A sport physician's perspective

Reduced performance and fatigue is a common presentation for sports physicians, particularly when working with endurance athletes.12 Notably, however, it can be diagnostically challenging to distinguish between the normal physiological spectrum of fatigue/functional over-reaching (OR) in an athlete with high training volumes, and the multitude of medical conditions that can present in a similar way. With persistent fatigue and underperformance in athletes lasting 2 weeks or more despite adequate rest and recovery, many different causes should be considered. Any significant medical problem can contribute to underperformance but the most common causes seen in a younger athletic population are outlined in box 1 along with less common causes in box 2.12

Once the underperformance has been established, athletes should be assessed by a sports physician in order to promptly diagnose and treat any underlying medical causes. Given the breadth of possibilities, the initial consultation may be lengthy, with many areas covered and initial investigations undertaken. There may be one specific trigger for fatigue and underperformance, but more commonly, there is a combination of several contributing factors, for example, high training volumes with inadequate recovery; environmental conditions (altitude, heat); external stresses related to work, studies or relationships; recent illness or viral infection; nutritional deficits. Clearly, significant medical problems need to be excluded through a detailed history with systematic questioning (box 3), a targeted physical examination (box 4) and appropriate baseline (box 5) and targeted investigations at the clinician's discretion (box 6).

If significant medical causes have been excluded, a diagnosis of UUPS can be made if the athlete continues to underperform in conjunction with fatigue despite recovery and rest. There are often identifiable medical causes and thus the underperformance is explainable and treatable, and a diagnosis of UUPS is not appropriate. To complicate matters, in many cases, there are confounding factors such as recent viral illness, psychosocial factors, nutritional deficiencies, unfamiliar environmental conditions and sudden increases in training that contribute to the development of UUPS; part of the management will involve addressing these underlying issues. Accordingly, athletes with UUPS should be referred for assessment by a suitable qualified sports nutritionist/dietitian and an exercise physiologist. Where there are underlying psychological issues (and this should be the default rather than the exception position), the athlete should be referred early to a sport psychologist or other mental health professional for further assessment and treatment. After this return to training and competition, should be guided by the interdisciplinary team, with clear communication with the athlete and their coach on time scales, volume, intensity and frequency of training. Regular review and feedback using a variety of longitudinal monitoring tools is ideal in the progression back to full training.13 ,14

A performance nutrition scientist's perspective

Meeusen et al2 highlight a number of nutritional considerations in the prevention of UUPS giving priority to the importance of carbohydrate, energy and fluid intake for the prevention of glycogen depletion, a negative energy balance (EB) and dehydration.2 They address the importance of adjusting carbohydrate intake for periods of intensified training to prevent glycogen depletion and the resulting metabolic, endocrine, mood and performance disturbances that can accrue and are observed in over-reached states.15 ,16 However, there are other nutritional factors which warrant consideration in the prevention and management of UUPS.

For example, a negative EB is deemed to be a risk factor for UUPS. However, it is important to recognise that a negative EB per se is not detrimental to adaption and performance in athletes, although it is likely to increase fatigue and ratings of perceived exertion (RPE). Nor is it necessary for the athlete to be in a state of EB for improvements in athletic performance.2 ,17–19 Athletes will go through training periods with reduced energy availability (EA) and negative EB by a process of periodisation, with the manipulation of macronutrient intake catered for in order to optimise body composition and performance. Significantly, however, a sustained chronic lack of sufficient EA leads to a decline in bioenergetic hormones, poor recovery and maladaptation, placing the athlete at risk of both injury and UUPS.2 ,17 ,20 ,21 For example, Vanheest et al17 directly linked EA and performance in elite athletes. The athletes in whom performance declined across the 12 weeks by ∼8% were in a negative EB for the entire 12-week period (low EA; 10–12 kcal/kg fat-free mass (FFM)). In contrast, the athletes in which performance improved by ∼8% after 12 weeks, experienced ∼8–10 weeks of a negative EB, and were in EB at weeks 2 and 4 only (sufficient EA; 30–37 kcal/kg FFM). It should also be noted that performance was only adversely affected in the low EA group after 6 weeks of sustained low EA. Critically, the training volume and intensity were increased after week 4. This unique study highlights the importance of sufficient EA and periodised nutrition around intensified training periods to facilitate recovery and adaptation, and the prevention of underperformance. Moreover, a sustained chronic period of low EA is sufficient to induce a state of explained underperformance in endurance athletes, and highlights the importance of well-structured and designed monitoring programmes in athletes to prevent unexplained underperformance (UUPS). It is our experience that the use of bioenergetics hormones (eg, free triiodothyronine) can aid the prescription of nutritional support around the training response (stimulus and recovery) in elite healthy athletes.

