#101

Here’s what the “experts” think @John_Hemming: Risks of perturbed oxygen homeostasis: responses and adaptations to hyperoxia and hypoxia 2025

The possibility of hyperoxia blunting hypoxic adaptations also raises questions regarding intermittent hypoxia‒hyperoxia conditioning. This method has recently been suggested to be superior to hypoxia conditioning by itself,5 but the molecular and functional/clinical outcomes have not been sufficiently investigated in appropriate (placebo-controlled) trials. In general, the dose of applied hyperoxia most likely determines its risk. While the moderate hyperoxia (often 30–34% oxygen, for a few minutes between several bouts of moderate hypoxia) used in intermittent hypoxia‒hyperoxia conditioning likely does not interfere with hypoxia adaptations (although this remains to be experimentally confirmed), 80–100% oxygen – especially if administered repeatedly for more than 10–15 minutes or continuously for several hours or longer – probably does.

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#102

The difficulty with this is that there are a large number of variables and a number of different mechanisms.

#103

Hypoxia is reaching the mainstream, Eric Topol has just tweeted that article:

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Tweet: x.com

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#104

Practical questions:

  1. Which model of oxygen concentrator are you using?

  2. Are you doing it with manual switching, between hyperoxic level (i expect with a mask) to normoxia level (removing the mask or just shitting down) ?

  3. I am trying to look forward oxygen concentrator for night/sleep protocol implementation, looking for a computer programmable one. Did you ever encountered during your analys for oxygen concentrators hardware? I’d like to control from a computer or smartphone, so that while sleeping could have the oxygen fluctuation being done in a software-controlled way, by further controlling the flow checking SpO2 from the Garmin watch (or ouraring sensor) .

Fabio

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#105

Not necessary for the purposes of oxygen. (I know it is a typo)

I am using a Hacenor POC-05 and I just switch it off. I basically do it once in the morning.

I am not quite sure what I would suggest for overnight. I think HIF needs some time to get going hence continually alternating may not be that much good.

Also there are sound issues which would need to be sorted out to make sure it does not disrupt sleep.

#106

I’ve just booked 3 sessions of hypoxia therapy. I’m planning to do the following protocol:

  • 5 min hypoxia followed by 5 min normoxia (no hyperoxia)
  • 4 cycles
  • Session every other day
  • Starting from 16% FiO2 decreasing by 0.5 at each session if feeling OK.
  • Never going below SpO2 80%

If that does well I’ll do more sessions until I reach 12 to 13% FiO2.

Feedback welcome!

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#107

I would be cautious about taking SpO2 down that low, but it depends for how long.

Otherwise it is a question as to how to test any outcomes. It may be worth doing bloodwork immediately at the start (before starting) and immediately at the end (possibly on the last day).

I would use Randox for this as they do the broadest panel at a reasonable price. (their basic panel 2 for GBP 375 I think at the moment).

#108

Yes I might set a higher SpO2 threshold (82-84%) at least for the first session.

I’ll review the literature today to see what’s best. I’ll post it here.

Yes, hard to measure the outcomes…

#109

My concern about brain damage is that
a) It is a big potential problem
b) It may be hard to spot if marginal, but I would wish to avoid marginal damage
c) There are questions at times about how reversable it is.

Hence whereas I don’t mind trying out lots of things reducing the oxygen supply to the brain is something I am cautious about.

Most of the side effects of rapamycin, for example, are reversed by simply not taking it.

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#110

This has long interested me.

Im at 90% spo2 for 3 minutes everyday. I’m guessing the risk at 90% spo2 is zero and the benefits are questionable. But I have noticed that my brain will not let me go lower than 90% for more than a few seconds via shallow breathing….my brain makes the feeling so terrible that I don’t want to do it.

I don’t know if the sense is for a build up of co2 (probably) or too low o2…

The “advantage” of a hypoxia room or low O2 mask over shallow breathing is you can blow off co2 while still keeping the o2 low. But maybe that’s where the risk lies….the hypoxic room is outside of nature. The body’s defenses are undone. So the science better be right.

