The Scientific Review of Alternative Medicine

Intravenous hydrogen peroxide is an anomalous treatment offered as a near-panacea by some practitioners of “alternative” or “integrative medicine.” Its rationale is based almost entirely on the claims of the late Charles H. Farr, MD, PhD, the self-styled “father of oxidative medicine.” An evaluation of Farr’s writings and of the relevant basic science and clinical literature, however, demonstrate that the treatment is implausible and dangerous.

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Introduction

Hydrogen peroxide (H₂O₂) is a highly reactive compound that is caustic to living tissues. It spontaneously decomposes to water and oxygen, a reaction that is greatly accelerated in the presence of peroxidases (mainly catalase), which are ubiquitous in human blood and tissues. H₂O₂ has been used as a disinfectant for the mouth, the skin, fabric, and medical equipment, and as a bleaching agent for teeth and hair. H₂O₂ used as an irrigant in surgical fields or other large wounds or consumed in any form, including intravenously, has resulted in predictable, catastrophic complications: arterial and venous gas emboli, emphysema, respiratory arrest, strokes, multiple cerebral infarcts, seizures, colonic ulcers, intestinal gangrene, acute hemolytic crises, shock, cardiac arrest, and death.^1-7

In 1998, the late biochemist Saul Green wrote an important essay for SRAM on intravenous hydrogen peroxide (IV H₂O₂) and other “oxidative” treatments.¹ This article adds a clinical perspective and a bit of history to that essay; it also critiques, in some detail, the primary source that proponents cite to justify their use of IV H₂O_2.

Background: Charles H. Farr

For more than 25 years, a fringe group of practitioners has advocated the use of IV H₂O₂ for a multitude of indications.¹ The champion of this method was the late physician Charles H. Farr, MD, PhD (1927–1998), the self-styled “father of oxidative medicine.” Farr claimed to have discovered “a positive metabolic effect to intravenous infusions of hydrogen peroxide,” and authored an impressively thick “workbook” on the subject.^{8 (p. 2)} A search on PubMed (the online database of the National Library of Medicine) reveals no citations by Farr concerning H₂O₂. There is only one article, published in 1959, likely to have been authored by him at all.⁹

Farr advocated other dubious methods in addition to IV H₂O_2. Among these were: EDTA “chelation therapy;” Ozone Therapy; Ultraviolet Blood Irradiation (UVBI); dimethyl sulfoxide; and intravenous vitamin C.¹⁰ Farr was a founder of the American College for Advancement in Medicine (ACAM), the major advocacy organization for “chelation therapy,” and the founder and director of the International Bio-Oxidative Medical Foundation (IBOMF) and its close affiliate, the International Oxidative Medicine Association (IOMA), which have espoused such methods through conferences, advertisements, and “research.”^11,12 Recently, the IBOMF/IOMA appears to have been absorbed into the ACAM under the category “Oxidative Medicine Division.”¹³

In 1997, the FDA inspected the IBOMF Institutional Review Board (IRB) and found that it: had only a single member (a chiropractor); had violated numerous articles of federal code; and was inadequate to the task of protecting research subjects. The IBOMF IRB was, in essence, a charade. The FDA, in a letter to Farr, ordered the IRB to “withhold approval of all new studies” and “not to allow any new subjects to enter in or be added to open studies. . . .”^{14 (p. 4)}

In 1999, the IBOMF/IOMA listed 87 members.¹⁵ Of these, 27 (including current president Robert Rowen) have been disciplined by medical boards. One of those disciplined was physician assistant Robert L. White, whose Oklahoma physician’s assistant license was revoked in 2001 for “Fraud Unspecified.”¹⁶ White, who also lists “ND” (naturopathic doctor) and “PhD” after his name, worked at Farr’s “Genesis Medical Research Institute” in Oklahoma City for years and wrote an essay in which he claimed that Farr’s “work was submitted to the Nobel Foundation for consideration of the prestigious ‘Nobel Peace Prize’ in Medicine.”¹⁷

In 1978, Farr founded a company, “bio pro, inc.,” that sells “alternative medicine” products including the “Aquatron PU 050 IR” (an “Ultraviolett [sic] purification machine” for “only $3,675.00”) and “HOWW TOOOO. . . . The ‘must do’ seminars for those who own or are managing a Complimentary [sic] Medicine Practice.” The seminars teach, among other things, “How to protocol [sic] administration for Chelation, Oxidation, Chelox, TriOx, Ascorbates, UVBI” and “How to use public relations and marketing.”¹⁸ Farr’s widow, Skoshi Farr, still runs the company.

