Energy and macronutrient demands

Energy expenditure

Given the durations typical of ultra-marathon, it is not feasible to meet caloric demands in their entirety. Several scenarios can be examined to reinforce this hypothesis. First, consider that a 50 kg athlete undertaking a 50 mile (80 km) race at 8.0 km·h− 1 (~ 10 h) will expend ~ 3460 Kcal. For the same event contested at the same pace, a 70 kg athlete would expend ~ 4845 Kcal (an approximate Kcal range of 346–484 Kcal·h− 1). Second, a 50 kg athlete undertaking a 100 mile (161 km) ultra-marathon at an average pace of 6.5 km·h− 1 may expend ~ 6922 Kcal in ~ 25 h, whereas at the same pace, a 70 kg athlete would likely expend ~ 9891 Kcal (range of 277–395 Kcal·h− 1). These values are similar to the estimated energy expenditures of 200–300 kJ·km− 1 (47.8–71.7 Kcal·km− 1) reported elsewhere [31]. When offset against the energy intakes observed in a typical ultra-marathon, runners are likely to exhibit a net calorie loss [92]. Accordingly, in addition to implementing an in-race nutrition strategy, an effort should be made to minimize caloric deficits before and after the race, and should be considered part of the overall holistic approach. Indeed, CHO availability for racing can be maximized by adhering to a contemporary loading strategy (i.e., ~10 g·kg− 1·d− 1) in the 48 h leading into the event [42, 44], with care taken to avoid GI distress. On race-day, runners are advised to consume a familiar, easily-digestible pre-race meal, rich in low-glycemic index CHO, while avoiding food with high fat and/or fiber content to minimize gut discomfort during the race.

Energy intake

Field studies indicate that successful completion of ultra-marathon is generally associated with greater energy and fluid intake [14, 15], even when accounting for variations in performance time [15]. A nuance of the longer distance event is that the lower average work rate permits a faster rate of gastric emptying, which tends to be compromised only at exercise intensities > 70% maximal oxygen uptake (V̇O 2 max) [93]. Consequently, relative to shorter races contested at a higher intensity, ultra-marathon runners can usually accommodate greater energy intake and more calorie-dense foods to the level of individual tolerance [94].

There is variability with respect to the absolute rate of energy intake reported during racing, but a sensible range can be determined. In 213 runners contesting one-of-three race distances (44, 67, or 112 km; Ultra Mallorca Serra de Tramuntana; Spain), mean energy intake was 183 Kcal·h− 1, with no discernible difference among race distances [95]. By contrast, in longer races (100 mile, 161 km), caloric intakes of < 200 Kcal·h− 1 tended to result in race non-completion [15], with race finishers consuming a significantly greater number of hourly calories when compared to non-finishers (4.6 ± 1.7 versus 2.5 ± 1.3 Kcal·kg− 1·h− 1). These findings have been reported elsewhere under similar race conditions [92]. Moreover, elite runners contesting a series of sixteen 100 mile (161 km) ultra-marathons, reported average energy intakes of 333 ± 105 Kcal·h− 1 [96]. Greater caloric intakes may, therefore, be necessary for longer races to enable performance.

Based on previous estimates of energy expenditure during running, and the above-mentioned research, the ISSN recommends a caloric intake of ~ 150–300 Kcal·h− 1 for race distances up to and including 50 miles (~ 81 km) during which any caloric deficits may be better tolerated. By contrast, in longer races when the magnitude of caloric deficits is greater and less likely to be well-tolerated, higher intakes of ~ 200–400 Kcal·h− 1 are suggested. Where GI distress is an issue, transient reductions in energy intake to the lower-end of this range are reasonable, congruent with a reduction in race pace. However, persistent calorie intakes of < 200 Kcal·h− 1 are not recommended, and when nausea precludes this rate of intake, a degree of perseverance/stubbornness with respect to feeding (within tolerance levels) may be required. This may be particularly pertinent in the latter stages of a race in order to minimize the risk of hypoglycaemia which can result in race non-completion, and reinforces the importance of progressive gut training during the preparation phase [97].