#111

I am not certain but it may be more excess co2

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#112

I checked the recent papers on hypoxia. Here are some interesting ones:

Is hypercania needed?

Hypercapnic hypoxia as a potential means to extend life expectancy and improve physiological activity in mice 2019

regular hypercapnic-hypoxic exercises (PO2—90 mm Hg and PCO2—50 mm Hg)
Results suggest that with regular training, life span is extended significantly by 16%. This result was accompanied by improved reproductive and cognitive functions, increased motor and search activities, and physical stamina in old age mices.

Is sustained hypercapnia required to initiate plasticity in humans exposed to mild intermittent hypoxia? 2024

Combined therapeutic acute intermittent hypercapnic hypoxia and exercise-based respiratory training improve breathing after chronic cervical spinal cord injury 2024

We focus on a refined tAIH protocol that combines hypoxia with hypercapnia during each episode (therapeutic acute intermittent hypercapnic hypoxia; or tAIHH), since preliminary data suggests that tAIHH is a more potent stimulus to respiratory motor plasticity vs. tAIH alone.

Hypoxia and neurogenesis

New Insights into the Role of Mild Hypoxia in Regulating Neural Stem Cell Characteristics 2024

Hypoxia is characteristic of the niches of NSCs. As inhaled air enters the lungs and spreads throughout the body, the oxygen concentration gradually decreases. Therefore, physiological normoxia is regarded as hypoxia. In the central nervous system of mammals, the physiological concentrations of oxygen range from as low as 0.55% in the midbrain to 8% in the leptomeninges. In particular, in the subventricular zone niche, the oxygen concentration ranges from 2.5% to 3%.
As a result, the oxygen concentration in the brain is much lower than that in air. These data convincingly show that hypoxia is a normal physiological state.
Zhu et al. found that hypoxia promoted the proliferation of NSCs in an in vivo experiment. The rats were subjected to low pressure and low oxygen at simulated altitudes of 3,000 m or 5,000 m for 4 h/day for 2 weeks. The experimental results showed that, compared with those in the control group, the numbers of BrdU-positive cells in the inferior gyrus of the lateral ventricle and in the dentate gyrus of the hippocampus in rats increased by 62% and 35%, respectively, indicating that intermittent hypoxia promoted the in situ proliferation of NSCs.
Zhu et al. developed a depression model in rats by subjecting them to chronic stress. Preconditioning rats with low-pressure hypoxia at altitudes of 3,000 m and 5,000 m for 4 h/day for 14 days showed that intermittent low-pressure hypoxia had a marked antidepressant effect.

Hypoxia and cognition

Safety and effectiveness of acute intermittent hypoxia during a single treatment at different hypoxic severities 2025

Thirteen human participants performed 30-min of AIH in 60-s intervals at FiO2’s of 0.21 (AIH21), 0.15 (AIH15), and 0.09 (AIH9).
Heart rate variability (root mean squared of successive differences; RMSSD), heart rate, oxygen saturation (SpO2), blood pressure, muscular strength, neuromuscular activation, cerebral hemodynamic responses, cognition, symptomology, and brain-derived neurotrophic factor (BDNF) responses were measured before (Pre-AIH), after (post-AIH), and at 20-min of recovery (Recovery-AIH)
AIH does not impact cognition or cerebral perfusion rates.
Both AIH15 and AIH9 increased BDNF Post-AIH (62 %) and Recovery-AIH (63 %)

Acute Intermittent Hypoxia Induces Motor and Cognitive Plasticity in Persons with Relapsing Remitting Multiple Sclerosis 2024