In a disciplinary case before the Board of Medical Examiners in Iowa in 1998, the respondent presented Farr as an expert in EDTA “chelation therapy,” intravenous vitamin C, and IV H₂O₂. The Iowa board noted that Farr had been “disciplined by his own state medical board twenty years ago for prescribing drugs without conducting a patient exam. He was subsequently charged with violating his probation.”^{19 (p.15)} The board also stated: “In his curriculum vitae, Farr provides the names of 12 physicians as references. Four of these physicians have been disciplined by their own state licensing boards.”^{id. (p.14)} In rejecting Farr’s claim to expertise in the subjects listed above, the Iowa board observed: “Dr. Farr concedes that none of his studies or articles which are listed in his curriculum vitae were published in peer reviewed journals. Dr. Farr’s curriculum vitae lists several distinguished faculty awards from the International Bio-Oxidative Medicine Foundation, of which Dr. Farr is the founding father.”^{id. (p.15)}

In 1998, Charles Farr declared, “no longer is the double-blind study the gold standard in medicine,” and claimed that a questionnaire “shows that alternative treatment protocols used at Genesis can significantly improve the health status of a group of chronically ill patients, compared to a normal population, regardless of their diagnosis, in a time span of only six months.”¹⁰

Farr’s “Workbook”: Questionable Basic Science

In his “Workbook,” Farr introduces his case for IV H₂O₂ as follows: “Its ability to oxidize almost any physiologic or pathologic substance, in addition to producing increased tissue and cellular oxygen tensions, has proven it to have therapeutic value.”^{8 (p.2)} Early in the treatise, he discusses free radicals, reactive oxygen species, and oxidation-reduction reactions. He correctly notes that H₂O₂ “is produced by all cells of the body for many different physiological reasons.”^{id. (p.2)} He cites its role in the destruction of infectious pathogens by phagocytes, and mentions that it is “involved in many metabolic pathways which utilize oxidases. . . .”^{id. (p.2)} He hints at exuberant subsequent claims: “hydrogen peroxide is involved in protein, carbohydrate, fat metabolism, immunity, vitamin and mineral metabolism, or any other system you might wish to explore.”^{id. (p.2)} A few pages later he presents his overriding thesis: “Because of its importance in regulating multiple metabolic functions, it could best be described as the ‘Master Regulating Molecule’ of the body.”^{id. (p.17)}

 Farr follows with several speculations about such regulation, extrapolated from evidence that is, at best, dubious. Two examples follow.

To support his assertion that H₂O₂ “regulates” the immune system, Farr states, “Hydrogen peroxide has been identified to stimulate several cell types (T-cells, Monocytes, Granulocytes, NK cell) to produce Cytokines.”^{id. (p.24)} In support of that statement he cites four articles. The first reported that macrophages in cell culture, once stimulated by gamma interferon, inhibited the intracellular growth of Chlamydia. This inhibition was oxygen-independent, i.e., it was not affected by H₂O₂.²⁰ The article reported nothing about H₂O₂ stimulating the cells to produce cytokines. The second citation reported that adding gamma interferon to the medium enhanced the ability of mouse macrophages to kill trypanosomes, and that this effect was prevented by catalase, suggesting that the killing mechanism involved H₂O₂. The article did not suggest that H₂O₂ “stimulated” the macrophages to produce gamma interferon or any other cytokine.²¹

The third citation similarly reported that adding gamma interferon enhanced the intracellular antimicrobial action of monocytes, and that both this effect and the cells’ release of H₂O₂ increased with longer incubations—again suggesting that H₂O₂ was involved in the mechanism of the cells’ antimicrobial action, but not that H₂O₂ stimulated the production of cytokines or was otherwise involved in regulating the phenomenon.²² Thus none of these citations supports Farr’s assertion. The final citation is to one of Farr’s own articles, which was not published in a recognized, peer-reviewed journal.

Farr states, “In hypothyroidism, the production of H₂O₂ is decreased proportionately to the decrease in thyroxine, and when thyroid is administered the level of H₂O₂ increases.” ^{8 (p.25)} Here, Farr cites a single study in rats²³ and continues: “In our studies we have found intravenous hydrogen peroxide will often convert hypothyroidism to euthyroidism.” And: “Hydrogen peroxide is necessary in regulating some hormone functions. . . . Thyroid production is dependent upon H₂O₂. . . .” Farr then cites a single in vitro study.²⁴ What Farr refers to as “our studies” remains problematic, as will be discussed further below; but even if the other two cited studies depict the real world of human biochemistry (a big “if”), it does not follow that H₂O₂ “regulates” the production of thyroid hormone.

