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On The Mechanisms Of Toxicity Of Chlorine Oxides
Against Malarial Parasites - An Overview
By Thomas Lee Hesselink, MD
Copyright September 6, 2007
- The purpose of this article is to propose research.
- Nothing in this article is intended as medical advice.
- No claims, promises nor guarantees are made.
Sodium chlorite (NaClO2) can be acidified as a convenient
method to produce chlorine dioxide (ClO2) which is a
strong oxidant and a potent disinfectant. A protocol has
been developed whereby a solution of these compounds can
be taken orally. This procedure rapidly eliminates malaria
and other infectious agents in only one dose. Chlorine
dioxide (ClO2) is highly reactive with thiols, polyamines,
purines, certain amino acids and iron, all of which are
necessary for the growth and survival of pathogenic
microbes. Properly dosed this new treatment is tolerable
orally with only transient side effects. More research
to better document efficacy in malaria and in other
infections is urgently called for.
Jim Humble, a modern gold prospecting geologist, needed
to travel to malaria infested areas numerous times.
He or his coworkers would on occassion contract malaria.
At times access to modern medical treatment was absolutely
unavailable. Under such dire circumstances it was found
that a solution useful to sanitize drinking water was also
effective to treat malaria if diluted and taken orally.
Despite no formal medical training Mr. Humble had the innate
wisdom to experiment with various dosage and administration
techniques. Out of such necessity was invented an easy to use
treatment for malaria which was found rapidly effective in
almost all cases.
MATERIALS AND METHODS
The procedure as used by Mr. Humble follows: A 28% stock
solution of 80% (technical grade) sodium chlorite (NaClO2)
is prepared. The remaining 20% is a mixture of the usual
excipients necessary in the manufacture and stabilization
of sodium chlorite powder or flake. Such are mostly sodium
chloride (NaCl) ~19%, sodium hydroxide (NaOH) <1%, and sodium
chlorate (NaClO3) <1%. The actual sodium chlorite present is
therefore 22.4%. Using a medium caliber dropper (25 drops
per cc), the usual administered dose per treatment is 6 to
15 drops. In terms of milligrams of sodium chlorite, this
calculates out to 9mg per drop or 54mg to 135mg per treatment.
Effectiveness is enhanced, if prior to administration the
selected drops are premixed with 2.5 to 5 cc of table vinegar
or lime juice or 5-10% citric acid and allowed to react for
3 minutes. The resultant solution is always mixed into a glass
of water or apple juice and taken orally. The carboxylic acids
neutralize the sodium hydroxide and at the same time convert
a small portion of the chlorite (ClO2-) to its conjugate acid
known as chlorous acid (HClO2). Under such conditions the
chlorous acid will oxidize other chlorite anions and gradually
produce chlorine dioxide (ClO2). Chlorine dioxide appears in
solution as a yellow tint which smells exactly like elemental
chlorine (Cl2). The above described procedure can be repeated
a few hours later if necessary. Considerably lower dosing
should be applied in children or in emaciated individuals
scaled down according to size or weight. The diluted solution
can be taken without food to enhance effectiveness but this
often causes nausea. Drinking extra water usually relieves
this. Nausea is less likely to occur if food is present in
the stomach. Starchy food is preferable to protein as protein
quenches chlorine dioxide. Significant amounts of vitamin C
(ascorbic acid) must not be present at any point in the
mixtures or else this will quench the chlorine dioxide (ClO2)
and render it ineffective. For the same reason antioxidant
supplements should not be taken on the day of treatment.
Other side effects reported are transient vomiting, diarrhea,
headache, dizziness, lethargy or malaise.
I first learned of Jim Humble's remarkable discovery in the
fall of 2006. That sodium chlorite or chlorine dioxide could
kill parasites in vivo seemed immediately reasonable to me
at the onset. It is well known that many disease causing
organisms are sensitive to oxidants. Various compounds
classifiable as oxides of chlorine such as sodium hypochlorite
and chlorine dioxide are already widely used as disinfectants.
What is novel and exciting here is that Mr. Humble's technique
seems: 1) easy to use, 2) rapidly acting, 3) successful,
4) apparently lacking in toxicity, and 5) affordable.
If this treatment continues to prove effective, it could be
used to help rid the world of one of the most devasting of all
known plagues. Especially moving in me is the empathy I feel
for anyone with a debilitating febrile illness. I cannot forget
how horrible I feel whenever I have caught influenza. How much
more miserable it must be to suffer like that again and again
every 2 to 3 days as happens in malaria. Millions of people
suffer this way year round. 1 to 3 million die from malaria
every year mostly children. Thus motivated I sought to learn
all I could about the chemistry of the oxides of chlorine.
I wanted to understand their probable mechanisms of toxicity
towards the causative agents of malaria (Plasmodium species).
I wanted to check available literature pertaining to issues
of safety or risk in human use.
OXIDANTS AS PHYSIOLOGIC AGENTS
Oxidants are atoms or molecules which take up electrons.