AIH consisted of 15 brief exposures of low oxygen (9% O2) alternating with normoxia (i.e., room air). Sham AIH comprised of normoxic episodes.”
Participants showed a significant increase in both plantarflexion and dorsiflexion ankle torque (p < .05), alongside significant enhancements in cognitive processing speeds as measured by the Symbol Digit Modalities Test (p < .01) after AIH. No changes were observed in auditory/verbal memory, and no adverse events were reported.”
AIH presents a promising intervention for inducing neuroplasticity and improving rehabilitation outcomes in MS, suggesting the need for further exploration into its long-term impacts and mechanisms.
One of the intriguing findings in our study was the marked improvement in cognitive processing following AIH treatment, as indicated by the notable increase in SDMT scores. The increase of 10.1 points from pre to post-AIH SDMT scores is significantly higher than the clinically meaningful threshold of 4 points. The relationship between AIH and BDNF expression could offer a potential explanation for this finding. Animal studies suggest that AIH upregulates BDNF protein levels in the CNS and facilitates BDNF-dependent signaling cascades. Considering that epigenetic-mediated changes in BDNF gene expression impact cognitive processing also, the increase in BDNF levels induced by AIH could be responsible for the cognitive improvements we observed. Additional larger studies are warranted to confirm this hypothesis.

(poke @John_Hemming, that’s reassuring, even at 9%!)

Intermittent hypoxia training improves cerebral blood flow without cognitive impairment 2024

short-term IH protocol (13% hypoxia interspersed by normoxia for 5 min, 4 cycles per session, twice a day for 5 days)
Although the absolute differences in CBF observed in our study are modest, their clinical relevance should be considered within the context of specific disease states. For instance, in ischemic stroke, even a small increase in CBF can significantly impact patient outcomes. Similarly, in conditions characterized by chronic cerebral hypoperfusion, such as vascular dementia and Alzheimer’s disease, slight improvements in CBF have been associated with enhanced cognitive performance and may contribute to slowing the progression of cognitive decline.

Intermittent hypoxia training effectively protects against cognitive decline caused by acute hypoxia exposure 2023

Second, we found that IHT improved participants’ cognitive and neural alterations when they were exposed to hypoxia. Specifically, impaired working memory performance, decreased conflict control function, impaired cognitive control, and aggravated mental fatigue induced by acute hypoxia exposure were significantly alleviated in the IHT group. Furthermore, a reversal of brain swelling induced by acute hypoxia exposure was visualized in the IHT group using magnetic resonance imaging. An increase in cerebral blood flow (CBF) was observed in multiple brain regions of the IHT group after hypoxia exposure as compared with the control group.

Post-stroke recovery

Acute Intermittent Hypoxia With High-Intensity Gait Training in Chronic Stroke: A Phase II Randomized Crossover Trial 2024

Participants received up to 15 sessions of AIH for 30 minutes using 15 cycles of hypoxia (60–90 seconds; 8%–9% O2) and normoxia (30–60 seconds; 21% O2), followed by 1 hour of HIT targeting >75% heart rate reserve.
revealing greater gains in self-selected speeds (0.14 [0.08–0.18] versus 0.05 [0.01–0.10] m/s), fastest speed (0.16 [0.10–0.21] versus 0.06 [0.02–0.10] m/s), and peak treadmill speed (0.21 [0.14–0.29] versus 0.11 [0.06–0.16] m/s) following AIH+HIT versus normoxia+HIT (P<0.01) with no order effects. Greater gains in spatiotemporal symmetry were observed with AIH+HIT

Lasting effect of hypoxia therapy

Repeated Exposure to Mild Intermittent Hypoxia Improves Walking Endurance in OSA Patients for 4 - 8 Weeks Post Therapy 2024

Previously, we reported that daily exposure to mild intermittent hypoxia (MIH) reduces blood pressure following 3 weeks of treatment. These reductions in pressure could be coupled with improvements in microvascular function, fatigability and exercise performance.
both males and females with severe OSA and hypertension were randomly assigned to receive an MIH intervention (n=9) or Sham MIH (n=10)”
The MIH protocol consisted of twelve 2-minute hypoxic episodes (PETO2 ~ 50 mmHg), interchanged with 2 minutes of normoxia administered each day for 15 days. PETCO2 was sustained 2 mmHg above baseline throughout the protocol.”
following therapy, the MIH group was able to walk further (p = 0.005), faster (p = 0.005), and were less fatigued (p = 0.009). These improvements were maintained for up to 8 weeks following treatment with MIH but not sham MIH”

