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Effects of strength training under hypoxic conditions on muscle performance, body composition and haematological variables

The addition of a hypoxic stimulus during resistance training is suggested to increase the metabolic responses, enhancing hypertrophy and muscle strength. The purpose of this study was to investigate the effects of resistance training performed at submaximal intensities combined with normobaric hypoxia on muscular performance, body composition and haematological parameters. Thirty-two untrained subjects participated in this study (weight: 74.68±12.89 kg; height: 175±0.08 cm; BMI: 24.28±3.80 kg/m2). They were randomized to two groups: hypoxia (FiO2 = 13%) or normoxia (FiO2 = 20.9%). The training programme lasted 7 weeks (3 d/w) and several muscle groups were exercised (3 sets x 65−80% 1RM to failure). Measurements were taken before, after the training and after a 3-week detraining period. Body composition and muscle mass were assessed through skinfolds and muscle girths. Muscle strength was evaluated by the 1RM estimated test. Finally, haemoglobin and haematocrit were taken from the antecubital vein. Both groups improved their strength performance and muscle perimeters, but the hypoxia group obtained a greater increase in muscle mass (hypoxia: +1.80% vs. normoxia: +0.38%; p<0.05) and decrease in fat mass (hypoxia: -6.83% vs. normoxia: +1.26%; p<0.05) compared to the normoxia group. Additionally, haematocrit values were also higher for the hypoxia group after the detraining period (hypoxia: +2.20% vs. normoxia: -2.22%; p<0.05). In conclusion, resistance training under hypoxic conditions could increase muscle mass and decrease fat mass more effectively than training performed in normoxia, but without contributing to greater muscle strength.


INTRODUCTION
Hypoxic training has become available to more people in recent years through altitude chambers (hypobaric hypoxia) and hypoxic tents (normobaric hypoxia) [1]. Muscular and haematological adaptations are the main benefits of time spent at moderate altitude [2,3]. With regard to muscular adaptations, high-intensity resistance training has a potent effect in promoting increases in muscle size and strength of skeletal muscles due to improvements in muscular endurance and the promotion of angiogenesis in skeletal muscle [4]. In line with this, the addition of a hypoxic stimulus is suggested to increase the metabolic and hormonal responses to resistance exercise [5].
In addition, the combination of hypoxia and resistance training is used to increase hypertrophy and muscular strength [6,7]. Both methods, blood flow restriction (BFR) and intermittent hypoxic resistance training (IHRT) are commonly used to achieve these improvements. However, unlike BFR strategies, the use of normobaric hypoxia devices allows training the trunk musculature under hypoxic conditions with the limbs [5].

Effects of strength training under hypoxic conditions on muscle performance, body composition and haematological variables
improve body composition through lean body mass increase and decrease body fat. We additionally hypothesized that the addition of hypoxia to the training programme would increase muscular performance and haematological variables.

Participants
Thirty-two untrained male subjects (age: 25.7±6.42 years; height: 176±0.07 cm; weight: 78.41±12.07 kg) volunteered to participate in this study and were assigned to hypoxia (HYP) and normoxia (NOR) groups (n = 16 per group). All the participants were sea-level residents and had not been exposed to an altitude or hypoxia environment of more than 1 800 m within the 4 months before participation. We define the participants as totally untrained due to none of them having been involved in a regular strength training programme within 1 year before at the beginning of the study. Each participant was informed of the procedure to be followed during the study and they all provided written consent. This study was approved by the Institutional Science Ethic Committee that conforms to the 2008 Helsinki Declaration for Human Research Ethics.

