The Most Overlooked, Effective Prescription Drug

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The Most Overlooked Effective Prescription Drug

The Most Overlooked, Effective Prescription Drug

Hyperbaric oxygen treatment is recognized by Medicare in the United States as a reimbursable treatment for 14 "approved" conditions. Indeed, it is one of the most natural and effective prescriptions offered by conventional medicine today.

[Disclaimer: Nothing herein should be construed as personal medical advice.]

Oxygen makes up almost 21% of every breath we take. It is fundamental to life. Without it, we die in minutes. It is an odorless, colorless gas that is poorly understood by most doctors, even though it is regulated as a prescription drug in most countries. Many doctors have a visceral mistrust of oxygen due to complicated and erroneous things they were taught in medical school about too much oxygen suppressing the need to breathe in patients with chronic lung disease or causing blindness in premature newborns. Throw in some half baked ideas about sick people having high free radicals and supplemental oxygen inducing free radical formation and voila! The overlooked arrow in the quiver. It comes out of the walls at the hospital, is administered by nurses and respiratory therapists and is generally thought of as an adjunct only, not an important treatment in its own right. Rather, it is more comfortable for the conventionally trained doctor to prescribe ever more dangerous drugs when confronted with a chronically ill patient.

Doctors generally believe that if the oxygen carrying capacity of your blood is normal (O2 Sat), then you don't need supplemental oxygen, except in a few emergency situations. But many chronically ill people exist in a state of cellular hypoxia, meaning there is not enough oxygen reaching the inside of the cells to fuel cellular machinery. In particular, oxygen is required inside mitochondria to act as a substrate for cellular respiration, the Kreb cycle and oxidative phosphorylation, to produce ATP, the energy currency of the body. Oxygen gets into cells by passive diffusion along a pressure gradient. A simple way to think about it is, if the membranes are gummed up by illness, it requires more pressure to push the oxygen in.

There is a vast literature supporting that HBOT, hyperbaric oxygen therapy, is anti-inflammatory, neuroprotective, anti-infective and promotes healing of injured tissue [1] [2] [3] [4]. However, access is limited by a short list of indications for which insurance companies will pay hospitals exorbitant prices. There is a medical association, the UHMS, or Undersea and Hyperbaric Medical Society, that is the gate keeper. Anything outside of their list of approved indications is off label, legal for a doctor to treat, but insurance won't pay. There are many private centers around the country that do an excellent job delivering treatments for a small fraction of the cost that hospitals charge. So here we have a powerful treatment that is not patentable, thus no major money to be made, except by treating patients. Doctors and hospitals want to make a lot of money for their time and equipment, so better to keep the present equilibrium with the insurance industry willing to pay a lot for a few, to prevent having to pay for the many who might benefit.

I was a hyperbaricist from '00-'04. I had a large multiplace chamber in Great Barrington, MA where I treated the late effects of brain injury and other promising but off label indications with hyperbaric oxygen, including neuroinflammatory conditions like autism and treatment resistant Lyme Disease. I witnessed extraordinary benefit in certain individuals in that practice and some improvement in many thought beyond help. There is a small but growing body of literature to support widening the tightly controlled indications list. In particular, Dr. Daniel Rossignol et al have published several very important papers about HBOT for autism and inflammatory bowel disease. The concepts in these papers support the possibility of efficacy in a very wide range of neuroimmune diseases [5] [6] [7] [8].

In the UK there is a network of charity chambers salvaged from the North Sea that treat MS and, more recently, cerebral palsy and other brain injured children for free or a minimal donation. More than a million treatments have been given over a couple of decades. Their experience is completely uncontrolled, but HBOT is not that much fun and people will not keep going unless they are pretty sure it's helping, even if it is free. Their enormous collective experience has shown it to be a very safe treatment in this setting.

