Another means by which amino acid supplementation might provide an advantage during ultra-marathon racing is in offsetting central fatigue. Prolonged exercise increases the synthesis and metabolism of 5-hydroxytryptamine (5-HT; serotonin) in the brain, which is associated with lethargy, drowsiness, and reduced motivation [108]. Critically, tryptophan (the 5-HT precursor) competes with BCAAs to cross the blood-brain barrier [109], with the hypothesis that increasing the circulating concentrations of BCAAs might mitigate 5-HT accumulation, attenuate the seretonin:dopamine ratio [110], and potentially offset central fatigue. Indeed, athletes showed reduced effort perceptions when BCAAs were supplemented during submaximal cycle exercise performed in a glycogen-depleted state [111]. Moreover, when trained cyclists undertook several hours of exercise in the heat to exacerbate the central component of fatigue, BCAA supplementation prolonged time to exhaustion [112]. It is feasible that the role of BCAAs in offsetting central fatigue may be further pronounced during the extreme-distance ultra-marathons, the conditions of which are rarely replicated, and difficult to perform reliably, in a laboratory environment. The effect of BCAAs on central fatigue is far from certain, and further studies specific to ultra-marathon running are needed to elucidate the mechanisms that might underpin any beneficial effects.
Thermoregulation during exercise is largely dependent on the mammalian sweat response to evoke evaporative heat loss. Insufficient fluid replacement, therefore, results in a net loss of body water, the main consequence of which is dehydration-induced cardiovascular drift; i.e., a reduction in plasma volume and a necessary increase in heart rate to maintain cardiac output [117]. The result is a diminished exercise capacity [118], and an increased risk of heat illness and rhabdomyolysis [118]. Dehydration may also diminish cognitive performance [11, 118] and increase perceived exertion [119]. All of the above may compromise performance and exacerbate the risk of injury and/or illness during ultra-marathon, particularly in arduous races, those requiring navigation, or those contested on technical terrain. Although dehydration can result from running in cold conditions due to a blunting of the thirst response, dehydration is more of a risk during races in hot and/or humid conditions when sweat rates are increased [120]. Moreover, consideration should be given to whether hot ambient conditions are dry or wet since the latter will compromise evaporative heat loss, increase fluid requirements, and increase the risk of heat illness.
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To mitigate the extreme peripheral stress associated with competition, ultra-marathon runners commonly use analgesics including NSAIDs (Ibuprofen or aspirin), non-opioid analgesics (paracetamol), and compound analgesics (co-codamol) [179]. The prevalence of NSAID use among ultra-marathon runners is as high as 60%, with 70% of runners using NSAIDs during racing [180, 181]. There are several reports of attenuated exercise-induced muscle inflammation, circulating creatine kinase levels, and muscle soreness when NSAIDs were administered prophylactically before exercise [182, 183]. By contrast, a number of studies have found no effect of NSAIDs on analgesia or inflammation during exercise [184,185,186,187,188]. Notwithstanding, NSAID use can cause serious adverse effects on cardiovascular, musculoskeletal, gastrointestinal, and renal systems, all of which might be exacerbated by ultra-marathon running (for review, see [179]). There is an increased risk of GI-injury with NSAID use, and this may be exacerbated in long-distance runners (contesting marathon and ultra-marathon) who already exhibit a greater incidence of GI-bleeding [189,190,191]. Frequent prophylactic use of NSAIDs is also associated with increased risk of renal side-effects [192, 193], and concern has been expressed about a possible causative role of NSAIDs on exercise-induced hyponatremia [194]. Given the equivocal evidence-for-efficacy and the acute contraindications, NSAID use during ultra-marathon is strongly discouraged. Importantly, up to 93% of endurance runners are naïve to any contraindications of NSAID use [195], indicating the need for greater education in this respect. We thereby recommend race organizers to discourage NSAID use among their participants. 2ff7e9595c