Carbohydrate versus fat intake

The mechanistic link between glycogen depletion in skeletal muscle and liver, and a subsequent early-onset fatigue during prolonged exercise was made in the 1960s [98]. In addition to negatively impacting endurance performance, the reduction in plasma glucose concentration that follows glycogen depletion is associated with acute cognitive decline; this, in turn, can compromise athlete safety on ultra-marathon courses of technical terrain or those requiring navigation. Nevertheless, the absolute CHO requirements for ultra-marathon racing are unclear. There is certainly a lower rate of CHO utilization during ultra-marathon relative to marathon. Laboratory data demonstrate that respiratory exchange ratio (RER) gradually decreases until the 8th hour of a 24 h treadmill run, and plateaus thereafter, reflecting a reduced rate of energy derived from CHO; moreover, this is congruent with a diminished running velocity [99]. As muscle glycogen diminishes, there is a compensatory increase in fat oxidation, with rates of 0.2–0.5 g·min− 1 typically observed during endurance exercise [100], and higher values of 1.0–1.5 g·min− 1 reported in a single subject after 6 h of running [101, 102]. The prolonged durations and slower relative running speeds that characterize ultra-marathon appear, therefore, to permit increased rates of fat oxidation for adenosine triphosphate (ATP) re-synthesis [100]. However, there is still a risk of glycogen depletion during ultra-marathon if work rate is too high, or if nutrition is poorly managed. Worthy of note is that extremes of both temperature and altitude will increase the absolute rate of CHO oxidation during exercise [102], and the nutrition strategy should accommodate these variations.

With respect to the absolute amounts of CHO and fats to be consumed during ultra-marathon, individual strategies vary greatly. There are reports that amateur runners contesting races of up to 70 miles (112 km) ingested CHO at a mean rate of 30 g·h− 1 [95]. In longer races (100 miles, 161 km), similar rates of CHO ingestion may be typical for slower finishers (31 ± 9 g·h− 1 [103];), both of which were lower than faster finishers (44 ± 33 g·h− 1); these data reinforce the notion of broad variance in the strategy used pending race pace or duration. Over the same distance, others report greater CHO intakes of 65.8 ± 27.0 g·h− 1 (range: 36–102 g·h− 1 [15];) compared to 41.5 ± 23.2 g·h− 1 for non-finishers (range: 13.8–83.8 g·h− 1). When expressed relative to body-mass, finishers consumed nearly double the amount of CHO than non-finishers (0.98 ± 0.43 versus 0.56 ± 0.32 g·kg− 1·h− 1). Similar values are reported in elite runners (71 ± 20 g·h− 1) during single-stage races [96]. Although current literature advocates CHO ingestion rates up to ~ 90 g·h− 1 for events > 120 min, particularly when using ‘multiple transportable carbohydrates’ containing glucose and fructose [104], such high rates of ingestion may be unrealistic for longer ultra-marathon races (> 6 h). Moreover, this rate of ingestion may lead to nutrient malabsorption and GI distress [105]. Worthy of consideration is that a CHO target of 90 g·h− 1 would necessitate a race diet almost exclusively comprising CHO (360 Kcal·h− 1) which is typically unsustainable given the greater preference for fat and salt that manifest in longer races.

With increasing race distance, a greater proportion of calories from exogenous fat may be critical for success [95]. Throughout a 100-mile race, finishers consumed a total of 98.1 ± 53.0 g of fat, which was approximately 5-fold greater than that of non-finishers (19.4 ± 21.1 g); moreover, when normalized for body mass and running velocity, this equated to a rate of fat ingestion that was three times greater in finishers (0.06 ± 0.03 versus 0.02 ± 0.02 g·kg− 1·h− 1 [15]). Collectively, these data suggest that successful completion of ultra-marathon likely requires a higher degree of tolerance to both CHO and fat intake (either as solids or fluids). Foods with a greater fat content are advantageous during racing in terms of caloric provision per unit of weight, and this is pertinent for minimizing pack weight when running self-sufficient. Moreover, foods with a greater fat content (see Table 4) often contain more sodium, which may help mitigate the risk of exercise-associated hyponatraemia.

Table 4 Example foods consumed by athletesa during single-stage ultra-marathon (35–100 miles, 56–161 km) Full size table

Protein intake

Protein ingestion during racing is often neglected, for two possible reasons: i) protein plays a secondary role in energy metabolism under race conditions and athletes, therefore, prioritize the ingestion of CHO and fat; and ii) strategic ingestion of protein is difficult when runners rely solely on fixed checkpoints for the supply of energy/fluid and are, therefore, at the mercy of race organizers to supply foods with adequate protein. Nevertheless, it is plausible that protein ingested during an ultra-marathon would mitigate the ill-effects of muscle damage and/or positively influence energy metabolism. Indeed, finishers of a 100-mile (161 km) race had a significantly greater protein intake relative to non-finishers (131.2 ± 79.0 versus 43.0 ± 56.7 g) and, when expressed as a relative ratio per hour, race finishers consumed twice the quantity (0.08 versus 0.04 g·kg− 1·h− 1) [15]. Gastrointestinal distress and a lack of appetite in non-finishers may explain their lower overall intake.