There are two ways to increase the dose of oxygen above room air at sea level. You can increase the percentage of oxygen in the inspired air or you can increase the ambient pressure by using a chamber; both increase the number of oxygen molecules in each breath, so more is carried by the blood to the tissues. Putting the two together, you can deliver very high doses of oxygen with HBOT. I am currently using high flow oxygen by non-rebreather mask, without pressure, to good effect in my practice.

Soft portable chambers or Gamow bags were developed to treat mountain climbers who develop altitude sickness. At the time that I was practicing hyperbaric medicine, I was worried about the possibility of an explosive decompression, a potentially lethal event, in one of these chambers, as they are not rated for hundreds of duty cycles. I was opposed to home treatment on that basis, not because of any inadequacy of the treatment, though it is a considerably smaller dose than is generally used in a hard chamber. Since then, my understanding is that there have been more than 10,000 FDA approved soft chambers sold, and the thing I was fearing has not happened. Unless a soft chamber is modified to go to higher pressure than its rating, it should be a safe alternative. The experience has been that if they do leak, they don't lose pressure suddenly. With some training, mild HBOT can be safely used at home. It a very simple treatment to deliver, once you get the hang of the concepts. I would stick to models that have a track record and FDA approval.

Accumulated experience from the Navy and the diving industry have taught us that repeatedly diving over a long period of time on compressed air causes cumulative damage to the brain and joints from nitrogen bubbles. That's one of the reasons professional divers use Nitrox, a gas mix with a higher percentage of oxygen than room air. So although soft chambers are approved for use without oxygen, they are probably, in fact, safer over the long haul if used with oxygen, just like diving with Nitrox instead of air. The mild chambers are equipped with a penetrator that allows them to be hooked up to a concentrator, so while the chamber is pressurized with air, the patient can breathe oxygen enriched air through a mask.

Some of the doses reported to be helpful with mild HBOT are extremely low (1.3 ATA with 24% O2) and the equivalent dose can be reproduced without the use of a chamber. It is not known whether there is an independent pressure effect or not. It is a difficult thing to study as there is no suitable placebo for HBOT; patients know if they are being pressurized or not. As you read papers about HBOT, you will find a few important "negative" controlled studies where both the treatment and control groups improved, but without much difference between them. Be aware that a tiny amount of pressure, even with no additional oxygen, is still a treatment, powerful enough in the right circumstances to save a mountain climber's life. Oxygen starved tissue is exquisitely sensitive to even small increases in oxygen tension. It is even quite possible that for many applications, less is more.

In my current practice, I treat ME or Myalgic Encephalomyelitis (aka CFIDS or CFS), a neuroimmune illness with pathophysiological similarities to autism, Gulf War Illness, chronic Lyme Disease and Multiple Sclerosis. I prescribe a concentrator or tanks to deliver the highest doses of oxygen I can get without a chamber. Some of my patients are completely or nearly homebound. Ease of access is essential for these patients as travel to a chamber isn't possible.

An oxygen concentrator delivers oxygen through a tube to the patient via a cannula in the nose, a simple mask, or a non-rebreather mask. A non-rebreather mask has a reservoir which holds pure oxygen until the breath is taken; it has one way valves to prevent inspiration of ambient air and to allow exhalation gases out so carbon dioxide is not retained. Tanks are quieter, but at the high flows I'm using, need to be replaced frequently. Concentrators are noisy, but easier to move around and never run out, as they extract the oxygen directly from the air in the room. Concentrators can be portable, but most portables only produce 1-2 L/min (liters of flow per minute). The delivery device needs to match the flow rate. A nasal cannula can be used from 1-4 L/min (more than 2 L/min is hard on the nose) delivering 24-36% depending upon the flow rate and how the patient breathes. Most concentrators go up to 5 or 6 L/min and can be used with a simple mask (delivering up to 40% oxygen). Some concentrators go to 10 L/min and can be used with a non-rebreather mask (delivering >60% oxygen depending upon how the mask fits). A non-rebreather mask should only be used if there is enough flow to keep the bag inflated (>8 L/min).