Farr’s insistence that H₂O₂ is the “Master Regulating Molecule,” or even that it is merely involved in many normal biochemical processes, raises another question: why should adding more of it be beneficial? The processes in which H₂O₂ is involved, such as lipid peroxidation or the killing of microorganisms by white cells, are intracellular processes. The production and degradation of H₂O₂ and other reactive oxygen species are tightly controlled and sequestered within intracellular organelles called “peroxisomes,” because elsewhere these highly reactive molecules can, and do, wreak general havoc.^25,26 It simply doesn’t follow, merely from the idea that H₂O₂ is involved in many normal oxidative processes, that giving it intravenously ought to be safe or useful.

Farr appears to have thought of this objection, which he counters by citing a study reporting the finding of micromolar concentrations of H₂O₂ in human plasma.²⁷ According to Farr, there is a hydrogen peroxide “pool” that “is available for numerous intracellular and extracellular functions.”^{8 (p.17)} He adds: “Hydrogen peroxide is a small, highly diffusible molecule which rapidly diffuses throughout the surrounding environment. . . .”^{8 (p.23)} It regulates, in Farr’s view, diverse, useful biochemical functions—which are enhanced by adding H₂O₂ to the extracellular milieu. But this claim remains speculative and is not backed by a body of scientific literature, as will be discussed further below.

Farr also claims that intravenous H₂O₂ “can be used to produce an increase in tissue and serum oxygen concentrations.”^{8 (p.2)} But this claim is easily refuted by the oxygen-hemoglobin dissociation curve and the relative insolubility of oxygen in plasma. Virtually all oxygen in blood is bound to hemoglobin, and this binding is nearly maximized (that is, the oxygen saturation is nearly 100%) after each pass through the lungs. Thus the contribution of oxygen from the breakdown of H₂O₂ must be trivial, because blood cannot be more than 100% saturated. Moreover, even if the oxygen released from Farr’s recommended dose were completely bound to hemoglobin or dissolved in plasma, it would not add significantly to physiologic oxygen requirements.¹ Curiously, Farr acknowledged this in two patient brochures²⁸:

The amount of Oxygen produced by the degradation of Hydrogen Peroxide for Oxygenation is miniscule compared to the powerful metabolic effect it exerts in the body as an Oxidizer.

And:

The amount of oxygen produced by a therapeutic infusion of Hydrogen Peroxide is very small. A single breath of fresh air contains many times more oxygen than found in . . . a therapeutic infusion. . . .

Similar contradictions are found throughout Farr’s treatise.

Experimental or Proven?

In the remainder of the “Workbook,” particularly the “Protocol,” Farr makes claims for clinical efficacy of IV H₂O₂ and discusses indications, contraindications, precautions, side effects, preparation, and administration. He admits that there has been a “limited amount of clinical data on H₂O₂ accumulated to date . . .” and resolves, “The intravenous use of Hydrogen Peroxide must be considered experimental and nothing herein should be considered to be otherwise”—only to contradict himself in the next sentence: “It is the responsibility of each physician to act according to his or her own interpretation of the information presented, and be guided thereby for the safe and effective intravenous administration of Hydrogen Peroxide.”^{8 (p.32)} Later in the treatise, Farr asserts, “Each physician who explores the benefits of this new therapy, has a responsibility to report their findings for the mutual benefit of all patients and physicians.”^{8 (p.44)} Yet Farr never reported his own avowed findings in a recognized, peer-reviewed journal.

The rest of the text is equally erratic and contradictory. Farr asserts that “no distinct group of patients or classification of diseases can be considered the ‘proper selection’ at this time”^{8 (p.43)}—but then recommends H₂O₂ for myriad problems, including influenza, bronchitis, herpes zoster, “asthmatic reactions,” Epstein-Barr virus, CMV, HIV, type II diabetes, COPD, vascular disease, arthritis, chronic pain, Alzheimer’s disease, “toxic dementia,” Parkinsonism, migraine headaches, and “immune regulation.” Elsewhere in the text he claims that H₂O₂ can change hypothyroidism to euthyroidism, remove atheromatous plaques, protect ischemic myocardium, convert ventricular fibrillation, abort an impending stroke, and destroy tumor cells. He asserts that IV H₂O₂ is “an important therapeutic tool for every physician.”^{8 (p.44)}

Farr: Work-Up, Contraindications, Side Effects, Risks

Farr calls for “a complete medical history with a thorough head-to-toe physical examination” prior to H₂O₂ treatment.^{8 (p.44)} He recommends many laboratory tests, including two that deviate from accepted scientific and medical standards: “whole blood analysis”²⁹ (not the same as a peripheral blood smear) and “hair analysis.”³⁰

Farr lists these contraindications to IV H₂O₂ treatment: pregnancy; “chronic granulomatous disease;” and “any disorder of cell membrane stability (i.e., anemias).”^{8 (p.56)} He describes these side effects: pain at injection site; cough; reduced heart rate; local histamine reactions; chest “discomfort” or shortness of breath; and Herxheimer reaction (aching, nausea, fever, chills, headache).

