Angiotensin-converting gene and hypoxic exercise tolerance: a randomized crossover trial

Abstract

Hypoxic training enhances endurance sports tolerance. However, individual responses vary due to physiological differences. This study investigated the relationship between genetic factors and exercise tolerance in hypoxic conditions. This randomized crossover study included 22 male university students (age 20.8±1.3 years, peak oxygen uptake 54.5±6.5 mL/min/kg). Incremental load tests were conducted to assess the symptomatic limit on separate days under normoxic and hypoxic conditions (oxygen concentration 15.4±0.8%) using an ergometer. The initial test environment was randomized. The peak oxygen uptake and blood lactate were monitored every minute, and Δ peak oxygen uptake (peak oxygen uptake under hypoxia – peak oxygen uptake under normoxia) was calculated. Sixteen genotypes linked to exercise tolerance (such as angiotensin-converting enzyme [ACE]) were examined. Peak oxygen uptake significantly decreased under hypoxia (p<0.01). Δ peak oxygen uptake varied among individuals (minimum: 0.7 and maximum: − 18.9). Among analyzed genetic polymorphisms, ACE-II genotypes showed significantly greater Δ peak oxygen uptake than ACE-ID/ACE-DD genotypes (p=0.02). ACE-II genotypes exhibited lower blood lactate elevation at peak exercise in normoxic (p=0.01) and hypoxic (p=0.03) conditions. Participants with the ACE-II genotype had lower lactate concentrations and greater reductions in peak oxygen uptake under hypoxic conditions. Optimizing hypoxic training requires individualized programs incorporating genetic analysis.

Keywords

alleles - athletes - cycling training - lactate - lactic acid - oxygen saturation