There is a small amount of literature to support the efficacy that I observe in practice. 100% normobaric oxygen by demand valve has become approved therapy for cluster headache and there are a few papers in the literature supporting the use of normobaric oxygen for other indications, e.g. all cause headache [9 ], trigeminal neuralgia [10 ], mitochondrial myopathy [11] [12] and interestingly, schizophrenia [13]. A few studies show normobaric oxygen to be comparable to HBOT and others suggest it is less powerful, but still with positive effect. [14] [15].

The evidence based literature may be meager for many conditions that might benefit from a trial of home oxygen, however, it is an exceedingly low risk thing to try. My patients are canaries in the coal mine. The risk benefit ratio is more favorable by far than for any pill I can prescribe. Oxygen supplementation is a perfect intervention for fragile people who need to start low and go slow with new therapies, as the dose can be easily titrated. The dose does need to be individualized, as a few patients respond to high doses with a "herx" or die off reaction. In my opinion, this is not a positive thing if it is prolonged, but a smaller dose may still be helpful after the reaction clears, and bigger doses may be tolerated after the patient has some treatment under their belt. I prescribe O2 at 10 L/min for up to an hour by non-rebreather mask, once or twice day. I start my patients for 20 minutes at a time. If there are any untoward effects, unlike a pill already swallowed, it can be turned off and it is gone minutes after stopping it.

If it is gone from the body in minutes, why does it work? Like anything, including water, very high doses of oxygen can injure or kill. It takes a chamber to reach lethal doses, but the critical care literature suggests that even continuous high dose normobaric oxygen is damaging and does not produce the benefits seen with periodic treatment [16]. The principle of hormesis explains our clinical observations. It is the same principle that makes exercise good for you, despite stress to the system and free radical production. The right amount of stress activates cellular protective mechanisms, including induction of the antioxidant system. Or, what doesn't kill you, makes you stronger. So although extra oxygen produces an increase in reactive oxygen species during administration, free radicals kill bugs and changes are induced in the cellular environment that leave it stronger than before the treatment [17] [18] [19]. HBOT has a powerful effect on gene expression involving critical pathways that protect the cell from oxidative stress [20] [21]. Also stem cells are mobilized by HBOT [22] [23]. 

HBOT, no matter how useful, is difficult and expensive to access, though portable chambers are fairly cost effective over time and can be shared by families. High dose pulsed normobaric oxygen, while probably somewhat less effective over the short run than HBOT, can be continued long term and, for responders, the effects may be additive. It doesn't help everyone, but when it does help a stubborn condition, it is a great gift. There is little lost by trying it. We are faced with huge and growing numbers of people afflicted with chronic incurable neuroimmune illnesses. How sad, that such a simple, safe therapy as normobaric oxygen is not even on the table for discussion.

Addendum: Relative contraindications to HBOT are seizure disorder, inability to clear ears for pressurization, though this should be able to be handled in almost all cases, without barotrauma, but takes patience on the part of the chamber operator, as well as good communication with the patient. Severe COPD with CO2 retention, is another relative contraindication, although in practice CO2 narcosis only happens in the setting of acute decompensation. Asthma is a concern, because wheezing can cause air trapping and a wheezing patient should not be decompressed as trapped gases will expand and cause barotrauma. Asthmatic patients should be pretreated. Hereditary spherocytosis because of red cell fragility. Pregnancy and cancer are considered relative contraindications because of the unknown, although there are hints that HBOT may in fact be helpful for cancer. Certain prior ear surgeries are a concern and should be discussed with an otolaryngologist. Also some eye problems should be carefully considered. Hyperbaric oxygen may accelerate the maturation of existing cataracts, though if this is true, it takes a lot; HBOT does not cause cataracts de novo, except for a single case report in literature in a patient treated at high pressure. Temporary myopia with treatment is not uncommon. An exam by an ophthalmologist is a good idea prior to embarking on hyperbaric treatment. There have been cases of optic neuritis that worsened with hyperbaric treatments. Implanted devices should be checked prior to treatment with the manufacturer as to whether they are hyperbaric safe. The only absolute contraindications to HBOT is the presence of an untreated pneumothorax (collapsed lung) and recent prior or concurrent treatment with doxyrubicin, cisplatinum, Sulfamylon or disulfiram (Antabuse). 


