Sleep apnea and orthostatic hypotension or reduction in blood flow upon standing might be hidden dangers then.
I’ll call them “micro hypoxic events”, and in late life they could happen 1000x+ times, who knows.
Surprisingly sleep apnea confers a longevity benefit. I’ll merge these two threads to avoid repeating myself…
If it’s the 2009 citation: https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2869.2009.00754.x
The observed benefit was in elderly (and in the paper they cite younger demographics have increase in mortality), likewise simply being in the group of testing for sleep apnea trended towards a decrease in mortality by 30%, with RDI below 20 same as asymptomatic, presumably what they’re comparing with. Might be residual confounding there, but they did adjust for some confounding factors. Since it’s a relatively small study they can’t adjust for too many.
The altitude/hypoxic ranges in the mouse article for chronic exposure to 13-15% seems to agree with the paper below. Moderate altitudes are protective while high altitude can be damaging.
Consequently, it could be speculated that living at higher altitude, and therefore in hypoxic conditions, accelerates aging. This assumption is indeed supported by evidence from populations residing at very high altitudes (>3,500 m). In contrast, accumulating evidence suggests that living at moderate altitudes (1,500–2,500 m) is protective rather than injurious, at least for some body systems.
Yes, it’s the 2009 study, cited in this review: Oxygen, hypoxia and hyperoxia - #77 by adssx
Another paradox: several papers showed that intermittent hypoxia exposure seems to improve sleep apnea symptoms: Effects of Intermittent Hypoxia Protocols on Cognitive Performance and Brain Health in Older Adults Across Cognitive States: A Systematic Literature Review 2024
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@John_Hemming: could roxadustat (approved for anemia) be hypoxia in a pill? See: Hypoxia-inducible factor prolyl hydroxylase inhibitors for anaemia in chronic kidney disease: a clinical practice document by the European Renal Best Practice board of the European Renal Association 2024
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It reads as such, but I would need to spend some time reading more than glancing at that paper.
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Acute intermittent hypercapnic hypoxia augments left ventricular contractility 2025
Chronic intermittent hypoxia increases cardiac contractility associated with cardiac sympathetic and structural remodelling. However, whether increases in contractility manifest acutely following intermittent hypercapnic hypoxia is unknown.
We show increases in indices of cardiac systolic performance at rest and across progressive hypovolaemia following acute intermittent hypercapnic hypoxia.
Diastolic relaxation was unchanged, but reductions in the ratio of passive filling to atrial kick during diastole, potentially as a result of increased mitral inflow velocity during atrial filling, suggest that the increases in contractility may extend to the atria.
From that paper:
“Chronic intermittent hypoxia (CIH) over days to weeks facilitates ostensibly adaptive, sympathetically-mediated increases in cardiac contractility (Détrait et al., 2021; Marullo et al., 2023; Naghshin et al., 2009; Rodriguez et al., 2014), whereas extended exposure over months shifts towards the clinical phenotype of contractile dysfunction via accumulated oxidative stress (Chen et al., 2005, 2008).”
So there’s “chronic” over days to weeks and also “chronic” over months with disparate effects? How is “exposure” defined here?
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I just wanted to add one datapoint, about Summit County, Colorado:
The terrain of the county is mountainous with elevations ranging from 7,957 feet (2,425 m) at Green Mountain Reservoir to 14,270 feet (4,350 m) at Grays Peak.
Life expectancy:
According to a report in the Journal of the American Medical Association, residents of Summit County had a 2014 life expectancy from birth of 86.83 years in 2014, the longest in the United States.
Of course, it could be a mirage. e.g. if someone lives at high elevation and then gets sick, they might choose to move somewhere else, at lower elevation; and then they don’t get counted in the stats for Summit County.
Although many studies have investigated whether aerobic training in hypoxia (IHT) could bring advantages to maximal oxygen uptake (V̇O2max) and sea-level performance when compared to analogous normoxic training (NT), the literature results are inconsistent. This variability may come from differences in population, training protocols, hypoxic methods, and potential bias. Therefore, a comprehensive meta-analysis with strict inclusion criteria is needed to assess the effects of aerobic IHT on V̇O2max and performance. This study aims to review previous meta-analyses and analyze all parallel-design studies examining the effect of aerobic IHT compared to NT on V̇O2max and sea-level aerobic performance. Systematic research was conducted following PRISMA guidelines regarding the effects of aerobic IHT on sea-level V̇O2max and performance outcomes. The analysis accounted for characteristics of the population, training protocol, hypoxic environment, and publication details. A total of 35 studies involving 524 participants were included. The analysis showed that IHT, compared to NT, did not significantly improve V̇O2max (p = 0.333), peak power output (p = 0.159), and time to exhaustion (p = 0.410). Subgroup analyses identified no significant differences based on fitness level (p = 0.690) and exercise modality (p = 0.900); however, a publication bias was found (p = 0.004). These results suggest that, despite some enthusiastic findings in the literature, possibly influenced by publication-related biases, aerobic IHT does not offer superior improvement in V̇O2max and performance compared with NT. Therefore, adding hypoxia to aerobic exercise does not enhance training adaptations.