Experimental design
To test the effects of 7 weeks of an IHRT protocol in normoxia and hypoxia on body composition, muscle performance and haematological variables, a single-blinded randomized controlled trial with pre-, post-and detraining tests was developed. Thirty-two untrained university students were randomly assigned to 2 experimental groups [hypoxia group (HYP; n = 16) and normoxia group (NOR; n = 16)] who finished the same resistance training protocol (7 weeks) under normobaric hypoxia (FiO 2 = 13%) or normoxia (FiO 2 = 21%), respectively, in a single-blinded manner. The week prior to starting the training sessions all participants visited the laboratory to familiarize themselves with testing and training procedures. Maximal dynamic strength (1RM) was estimated in all exercises that were part of the training circuit. In addition, anthropometry, body composition, haemoglobin and haematocrit were measured under normoxic conditions. These measurements were also performed after the training and after a three-week detraining period. The detraining period was carried out under normoxia conditions for all participants. In addition, participants were instructed to maintain their regular dietary consumption and not practise any intense exercises during the entire measurement and training phases.

Systemic hypoxia exposure
Both groups performed the training sessions in a normobaric chamber (CAT 430, Colorado Altitude Training, USA) where oxygendepleted air was pumped from a hypoxia generator (CAT-12, Colorado Altitude Training, USA) to create simulated hypoxic conditions (FiO 2 = 13%, equivalent to 4 300 m altitude) where barometric pressure in the tent was equivalent to sea level. Ambient O 2 was performed high-intensity (6RM) circuit training in hypoxia (FiO 2 = 15%) for 8 weeks. However, the strength gain was similar in both groups. Conversely, Inness et al. [12] reported a greater improvement in absolute and relative 1RM of squat in the hypoxia group after 7 weeks of IHRT (FiO 2 = 14.3%) with heavy loads (75% 1RM), but no changes were found in lean mass. Moreover, Mayo et al. [13] found small improvements in upper-body strength after 3 weeks of hypoxic training (FiO 2 = 14.4%) with loads between 85 and 92.5% of 1RM. However, both studies were the only ones to include highly trained individuals in their sample. Therefore, it is possible that the initial training status of the participants directly conditions the responses to hypoxia training [16].
Despite this, the aforementioned studies established a fixed number of repetitions per set. In contrast, the present study proposed an IHRT protocol to muscle failure in each set. This approach has been carried out only by a previous acute study that reported increases in metabolic stress and rating of perceived exertion (RPE) [18]. However, to the best of our knowledge, there are no studies that analyse the effect of this type of protocol to muscle failure over several weeks of IHRT in hypoxia on performance variables. In addition, none of the previous studies carried out an assessment of the potential benefits of the IHRT after a short-term detraining period. Detraining is the cessation of training volume, intensity, or frequency resulting in reduced performance [19]. It appears that the duration of the detraining period is important for the magnitude of changes, and may occur during short periods (<4 weeks) or long periods (>4 weeks) [20].
However, there are no previous references to establish possible adaptations caused by this detraining period.
In addition, when the amount of tissue oxygen in the body decreases due to hypoxia, the secretion of transcription factor hypoxiainducible factor (HIF-1α) increases exponentially, and this fact has been associated with an increases in EPO secretion [25]. However, several studies have shown that intermittent training in hypoxia may not be useful in enhancing erythropoiesis [26,27]. Conversely, Camacho-Cardenosa et al. [28] reported higher values of haemoglobin (Hb) and haematocrit (Hct) in active participants in the detraining period (3 weeks) after eight repeated sprint training sessions in normobaric hypoxia. Despite this, with regard to resistance training, only Kon et al. [4] and Álvarez-Herms et al. [29] reported the effects of training under normobaric hypoxia and hypobaric hypoxia, respectively, on Hb concentration and Hct mass. However, these studies failed to find differences for either of the two values when comparing the two training groups.
Therefore, the aim of this study was to analyse the effect of 7 weeks of resistance training to muscle failure combined with normobaric hypoxia on muscular performance, body composition and haematological parameters. Our hypothesis was that hypoxic training would continuously monitored by a digital controller (Handi+, Maxtec, USA) to maintain the hypoxic conditions in the chamber. For training in normoxic conditions, the ambient FiO 2 was not manipulated at a natural altitude of about 440 m.