Hypoxia and insulin sensitivity

Mechanistic Effects of Intermittent Hypoxia (IH) on ß-Cells, Glucose Homeostasis, and Predisposition to Type 2 Diabetes (T2D) 2024

The fractional inspired O2 between 21% and 5% in 30 second intervals (~ 60 episodes/hr), for 12hrs/day for 7, 14, and 28-days in C57B6J mice. IH resulted in improved glucose tolerance and insulin sensitivity.

Enhanced glucose utilization of skeletal muscle after 4 weeks of intermittent hypoxia in a mouse model of type 2 diabetes 2024

intervention groups with 1 hour (acute) or 4 weeks (1 hour/day, 6 days/week) exposure to a hypoxic envrionment (0.15 FiO2), exercise (treadmill run) in normoxia, and exercise in hypoxia, respectively
Compared with diabetes control group, the mice treated in the hypoxic environment for 4 weeks showed a significantly higher pyruvate levels and lower lactate/pyruvate ratios in the quadriceps muscle, and the mice exposed to hypoxia without or with aerobic exercise for either for 4 weeks or just 1 hour showed higher NAD+ levels and lower NADH/NAD+ ratios.

Intermittent hypoxia increases lipid insulin resistance in healthy humans: A randomized crossover trial 2024

8 hr of IH between 22:00 hours and 06:00 hours for 14 consecutive nights
FiO2 of 0.13
The nasal cannula restored oxygen saturation (range 95%–98%) via a 15-s bolus of oxygen every 120 s
Individuals were switched from normal air to 13% FiO2, allowing a range of SaO2 from 95% to 85%, 30 cycles per min during 8 hr of sleep
We previously demonstrated an increase in sympathetic tone by using the reference method of muscle sympathetic activity

Age and sex-dependent effects

Daily Acute Intermittent Hypoxia Elicits Age & Sex-Dependent Changes in Molecules Regulating Phrenic Motor Plasticity 2024

Intermittent hypoxia therapy for sleep apnea

This one is interesting as OSA is characterized by intermittent hypoxia but hypoxic preconditioning before sleep still seems beneficial:

A randomized controlled crossover trial of acute intermittent and continuous hypoxia exposure in mild-moderate obstructive sleep apnea: A feasibility study 2023

Over three single-night sessions, subjects were alternately exposed to normoxia, acute continuous hypoxia and acute intermittent hypoxia before sleep.
In conclusion, acute intermittent hypoxia exposure improved apnea-hypopnea index and oxygen desaturation index in patients with mild-moderate obstructive sleep apnea

Effect on inflammation

Effects of intermittent hypoxia and whole-body vibration training on health-related outcomes in older adults 2024

The results showed that IH and WBV had a positive synergistic effect on inflammatory parameters (CRP and IL-10), bone formation biomarker (PINP), and body composition (muscle and bone mass).
FiO2 of 16.1%
For safety reasons, a finger pulse oximeter was used to ensure that blood oxygen saturation (SpO2%) did not fall below 85%.

Intermittent hypoxia preconditioning can attenuate acute hypoxic injury after a sustained normobaric hypoxic exposure: A randomized clinical trial 2024

IH preconditioning also showed greater effects on serum protein gene product 9.5 (3.89 vs. 29.16 pg/mL; p = 0.048) and C-reactive protein (−0.28 vs. 0.41 mg/L; p = 0.023).

For performance: no effect?

