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Pain & inflammation

Lyme disease and co-infections

The evidence for hyperbaric oxygen in Lyme is early and we present it as such. The best-known study is a 1998 Texas A&M series of 91 people with persistent symptoms after antibiotics, in which most reported improvement, but it was uncontrolled and only ever published as a conference abstract. Lab work shows the Lyme bacterium has weak defences against oxygen, which is the theory behind the approach. We could find no published studies of hyperbaric oxygen for the common co-infections (Babesia, Bartonella), so we do not make claims about them.

Evidence so far
Early
Reading timeAbout 12 minutes

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Why this is being studied

Lyme disease is caused by the spirochete Borrelia burgdorferi, transmitted by tick bite, and a proportion of people report fatigue, joint pain and neurological symptoms that persist long after standard antibiotics. Interest in oxygen comes from the organism's biology: Borrelia grows in low-oxygen tissue and lacks the catalase and peroxidase enzymes that protect most bacteria from oxidative damage (Whitehouse 1997), so raising tissue oxygen sharply may in theory harm it. It is important to be clear that the human evidence consists of one uncontrolled 1998 case series and isolated case reports; there are no randomised or sham-controlled trials of HBOT for Lyme disease, and no published HBOT studies at all for co-infections such as Babesia or Bartonella.

Where the evidence stands

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The mechanism

What is going on, and why this might help

What is going on in the body

Lyme disease is caused by the spirochaete Borrelia burgdorferi and related species, sometimes alongside co-infections such as Babesia, Bartonella or Anaplasma. Borrelia is a microaerophilic organism: it grows best at low oxygen levels and, unusually, lacks the enzymes catalase and peroxidase that most bacteria use to neutralise reactive oxygen species. It can also change form, evade the immune system and persist in poorly perfused tissues such as joints, tendons and connective tissue. Persistent symptoms after antibiotic treatment are debated: proposed contributors include ongoing infection, residual bacterial debris driving inflammation, autoimmune activation, and damage already done to nerves and tissue.

Where oxygen comes in

The most specific argument concerns the organism itself. Because Borrelia lacks catalase and peroxidase, it is vulnerable to oxidative stress, and laboratory work has shown that high oxygen tensions inhibit its growth. Hyperbaric oxygen raises tissue oxygen to levels that microaerophilic organisms find hostile, and increases neutrophil killing capacity, which is oxygen-dependent. Delivery of dissolved oxygen into poorly perfused connective tissue may reach niches that antibiotics penetrate poorly. Separately, anti-inflammatory effects on TNF-α, IL-1β and IL-6 and improved perfusion are relevant to the persistent-symptom picture whether or not live organisms remain. A Jarisch-Herxheimer-type worsening has been described in case series, which some interpret as evidence of bacterial killing, though this is not proven.

How solid is this

The bactericidal mechanism is supported by in-vitro work and the known biology of Borrelia, but not by controlled human trials. Human evidence is limited to an unpublished series of 91 people (Fife 1998), a case report (Huang et al. 2014) and small open-label reports, so for Lyme disease this remains theoretical with laboratory support. Key references: Austin 1993 (oxygen sensitivity of Borrelia in vitro); Fife 1998 (Texas A&M series).

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The studies

Every study is laid out the same way: what the researchers wanted to find out, who took part, what they actually did, what they found, why it might work and where the limits are. No jargon, and a link to the original if you want to read it yourself.

Each study is laid out the same way: what the researchers asked, who took part, what they did, what they found, why it might work, and where the limits are. The clinician layer at the end of each one carries the numbers.

Paper 1

Treatment of Lyme disease with hyperbaric oxygen therapy

Fife and Freeman · Undersea and Hyperbaric Medical Society meeting · 1998 · uncontrolled case series, n=91 (conference abstract, not peer-reviewed)

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What they asked

In the 1990s, Dr William Fife and colleagues at Texas A&M University asked whether hyperbaric oxygen could help people with Lyme disease whose symptoms had persisted despite intravenous antibiotics. The rationale was laboratory work by Austin showing that the Lyme spirochete, Borrelia burgdorferi, survives poorly when oxygen levels rise above the low concentrations found deep in tissue. This report was presented as a conference abstract at the Undersea and Hyperbaric Medical Society meeting, not as a peer-reviewed full paper.

Who took part

Ninety-one people completed treatment. All met CDC criteria including a positive Western blot, and all had failed at least one course of intravenous antibiotics, with many still deteriorating on antibiotics when they enrolled. Nine were later excluded from analysis for other medical problems. There was no comparison group.

What they did

Participants breathed 100 per cent oxygen at 2.36 ATA for 60 minutes, typically twice a day for five days followed by two days' rest. Most had between 10 and 30 sessions; one person had 145 over three months. In total 1,995 sessions were given. Symptoms were scored before and after on a simple 0-to-10 questionnaire covering multiple complaints, and the researchers noted whether participants experienced a Jarisch-Herxheimer reaction, the temporary worsening thought to occur when large numbers of bacteria die.

What they found

About 85 per cent reported significant improvement and 13 per cent reported none. The average total symptom score fell from about 114 to about 49. Ninety of 91 people experienced marked Herxheimer-type reactions, usually starting within the first five days and sometimes continuing for a month after the course. In some people improvement continued for eight months.

Why it might work

Borrelia lacks the enzymes catalase and peroxidase that most bacteria use to neutralise reactive oxygen species (Whitehouse and colleagues, Infection and Immunity 1997), which makes it unusually vulnerable to oxidative damage. Austin's culture work suggested it could not survive transfer into ordinary air. Hyperbaric oxygen raises tissue oxygen to levels far above those found in the joints, connective tissue and nervous tissue where the organism is thought to persist, so the hypothesis is that it either damages the bacteria directly or makes them more susceptible to antibiotics and immune attack.

