Hydrogen Peroxide Antioxidant Vitamins

277 Pages·2006·4.35 MB·English

Hydrogen Peroxide
Monograph 1: Scientific, Medical and Biochemical Overview
Antioxidant Vitamins: A, C & E
Monograph 2: Equivocal Scientific Studies
By
Prof. Hon. Randolph M. Howes M.D., Ph.D.
HYDROGEN PEROXIDE:
MONOGRAPH 1: SCIENTIFIC, MEDICAL and BIOCHEMICAL OVERVIEW

&
ANTIOXIDANT VITAMINS A, C & E:
MONOGRAPH 2: EQUIVOCAL SCIENTIFIC STUDIES
[The third in a series and a companion book to U.T.O.P.I.A. © 2004
Unified Theory of Oxygen Participation In Aerobiosis and
The Medical and Scientific Significance of
Oxygen Free Radical Metabolism © 2005]
A Selective World Literature Review

BY
PROF. HON. RANDOLPH M. HOWES, M.D., Ph.D.
Orthomolecular Surgical Scientist and Quantum Biochemist

Adjunct Assistant Professor of Plastic Surgery,
The Johns Hopkins Hospital, Baltimore, MD. USA

Espaldon Professor of Plastic and Reconstructive Surgery,
University of Santo Tomas, Manila, Philippines

Adjunct Professor of Biological Sciences,
Southeastern Louisiana University

Professor of Surgery, Biophysics and Biochemistry,
Louisiana University of Medical Sciences

Dean, Louisiana University of Medical Sciences

(Also holds an Honorary Doctorate of Humanities)
The Instructor’s Manual
For Oxygen-Dependent (Obligate-Aerobic),
Carbon-Based Life Forms

Copyright © 2006
Free Radical Publishing Co.
ISBN: 1-885458-03-7
Monograph I: HYDROGEN PEROXIDE
PREFACE
Part I - Hydrogen Peroxide: A Crucial Molecule for Aerobic Life
1.0 INTRODUCTION

1.1 Oxidative-Cure and the Peroxide-Spike
1.2 A Matter of Life and Breath
1.3 H O , the Most Common Oxidant in Vivo
2 2

2.0 UBIQUITOUS HYDROGEN PEROXIDE (A PRODUCT OF
NATURAL METABOLISM)

3.0 NATURAL CELLULAR H O SOURCES
2 2

3.1 All Aerobic Cells and H O
2 2
3.2 The Red Blood Cell
3.3 Vascular Cells
3.4 The Lung
3.5 The Liver

3.6 The Neutrophil
3.7 Fibroblasts
3.8 The Brain and H O
2 2
3.9 H O from the Cornea
2 2

3.10 The Peroxisome
3.11 Hydrogen Peroxide in Breath Condensates
3.12 Hydrogen Peroxide in the Breath
3.13 The Electron Transport Chain
3.14 Aging Deficiencies and Exercise

3.15 Breast Cancer and Exercise

3.15.1 EMODs and Breast Tumors
3.15.2 H O Is Not a Mutagen but Rather an Epigenetic Toxicant
2 2
3.15.3 Gap Junction Communications and EMODs

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4.0 H O AS INTRACELLULAR MESSENGER (REDOX STATUS)
2 2

4.1 Mitogen-Activated Protein Kinases (MAP Kinases)
4.2 EMOD Response to Injury

5.0 INTRACELLULAR KILLING AND DIGESTION OF
PATHOGENS

5.1 Oxygen-Dependent Mechanisms
5.2 Oxygen-Independent Killing
5.3 H O from Vaginal Bacteria
2 2

6.0 H O PRODUCTION
2 2

6.1 Cell H O Reaction is Concentration Dependent
2 2
6.2 Low Levels of H O
2 2
6.3 H O and O .- Facts and Singlet Oxygen
2 2 2

7.0 PEROXIDE AND CANCER (also see sections 14.3 and 20.0)

7.1 Hydrogen Peroxide and Hydroxyl Radical Antineoplastic Cytotoxicity
7.2 Scavengers of H O
2 2
7.3 Hyperoxia

7.4 Vitamin C
7.5 Increased CAT and GSH-Px Increase Cancer Rate
7.6 MnSOD Increased in a Direct Relationship with Tumor Grade
7.7 Antioxidant Enzymes and Thyroid Cancer
7.8 Chronic Inflammation and Cancer
7.9 Helicobacter Pylori
7.10 Viral Infections
7.11 Noninfectious Causes of Chronic Inflammation