Farr also discusses risks of treatment and recommended emergency equipment:  “. . . it is prudent for the clinician to be familiar with the signs and symptoms of pulmonary embolism should it occur . . . tachypnea, pallor, early cyanosis, weakening of pulse, cardiac arrhythmias, complete cessation of heart action and respiration.”^{8 (pp.46–47)} And: “Equipment should be available for cardiopulmonary resuscitation.”^{id. (p.60)}

Farr claims that his regimen is safe: “no significant acute toxicity has been observed in several hundred patients, some receiving up to 40 to 50 infusions with concentrations up to 0.3% [several times his recommended concentration]. . . . Also, no chronic or long term toxicity has been observed up to two years post-multiple infusionsÉThis suggested intravenous infusions [sic] of Hydrogen Peroxide is extremely safe and has a very wide therapeutic range.”^{8 (p.59)} Neither Farr nor anyone else has ever presented data to the FDA to establish such safety.^31,32 Recently, a 53-year-old woman in South Carolina developed signs of acute hemolytic crisis shortly after a single infusion of hydrogen peroxide, reportedly given according to the “well-established protocols” of the International Oxidative Medicine Association.³³ She was dead within four days. The coroner reported: “In summary, this unfortunate woman died as a direct result of iatrogenic infusion of hydrogen peroxide.”^34,35

Farr denies that bubbles will occur with his regimen,^{8 (p.46)} but he describes bubble formation on a wet blood smear as the preferred assay for activity of the fully diluted preparation.^{8 (p.43)} If bubbles are formed in that setting, by catalase in the blood smear acting on the hydrogen peroxide, they must also be formed in a patient’s bloodstream—where there is an identical concentration of catalase acting on an identical concentration of H₂O₂. Regarding the lungs of the woman reported in the previous paragraph, the coroner reported: “Of note, many of the blood vessels demonstrate circular cleared defects within the contained column of blood consistent with air emboli.”³⁴

Inadequate Clinical Evidence

Farr cites approximately 150 references to support his assertions, but few of these are relevant to clinical use; most are biochemical studies or in vitro studies of microorganisms or mammalian cells in culture. A few articles deal with in vivo studies in humans and animals, the H₂O₂ given either intravenously or intra-arterially. There was a small flurry of interest in intra-arterial H₂O₂ during the1960s, when researchers tested its use in humans and animals for regional oxygenation of ischemic limbs or of tumors to enhance susceptibility to radiation therapy. The studies were uncontrolled and had inconsistent outcomes. The positive studies were all reported by the same group.^36–39 Another group was unable to replicate these findings.^40,41 Enthusiasm for the technique waned thereafter, as evidenced by the absence of subsequent studies in the English literature, and by the absence of clinical use of H₂O₂ for these purposes since that time. For example, a radiation therapist who trained at Dana-Farber Cancer Center in the early 1980s had never heard of the use of intra-arterial H₂O₂ to potentiate tumor sensitivity to radiation.⁴²

Two favorable studies of intra-arterial H₂O₂ in limb ischemia from the former Soviet Union were published in the 1980s.^43–44 Their authors, however, appear not to have continued this line of investigation, although other citations by them can be found as recently as 2004.

A 1948 study investigated intravenous infusions of H₂O₂ in animals. It cited a few case reports in humans suggesting clinical usefulness. It established some parameters for dose-related toxicity in animals, and noted that in animals with low catalase levels the major toxicity was methemoglobinemia, whereas in those with higher catalase levels—comparable to those found in humans—the major toxicity was gas embolus. The study concluded: “In animals very little therapeutic value could be found for intravenous treatment with hydrogen peroxide.”⁴⁵

Two studies of intravenous H₂O₂ to treat microbial infections in animals were reported in the 1980s. In the first, IV H₂O₂ was reported to kill malaria parasites in mice.46 In spite of this the study’s two authors did not publish more articles investigating H₂O₂ as a treatment for infection, although both have published frequently as recently as 2004. The second study found no antibacterial activity of IV H₂O₂ on E. coli in rabbits.⁴⁷ The authors concluded that this was likely a result of extracellular catalase having rapidly broken down the H₂O₂. They suggested that the effect seen by the previous authors, on malaria parasites, may not have been due to a direct effect of H₂O₂ on the organisms, but rather due to its destruction of the red cells harboring the parasites.

