Adding argon to low-oxygen training air: effects on fitness and tolerance to low oxygen

ISRCTN	ISRCTN17346452
DOI	https://doi.org/10.1186/ISRCTN17346452
Sponsor	Research Institute of Geroprotective Technologies, Saint Petersburg, Russia
Funder	Investigator initiated and funded

Submission date: 18/07/2026
Registration date: 20/07/2026
Last edited: 20/07/2026

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Other

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Background and study aims
Hypoxic (low-oxygen) training is commonly used to improve endurance performance, but reducing oxygen levels further to increase the training stimulus often causes greater discomfort and strain, limiting how hard athletes can train. This study examined whether adding argon, an inert gas, to the training air could allow a deeper level of low-oxygen exposure without extra physical strain, and whether this approach produced greater improvements in aerobic fitness and tolerance to low oxygen compared with standard low-oxygen training.

Who can participate?
Healthy men aged 19–35 years, with a body mass index of 21–28 kg/m², who exercised recreationally but were not competitive athletes

What does the study involve?
Participants were allocated to one of four groups, each completing 15 training sessions (4 hours each) that combined 2 hours of stationary cycling with 2 hours of rest, while breathing one of four different air mixtures: standard reduced-oxygen air, more strongly reduced-oxygen air, reduced-oxygen air enriched with argon, or normal air (control group). Aerobic fitness and tolerance to low oxygen were measured before training, 3 days after, and 3 weeks after training ended.

What are the possible benefits and risks of participating?
Participants may have benefited from improved aerobic fitness as a result of the training programme. Risks included typical symptoms of exercise under reduced-oxygen conditions, such as breathlessness, dizziness, headache, or fatigue, which were closely monitored throughout each session by supervising staff.

Where is the study run from?
Training and testing were conducted at a specialized adaptation-training complex in Saint Petersburg, Russia.

When is the study starting and how long is it expected to run for?
August 2025 to December 2025

Who is funding the study?
Investigator initiated and funded

Who is the main contact?
Dr Arseny Kuzmin, ars6786@gmail.com

Contact information

Dr Arseny Kuzmin
Public, Scientific, Principal investigator

Bolshaya Dorogomilovskaya str., 5
Moscow
121059
Russian Federation

ORCID ID	0000-0003-4196-5100
Phone	+7 (0)9110233866
Email	ars6786@gmail.com; ars6786@mail.ru

