Altitude training (AT) has been employed by well-trained athletes for almost 60 years since the 1968 Mexico Olympics (Buskirk et al., 1967; Wilber, 2007; Girard et al., 2023). Currently, this method has led to the development of several matured variants following the conventional “live-high train-high” approach (HH), i.e., living and training at low or moderate altitudes throughout the day (Buskirk et al., 1967). In contrast to the HH approach, the training site for “live-high train-low” (HL) is set at sea level or low altitudes (Levine and Stray-Gundersen, 1997; Bonetti and Hopkins, 2009). Besides, given the type of hypoxia in residential environments, HL can be simulated and natural (Coppel et al., 2015; Girard et al., 2023). However, considering the time involved in HH and HL training, IHE has induced wide attention over the past few years for its shorter but more intense hypoxia protocols during rest (Millet et al., 2010; Wilber, 2007). Training under short-term hypoxia is defined as an LLTH practice, which includes varying forms (e.g., intermittent hypoxic training [IHT]) (McLean et al., 2014). Live-high and train-high/low (HHL) has been reported as a novel hypoxic combination that is implemented during the application of HL, where athletes train under normoxic and hypoxic conditions (Millet et al., 2010).

Although AT has been extensively applied and is trusted by coaches and athletes (Daniels and Oldridge, 1970; Solli et al., 2017), its effectiveness on aerobic performance remains unclear (Millet and Brocherie, 2020; Siebenmann and Dempsey, 2020). In general, the ambiguity originates from two aspects: 1) Potential negative effects of chronic hypoxia exposure (various types of acute altitude sickness) (Imray et al., 2010; Schommer et al., 2012), which outweighs potential benefits and 2) unreasonable hypoxic doses (Wilber et al., 2007). Given the high cost of AT, its effectiveness should be determined, and a reasonable dosage range should be set. Although existing meta-analyses and dose-effect research have partially addressed the above-mentioned issues, most may contain flaws and controversies.

1. The above-described studies were inconclusive since there rarely was direct evidence on the comparison of different types of AT and since they failed to report a clear hierarchy (Bonetti and Hopkins, 2009; Hamlin et al., 2018; Lobigs et al., 2018)

Accordingly, to fill the gap in comparing the effect of a wide variety of AT variants on athletes’ aerobic performance and explore reasonable hypoxic dose ranges, a network meta-analysis was conducted in this study. We aimed to compare and rank different hypoxic types for the improvement of VO₂max in athletes. Subsequently, a novel technique (Bayesian model-based dose-response network meta-analysis) was adopted to examine the dose-response correlation between hypoxic doses and VO₂max in athletes.

This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Network Meta-Analyses (PRISMA-NMA) guidelines (Shamseer et al., 2015). Moreover, this study is registered with PROSPERO (registration number: CRD42023401488).

In this study, the effect of varying hypoxic methods on athlete’s VO₂max was comprehensively compared and ranked, and the reasonable hypoxic doses range for the respective form was explored. In general, the results showed that HL, HH, and IHT, not IHE and HHL, significantly outperformed normoxic training in enhancing VO₂max. HL with low altitude training was the optimal effective method (natural HL slightly better than simulated HL), whereas the effects of IHT reached the minimum. Besides, as indicated by the result, the hypoxic dosage of HL, HH, and IHT displayed a U-shaped relationship with a change in VO₂max. The effective dosage for HH ranged from 470 kmh to 1,130 kmh. For HL, the effective dosage was from 500 kmh to 1,415 kmh. Furthermore, for IHT, the significant effect disappeared when the dosage exceeded 42.5 kmh.

In this study, the efficacy of HL in enhancing aerobic performance at sea level was confirmed (Fulco et al., 2000; Bonetti and Hopkins, 2009), and the reasonable range of hypoxic dosages was determined [a U-shaped relationship was found between the change in VO₂max and hypoxic dosages (500–1,415 kmh)]. Despite variations in selected indicators, the effective hypoxic dosage in previous studies aligns closely with the reasonable range explored in this study (Rusko et al., 2004; Wilber, 2007; Gore et al., 2013). The U-shaped curve and upper limit of the reasonable dosage are novel findings that may arise from the adverse effects exerted by prolonged chronic hypoxia such as disrupted sleep quality (Kinsman et al., 2005; Sargent et al., 2013), oxidative disorders or pulmonary edema (Gaur et al., 2021; Rytz et al., 2022), accumulated fatigue (Bergeron et al., 2012; Koehle et al., 2014), etc.