Blood sampling
The testing sessions began upon arrival in the morning. and thigh (measurement of the mid-thigh position), as well as skinfolds of the abdomen, iliac crest, subscapular, triceps, medial calf and front thigh, were measured in order to calculate skeletal muscle.
Skinfolds and girths were measured in duplicate or triplicate if the difference between the first two measures was greater than 1.0 mm in skinfolds and 1.0 cm in girths. Hydration prior to body composition testing was not allowed. For the calculation of the fat weight and its percentage, the equation of Siri [31] was used. Muscle mass and percentage were calculated from the Lee equation [32]. Finally, bone mass and percentage were calculated using the Von Döbeln equation [33] modified by Rocha [34].

Strength test
Maximal dynamic strength was calculated in the first session, after resistance training and after the three-week detraining period. Initially, all subjects carried out a familiarization session, during which they were familiarized with the proper technique of all the exercises that were part of the circuit training. Approximately 2-3 days after the familiarization, the 1RM of bench press, EZ -Bar biceps curl, lying EZ -Bar French press, Pendlay row and half squat was estimated from a 3RM in normoxia using the predictive equation described by Brzycki [35] as a measure of maximal dynamic upper and lower-body strength and to determine the training load for all participants in the training intervention. Prior to testing, subjects warmed up on a stationary bicycle for 5 min at 75 W. Afterwards, subjects performed ten repetitions at 50% of the estimated 1RM. Then, each subject carried out 3-4 attempts with progressively increasing weights to achieve their 3RM, with a 3 min rest period between attempts.
1RM was estimated again under normoxic conditions after 7 weeks of resistance training and after a three-week detraining period at the same time of day as the baseline performance in each subject.

Resistance training programme
The resistance training programme lasted for 7 weeks and was the same for both the HYP and NOR groups.

Values of body composition, anthropometry and haematological vari-
ables are shown in Table 1 [39]. Moreover, it has been previously shown that training in normobaric hypoxia conditions does not cause a decrease in the concentration of nitric oxide in plasma [40]. Thus, nitric oxide is a potent reactive species that mediates the activation of skeletal muscle satellite cells, which contributes directly to the mechanisms that generate hypertrophy [41]. In our study, direct measurement of anabolic hormonal responses was not carried out.
However, several studies have shown that hypoxic environments increase the hormonal secretion more than normoxic environments [4,12,42], so we can speculate that the low partial fraction of oxygen used (FiO 2 = 13%) caused greater secretion of circulating anabolic hormones in the hypoxia group, increasing the muscle percentage after 7 weeks of training.
With regard to the fat loss observed in the present study, recent studies show that strength exercises with loads can be more effective than aerobic exercise [43], particularly in reducing body fat [44].
Moreover, the addition of a hypoxic stimulus to strength training induces the activation of HIF-1α, which causes changes in cell metabolism and the activation of different peripheral pathways in conjunction with the central nervous system, leading to greater metabolic and endocrine responses that could affect energy expenditure and energy balance [13,44]. In line with this, it has been shown that HIF-1α can modulate responses to fat loss by increasing lipid metabolism [45]. Despite this, Ho et al. [10] did not observe Compared to the differences between groups, greater improvements in lean body mass and loss in fat mass were observed after IHRT compared to normoxia training. In line with this, Yan et al. [9] reported a greater increase in lean body mass with a high level (FiO 2 = 12.6%) and moderate level of hypoxia (FiO 2 = 16%) after 5 weeks' resistance training of barbell back squat compared to the normoxia group. In addition, Nishimura et al. [7] reported a significant increase in the muscle cross-sectional area (CSA), which was only observed in the hypoxia group after 6 weeks of bilateral elbow  In contrast, in our study, a full-body workout routine of five exercises was performed. It has been previously reported that the amount of muscle mass involved in a training programme significantly affects acute metabolic demands and anabolic hormonal response, directly influencing the increase in lean body mass and reductions in body fat [46]. Furthermore, it is possible that the type of muscle trained and protocol used condition the response in the reduction of fat mass, due to the fact that each muscle group is unique in its capacity for trainability and adaptability [47].
In relation to muscle strength, resistance training is a potent factor for increasing muscular strength and promoting muscle hypertrophy [48]. Both training protocols, regardless of the oxygenation condition, achieved improvements in the 1RM in all exercises, suggesting that loads over 65% 1RM were sufficient to induce muscular strength gains after long-term resistance exercise [46]. However, with the exception of strength in the biceps curl, no significant inter-group difference was observed. Although Kon et al. [4,49] have reported that hypoxia is a potent factor for the enhancement of GH responses to moderate intensity resistance exercise, other studies have not found greater increases in muscle strength after performing the training under hypoxic conditions [7,10,11,50]. These results may indicate that other training variables (such as intensity, recovery times, training status or muscle group involved) could play a more important role than hypoxia in achieving improvements in muscle strength.
In terms of inter-set rest periods, Scott et al. [51] hypothesized that low and moderate-load IHRT might only provide added benefit when relatively brief inter-set rest periods are used (30−60 s). The inter-set rest period time in the present study (90 s between sets) could explain the lack of improvement in muscle strength of the majority of the muscle groups investigated, as in previous studies [4,10]. However, the training protocols of all the previous studies established a fixed number of repetitions per set. In contrast, in our training protocol we reached muscle failure in each series. Consequently, we established a relatively short inter-set rest period in order to increase intramuscular metabolic stress, because the training focused on hypertrophic responses [52]. Nonetheless, it is possible that this recovery between sets during this moderate-load training will limit the accumulation of metabolites, attenuating any hypoxiamediated benefits during this type of training [51], not allowing high levels of tension in successive series, and so the training stimulus would not be effective enough to trigger the desired adaptations [11,24]. In agreement with these explanations, the gain in strength in the biceps curl could be attributed to the fact that the initial levels of kilograms raised in the biceps curl were lower in the hypoxia group. This experimental group could have had a greater room for improvement throughout the protocol, or the gain in muscle strength could even be related to the individual trainability and adaptability of each muscle group [21]. On the other hand, the level of hypoxia used in IHRT protocols can also influence long-term muscle adaptations and gains in muscle strength [9].
According to haematological variables, haemoglobin values did not change significantly with either training protocol. This is in agreement with previous studies that did not find changes in this variable after a resistance training programme under normobaric [4] and hypobaric [29]  Additionally, they observed that short-term hypoxic exposure suppressed the plasma acylated ghrelin concentrations, which are directly been established to influence directly the hypertrophic and strength responses. Third, the caloric intake of participants was not checked during the 8 weeks of training, which may have affected the results.

