Ozone Acting on Human Blood: The Hormetic Dose-Response Relationship (2011 Review)

September 20, 2026

Background

Hormesis is the name for a pattern seen across biology: a small dose of something that is harmful in large amounts can produce a benefit, because the body over-corrects in response to the mild challenge. Exercise, heat, cold and brief interruptions of blood supply are well-known examples. In this review, Professor Velio Bocci and colleagues Iacopo Zanardi and Valter Travagli, all of the University of Siena, argue that medical ozone follows the same pattern, and they use their laboratory data on ozonated human blood to explain why.

Study design

This is a narrative review published in the open-access Journal of Translational Medicine. It brings together the Siena group's own experiments - in which human blood was mixed with precisely measured oxygen-ozone gas outside the body, as in clinic-based autohaemotherapy - with the wider literature on hormesis and with clinical experience, mainly in peripheral arterial disease (poor circulation in the legs). It is not a clinical trial and there was no systematic search.

Findings

Ozone is gone within minutes. In the authors' experiments ozone was fully used up within the standard five minutes of mixing with blood. In that time most of the vitamin C in plasma, and a smaller share of the uric acid, was oxidised - these circulating antioxidants take the first hit. Ozone itself does not enter the blood cells.

The antioxidant reserve dips, then recovers. Total antioxidant capacity of whole blood fell by between roughly a tenth and a third, depending on the dose, and returned to its starting value within about 20 minutes as the red cells regenerated the spent antioxidants. About a fifth of the glutathione inside red cells was oxidised in the first minute and was likewise restored within 20 minutes.

Two messengers carry the effect. Hydrogen peroxide acts first and briefly, diffusing into blood cells. Lipid oxidation products, including 4-hydroxynonenal, act later and travel further. The authors describe how the blood protein albumin binds these compounds - a single albumin molecule can carry several - which both limits their toxicity and transports them around the body, where they are diluted, broken down by enzymes and excreted.

What the messengers do. In red cells, sugar metabolism speeds up, raising ATP and 2,3-DPG so that haemoglobin releases oxygen more readily. With repeated treatments the authors report younger red cells carrying more of the protective enzyme G6PD. White cells become more active, platelets release growth factors in proportion to the dose, and the cells lining blood vessels produce more nitric oxide, which relaxes the vessels.

The inverted U. Below a threshold the dose is entirely neutralised by plasma antioxidants and nothing happens. Within the therapeutic window the biological and clinical effects appear. Above it, antioxidant reserves are depleted and side effects emerge - the authors mention deep fatigue, seen in around one in ten patients with advanced arterial disease, particularly when early sessions used high doses. Their practical advice is to start low and go slow, stepping the dose up over a course of 15 to 20 sessions.

What the authors concluded

The authors conclude that the dose-response relationship for ozone in peripheral arterial disease can be drawn as an inverted U-shaped hormetic curve. They describe ozone as a pro-drug that acts through its messengers, and as an inducer of the body's own antioxidant enzymes. They call for large trials comparing ozone with standard treatments, and repeat the warning that inhaled ozone damages the lungs.

Limitations of this study

This is a narrative review by a research group with a long-standing commitment to ozone therapy, and much of the evidence is the group's own laboratory work. The measurements were made on blood treated outside the body; the paper notes that rectal insufflation is used in some countries but does not present equivalent data for it.

The authors themselves limit the conclusion: the U-shaped curve, they write, is meaningful only for peripheral arterial disease, and how ozone behaves in stroke, heart disease or autoimmune conditions remained unknown. The clinical observations behind the curve come from case series, not randomised trials.

The dose figures in the paper apply to a clinic blood procedure carried out by trained staff and are not instructions for home use. Ozone therapy is a complementary approach and should be discussed with your healthcare practitioner.