Nutrition and Altitude: Strategies to Enhance Adaptation, Improve Performance and Maintain Health: A Narrative Review

While the effects of high-altitude exposure on endocrine systems, EI, resting metabolic rate (RMR) and ultimately BM are consistent and severe, the handful of research findings at low–moderate altitudes are much less consistent and appear to be far less pronounced. Indeed, emerging case-study data include loss of appetite reported by four rowers who reported increased fatigue during a 12-day intense training block at 1800 m [38]. Conversely, data from five elite runners reported an increased appetite, with no change in EI, after 4 weeks of living and training at 2200 m [39]. However, it is important to point out that the rowers increased their training load at altitude by 113% [38], while the runners only increased their training load 37% [39], compared to sea-level training loads. Furthermore, both negative [40, 41] as well as optimal energy balance (EB) [42] have been reported in both elite Kenyan and Ethiopian runners at moderate altitudes. Meanwhile, when 48 elite female and male distance athletes maintained moderate EA (33–36 kcal/kg FFM/day, assessed over a 1-week period) across 3–4 weeks of training at 2150 m, BM remained stable [32, 37]. However, it should be noted that dietary records [43] are poor estimates of EA when used in isolation (Table 1), and the variability of these BM and EA outcomes demonstrate that more research is required.

With respect to RMR, to our knowledge, only two studies have investigated the effects of moderate altitude on this variable in elite athletes. The first study observed five elite runners for 4 weeks at 2200 m, reporting an increased RMR, by 19% [39]. In comparison, the second study followed four elite rowers, who reported no change in RMR after 12 days at 1800 m [38]. Collectively, this work presents the notion that when EA is adequate (as indicated via no change in BM in the study by Woods et al. [39]), it appears that RMR is increased at moderate altitudes similarly, albeit to a smaller extent, to high/extreme altitudes. However, given the small participant populations used here, more research is required to confirm these findings that RMR is increased at low–moderate altitudes (Table 1).

In terms of changes in BM during altitude training camps (~ 3 weeks), studies report no change [32, 39, 40, 42, 44] or minor BM decreases [38, 41, 45] when exposed to moderate altitudes. The decreases in BM may reflect low EA and have been associated with negative EB [41] and stable RMR [38]. Meanwhile, when BM was maintained (suggesting optimal EA), stable hormone concentrations [32] and increased RMR [39] were noted across an altitude camp. The importance of maintaining BM via optimal EA is highlighted by studies showing that a failure to do so may negatively influence hematological adaptations to altitude. For example, McLean et al. [33] reported that football players who lost ≥ 2 kg BM during training at 2100 m only increased HBmass by 2.5% as compared to 5.0% in those who maintained BM. Furthermore, elite male cyclists significantly lost BM (− 1.2 kg) and FFM (− 1.0 kg) while failing to increase HBmass over a 31-day altitude camp, likely due to overtraining and/or illness [45]. Conversely, unpublished observations from four separate altitude training camps (of ~ 3–4 weeks duration, from 2015 to 2018) with the same HBmass procedure/laboratory (Hypo2, Flagstaff, AZ, USA), featuring 114 observations, demonstrated a − 0.6 ± 1.5% BM decrease and a 5.6 ± 4.1% increase in HBmass, with no relationship between changes in HBmass and BM reported, and no relationship with illness (Fig. 2). However, changes in BM alone are a poor indicator of EA status, as prolonged and/or severe reductions in EI may lead to adaptive thermogenesis, which promotes maintenance or gain of BM despite low EA [46]. It is also important to note that upon arrival to altitude there is a contraction of plasma volume (PV) [47, 48] and typical altitude associated dehydration. Accordingly, acute small weight loss (i.e., < 2% BM) should not be confused with an actual reduced EA, as BM alone is a poor indicator of EA. Indeed, loss of body water due to increased ventilation and diuresis is an essential short-term adaptation to altitude which serves to increase arterial oxygen content via increased hemoglobin concentration prior to longer-term erythropoietic adaptation [49]. Residual BM loss associated with PV contraction is typically reversed upon return to sea level [31]. Overall, the impact that training at moderate altitudes has on BM, EA, and subsequent endocrine and metabolic (e.g., RMR) effects warrants further investigation (Table 1).