Farr acknowledges the study that found no antibacterial activity of IV H₂O₂ on E. coli, but offers this rejoinder: “It has been shown, however, to destroy murine malaria parasites, and the bactericidal properties of H₂O₂ produced by neutrophils is well documented.”^{8 (p.32)} Thus Farr fails to consider the alternative explanation for the finding in malaria parasites, and turns the usual logic for clinical efficacy on its head: since there is some basis for believing it might work, that is, “the bactericidal properties of H₂O₂ produced by neutrophils,” then it must work—disconfirming studies notwithstanding.

The final article is the oldest, but is worth discussing because it is the one most commonly cited by peroxide enthusiasts. In 1919, two British army physicians in the Middle East were in the midst of “a severe epidemic of influenza . . . accompanied by an exceedingly toxemic and fatal broncho-pneumonia.”⁴⁸ As a last-ditch effort, they gave IV H₂O₂ to 25 gravely ill Indian soldiers. 12 soldiers died and 13 recovered. The physicians compared this to a death rate of 80% among purportedly similar cases at “a large Indian hospital.” They suggested, furthermore, that the timing of recovery seemed to have corresponded to the administration of H₂O₂. 

At best, what this report suggested was that IV H₂O₂ may have been worthy of further investigation. The sample size was small. The study was uncontrolled. The comparison group, consisting of hospitalized patients thousands of miles away, cannot be considered comparable to the treated group. The diagnosis was not exact. The disease may have been part of the influenza pandemic of 1918, but we can’t know for sure; its viral etiology was not known at that time. Even if it was viral influenza, we can’t know whether bacterial superinfections were involved. If so, we can’t know that the comparison group in the Indian hospital had the same organisms. It is also possible that those hospitalized patients were at higher risk for nosocomial infections than the group that received H₂O₂.

Even if the treated patients benefited in some way, we can’t know that this was due to H₂O₂ per se or to other, confounding factors. For example, IV hydration was virtually unknown at that time, but the treated patients each received 300 ml of saline along with H₂O₂. Most were treated only once, but one several times. Although 300 ml is not a lot of fluid, it could have made the difference between living and dying for a few profoundly dehydrated patients. Finally, in spite of the authors’ apparent enthusiasm for the technique, they apparently were not impressed enough to pursue it further, even though it would be several years before the advent of effective antibacterial medicines.

In his “Workbook,” Farr cites several of his own reports that do not appear in peer-reviewed journals, but seem to have been self-published by the IBOMF or Genesis Medical Center. These are not generally available and I have not read them, with the following exceptions. He includes eight “actual case reports” describing dramatic cures or symptom resolutions in patients with these problems: “acute herpes zoster;” “acute influenza syndrome;” “chronic systemic candidiasis” [an unlikely diagnosis]; “severe COPD;” “acute asthmatic attack (12 yr old girl);” “diabetes mellitus type II” (in which the patient, a diabetic for 25 years who had been taking 60 units of NPH insulin/day, was cured after 10 IV H₂O₂ treatments); “chronic post herpetic neuralgia;” and “impending cerebral vascular accident.”

The final case is worth quoting in its entirety. It demonstrates a paucity of the corroborating diagnostic and therapeutic information that is reasonably expected in a case report, and illustrates the recklessness with which Farr employed his favorite treatment at the exclusion of proven interventions:

Impending Cerebral Vascular Accident. 71 year old man with sudden onset two hours previously of confusion, paralysis, and weakness on left side of body, and drooling and unable to speak distinctively. Initial brood [sic] pressure 190/100, pulse normal. Given 250ml of 0.03% H2O2 started immediately. All symptoms significantly improved within 30 minutes and completely resolved after 1 hour.

Comment: Patient did not return for followup evaluation but was asymptomatic with blood pressure of 140/90 when he left the office.^{8 (pp.55–56)}

Farr concludes his case reports with these words: “Each physician, as they [sic] become more experienced using Intravenous Hydrogen Peroxide, will develop their own protocols commensurate with their type of practice and objectives.”^{8 (p.56)}

At the end of his treatise, Farr reports a controlled study in which he gave IV H₂O₂ to patients with “Type A/Shanghai influenza” during the winter of 1989–1990. He reports that 20 treated patients lost an average of only 0.25 days from work, compared to an average of 2 lost days for those in the control group.

The report, however, is not interpretable. There is no direct evidence that the patients had the disease in question. There is no evidence that the control group was comparable to the treatment group. There is no mention of blinding. The control group is said to have been treated with “the conventional medical protocol of antibiotics . . .”, but antibiotics are not indicated for uncomplicated cases of influenza.^{8 (p.72)} There is no mention of informed consent or IRB approval. Finally, the study was never published in a peer-reviewed journal. It cannot be considered reliable.

