Altitude and hypoxic training are common among many personal or team sports athletes and recommended by many coaches and scientists for normoxic exercise performance¹.

Generally, normoxic exercise performance can be improved using three methods through altitude and hypoxic training². First, living high-training high (LHTH) was the first design of living and training at 1500-4000 m in altitude environments that enhances erythropoiesis and exercise performance at sea level. However, LHTH has a major limitation, that is, failure to perform training of the same intensities (e.g., running speed), as compared with the sea-level training³. Several studies demonstrated that absolute training intensities during continuous and interval workout significantly decreased at 2500 m, as compared with the sea-level training^{4, 5}.

Second, intermittent hypoxic training (IHT) commonly involves shorter hypoxic exposure (approximately two to five sessions per week of < 3 h) and lesser cost, effort, and time than other altitude and hypoxic training methods⁶. However, the efficacy of IHT for the enhancement of normoxic exercise performance is more of a matter of debate owing to the methodological differences, including in the dose of hypoxic stimulus, type and intensity of training, participant training status, and time-point of the measurement of exercise performance^7-9.

Third, living high-training low (LHTL) was developed for potential improvements in the limitation of LHTH. LHTL simultaneously offers athletes the beneficial effects of acclimation in altitudes and hypoxic residing (e.g., erythropoiesis) and training at or near sea level (i.e., maintenance of training intensity). Therefore, despite ongoing debate regarding the efficiency of altitude and hypoxic training methods for normoxic exercise performance or the nature of its underlying mechanism, LHTL in altitude and hypoxic training is widely recognized as the “gold-standard” for normoxic exercise performance via erythropoiesis and maximal oxygen consumption (VO_2max) in athletes^{1, 4, 10}.

Normoxic exercise performance is highly related to a number of factors that can be altered through various altitude and hypoxic training methods, including increases in the exercise economy¹¹, acid-base response in the muscle²⁹, skeletal muscle oxygenation²⁷, cardiac function¹³, vascular function³⁰, and microcirculation³¹ as well as oxygen transport capacity (e.g., erythropoiesis)¹ and VO_2max³. Considering previous studies related to the improvement of athletic performance via LHTL, Levine and Stray-Gunderson³² assumed that acclimatization to a moderate altitude (2,500 m) plus training at a low altitude (1,250 m) (LHTL) improves sea-level performance in well-trained runners more than an equivalent sea-level or altitude control. As a result, 4 wk of applying LHTL improves sea-level running performance in trained runners owing to an increase in the red cell mass volume and VO_2max and maintenance of sea-level training velocities, most likely accounting for the increase in the velocity of the VO_2max. Further, Robach et al²¹ tested whether LHTL enhances aerobic performance in athletes and whether any positive effect may last for up to 2 wk after LHTL. They concluded that LHTL may stimulate red cell production, without any concurrent amelioration of aerobic performance, and the absence of any prolonged benefit after LHTL suggests that this LHTL model cannot be recommended for long-term purposes. Siebenmann et al³³ verified LHTL efficacy in athletic performance with the use of a placebo-controlled, double-blinded design; they tested the hypothesis that LHTL-related improvements in endurance performance are mediated through physiological mechanisms and not through a placebo effect. Their results indicate that LHTL, using normobaric hypoxia, may not improve endurance performance at sea level or moderate altitude more than conventional training.

Similarly, most previous studies related to LHTL for the improvement of exercise performance at sea level have focused on the oxygen transport capacity of the blood (e.g., erythropoiesis), VO_2max, and energy metabolism during submaximal exercises; however, the results of these studies are not consistent. Thus, it is very valuable to investigate the changes in the cardiac function and skeletal muscle oxygenation, which are very important factors for normoxic exercise performance, via LHTL application.

Therefore, using a randomized and controlled design, this study aimed to investigate the efficiency of the application of LHTL on cardiac function and skeletal muscle oxygenation during submaximal exercises at sea level in athletes.

The participants’ compliance and adherence to the study design were 100% in all groups, based on the daily activity records. The characteristics of the selected athletes between the two groups showed no significant difference (Table 1).

A number of studies have been conducted on the efficacy of the application of altitude and hypoxic training interventions on normoxic exercise performance in athletes. These studies reported positive and negative results owing to the physiological characteristics (e.g., body weight, percent of body fat, sex differences, and individual differences) and training conditions (e.g., method, intensity, frequency, duration, and time of training)¹³.