There are several factors that impact an athlete’s HBmass response at altitude, including the hypoxic dose (~ + 1% increase per 100 h at ~ 2000 m [34, 51]) and baseline HBmass [32, 52]. Beyond this, the nutrition intervention receiving the most scientific attention with regards to optimizing adaptations to moderate altitudes is the mineral iron. In 1992, investigators such as Benjamin Levine, James Stray-Gunderson and colleagues were amongst the first to highlight that pre-existing iron deficiency (serum ferritin of 15 ± 3 vs. 69 ± 10 μg/l) without iron supplementation at 2500 m of altitude compromised the red blood cell adaptive response to altitude training [53]. Accordingly, pre-altitude ferritin cut-offs of < 30 ng/ml and < 40 ng/ml have often been used as a pre-altitude “check” to ensure optimal adaptations and/or whether to supplement iron in females and males, respectively [11]. However, these pre-altitude ferritin cut-offs, in combination with iron supplementation, have not been scientifically validated (Table 1), although they have been utilized in a recent altitude study that showed expected HBmass increase after 3 weeks at moderate altitude (+ 4.7% [44]). Furthermore, anecdotally, athletes who have low pre-altitude ferritin (> 15 but < 30 ng/ml) with normal pre-altitude hemoglobin, but who are supplemented with iron throughout an altitude camp, appear to still exhibit optimal HBmass adaptations. Indeed, several studies have shown no relationship between pre-altitude ferritin stores and the magnitude of the HBmass response [44, 54, 55]. To add to this, re-analysis of data from 49 elite athletes training at 2100 m while consuming ~ 100–200 mg of elemental iron daily also supports no relationship between pre-altitude ferritin and subsequent HBmass responses, as long as athletes supplement with iron throughout the altitude camp (Pearson correlation between baseline ferritin and percentage change in HBmass = − 0.1296, p = 0.38 [32]).

Current recommendations are to assess iron status 8–10 weeks prior to altitude training [11] and to commence oral supplementation 2–3 weeks prior to altitude exposure, and to continue this supplementation throughout (Fig. 3 [55‐57]). However, iron stores can change appreciably in 8–10 weeks [58, 59], and our current recommendation is to aim for pre-altitude blood work ~ 4–6 weeks prior to allow for more precise pre-altitude ferritin assessment, yet time to still supplement and correct prior to altitude if required (Fig. 3). Regarding the optimal iron dose at low–moderate altitudes, retrospective analysis of hematological data collected from athletes (n = 178) engaged in altitude training at moderate altitudes (1350–3000 m) demonstrated greater HBmass increases in iron-supplemented athletes versus those who were not supplemented [60]. In this study, athletes who did not supplement with iron had HBmass increases of only 1.2%, while athletes who supplemented with 105 mg or 210 mg had HBmass increases of 3.3% and 4.0%, respectively. Our altitude iron recommendations established on ferritin cut-offs of < 100, ~ 100–130 and > 130 ng/ml (Fig. 3) are based on interpolation and/or extrapolation of existing data [56, 57, 60]. Accordingly, a blunted erythropoietic response was also observed in non–iron-supplemented athletes during simulated live-high train-low (LHTL) despite being iron replete [55]. Furthermore, altitude studies that have supplemented ~ 200 mg of elemental iron per day have only shown modest increases in pre- to post-ferritin levels (~ 5–30% [57, 60]), indicating the increased iron utilization at altitude and the low risk for iron overload. Nevertheless, these ferritin cut-offs require further scientific validation, as no definitive iron dose–response study at low–moderate altitudes in athletes currently exists.

Taken together, current evidence suggests that most athletes will maximize the hypoxia-induced increases in HBmass while consuming ~ 100–200 mg of elemental iron daily in oral form, with most evidence relating to iron salts. Recent advances in intravenous (IV) iron formulations have radically changed the accessibility and safety associated with IV iron delivery [61], raising questions surrounding its suitability and efficacy as a supplementation option during altitude exposure. However, IV iron did not further augment the HBmass response to 3 weeks of simulated altitude training compared with standard oral supplementation practices (105 or 210 mg of elemental iron/daily) in non-anemic, trained endurance athletes [55]. Thus, it would appear that oral iron supplementation remains the most appropriate option for iron-replete individuals, which better aligns with the “no needle” policies of many sporting organizations’ governance processes.