Limits

This is an uncontrolled case series reported only in abstract form, with no placebo group, no blinding, no independent confirmation of diagnosis and a self-scored questionnaire, so expectation and natural fluctuation could account for much of the change. Whether antibiotics were continued alongside is not stated. Follow-up was informal. Nearly three decades later there are still no randomised controlled trials of HBOT for Lyme disease and no published human studies at all for co-infections such as Babesia or Bartonella, so this remains a hypothesis-generating report rather than evidence of effectiveness.

Paper 2

Hyperbaric oxygen therapy and chronic Lyme disease: the controversy and the evidence

Fife and Eckert · Textbook of Hyperbaric Medicine, Springer · 2017 · review chapter

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What they asked

Nearly twenty years after the original Texas case series, Caroline Fife (a hyperbaric and wound physician) and Kristen Eckert wrote a chapter for the Textbook of Hyperbaric Medicine reviewing what is and is not known about hyperbaric oxygen for Lyme disease and so-called chronic Lyme disease. The chapter title, which refers to controversy and evidence, signals its purpose: to set the anecdotes against the evidential standards used for approved hyperbaric indications. We had access only to the abstract and preview, not the full chapter.

Who took part

As a review chapter it enrols no participants. The material it draws on consists of the 1998 uncontrolled series, individual case reports including Huang 2014, laboratory studies of the organism's oxygen tolerance, and the broader clinical literature on persistent symptoms after Lyme disease.

What they did

The authors summarised the biological rationale, described the published clinical reports and their protocols (broadly 2.0 to 2.5 ATA for 60 to 90 minutes, in courses of 10 to 40 sessions), and weighed them against the standards required to make HBOT an accepted indication. They also considered the contested definition of chronic Lyme disease itself, since disagreement about whether persistent infection exists shapes how any treatment claim is judged.

What they found

Their conclusion is careful: evidence is scarce, some dramatic individual improvements have been reported, and neither Lyme disease nor chronic Lyme disease is an approved indication for HBOT in the United States or Europe. Rather than recommending or dismissing treatment, they proposed establishing a registry of Lyme patients treated with HBOT so that outcomes could be collected systematically and used to design the prospective trials that are needed.

Why it might work

The chapter restates the oxygen-sensitivity argument: Borrelia is a microaerophilic organism that grows in around 4 per cent oxygen, lacks catalase and peroxidase, and so has weak defences against the reactive oxygen species generated when tissue oxygen rises sharply. Hyperbaric oxygen may also improve the function of immune cells and enhance antibiotic penetration in poorly perfused tissue. None of these mechanisms has been demonstrated in infected humans.

Limits

This is expert opinion built on a very thin literature, and the authors say so. There are no randomised or sham-controlled trials, no standardised outcome measures, and no published studies of HBOT for the co-infections (Babesia, Bartonella and others) that often feature in discussions of persistent tick-borne illness. Case reports are subject to publication bias, since improvements are reported and failures are not. The chapter appears in a specialist textbook and reflects the authors' clinical perspective.

Paper 3

Hyperbaric oxygen therapy as an effective adjunctive treatment for chronic Lyme disease

Huang et al. · Journal of the Chinese Medical Association · 2014 · single case report

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What they asked

Huang and colleagues at a hospital in Taipei reported a single patient whose Lyme disease symptoms had persisted for years through multiple courses of antibiotics, and asked whether a course of hyperbaric oxygen might help. A case report of this kind documents what happened to one person; it cannot prove that the treatment caused the outcome.

Who took part

One man, aged 31, working in finance. His illness began in 2003 with intermittent fevers, fatigue and bone pain, followed months later by joint pain and the expanding skin rash (erythema migrans) typical of Lyme disease. Borrelia IgG antibodies were positive. The report does not describe Western blot or PCR confirmation. Between 2004 and 2011 he received amoxicillin, doxycycline, co-amoxiclav, intravenous penicillin and oral cefuroxime, with only partial or minimal improvement.

What they did

He was treated with 100 per cent oxygen at 2.5 ATA for 90 minutes per session, 30 sessions in total, delivered in three blocks of ten. The report does not clearly state whether antibiotics were continued during the hyperbaric course, nor over what calendar period the sessions were spread.

What they found

The authors describe a stepwise improvement: nervous-system symptoms eased first, followed by musculoskeletal complaints, and by the end of the third block his long-standing symptoms had resolved. No specific duration of follow-up is given. The authors concluded that HBOT might be an effective adjunctive treatment for people with chronic Lyme disease who have not responded to antibiotics, while noting it is not a routinely recommended therapy in Taiwan.

Why it might work

The authors draw on the same reasoning as the earlier American work: Borrelia thrives in low-oxygen tissue and lacks the catalase and peroxidase enzymes that protect most bacteria from oxidative stress, so raising tissue oxygen sharply may harm the organism or make it more vulnerable to antibiotics and immune clearance. High oxygen may also reduce inflammation in affected joints and nerves. These are plausible explanations, not demonstrated ones.

Limits

A single case is the weakest form of clinical evidence. Symptoms of persistent Lyme disease fluctuate naturally, and after eight years of illness a spontaneous improvement coinciding with treatment cannot be excluded. Diagnosis rested on serology alone, there was no blinding or control, outcome was the patient's own report, and follow-up is unspecified. Cases that improve are far more likely to be written up than those that do not. This report, together with the 1998 series, is essentially all that exists in the human literature; there are no controlled trials and nothing published on co-infections.