Altitude and hypoxic training have positive effects on exercise economy, acid-base response in the blood and muscle, erythropoiesis, glycolytic enzyme, muscle buffer capacity, VO_2max, and erythropoiesis^{1, 2, 6, 13, 17, 18}. Together with its positive effects, altitude and hypoxic training also negatively affect blood viscosity, muscle blood flow, cardiac output, HRmax, protein synthesis, and Na⁺-K⁺- ATPase activity and decrease training quality and quantity^19-22. Similarly, normoxic exercise performance is highly related to a number of factors that can be altered through altitude and hypoxic training methods, including increases in the exercise economy¹¹, acid-base response in the muscle²⁹, skeletal muscle oxygenation²⁷, cardiac function¹³, vascular function³⁰, and microcirculation³¹ as well as oxygen transport capacity (e.g., erythropoiesis)1 and VO_2max³.

Most studies related to altitude and hypoxic training, specifically LHTL, for the improvement of exercise performance at sea level have focused on the oxygen transport capacity of the blood (e.g., erythropoiesis), VO_2max, and energy metabolism during submaximal exercises; the results of these studies are not consistent^{21, 32, 33}. Therefore, we investigated the efficiency of the application of LHTL on cardiac function and skeletal muscle oxygenation during submaximal exercises at sea level in athletes. As a result, the 4-wk LHTL was sufficient to enhance the cardiac function and can potentially improve the skeletal muscle oxygenation in athletes.

LHTL enhances erythropoiesis and oxygen transport and utilization capacities by residing at high-altitude or hypoxic environments and performing high-intensity trainings at or near sea level^{1, 5, 6, 13, 19, 21}. Cardiac function is the most important variable for oxygen transport capacity, which is a determinant of the improvement of normoxic exercise performance^{11, 23}. In general, LHTL increases energy availability that stimulates the parasympathetic nervous system through activation of β-adrenergic receptors in the cardiac muscles and improves SV with enhanced left ventricular contractility²⁴. Further, several studies have found that LHTL led to higher left ventricular contractility and oxygen utilization in the cardiac and skeletal muscles^24-26. To verify the effect of LHTL on cardiac function, which is one of the major determinants of performance, Liu et al²⁴ divided 21 well-trained triathletes into control (n = 10, living and training at sea level) and LHTL groups (living at 1980-m altitude ≥ 12 h/d and training at sea level); the cardiac function of these triathletes was examined via Doppler echocardiography before and at the end of the 2-wk program. As a result, the left ventricular end-systolic diameter of the LHTL group was lower than that of the control group. Further, the shortening fraction and EF in the LHTL group increased by 9% and 17%, respectively; their SV and CO also increased. They suggested that LHTL improved the systolic function underlined by the incremented left ventricular contractility, which might be associated with increased adrenergic receptors or improved myocardial energy utilization.

Our study revealed that LHTL significantly decreased the HR and increased the SV during the submaximal exercises. EDV significantly increased in both groups; however, ESV significantly increased only in the LLTL group. Although LLTL and LHTL increased the preload (the pressure that stretches the right or left ventricle of the heart to its greatest dimensions under variable physiologic demands), only LHTL increased the afterload (the pressure in the wall of the left ventricle during ejection). In other words, ventricular relaxation depending upon the EDV is caused by enhanced venous return and left ventricular volume through exercise training, and not by stimulation of hypoxic conditions. However, LHTL should increase ventricular contractility and SV. Our results are consistent with those of several studies showing that the improvement in the ventricular contractility through ESV and SV should result from the activation of β-adrenergic receptors and increased energy efficiency in the cardiac muscles^24-26. Furthermore, the decrease in the HR in the LHTL group during the submaximal exercises would be linked to the decreased sympathetic nerve activity and increased parasympathetic nerve activity, resulting in the activation of α2-adrenergic receptors^{11, 24}. Conversely, our data showing no change in the CO after LHTL attributes to the changes in the HR and SV (the actual effects on the CO), in contrast with those of previous studies^{13, 24}.

Nevertheless, we verified the adaptation effect of LHTL on oxygen utilization capacity in the mitochondria during the submaximal exercises by measuring the skeletal muscle oxygenation profiles of the left vastus lateralis using the commercially available NIRS system^{27, 28}. Although the O₂Hb, HHb, and TOI did not significantly change, all skeletal muscle oxygenation profiles increased during the submaximal exercises via LHTL. Consequently, we verified that LHTL enhanced the oxygen utilization capacity in the mitochondria in the skeletal muscle.

The present study demonstrates that LHTL had a positive effect on cardiac function and can potentially improve the skeletal muscle oxygenation during submaximal exercises in athletes compared with LLTL. In addition, our study provides some novel possibilities regarding greater exercise performance via enhanced cardiac function and skeletal muscles in athletes. Therefore, more facilities that can apply LHTL are needed to improve the competitiveness of Korean elite athletes.