8.0 ACUTE H O TOXICITY
2 2
8.1 Adverse Drug Reactions: Fatalities and Hemorrhage
9.0 GENERAL INFORMATION ON HYDROGEN PEROXIDE
9.1 The Central Nervous System
9.2 Pancreatic Beta Cells and H O
2 2
9.3 Pharmacokinetics
9.4 Interferon Inducing Activity of H O
2 2
9.5 Tumoricidal Activity of H O
2 2
9.6 H O Regulation of T Cells
2 2
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9.7 Protein Tyrosine Phosphatases

10.0 BAYLOR UNIVERSITY SCHOOL OF MEDICINE STUDIES
OF H O
2 2

10.1 Intra-Arterial H O Regional Oxygenation
2 2
10.2 H O Cardiac Resuscitation
2 2
10.3 Wound Healing
10.4 Arteriosclerotic Plaques
10.5 Shock Reversal
10.6 Oxygenation of the Ischemic or Anoxic Myocardium of Small Animals
10.7 Human Observations
10.8 Ventilation of Rabbits with a H O Aerosol
2 2
10.9 Wound Healing with Hydrogen Peroxide Infusion
10.10 H O Cardiac Resuscitation
2 2
10.11 Regional H O for Clostridia Myositis
2 2

Part II - Hydrogen Peroxide and Superoxide: Essentials for Aerobic
Life, Prooxidant Protection and Oxidative Self-Healing
11.0 NADPH OXIDASE (NOX) BRIEF REVIEW
11.1 NAD(P)H Oxidase 1 (Nox1)
11.2 NAD(P)H Oxidase 3 (Nox3)
11.3 NAD(P)H Oxidase 4 (Nox4)
11.4 NAD(P)H Oxidase 5 (Nox5)
11.5 Dual Oxidases (Duox1 and Duox2)
11.6 Functional Partners of Nox Isoforms
11.7 Conclusion
12.0 CHRONIC GRANULOMATOUS DISEASE
12.1 Clinical Features of CGD
12.2 Treatment of CGD
13.0 CATALASE (CAT)

13.1 Catalase Regenerates Oxygen
13.2 Catalase Deficiency in Humans (Normal Development)
13.3 Catalase Deficiency in Mice (Normal Development)
13.4 Catalase Can Produce Peroxidations of Alcohols
13.5 Lipid Peroxides Serves as a Source of H O
2 2
13.6 H O Modulates Vascular Smooth Muscle Cell Survivability and
2 2
Proliferation
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13.7 Mn-SOD and Vascular Physiology

14.0 PEROXIDASES

14.1 Lipoxygenase (LOX)
14.2 Thyroid Cancer
14.3 EMOD Killing of Cancer Cells
14.4 Prostate Cancer
14.5 EMODS, Hormones and Cancer
14.6 GPx (Glutathione Peroxidase)
14.7 Determining the Identity of the Bactericidal Species

15.0 GPx Can Block or Cause Apoptosis

15.1 GPx4
15.2 Animals Null for CAT and Gpx1 and Gpx2 Develop Normally

16.0 MYELOPEROXIDASE

16.1 Clinical Manifestation
16.2 Myeloperoxidase Deficiency Increases Infections and Cancer

17 SUPEROXIDE GENERATION

17.0 O . - Produced Daily
2
17.1 Antioxidant Enzyme Defenses
17.2 SOD is a Prooxidant Enzyme
17.3 MnSOD Deficiency is Lethal in Mice
17.4 Cancer Cells are Low in MnSOD
17.5 Overexpression of CuZnSOD Inhibits Tumor Cell Growth
17.6 SOD Increases H O
2 2
17.7 Mn-SOD
17.8 EC-SOD
17.9 Autoxidation
17.10 Vitamin D (1,25(OH) D ), a Prooxidant
2 3
18.0 H O PRODUCTION BY BACTERIA
2 2
18.1 H O as Protection for Bacteria
2 2
18.2 Streptococcal Production of H O
2 2
18.3 Enterococcus H O Production
2 2