Moreover, the effect of training site altitude and type of hypoxic residential environment on the efficacy of HL was investigated. The results showed that the altitude of the training location is the primary determinant of the efficacy of HL, whereas the type of hypoxia in a residential environment has little impact on the outcomes. Extensive research has suggested that the discernible variations in effective HL camps with different training heights are primarily attributed to two underlying factors. 1) Differences in total hypoxic dose: compared with training at sea level, training at low altitudes can provide additional hypoxic exposure (low degree) accompanied with an increase in hypoxic dose, this appropriate dose escalation is capable of inducing greater physiological adaptations accompanied by improvements in blood oxygen carrying capacity and VO₂max and 2) the dual stimulation of environmental and exercise hypoxia: exposure to low altitudes compared with exposure to sea level altitudes can provide moderate hypoxic stress relative, such that appropriate metabolic and neural adaptations can be stimulated (without excessive damage to training quality such as training in moderate altitudes) (Zoll et al., 2006; Rodríguez et al., 2015). The findings of the influence of training altitude on the intervention efficacy of HL camps are highly relevant to the selection of an altitude base. No marked difference in chronic adaptive changes between simulated HL (HL_SIM/TAL) and natural HL (HL_NAT/TAL) was found when the altitude of the training site was similar. This observation is supported by several previous studies (Hauser et al., 2016; Saugy et al., 2016; Bourdillon et al., 2017), although athletes exhibit varying physiological reactions to acute normobaric and hypobaric hypoxia exposure (Loeppky et al., 1997; Girard et al., 2012; Beidleman et al., 2014; Coppel et al., 2015). In practical applications, simulating HL appears to be a more favorable method due to lower adverse impact risks (Saugy et al., 2016), economic and time costs (Carr et al., 2019; Millet et al., 2010), and more flexible operations (Millet et al., 2010).

Although HL has become the dominant training method in academic circles, classic HH remains a preferred choice among many elite athletes worldwide (Álvarez-Herms et al., 2015). This study indicates that HH camps with a recommended dosage range of 470–1,130 kmh can significantly improve athletes’ VO₂max compared with that observed with normoxic training. Regarding effectiveness, HH ranked lower than HL with low altitude training. The above-mentioned observations may be explained by previous reports that the critical limitation of HH relative to HL is the heightened hypoxic stress at moderate altitudes (Levine and Stray-Gundersen, 1997; Carr et al., 2015), which can impede the generation of necessary training intensities for eliciting beneficial adaptations (Wehrlin and Hallén, 2006). Furthermore, except for the interference of various confounding factors, the lower upper limit and wider CI for the dose-response curve may correlate with an additional drawback of HH; the risk of adverse reactions in an HH condition is higher than in an HL condition due to greater hypoxic continuity (Brocherie et al., 2017; Mujika et al., 2018). Thus, to minimize this potential risk and maximize the benefits of AT, an effective health and load monitoring system should be developed (Sperlich et al., 2016; Schmitt et al., 2018; Mujika et al., 2019) and adequate nutritional support should be provided (Govus et al., 2015; Stellingwerff et al., 2019). Currently, the investigated lower limit of the hypoxic dose of HH is lower than the previous study results (Millet et al., 2010). Our findings indicate that athletes who partake in 2–3 weeks of low altitude camps can effectively enhance their VO₂max (Gore et al., 1997; Carr et al., 2015). Compared with moderate and sea level altitudes, low altitude provides less hypoxic stimulation but maintains higher training quality and also offers dual stimulation of hypoxia and training. This makes low altitude camping a valuable adaptive measure for athletes preparing for higher altitude training or competitions (Saunders et al., 2009). Lastly, it is worth noting that HL with sea level training had effects similar to those of HH, which has also been reported in a similar study by Carr et al. (2019). The above perspective shows that passive hypoxia exposure alone may not maximize performance gains.

It is currently understood that the noteworthy enhancement of VO₂max following HH or HL stems predominantly from hematological adaptation following chronic hypoxia exposure, which increases the total amount of hemoglobin accompanied by the enhancement of oxygen-carrying capacity (Hahn and Gore, 2001). Multiple studies have presented compelling evidence on aerobic adaptation under hypoxic conditions, with molecular mechanisms underlying the above-described hematological changes being elucidated. Furthermore, multiple studies have presented molecular-level evidence supporting these alterations in hematology such as hypoxia-inducible factor-1 (HIF-1), which is vital to the transcriptional regulation of erythropoietin (Bhattarai et al., 2018; Koyasu et al., 2018). However, Saunders et al.’s study shows a correlation between VO₂max and hemoglobin mass changes with an r ² of only 0.15, suggesting that factors beyond hematological indices may account for 85% of the variation in VO₂max (P. U. Saunders et al., 2013). Besides activating the EPO transcription gene, HIF-1 is also required for inducing other genes (e.g., encoding glycolytic enzymes, VEGF, GLUT-1, and metabolic proteins), which causes molecular changes and triggers non-hematological physiological adaptations such as increased citrate synthase activity, mitochondrial density, capillary-to-fiber ratio, and muscle buffering capacity (Wang et al., 1995; Vogt et al., 2001; Gore et al., 2007). The above changes may partially account for the improvement in VO₂max independent of hematological adaptions.

