My colleagues at the Institute and I routinely prescribe hydrogen peroxide foot soaks for patients with acute and chronic lower leg edema caused by peripheral arterial insufficiency, varicose veins, unresolved trauma, low-grade chronic infectious and atopic processes. Based on clinical results obtained in several hundred patients, I now consider this therapy (described later in this article) to be the safest and most effective therapy for those conditions.

We have also prescribed intravenous hydrogen peroxide infusions for over 3,000 patients with varying degrees of respiratory-to-fermentative (RTF) shift in ATP generation associated with chronic fatigue states. (1,2) Based on that experience, we now consider that therapy as one of the safest and most effective therapies for such patients. The long-term clinical outcomes of integrative protocols with focus on hydrogen peroxide infusions have been published. (3) In this article, I briefly review some basic aspects of hydrogen peroxide chemistry and therapeutics, and then present newer information about hydrogen peroxide signaling that sheds light on the molecular mechanisms that explain our clinical observations.

Discovery and Natural Occurrence

Hydrogen peroxide was discovered in 1818 by the French chemist Louis-Jacques Thenard. He coined the term eau oxygenee, to express his belief that it was an oxygenated form of oxygen. It is not clear if he fully understood the enormous medical significance of his discovery. Hydrogen peroxide is colorless, heavier than water, and has a larger liquid range than water, the melting point ranging from -11C(70%) to -39C (70%). It is produced within the plant biomass and plays diverse and pivotal roles in the cellular communication and energetic systems in the plant kingdom. It is present in trace amounts both in rainwater and snow. Interestingly, it is found in higher concentrations in natural spring waters of many healing shrines, most notably in Lourdes in France, Fatima in Portugal, and St. Anne's in Quebec. In light of my observations of the clinical benefits of H2O2 therapies in a host of clinical entities, I am tempted to speculate that many of the putative benefits of the shrine waters accrue from the oxystatic roles of H2O2. It is also likely that the mineral compositions of such waters enhance their oxystatic benefits.

Hydrogen Peroxide: A Misunderstood Molecule

Hydrogen peroxide is a misunderstood molecule. It is a potent in vitro oxidant. And yet, it serves as an effective in vivo antioxidant in clinical states associated with chronic accelerated oxidative molecular stress. (4,5) It is procoagulant under certain conditions and anticoagulant under others. (6) It is proinflammatory in some roles and anti-inflammatory in others. (7) It induces some genes and suppresses others. (8,9) It is a critically important second messenger in many pathways. (10-14) It is procancer in some aspects and anti-cancer in others.

Hydrogen peroxide plays multiple Dr. Jekyll/Mr. Hyde roles in enzymatic dynamics of the body, inducing some and impairing the functions of others, (15-19) including: (1) inactivation of xanthine oxidase by reactions that involve formation of hydroxyl radicals; (2) oxidation of the oxidation-sensitive thiol groups at the active site of glucose-3-phosphate dehydrogenase and so inhibits the enzyme, thus reducing ATP-dependent synthesis of many proteins; (3) inhibition of glyceraldehyde phosphate dehydrogenase (GAPDH), providing a mechanism by which hydrogen peroxide exerts a regulatory effect on endothelial pathophysiology; (4) regulation of activities of crucial energy enzymes, such as sodium-potassium ATPase (18); activation of potent enzymatic antioxidant defenses, including glutathione peroxidase. (19)

Other important metabolic aspects of hydrogen peroxide include: (1) hexose monophosphate shunt (20); (2) mitochondrial enzymatic pathways (21); (3) enzymes of membrane transport systems (22); (4) thyroglobulin iodinases (23); (5) prostaglandin synthesis (24); (6) bioamine metabolic pathways, including those of norepinephrine, dopamine, and serotonin (25); and (7) progesterone and estrogenic synthetic pathways. (26) By those and other roles, hydrogen peroxide activates a host of oxyenzymes--enzymes that are directly involved in oxygen homeostasis--and alters the expression of oxygenes in many ways.

The Beginning of H2O2 Therapeutics

In 1898, Cortelyou of Marietta, Georgia, reported successful results obtained in patients with disorders of the nose and throat. (27) In the same year, I.N. Love reported his successful use of H2O2 for treating scarlet fever, diphtheria, pneumonia, and uterine cancer in the Journal of the American Medical Association. (28) A clear record of what appears to be the first clinical use of intravenously administered hydrogen peroxide appeared in an article published in Lancet in 1920 by Oliver and Cantab. (29) They were military physicians treating Indian Gurkha soldiers. During an influenza epidemic, they encountered 80% mortality among soldiers who developed pneumonia. In desperation--possibly emboldened by a lack of fear of serious censure if the treatment were to be fatal for some terminally ill Indian soldiers--they undertook intravenous infusions of hydrogen peroxide to treat pneumonia. They were fortunate. In their landmark paper, they reported more than 50% reduction in mortality--13 of 25 treated soldiers survived! There were no cases with clinical or pathologic evidence of air embolism. It puzzles me why that report was not followed by widespread use of that treatment of pneumonia in Britain.