19.0 HYPOXIA AND TUMORS

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20.0 THE BEST FOR LAST: PEROXIDE CAN KILL CANCER
CELLS (also see sections 7.0, 9.5, 14.2, 14.3, 14.4, 14.5, 16.2, 17.4,
and 17.5)

20.1 Resveratrol (RSV)
20.2 Cytosolic Acidification
20.3 Increased H O Levels Kill Cancer Cells
2 2
20.4 H O Kills Giant Cell Tumor Cells
2 2
20.5 H O , NaOCl, Singlet Oxygen and Selectivity in Cancer Cell Kill
2 2

21.0 PEROXIDE, SUPEROXIDE AND CADIOVASCULAR DISEASE

21.1 Sources of Oxidants in the Vascular Wall
21.2 Transition Metals
21.3 Probucol (Antioxidant)
21.4 Hyperbaric Oxygen, EMODs and Plaque Regression
21.5 H O , Heat and Cytotoxicity
2 2
22.0 CONCLUSIONS
Monograph II: ANTIOXIDANT VITAMINS

22. INTRODUCTION

23. PROOXIDANTS vs. ANTIOXIDANTS (Vitamins and Supplements)

24. THE FREE RADICAL THEORY

25. EXPERTS URGE LESS FOCUS ON ANTIOXIDANTS

26. GOOD DATA AND A BAD THEORY (Paradoxes)

27. ANTIOXIDANTS INCREASE DISEASES AND MORTALITY
28. VITAMINS, ANTIOXIDANTS, CARDIOVASCULAR RISK, MALARIA
AND CANCER
29. AGING NOT PREVENTED OR REVERSED BY ANTIOXIANTS
30. ANIOXIDANT HORMONES COMBINED WITH VITAMINS
31. ESTROGEN, AN ANTIOXIDANT (CONVERTS TO A QUINOL)

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32. VITAMINS AND ANTIOXIDANT SUPPLEMENTS ARE NOT
RECOMMENDED
33. HARMFUL EFFECTS OF ANTIOXIDANTS

34. ANTIOXIDANTS FAILED IN CANCER TRIALS

35. VITAMIN C
36. LARGE CLINICAL TRIAL FAILURES AND DISAPPOINTMENTS
(SUMMARIES)

37. FOOD ANTIOXIDANTS
38. ANTIOXIDANTS IN WINE
39. ALZHEIMER’S AND PARKINSON’S DISEASES
40. CONCLUSIONS

DISCLOSURE AND DISCLAIMER
THE CONTENT OF THE MATERIAL PRESENTED HEREIN IS PROVIDED FOR
INFORMATIONAL PURPOSES ONLY.

ANY DECISION BY THE READER TO ACT UPON THE MATERIAL PRESENTED
HEREIN IS AT THE SOLE DISCRETION OF THE READER. NO ASSURANCE IS
GRANTED OR IMPLIED AS TO THE ACCURACY OR COMPLETENESS OF THE
MATERIAL HEREIN. ACTUAL PERFORMANCE, OR THE LACK THEREOF, MAY
BE DIFFERENT THAN THE ESTIMATED PRESENTATIONS WITHIN THE
MATERIAL. IN NO EVENT SHALL THE AUTHOR BE HELD LIABLE FOR
DAMAGES, AND/OR ANY ALLEDGED HARM, INCURRED FROM THE USE OF, OR
THE RELIANCE ON, THE CONTENT OF THE MATERIAL HEREIN CONTAINED.
ALL DECISIONS REGARDING PERSONAL HEALTH AND MEDICAL ISSUES
SHOULD BE MADE IN CONSULTATION WITH A LICENSED MEDICAL
PRACTIONER.