Protein is likely an important component for prolonged endurance exercise because of the substantial proteolysis and muscle damage that can manifest before the conclusion of a race. In controlled studies, however, there are conflicting results. Protein co-ingested with CHO during 6 h of running and cycling improved net protein balance to a greater extent than the ingestion of CHO alone [106]. By contrast, when ultra-marathon runners were supplemented with 52.5 g of amino acids or a placebo prior to, and during, a 62-mile (100 km) race, there were no significant differences in markers of muscle damage or overall performance [107]. As such, the equivocal findings may result from the co-ingestion of protein and CHO, and/or differences in the exercise modality used between studies. Irrespective, nutrition strategies should be implemented that mitigate the consequences of prolonged protein abstinence, and a balance of macronutrients should be consumed.

A degree of self-sufficiency when racing may provide an opportunity for runners to follow a more bespoke nutrition strategy to better satisfy individual protein needs (see Table 4 for example foods). Protein-rich foods can be carried in running belts and/or backpacks and consumed ad libitum, but race organizers are also encouraged to provide high-protein options at checkpoints. Runners who are concerned that consuming calories from protein might compromise energy availability (i.e., by necessitating fewer calories from CHO and fat) might consider BCAA supplements (as liquid or tablets) as an alternative, particularly when the availability of protein-rich foods is limited. Where possible, ultra-marathon runners should strive to meet the typical dietary guidelines by consuming ~ 20–30 g of protein every 3 h [69].

The central fatigue hypothesis

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.

Savory vs. sweet

A key consideration for the ultra-marathon runner should be the palatability of food (and fluid), particularly in longer races. Moreover, tastes and food preferences will likely change throughout the course of the race [113]. There are several reports of runners complaining of the unpalatability of sweet foods, particularly energy gels and sports drinks, both in the heat [114] and in ultra-marathons > 60 miles contested in thermoneutral environments [115, 116]. These data indicate that the aversion to simple CHO is not exclusively dependent on ambient conditions but is also influenced by race distance and/or duration. The mechanisms underpinning the proclivity for high-fat/salty foods are unclear, but it has been speculated that athlete food preferences are made to maintain a consistent chemical balance in the body [115]. In the aforementioned studies, runners tended to exhibit a penchant for savory food (i.e., flavoursome, non-sweet, and containing greater relative amounts of fat and salt) in the latter stages of ultra-marathon, thereby supporting the notion that changes in food preference may reflect nutrient inadequacies resulting from long-duration activity. An important consideration is to what extent one must rely on food provided by organizers at pre-determined checkpoints, given that the nature of such food is unpredictable and may be in limited supply. Accordingly, it is recommended that runners anticipate food availability, and carry their own food to more accurately fulfil their individual needs. Finally, race organizers are encouraged to provide a variety of foods at checkpoints (including a mixture of proteins, carbohydrates, and fats; see Table 4), and to publish in advance the list of foods to be served at feed-stations, so as to aid athletes in their race preparation. In longer races (> 50 miles / 80 km) that require athletes to skip multiple meals, organizers should consider providing at least one hot, calorie-dense meal served at a strategic point in the race. This will break the monotony associated with repetitive feed stations, and afford the runner an opportunity to mitigate caloric deficits that will likely accumulate.

Evidence statement (category C)

Athletes should follow a contemporary CHO-loading approach in the 48 h prior to racing in order to commence fully-replete. Calorie deficits during racing are expected but can be minimized by consuming 150–400 Kcal·h− 1, pending differences in body mass, race distance/pace, and individual gut tolerance.

Evidence statement (category C)

Calories should be consumed from a combination of protein (5–10 g·h− 1), CHO (30–50 g·h− 1), and fat; however, foods with greater fat content may be preferred in longer races.

Evidence statement (category D)

As race duration increases, runners tend to favor savory foods, likely reflecting energy and electrolyte insufficiencies.

Offsetting dehydration

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.

