View source for The Science of Intermittent Hypoxic Exposure

Use of [[Intermittent Hypoxic Exposure]] (IHE) is relatively new in the west, but the USSR (and later CIS) has been researching and using IHE since the 1930's. Usage includes sports, altitude acclimatization, and treatment of clinical disorders, including chronic lung diseases, bronchial asthma, hypertension, diabetes mellitus, Parkinson's disease, emotional disorders, and even radiation toxicity. 
==Mechanisms==
There appear to be three mechanisms underlying the effects of IHE: regulation of respiration, mitochondrial respiration, and free-radical production. 
* The regulation of respiration results in increased sensitivity of [[Breathing|breathing]] rate to altitude, improved gas exchange in the lungs and changes to the autonomic nervous system. 
* Improvements in mitochondrial respiration results in optimized use of oxygen in energy production.
* Exposure to both low and normal oxygen levels improves the body's antioxidant defense. 
The research shows that there is wide individual variation in the response to IHE and altitude. This variation exists in both humans and animals, and appears to be due to mechanisms beyond simple iron insufficiency. 
==IHE and Athletic Performance==
*A lot of research on IHE has come from the former USSR<ref name="Serebrovskaya-2002"/>. 
** Expose subjects to 15,000 feet for 1 hour per day over several days for 7 to 11 sessions showed increased blood O<sub>2</sub> saturation compared with initial exposure and the benefits were detectable for up to 4 weeks.
** Exposure of 30 min to 3 hours every 2 to 3 days for 9 exposures increased hemoglobin by 12% and red blood cells by 22%
** Exposure of 3x (6 min low O2, 4 min normal air) per day for 14 days increased breathing volume at altitude by ~50%. Partial pressure of O<sub>2</sub> started at 50 mmHg (20,000 ft) dropping to 35 mmHg (28,000 ft). Several studies have shown similar results. 
** 5x (15 min 11% O<sub>2</sub> + 15 min recovery) for 14 day produced changes to the metabolic pathways that optimize the use of oxygen.
** Other studies in rats indicate that IHE changes the ratio of fat to [[Protein|protein]] burning in favor of fats by 80%.
** Recent studies indicate that IHE stimulates NO (Nitric Oxide) production, with the excess stored in the vascular walls. This improves blood pressure. 
* Research<ref name="Julian-2004"/> using highly trained runners showed no running improvement with IHE. However, this study used IHE for 4 weeks and had O<sub>2</sub> saturation values of 89.9, 86.3, 85.9, and 81.4 for each week. The value of IHE is dependent upon the O<sub>2</sub> saturation levels, with little effect until values under 89%<ref name="HTI"/>. The athletes in the study therefore only received significant hypoxia for about one week. The athletes were given 5 min hypoxic, 5 min normal for 70 minutes total for five days per week, 4 weeks total. 
* A similar research<ref name="junis"/> study showed a significant improvement in 3K running performance. This study used 90 minutes of IHE (5 hypoxic:5 normal) for 15 days over a three week period, using 13,000 feet at the start to 19,000 feet at the end.  
* A study<ref name="Knaupp-1992"/> looking at Hypoxia EPO, a hormone that stimulates red blood cell production showed a ~50% increase in EPO from 4 hours of IHE or 2 hours of continuous hypoxia, but no response from 5 minutes or 1 hour. The IHE was a simulated altitude of 18,000 ft.
* Subjects exposed hypoxia in a hypobaric chamber showed elevated EPO levels after 114 min at 9,000 feet and or after 84 minutes at 12,000 feet. EPO levels continued to rise with longer exposure. <ref name="Eckardt-1989"/>
* Research using the [[AltoLab]] system showed a significant improvement in sprint speed. The study used 6 min hypoxia (10,000 to 18,000 ft) with 4 min recovery for an hour a day for 15 days. The study shown a tiny improvement in blood parameters (hemoglobin/hematocrit) normally associated with [[Altitude Training|altitude training]].<ref name="alto"/>
* A study of elite triathletes showed no changes in blood parameters or running performance after 17 days AltoLab IHE<ref name="Humberstone-Gough-2013"/>. However, the protocol used has a gradually decreasing O<sub>2</sub> level, so that only towards the end of the training is there a significant training stimulus.
