This article will cover arguments, that carbonmonoxide inhalations might cause increased erythropoiesis, mitochondrial efficiency and mitochondrial density – speculatively also might be a performance enhancer explaining recent quantum jumps in perfomances in pro cycling.
Recently we have heard speculations on social media, that in pro cycling, carbon monoxide is the new perfomance enhancer, being used by Visma Lease a bike and UAE – while they of course deny that they use it for other than measurement of blood parameters, it might be a true new performance enhancer, although exposure to carbonmonoxide is not something new in terms of human evolution and history.
Carbon monoxide can be a severely toxic compound when inhaled in high doses, as it causes a direct inhibiton of cytochrome c oxidase in the electron transport chain, and thereby an inhibition of oxidative phosphorylation in the mitochondria.
https://pubmed.ncbi.nlm.nih.gov/12969439/
However, before the oxygen can even reach the mitochondria, it has to be transported through hemoglobin in the red blood cells. Hemoglobin has a 100 fold higher affinity for carbonmonoxide than oxygen, and too much inhaled carbonmonoxide can cause hemoglobin to be unable to bind oxygen, and thereby decrease oxygen delivery to the tissues, causing hypoxia and potentially death.
Modern cycling as always, is trying to move the bar for what is humanly possible, and this time they have alledgedly been using carbon monoxide inhalations as a new performance enhancer.
This years Tour de France that has just finished, has seen energy outputs the like of which the world has never seen before.
And it it potentially seems that the controlled use of a known potential toxin and also natural product of cellular function, might be one of the new methods of madness that has arrived in the pro peleton.
In a 2020 study, the effects on hemoglobin mass and vo2 max has been documented – coinciding with the huge leaps in performances in procycling since 2020
In this protocol, the use of carbonmonoxide inhalations 5 times a day, increased hemoglobin mass by 4.8 % and had corresponding increases in vo2 max compared to the placebo group.
https://pubmed.ncbi.nlm.nih.gov/32118696/
A 4.8 percent increase by doing no training and at sea level is a massive increase!
But theres probably more to than just increase in hemoglobin mass.
Cytochrome c oxidase/complex 4 efficiency
It seems Carbonmonoxide might also be interacting with mitochondrial enzymes making the oxidative phosphorylation more efficient – The increase in Carbonmonoxide causes an increase Hypoxia inducible factor 1(HIF-1) (which is also known to stimulate erythropoises)- HIF interacts with cytochrome c oxidase/complex 4 by somehow increasing the subunit efficiency, causing an overall increase in cytohrome c oxidase efficiency!
“Fukuda et al. have shown that activation of hypoxia-inducing factor-1 (HIF-1) was involved in the regulation of cytochrome coxidase subunits for optimizing the efficiency of mitochondrial respiration [24] and in macrophages CO-activated HIF-1 without increasing the rate of glycolysis [25]. Thus, one can speculate that CO improves COX activity by activation of HIF-1.”
https://onlinelibrary.wiley.com/doi/10.1155/2012/749845
This means that the electrons can more easily go through complex 4 and reduce oxygen to H2O, and not be “Stuck” at complex 4 causing an upstream increase in reduced electron carriers NADH and FADH2 – when there’s too much reduction in the redox balance, because of “stuck” electrons, it has to go to the emergency oxidizer which is pyruvate that can oxidize NADH to NAD+ which also creates lactate – this means that glycolysis has to be activated, which causes a dip in performance if it goes on for too long, creating lactic acidosis and a quick combustion of glycogen.
Mitochondrial biogenesis and an increase in mitochondrial density
It seems that carbonmonoxide not only increases efficiency of oxidative phosphorylation – it also increases the population of mitochondria.
Even short term exposures to Carbon monoxide Seems to activate mithondrial division, and thereby total number of mitochondria, which in the end makes it possible to produce more ATP that is used for muscle contraction and thereby converting biochemical energy to mechanical energy. as long as oxygen is present for the mitochondria to oxidise, a higher concentration of mitochondria, means higher energy output in the end.
This is well documented in studies on cells, but has also been documented to be true for human skeletal muscle.
In one study, it seems that 1 hour daily inhalation for 5 days of small amounts of carbonmonoxide, increases the amount mitochondrial DNA transcription, and interestingly, also causes an increase in cytochrome c oxidase subunits. This means that more mitochondrial enzymes are produced, and that mithochondrial density is increased.
“Using a daily regimen of 1 h of 100 ppm CO breathing for 5 days after a single V̇o2max test, we found increases in muscle mRNA for two key nuclear regulators of mitochondrial biogenesis, PGC-1α and NRF-1, as well as for Tfam and Polγ. Also, CO plus V̇o2max testing increased the muscle mitofusin and OPA-1 protein content coincident with COX-I and ATPase-6 protein expression; the latter is consistent with new mtDNA transcriptional and protein synthetic activity.”
It seems that mitochondrial density is an important determinant of vo2 max, especially at altitude and at submaximal efforts:
“Rodent studies indicate that mitochondrial density is an important determinant of V̇o2max (21, 28), and mitochondria may play a larger role in governing V̇o2max at altitude (9) or in sustaining submaximal exercise”
https://journals.physiology.org/doi/full/10.1152/ajpheart.00164.2009
But what about the biological passport you might ask?
This is where altitude training comes in. Altitude training above 1000 metres allows for bigger margins of fluctuations in the biological passports – and they might be using the altitude camps to both enhance the effects of CO breathing, and also conceal the fluctuations in blood values- using altitude as a plausible deniability for huge increases in performance and blood values. This is mostly speculation on my side, but it could easily be used as a cover.
Closing thoughts
Whatever has caused the quantum leaps in the recent years in terms of performance, might be partly explained by the use of Carbonmonoxide inhalations, but one thing I do not doubt, is that there are new methods or drugs on the market, that is right now pushing the limits of human physiology.
Seabridge Bioenergetics 
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