Drinking-to-thirst is an acknowledged means of maintaining hydration during short-duration exercise (<90 min), when environmental conditions are cool, and/or when exercise intensity is low (e.g., < 60% V̇O 2 max) [121]. Moreover, this strategy is considered the most appropriate method of minimizing the risk of hypo- or hyper-hydration during ultra-marathon [16]. However, given that most athletes choose to consume electrolyte formulas by ingesting fluids, drinking-to-thirst may result in the under-consumption of sodium and other vital electrolytes. In long-distance ultra-marathons, the most common hydration plan is drinking according to an individualized schedule [122]. Moreover, finishers tend to consume fluid at a greater rate than non-finishers [92]. Mean fluid ingestion rates of ~ 0.5 L·h− 1 have been observed during a road ultra-marathon of 62 miles (100 km), with a broad range in the total volumes consumed (3.3–11.1 L) [123]. Slightly higher ingestion rates of ~ 0.75 L·h− 1 have been reported in races of 100 miles (161 km [92]). Collectively, the available data suggest that there are broad individual intakes among ultra-marathon runners, but that successful runners tend to meet the lower-limits of recommended values.

Fluid ingestion that results in diluted plasma sodium may be indicative that runners are not meeting their sodium needs [92]. Over-hydration, and the consequent dilution of plasma sodium, can have severe adverse effects on health (see Exercise-associated hyponatraemia), and there are case-reports of water intoxication in runners who aggressively rehydrate [124]. Runners contesting ultra-marathon should aim to consume 150–250 mL of fluid approximately every 20 min during exercise [31, 125], but fluid intake should be adjusted pending environmental conditions, race duration, work rate, body mass, the degree of fluid tolerance, and prior gut training. Individuals wishing to optimize performance should determine their individual sweat rates, in advance, under conditions which resemble competition (i.e., a similar exercise intensity, terrain, environment) [121]. An accessible means of estimating sweat rate is to measure nude body mass pre- and post-exercise; this will allow for an individualized fluid ingestion strategy.

Exercise-associated hyponatraemia (EAH)

Sodium is the major ion of the extracellular fluid and contributes to the generation of action potentials for muscle contraction, but it also has an important role in fluid retention [118]. Hyponatraemia, a potentially fatal condition of cell-swelling, is clinically-defined as a serum sodium concentration < 135 mmol·L− 1. Modest symptoms include headache, fatigue, and nausea, but can result in seizures and death in severe cases [9]. Two key, interrelated mechanisms are responsible for hyponatraemia: i) excessive sodium loss from the extracellular fluid resulting from a high sweat rate (e.g., while exercising in the heat) and prolonged sweating (e.g., during long-duration exercise); ii) aggressive hydration strategies using non- or low-electrolyte-containing fluids, which precipitate overload of the extracellular fluids, thereby diluting serum sodium [9]. Although the condition is rare, and individual susceptibility plays a role in prevalence, the earliest reported cases were observed in ultra-marathon runners and Ironman triathletes [9] (i.e., during ultra-endurance exercise), and the athletes most commonly developing symptomatic hyponatremia typically participate in distance running events of > 26.2 miles (> 42.2 km) [126].

In order to reduce the risk of hyponatremia during long-duration exercise, runners should consume sodium in concentrations of 500–700 mg·L− 1 of fluid [118]. Slightly greater amounts of sodium (and other electrolytes) will be required in hot (e.g., > 25 °C / 77 °F) and/or humid (e.g., > 60%) conditions when sweat rates are elevated; in such conditions, runners should target ~ 300–600 mg·h− 1 of sodium (1000–2000 mg of NaCl). If consumed in fluid, sodium concentrations greater than ~ 1000 mg·L− 1 (50 mmol·L− 1) should be avoided as this may reduce drink palatability [127]. Indeed, there is anecdotal evidence that effervescent (dissolvable) electrolyte tablets, and liquid electrolytes added to water, can compromise drink palatability, particularly during long races or those contested in the heat, thereby resulting in reduced fluid consumption. As such, capsules or tablets that can be swallowed whole are recommended, thus leaving water untreated. The amounts taken should also be offset against the sodium consumed from salt-containing foods, although it should be noted that it is unlikely that the recommended rate of sodium intake will be achieved from foods alone. In addition, the concentrations of some electrolytes (e.g., sodium) in many commercially-available electrolyte replacement products are insufficient to meet the recommended intakes. As such, runners are encouraged to pay close attention to the ingestion method and composition of their electrolyte formula.