The regulation of the peptide hormone hepcidin needs to be considered when looking to maximize iron bioavailability in hypoxia. Hepcidin is often referred to as the “master iron regulator,” as increased hepcidin causes a decrease in iron absorption and iron recycling within the body [62]. Hepcidin is suppressed in hypoxic conditions [57, 63], but is upregulated when high amounts of iron are present in the circulation and subsequent to exercise training [64], which, in turn, reduces iron availability since both dietary iron uptake from the gut and expression of iron on macrophages are impaired [65]. Accordingly, a number of iron dosing protocols are possible, such as single or split daily doses, or dosing every other day [66, 67]. Interestingly, at sea level, multiple daily doses of iron caused an increase in hepcidin, and a decrease in the percent of iron absorbed from subsequent iron doses in iron deficient females [66], suggesting single dosing protocols may be superior. However, despite elevated hepcidin and decreased bioavailability (% relative absorbed) with two doses per day [66], or daily iron dosing compared to alternate days [67], the total iron absorbed remains greater with a higher frequency of supplementation [notwithstanding any individual gastro-intestinal (GI) issues with greater individual doses].

Further support for a single daily iron dosing protocol comes from a recent applied study in elite runners over a training camp at 2100 m [57]. This study compared a split (100 mg elemental iron at 7–8 AM plus 100 mg between 9 and 10 PM) versus a single (200 mg elemental iron at 9–10 PM) equivalent dose of ferrous fumarate daily for ~ 3 weeks. While both supplemented groups experienced a significant increase in HBmass post altitude, the single-dose group had a significantly greater increase (6.7 ± 6.3%; p = 0.048) compared to the split-dose group (4.6 ± 3.9%). The trade-off may be greater reports of GI concerns with the single dose, as there was a 37% increase in the overall GI distress score associated with the single versus split dose over the first 2 weeks. However, this difference was not apparent by week 3, suggesting gut adaptation can occur to the greater single dose [57]. Also, there may be different GI tolerance to different types of oral iron supplements [68], which also may be individually trialed. Of note, the efficacy of an alternate-day iron supplementation protocol is yet to be explored in athletes at altitude, but offers a promising possible avenue for further research (Table 1).

In conclusion, since no correlation has been observed between pre-altitude ferritin stores and the magnitude of the erythropoietic/HBmass response [32, 54, 55], it appears that iron availability via supplementation during altitude is more important for optimal adaptations than pre-altitude iron stores [56, 57]. Nevertheless, optimizing iron bioavailability, via optimal iron dose timing, requires an appreciation of the temporal effects of hepcidin that are influenced by baseline ferritin [64], timing of multiple daily iron doses [66, 67], timing, duration and intensity of training [64], and diurnal effects [69]. Figure 3 highlights our current knowledge and recommendations regarding blood health screening and supplemental iron recommendations before, during and after altitude, including highlighting factors that will increase or decrease oral iron bioavailability. We recommend the involvement of a sports medicine physician in this process, as excess iron supplementation and clinically elevated endogenous iron stores can have negative health consequences [70, 71].

Exercise at moderate altitudes is associated with increased production of RONS with reduced antioxidant capacity, leading to oxidative stress [72, 73]. The excessive overproduction of RONS, in excess of the endogenous antioxidant defense systems, can cause damage to lipids, proteins and DNA which may impair cell and immune function, resulting in delayed post-exercise recovery [74]. Both acute [75, 76] and chronic exposure to hypoxia [72, 77, 78] augments oxidative stress in well-trained athletes, while reduced antioxidant capacity may persist for up to 2 weeks following altitude training [79]. Interestingly, normobaric hypoxia appears to produce a larger increase in oxidative stress than hypobaric hypoxia [80], while a recent study in a team sport setting showed no impact of intermittent hypoxia on biomarkers of oxidative stress [81]. Although several factors can modulate the oxidative stress response to altitude (e.g., the intensity and type of training [82]), it can be generalized that a greater level of hypoxic stimulus results in greater oxidative stress (Fig. 1 [83, 84]). The clinical implications of altitude-induced oxidative stress are not entirely clear [85, 86], beyond being linked to acute mountain sickness (AMS) at high altitudes [87, 88]. At moderate altitudes, some studies have shown increased inflammation and illness in association with higher levels of oxidative stress [89, 90], but others have not [81]. It is important to note that, although there is some evidence of immunological biomarker disturbances at low–moderate altitudes in elite athletes [91, 92] and anecdotally there is an assumption of increased rate of illness at altitude, there is actually limited evidence of an increased rate of illness at low–moderate altitudes. In fact, a recent athlete and immune function review by Walsh et al. [93] highlights that there is no evidence that exercising in extreme environments poses any additional immune threat, and some recent evidence suggests that immune health may actually be enhanced by regular intermittent environmental stressors.