In this regard, there is increasing interest surrounding the athlete exercising with low carbohydrate availability on muscle physiology and indeed performance, referred to as train low, or fasted training and of late, sleep low.22 ,23 The latter approach may confer a greater risk for UUPS given the crucial role for sleep in athletic performance,24 dietary carbohydrates for sleep onset25 and calorie intake for sleep quality.24 However, increasing dietary protein may serve to attenuate the risk, given the capacity for protein to enhance sleep quality24 and recovery.26 Although there are physiological benefits to the athlete performing structured training sessions in the presence of low carbohydrate availability,27–32 there are risks associated with such practices. Indeed, such sessions should be planned in to the athletes training cycle along with appropriately structured monitoring (physiological, biochemical, hormonal, immunological, psychological, performance), and be relevant to the athlete's physiological development (eg, training age), training goals and performance requirements.32 The practitioner, or athlete self-imposing a restricted carbohydrate diet without monitoring and guidance, with a view to reducing fat mass or enhancing muscle oxidative capacity, for example, may cause chronic low EA and this carries a high risk of maladaptation, infection, reduced performance and UUPS.2 ,17 ,20 Exercising with low carbohydrate availability will increase inflammatory cytokine release,33 and it has been proposed that excessive cytokine release and inflammatory state during and postexercise may lead to UUPS.34 The cytokine, interleukin-6 (IL-6), previously referred to as a ‘fatigueogen’, increases under conditions of low carbohydrate availability.33 ,35 Indeed, IL-6 has been implicated in fatigue and UUPS,33 with elevated concentrations reported to impair exercise performance.36 Furthermore, altered cytokine responses to exercise (eg, elevated IL-6) have been observed in illness prone athletes,37 and athletes presenting with UUPS frequently report infective illnesses.34 Nutritional support for the immune system should be prioritised through intensified training and competition periods, especially in those athletes with a history, or at an increased risk of UUPS, for example, known psychological stress, illness prone athletes and junior athletes. It is beyond the scope of this paper to address the immune support of the elite athlete, which is comprehensively reviewed elsewhere.38 Finally, exercising with low muscle glycogen availability increases skeletal muscle breakdown, amino acid oxidation, serum and sweat nitrogen losses39 ,40 and lowers plasma glutamine concentrations;41 the latter an observation reported in chronically fatigued elite athletes.42 ,43

Adequate dietary protein is integral for health, immunity, adaptation and athletic performance,26 ,44 ,45 with inadequate dietary protein reported in chronically fatigued athletes,43 and significant alterations in plasma amino acids observed in fatigued versus healthy athletes, that is, glutamine and glutamate.42 ,43 ,46–49 In addition, increased dietary protein (3 g/kg/day) intake during a period of overload training in endurance athletes has been shown to attenuate the decline in performance and increase in symptoms of stress.26 Furthermore, increasing dietary protein (3 g/kg/day) during a 2-week block of high-intensity training in cyclists restored the exercise-induced leucocyte trafficking impairment, with fewer symptoms of upper respiratory tract infections.50 In accordance with the aforementioned studies in endurance training models of OR, additional protein in the form of amino acids served to attenuate decrements in performance and increases in muscle damage observed in high volume resistance training OR.51 Periodised adjustments to the athlete's protein intake may serve to modify the impact of intensified periods of training on measures of fatigue and immunity, and enhance performance outcomes. Indeed, it should be emphasised that the periodisation of nutritional support, consisting of adjustments to energy and macronutrients (eg, carbohydrate and protein) and micronutrient intakes around training phases (eg, iron, magnesium, vitamin D), and most crucially intensified training blocks, are a critical element of the successful optimisation of performance, and prevention of UUPS.

