Low-dose carbon monoxide inhalation to increase total hemoglobin mass and endurance performance: scientific evidence and implications

TL;DR

This perspective reviews evidence that chronic intermittent low-dose carbon monoxide (CO) inhalation may increase total hemoglobin mass and potentially endurance performance, but findings are mixed and safety and anti-doping concerns remain. WADA could consider non-diagnostic CO inhalation a prohibited method under “M1. Manipulation of Blood and Blood Components.”

Key findings

• Anti-doping: CO inhalation to increase red blood cell mass and performance could already be prohibited at all times under WADA “M1. Manipulation of Blood and Blood Components”; this would not apply to diagnostic CO use such as tHb-mass or lung diffusion capacity measurement.
• Efficacy evidence is mixed: acute low-dose CO reduces oxygen-carrying capacity and VO2max transiently, with CO typically cleared within 12 h; 12-day single daily CO inhalation (1.2 mL/kg body weight) did not significantly affect tHb-mass, VO2max, lactate threshold, economy, or peak power in moderately trained men (VO2max 49 mL/min/kg) (Ryan et al., 2016). Wang et al. reported a 3.7% tHb-mass increase in trained soccer players (VO2max 58 mL/min/kg) with CO bolus (1 mL/kg body mass) five times/week before treadmill training, but the control group also increased 2.8%.
• Schmidt et al. (2020) found chronic intermittent low-dose CO targeting about 5% COHb over 3 weeks increased tHb-mass by 4.8%; EPO tended to increase after 1 week, as did reticulocytes and immature reticulocyte fraction, and EPO was suppressed after CO ceased; VO2max was not significantly increased, though a relationship of approximately 4 mL/min VO2max increase per 1 g tHb-mass increase was reported. Urianstad et al. (2024) found twice-daily CO inhalation (increasing CO levels to ∼10%) added to live-high/train-high (3 weeks at 2,100 m) induced larger tHb-mass increases than LHTH without CO in male cyclists (VO2max >70 mL/min/kg), but performance improvements were similar between LHTH groups with and without CO.
• Safety: clinical trials have concluded COHb up to 6.4% can be considered safe; CO-rebreathing for tHb-mass determination has reported COHb up to 10%; regular smokers have COHb around 3–8% and heavy smokers may exceed 20%; mild symptoms may occur at COHb >10% and severe symptoms at >20–25%; no safe upper limit for continuous intermittent CO use can currently be established due to limited long-term studies.

Methods

• Perspective article; no primary data are presented. It narratively synthesizes existing literature on low-dose CO inhalation, total hemoglobin mass, endurance performance, health concerns, and anti-doping interpretation.
• Discusses studies with participants ranging from recreationally active to highly trained, including reported VO2max values of 49, 56, 58, and >70 mL/min/kg.
• Main analysis is qualitative: comparison of study results, methodological issues, safety considerations, and WADA prohibited-list interpretation; no systematic review or meta-analysis is described.

Limitations

• Stated: the limited number of studies, participants of varying fitness levels, and inconsistent results do not allow a definitive conclusion. Methodological issues are noted, e.g., Wang et al. (2019) lacked statistical indicators such as main- and interaction effects.
• Stated: it is not possible to establish a safe upper limit for continuous intermittent CO use due to limited long-term studies; there is also scientific debate about whether tHb-mass increases and sea-level endurance performance improves after altitude training in elite athletes.
• Evident: as a perspective/narrative review, it provides no new experimental data, no systematic search strategy, and no formal risk-benefit quantification; efficacy in elite athletes is not proven.