The History of EBO2 (EBOO): From Bocci's Lab to Today's Wellness Clinics

EBO2 (also called EBOO) is the newest chapter in a much older story about ozone and medicine, one that runs from 18th-century chemistry through a specific Italian research group in the 1990s to the wellness clinics marketing it today. This guide traces that history using what its sources actually document. Where a date or a name is not established in the sources we could verify, we say so plainly rather than filling the gap with a tidier story.

Ozone before medicine

Ozone was noticed before it was understood. In 1785, the Dutch physicist Martinus van Marum recorded a distinctive smell while running electricity through oxygen, the first documented observation of what the gas would later be identified as [1]. It took over fifty years for the substance itself to be named: the chemist Christian Friedrich Schönbein identified and named the gas “ozone,” from the Greek word for smell, in 1840 [1]. Medical use followed within a generation. By 1859, the physician Theophilus Thompson had documented using ozonized oils to treat respiratory conditions, an early example of ozone applied therapeutically rather than studied as a chemical curiosity [1]. Ozone therapy in this era, and for long after, was applied and described more confidently than controlled evidence has since been able to support. A widely cited 2011 clinical review of the field is itself an example of that pattern rather than a critique of it: it describes ozone therapy as having been “utilized and heavily studied for more than a century” and asserts, without a qualifying caveat, that its effects are established and safe [2]. Later, more rigorous evidence for specific ozone treatments has not matched that confidence. A 2015 Cochrane review of ozone for diabetic foot ulcers, pooling three small trials, concluded its authors were unable to draw any firm conclusion about effectiveness [14], and a 2024 meta-analysis of ozone injections for knee osteoarthritis found outcomes merely statistically similar to a comparison treatment rather than superior to it, with no placebo-controlled arm [15]. That gap, between how confidently ozone therapy has long been described and what controlled comparisons actually find, is a thread running from this early period through EBOO’s own development decades later.

MAH and the German tradition

The therapy that would eventually lead to EBOO took shape in 20th-century Germany. The surgeon Erwin Payr began applying ozone to control bacteria in surgical settings in the 1930s, work influenced by earlier dental use of ozone by the Swiss practitioner E.A. Fisch [1]. Institutional ozone therapy, in the form recognizable today, developed in the decades after. In 1953, the German physician Hans Wolff established the first dedicated ozone therapy training school, and by 1961 he had introduced the techniques known as major and minor autohemotherapy (MAH), in which a batch of blood is drawn, mixed with ozone gas, and reinfused into the same patient [1]. Wolff’s collaborator Joachim Hänsler developed a more precisely calibrated ozone generator in 1957 and 1958, and the two later cofounded the German Ozone Therapy Association in 1972, giving the practice a formal professional home in Europe [1]. MAH is the direct ancestor of EBOO: EBOO was later designed explicitly to treat a larger blood volume more continuously than the batch-based MAH technique allowed, rather than as an unrelated invention.

Bocci, Siena, and the scientific case for ozone as a signaling molecule

Velio Bocci, born December 21, 1928, earned his medical degree from the University of Siena in 1954 and spent his career there in the Department of Physiology, later named Emeritus Professor in May 2003 [8]. Over roughly five decades he authored close to 480 publications and three books on oxygen-ozone therapy, more than any other researcher in the field, and served as the first president of the International Scientific Committee of Ozone Therapy (ISCO3) [8][9]. His most cited book, “Ozone: A New Medical Drug,” was published by Springer in 2005 and laid out the mechanistic case, developed across his research career, that a precisely controlled dose of ozone dissolved in blood acts as a signaling molecule, triggering antioxidant and immune responses rather than simply behaving as the toxic gas it is when inhaled [7]. A later review he coauthored describes this as the “ozone paradox”: the same molecule that damages lung tissue on inhalation is proposed to produce a controlled, therapeutically useful stimulus when a calibrated dose is dissolved in blood outside the body [6]. This mechanistic framework, developed and defended primarily by Bocci and close collaborators over decades, is the scientific case that EBOO was built on top of. Sources available for this guide document Bocci’s career in detail but do not give a date of death; an ozone-therapy association’s 2019 tribute describes his death as a recent loss to the field at that time without stating the date itself, so we treat his date of death as unresolved [9].