The Impact of Normobaric Hypoxia and Intermittent Hypoxic Training on Cardiac Biomarkers in Endurance Athletes: A Pilot Study 2024

Strength and muscle mass development after a resistance-training period at terrestrial and normobaric intermittent hypoxia 2024

Drug interactions

Metformin protects the heart against chronic intermittent hypoxia through AMPK-dependent phosphorylation of HIF-1α 2024

we found that metformin inhibits IH-induced mitophagy in myocardium and decreases HIF-1α nuclear expression in mice subjected to IH

Melatonin attenuates intermittent hypoxia-induced cognitive impairment in aged mice: The role of inflammation and synaptic plasticity 2025

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#113

I had my first session today:

  • 5 min hypoxia (FiO2 16%), 5 min normoxia
  • 4 cycles

My SpO2 never went below 93%. Being in hypoxia felt quite good, some tingling in the body, the return to normoxia felt “boring” (I don’t know how to describe that). My heart rate increased during hypoxia (+10 bpm?), more so in the first cycle vs last cycle (some adaptation of the body?).

Other than that: zero effect?

Next session on Saturday. I’ll go lower to 15% or 15.5% FiO2.

3 Likes
#114

Chinese paper, just published: Intermittent hypoxic perconditioning improves cognitive function in a mouse model of vascular cognitive impairment and dementia with comorbidities by recovering cerebral blood flow 2025

Vascular cognitive impairment and dementia is a debilitating neurological disorder caused by chronic cerebral hypoperfusion, for which no effective causative treatments are currently available. Intermittent hypoxia has been shown to enhance cerebral blood flow in mice, but its efficacy in a model of vascular cognitive impairment and dementia remains unclear. In this study, we established a mouse model of vascular cognitive impairment and dementia by bilateral carotid artery stenosis. Intermittent hypoxia was induced before and after this stenosis. We found that intermittent hypoxia increased cerebral blood flow, oxygen saturation, and microcirculation in the prefrontal cortex and hippocampus in the model mice, without causing neurovascular damage. Additionally, intermittent hypoxia significantly improved cognitive function in the mouse model of vascular cognitive impairment and dementia, with perconditioning showing greater efficacy than preconditioning. Improvements in cerebral microcirculation and blood flow were positively correlated with cognitive recovery. Even in a mouse model of vascular cognitive impairment and dementia with comorbidities induced by a high-fat, high-fructose diet, intermittent hypoxic perconditioning demonstrated protective effects on cognitive function. Proteomic analysis indicated that mitochondrial protection is a key mechanism, particularly through upregulating NDUFB8 expression and increasing the activity of mitochondrial complex I. These findings suggest that intermittent hypoxia is a potential non-invasive strategy for the prevention and treatment of vascular cognitive impairment and dementia.
Intermittent hypoxia treatment
Mice were placed in gas-controlled chambers and exposed to 10 cycles of 5-minute normoxia (21% O 2) and 5-minute hypoxia (13% O 2) every day for 14 consecutive days. Control mice were placed in the same gas- controlled chambers for the same period, but with normal air circulating continuously (Guan et al., 2023b). All mice had free access to food and water during treatment. Based on different intervention time points, we divided intermittent hypoxia into preoperative IH preconditioning and postoperative perconditioning (meaning IH intervention during disease progression).

Other than that I had my second hypoxia session yesterday. FiO2 set to 15.5% (instead of 16%). Went well. I feel like my body already reacted better to hypoxia (smaller heart rate increase). SpO2 similar to last time. Next session on tomorrow. I’ll try 15% FiO2.

During the session my SpO2 sensor fell from my finger and the machine immediately stopped hypoxia and sent hyperoxia for safety. Good to know that the safety mechanism works :slight_smile:

1 Like
#115

Hi adssx. Do You follow some biomaker for to see if its worth in terms of lifespan or longspan? Tank you very mach

#116

Unfortunately not… I could look at the following, though:

But my main goal is to see subjective improvements in how I feel…

#117

Nice. My goal also is more area under the “feeling good” curve. Alcohol makes me feel good but it’s only a loan from the future that has to be paid back with interest.

Who in the movie Platoon said, Feelin’ good is good enough”? (He meant stoned but it’s a good line).