Summary and Conclusion

In summary, the evidence that IV H₂O₂ is a safe and effective therapy—for any disease—is lacking. There is no growing body of support from basic science, animal studies, or human studies. Specifically, there would need to be systematic animal studies showing real promise, followed by Phase I, II and III human trials to establish safety and efficacy of IV H₂O₂ for at least one indication. Instead there have been a few conflicting preliminary reports, without independent confirmation of the very few that appeared favorable.

Farr’s opinions cannot be considered authoritative. His panacea claims for IV H₂O₂ are implausible and typical of medical quackery. He never published his purported findings in a peer-reviewed journal. He used his endorsement of this and other dubious treatments in an entrepreneurial fashion. His own state medical board disciplined him for substandard practice, and the FDA disciplined him for presiding over a bogus IRB.

Prudence dictates that informed, scientifically trained practitioners view IV H₂O₂ skeptically. Extracellular H₂O₂ in blood is rapidly broken down to oxygen and water by the enzyme catalase, which results in the formation of dangerous bubbles. Any intact H₂O₂ that comes into contact with a cell is not likely to enter the cell in an orderly fashion, but rather to damage the cell membrane because the molecule vigorously reacts with lipids. Thus it is unlikely that H₂O₂ given intravenously would have any significant intracellular role, which is where it would need to be in order to fulfill Farr’s claims. Rather, it would result in the formation of oxygen bubbles in the bloodstream and in the destruction of cells, exactly as have been reported. ^3–7

Farr claimed that his regimen was safe because the H₂O₂ was sufficiently diluted. But even with a regimen that reportedly “had followed [the] ‘well-established’ protocols” of Farr’s organization, the IOMA, a woman died in 2004 shortly after a single infusion; the coroner subsequently reported that her death had been due to hemolytic crisis and gas emboli.⁷ Thus Farr’s claim of safety cannot be accepted as reliable.

In conclusion, the information that “oxidative medicine” practitioners rely upon as the basis for their prescribing intravenous hydrogen peroxide is wholly inadequate to justify such treatment.

References

1. Green S. Oxygenation Therapy: Unproven Treatments for Cancer and AIDS. Scientific Review of Alternative Medicine 1998;2,1:6–12. Available at: http://www.quackwatch.org/01QuackeryRelatedTopics/Cancer/oxygen.html. Accessed September 18, 2008.
2. Anon. Hydrogen Peroxide. In: Klasco RK (Ed): DRUGDEX¨ System (electronic version). Thomson Micromedex, Greenwood Village, Colorado, USA. Available at: http://www.thomsonhc.com. Accessed September 18, 2008.
3. Jordan KS, Mackey D, Garvey E. A 39-year-old man with acute hemolytic crisis secondary to intravenous injection of hydrogen peroxide. J Emerg Nurs. 1991;17:8–10.
4. Before the North Carolina State Medical Board. In re: John Carl Pittman, MD. Notice of Charges and Allegations, 05/15/2002. Available at: http://glsuite.ncmedboard.org/DataTier/Documents/Repository/LegacyImages/00/00/81/00008149.tif. Accessed September 18, 2008.
5. Hirschtick RE, et al. Death from an unconventional therapy for AIDS. Ann Intern Med 1994;120:694.

6. Gordon SM, et al. Hemolysis associated with hydrogen peroxide at a pediatric dialysis center. Am J Nephrol 1990;10:123–7.