• References

• 1 Wehrlin JP, Hallén J. Linear decrease in.VO₂max and performance with increasing altitude in endurance athletes. Eur J Appl Physiol 2006; 96: 404-412
• 2 Angermann M, Hoppeler H, Wittwer M. et al. Effect of acute hypoxia on maximal oxygen uptake and maximal performance during leg and upper-body exercise in Nordic combined skiers. Int J Sports Med 2006; 27: 301-306
• 3 Martin D, O’Kroy J. Effects of acute hypoxia on the VO₂ max of trained and untrained subjects. J Sports Sci 1993; 11: 37-42
• 4 Subudhi AW, Dimmen AC, Roach RC. Effects of acute hypoxia on cerebral and muscle oxygenation during incremental exercise. J Appl Physiol (1985) 2007; 103: 177-183
• 5 Chapman RF. The individual response to training and competition at altitude. Br J Sports Med 2013; 47: i40-i44
• 6 Durand F, Raberin A. Exercise- induced hypoxemia in endurance athletes: Consequences for altitude exposure. Front Sports Act Living 2021; 3: 663674
• 7 Kumagai H, Tobina T, Ichinoseki-Sekine N. et al. Role of selected polymorphisms in determining muscle fiber composition in Japanese men and women. J Appl Physiol (1985) 2018; 124: 1377-1384
• 8 Puthucheary Z, Skipworth JR, Rawal J. et al. The ACE gene and human performance: 12 years on. Sports Med 2011; 41: 433-448
• 9 MacArthur DG, Seto JT, Raftery JM. et al. Loss of ACTN3 gene function alters mouse muscle metabolism and shows evidence of positive selection in humans. Nat Genet 2007; 39: 1261-1265
• 10 Ipekoglu G, Bulbul A, Cakir HI. A meta-analysis on the association of ACE and PPARA gene variants and endurance athletic status. J Sports Med Phys Fitness 2022; 62: 795-802
• 11 Varillas-Delgado D, Del Coso J, Gutiérrez-Hellín J. et al. Genetics and sports performance: The present and future in the identification of talent for sports based on DNA testing. Eur J Appl Physiol 2022; 122: 1811-1830
• 12 Masschelein E, Puype J, Broos S. et al. A genetic predisposition score associates with reduced aerobic capacity in response to acute normobaric hypoxia in lowlanders. High Alt Med Biol 2015; 16: 34-42
• 13 Gaskill SE, Ruby BC, Walker AJ. et al. Validity and reliability of combining three methods to determine ventilatory threshold. Med Sci Sports Exerc 2001; 33: 1841-1848
• 14 Faude O, Kindermann W, Meyer T. Lactate threshold concepts: How valid are they?. Sports Med 2009; 39: 469-490
• 15 Kurihara K, Kikukawa A, Kobayashi A. et al. Frontal cortical oxygenation changes during gravity-induced loss of consciousness in humans: A near-infrared spatially resolved spectroscopic study. J Appl Physiol (1985) 2007; 103: 1326-1331
• 16 Grassi B, Pogliaghi S, Rampichini S. et al. Muscle oxygenation and pulmonary gas exchange kinetics during cycling exercise on-transitions in humans. J Appl Physiol (1985) 2003; 95: 149-158
• 17 Ishii K, Liang N, Oue A. et al. Central command contributes to increased blood flow in the noncontracting muscle at the start of one-legged dynamic exercise in humans. J Appl Physiol (1985) 2012; 112: 1961-1974
• 18 Kowalchuk JM, Rossiter HB, Ward SA. et al. The effect of resistive breathing on leg muscle oxygenation using near-infrared spectroscopy during exercise in men. Exp Physiol 2002; 87: 601-611
• 19 Yoshida T, Udo M, Chida M. et al. Arterial blood gases, acid-base balance, and lactate and gas exchange variables during hypoxic exercise. Int J Sports Med 1989; 10: 279-285
• 20 Springer C, Barstow TJ, Wasserman K. et al. Oxygen uptake and heart rate responses during hypoxic exercise in children and adults. Med Sci Sports Exerc 1991; 23: 71-79
• 21 McAuley ABT, Hughes DC, Tsaprouni LG. et al. Genetic association research in football: A systematic review. Eur J Sport Sci 2021; 21: 714-752
• 22 Skidgel RA, Erdos EG. The broad substrate specificity of human angiotensin I converting enzyme. Clin Exp Hypertens A 1987; 9: 243-259
• 23 Jones A, Woods DR. Skeletal muscle RAS and exercise performance. Int J Biochem Cell Biol 2003; 35: 855-866
• 24 de Kloet AD, Krause EG, Kim DH. et al. The effect of angiotensin-converting enzyme inhibition using captopril on energy balance and glucose homeostasis. Endocrinology 2009; 150: 4114-4123
• 25 Ryan AS, Nicklas BJ, Berman DM. et al. The insertion/deletion polymorphism of the ACE gene is related to insulin sensitivity in overweight women. Diabetes Care 2001; 24: 1646-1652
• 26 Feng Y, Niu T, Xu X. et al. Insertion/deletion polymorphism of the ACE gene is associated with type 2 diabetes. Diabetes 2002; 51: 1986-1988
• 27 Wagle JP, Carroll KM, Cunanan AJ. et al. Preliminary investigation into the effect of ACTN3 and ACE polymorphisms on muscle and performance characteristics. J Strength Cond Res 2021; 35: 688-694
• 28 Czuba M, Waskiewicz Z, Zajac A. et al. The effects of intermittent hypoxic training on aerobic capacity and endurance performance in cyclists. J Sports Sci Med 2011; 10: 175-183
• 29 Kanazawa H, Otsuka T, Hirata K. et al. Association between the angiotensin-converting enzyme gene polymorphisms and tissue oxygenation during exercise in patients with COPD. Chest 2002; 121: 697-701
• 30 Kanazawa H, Hirata K, Yoshikawa J. Influence of oxygen administration on pulmonary haemodynamics and tissue oxygenation during exercise in COPD patients with different ACE genotypes. Clin Physiol Funct Imaging 2003; 23: 332-336
• 31 Flück M, Vaughan D, Rittweger J. et al. Post-translational dysregulation of glucose uptake during exhaustive cycling exercise in vastus lateralis muscle of healthy homozygous carriers of the ACE deletion allele. Front Physiol 2022; 13: 933792
• 32 Czuba M, Fidos-Czuba O, Płoszczyca K. et al. Comparison of the effect of intermittent hypoxic training vs. the live high, train low strategy on aerobic capacity and sports performance in cyclists in normoxia. Biol Sport 2018; 35: 39-48