Hypoxia and EPO production.

Hard to know without some way to check 02 levels in the core. I assume the upper graph is heart rate. If so, it looks like your DR is kicking in reasonably strong. That will limit blood flow to the arms and mean that the 02 level in the core is higher than your finger measurement. How much is anybody's guess.

It might be easier to test EPO levels after lot of similar 02 tables.

So basically you are asking whether and how you can optimize your training strategy to increase the amount of red blood cells. Like usual, interesting question Xristos . Here is my take on it:

First, the following needs to be taken into consideration:
- To assess changes in oxygen carrying capacity of the blood, total hemoglobin mass (Hbmass) should be measured (most common method involves a CO-rebreathing procedure). This way, you accurately estimate the absolute amount of circulating hemoglobin (gram or gram/kg body weight).
- Venous blood draws to analyze changes in hematocrit tell you something about the relative concentration of Hb in the blood, which is subject to many cofounding factors (i.e., hydration status, body position, etc.) and does not give you a proper indication of the total oxygen carrying capacity of the blood.
- Measurements shortly after exercise or breath holds need to be interpreted against the light of transient increases in circulating Hb due to spleen contractions.

Second, there are various methods to lower oxygen saturation and therefore elicit an EPO response.
- Traditional breath holding: during statics and dynamics.
- Voluntary hypoventilation: Typically performed during exercise (either in or outside the water). Just decrease the amount of ventilation by for instance doing brief holds at FRC (a few seconds or number of steps while running), followed by exhalation to RV and spontaneous inhalation and repeat this cycle. Note that this can give you quite a headache though if you do this too long at the time... If you implement this in your normal running routine, I suggest that you build in several blocks of this breathing method into your training sessions and alternate it with periods of normal breathing to get rid of the excess CO2. I think some pranayama techniques at rest (don't ask me the name of it) in which you continuously breath at very low minute ventilation and very low breathing frequencies may likewise result in increased PaCO2 and lowered PaO2 – whilst concurrently working on your relaxation (because of the relaxation aspect I like this latter method a lot). I have not yet measured SpO2 during such exercise yet...
- Intermittent hypoxic training by breathing air with lower O2 concentrations (normobaric altitude room or 'hypoxic' masks). Typically performed several times a week whilst training at high intensity, with repeated sprint training showing the most promising results for dry land repeated sprint performance.
- Longer term stay at altitude. Note that in contrast to the above methods, due to a normal and healthy breathing reflex called hypoxic ventilatory response, arterial CO2 levels will be decreased rather than increased for prolonged period of time.

Before this post is getting too long: this is what I wanted to say:
All the above mentioned methods with exception of long-term (>2 weeks) stay at altitude (>2200 m) for ~10-12 hours per day will not increase your Hbmass – they may serve other purposes (!), but that’s another topic.
Yes, they will transiently increase EPO concentrations proportionally to the hypoxic stimulus given by your selected training method, but transient increases in EPO concentrations by doing let’s say 3 of 4 of these training sessions a week are unfortunately not adequate to increase Hbmass. Is that because the total time of elevated serum EPO concentrations is too short, or because EPO concentrations after a period of hypoxic exposure tend to fall below baseline once breathing normal air again (this signals the destruction of young red blood cells), or a combination of those two, I am not sure.

So yes you can use your SpO2 meter to measure the hypoxic stimulus you provide by a given exercise, but don’t expect this to increase your total hemoglobin mass.

Cheers,
SDS

Baseline total blood volume and Hbmass is mostly determined by genetics indeed, and they correlate very well with aerobic exercise performance.
I would like to see data on the association between Hbmass and breath hold performance. Sounds reasonable to me to expect a small correlation provided that Hbmass forms a small oxygen reservoir. That being said, I still struggle to understand the underlying mechanism for the reason why elite freedivers are switching to max performance attempts without warming up dives enabling oxygenation of newly available Hb in the circulation (spleen contraction).

Exercise training increases blood volume primarily by expansion in plasma volume. Current opinion is that exercise is likely to increase Hbmass as well, but to a much smaller extent. Note that athletes may suffer true anemia due to various factors indeed, but in quite a few cases they actually still have high Hbmass but low hematocrit levels due to plasma volume expansion (dilutional pseudoanemia).

It is interesting that elite freedivers do report hematological adaptations. I wonder whether this is due to the amount of time spent in the water and thus the repetitive and accumulated hypoxic dose (way more than the hypoxic dose provided by occasional dry land breathing exercises)?

No warm up dives increase the strength of dive response. That's the point. Dive response (for the day at least) gets blunted with repeated triggering.

EPO production is increased under various forms of diminished oxygen supply such as anemic or hypoxic hypoxia. In the adult organism, the kidneys are the major source of EPO. The precise nature of the cells responsible for renal EPO production, however, has not yet been elucidated. Most likely, peritubular cortical cells, e.g. interstitial or endothelial cells, are involved in the elaboration of the hormone. From the observation that isolated perfused rat kidneys produce EPO in an oxygen-dependent fashion we conclude that the ‘oxygen sensor’ that controls hypoxia-induced EPO synthesis is located in the kidney itself.

growingupninja said:

No warm up dives increase the strength of dive response. That's the point. Dive response (for the day at least) gets blunted with repeated triggering.