Given the inherent risks associated with EAH, greater care should be taken to educate ultra-marathon runners on its deleterious consequences. For example, there are data to suggest that although sodium ingestion may help attenuate the likelihood of developing EAH, sodium intake is not sufficient for this purpose when simultaneous with excessive fluid ingestion [89]. As a result, runners sometimes adopt a low-volume drinking plan instead of increasing sodium intake congruent with their needs [122]. Such poor practice must be challenged, since it is possible to consume adequate amounts of both fluid and sodium during prolonged exercise, with sufficient practice.

Evidence statement (category C)

Fluid volumes of 450–750 mL·h− 1, or 150–250 mL every 20 min, are recommended during racing. Electrolyte concentrations (particularly sodium) from commercial products may not be sufficient for optimal hydration, especially in hot/humid conditions, and additional sources of sodium should be considered with the aim of ingesting 500–700 mg·L− 1.

Gastrointestinal (GI) distress

A common cause of non-completion and/or reduced performance in ultra-marathon racing is GI discomfort or distress. A conservative estimate is that 30–50% of athletes experience GI-related issues during ultra-marathon [128], although values of 70–80% have been reported [129, 130]. The type, duration, and severity of symptoms vary on an individual basis, with upper GI-tract related issues (e.g., nausea, vomiting, heartburn) more common in longer races compared with complaints relating to the lower GI-tract (e.g., bloating, diarrhea) [115]. In a large cohort of males and females (n = 272) competing in the Western States Endurance Run (100 mile; 161 km), the majority of athletes (96%) experienced GI symptoms at some point during the race, particularly at the hottest and likely most challenging part of the course, with 44% indicating that GI issues negatively impacted race performance. Nausea was cited as the most common symptom likely to affect race strategy (reported in 60% of athletes) [130], perhaps due to the subsequent impact on the ability to ingest food and fluid.

The pathophysiology of GI distress during ultra-marathon training and racing is multifactorial, but is likely the result of reduced mesenteric blood flow [131, 132], leading to relative GI hypoperfusion [133]. This is often predicated by dehydration and/or increased core temperature, which can further compromise gastric emptying and paracellular transport [134]. An increased appearance of systemic lipopolysaccharides (LPS) from gram-negative intestinal bacteria may result from acute intestinal tight-junction protein disruption, thereby provoking an immune response, as well as endotoxin-mediated GI distress [134]. In one study, 81% of runners requiring medical attention at the end of a 56 mile (90 km) ultra-marathon (Comrades Marathon, South Africa) were reported to have LPS concentrations exceeding 100 pg·ml− 1 [135], with 81% reporting both upper- and lower-GI distress (nausea, vomiting, and diarrhoea). While such post-race endotoxin concentrations are considered severe in athletes, other researchers have noted a ‘bi-phasic’ endotoxin response in 68% of athletes competing in an Ironman triathlon, which corresponded with acute recovery phase cytokinemia [136]. This ‘low-grade endotoxemia’ may, in part, influence individual recovery responses during the short-term (<12 h) and chronic (>36 h) post-race period.

Strategies to minimize GI distress

Symptoms pertaining to exercise-associated GI distress are highly individualized and may be related to predisposition, intestinal microbiome activity (based on bacterial quantity and species diversity), and feeding tolerance [137]. The primary nutritional cause of GI upset during ultra-marathon is the high intake of CHO, particularly hyperosmolar solutions (e.g., > 500 mOsm·L− 1 and > 8% CHO concentration) [128]. Runners experiencing upper-GI discomfort were reported to have a greater energy and CHO intake than runners not experiencing symptoms [115]. This supports the notion that high rates of CHO ingestion, although being beneficial for race completion, might actually exacerbate symptoms of GI distress. In addition, strategies that could mitigate the likelihood of LPS release into the blood and, thus, endotoxin-associated symptoms, include limiting the consumption of saturated fat [138], avoiding the consumption of non-steroidal anti-inflammatory drugs (NSAIDs) [139], and maintaining an adequate water intake [139].

The use of ‘multiple transportable carbohydrate’ solutions (i.e., those containing glucose, fructose, and/or maltodextrin) has been shown in trained individuals to increase overall intestinal absorption, facilitate increased total CHO oxidation rates, and limit the degree of gut discomfort typically observed with single CHO solutions (e.g., fructose) [104, 140]. Although many ultra-marathon runners rarely rely solely on sports drinks for energy and/or CHO intake during racing, use of solutions with multiple transportable carbohydrates may be an effective short-term strategy to limit the likelihood of non-completion due to energy under-consumption. Recognizing the early onset of GI distress, and strategizing to maintain energy intake close to target values regardless, may be the key to managing some GI-related issues. Although counterintuitive, there may be some instances when eating regardless of nausea will give the most relief from such symptoms, especially when nausea is caused by hypoglycemia.