==Intermittent Hypoxic Exposure and Diseases==
IHE has been looked at for a number of diseases<ref name="XiSerebrovskaya2012"/>. 
===Intermittent Hypoxic Exposure and Asthma===
Studies have reported an improvement in asthma, with reduced attacks, reduced severity of attacks and reduced need for medication. Note that none of these studies has looked at specifically at exercise induced asthma.
* IHE increased lung force in asthmatic and non-asthmatic athletes<ref name="asthmatic"/>. There was no deterioration in asthma status from the trial, and half of the asthmatics reported a reduction in the need for medication. The trial used 15 sessions over three weeks, with each session being 5 min hypoxia followed by 5 min normal air, repeated for 60 minutes. The hypoxia was equivalent to 22,500 ft. 
* IHE has been shown to reduce the shortness of breath and congestion of childhood bronchial asthma, reducing or eliminating the attacks<ref name="Serebrovskaya-2012"/>. The protocol was 4 repeats of 5-7 minutes with 12% O<sub>2</sub> which resulted in a [[SpO2|SpO<sub>2</sub>]] of 89-92%. 
* IHE reduced the bronchial resistivity by 31–37% in bronchial asthma patients<ref name="Levashov-2012"/>. IHE also increased reserves of lung ventilation, restored the physiological level of alveolar ventilation in 78% of patients with chronic obstructive pulmonary disease (COPD)<ref name="Levashov-2012"/>.
* Studies have shown IHE reduces the oxidant stress associated with bronchial asthma, however, the study had large variations in individual response<ref name="Serebrovskaya-2002"/>.
===Neuroprotective Mechanisms of Intermittent Hypoxia===
There are a number of studies that show that mild hypoxic exposure provides neural protection against prolonged [http://en.wikipedia.org/wiki/Ischemia ischemia]<ref name="SkiboOrlovsky2012"/>. This may provide benefits to those with a high risk of stroke, or other risk of impaired blood flow to the brain.
===Intermittent Hypoxic Exposure and Parkinson's Disease===
A study of IHE on adult rats, old rats and old rats that have experimental dopamine deficiency showed an increase in dopamine in the both groups of old rats<ref name="Belikova"/>. The study used 5 repeats of 15 minutes of 12% O<sub>2</sub> with 15 minute recoveries for two weeks. While this is an early study, the low risk nature of IHE makes this a promising treatment. 
===Intermittent Hypoxic Exposure and Alzheimer's Disease===
A study of rats that had induced Alzheimer's Disease through intracerebral injections of beta-amyloid showed that adaptation to IHE may improve the brain's self-defense mechanisms which slow the progression of Alzheimer's. Again, this is an early study on animal, but it shows some promise<ref name="Manukhina-2012"/>.
===Intermittent Hypoxic Exposure and Cancer===
A study of mice with [http://en.wikipedia.org/wiki/Acute_myeloid_leukemia Acute Myeloid Leukemia] (AML) showed an increased survival time and an inhibition of the [http://www.cancer.gov/dictionary?cdrid=46349 infiltration] of the cancerous cells, and improved [http://www.cancer.gov/dictionary?cdrid=46445 differentiation]<ref name="Chen-2012"/>. Note that this is an animal study on one specific type of cancer. 
===Intermittent Hypoxic Exposure and Oxidative Stress===
* Studies in rats suggest that continuous exposure to altitude reduces anti-oxidant defenses, but IHE improves those defenses<ref name="Serebrovskaya-2002"/>.
* A study of workers that cleaned up after Chernobyl nuclear reactor explosion showed that they had higher levels of oxidant stress where higher than normal. Exposing the workers to IHE of 3x (5 min 7-8% [28,000+ ft] O<sub>2</sub> with 5 min normal air) for 14 days significantly reduced the oxidant stress. 