2 Likes
#118

Exercise responses to perceptually regulated high intensity interval exercise with continuous and intermittent hypoxia in inactive overweight individuals 2025

To investigate the acute effects of hypoxia applied during discrete work and recovery phases of a perceptually regulated, high-intensity interval exercise (HIIE) on external and internal loads in inactive overweight individuals. On separate days, 18 inactive overweight (28.7 ± 3.3 kg m−2; 31 ± 8 years) men and women completed a cycling HIIE protocol (6 × 1 min intervals with 4 min active recovery, maintaining a perceived rating of exertion of 16 and 10 during work and recovery, respectively, on the 6–20 Borg scale) in randomized conditions: normoxia (NN), normobaric hypoxia (inspired O2 fraction ∼0.14) during both work and recovery (HH), hypoxia during recovery (NH) and hypoxia during work only (HN). Markers of external (relative mean power output, MPO) and internal load (blood lactate concentration, heart rate and tissue saturation index (TSI)) were measured. MPO was lower in HH compared to NN, NH and HN (all P < 0.001), with HN also being lower than NN (P < 0.001) and NH (P < 0.023). Heart rate was higher in HN than NN, HH and NH (all P < 0.001). Blood lactate response was higher in NN than HH (P = 0.003) and NH (P = 0.008). Changes in the TSI area above the curve were greater in HN relative to NN, HH and NH (all P < 0.001). Hypoxia applied intermittently during the work or recovery phases may mitigate the declines in mechanical output observed when exercise is performed in continuous hypoxia, although hypoxia implemented during the work phase resulted in elevated heart rate and lactate response. Specifically, exercise performance largely comparable to that in normoxia can be achieved when hypoxia is implemented exclusively during recovery.
Intermittent hypoxia, implemented during either the work or recovery phase of HIIE attenuated significant declines in mechanical output associated with continuous hypoxia, but did not alter acute metabolic responses beyond that exercise in normoxia. The application of intermittent hypoxic exposure could be an effective method to harness the benefits of decreased oxygen saturation without compromising absolute exercise intensity, thereby enhancing the acute effects of exercise in this population.
Accordingly, HIIE in hypoxia has been suggested as a strategy to enhance these longer-term adaptations in athletes (Faiss et al., 2013). More recently, HIIE in hypoxia has been shown to be an effective strategy to improve cardiorespiratory fitness and cardiometabolic health in individuals with overweight (Camacho-Cardenosa et al., 2018; Kong et al., 2017). However, a potential drawback with conventional HIIE in hypoxia is a decline in absolute exercise intensity relative to HIIE in normoxia (Billaut & Buchheit, 2013). The resultant decline in exercise intensity may blunt the exercise-associated physiological and metabolic responses. Indeed, the decrease in absolute exercise intensity in individuals with overweight or obesity was postulated to explain the lack of additional cardiometabolic benefits resulting from an 8-week HIIE training programme in continuous hypoxia, beyond exercise training in normoxia (Ghaith et al., 2022).
Reduced oxygen availability may lead to increased anaerobic glycolysis (Gladden, 2004; Parolin et al., 2000) resulting in increased blood lactate levels.

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#119

Adding an additional stressor to high intensity interval training seems unlikely to be beneficial and possibly even counterproductive given that the adaptations occur due to maximally stressing your system in the first place. I’ll be curious if more studies are done to show the long term effects. Combining exercise with hypoxia seems far more amenable to low stress modalities like steady state/zone 2.

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#120

From a performance perspective, pro cyclists use altitude training to push the envelope despite the extra stress involved. The question for regular people who want health vs competitive performance is can we get some benefit from hypoxia (whether during training or not). I think AUC matters… so would a 1 hour session in a chamber every week matter (1/169th of time)? Probably not. Would my 10 minute breath holds / shallow breathing matter (10/1440th of time)? Probably not.

I think I get a co2 tolerance benefit but probably no epigenetic signaling.

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