Lurie Center for Autism: Hyperbaric oxygen therapy

Hyperbaric oxygen therapy (HBOT) is sometimes discussed as a Complementary and Alternative Medicine (CAM) for individuals with autism spectrum disorders (ASD). Lurie Center clinicians summarize current research on HBOT.

Hyperbaric oxygen therapy (HBOT) is the medical use of oxygen at a higher level than normal atmospheric pressure. During HBOT a patient breathes an increased oxygen concentration (up to 100% – in comparison, room air has about 21% oxygen) using a pressure chamber. In the 1930’s HBOT was found useful in the treatment of decompression sickness (“the bends,” from deep water diving) and also has been shown effective in treating conditions such as gas gangrene and carbon monoxide poisoning. More recent research has examined the use of HBOT for conditions affecting the brain and nervous system such as cerebral palsy and multiple sclerosis, but studies have shown no benefit. The Undersea and Hyperbaric Medical Society (UHMS) oversees the ethical use of HBOT and has approved it to treat specific conditions based on research data. Autism is not included in the list because there is not enough evidence showing its effectiveness in this disorder.

The use of HBOT for autism was originally suggested due to three areas of research:

1. Some research studies have demonstrated that individuals with autism have hypoperfusion (decreased    blood flow) in several areas of the brain compared to controls 1,2. It was assumed that there must be a lack of oxygen due to low blood flow, since blood carries oxygen in the red blood cells to all parts of the body. Thus, using HBOT to administer more oxygen to autistic children was suggested as a way to treat the symptoms of autism.

Unfortunately, the reasons for finding hypoperfusion in autism are unknown. It cannot be assumed that because an abnormality in blood flow exists, that the tissue is hypoxic (lacking in oxygen). In addition, it is not simply oxygen delivery to cells that helps tissues in HBOT-treatable conditions. Human tissue will only use extra oxygen if chemical signals are present that tell the cells they need oxygen (that is, if they are hypoxic). There is no evidence of hypoxia in the brains of children or adults with autism.

2. Markers of oxidative stress have been found in the blood of individuals with autism3,4. Oxidative stress refers to an imbalance in cells between a) production of metabolic by-products that can be harmful if they accumulate, and b) activation of chemical pathways that result in clearing of those by-products. Oxygen is involved in the normal clearance of these by-products, so it has been suggested that HBOT might help alleviate oxidative stress in autism and improve symptoms.

It is unknown whether correcting lab values of oxidative stress in autism will improve outcome in the short term or over the lifespan. Oxidative stress is also present in people with mitochondrial diseases. Mitochondria are small parts of cells that generate energy and use oxygen to do this. HBOT is not useful in those conditions because the problem lies in abnormal enzymes and proteins in the chemical pathways involved, not in levels of oxygen.

3. Postmortem brain study of autistic children and adults show higher levels of markers of immune activation5. Since the publication of this study, this has often been assumed to mean that there is inflammation in the autism brain. Inflammation often creates metabolic by-products, or free radicals, that are harmful if they accumulate at high levels (this is referred to as oxidative stress). Oxygen is involved in the normal clearance of these by-products, so it has been suggested that HBOT will help normalize any damage done by the presumed inflammation.

A problem with this approach is that the meaning of increased levels of immune markers in autism brain is still unknown. Immune activation was present in the brain specimens in the Vargas study, but immune inflammation and damage was not. Because an abnormal finding exists in autistic patients does not necessarily mean it signifies a cause of the disorder that needs to be treated. Many of the immune markers, or proteins expressed on the brain’s immune cells (microglia), in the Vargas study act as growth factors in early life and others are found in healing tissue. In lab research studies, an antibiotic called minocycline decreases the amount of those same markers on microglia that were found by Vargas5. The NIH conducted a trial of minocycline in children with autism but no differences were reported in the behavior of the treated children (the study is not yet published).

Studies of HBOT in autism

In 2009 a double-blind study of autistic children concluded that HBOT treatment provided significant improvement in the children's behavior immediately after treatment sessions6. The study relied heavily on parent report, including a checklist that has not been validated in the scientific community. The results also indicated a significant placebo effect. The study had many other problems in design and outcome measures, many of which are discussed in Jepson et al., 2011, a study funded by an organization based on Applied Behavior Analysis (ABA). Since autism is an individualized disorder, the Jepson study looked for changes in 11 autism behaviors for each child after multiple baseline measures were taken. They compared each child to him or herself after the HBOT treatments. They found that hyperbaric oxygen therapy does not have a significant effect on the symptoms of autism 7.

Several deaths have been reported during HBOT but were due to explosions and fires in the chambers being used at home without professional supervision, not to adverse reactions to the therapy itself. The treatment is quite expensive, costing $150-900 dollars per treatment or $14,000-17,000 for a home chamber. HBOT diverts energy, emotions and resources away from more productive, evidence-based therapies.


References

1. Ryu YH, Lee JD, Yoon PH, Kim DI, Lee HB, Shin YJ. 1999. Perfusion impairments in infantile autism on technetium-99m ethyl cysteinate dimer brain single-photon emission tomography: comparison with findings on magnetic resonance imaging. Eur J Nucl Med. 26:253-259.

2. Wilcox J, Tsuang MT, Ledger E, Algeo J, Schnurr T. 2002. Brain perfusion in autism varies with age. Neuropsychobiology. 46:13-16.

3. James SJ, Cutler P, Melnyk S, Jernigan S, Janak L, Gaylor DW, Neubrander JA. 2004. Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism. Am J Clin Nutr. 80:1611-1617.

4. Ming X, Stein TP, Brimacombe M, Johnson WG, Lambert GH, Wagner GC. 2005. Increased excretion of a lipid peroxidation biomarker in autism. Prostaglandins Leukot Essent Fatty Acids. 73:379-384.

5. Vargas DL, Nascimbene C, Krishnan C, Zimmerman AW, Pardo CA. 2005. Neuroglial activation and neuroinflammation in the brain of patients with autism. Ann Neurol. 57:67-81.

6. Rossignol DA, Rossignol LW, Smith S, Schneider C, Logerquist S, Usman A, Neubrander J, Madren EM, Hintz G, Grushkin B, Mumper EA. 2009. Hyperbaric treatment for children with autism: a multicenter, randomized, double-blind, controlled trial. BMC Pediatr. 9:21.

7. Jepson B, Granpeesheh D, Tarbox J, Olive ML, Stott C, Braud S, Yoo JH, Wakefield A, Allen MS. 2011. Controlled evaluation of the effects of hyperbaric oxygen therapy on the behavior of 16 children with autism spectrum disorders.    J Autism Dev Disord. 2011. 41:575-88.

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