Prior race strategies that either ‘train the gut’ or include/omit some food groups may provide a solution to limit the negative impact of GI symptoms during racing. While ultra-marathon training may elicit progressive behavioral changes (e.g., greater confidence in trialing personalized nutrition strategies) and physiological adaptations (e.g., increased intestinal tight-junction integrity and enhanced immunological response to endotoxin release [135]), targeted nutrition strategies may confer a degree of individual benefit. It is apparent that well-trained athletes can tolerate higher intakes of CHO during running [128], and that habituation to a high CHO diet enhances total carbohydrate oxidation rates which may be important for sustained race performance [141] and reduced GI upset. Where symptoms of irritable bowel syndrome (IBS) are present, practicing a low FODMAP (fermentable oligosaccharide, disaccharide, monosaccharide and polyol) diet has been shown to reduce GI distress acutely [142, 143]. While responses to low FODMAP diets may be highly individual, strategic implementation (under guidance of a qualified nutrition professional) in the days preceding a race, or during training when acute symptoms occur, may confer GI support. Nevertheless, further research is warranted to confirm whether such benefits are applicable during sustained running.

Finally, the use of probiotic bacteria, particularly including the gram-positive genera Lactobacillus and Bifidobacterium species, has been shown to modify GI microbiota [144] and may provide an adjunct nutritional strategy in cases pertaining to acute GI disruption (e.g., GI dysbiosis, exercise-associated GI permeability). There is evidence of reduced GI symptom prevalence and severity following the administration of probiotics [145, 146] although benefits may be individualized and strain-specific. Recently, 4 weeks of supplementation with Lactobacillus acidophilus (CUL60 and CUL21), Bifidobacterium bifidum (CUL20), and Bifidobacterium animalis subs p. Lactis (CUL34) was shown to reduce GI symptoms, and may be associated with the maintenance of running speed in the latter stages of marathon [147]. Chronic multi-strain interventions have also been shown to reduce fecal zonulin levels by ~ 25% in endurance-trained athletes, attributed to improved GI epithelial integrity [148]. The inclusion of dietary prebiotic nutrients (e.g., fructooligosaccharides, inulin, pectin) may also play an important role in short-chain fatty acid production, which may support epithelial integrity (for review, see [149]). The use of pre/probiotics has, however, been contested [105] and, at present, there is limited evidence of a beneficial effect in ultra-marathon racing; as such, caution is recommended before implementing a new strategy.

Evidence statement (category B/C)

Symptoms of upper-GI distress, particularly nausea, are commonly reported during ultra-marathons, are a cause of non-completion, and are more prevalent in longer races.

Evidence statement (category C)

To mitigate GI distress, runners should avoid highly concentrated CHO, and minimize dehydration. When symptoms manifest, runners can slow their pace and decrease their calorie intake, although persistent intakes of < 200 Kcal·h− 1 should be avoided in longer races.

Evidence statement (category B)

Nutritional strategies should be practiced in training, well in advance of racing, to allow sufficient time for GI adaptations that optimize CHO absorption, and mitigate GI distress.

Supplements and drugs

Caffeine

Caffeine is widely consumed as part of a normal diet, and there is clear evidence-for-efficacy regarding its ergogenic properties in a variety of sports [150,151,152], although the extent of the ergogenic effect is largely dependent on inter-individual genetic variance [153]. Caffeine works via two potential mechanisms: firstly, there is a centrally-mediated ergogenic effect, whereby caffeine blocks adenosine receptors in the brain and inhibits the binding of adenosine, resulting in improved cognitive function and concentration; secondly, caffeine potentiates intramuscular calcium release, thereby facilitating excitation-contraction coupling to increase muscle contractile function (for review, see [154]). Caffeine can cause a number of side effects, however, including GI distress, headaches, and anxiety [155]. Caffeine strategies should, therefore, be carefully planned and practiced in advance of competition. It should be noted that while there is some evidence that reducing habitual intake prior to competition might enhance caffeine sensitivity on race day [156], the hypothesis has been contested [157].