[1] Mu J, Krafft PR, Zhang JH.  

Hyperbaric oxygen therapy promotes neurogenesis: where do we stand? 

Med Gas Res. 2011 Jun 27;1(1):14. 

PMID: 22146131

[2] Calvert JW, Cahill J, Yamaguchi-Okada M, Zhang JH. 

Oxygen treatment after experimental hypoxia-ischemia in neonatal rats alters the expression of HIF-1alpha and its downstream target genes.

J Appl Physiol. 2006 Sep;101(3):853-65. Epub 2006 May 25.

PMID: 16728520

[3] Li F, Fang L, Huang S, Yang Z, Nandi J, Thomas S, Chen C, Camporesi E.

Hyperbaric oxygenation therapy alleviates chronic constrictive injury-induced neuropathic pain and reduces tumor necrosis factor-alpha production.

Anesth Analg. 2011 Sep;113(3):626-33. doi: 10.1213/ANE.0b013e31821f9544. Epub 2011 May 19.

PMID: 21596875


[4] Kuffler DP. 

The role of hyperbaric oxygen therapy in enhancing the rate of wound healing with a focus on axon regeneration.

P R Health Sci J. 2011 Mar;30(1):35-42.

PMID: 21449496


[5] Rossignol DA, Bradstreet JJ, Van Dyke K, Schneider C, Freedenfeld SH, O'Hara N, Cave S, Buckley JA, Mumper EA, Frye RE.

Hyperbaric oxygen treatment in autism spectrum disorders.

Med Gas Res. 2012 Jun 15;2(1):16. doi: 10.1186/2045-9912-2-16.

PMID: 22703610


[6] Rossignol DA, Rossignol LW, Smith S, Schneider C, Logerquist S, Usman A, Neubrander J, Madren EM, Hintz G, Grushkin B, Mumper EA.

Hyperbaric treatment for children with autism: a multicenter, randomized, double-blind, controlled trial.

BMC Pediatr. 2009 Mar 13;9:21. doi: 10.1186/1471-2431-9-21.

PMID: 19284641


[7] Rossignol DA, Rossignol LW, James SJ, Melnyk S, Mumper E.

The effects of hyperbaric oxygen therapy on oxidative stress, inflammation, and symptoms in children with autism: an open-label pilot study.

BMC Pediatr. 2007 Nov 16;7:36.

PMID: 18005455


[8] Rossignol DA.

Hyperbaric oxygen treatment for inflammatory bowel disease: a systematic review and analysis.

Med Gas Res. 2012 Mar 15;2(1):6. doi: 10.1186/2045-9912-2-6.

PMID: 22417628


[9] Ozkurt B, Cinar O, Cevik E, Acar AY, Arslan D, Eyi EY, Jay L, Yamanel L, Madsen T.

Efficacy of high-flow oxygen therapy in all types of headache: a prospective, randomized, placebo-controlled trial.

Am J Emerg Med. 2012 Nov;30(9):1760-4. doi: 10.1016/j.ajem.2012.02.010. Epub 2012 May 3.

PMID: 22560101


[10] Lambru G, Matharu M.

Management of trigeminal autonomic cephalalgias in children and adolescents.

Curr Pain Headache Rep. 2013 Apr;17(4):323. doi: 10.1007/s11916-013-0323-1.

PMID: 23475698


[11] Trenell MI, Sue CM, Thompson CH, Kemp GJ.

Supplemental oxygen and muscle metabolism in mitochondrial myopathy patients.

Eur J Appl Physiol. 2007 Mar;99(5):541-7. Epub 2007 Jan 12.

PMID: 17219172


[12] Winograd CH, Newman AB.

Oxygen therapy for mitochondrial myopathy.

Chest. 2002 Oct;122(4):1496-7.