==Risks of Hypoxic Exposure==
There is a case study of an individual who had a seizure after hypoxic exposure<ref name="MoniagaGriswold2009"/>. This military officer was undergoing hypoxia training with a Reduced Oxygen Breathing Device. This device is routinely used to protect and prepare for sudden decompression at altitude. The seizure occurred after sleep deprivation (4hr/night for 3 nights) and breathing 7.11% O2, equivalent to 25,000'. Their [[SpO2|SpO<sub>2</sub>]] dropped to 69%, which is lower than what is normally considered the safe lower limit of 75%. There is also a study of rats that indicates hypoxia may increase seizure susceptibility<ref name="Kubová-2007"/>. Therefore it seems prudent for individuals with epilepsy to avoid hypoxic training without specific medical approval. 
==A note on terminology==
Some literature considers sleeping at altitude (or with low oxygen levels) to be 'IHT'. This Wiki uses IHT to be separate from LHTL and to mean shorter periods than overnight [[Zeo Sleep Monitor|sleep]] and generally at much lower oxygen concentrations. There is also confusion between the terminology for Intermittent Hypoxic Exposure and [[Intermittent Hypoxic Training]]. There is also a use of the term 'Intermittent Normobaric Hypoxic Training', or 'Intermittent Normobaric Hypoxic Treatment' for IHE. 
==See Also==
* [[The Science of Altitude Training]]
* [[Comparison of Altitude Training Systems]]
* [[Book Review - Altitude Training and Athletic Performance]]
* [[Intermittent Hypoxic Exposure]] 
* [[Intermittent Hypoxic Training]] 
* [[AltoLab]]
==References==
<references>
<ref name="Humberstone-Gough-2013">CE. Humberstone-Gough, PU. Saunders, DL. Bonetti, S. Stephens, N. Bullock, JM. Anson, CJ. Gore, Comparison of live high: train low altitude and intermittent hypoxic exposure., J Sports Sci Med, volume 12, issue 3, pages 394-401,  2013, PMID [http://www.ncbi.nlm.nih.gov/pubmed/24149143 24149143]</ref>
<ref name="Knaupp-1992">W. Knaupp, S. Khilnani, J. Sherwood, S. Scharf, H. Steinberg, Erythropoietin response to acute normobaric hypoxia in humans., J Appl Physiol (1985), volume 73, issue 3, pages 837-40, Sep 1992, PMID [http://www.ncbi.nlm.nih.gov/pubmed/1400046 1400046]</ref>
<ref name="Eckardt-1989">KU. Eckardt, U. Boutellier, A. Kurtz, M. Schopen, EA. Koller, C. Bauer, Rate of erythropoietin formation in humans in response to acute hypobaric hypoxia., J Appl Physiol (1985), volume 66, issue 4, pages 1785-8, Apr 1989, PMID [http://www.ncbi.nlm.nih.gov/pubmed/2732171 2732171]</ref>
<ref name="alto">http://www.pharmapacific.com/images/AltoLab_Clinical_Research_Study.pdf Running performance and altitude exposure</ref>
<ref name="Julian-2004">CG. Julian, CJ. Gore, RL. Wilber, JT. Daniels, M. Fredericson, J. Stray-Gundersen, AG. Hahn, R. Parisotto, BD. Levine, Intermittent normobaric hypoxia does not alter performance or erythropoietic markers in highly trained distance runners., J Appl Physiol (1985), volume 96, issue 5, pages 1800-7, May 2004, doi [http://dx.doi.org/10.1152/japplphysiol.00969.2003 10.1152/japplphysiol.00969.2003], PMID [http://www.ncbi.nlm.nih.gov/pubmed/14672967 14672967]</ref>