Given that exogenous antioxidants neutralize free radicals, it is logical to hypothesize that antioxidant supplementation would be a worthy intervention to combat altitude-induced oxidative stress and its potentially associated perils. Although early investigations have shown that antioxidant supplements had modulating effects on oxidative stress and AMS symptoms at high altitudes [94, 95], more recent studies indicate no effect [96‐98] or mixed results [99]. Importantly, the majority of the studies have been conducted in military training settings and/or at altitudes > 4000 m, and thus, do not reflect the contemporary altitude training regimes of athletes. Furthermore, none of these studies have assessed the impact of antioxidant supplementation on training adaptation. With the current understanding of the essential role of RONS in initiating the positive adaptive response to endurance training [100], hypoxia [101] and upregulation of the endogenous antioxidant defenses [102], dampening RONS with antioxidants might actually be counterproductive and reduce the adaptive responses to altitude training (Table 1), which has been shown at sea level [103‐105]. Two recent studies have examined the effect of antioxidants from food sources on the adaptive response to altitude training [44], and oxidative stress and inflammation [106]. The first study [44] revealed that more than doubling the daily intake of antioxidant-rich foods during a 3-week altitude camp (2320 m) did not interfere with the training responses in elite endurance athletes [measured as HBmass and maximum rate of oxygen consumption (VO_2max)]. While the follow-up study showed that the food-based antioxidant intervention elevated plasma antioxidant capacity and attenuated some of the altitude-induced increases in systemic inflammatory biomarkers, it had no impact on altitude-induced oxidative stress in the elite athlete population [106].

Collectively, there is not sufficient evidence to recommend high-dose single antioxidant supplementation to attenuate altitude-induced oxidative stress, especially at low–moderate altitudes. Furthermore, the impact of antioxidant supplements on the adaptive training response to altitude requires further research (Table 1). At present, integrating ample amounts of antioxidant-rich foods into athletes’ daily dietary regimes while training at altitude seems the most reasonable advice, including a vitamin C source (e.g., orange juice, low-dose vitamin C supplement) with the athletes’ iron supplement to optimize bioavailability (Fig. 3).

Nitric oxide (NO) is a pleiotropic signaling molecule and a regulator of many physiological and adaptive processes that are endogenously stimulated by hypoxia. Therefore, dietary nitrate (NO₃; an NO precursor) supplementation, usually in the form of concentrated beetroot consumption, during hypoxia has garnered much recent attention [108, 109]. Accordingly, one might hypothesize even greater effects of NO₃⁻ supplementation at altitude. Similar to the data found in normoxia, there are several studies confirming enhanced exercise economy (reduced steady-state VO₂), by ~ 5–10%, in hypoxia and/or enhanced performance outcomes in recreationally active subjects after NO₃⁻ supplementation [110‐112]. However, also similar to the normoxic literature, four recent hypoxia-based studies have failed to show these outcomes in elite endurance trained subjects (VO_2max > 60 ml/kg/min); although some individuals appeared to benefit [113‐117], this is not always the case [118]. Therefore, similar to the normoxic data, the majority of studies in elite endurance-trained subjects show no further benefits of NO₃⁻ supplementation in hypoxia.

Perhaps not surprisingly, given that NO₃⁻ supplementation increases O₂ delivery, in both recreational [111, 112] and elite [116] subjects, NO₃⁻ supplementation has resulted in a small 1–4% increase in arterial O₂ saturation (S_aO₂) via pulse oximetry during hypoxic exercise (thus less desaturation). However, given the links between decreases in S_aO₂ and EPO release [119] and HIF-1-alpha responses, one might question whether chronic NO₃⁻ supplementation while training at altitude might actually attenuate some of the hypoxia-induced adaptations. Indeed, several studies have shown no performance enhancing or training adaptation effect of chronic NO₃⁻ supplementation during hypoxic training over 5–6 weeks [120, 121], suggesting that chronic NO₃⁻ intake might attenuate training adaptations by decreasing the drop in arterial (S_aO₂) and muscle O₂ saturations—factors that serve as “signals” for hypoxic adaptations [120]. Taken together, given the lack of consistent data and/or several studies suggesting contraindications [120, 122], we cannot conclusively recommend NO₃⁻ supplementation during altitude training in elite athletes unless individual outcomes have been quantified.

