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Intravenous Hydrogen Peroxide


HYDROGEN PEROXIDE THERAPIES: RECENT INSIGHTS INTO OXYSTATIC AND ANTIMICROBIAL ACTIONS
Majid Ali, M.D.

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 ATPase18; activation of potent enzymatic
antioxidant defenses, including glutathione peroxidase.19 Other important metabolic aspects of hydrogen peroxide include: (1)
hexose monophosphate shunt20; (2) mitochondrial enzymatic pathways21; (3) enzymes of membrane transport systems22; (4)
thyroglobulin iodinases23; (5) prostaglandin synthesis24; (6) bioamine metabolic pathways, including those of norepinephrine,
dopamine, and serotonin25; 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.

A pioneer of intravenous H2O2 therapy was Charles Farr. During the mid-1990s, he honored me by having me serve as his co-
director of courses on bio-oxidative therapies. Farr made several important original clinical and experimental observations about
intravenous hydrogen peroxide infusions. He documented short-term and long-term effects of that therapy on various aspects of
the immune system. One of his astute observations concerned the dramatic changes—up to 100% increase from the pre-
infusion levels—in oxygen consumption rate. He clearly established the fact that biologic effects of that therapy cannot be merely
attributed to the miniscule amounts of oxygen liberated from the infused hydrogen peroxide.30

Mechanisms by Which H2O2 Improves Arterial, Venous, and Lymphatic Circulations

A large number of short-term and long-term observations have convinced us that H2O2 improves arterial, venous, and lymphatic
circulation. Those effects are mediated by a host of mechanisms. Personal morphologic observations with phase-contrast
microscopy have convinced me that the most important of those mechanisms is control of oxidative coagulopathy by myriad
molecular mechanisms listed below. Microclots and microplaques in the circulating blood are readily detected by examination of
freshly prepared and unstained smears of the peripheral circulating blood with high-resolution, phase-contrast microscopy.31-33

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The arrest of oxidative lymphopathy occurs concurrently with control of oxidative coagulopathy, though a suitable lymph
specimen for direct documentation of that phenomenon is generally not forthcoming.

The primary mechanism by which H2O2 exerts those circulatory effects is proteolytic dissolution of microclots and microplaques
in the vascular channels. Less important effects of H2O2 include the following: (1) peripheral vasodilatation34; (2) coronary
vasodilatation35; (3) cerebral arteriolar dilatation36; and (4) pulmonary vasodilatation37; and (5) peripheral vasodilatation.36

H2O2 and Phagocytosis

Antimicrobial properties of hydrogen peroxide were recognized soon after its discovery. It was to be expected that the seminal
work of the Russian biologist, Elie Metchnikoff, concerning humoral immunity during the late nineteenth century would also bring
hydrogen peroxide into sharper focus. That, indeed, happened. The classical concept of phagocytic microbial killing may be
summarized as follows38-42: (1) The invading microbes are exposed to serum factors, opsonized, and engulfed within the
phagocytic cells; (2) The engulfed microbes are encapsulated by a series of fusion processes culminating in the development of
the mature phagosome41; (3) Phagosomes merge with early endosomes to increase the vesicle size; (4)Membrane-bound
vacuolar ATPases and proteolytic enzymes necessary for particle and microbial degradation are acquired42; (5) Bactericidal
molecular machinery of cytoplasmic granules is brought into action with the release of their granules; and (6) Actual demise of
microbes is attributed to production of free radicals—superoxide, hydrogen peroxide, and others—during respiratory burst.43

H2O2, Matrix Regulation, and Microbial Killing

Recent studies have revealed that actual molecular dynamics of microbial killing are far more complex than simple destruction of
mirobes by free radicals.44,45 Specifically, certain conditions of the granular matrix are essential for completing the process of
microbial disintegration. The matrix within the granules is highly charged. Granular proteases are normally adsorbed to it in an
inactive form. When the ionic strength in the vacuoles rises, the enzymes are activated and unleashed to serve their
microbiocidal roles. Those enzymes function optimally at elevated pH levels which exist in the vacuoles under those conditions.
The respiratory burst within the phagocytic vacuoles is accompanied by a surge in the intravacuolar pH—from 6 to nearly 8. A
large influx of potassium ions through the vacuolar membrane occurs and offsets the anionic charge. That happens in spite of
the release of predominantly acidic granular contents since protons are consumed in neutralizing the excess of basic superoxide
ions and other radicals.46,47

Concurrently, osmotically potent degradation products are released from disintegrating microbes, rendering the vacuole
markedly hypertonic and shrinking the viable bacteria by as much as 50%. Such microbial shrinking is prevented if protease
inhibitors are introduced into the system. Undue expansion of the vacuoles is prevented by a dense network of membrane
cytoskeletal proteins.