<ref name="Serebrovskaya-2002">TV. Serebrovskaya, Intermittent hypoxia research in the former soviet union and the commonwealth of independent States: history and review of the concept and selected applications., High Alt Med Biol, volume 3, issue 2, pages 205-21,  2002, doi [http://dx.doi.org/10.1089/15270290260131939 10.1089/15270290260131939], PMID [http://www.ncbi.nlm.nih.gov/pubmed/12162864 12162864]</ref>
<ref name="asthmatic">http://www.hypoxico.com/images/pdfs/Does_IHE_effect_the_lung_function_of_asthmatic_athletes.pdf Does IHE effect the lung function of asthmatic athletes</ref>
<ref name="junis">Hamlin, M. J., and J. Hellemans. "Intermittent Hypoxic Training in Endurance Athletes." Report of Australian Conference of Science and Medicine in Sport. October 25. Vol. 28. 2003.</ref>
<ref name="HTI">http://en.wikipedia.org/wiki/Hypoxic_Training_Index Hypoxic Training Index</ref>
<ref name="Serebrovskaya-2012">Serebrovskaya, Tatiana V., et al. "Intermittent Hypoxia in Treatment of Bronchial Asthma in Childhood." Intermittent Hypoxia and Human Diseases. Springer London, 2012. 135-143.</ref>
<ref name="Levashov-2012">Levashov, Mikhail I. "Beneficial Effects of Intermittent Normobaric Hypoxic Training on Respiratory Function in Patients with Chronic Pulmonary Diseases." Intermittent Hypoxia and Human Diseases. Springer London, 2012. 115-126.</ref>
<ref name="Belikova">Belikova, Maria V., Evgenia E. Kolesnikova, and Tatiana V. Serebrovskaya. "Intermittent Hypoxia and Experimental Parkinson's Disease." Intermittent Hypoxia and Human Diseases. Springer London, 2012. 147-153.</ref>
<ref name="Manukhina-2012">Manukhina, Eugenia B., et al. "Protective Effects of Adaptation to Hypoxia in Experimental Alzheimer's Disease." Intermittent Hypoxia and Human Diseases. Springer London, 2012. 155-171.</ref>
<ref name="Chen-2012">Chen, Guo-Qiang, and Wei Liu. "Anticancer Effects of Intermittent Hypoxia in Acute Myeloid Leukemia." Intermittent Hypoxia and Human Diseases. Springer London, 2012. 229-238.</ref>
<ref name="XiSerebrovskaya2012">Lei Xi, Tatiana V. Serebrovskaya, Intermittent Hypoxia and Human Diseases, Accessed on 4 September 2013, date 5 June 2012, publisher Springer, isbn 978-1-4471-2906-6</ref>
<ref name="SkiboOrlovsky2012">Galina Skibo, Maxim Orlovsky, Anastasiia Maistrenko, Victor Dosenko, Iryna Lushnikova, Neuroprotective Mechanisms of Intermittent Hypoxia: An In Vitro Study, 2012, pages 173–180, doi [http://dx.doi.org/10.1007/978-1-4471-2906-6_14 10.1007/978-1-4471-2906-6_14]</ref>
<ref name="MoniagaGriswold2009">Natalie C. Moniaga, Cheryl A. Griswold, Loss of Consciousness and Seizure During Normobaric Hypoxia Training, Aviation, Space, and Environmental Medicine, volume 80, issue 5, 2009, pages 485–488, ISSN [http://www.worldcat.org/issn/00956562 00956562], doi [http://dx.doi.org/10.3357/ASEM.2397.2009 10.3357/ASEM.2397.2009]</ref>
<ref name="Kubová-2007"> H. Kubová, P. Mares, Hypoxia-induced changes of seizure susceptibility in immature rats are modified by vigabatrin., Epileptic Disord, volume 9 Suppl 1, pages S36-43, Dec 2007, doi [http://dx.doi.org/10.1684/epd.2007.0150 10.1684/epd.2007.0150], PMID [http://www.ncbi.nlm.nih.gov/pubmed/18319199 18319199]</ref>
</references>