Mitochondrial Training
Intermittent hypoxia-hyperoxia training (IHHT)
IHHT is a breathing therapy. Through a mask you inhale air with less oxygen than usual for a few minutes, then air with more, in cycles of 30 to 40 minutes. The alternation trains the mitochondria, the cell's energy producers, and is used at St. George Hospital in the Long COVID, ME/CFS and chronic Lyme programs.
What is IHHT?
Intermittent Hypoxia-Hyperoxia Training is a therapy in which you breathe alternating intervals of low-oxygen and high-oxygen air through a face mask while resting. It borrows the stimulus of altitude training and puts it under medical control: the device, the saturation limits and the nurse at your side. At St. George Hospital it is one component of the Post-COVID program and of the ME/CFS program, where impaired cellular energy is one of the measured findings.
The target is the mitochondria. In chronic illness and with age, damaged mitochondria accumulate and produce less energy and more oxidative stress. Brief, repeated oxygen shortage signals the cell to clear damaged mitochondria and to build new ones; the oxygen-rich interval that follows supports the rebuilding. In ME/CFS a Norwegian group found a measurable shift in energy metabolism, with impaired pyruvate dehydrogenase function (Fluge et al., 2016), which is one reason the therapy belongs in that program.
How does IHHT work?
You breathe through a mask connected to a device that sets the oxygen concentration. Hypoxic intervals of 9 to 13 percent oxygen, lasting three to five minutes, alternate with hyperoxic intervals of 30 to 40 percent oxygen of similar length. One session repeats the cycle for 30 to 40 minutes. Room air is 21 percent oxygen, so the low intervals correspond to an altitude of roughly 3,000 to 5,000 meters.
The low-oxygen minutes activate hypoxia-inducible factor, the cell's oxygen sensor, which starts the clearance of damaged mitochondria (mitophagy) and the pathways that build new ones. The oxygen-rich minutes shorten the stress and let the cell finish the rebuilding. Over 10 to 15 sessions the share of efficient mitochondria rises, and with it the capacity to produce energy without a crash afterwards.
Which programs use IHHT?
IHHT is never the whole plan. In Long COVID it runs alongside H.E.L.P. apheresis, which clears microclots and fibrinogen from the plasma so that oxygen reaches the tissue the mitochondria are being trained in, and alongside hyperbaric oxygen, which raises tissue oxygen directly. Patients with low NAD+ or CoQ10 on the mitochondrial panel receive those by infusion in the same weeks. In ME/CFS the mitochondrial findings decide whether IHHT is scheduled daily or every second day. In chronic Lyme disease it supports the energy recovery after antimicrobial and whole-body hyperthermia blocks.
Who it is for: patients with fatigue, post-exertional malaise or exercise intolerance whose mitochondrial and metabolic markers are abnormal, and patients in a longevity or pre-surgical program who want to raise their capacity under supervision. Who it is not for: anyone with unstable angina, severe COPD, an acute infection, uncontrolled hypertension or pregnancy. The physician checks this before the first session. The Long COVID and ME/CFS apheresis program page explains how IHHT is scheduled around apheresis days and rest.
Conditions treated
- ME/CFS with measured mitochondrial or metabolic impairment
- Post-COVID syndrome with fatigue and exercise intolerance
- Chronic Lyme disease with mitochondrial dysfunction
- Age-related metabolic decline
- Cardiovascular risk reduction and cardiac rehabilitation
- Pre-surgical conditioning
- Athletic performance under medical supervision
Could this belong in your plan?
That depends on your findings, not on the therapy. Write to the International Office with a short history; it requests your records afterwards, and a physician reviews them before the video consultation and tells you whether IHHT belongs in your program and what it would be combined with.
What a session feels like
- Before You recline, a mask goes over your nose and mouth, and a pulse oximeter clips onto a finger. The nurse enters the limits your physician has set: the lowest permitted saturation and the length of each interval.
- During For 30 to 40 minutes the device alternates "mountain air" and oxygen-rich air on its own. You may notice your breathing deepen or a light head during the low-oxygen intervals; it passes when the oxygen-rich interval starts. Saturation and heart rate are on a screen the whole time, and the device switches to oxygen early if your saturation drops below the limit. Most people read or rest.
- Afterwards Nothing to recover from. You can walk to your next therapy or rest in your room. On apheresis days IHHT is scheduled at a different time, with rest between the two.
Evidence and safety
The evidence is moderate in the older and cardiometabolic patients tested in controlled trials, and limited in Long COVID, where no randomized trial exists yet. Mitochondrial markers are measured before and after the course.