Inflammation, oxidative stress (OS) and alterations in redox homoeostasis (ARH) have been implicated in the pathophysiology of OTS,52–54 with ARH reported in athletes diagnosed with OTS.53 In chronic fatigue syndrome (CFS; a conditioned likened to OTS), OS is associated with the degree of fatigue at rest and postexercise,55–57 with several studies demonstrating increased OS in CFS versus healthy controls.56 ,58–62 CFS can be said to represent the extreme end of the OTS continuum. In well-trained athletes, the short-term (2 weeks) restriction of fruit and vegetable intake (ie, low antioxidant diet), to just one-two servings per day, results in increased OS, exercise RPE and inflammation, albeit with no change in performance.63 ,64 However, the lack of a significant change in performance may merely reflect the short-term nature of the studies. Polyphenols, constituents of fruit and vegetables, have been shown to attenuate OS in athletes and reduce the inflammatory response to exercise, including IL-6, improve sleep duration and quality, and enhance skeletal muscle regeneration.65–69 It is interesting to speculate that a chronic lack of sufficient dietary fruits and vegetables (recognising the vast array of different chemicals present70) may lead to slower rates of skeletal muscle regeneration in the athlete, thus placing the athlete at greater risk of UUPS. It is known that the skeletal muscles of healthy endurance athletes display evidence of structural damage, while those endurance athletes diagnosed with acquired training intolerance (ie, UUPS) display significantly greater evidence still of skeletal muscle pathology.71 Vitamin E (α-tocopherol) is integral to skeletal muscle membrane repair72 with serum vitamin E inversely associated with muscle pain thresholds generated via electrical stimulation and fatigue in CFS and healthy controls.55 Low dietary intakes of vitamin E are reported in some athletes73 ,74 but not others,75 with increased postexercise red blood cell haemolysis observed in female athletes with low fat intakes and reduced serum vitamin E concentrations.74 A relationship with red blood cell fragility and serum vitamin E was also reported in elite male swimmers.76 Increased skeletal muscle uptake of vitamin E and the carotenoid β-carotene occurs with exercise,77 and there is evidence for specific training methodologies (ie, 18 days of live-high-train-low) impacting negatively on elite athletes antioxidant status (eg, serum vitamin E and carotenoids) in some studies,78 ,79 but not others;80 for a review see Lewis et al.81

Environmental factors (eg, overseas training camp, altitude, heat stress) may influence the risk of UUPS through (1) enforced dietary changes coupled with added physiological stress such as increased training volume or competition; recognising short-term dietary omissions influence recovery and fatigue, and (2) combination of heat stress, dehydration and high-intensity exercise resulting in mucosal injury, gut permeability, and increased bacterial and inflammatory challenge and OS.82 ,83 Notably, oxidants are implicated in ischaemia-induced gut injury and associated bacterial translocation, with antioxidants (ie, ascorbic acid) preventing exercise-induced endotoxaemia resulting from maximal exercise.83 Through our own observations (unpublished data), biomarkers of redox status should be assessed in athletes with UUPS. Clearly, the micronutrient status of an athlete will deteriorate with a reduction in fruits, vegetables or the omission of any food group. Nutritional deficiencies are a cause of fatigue and should be considered as part of the examination of the athlete presenting with fatigue and UUPS. To our knowledge, no published data exist on the micronutrient status of athletes diagnosed with UUPS.

To summarise, the quality of the diet is important for short-term and long-term health of the athlete, with a diet lacking in the basic components comprising recovery and constituting an increased risk for UUPS, particularly when significant ‘stressors’ are present or increased. A failure to appropriately periodise and individualise the nutritional support, and monitor the athlete effectively throughout the season further increases the risk of UUPS. Finally, it is noteworthy that young athletes with a history of UUPS report loss of appetite with periods of heavy training;10 emphasising the importance of periodised nutrition plans, monitoring, education and guidance in prevention.

An exercise physiologist's perspective

Typically, the literature around the physiology of OR, NFOR and OTS/UUPS begins with an explanation of the stress-recovery-adaptation curve, first described in the seminal work of Seyle,84 with many variations on this fundamental principle since then. Meeusen et al2 bring together a summary of aspects of the literature, system by system, alluding to the fact that the stress-recovery-adaptation curve is too general and the diagnosis of UUPS requires a process of exclusion, beginning in the clinic and extending to the sports science team to take into account non-clinical aspects including training volume, EB and nutrition, recovery habits, and psychology.