ANY REPRODUCTION OR REDISTRIBUTION IS PROHIBITED WITHOUT THE
PRIOR, WRITTEN CONSENT OF THE AUTHOR.
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PREFACE
My review of the literature on hydrogen peroxide has solidified its position as a most
important secondary cellular messenger and illustrates the fact that it is likely the most
abundant oxidant in aerobic cells. We now know that it is involved in signal modulation
for over 200 genes and transducing protein molecules. It is ubiquitous in aerobic cells
and its continual steady state levels attests to both its crucial nature and to it low toxicity.
Cellular proliferation, arrest and apoptotic execution are all triggered by varying
concentrations of hydrogen peroxide. It is intimately involved in inter and intracellular
signaling.
A plethora of data demonstrates its involvement in bactericidal, fungicidal, virucidal,
parasiticidal and tumoricidal prooxidant protective qualities, especially when one
considers its interactions with other electronically modified oxygen derivatives
(EMODs). It also has a solid role in oxidative self-healing, as it relates to collagen
synthesis and injury repair. Without question, EMODs are essential in maintaining the
redox cellular status and homeostatic modulation.
Unfortunately, for the past half of a century, the prevalent free radical theory has
demonized all oxygen radicals and oxygen derivatives but I firmly believe that we have
seen the rise and fall of this overly-generalized, flawed theory. I believe that Dr.
Harman’s free radical theory is “radically wrong.” The “paradox-ridden” free radical
theory has been invalidated by its lack of predictability.
Non-radicals such as hydrogen peroxide, singlet oxygen and hypochlorous acid are of
extreme significance in both prooxidant protection and oxidative self-healing. This is not
to say that all biochemical effects of EMODs are salutary but I believe that the vast
majority are beneficial to and for obligate, aerobic, carbon-based life forms. As can be
seen with HIV/AIDS and chronic granulomatous disease, there can be no doubt that in
circumstances which result in deficiencies of EMODs, there are increased risks of
infections, neoplasia and death. Unquestionably, blocking all free radical reactions in
aerobic cells is a death sentence.
Due to the common use of confusing and incorrect terminology, there is a dire need to
standardize the terms used when referring to EMODs. Also, we must discuss the
individual EMODs in light of their specific reaction characteristics. The time for placing
all reactive oxygen species into one meaningless category (metabolites, intermediates,
active species, etc.) has passed. Certainly we have the biochemical sophistication and
savvy to discuss EMODs and their biochemical roles with the individual precision which
they deserve.
Finally, I truly believe that we will develop ways to combine oxidative techniques for
therapeutic use in many diseases. Just as our bodies generate prooxidant protective
measures during normal metabolism, I believe that we should attempt to mimic these
measures by the utilization of individual or combined oxidative therapies. Many of our
current treatments, such as chemotherapy and radiation, destroy some of the valuable
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oxidative aspects of our immune system. I hope that this book serves as the scientific
basis for some of the currently used oxidative therapies and opens our minds for the
development of future therapies. Politics or power structures must not make us turn our
backs on an area which is rife with such promising potential for human disease control
and/or cure and for the relief of pain and suffering.
There is agreement that vitamins are necessary for those individuals with vitamin
deficiencies. However, it is time that we recognize and acknowledge the fact that large
randomized, double-blind, controlled human studies have shown that antioxidant
vitamins do not stop, reverse or cure many of the diseases, which have been
surreptitiously ascribed to EMODs. Further, many studies indicate that the use of these
antioxidant vitamins increases the incidence of heart disease, strokes, cancer and overall
mortality in humans. However, I do believe that some antioxidants are useful in redox
cycling and in the maintainance of cellular homeostasis, especially if they have a strong
prooxidant potential.
Nonetheless, since oxidative mechanisms are responsible for both prooxidant protection
and oxidative self-healing, one may be hesitant and circumspect about the indiscriminant
or over-use of antioxidants.
I caution patients to be prudent and aware of the many specious claims made by those
who market antioxidant vitamins and supplements. Repeatedly, the data indicates that
diets containing fresh vegetables and fruits are superior to the ingestion of synthetic
supplements. I explain that there is not a classic war game between the villainized “bad”
oxygen free radicals and the alleged “good” antioxidants. Most antioxidants either
become free radicals or possess prooxidant capabilities. It is also quite possible that the
injudicious use of antioxidants can negate the effects of tumoricidal agents, which work
via oxidation and stimulation of EMOD production.
My hope is that you will share some of my enthusiasm for this most exciting area of
biochemical science. My dream is to see the widespread application of EMOD
technology at the patient’s bedside in my lifetime.

Randolph M. Howes, M.D., Ph.D.

Disclaimer: This information may not cover all possible claims, uses, actions,
precautions, side effects or interactions of oxidative agents. It is not intended as medical
advice, in the treatment of any illness or medical condition and should not be relied upon
as a substitute for consultation with your doctor, who is familiar with your medical
situation.
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