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Low-dose carbon monoxide inhalation to increase total hemoglobin mass and endurance performance: scientific evidence and implications
Open accessAbstract
Recently, chronic intermittent inhalation of low-dose carbon monoxide (CO) has been postulated as a practice to increase total hemoglobin mass with potential beneficial effects on endurance performance. In this perspective article, we discuss the potential performance enhancing capabilities as well as the safety concerns, which include individual variability in CO response, and acute and chronic health effects. It is also important to note that according to the World-Anti-Doping-Agency (WADA), CO inhalation could fall under “M1. Manipulation of Blood and Blood Components“ and therefore could be considered a prohibited method if used as a non-diagnostic tool.
Overview
CoChat Summary
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.
Model-written summary. Check it against the paper before relying on it.
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Claims the paper makes
0 Valid · 0 Not valid · 34 Not checked · 3 Own results and interpretations
In the paper
“While high doses of CO are undeniably lethal (Smollin and Olson, 2010), the safety of low-dose exposure remains a subject of debate.”
§ Low-dose carbon monoxide inhalation to increase total hemoglobin mass and endurance performance: scientific evidence and implications > 4 Potential health concerns and other considerations
What the sources say
- Not checked yetcites Schmidt et al., 2020 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Studies investigating the effects of low-dose CO on tHb-mass and exercise performance have yielded mixed results.”
§ Low-dose carbon monoxide inhalation to increase total hemoglobin mass and endurance performance: scientific evidence and implications > 3 Effects of low-dose CO inhalation on total hemoglobin mass and exercise performance
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Single measurements seem not to influence performance (Ryan et al., 2016).”
§ Low-dose carbon monoxide inhalation to increase total hemoglobin mass and endurance performance: scientific evidence and implications > 5 Conclusion
What the sources say
- Not checked yetcites Ryan et al., 2016 source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Pecorella et al. (2015) reported no improvement in single-leg VO2max after CO inhalation (1 h/day for 5 days, 200 ppm) in healthy subjects, although increases in muscle mitochondrial density, myoglobin content and glucose transporter (GLUT 4) were found (Pecorella et al., 2015).”
§ Low-dose carbon monoxide inhalation to increase total hemoglobin mass and endurance performance: scientific evidence and implications > 3 Effects of low-dose CO inhalation on total hemoglobin mass and exercise performance
What the sources say
- Not checked yetcites Pecorella et al., 2015 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Acute low-dose CO administration has been shown to reduce oxygen-carrying capacity and decrease maximal oxygen uptake (VO2max) as CO occupies O2 binding sites on Hb and prevents Hb from fulfilling its role in oxygen transport (Schmidt and Prommer, 2005; Klausen et al., 1983).”
§ Low-dose carbon monoxide inhalation to increase total hemoglobin mass and endurance performance: scientific evidence and implications > 3 Effects of low-dose CO inhalation on total hemoglobin mass and exercise performance
What the sources say
boostedstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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Citations
Cites
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Variability in hemoglobin mass response to altitude training camps
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Hypoxic Training Is Not Beneficial in Elite Athletes
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Cited by
Compelling Evidence: A Critical Update on the Therapeutic Potential of Carbon Monoxide
Bauer, N., Mao, Q., Vashistha, A., Seshadri, A. J., Du, Y. N., Otterbein, L. E., Tan, C., de Caestecker, M. P., & Wang, B. (2025) · Medicinal Research Reviews · doi:10.1002/med.22116 · Cited by 33
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How reducing oxygen-transport may lower the risk of developing Parkinson’s disease
Burtscher, J., Debertin, D., Kopp, M., Burtscher, M., Djamshidian, A., & Federolf, P. (2025) · npj Parkinson s Disease · doi:10.1038/s41531-025-00929-w · Cited by 3
Woyke, S., Oberacher, H., Plunser, D., Siebenmann, C., Turner, R., Regli, I. B., Schlittler, M., Strapazzon, G., Brugger, H., Ströhle, M., et al. (2025) · European Journal of Applied Physiology · doi:10.1007/s00421-025-05806-1 · Cited by 3
Self-citationLiu, D., Mao, Q., Yang, X., Bauer, N., Challa, S., & Wang, B. (2025) · Medicinal Chemistry Research · doi:10.1007/s00044-025-03405-5 · Cited by 2
Metadata
- Authors
- Gatterer, H., Dünnwald, T., Woyke, S., Faulhaber, M., Schumacher, Y. O., & Schobersberger, W.
- Affiliations
- Eurac Research (IT)
- UMIT TIROL - Private University for Health Sciences and Health Technology (AT)
- Innsbruck Medical University (AT)
- Universität Innsbruck (AT)
- Qatar Orthopaedic and Sports Medicine Hospital (QA)
- Corresponding author
- Schobersberger, Wolfgang
- ORCID
- Venue
- Frontiers in Physiology
- Publisher
- Frontiers Media SA
- Published
- 2024-10-15
- Volume
- 15
- Pages
- 1490205-1490205
- ISSN
- 1664-042X (ISSN-L)
- PMC
- PMC11519625
- OpenAlex
- W4403434268
- Semantic Scholar
- 4ee8cee6597bb1a72d58ec7396af6ce939543b61
- Cited by
- 13
- References
- 32
- Citations by year
- 2026: 8 · 2025: 5
- FWCI
- 1.41
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Physiology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Open Research (University of Surrey) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heme Oxygenase-1 and Carbon Monoxide
- Health Sciences › Medicine › Physiology (medical) › Cardiovascular and exercise physiology
- Health Sciences › Medicine › Physiology (medical) › Exercise and Physiological Responses
- Keywords
- carbon monoxide inhalation, total hemoglobin mass, endurance performance, blood doping, anti-doping regulations
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