During progressively intense exercise, the drop in muscular pH via hydrogen ion (H⁺) production, which is exacerbated by hypoxia at the same absolute workloads, has been shown to negatively affect metabolic processes, such as the inhibition of glycolysis and muscle contraction processes, ultimately resulting in fatigue and decreased performance [123]. Therefore, the enhancement of both intra- (inside) and extra-muscular (outside) buffering of H⁺ should lead to an increase in performance where metabolic acidosis is a limiting factor. Accordingly, humans have evolved to have many varying endogenous mechanisms contributing to total buffering capacity, which are innately enhanced upon ascent to altitude [6] and potentially increased by several nutrition-based ergogenic aids. These ergogenic aids with significant sea-level evidence [107] include (1) β-alanine (BA) supplementation leading to intra-cellular muscle carnosine synthesis (3–6 g BA/daily for 6–8 weeks) and (2) sodium bicarbonate (NaHCO₃) or citrate supplementation leading to extra-cellular increases in bicarbonate (HCO₃⁻) [acutely, ~ 300 mg NaHCO₃/kg BM taken 1–2 h prior to competition]. It is beyond the scope of this review to unravel the complexities of anaerobic performance determinants and associated potential ergogenic aids (for recent reviews, see Peeling et al. [107] and Stellingwerff et al. [124, 125], as well as the extensive literature on acid–base regulation during exercise [123] and/or during hypoxia [126]). Instead, this section will briefly overview the buffering changes upon ascent to altitude and then examine the scant data on whether exogenous buffering supplements should be considered at altitude (Fig. 1).

Upon immediate ascent to altitude, there is a very rapid hyperventilatory response to hypoxia to raise PO₂, which leads to respiratory alkalosis, resulting in decreased H⁺, increased pH and increased renal HCO₃⁻ excretion, resulting in decreased blood HCO₃⁻; for reviews see Gore et al. [6] and Cerretelli and Samaja [126]. Subsequent to this immediate response, chronic altitude (days to weeks) actually increases intra- and extra-cellular buffering capacity [127‐129]. Indeed, hypoxia-induced changes in blood pH can occur in elite 400-m runners in just several days [130]. In fact, enhancement of critical buffering transporters in blood erythrocytes (via increased monocarboxylate and bicarbonate (Cl⁻/HCO₃⁻) transporters [127]) and a 5–6% increase in muscle buffering [128, 129] have both been shown in just 2 weeks of hypoxia. Therefore, given the drop in blood HCO₃⁻, one might hypothesize that exogenous NaHCO₃ or citrate supplementation may actually be more advantageous for performance in hypoxia. However, in the handful of studies that have used NaHCO₃ or citrate in hypoxic conditions, six studies have shown no ergogenic effect [131‐136], while one study has shown an increase in the anaerobic (W′) component, which would be suggestive of a performance enhancement, at simulated altitude (14.5% O₂; ~ 2800 m [137]). Regardless, it is difficult to compare any of these studies, because of different levels of hypoxia, performance protocols and states of hypoxic adaptation, as well as several of the studies being potentially under-powered to detect a performance difference (n ≤ 7 [131, 134, 135]). Obviously, much more research is required to better understand the limiting effects of performance in hypoxia, the time course and impact of these extracellular buffering changes in elite athletes at low–moderate altitudes, as well as the mechanism(s) responsible for the subsequent enhanced muscle buffering capacity (Table 1).

The chronic utilization of nutritional buffers to potentially enhance training adaptations is not well understood. For example, there are only a few studies examining the chronic effect of NaHCO₃ supplementation (5–7 days) in normoxia, all of which have initially demonstrated promising outcomes [138‐141]. However, some individuals will suffer from GI upset and/or increased fluid retention and BM increases (+ 1–3% BM) due to the high sodium ingestion [142, 143] following NaHCO₃⁻ supplementation, potentially negating the performance outcomes [144‐146]. All of these negative side effects may be exacerbated with prolonged chronic NaHCO₃⁻ protocols. Additionally, two studies have examined whether augmented carnosine via BA supplementation may lead to an enhanced training effect, with one study showing a trend for greater resistance-training volume [147] and another finding no influence of BA to further enhance high-intensity interval training [148]. We are unaware of any prolonged chronic NaHCO₃ supplementation studies conducted at altitude/hypoxia. Conversely, we are only aware of a single study examining the acute effects of NaHCO₃ supplementation both prior to and after 5 weeks of BA supplementation. All of these trials were conducted in simulated hypoxia (15.5% O₂ = ~ 2400 m), in which neither BA nor NaHCO₃ caused any performance benefits [149]. Obviously, our global understanding of the adaptive effects of buffers is not well understood at either sea level or altitude (Table 1).

