If you've spent any time in the hyperbaric world, you've probably heard the debate: is it the oxygen that heals, or does the pressure itself matter? One of the most influential voices on this question is Dr. Paul Harch — Clinical Professor at Louisiana State University School of Medicine, Director of LSU's Hyperbaric Medicine Department, Johns Hopkins-trained physician, and author of The Oxygen Revolution. His published research makes a case that should change how every one of us thinks about what happens inside a hyperbaric chamber.
Here's his argument, and it's backed by peer-reviewed science.
The 60-Year Mistake
For the entire modern era of hyperbaric medicine, HBOT has been officially defined as treatment with 100% oxygen at pressures above 1.4 ATA. The focus has been almost entirely on the oxygen component. Pressure? Just the delivery vehicle. A way to push more O₂ into the blood.
Dr. Harch calls this definition arbitrary — and he's been publishing papers to prove it.
In his landmark 2015 paper in Medical Gas Research (PMC4499900), he pointed out an absurdity baked into the traditional definition: treatment at 1.4 ATA qualifies as HBOT, but treatment at 1.399999 ATA does not. Yet there is zero published evidence showing any clinical difference between these two pressures. Furthermore, the definition excludes an entire body of Russian hyperbaric literature from the Soviet era, where pressures between 1.1 and 1.4 ATA were routinely used with documented benefits.
But the deeper problem, according to Harch, is that this oxygen-centric definition completely ignores something that basic science has known for decades: pressure itself is biologically active.
The Science of Pressure Bioactivity
This is where it gets fascinating. Dr. Harch references an extensive basic science literature — particularly the work of Macdonald & Fraser (1999), a major review published in Comparative Biochemistry and Physiology — showing that dozens of investigators have documented widespread biological effects of increased pressure across virtually all living organisms. These effects begin as early as 30 seconds after compression.
That's worth repeating: measurable biological changes happen within half a minute of pressure change, across species from single-cell organisms to mammals. This isn't an oxygen effect — it's a direct pressure effect on cellular biology.
Yet, as Harch writes, this body of knowledge was essentially unknown to the clinical hyperbaric medicine community, despite being well-established in basic science.
8,101 Genes — Not Just Oxygen
Perhaps the most striking data Dr. Harch presents comes from gene array studies. He cites research (Godman et al., 2009) showing that a single HBOT session can up- or down-regulate up to 8,101 human genes. The pattern is therapeutically significant: growth, repair, and anti-inflammatory genes get turned up, while pro-inflammatory and cell-death (apoptotic) genes get turned down.
But here's the key insight: these genetic effects come from the combination of increased pressure AND increased oxygen. Studies have shown that independent and overlapping sets of genes respond to pressure alone, oxygen alone, or the combination (Chen et al., 2009). They are not the same genes. Pressure activates pathways that oxygen alone does not.
One particularly revealing study (Kendall et al., 2013) found differential suppression of inflammatory genes at different oxygen pressures — 1.0, 1.5, and 2.4 ATA — with maximum anti-inflammatory suppression occurring at 1.5 ATA, not at the highest pressure. More is not always more.
The "Sham" That Wasn't a Sham
This understanding has massive implications for how we interpret clinical research. Dr. Harch has been especially vocal about the U.S. Department of Defense TBI studies, which used pressurized air at 2.0 ATA as a "sham" control — and then concluded HBOT didn't work because both the treatment and "sham" groups improved.
Harch's argument is straightforward: a 2.0 ATA pressurized air exposure is NOT a sham. It is a different dose of hyperbaric therapy. Pressure at 2.0 ATA is biologically active. Oxygen at 0.42 ATA (the partial pressure of O₂ in air at 2.0 ATA) is biologically active. Calling it a placebo is scientifically wrong. Of course both groups improved — both groups received treatment. They just received different doses.
When you reframe these studies as multi-dose trials comparing different combinations of pressure and oxygen rather than treatment-vs-placebo, the results actually align with civilian studies showing positive outcomes. The data isn't conflicting — it was just being misread.
The Surprising Finding: More Pressure Doesn't Mean More Benefit
One of the most thought-provoking studies Harch references in his work comes from Kendall et al. (2013), published in Undersea and Hyperbaric Medicine. The researchers wanted to understand how different treatment pressures affect inflammatory gene expression — so they exposed human endothelial cells to a chronic wound environment (hypoxia combined with inflammatory triggers), and then treated them with oxygen at three different pressures: 1.0 ATA (normobaric), 1.5 ATA, and 2.4 ATA.