A major ‘input’ into the athlete's capacity to recover and adapt is the dose of training, taking into account intensity, duration and frequency. Anecdotally, high performance athletes with a detailed and individualised training plan and regular indicators of progress to inform the training and recovery process may be protected to some degree from UUPS. Unpublished data from British Cycling (Leeder) indicates that UUPS is generally absent from the GB Olympic squad athletes in recent years (presented at the British Association of Sport and Exercise Medicine Spring Conference 2014: http://blogs.bmj.com/bjsm/2014/04/16/the-fatigued-athlete-and-red-s-lessons-from-the-field-and-the-basem-spring-conference-2/); however, those without the support of an effective sports science and medicine team are vulnerable.

Meeusen's position stand recognises that the intensification of training is often concurrent with the development of fatigue.2 The contrasting metabolism of low-intensity vs high-intensity exercise is fundamental to this. It is well described that fat oxidation rates peak at ∼60% to 65% of maximal oxygen consumption (VO₂max) and once blood lactate is accumulating, fat metabolism dramatically diminishes and may be negligible above 90% of VO₂max in favour of carbohydrate to fuel a high ATP turnover and maintain workload.85 This has significant implications for glycogen use, recovery duration and, therefore, EB. Furthermore, training at altitude or in the heat will further increase glycogen turnover and decrease exercise efficiency,86 as will training in a fatigued or depleted state.87 Accordingly, consideration should be given to the contrasting metabolic demands of training sessions when designing a training programme. Assisting coaches and athletes to progress training appropriately to avoid UUPS by managing periods of OR is a key role of the sports physiologist.

Training and redox homoeostasis may be an important feature of the stress-adaptation response through the process of hormesis,88 although again few data relating to redox homoeostasis exist in elite athletes with UUPS.81 It is possible that there is an optimum ‘dose’ of exercise and associated production of reactive oxygen and nitrogen species that results in adaptation (see Vollard et al89). A recent study of OR over 6 weeks demonstrated an increase in OS with cumulative overload, apparently overwhelming antioxidant defence system by week 6.90 Additionally, in functionally over-reached state (F-OR), a taper will result in supercompensation and an expected level of performance.

UUPS also has implications for the taper. In an elegant study, Aubry et al.91 demonstrated that athletes in a F-OR, performed worse after a 2-week taper than a similar group defined as acutely fatigued from training. This highlights the importance of training management, and adds weight to the notion that 2 weeks should be adequate for a positive improvement in performance. Even in the F-OR group, there was a small increase in performance with a taper that would be absent in UUPS.

The assessment of heart rate variability may be an attractive option for preventing UUPS in endurance athletes; however, the data in this area are sparse. A recent study of trained triathletes demonstrated that in F-OR, a progressive tendency towards parasympathetic modulation of heart rate was evident. The study concluded that the heart rate variability should be assessed on a daily basis to account for noise in the signal.92 Together with many other considerations, the appropriate management and monitoring of workload and recovery is fundamental to the avoidance of UUPS. Various software exist that track training volume, and there are examples that use algorithms to yield an index of overall recovery; however, to our knowledge, none of these have been validated. However, a battery of monitoring tools could be effective in avoiding UUPS, including the measurement of physiological and psychological variables, together with logs of dietary and training practices.

It is recognised that key to the training and adaptation cycle is energy homoeostasis. Indeed the IOC has recently introduced a new term: Relative Energy Deficiency in Sport (RED-S20 ,21) that implicates energy deficiency in a host of pathologies, underperformance problems and conditions, including the Female Athlete Triad, but not restricted to female athletes. Further, RED-S is implicated in a range of symptoms associated with the diagnosis of UUPS including decreased endurance performance and decreased training response. Energy homoeostasis can be assessed globally through changes in body weight and body composition; however, biomarkers of energy homoeostasis may also be of use including hormones, peptides and cytokines, comprehensively reviewed by Jürimäe et al.93

The other major component of the stress-recovery-adaptation is of course recovery and sports physiologists have strived to offer techniques of promoting or enhancing recovery in athletes, including (in addition to nutritional interventions described above) compression,94 cold water immersion95 and sleep.24 Evidence that athletes with UUPS are failing to achieve sufficient sleep (quality and quantity) is absent from the literature. However, sleep remains a cause for concern, particularly given the clear and growing association between sleep deprivation and a range of negative associations including compromised immune function;96 compromised daytime performance;97 and generally lower quality and quantity of sleep in elite athletes compared with healthy non-athlete controls.98 Furthermore, one recent study using wristwatch actigraphy assessed sleep in the F-OR athlete, observing a significant decrease in sleep duration, sleep efficiency and immobile time during sleep (−7.9%, −1.6% and −7.6%, respectively99), implying that chronic sleep deprivation could be a critical factor in the aetiology of UUPS.