Show studies, risks and side effects
The evidence for IHHT is moderate in the populations where it has been tested in controlled trials, and limited in Long COVID, where no randomized trial exists yet. A 2022 systematic review of intermittent hypoxia-hyperoxia in humans found effects on exercise capacity, blood pressure and metabolic markers across the included trials, most of them in older or cardiometabolic patients (Behrendt et al., 2022). In coronary artery disease a controlled study reported improved exercise tolerance and blood pressure after a course of IHHT added to rehabilitation (Glazachev et al., 2017), and a meta-analysis of intermittent hypoxia conditioning in cardiovascular disease rated the method safe when saturation is monitored (Glazachev et al., 2021).
In older adults, IHHT improved cognitive performance in a geriatric rehabilitation setting (Bayer et al., 2017) and, in a randomized controlled trial, mobility and perceived health when added to multimodal training (Bayer et al., 2019). In prediabetes, a randomized comparison found hypoxia-hyperoxia cycles acted on glucose metabolism where hypoxia-normoxia cycles did not (Serebrovska et al., 2019). That comparison is the reason the hospital uses the hyperoxic variant rather than hypoxia alone.
Side effects are mild and short: light-headedness or a headache during the first sessions, occasionally tiredness afterwards. Contraindications are unstable angina, severe COPD, acute infections, uncontrolled hypertension, pregnancy and any condition in which a brief fall in oxygen saturation is unsafe. In Long COVID and ME/CFS the hospital uses IHHT as part of an individual treatment concept, decided with the patient after medical consultation; what the evidence does not show is how much of the measured gain in those patients comes from IHHT and how much from the therapies it is combined with, which is why we measure the mitochondrial markers before and after the course.
What IHHT costs
IHHT is billed per session inside the written, itemized estimate you receive after a physician has reviewed your findings and before you travel. Costs are a package price plus individual add-ons, and a deposit is paid before admission. Treatment is self-pay. The invoice carries diagnoses and procedure descriptions and can be submitted to your insurer, which decides about reimbursement. Costs and insurance explains how the estimate is read and how payment works.
Questions patients ask about IHHT
Is IHHT safe?
For patients screened by a physician, yes. The device lowers oxygen only within set limits, a pulse oximeter shows your saturation throughout, and the nurse ends the hypoxic interval early if it falls below the threshold. IHHT is not used in unstable angina, severe COPD, acute infections, uncontrolled high blood pressure or in pregnancy.
Does IHHT hurt, and what does it feel like?
Nothing hurts. During the low-oxygen minutes you may notice your breathing deepen or a light head, as on a mountain pass; during the high-oxygen minutes this settles. Most patients read or rest. There is nothing to recover from afterwards, and you can go to your next therapy the same day.
How many IHHT sessions do I need?
A course is 10 to 15 sessions over two to three weeks, usually one per day on treatment days. The physician sets the number from your findings and your response, and the written proposal states it before you travel.
Is IHHT the same as hyperbaric oxygen?
No. Hyperbaric oxygen (HBOT) raises the oxygen supply to the tissues under pressure in a chamber. IHHT alternates low and high oxygen at normal pressure to train the cells' response to oxygen shortage. The two are often combined in the same plan; the physician decides which, or both, after the work-up.
How much does IHHT cost?
IHHT is billed per session as part of the written, itemized estimate you receive after a physician has reviewed your findings. The written cost overview shows the package price plus the individual add-ons your plan needs. Treatment is self-pay; the itemized invoice can be submitted to your insurer. The hospital cannot promise reimbursement.
References
- Effects of Intermittent Hypoxia-Hyperoxia on Performance- and Health-Related Outcomes in Humans: A Systematic Review. Sports Medicine - Open 2022. PMID 35639211
- Adaptations following an intermittent hypoxia-hyperoxia training in coronary artery disease patients: a controlled study. Clinical Cardiology 2017. PMID 28323322
- Intermittent hypoxic-hyperoxic training on cognitive performance in geriatric patients. Alzheimer's & Dementia: Translational Research & Clinical Interventions 2017. PMID 29067323
- Effects of intermittent hypoxia-hyperoxia on mobility and perceived health in geriatric patients performing a multimodal training intervention: a randomized controlled trial. BMC Geriatrics 2019. PMID 31200649
- Intermittent Hypoxia/Hyperoxia Versus Intermittent Hypoxia/Normoxia: Comparative Study in Prediabetes. High Altitude Medicine & Biology 2019. PMID 31589074
- Safety and Efficacy of Intermittent Hypoxia Conditioning as a New Rehabilitation/Secondary Prevention Strategy for Patients with Cardiovascular Diseases: A Systematic Review and Meta-analysis. Current Cardiology Reviews 2021. PMID 33992064
- Metabolic profiling indicates impaired pyruvate dehydrogenase function in myalgic encephalopathy/chronic fatigue syndrome. JCI Insight 2016. PMID 28018972
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