PMID: 12377891


[13] Bloch Y, Applebaum J, Osher Y, Amar S, Azab AN, Agam G, Belmaker RH, Bersudsky Y.

Normobaric hyperoxia treatment of schizophrenia.

J Clin Psychopharmacol. 2012 Aug;32(4):525-30. doi: 10.1097/JCP.0b013e31825d70b8.

PMID: 22722511


[14] Rockswold SB, Rockswold GL, Zaun DA, Zhang X, Cerra CE, Bergman TA, Liu J.

A prospective, randomized clinical trial to compare the effect of hyperbaric to normobaric hyperoxia on cerebral metabolism, intracranial pressure, and oxygen toxicity in severe traumatic brain injury.

J Neurosurg. 2010 May;112(5):1080-94. doi: 10.3171/2009.7.JNS09363.

PMID: 19852540


[15] Malek M, Duszczyk M, Zyszkowski M, Ziembowicz A, Salinska E.

Hyperbaric oxygen and hyperbaric air treatment result in comparable neuronal death reduction and improved behavioral outcome after transient forebrain ischemia in the gerbil.

Exp Brain Res. 2013 Jan;224(1):1-14. doi: 10.1007/s00221-012-3283-5. Epub 2012 Oct 2.

PMID: 23283415


[16] Haffor AS, Alttas OS.

Effects of exposure of rats to periodic versus continuous hyperoxia on antioxidant potentials and free radical production in relation to ultrastructural changes in myocardial cells.

Inhal Toxicol. 2010 Aug;22(10):797-804. doi: 10.3109/08958370903456629.

PMID: 20560719


[17] Wetzker R, Rubio I.

Hormetic signaling patterns.

Dose Response. 2012;10(1):83-90. doi: 10.2203/dose-response.11-012.Wetzker. Epub 2011 Oct 14.

PMID: 22423231


[18] Ristow M, Zarse K.

How increased oxidative stress promotes longevity and metabolic health: The concept of mitochondrial hormesis (mitohormesis).

Exp Gerontol. 2010 Jun;45(6):410-8. doi: 10.1016/j.exger.2010.03.014. Epub 2010 Mar 27.

PMID: 20350594


[19] Dave KR, Prado R, Busto R, Raval AP, Bradley WG, Torbati D, Pérez-Pinzón MA.

Hyperbaric oxygen therapy protects against mitochondrial dysfunction and delays onset of motor neuron diseasein Wobbler mice.

Neuroscience. 2003;120(1):113-20.

PMID: 12849745


[20] Godman CA, Joshi R, Giardina C, Perdrizet G, Hightower LE.

Hyperbaric oxygen treatment induces antioxidant gene expression.

Ann N Y Acad Sci. 2010 Jun;1197:178-83. doi: 10.1111/j.1749-6632.2009.05393.x.

PMID: 20536847


[21] Godman CA, Chheda KP, Hightower LE, Perdrizet G, Shin DG, Giardina C.

Hyperbaric oxygen induces a cytoprotective and angiogenic response in human microvascular endothelial cells.

Cell Stress Chaperones. 2010 Jul;15(4):431-42. doi: 10.1007/s12192-009-0159-0. Epub 2009 Dec 1.

PMID: 19949909


[22] Milovanova TN, Bhopale VM, Sorokina EM, Moore JS, Hunt TK, Hauer-Jensen M, Velazquez OC, Thom SR. 

Hyperbaric oxygen stimulates vasculogenic stem cell growth and differentiation in vivo.

J Appl Physiol. 2009 Feb;106(2):711-28. doi: 10.1152/japplphysiol.91054.2008. Epub 2008 Nov 20. 

PMID: 19023021


[23] Thom SR, Bhopale VM, Velazquez OC, Goldstein LJ, Thom LH, Buerk DG.

Stem cell mobilization by hyperbaric oxygen.

Am J Physiol Heart Circ Physiol. 2006 Apr;290(4):H1378-86. Epub 2005 Nov 18.

PMID: 16299259

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