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Thanks for your insights - I didn't know that!
I falsely assumed that spleen volume would further decrease (and thus further increase circulating Hbmass) with consecutive dives. That doesn't seem the case (image reproduced from Baković and colleagues, J Appl Physiol 2003):

digixpjaipur said:

EPO production is increased under various forms of diminished oxygen supply such as anemic or hypoxic hypoxia. In the adult organism, the kidneys are the major source of EPO. The precise nature of the cells responsible for renal EPO production, however, has not yet been elucidated. Most likely, peritubular cortical cells, e.g. interstitial or endothelial cells, are involved in the elaboration of the hormone. From the observation that isolated perfused rat kidneys produce EPO in an oxygen-dependent fashion we conclude that the ‘oxygen sensor’ that controls hypoxia-induced EPO synthesis is located in the kidney itself.

Index of /

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Though maybe going a bit too much off topic, I believe that we have a relatively good understanding of the molecular pathway of EPO production. Very brief, transcription factor 'hypoxia-inducible factor' (HIF) HIF-2a controls both the number and expression levels (thus EPO producing activity) of renal (and hepatic) EPO-producing cells. If interested, check out the scientific work of Jelkmann (i.e., J Phyiosol 2011), Wenger et al (Am. J. Physiol. Renal Physiol 2010), and Haase (Blood Rev 2013) to name a few.

xristos said:

Campenaerts takes altitude training to further extremes

Belgian spending an hour a day at 10,000 metres

www.cyclingnews.com

At 10.000m it is estimated SaO2 would drop to 40% maybe Victor body can stay at 50-60%? Doing 1 hour of that sounds extreme but maybe is the correct dose of stimulus?

Or is it a media stunt to bait some of the competition to serious overtraining?

I am curious what the Rate of Perceived exertion (RPE) is of hypoxic mask versus the classic O2 table to accumulate 1 hour below given SaO2. I am keen to try but I am not too optimistic of it being repeatable.

What do you think?

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It is an ongoing hypothesis that the precious gains in Hbmass made after a period of ‘living high’ could be better maintained by use of intermittent hypoxic exposure. To my knowledge, however, this has not yet been experimentally tested or confirmed (though I am not up to date with this type of research since more than a year). Till now, intermittent hypoxic exposure at moderate to high simulated altitudes has never yielded satisfying benefits on the blood profile. But I have never known anyone exposing themselves to such extreme simulated altitude levels. Must elicit a big EPO response indeed, but wondering what happens in the immediate period after the initial EPO response. I wouldn’t be surprised to see a drop below baseline (signaling for destruction of young red blood cells).

Bit surprised that this is in fact even feasible, would have expected him to become ill quite fast (varying symptoms of high altitude sickness), if not even risk a black out. He probably has an excellent hypoxic ventilatory response (read: he will be spontaneously hyperventilating), due to genetics and previous hypoxic exposure. That will enable him to maintain relatively high SpO2 values compared to more mortal individuals like us .

It is so much harder to reduce SpO2 by voluntary hypoventilation compared to hypoxic exposure using an altitude tent/mask. No comparison. Don’t forget that these are two distinct environments and physiological stresses. With hypoventilation comes hypercapnia (and contractions). Breathing hypoxic air will come with hypocapnia hence without a single involuntary contraction of the diaphragm or other breathing muscles.

EPO response has been experimentally shown to be much greater when muscles are under load and working.

A long time ago at least one former world champion I know of slept in a hypoxic tent, but her coach has told me they wouldn't do it that way again. Besides inconvenience they decided it was unnecessary given her other training.

growingupninja said:

EPO response has been experimentally shown to be much greater when muscles are under load and working.

A long time ago at least one former world champion I know of slept in a hypoxic tent, but her coach has told me they wouldn't do it that way again. Besides inconvenience they decided it was unnecessary given her other training.

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Interesting! I imagine that living near the sea enables you to conveniently provide the required stimulus for maximal training adaptations (in particular enhanced dive reflex)? Thus making an additional hypoxic stressor with hypoxic tents redundant? I believe the idea of periodisation with dryland hypoxic strategies should nonetheless not yet be dismissed.

It is not only red blood cell expansion which should be focused on, spleen volume and contraction are also influenced by hypoxic exposure. In fact, all parameters of the mammalian dive reflex may be subject to training, environment, and genetics (though should still be investigated). Take a look at this recent study from Shagatay’s group: https://www.frontiersin.org/articles/10.3389/fphys.2020.00647/full. Experimental data in Sherpas living high (>2500 m + climbing expeditions), Sherpas living low (migrated to Kathmandu at ~1370 m for at least 2 years), and Nepalese lowlanders (born and permanently residing in Kathmandu) indicate that:
1. Genetic components contribute to baseline spleen volume. Spleen volume at rest was higher in Sherpas compared to Nepalese lowlanders. Also remember that study that showed that the Bajau sea nomads, who have a spearfishing tradition for thousands of years, have a genetic variant which codes for greater spleen volume (Ilardo et al. Cell 2018).
2. Also environmental components contribute to baseline spleen volume. Spleen volume at rest was higher in Sherpas living high compared to Sherpas living low. Apnea-induced spleen contractions were greater in both Sherpa groups compared to Nepalese lowlanders, though it did not differ between Sherpas living high versus low. This indicates a genetic contribution. However, studies from the same research group have previously demonstrated that apnea-induced spleen contraction may be enhanced following high-altitude climbing expeditions (Engan et al. HAMB 2019). Data from another recent study in 13 Belgian lowlanders showed 8 weeks of static training to increase spleen volume (Bouten et al. Resp Physiol Neurobi 2019). Environment and training thus seem potent to enhance spleen volume and apnea-induced spleen contraction.


Figure reproduced from Holmström et al. Front Physiol 2020.