Int J Sports Med 2025; 46(04): 246-254
DOI: 10.1055/a-2477-0512
Physiology & Biochemistry

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

1   Institute for Integrated Sports Medicine, Keio University School of Medicine, Tokyo, Japan (Ringgold ID: RIN34787)
1   Institute for Integrated Sports Medicine, Keio University School of Medicine, Tokyo, Japan (Ringgold ID: RIN34787)
,
Mizuki Momoi#
2   Department of Cardiology, Keio University School of Medicine, Tokyo, Japan (Ringgold ID: RIN34787)
1   Institute for Integrated Sports Medicine, Keio University School of Medicine, Tokyo, Japan (Ringgold ID: RIN34787)
,
Daisuke Nakashima
3   Department of Orthopedic Surgery, Keio University School of Medicine, Shinjuku, Tokyo, Japan (Ringgold ID: RIN34787)
,
Kakeru Omae
4   Keio University School of Medicine, Tokyo, Japan (Ringgold ID: RIN34787)
,
Kazuhisa Sugai
1   Institute for Integrated Sports Medicine, Keio University School of Medicine, Tokyo, Japan (Ringgold ID: RIN34787)
,
Kyohei Daigo
2   Department of Cardiology, Keio University School of Medicine, Tokyo, Japan (Ringgold ID: RIN34787)
,
Yuji Iwasawa
2   Department of Cardiology, Keio University School of Medicine, Tokyo, Japan (Ringgold ID: RIN34787)
,
Genki Ichihara
2   Department of Cardiology, Keio University School of Medicine, Tokyo, Japan (Ringgold ID: RIN34787)
,
Hiroki Okawara
3   Department of Orthopedic Surgery, Keio University School of Medicine, Shinjuku, Tokyo, Japan (Ringgold ID: RIN34787)
,
Tomonori Sawada
3   Department of Orthopedic Surgery, Keio University School of Medicine, Shinjuku, Tokyo, Japan (Ringgold ID: RIN34787)
,
Akira Kinoda
1   Institute for Integrated Sports Medicine, Keio University School of Medicine, Tokyo, Japan (Ringgold ID: RIN34787)
,
Yuichi Yamada
1   Institute for Integrated Sports Medicine, Keio University School of Medicine, Tokyo, Japan (Ringgold ID: RIN34787)
,
Takeshi Kimura
1   Institute for Integrated Sports Medicine, Keio University School of Medicine, Tokyo, Japan (Ringgold ID: RIN34787)
,
Kazuki Sato
1   Institute for Integrated Sports Medicine, Keio University School of Medicine, Tokyo, Japan (Ringgold ID: RIN34787)
,
Yoshinori Katsumata
1   Institute for Integrated Sports Medicine, Keio University School of Medicine, Tokyo, Japan (Ringgold ID: RIN34787)
2   Department of Cardiology, Keio University School of Medicine, Tokyo, Japan (Ringgold ID: RIN34787)
› Author Affiliations
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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.

# Yuki Muramoto and Momoi Mizuki are co-first authors.


Supplementary Material



Publication History

Received: 14 March 2024

Accepted after revision: 12 November 2024

Article published online:
09 January 2025

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