Caffeine has been shown to positively impact endurance performance [158], but there is a paucity of data on the use of caffeine during ultra-marathon. One of the only studies to assess the caffeine habits of ultra-marathon runners found that elite athletes contesting a 100-mile (161 km) single-stage race reported total intakes of ~ 912 ± 322 mg, spread over 15–19 h of running [96]. It is the stimulant properties that are likely to be most important for runners, particularly in races of > 24 h when sleep deprivation will affect performance and athlete safety. However, the dose response is not linear (i.e., larger caffeine doses do not necessarily confer greater performance), and moderate rates of ingestion are likely sufficient to optimize ergogenic gains [159]. A conservative strategy may also mitigate the likelihood of side-effects. While single boluses of ~ 4–6 mg·kg− 1 (280–420 mg for a 70 kg athlete) are common in short-duration activities, frequent dosing of this magnitude is not recommended. If frequent doses are to be taken during ultra-marathon, then lower (more sustainable) amounts (e.g., 1–2 mg·kg− 1; 70–140 mg for a 70 kg athlete) are more appropriate and safer over several hours. Importantly, caffeine has been shown to be effective when taken in the latter stages of endurance exercise [160]; accordingly, ultra-marathon runners are encouraged to target any caffeine intake for the latter stages of competition. Although there are no specific guidelines pertaining to caffeine intake during prolonged ultra-marathon, repeat doses of 50 mg·h− 1 are likely to be well-tolerated, principally reserved for night-running when circadian rhythms are likely to be affected. Individual sensitivity should, of course, be carefully considered, and strategies well-rehearsed. Finally, given the ergolytic and/or dangerous effects of caffeine overconsumption, athletes are advised to double-check their doses, ensure their intakes are congruent with the empirical data and safety guidelines, and give special consideration to the method of delivery (fluid vs. tablets vs. gum).

Medium-chain triglycerides (MCTs) and ketone esters

Although enhanced fat oxidation may be facilitated by nutritional ketosis (evoked via caloric restriction, carbohydrate restriction, or chronic high-fat diets), current evidence does not indicate an ergogenic effect when compared to diets that have a moderate-to-high CHO content. For example, exogenous fatty-acid supplementation (e.g., MCTs) has been proposed as a strategy to enhance aerobic metabolism through the rapid absorption and utilization of fatty acids (or converted ketone bodies). Animal models indicate a potential mechanistic benefit for the inclusion of MCTs to enhance mitochondrial biogenesis through both Akt and AMPK signalling, thereby enhancing endurance performance [161]. Nevertheless, controlled studies show limited impact of MCTs on fuel utilization during exercise when human subjects are in a low-glycogen or a glycogen-replenished state [162]. A further consideration is that, in order to mitigate the likelihood of GI distress during exercise, MCT oil should only be taken in relatively small amounts (i.e., < 30 g), and such low doses may have a negligible influence on fuel utilization [102] and endurance performance [163]. Nevertheless, there are anecdotal reports of MCT use by ultra-marathon runners, during both training and racing, which warrant further study.

More recently, novel ketone esters have been shown to optimize fuel utilization without the need of evoking ketosis via carbohydrate and/or caloric restriction. Within 60 min of ingestion, a 500 mg·kg− 1 ketone ester increased beta-hydroxybutyrate (D-βHB) concentrations to levels associated with nutritional ketosis (~ 3 mmol·L− 1), and increased intramuscular fat oxidation even in the presence of replete glycogen stores or when co-ingested with CHO [50, 164]. Moreover, such metabolic flexibility resulted in a significant (2%) increase in endurance performance [50], although this was during exercise lasting < 120 min. Performance benefits have, however, been repeatedly refuted [165, 166]; as such, despite the compelling mechanistic basis for ketone esters to facilitate ultra-marathon performance, there is currently no direct evidence to this effect, and further research is needed.

Vitamins and minerals

In general, studies have found no benefit of chronic vitamin and/or mineral supplementation on exercise performance [167, 168]. However, in a report on the supplement habits of 20 ultra-marathon runners, 30% of respondents reported taking multivitamins, and 20% reported taking vitamin C before races [169], although consumption rates as high as ~ 70% have been reported in small cohorts [170]. To date, only one study has assessed the effect of vitamin/mineral supplementation on ultra-marathon performance, finding that daily ingestion of multivitamins and minerals for ~ 4 weeks before competition did not result in statistically significant differences in performance time between supplement users and non-users (The Deutschlandlauf Marathon, Germany) [169]. Accordingly, there is insufficient evidence that multivitamin and/or mineral supplementation is beneficial for ultra-marathon, except in the instance of a clinically-determined, pre-existing nutrient deficiency or dietary insufficiency. Athletes should ensure that normal dietary intake is sufficient to provide an appropriate variety and quantity of micronutrients.