Taken together, current evidence would not support the use of exogenous NaHCO₃ or citrate supplementation to augment acute hypoxic performance. Furthermore, given the remaining questions around the innate magnitude and timing of acid–base/buffering changes in elite athletes at low–moderate altitudes, let alone the potential adaptive impact of chronic exogenous buffers, we also cannot conclusively recommend the chronic use of NaHCO₃ or citrate supplementation. However, due to BA’s long supplementation period (~ 6–8 weeks) to augment muscle carnosine, one might consider its utilization if the timing were critical for post-altitude competitions, with no current anecdotal evidence to report any apparent negative side effects (unpublished observations).

Limited evidence exists for alternative nutritional supplements that have extensive data as potential ergogenic aids for enhancing adaptation to altitude. For example, we are unaware of any intervention studies investigating the impact of vitamins B₆, B₁₂ and D or glutamine or branched chain amino acids in athletes at low–moderate altitudes. Therefore, whether a higher intake of these vitamins and proteins (in the form of supplements) would have additional benefits has not been investigated and again highlights areas for future research. However, when looking beyond the aforementioned prospects of nitrate and buffers, the thiol-containing compound N-acetylcysteine (NAC) seems to show mechanistic promise. Previous work has shown that NAC increases circulating free cysteine levels, which, in the presence of increased glutathione demand, can support glutathione synthesis and prevent its depletion [150]. Interactions between NAC, cysteine and glutathione are suggested to act in potentially numerous mechanistic ways that may be beneficial for athlete performance, recovery and adaptation. For instance, NAC ingestion is proposed to result in an anti-oxidant effect that minimizes the oxidative stress and inflammatory response imposed from physical activity [151] (see Sect. 4.2). Furthermore, NAC is proposed to enhance fatigue resistance [152] and improve athletic performance [151]; to enhance immune system function [153], hemodynamics and muscle blood flow [154]; and to modulate EPO production and the hypoxic ventilatory response [155]. Intuitively, each of these mechanisms appears likely to support a positive adaptation to hypoxic environments such as altitude exposure. However, scant literature exists to explore such a prospect in applied athlete settings where an altitude sojourn has occurred. Regardless, the previous literature showing a positive impact of NAC supplementation on these relevant physiological outcomes has generally provided the thiol compound in oral dosages ranging from 600–1200 mg/day for a 5- to 9-day period [151, 154, 155]. However, it should be noted that not all literature supports the positive modulation of NAC on EPO production [156], and when consumed in high doses for prolonged periods of time (i.e., 1200 mg/day for 4 weeks, followed by 2400 mg/day for a further 2 weeks), pro-oxidant, rather than anti-oxidant, effects have been reported [157], which may actually serve to attenuate aerobic adaptations (see Sect. 4.2). With this in mind, further research is clearly required before NAC can be recommended as a useful supplement for use prior to and/or throughout altitude exposure in athletes, with factors such as dose, duration of consumption and the resultant potential for mechanistic promise to convert to enhanced adaptation all needing further clarification.

Any indirect benefits of a supplement that might support an athlete’s immune function are of key interest, since it is well-documented that unaccustomed altitude exposure places an additional burden on the immune system [158]. Maintaining an athlete’s immune function and/or reducing the impact of any altitude-induced illness while under such environmental stress may lead to enhanced overall adaptations. With this in mind, there appears to be potential for the use of the herb extract G. biloba (GBE), with proposed mechanisms such as reducing tissue hypoxia, increasing vasodilation and, via its anti-oxidant properties, possibly reducing the incidence of a mild AMS [159], characterized by headache, lightheadedness, fatigue, nausea, and insomnia [160]. Such effects can negatively impact on an athlete’s ability to train, and therefore, their overall adaptation to an altitude exposure may be compromised [161]. Although a promising prospect, recent meta-analyses of GBE shows equivocal outcomes of its impact on AMS prevention (only 57% of included studies showed a positive outcome [159]). Investigations exploring the potential prophylactic nature of GBE have used daily split doses of 80–120 mg, consumed over a 3- to 5-day period both before and/or during the altitude sojourn [160, 162]; however, it should be considered that the majority of these studies have focused on trekkers at high to extreme altitudes, rather than athlete populations at low–moderate altitudes. Therefore, similar to NAC supplementation, more research is needed before confident recommendations on GBE supplementation for reductions in altitude-induced illness and/or AMS symptoms can be made.