Neutrophilic myeloperoxidase, itself capable of destroying microbes, appears to protect proteases from oxidative damage, to
which they are vulnerable, especially cathepsin G.48

The Role of Potassium Ions

The passage of electrons across the vacuolar membrane is electrogenic. Specifically, the superoxide-generating NADPH
oxidase of human neutrophils is electrogenic and is associated with an H+ channel.49 There are important changes in H+
dynamics during phagocytosis. For example, protein C kinase activates an H+-(equivalent) conductance in the plasma
membrane of human neutrophils. Activation of NADPH oxidase-related proton and electron currents occurs simultaneously in
human neutrophils. Potassium ions play a central role in the microbial killing process. Oxidases generate a potential difference
across the membrane. Potassium ions move to compensate for that difference and in doing so enable the pH to rise to a level
necessary for optimal function of proteases. Potassium ions activate granule enzymes. When phagocytes are inactive (not
engulfing and killing microbes), the granules contain a strongly anionic sulfated proteoglycan matrix that binds tightly to cationic
proteases. In the bound form, proteases cannot digest microbes. There is evidence that hypertonic K+ driven into vacuoles by
NADPH oxidase is responsible for unleashing (by solubilizing) those enzymes, since elevated pH on its own is unable to activate
proteases. 50

Would one expect the other ionic channels to sit out the action of phagocytosis? Hardly, in view of Nature's preoccupation with
complementarity and contrariety. Free calcium ions initiate, augment, or perpetuate an enormous variety of cellular processes.
For example, calcium is involved with coupling of diverse stimuli to their respective specific responses,51,52 including: (1) light;
(2) touch; (3) gravity; (4) cold shock; (5) hormones; (6) bacterial compounds; and (7) mycotoxins. Stimulus specificity appears to
be encoded through a multitude of Ca2+ mobilization pathways. For example, vacuolar ligand-gated Ca2+ mobilization pathways
may involve both Ca2+- and voltage- operated Ca2+ release channels in the same membrane, acting singly or coordinately.
Directly or indirectly, such calcium-related responses are involved in nearly all crucial steps in phagocytosis. Not unexpectedly,
many of the specific calcium responses depend on their spatio-temporal concentrations. To render the calcium-related cellular
happenings yet more fascinating, some nuclear processes appear to be executed in response to an autonomously regulated
nuclear calcium signal. It may be added parenthetically that chloride ions also play a role in phagocytic dynamics. Specifically,
chloride efflux regulates adherence, spreading, and respiratory burst of neutrophils stimulated by tumor necrosis factor- (TNF) on
biologic surfaces.53

In discussion of the structure and function of the matrix, little, if any, attention is given to the matrix within the cell as well as
within cellular organelles. And yet, the matrix in those locations serves key redox metabolic and defense roles. The complexities
in the phagocytic destruction of microbes should not be surprising because Nature, first and foremost, has to protect cells and
vacuoles from the self-destructive impulses of their own enzymatic arsenals. An enormous number of phagocytic cells infiltrate
the inflamed tissues invaded by microbes. Such cells deliver a huge load of autolytic enzymes fully capable of damaging
autologous tissues. Thus, the 'packaging' of the enzymes provides the needed defense against self-inflicted injury triggered by
free radical sparks. It may be added here that the matrix of phagocytic granules — seldom a point of focus — also plays a
central role in destruction of microbes after phagocytosis.

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Table 1. Composition of Hydrogen Peroxide - I


Nutrient Concentration Volume

Hydrogen peroxide 3.75% 0.35 ml

Sodium Bicarbonate 0.5 mEq/ml = 1.25 mEq 2.5 ml

Normal saline 0.9% 150 ml

Table 2. HYDROGEN PEROXIDE-II


(Hydrogen Peroxide-I Followed By Infusion Given Below In 30-45 Minutes

Nutrient Concentration Volume

Magnesium sulfute. 500 mg/ml =1.5 ml 750 mg

Zinc 5 mg/ml = 2 ml 12 mg

Calcium gly/lac 10 mg/ml = 7.5 ml 75 mg

Pantothenic acid 250 mg/ml = 1.5 ml 375 mg

Pyridoxine 100 mg/ml = 1 ml 100 mg

Vitamin C 500 mg/ml = 1 ml 0.5 gm

Vit. B Complex * 1 ml

Molybdenum 25 mcg/ml = 5 ml 125 mcg

Sodium Bicarbonate 2.5 mEq/5 ml = 1.5 ml ---------

Lidocaine 20 mg/ml = 1.5 ml 30 mg

0/45% Saline 50 ml

I might point out here that matrix proteases perform the microbial killing rituals, but oxygen and the oxygen-driven oxidative
phenomena provide the initial sparks.

Protocol for Hydrogen Peroxide Foot


Soaks and Baths

Hydrogen peroxide soaks can be used with different concentrations of and H2O2 and salt. The following is the standard protocol
prescribed at the Institute protocol:

H2O2 Soaks Protocol

Water 20 parts
H2O2 3% 1 part
Salt One teaspoon
Time 20 minutes

The recommended choices of salt are as follow: (1) Epsom salt; (2) sea salt; and (3) common table salt.

Stronger solutions of H2O2, such as one part of H2O2 and 10 parts of water or 1 part of H2O2 and 15 parts of water may also
be tried to test for variations in efficacy for individual persons.

For chronic conditions, I generally prescribe foot soaks on a four or five day a week basis. For subacute conditions, daily soaks
are recommended. Uncommonly, I have prescribed such soaks on a twice daily basis.

There are several good brands of foot soak and foot massage units available on the market. The one made by Brookstone
Company creates effective whirlpool conditions and includes a "nodule" for effective massaging of tender points on the feet or
ankles.

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