Given the substantial oxidative stress associated with ultra-marathon competition, isolated vitamin C has been hypothesized as a means of attenuating the high prevalence of post-race immunosuppression, although the data are conflicting. For example, a relatively high dose of vitamin C (1500 mg·d− 1) for 7 days prior to a 50 mile (80 km) single-stage race (The Umstead race; NC, USA) failed to induce any group differences in oxidative or immune responses, including lipid hyrdroperoxide and plasma interleukin (IL)-6 [171]. By contrast, a randomized, placebo-controlled trial by Peters et al. [172] reported a significantly lower prevalence of upper-respiratory-tract infection (URTI) in finishers of a 56-mile (90 km) single-stage race following daily ingestion of 600 mg of vitamin C, for 14 days post-race. Moreover, in a 31-mile (50 km) race, Mastaloudis, et al. [173] observed a significant protective effect against lipid peroxidation in runners who had been supplemented with antioxidants (α-tocopherol at 300 mg·d− 1, and ascorbic acid 1000 mg·d− 1) for 7 weeks prior. Accordingly, acute supplementation in the immediate pre- or post-race period may mitigate oxidative damage and immunosuppression that precedes URTI, although further research is needed to corroborate these findings and establish the effects of acute, in-task supplementation. Chronic, daily supplementation with antioxidants is not recommended due to the potential blunting effect on several aspects of exercise-induced physiological adaptation (for review, see [174]).

L-glutamine

L-glutamine is the most abundant amino acid in the body, with an essential role in lymphocyte proliferation and cytokine production [175]. In catabolic and hypercatabolic situations, L-glutamine can be essential to help maintain normal metabolic function and is, therefore, included in clinical nutritional supplementation protocols and recommended for immune-suppressed individuals [175]. Nevertheless, in terms of mitigating immunodepression after exercise, the available evidence is not sufficiently strong for L-glutamine supplements to be recommended for athletes (for review, see [176]). By contrast, there is emerging research that, in addition to probiotic use, L-glutamine may provide adjunct nutritional support for GI epithelial integrity [177]. In a recent study under controlled conditions, GI permeability (assessed via serum lactulose:rhamanose; L:R) was attenuated following demanding exercise performed at 30 °C when participants consumed a pre-exercise beverage containing 0.25 g·kg− 1 fat-free mass of L-glutamine compared with placebo. Furthermore, the authors highlighted a potential dose response, with higher concentrations (0.9 g·kg− 1 fat-free mass) further attenuating the L:R ratio. It has been proposed elsewhere that L-glutamine supplementation may be associated with heat-shock factor-1 (HSF-1) expression, providing a mechanistic link to GI integrity via regulation of occludin tight-junction proteins [178]. Further research is warranted with respect to L-glutamine supplementation in the context of ultra-marathon.

Analgesics and anti-inflammatories

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.

Non-NSAID analgesics (e.g., paracetamol) are not prohibited by The World Anti-Doping Agency (WADA), principally because they are not considered performance enhancing, per se, but rather performance enabling. This group of analgesics appears to be better tolerated than NSAIDs during competition; nevertheless, concealing symptoms of pain might facilitate and/or exacerbate injury, and the importance of afferent pain signals to indicate potential tissue damage cannot be underestimated. Caution is urged, therefore, against the frivolous and systematic use of analgesics for symptom-masking.

Finally, there is evidence that up to 15% of legal supplements are inadvertently or deliberately contaminated with illegal drugs, which remain in the system for several hours following consumption, and that would result in a positive test for banned substances [196, 197]. Accordingly, there is a growing need for greater batch-testing of supplements, and special consideration should be given when athletes are entering races that are overseen by anti-doping organizations. This will be critical in minimizing the risk of inadvertent positive tests.

Evidence statement (category A)

Caffeine is a potent stimulant that may be beneficial during racing, particularly in the latter stages of longer events (> 24 h), when sleep deprivation might attenuate performance and jeopardize athlete safety on technical terrain.

Evidence statement (category B/C/D)

Despite the potential efficacy of other ergogenic aids (e.g., ketone esters, MCTs, vitamins, etc.), there are limited data to support their use, and further research is warranted.

Evidence statement (category B/C)

Runners should abstain from NSAIDs (e.g., Ibuprofen, aspirin), due to multiple contraindications including increased renal loads that are already exacerbated during ultra-marathons. Analgesics may provide effective pain-relief, but conservative use is advised in order to avoid the inadvertent masking of serious symptoms.