CONCLUSIONS
In this study, 7 weeks of IHRT under high-level hypoxia (FiO 2 = 13%) caused a greater increase in muscle mass and a greater reduction of the fat mass in untrained subjects. Furthermore, IHRT improved strength performance after 7 weeks of training in untrained participants, but without inter-group differences. These findings may be of interest to coaches and other researchers for optimizing performance through improvements of body composition in men previously untrained in resistance exercise.

Acknowledgment
The authors would like to thank the Council of Extremadura (Fundings for research groups GR18003). No conflicts of interest, financial or otherwise, are declared by the authors. The experiments comply with the current laws of the country in which they were performed.

Declarations of interest
none implicated in the anorexia phenomenon. Nonetheless, an increase in fat percentage in our study due to the increase in appetite when hypoxic stimulus finished could be very speculative due to no marker having been measured; nor was caloric intake monitored throughout the study.
In the present study, the detraining period decreased the performance in all the exercises of the training programme, although the strength gains remained elevated with respect to the initial levels.
By comparison, Kraemer et al. [60] observed maintenance of the maximum dynamic strength in individuals trained after 6 weeks of detraining. However, Häkkinen et al. [57] reported a decrease in 1RM squat in Olympic lifters after 4 weeks of detraining. It is possible that the magnitude of maintenance or loss of performance after a period of detraining may be influenced by the level or initial physical condition of the athlete. However, further research to elucidate this point is needed.

Limitations
Several limitations of this study need to be addressed. The first is the impossibility of using dual X-ray absorptiometry (DEXA) for measuring changes in body composition. Second, we could not measure the hormonal response to resistance training in hypoxia, which has