Veterans Affairs preprint: Mild Intermittent Hypoxia May Improve Autonomic Dysfunction in Persons Living with Spinal Cord Injury: A Preliminary Snapshot 2025
Persons with spinal cord injuries (pwSCI) often suffer from autonomic dysfunction, sleep disordered breathing, and impaired mitochondrial capacity. Current treatment options for these individuals are limited and often have significant side effects. Thus, new interventions that target multiple physiological systems and circumvent physical limitations would be a significant development for pwSCI. One potential intervention is daily mild intermittent hypoxia (MIH) which has been shown to improve blood pressure control and upper airway function during sleep. Four individuals with chronic motor incomplete SCI underwent 8 days of MIH (ClinicalTrials.Gov ID #NCT05351827, ClinicalTrials.gov). The MIH protocol was administered each morning during wakefulness with end-tidal oxygen maintained at 55-60 mmHg. End-tidal carbon dioxide was maintained at +3 mmHg above baseline during the MIH. Autonomic dysfunction (autonomic dysreflexia and orthostatic hypotension), sleep quality, upper airway function, mitochondrial capacity, and microvascular function were tested before, the day after, and 2 weeks following the MIH protocol. Systolic autonomic dysreflexia improved by 46 ± 14% and orthostatic hypotension improved by 160 ± 63% after MIH. Reductions in the apnea hypopnea index were observed, alongside a concurrent reduction in arousals during sleep. Upper airway function, improved and mitochondrial capacity increased following 8 days of MIH. These preliminary data from four participants in an ongoing clinical trial suggest that 8 days of MIH may improve autonomic dysfunction, sleep quality, and mitochondrial capacity in pwSCI. The recruitment of additional participants is required to support these preliminary findings.
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According to clinical trials.gov it is breathed oxygen at 7-8% in the latter one. I don’t know what end-tidal would be for breathed oxygen at that. ChatGPT makes a stab at 1%.
7-8% breathed is quite low.
Either their clinical trials record is wrong or the abstract is wrong. ChatGPT says for 15% breathed oxygen end tidal would be 7-8% so that might be what they mean. Hence ClinicalTrials.gov record is probably wrong.
Experimental: Mild Intermittent Hypoxia
This arm of the protocol will receive mild intermittent hypoxia (8% Oxygen) with end-tidal carbon dioxide maintained 1-3 millimeters of mercury above baseline, while in the laboratory. If diagnosed with sleep apnea, participants will be treated with continuous positive airway pressure for the duration of the intervention. Other: Mild Intermittent Hypoxia
- Participants will breathe 8% oxygen through a non-diffusable bag that is connected to a 5-way stopcock. The inspiration side of the system is then connected to a 2-way non-rebreathing valve which is connected to a pneumotachometer that is connected to a tight fitting facemask. 100% oxygen and carbon dioxide are titrated into the system to ensure the appropriate hypoxic and hypercapnic stimulus is delivered. The investigators will lower oxygen to 55-60 mmHg and maintain end-tidal carbon dioxide 1-3 mmHg above individual baseline values. The protocol starts with 10 minutes of baseline breathing (room air) then followed by 10 more minutes of breathing room air with the additional carbon dioxide. Thereafter, individuals undergo 12 2-minute bouts of hypoxia with 2 minutes of normoxia (room air) interspersed between episodes. The intervention protocol concludes with 20 minutes of monitoring all breathing and cardiovascular measurements.
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Surprising Turkish-Korean-British preprint: exposure to hypoxia in parents protects offspring from stroke!
Intermittent hypoxia in parents acts as an intergenerational conditioning stimulus, conferring offspring resilience to ischaemic stroke. This neuroprotective phenotype is supported by coordinated molecular adaptations in key pathways involved in survival and stress response. These findings highlight the potential for parental environmental conditioning to shape stroke outcomes in offspring, opening new avenues for therapeutic exploration.
There is an extent to which living things are problem solving. Hypoxia is a problem.
https://journals.physiology.org/doi/full/10.1152/japplphysiol.00369.2022
A consequence of hypoxia generated by life at a high elevation is appetite suppression. I found this out first hand on a recent trip to Peru. Despite much backpacking and hiking at high elevations in Colorado I was taken off guard by how much my appetite was affected by the increase in altitude in Peru. We acclimated in Huaraz (10,000 ft) for a week doing climbs up to 15,000 ft. Then went out for a week to the Cordillera Huayhuash backpacking where the base elevation was around 14,000 ft with some passes at 16,500 ft. I have never had my appetite fall off so much despite covering 10+ miles/day with a backpack over high passes.
Those living at higher elevation are consistently less likely to suffer from obesity. Colorado is the least obese state in the nation. Switzerland is the same way along with Peru. The changes in caloric intake induced by hypoxia at elevation could be part of the longevity found in these populations.
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yea, I live at 6400’ and have to force myself to eat most days
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The effect of intermittent normobaric hypoxia on the expression of hypoxia-inducible factor 1α (HIF-1α) and glucocorticoid receptors in the brain of male Wistar rats was studied in the context of developing neuroprotective methods of hypoxytherapy. Hypoxia in three modes of different effectiveness was modeled by three cycles of 5-min inhalation of a hypoxic mixture (9, 12, or 16% O2) with 15-min intervals of normoxia (21% O2) over 3 days. Immunopositive staining for glucocorticoid receptors and HIF-1α in rat brain increased, which correlated with the protective effectiveness of the regimen. The protective mode (9% O2) increased the expression of these proteins in all regions, the medium mode (12% O2) stimulated expression of glucocorticoid receptors only in layer V of the neocortex and HIF-1α only in the CA1 field. The least effective mode (16% O2) did not affect these parameters. Thus, neuroprotective normobaric hypoxia activates the same adaptive mechanisms as hypobaric hypoxia.
I think it is the delta in the partial pressure of O2.
Are you talking about this book?
https://www.amazon.com/Hypoxia-Conditioning-Health-Exercise-Sport/dp/1032515724/ref=sr_1_1