A sports psychologist's perspective

Building from Meeusen et al,2 and from a psychological perspective, the first thing to notice is the recovery time factor which seems to be inherent in distinguishing between F-OR, NFOR and OTS; most particularly the stagnation factor associated with NFOR and therefore, presumably, OTS. Indeed, this led Meeusen and colleagues to use the term ‘prolonged maladaptation’ as a distinguishing characteristic between these various forms. For practitioners, this emphasises the importance of athlete perception as an important discriminating factor, perhaps even more important than actual physical training load (cf. Birrer et al6), between who does or does not suffer with these problems. Certainly, in the absence of the clear test for UUPS which has been suggested, perception seems to be one of several factors which, rather than discriminating by degree, may be either cause or symptom, depending on the individual.

The other factor worthy of mention from Meeusen et al2 is the coaction and impact of psychology, over and above the well-examined mood state profiling which has dominated the literature. Meeusen et al2 provide a good coverage of this literature, together with the pitfalls of mood as an OTS indicator (eg, need for consistent protocols, faking by athletes, consistency of self-report, etc). What is less apparent, however, is the effect that this state (however protracted) will have on other markers, including hormonal levels, performance tests, etc. As such, psychology is clearly more than just mood and has a plethora of interactive effects; indeed, it is this that underpins the promise of perceived measures (eg, RPE, muscle soreness100 ,101) as preventative tests.

Indeed, recent work (eg, Cook and Beaven102) supports this contention on the role of perception as a cause of incidence or prevention, particularly on the delicate edge where the system can go either way. In any case, it seems fair to suggest that perception of the challenge and how close it is to your limits is an important concomitant which practitioners should monitor and, where possible, employ. Other studies have highlighted psychological traits (eg, optimism;103 self-determined motivation104) and states (eg, the switch in perception to external factors when fatigued;104 self-esteem105), which also seem to mediate the impact of physical challenges.

Certainly, as our understanding of stress extends from the homoeostasis position of Selyé` towards the new allostatic perspective (eg, McEwen106), that the importance of such complex interactions between psychological and physiological factors becomes clear as they can account for the varied responses which characterise UUPS and similar conditions.107 Certainly, the integrated model suggested by Grove et al108 in dance provides a good basis for applied work across other performance domains. A list of presetting conditions (both environmental and personality), antecedents and a mechanistic interaction of factors provides the structure by which practitioners can address the issue. In this regard, it is worth highlighting that non-training factors seem to have a clear association with UUPS, albeit (unsurprisingly) only in some cases.109 The ideas presented in this model on entrapment and restraining factors (relating, perhaps to a perceived lack of control) also hold some promise although, clearly and commonly, more research is needed. In simple terms, we know lots but discerning the exact blend to apply to any individual case remains a complex challenge,4 despite high-quality medical research, which is uncovering some of the mechanisms that seem to occur in some of the cases.110

In fact, the clearest and most significant point is the highly individualised nature of these complaints. In short, and as with so many human factors,111 a particular intraindividual blend of biopsychosocial elements is associated with the susceptibility to, and incidence of, UUPS.6 This inherent variability may well explain the use of OTS as a ‘diagnostic dustbin’ and the extreme variation in precursors and outcomes seem, to us, a likely part of the reconsideration of OTS as UUPS.3 ,4

Thus, these varied precursors, concomitants and outcomes point to the need for interdisciplinary and personalised support. Perhaps the best preventative strategy lies with coaches and support staff, who have good knowledge of the athletes, employing a variety of different and personalised markers, as is now often the case with daily monitoring for training readiness.48 ,112 In simple terms, the initial use of a broad testing spectrum, followed by a personalised refinement based on which markers appear most reactive to each individual, would seem the best general rule for progress. Further reflecting the psychological dimension, a focus on athlete perception as a sound general approach is to be encouraged; ensuring that athletes know what, why and when they are doing things and that they have confidence in the plan. Increased coach–athlete discussion, surely a sensible procedure across the development spectrum, is a major tool in this approach.

Finally, it is of utmost importance to ‘know your athlete’! What s/he thinks of the specific training, why s/he thinks that and, more broadly, their general disposition (eg, optimistic/pessimistic, high/low trait anxious, etc). The bottom line being, changing perceptions (although often easier said than done) can have a significant effect.