studies suggesting that protein [125] and/or free leading to impaired wound healing [95, 96]. However, 733
684 amino acids [126] may alleviate some indicators of muscle studies determining the appropriate or excessive doses in 734
685 damage. Any positive impact on recovery may be due to humans have not been conducted. Thus, caution is justified. 735
686 the branched-chain amino acid content of the protein [127, One obvious nutrient that is best avoided or at least 736
687 128]. The impact of protein has been attributed to increased ingested in only small amounts is alcohol. Alcohol inges- 737
688 MPS to enhance repair [124]. However, changes in indices tion impairs MPS in rats [132], as well as the response of 738
689 of muscle damage occur in the order of hours [124, 127, MPS to exercise in humans [133]. Moreover, it is clear that 739
690 128]. Given that the turnover of structural muscle proteins alcohol impairs wound healing, likely by reducing the 740
691 is quite slow [26, 129], it is difficult to accept this attri- inflammatory response [134], and increases muscle loss 741
692 bution. Moreover, other studies do not report an effect of during immobilization in rats [135]. Thus, whereas it may 742
693 protein or amino acids [130, 131]. The variable results are be self-evident, it is worth emphasizing that limited alcohol 743
694 likely due to varying supplementation patterns, types of ingestion during recovery is important. So, as tempting as it 744
695 exercise, and other design considerations [124]. Finally, may be to indulge in alcohol to drown sorrows or diminish 745
696 many of the volunteers in the studies were untrained and pain, only small amounts, if any, should be imbibed. 746

F
697 generalizability of the results to an athletic population may
698 be questioned. Thus, this equivocality makes it difficult to

OO
699 conclude that protein or amino acid supplementation 7 Summary and Conclusions 747
700 enhances recovery from muscle injury, particularly for
701 injured athletes. In fact, a recent systematic review con- In summary, there is much still to be learned about the best 748
702 cluded that the evidence for alleviation of symptoms of nutritional strategy to enhance recovery from exercise-in- 749
703 muscle injury by protein and amino acids is lacking [124]. duced injuries. There are claims for the efficacy of many 750
704 Provision of antioxidants and anti-inflammatory agents nutrients, yet direct evidence is sorely lacking. It is quite 751
705
706
707
to alleviate symptoms of muscle damage also has been a
popular strategy. However, at best, as with protein, the
literature can only be considered equivocal. The interested
PR
clear that a careful evaluation of each patient’s situation
must be conducted. Nutritional status and energy require-
ments should be assessed throughout recovery and nutrient
752
753
754
708 reader is referred to recent reviews [121, 123] for a more intake adjusted accordingly. Deficiencies, particularly 755
709 detailed examination of these studies. Clearly, given the those of energy, protein, and micronutrients, must be 756
710 disparity in the types of exercise, supplementation patterns, avoided. Energy balance is critical. Higher protein intakes 757
D
711 and other methodological issues, very little insight into (*2–2.5 g protein/kg BM/day) may be warranted, but at 758
712 nutrition for muscle injuries can be gleaned from exercise- the very least the absolute amount of protein intake should 759
713 induced muscle damage studies. Hence, it is not possible to be maintained even in the face of reduced energy intake. 760
SE

714 make solid recommendations regarding nutritional coun- There is promising—albeit it must be considered prelimi- 761
715 termeasures to exercise-induced muscle damage and nary—evidence for the efficacy of other nutrients in cer- 762
716 injuries. tain situations. Leucine, n-3FA, curcumin, and others have 763
been demonstrated to be beneficial in rodent studies, but 764
VI

information from studies on injured humans is yet forth- 765

717 6 What to Avoid coming. In some situations, higher intakes of these nutri- 766
ents may do harm. Moreover, even if they are efficacious 767
718 Thus far, the focus of the discussion has been on what for injured humans, there is no information regarding the 768
RE