Study information

Primary study design	Interventional
Allocation	Randomized controlled trial
Masking	Open (masking not used)
Control	Active
Assignment	Parallel
Purpose	To evaluate the effects of modifying inspired gas composition (argon-enriched normobaric hypoxia versus conventional normobaric hypoxia) during endurance training on the acute physiological cost of hypoxic exercise and on transfer effects to aerobic performance and hypoxic tolerance under normoxic conditions
Scientific title	Argon-enriched normobaric hypoxia enables deeper hypoxic exposure with comparable physiological cost and greater transfer effects
Study acronym	AENH-T
Study objectives	1. To determine whether argon-enriched normobaric hypoxia allows exposure to deeper hypoxia with comparable acute physiological cost (ventilatory and cardiovascular) compared with conventional normobaric hypoxia during endurance training. 2. To compare the transfer effects of argon-enriched versus conventional normobaric hypoxic training on aerobic threshold, assessed under normoxic conditions. 3. To compare the transfer effects of argon-enriched versus conventional normobaric hypoxic training on hypoxic tolerance (Stange breath-hold test), assessed under normoxic conditions. 4. To assess the tolerability and feasibility of conventional normobaric hypoxia, deeper conventional hypoxia, and argon-enriched normobaric hypoxia across a 15-session training protocol.
Ethics approval(s)	Approved 19/06/2025, Ethics Committee of I.M. Sechenov First Moscow State Medical University (Sechenov University) (Trubetskaya str., 8, Moscow, 119991, Russian Federation; +7 (0)4956229706; iec@staff.sechenov.ru), ref: No. 14–25
Health condition(s) or problem(s) studied	Physiological adaptation to hypoxic endurance training in physically active but non-competitive men
Intervention	Participants are stratified by age, baseline functional capacity, anthropometric characteristics, and tolerance to hypoxic exposure, then allocated to one of four parallel groups using stratified randomization. Group I (n = 14, conventional normobaric hypoxia): Participants complete 15 training sessions in which the fraction of inspired oxygen (FiO₂) is progressively reduced from 19% to 16–17% over the initial sessions and then maintained at 16–17% for the remainder of the protocol. Group II (n = 14, deeper conventional normobaric hypoxia): Participants undergo the same protocol as Group I, but FiO₂ is further reduced to 14-15%. Group III (n = 16, argon-enriched normobaric hypoxia): Participants are exposed to a fixed gas composition of 13-14% O₂ enriched with 33–35% argon throughout all 15 sessions. Group IV (n = 14, normoxic control): Participants complete identical training under normoxic conditions (FiO₂ = 20.9%), without hypoxic exposure. Each of the 15 training sessions lasts 4 hours and consists of 120 minutes of continuous cycling at 50-75% of maximal oxygen uptake (V̇O₂max), performed in the assigned gas environment, followed by 120 minutes of passive exposure while remaining in that gas environment. Exercise intensity is individually prescribed based on baseline V̇O₂max testing and adjusted as needed to maintain the target intensity range. Gas mixtures are prepared using medical-grade gases (O₂, N₂, Ar) and continuously monitored for O₂ concentration, CO₂ level, and pressure throughout each session. Participants and investigators are not blinded to group assignment, as differing levels of inspired oxygen fraction across groups produce perceptible physiological symptoms of hypoxia (e.g., dyspnea, altered breathing effort) that cannot be masked, even though the gas delivery apparatus and chamber environment are standardized across groups.
Intervention type	Other
Primary outcome measure(s)	Aerobic threshold measured using power output (W) during an incremental cycling test with stepwise increases starting at 50 W (25 W increments per stage), determined using combined ventilatory criteria (first disproportionate increase in V̇E/V̇O₂ without concomitant rise in V̇E/V̇CO₂, and changes in respiratory exchange ratio), assessed on an electronically braked cycle ergometer with breath-by-breath metabolic system (SCHILLER CARDIOVIT CS-200) at baseline (3 days before intervention), 3 days post-intervention and 3 weeks post-intervention
Key secondary outcome measure(s)	Hypoxic tolerance measured using breath-hold duration (s) during the Stange test (maximal breath hold at end-inspiration, seated position) at baseline (3 days before intervention), 3 days post-intervention and 3 weeks post-intervention Ventilatory equivalent for oxygen measured using change in V̇E/V̇O₂ during standardized normobaric hypoxic exposure, assessed via breath-by-breath metabolic system (SCHILLER CARDIOVIT CS-200) at averaged across training sessions 1-15 Peripheral oxygen saturation measured using change in SpO₂ (%) during standardized normobaric hypoxic exposure, measured by pulse oximetry (MARG Microlux) at averaged across training sessions 1-15 Oxygen uptake measured using change in V̇O₂ (L·min⁻¹) during standardized normobaric hypoxic exposure, assessed via breath-by-breath metabolic system (SCHILLER CARDIOVIT CS-200) at averaged across training sessions 1-15 Cardiovascular cost during hypoxic exercise measured using change in heart rate (ΔHR, bpm) relative to normoxic resting values, recorded via wireless monitoring system (Polar) at training phases 1-5, 6-10, and 11-15 Tolerability measured using session completion rate, protocol modifications, and subjective symptom severity ratings; psychological well-being assessed using the SAN (Well-being-Activity-Mood) questionnaire at throughout the 15-session intervention
Completion date	22/12/2025

Eligibility

Participant type(s)
Age group	Adult
Lower age limit	19 Years
Upper age limit	35 Years
Sex	Male
Target sample size at registration	58
Total final enrolment	58
Key inclusion criteria	1. Healthy men aged 19–35 years 2. Body mass index (BMI) 21–28 kg/m² 3. Physically active but not competitive athletes, regularly engaged in recreational exercise (e.g., running, fitness training, swimming) 4. Written informed consent 5. Ability to maintain habitual physical activity throughout the study 6. Absence of cardiovascular, respiratory, metabolic, neurological, or psychiatric disease
Key exclusion criteria	Any condition that could compromise safety, adherence, or physiological responses to hypoxia or exercise
Date of first enrolment	01/08/2025
Date of final enrolment	02/09/2025

Locations

Countries of recruitment

Russian Federation

Study participating centres

Results and Publications

Individual participant data (IPD) Intention to share	No

Editorial Notes

20/07/2026: Study's existence confirmed by the Ethics Committee of I.M. Sechenov First Moscow State Medical University (Sechenov University).