The assumption most people would make is straightforward: higher pressure means stronger effect. But that's not what happened. The results showed that inflammatory gene suppression was different at each pressure — and the maximum anti-inflammatory response occurred at 1.5 ATA, not at 2.4 ATA. The highest pressure didn't produce the strongest healing signal. A moderate pressure did.
This is a finding that deserves far more attention than it gets. It challenges the deeply held assumption in hyperbaric medicine that clinical-grade, high-pressure treatments are always superior. It suggests that the relationship between pressure dose and biological response is not linear — more is not automatically better. Different pressures appear to activate different gene expression profiles, each with its own therapeutic signature. And a moderate pressure that falls squarely within the range of mild hyperbaric chambers produced the most powerful anti-inflammatory result in this study.
A New Definition for a New Era
In 2022, Dr. Harch published a formal proposal in Medical Gas Research (PMC9555024) to redefine the entire field. His proposal:
"Hyperbaric therapy" should be the overarching term — defined as medical treatment using increased barometric pressure and increased partial pressures of breathing gases. This acknowledges the independent bioactivity of pressure itself.
"Hyperbaric oxygen therapy" (HBO₂) becomes a subset — specifically where the breathing gas is near-100% oxygen.
This isn't just academic wordplay. This redefinition would formally recognize the 300-year history of pressurized air therapy (including its largely forgotten use in the 1918 Spanish Flu pandemic to save patients dying from respiratory distress), account for the full spectrum of pressure biology research, and — critically — explain why treatments at pressures and oxygen concentrations below the traditional thresholds have consistently shown clinical benefits.
Why this matters for mild HBOT:
Dr. Harch himself has stated that dosing of hyperbaric therapy is still in its infancy — particularly in the pressure ranges between 1.0 and 2.0 ATA. There is an enormous, unexplored territory of pressure-oxygen combinations that may hold therapeutic value.
This is directly relevant to mild hyperbaric therapy. If pressure itself activates gene expression, triggers anti-inflammatory cascades, and produces biological changes within 30 seconds of compression — then every session in a mild chamber is doing more than simply delivering a modest increase in dissolved oxygen. The pressure cycling is a therapeutic mechanism in its own right.
Thousands of people in hyperbaric communities around the world are getting real, meaningful results from mild chambers operating with ambient air — no supplemental oxygen added. This has been clear from user experiences for a long time. What Harch's research does is explain why. If pressure itself activates over 8,000 genes, triggers anti-inflammatory cascades, and shifts cellular repair pathways — then a mild chamber with ambient air is already delivering a powerful therapeutic signal with every session. The military TBI studies accidentally demonstrated the same thing: groups breathing regular air under pressure showed significant improvement. Not because of extra oxygen — because of pressure.
As Harch concluded in his 2015 paper: hyperbaric oxygen therapy may be the oldest, most enduring, and most effective gene therapy in existence. And it works through both of its components — not just one.
Sources:
Harch PG. "Hyperbaric oxygen in chronic traumatic brain injury: oxygen, pressure, and gene therapy." Medical Gas Research. 2015;5:9. (PMC4499900) https://pmc.ncbi.nlm.nih.gov/articles/PMC4499900/
Harch PG. "New scientific definitions: hyperbaric therapy and hyperbaric oxygen therapy." Medical Gas Research. 2022;13(2):92-93. (PMC9555024) https://pmc.ncbi.nlm.nih.gov/articles/PMC9555024/
Macdonald AG, Fraser PJ. "The transduction of very small hydrostatic pressures." Comp Biochem Physiol A Mol Integr Physiol. 1999;122(1):13-36.
Chen Y, et al. "Microarray analysis of gene expression in rat cortical neurons exposed to hyperbaric air and oxygen." Neurochem Res. 2009;34:1047-56.
Godman CA, et al. "Hyperbaric oxygen induces a cytoprotective and angiogenic response in human microvascular endothelial cells." Cell Stress and Chaperones. 2009.
Kendall AC, et al. "Different oxygen treatment pressures alter inflammatory gene expression in human endothelial cells." Undersea Hyperb Med. 2013;40(2):115-23.