EBOO: what problem it was designed to solve, and the papers that introduced it

Nicola Di Paolo, a nephrologist at the University of Siena, led the group that developed EBOO. A 2005 paper from that group states plainly that “since 1990 our group has been using extracorporeal circulation to ozonate blood,” dating the technique’s origin to that year [4]. The stated goal was to improve on MAH: by running blood continuously through an external circuit rather than treating it in batches, and by adding a filtration step, the Siena group aimed to deliver a more controlled ozone dose across a larger share of a patient’s blood volume than MAH could reach in one session [5]. The first published human report followed in 2000, describing early use of the apparatus including self-experimentation by one of the researchers, who reported the disappearance of lipomas after six treatments, followed by use in a patient with Madelung disease and several patients with atherosclerotic vascular disease [3]. That paper, along with the case reports and small trials that followed it through the mid-2000s, constitutes the original published record of EBOO; it is a small literature, produced almost entirely by the technique’s own developers, not an independent multi-center body of research.

Why it stalled in academic medicine

The EBOO literature did not grow much past its Siena origins. The published record consists mainly of case reports, a small controlled trial, and reviews from the same research group and its close collaborators, rather than the larger, independent, multi-center trials that would normally follow a promising preliminary result in mainstream medicine [3][4][5]. Ozone therapy generally shares this pattern: the field has produced case reports, small trials, and advocate-authored reviews at a much higher rate than it has produced large, independent, placebo-controlled trials, and the more rigorous systematic reviews that do exist for specific ozone treatments tend to land on equivocal results rather than a clear benefit [14][15].

A few structural reasons help explain why. EBOO requires a dedicated extracorporeal circuit and gas-exchange device that most hospitals and research centers have no reason to acquire for a therapy without an approved indication, which limited independent replication to groups willing to build or import the equipment themselves. Funding for a large trial typically follows a plausible path to regulatory approval and reimbursement, and ozone’s fixed regulatory status as a non-approvable therapeutic gas removed that incentive for mainstream device and pharmaceutical sponsors from the start. Without that evidence base, and without an FDA-approved use to build a reimbursement pathway around, EBOO remained a niche technique practiced at a small number of clinics rather than becoming a standard offering in nephrology or vascular medicine, the specialties where it was originally studied.

Rebranding as EBO2 and the US wellness-clinic wave

At some point the same technique began appearing under a second name, EBO2, alongside the original EBOO, and today clinics and device makers use the two interchangeably. Exactly when or by whom the term “EBO2” was first used is not documented in the sources available for this guide, and we treat that specific point as unresolved rather than assign it a date we cannot support. What is documented is the broader pattern: a 2026 newspaper investigation into wellness and longevity medicine found ozone therapy, offered under both names, now sold alongside NAD+ infusions and peptide treatments at med spas and longevity clinics across the country, marketed to healthy people rather than to the vascular and dialysis patients the original Siena studies focused on [10]. Our longevity guide covers that specific marketing and what evidence it does and does not rest on. Equipment suppliers now market complete EBOO and EBO2 systems, built around a calibrated ozone generator and a hollow-fiber filtration cartridge, directly to clinics wanting to add the service [11]. The technique moved from a narrow nephrology research program to a wellness-industry offering without a corresponding expansion of the clinical evidence behind it.

Regulatory arc

US regulatory treatment of ozone has not changed for decades: ozone is not FDA-approved to treat any condition, and the FDA’s own device rules describe it as a toxic gas with no known useful medical application in specific, adjunctive, or preventive therapy, a standard that predates EBOO’s development entirely [13]. That standard has been enforced against modern EBOO equipment directly. In July 2025, the FDA warned a Michigan device maker that its EBOO Full Spectrum UV and related autohemotherapy equipment, marketed for treating autoimmune, cardiovascular, and respiratory disease, lacked the premarket clearance required to make those claims and that the company had not notified the agency before introducing the devices [12]. The underlying regulatory position, ozone has no approved medical use, is the same one that applied when Bocci and Di Paolo were first publishing on EBOO in the 1990s and 2000s; only the specific enforcement targets have changed.

Where the research stands today

The evidence base has not fundamentally changed shape since EBOO’s original publications: small studies and reviews from a limited set of researchers, without the large independent trials that would settle the question either way, and no trial at all for many of the uses now marketed at wellness clinics, including longevity and anti-aging claims. See our research page for the underlying studies cited across our EBO2 coverage, and what EBO2 is and how the current evidence looks overall for the full picture.

Bottom line

EBO2 descends from a specific, documented lineage: 19th-century ozone chemistry, a German therapeutic tradition built through the mid-20th century [1], and a Siena nephrology group that built EBOO starting in 1990 to improve on older autohemotherapy techniques [4]. Velio Bocci supplied much of the mechanistic argument for why any of this might work [6][7]. What is not documented is exactly when the therapy picked up its second name, EBO2, or when it left nephrology research to become a wellness-clinic offering; those transitions happened without the kind of paper trail that marks the earlier history. The regulatory position has not moved during any of it: ozone has never been FDA-approved for a medical use, then or now [13].