6. Breed AG, Associated Press. Peroxide therapy leads to a patient’s death in South Carolina. The Barre Montpelier Times Argus. Jan. 2, 2005. Available at: http://www.timesargus.com/apps/pbcs.dll/article?AID=/20050102/NEWS/501020313/1014. Accessed September 18, 2008.
7. Farr CH. Workbook on Free Radical Chemistry and Hydrogen Peroxide Metabolism. Including Protocol for the Intravenous Administration of Hydrogen Peroxide. Common Law Copyright, 1989-1996, IBOM Foundation, Oklahoma City, OK.
8. Farr CH. Possible mechanisms of action of digitalis in cardiac muscle. J Okla State Med Assoc. 1959;52:138–46.
9. Contact Reflex Analysis and Nutritional Research Foundation Website. Patient Outcomes to Alternative Medicine Therapies as Measured by the SF-36: Preliminary Report. Based on original research by Dr. Charles H. Farr, MD, PhD and presented at the Ninth International Conference on Oxidative Medicine, April 18, 1998 in San Antonio, Texas. Available at: http://web.archive.org/web/20000421222812/http://www.crahealth.org/news/9907-patient_outcomes.htm. Accessed September 18, 2008.
10. Atwood KC, Woeckner E, Baratz RS, Sampson WI. Why the NIH Trial to Assess Chelation Therapy (TACT) should be abandoned. Medscape J Med. 2008;10:115. Available at: http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3494&itool=AbstractPlusnondef&uid=18596934&db=pubmed&url=http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=18596934. Accessed September 18, 2008.
11. Trowbridge JP. Historical Perspectives on the Development of Chelation Therapies. 1998. Available at:  http://www.healthchoicesnow.com/docs/CHELATIONHISTORYRTF1.doc. Accessed September 2005.
12. American College for Advancement in Medicine website. Oxidative Medicine Division. Available at: http://www.acamnet.org/site/c.ltJWJ4MPIwE/b.2176495/k.991F/Oxidative_Medicine_Division.htm. Accessed March 2008.
13. Warning letter from David A. Lepay, MD, PhD, Director, Division of Scientific Investigations, Office of Compliance, Center for Drug Evaluation and Research, Food and Drug Administration; to Charles H. Farr, MD, PhD, Director, International Bio-Oxidative Medicine Foundation, Inc. June 2, 1997. Available at: http://web.archive.org/web/20061129113758/http://www.fda.gov/foi/warning_letters/m962n.pdf. Accessed September 18, 2008. 
14. IBOMF Doctors Referral List. 1999. Available at: http://web.archive.org/web/20010710005248/bioproinc.com/ibomf_doctors_referral_list.htm. Accessed September 18, 2008.
15. Oklahoma Board of Medical Licensure and Supervision. WHITE, ROBERT LEROY. Revoked license. 05/03/2001. Available at:  http://www.okmedicalboard.org/display.php?content=med_directory:med_directory&ref=names&TYPE=NAME&PROFESSION=PA&LICENSE=33. Accessed September 18, 2008.
16. White RL. Oxidative Medicine. ANMA Monitor Online. Vol. 4, no. 1. Available at:  http://www.anma.com/mon41.html#ARTICLE2. Accessed September 18, 2008.
17. bio pro, inc. Amazing Anti-Aging Solutions. About us. Available at: http://www.bio-proinc.com/site/555888/page/45030. Accessed September 18, 2008.
18. Before the Board of Medical Examiners of the State of Iowa. In the matter of the complaint and statement of charges against V. Thomas Riley, MD. 20 March 1998. Available at:  http://www.docboard.org/ia/legal/Riley,V.Thomas,M.D.-02-1991-104,02-1991-229,02-1993-197.PDF. Accessed September 18, 2008.
19. Rothermel CD, Rubin BY, Jaffe EA, Murray HW. Oxygen-independent inhibition of intracellular Chlamydia psittaci growth by human monocytes and interferon-gamma-activated macrophages. J Immunol. 1986;137:689–92.
20. Wirth JJ, Kierszenbaum F, Sonnenfeld G, Zlotnik A. Enhancing effects of gamma interferon on phagocytic cell association with and killing of Trypanosoma cruzi. Infect Immun. 1985;49:61–6.
21. Murray HW, Scavuzzo D, Jacobs JL, Kaplan MH, Libby DM, Schindler J, Roberts RB. In vitro and in vivo activation of human mononuclear phagocytes by interferon-gamma. Studies with normal and AIDS monocytes. J Immunol. 1987;138:2457–62.
22. Swaroop A, Ramasarma T. Heat exposure and hypothyroid conditions decrease hydrogen peroxide generation in liver mitochondria. Biochem J. 1985;226:403–8.
23. Wildberger E, Kohler H, Jenzer H, Kampf J, Studer H. Inactivation of peroxidase and glucose oxidase by H₂O2 and iodide during in vitro thyroglobulin iodination. Mol Cell Endocrinol. 1986;46:149–54.
24. Devlin TM (ed.). Textbook of Biochemistry with Clinical Correlations. 5^th Edition. New York, Wiley-Liss. 2002. p. 22.