This study confirmed the positive effect of IHT on athletes’ VO₂max, which is consistent with a recent meta-analysis (Westmacott et al., 2022). Besides, we found two novel observations: 1) the minimum effect by IHT and 2) the reasonable hypoxic dosage range. First, the effectiveness of IHT may arise from its specific underlying mechanism or methodological design (Czuba, Fidos-Czuba et al., 2018). Unlike HH and HL, numerous studies have indicated that the hypoxic exposure of IHT is inadequate to substantially alter hematological parameters (Czuba et al., 2014; Czuba et al., 2019; Ambroży et al., 2020; Kim et al., 2021; Park et al., 2022; Teległów et al., 2022), and the potential mechanism for enhancing aerobic capacity primarily involves specific molecular adaptations in peripheral tissues (Ponsot et al., 2006; Zoll et al., 2006; Neya et al., 2007). It is worth noting that Czuba et al. posited that a hematological mechanism is more effective in enhancing aerobic capacity (Czuba et al., 2018), and the diverse adaptations due to IHT contributes greatly to exercise (Green et al., 2000; Hamlin et al., 2010; Park et al., 2016; Saunders et al., 2004), which can also serve as a valuable metric for evaluating aerobic performance (Levine and Stray-Gundersen, 2005). In summary, the physiological adaptations induced by IHT are unable to increase VO₂max as significantly as that observed with HH and HL.

Although this study has explored a relatively robust dose-effect model for IHT, we found, after reviewing the included studies, that the model is unreasonable due to the oversight of a crucial indicator, training intensity under hypoxia, which is essential for promoting muscle and metabolic adaptations (McLean et al., 2014). Unfortunately, it is difficult to standardize the specific training intensity in each study and simultaneously consider the combined effects of hypoxic and training loads. Notably, several studies have stated that IHT can enhance athletes’ anaerobic capacity (Hendriksen and Meeuwsen, 2003; Millet et al., 2014; Morton and Cable, 2005), which is to an extent significant in team and high-level endurance sports. In summary, although IHT had the least impact on VO₂max, it considerably important in practice due to the low cost and low risk of negative effects (Jung et al., 2020).

Theoretically, variant combining HHL with HL and LLTH should produce positive effects (Millet et al., 2010). However, our finding was not consistent with the theoretical expectation. Possible reasons include limited quantity of relevant experiments performed in the included studies, small sample sizes, and low statistical power. Furthermore, as revealed by most included studies, HHL can directly enhance time-trial performance (Robertson et al., 2010; Czuba et al., 2014), and some studies have reported no significant correlation between performance enhancement and changes in blood oxygen-carrying capacity (Czuba et al., 2014; Rodríguez et al., 2015). Although using VO₂max as the sole evaluation criterion for HHL is insufficient, the lack in both the depth and breadth of research makes it difficult to comprehensively assess the effect of HHL. In-depth research should prioritize exploring HL to identify the most effective combination with other training methods.

The effectiveness of IHE in augmenting the aerobic performance of athletes has become a contentious topic (Millet et al., 2010; Viscor et al., 2018), with detractors contending that IHE fails to elicit significant physiological adaptations (Brugniaux et al., 2006; Rodríguez et al., 2007). For physiological or kinematic indicators, IHE failed to demonstrate any substantial improvement as indicated by over half of the included studies (6/9). Compared with other practices, IHE employs an extremely lower overall hypoxic dose and lacks supplementary high-intensity training stimuli during hypoxia exposure. This relatively limited and inadequate stimulation of athletes makes the feasibility of IHE questionable, and the driving force behind the development of this method may be more commercial than scientific (Lundby and Robach, 2016).

The absence of blinding in most existing studies posed a high risk of bias in quality assessment and undermines the ability to rule out placebo effects. A cross-over design can be employed although blinding may not be feasible for AT in natural environments. Future relevant studies should adopt more rigorous experimental designs to improve the evidence on effectiveness and dosage accuracy. The efficacy of AT is not solely determined by the degree of hypoxia and exposure continuity, as various confounding factors that affect the final outcome have not been fully considered. These factors include the specific training content, load and intensity in hypoxic or normoxic environments, individual differences in hypoxic responses, and the criticality of various support work or specialty-specific factors (Burtscher et al., 2018). Unfortunately, quantifying the above-described variables is challenging and may increase the heterogeneity risk in this study.

The findings of this comprehensive network meta-analysis suggest that HL, HH, and IHT compared with normoxic training are capable of effectively improving the VO₂max of athletes. The effect of HL with low altitude training was optimal, and the hypoxic type of residential environments (simulated or natural) did not affect the results. This observation can provide a useful reference for future site selection of an altitude base. In addition, this study also found a dose-effect relationship between hypoxic dose and VO₂max variation for both HH and HL. As indicated by the results, hypoxic practices have maximum and minimum effective hypoxic dose thresholds, and both showed an inverted U-shaped curve between dose and efficacy. This observation may be correlated with the negative effects of chronic hypoxia, and it also provides sound recommendations regarding the time and height arrangements for altitude camps. Notably, as opposed to the previous study findings, HH camps organized at low altitudes can moderately enhance the VO₂max of athletes, suggesting that it can be a valuable adaptive measure for athletes preparing for higher AT or competitions. The small number of studies on HHL in this meta-analysis limits the confidence of our findings. Following a brief review of other indicators, the combined approach seems to be optional, and the depth and breadth of relevant explorations should be improved in the future. Lastly, the quality of most studies was low. To maximize the exclusion of placebo effects, future controlled trials on simulated altitudes should consider using a blinded method, and controlled trials on real altitudes can attempt using the cross-over design.