719 nutrients to consume. However, consideration of what to optimal dose of these nutrients. Thus, caution is warranted 769
720 avoid also should be made. As mentioned above, the most before recommendations for wholesale use of these nutri- 770
721 obvious nutrition consideration is to avoid nutrient defi- ents by injured athletes are made. 771
722 ciencies. This consideration was discussed earlier in the The best recommendation would be to adopt a ‘first, do 772
723 context of inactivity and immobilization and should be the no harm’ approach. The use and amount of each nutrient 773
724 number one overriding priority for nutrition related to should be considered in the context of a risk/benefit ratio. 774
725 injury. Additionally, nutrient excess should be avoided. Even if the benefit is uncertain, it may be worth trying if no 775
726 Excess energy could lead to increased total and fat mass, risks can be identified. Otherwise, if there is a risk of doing 776
727 particularly if activity is dramatically reduced. In light of harm with use of a particular nutrient, then perhaps that 777
728 the preliminary evidence for the efficacy of n-3FA in the nutrient should be avoided. As always, the basis of nutri- 778
729 context of several different injuries that has been discussed, tional strategy for an injured exerciser should be a well- 779
730 careful consideration of the dose should be made before balanced diet based on a diet of whole foods from nature 780
731 advising an injured athlete. Excess n-3FA consumption (or foods made from ingredients from those foods) that are 781
732 could excessively depress the inflammatory response minimally processed [136]. Whereas this advice may be 782

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783 considered mundane, boring, and lacking insight, it seems 13. Tipton KD, Phillips SM. Dietary protein for muscle hypertro- 842
784 still to be the best course of action. phy. Nestle Nutr Inst Workshop Ser. 2013;76:73–84. 843
14. Tipton KD, Witard OC. Protein requirements and recommen- 844
dations for athletes: relevance of ivory tower arguments for 845
785 Acknowledgments This article was published in a supplement practical recommendations. Clin Sports Med. 2007;26:17–36. 846
786 supported by the Gatorade Sports Science Institute (GSSI). The 15. Lorenz HP, Longaker MT. Wounds: Biology, Pathology, and 847
787 supplement was guest edited by Lawrence L. Spriet who attended a Management. In: Norton JA, Barie PS, Bollinger RR, Chang 848
788 meeting of the GSSI expert panel (XP) in March 2014 and received AE, Lowry SF, Mulvhill SJ, et al., editors. Surgery: basic sci- 849
789 honoraria from the GSSI for his participation in the meeting. He ence and clinical evidence. 2nd ed. New York: Spring Pub- 850
790 received no honoraria for guest editing the supplement. Dr. Spriet lishing Company; 2008. p. 191–208. 851
791 selected peer reviewers for each paper and managed the process. 16. Stechmiller JK. Understanding the role of nutrition and wound 852
792 Kevin Tipton attended a meeting of the GSSI XP in February 2014 healing. Nutr Clin Pract. 2010;25:61–8. 853
793 and received an honorarium from the GSSI, a division of PepsiCo, 17. Lin E, Kotani JG, Lowry SF. Nutritional modulation of immu- 854
794 Inc., for his meeting participation and the writing of this manuscript. nity and the inflammatory response. Nutrition. 1998;14:545–50. 855
795 The views expressed in this manuscript are those of the author and do 18. Lopez HL. Nutritional interventions to prevent and treat 856
796 not necessarily reflect the position or policy of PepsiCo, Inc. osteoarthritis. Part II: focus on micronutrients and supportive 857
nutraceuticals. PM R. 2012;4:S155–68. 858
797 Open Access This article is distributed under the terms of the

F
19. Lopez HL. Nutritional interventions to prevent and treat 859
798 Creative Commons Attribution 4.0 International License (http:// osteoarthritis. Part I: focus on fatty acids and macronutrients. 860
799 creativecommons.org/licenses/by/4.0/), which permits unrestricted PM R. 2012;4:S145–54. 861
800

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use, distribution, and reproduction in any medium, provided you give 20. Galland L. Diet and inflammation. Nutr Clin Pract. 862
801 appropriate credit to the original author(s) and the source, provide a 2010;25:634–40. 863
802 link to the Creative Commons license, and indicate if changes were 21. Ferrando AA, Lane HW, Stuart CA, et al. Prolonged bed rest 864
803 made. decreases skeletal muscle and whole body protein synthesis. Am 865
804 J Physiol. 1996;270:E627–33. 866
22. Ferrando AA, Stuart CA, Brunder DG, et al. Magnetic resonance 867
imaging quantitation of changes in muscle volume during 7 days 868
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