25. Traub SJ, Nelson LS. Chemical Principles: Reactive Oxygen Species. In: Goldfrank LR (ed.). Toxicologic Emergencies. 7^th Edition. New York, McGraw-Hill. 2002. pp. 190–192.
26. Varma SD, Devamanoharan PS. Hydrogen peroxide in human blood. Free Radic Res Commun. 1991;14:125–31.
27. Patient brochure submitted by respondents during the Massachusetts Board of Medicine’s 2004–2005 investigation of the use of IV H₂O₂ at Preventative Medicine Center, Yarmouth, MA. In a deposition, one respondent identified this brochure as having been published by Farr’s organization, the IBOMF.
28. Barrett S. Live Blood Cell Analysis: another gimmick to sell you something. Quackwatch website. Revised 7/2005. Available at: http://www.quackwatch.org/01QuackeryRelatedTopics/Tests/livecell.html. Accessed September 18, 2008.
29. Barrett S. Commercial Hair Analysis: a cardinal sign of quackery. Quackwatch website. Revised 1/2001. Available at: http://www.quackwatch.org/01QuackeryRelatedTopics/hair.html. Accessed September 18, 2008.
30. Anon. Hydrogen Peroxide. In: Klasco RK (Ed): DRUGDEX¨ System (electronic version). Thomson Micromedex, Greenwood Village, Colorado, USA. Available at: http://www.thomsonhc.com. Accessed September 18, 2008.
31. U.S. Congress, Office of Technology Assessment. Oxygen Treatments. In: Unconventional Cancer Treatments. OTA-H-405 (Washington, DC: U.S. Government Printing Office, September 1990). P.114. Available at: http://www.wws.princeton.edu/ota/disk2/1990/9044/9044.PDF. Accessed September 18, 2008.
32. Breed AG, Associated Press. Peroxide therapy leads to a patient’s death in South Carolina. The Barre Montpelier Times Argus. Jan. 2, 2005. Available at: http://www.timesargus.com/apps/pbcs.dll/article?AID=/20050102/NEWS/501020313/1014. Accessed September 18, 2008.
33. David W. Bibeau, Personal Representative of the Estate of Katherine Ann Kurtz-Bibeau, v. James Michael Shortt; Health Dimensions, LLC; and Congaree Pharmacy, Inc. Case No. 3 04 22306 10. Complaint. 2004-09-22. United States District Court District of South Carolina Columbia Division. Available at: http://www.quackwatch.org/11Ind/shortt.html. Accessed September 18, 2008.
34. Nichols CA. Report of Postmortem Examination of Katherine Bibeau. Date of autopsy: 3/15/2004.
35. Mallams JT, Finney JW, Balla GA. The use of hydrogen peroxide as a source of oxygen in a regional intra-arterial infusion system. South Med J 1962;55:230–232.
36. Mallams JT, Finney JW, Balla GA. Regional intra-arterial hydrogen peroxide infusion and irradiation in the treatment of head and neck malignancies: a progress report. Trans Am Acad Ophthal Otolaryngol 1963;67:546–553.
37. Balla GA, Finney JW, Aranoff BL et al. Use of intra-arterial hydrogen peroxide to promote wound healing. Am J Surg 1964;108:621–9.
38. Urschel HC. Cardiovascular effects of hydrogen peroxide: current status. Dis Chest 1967;51:180–92.
39. Germon PA, Faust DS, Rosenthal A, Brady LW. Regional arterial and tissue oxygen tensions in man during infusion with hydrogen peroxide solutions. Radiology 1967; 88:589–91.
40. Germon PA, Faust DS, Brady LW. Comparison of Arterial and Tissue oxygen measurements in humans receiving regional hydrogen peroxide infusions and oxygen inhalation. Radiology 1968;91:669–72.
41. Nancy Tarbell, MD, Professor of Radiation Oncology, Harvard Medical School. Personal communication. 2005.
42. Lebedev LV, Levin AO, Romankova MP, Rychkova KG, Arsen’eva IV. [Regional oxygenation in the treatment of severe destructive forms of occlusive arterial diseases of the limbs] Vestn Khir Im I I Grek. 1984;132:85–8. Russian.
43. Gusak VK, Klioner LI, Belinskii VE, Shlopov VG, Danilov IuV. [Possibilities of using weak solutions of hydrogen peroxide in the treatment of experimental ischemia of the lower extremities] Klin Khir. 1986;7:31–3. Russian.
44. Lorincz AL, Jacoby JJ, Livingstone HM. Studies on the parenteral administration of hydrogen peroxide. Anesthesiology 1948;9:162–174.
45. Dockrell HM, Playfair JHL. Killing of blood-stage malaria parasites by hydrogen peroxide. Infection and Immunity 1983;39:456–9.
46. Shenep JL, Stokes DC, Hughes WT. Lack of antibacterial activity after intravenous hydrogen peroxide infusion in experimental Escherichia coli sepsis. Infection and Immunity 1985;48:607–10.
47. Oliver TH, Murphy DV. Influenzal pneumonia: the intravenous injection of hydrogen peroxide. Lancet 1920: 432–3.

About the Author

Kimball C. Atwood, IV. Tufts University School of Medicine. Please send e-mail correspondence to: katwood@partners.org, or mail to: Newton-Wellesley Hospital, Department of Anesthesiology, 2014 Washington St., Newton, MA 02462.