Reductants are atoms or molecules which donate electrons
to oxidants. I was already very familiar with most of the
medicinally useful oxidants. I had taught at numerous
seminars on their use and explained their mechanisms of
action on the biochemical level. Examples are: hydrogen
peroxide, zinc peroxide, various quinones, various glyoxals,
ozone, ultraviolet light, hyperbaric oxygen, benzoyl peroxide,
anodes, artemisinin, methylene blue, allicin, iodine and
permanganate. Some work has been done using dilute solutions
of sodium chlorite internally to treat fungal infections,
chronic fatigue, and cancer; however, little has been
published in that regard.
Low dose oxidant exposure to living red blood cells induces
a change in oxyhemoglobin (Hb-O2) activity so that more
oxygen (O2) is released to tissues throughout the body.
Hyperbaric oxygenation (oxygen under pressure):
1) is a powerful detoxifier against carbon monoxide;
2) is a powerful support for natural healing in burns,
crush injuries, and ischemic strokes; and
3) is an effective aid to treat most bacterial infections.
Taken internally, intermittently and in low doses many
oxidants have been found to be powerful immune stimulants.
Sodium chlorite acidified with lactic acid as in the product
"WF10" has similarly been shown to modulate immune activation.
Exposure of live blood to ultraviolet light also has immune
enhancing effects. These treatments work through a natural
physiologic trigger mechanism, which induces peripheral white
blood cells to express and to release cytokines. These
cytokines serve as a control system to down-regulate allergic
reactions and as an alarm system to increase cellular attack
Activated cells of the immune system naturally produce strong
oxidants as part of the inflammatory process at sites
of infection or cancer to rid the body of these diseases.
Examples are: superoxide (*OO-), hydrogen peroxide (H2O2),
hydroxyl radical (HO*), singlet oxygen (O=O) and ozone (O3).
Another is peroxynitrate (-OONO) the coupled product of
superoxide (*OO-) and nitric oxide (*NO) radicals. Yet another
is hypochlorous acid (HOCl) the conjugate acid of sodium
hypochlorite (NaClO). The immune system uses these oxidants
to attack various parasites.
OXIDES OF CHLORINE AS DISINFECTANTS
All bacteria have been shown to be incabable of growing
in any medium in which the oxidants (electron grabbers)
out-number the reductants (electron donors). Therefore,
oxidants are at least bacteriostatic and at most are
bacteriocidal. Many oxidants have been proven useful as
antibacterial disinfectants. Hypochlorites (ClO-) are commonly
used as bleaching agents, as swimming pool sanitizers, and as
disinfectants. At low concentrations chlorine dioxide (ClO2)
has been shown to kill many types of bacteria, viruses and
protozoa. Ozone (O3) or chlorine dioxide (ClO2) are often used
to disinfect public water supplies or to sanitize and deodorize
waste water. Sodium chlorite (NaClO2) or chlorine dioxide (ClO2)
solutions are used in certain mouth washes to clear mouth odors
and oral bacteria. Chlorine dioxide sanitizes food preparation
facilities. Acidified sodium chlorite is FDA approved as a spray
in the meat packing industry to sanitized meat. This can also
be used to sanitize vegetables and other foods. Farmers use
this to cleanse the udders of cows to prevent mastitis, or
to rid eggs of pathogenic bacteria. Chlorine dioxide can be used
to disinfect endoscopes. Oxidants such as iodine, various
peroxides, permanganate and chlorine dioxide can be applied
topically to the skin to treat infections caused by bacteria
MALARIA IS OXIDANT SENSITIVE
From November 2006 through May of 2007 I spent hundreds of
hours searching biochemical literature and medical literature
pertaining to the biochemistry of Plasmodia. Four species are
commonly pathogenic in humans namely: Plasmodium vivax,
Plasmodium falciparum, Plasmodium ovale and Plasmodium
malariae. What I found was an abundance of confirmation that,
just like bacteria, Plasmodia are indeed quite sensitive to
oxidants. Examples of oxidants toxic to Plasmodia include:
artemisinin, artemether, t-butyl hydroperoxide, xanthone,
various quinones (e.g. atovaquone, lapachol, beta-lapachone,
menadione) and methylene blue.
Like bacteria, fungi and tumor cells, the ability of Plasmodia
to live and grow depends heavily on an internal abundance
of reductants. This is especially true regarding thiol compounds
also known as sulfhydryl compounds (RSH). Thiols as a class
behave as reductants (electron donors). As such they are
especially sensitive to oxidants (electron grabbers). Thiols
(RSH) such as glutathione and other sulfur compounds are
reactive with sodium chlorite (NaClO2) and with chlorine dioxide
(ClO2). These are the very agents present in Mr. Humble's
solution. The products of oxidation of thiols (RSH) using various
oxides of chlorine are: disulfides (RSSR), disulfide monoxides
(RSSOR), sulfenic acids (RSOH), sulfinic acids (RSO2H), and
sulfonic acids (RSO3H). None of these can support the life
processes of the parasite. Upon sufficient removal of the
parasite's life sustaining thiols by oxidation, the parasite
rapidly dies. A list of thiols (RSH) upon which survival
of Plasmodium species heavily depend includes:
lipoic acid and dihydrolipoic acid, coenzyme A and
acyl carrier protein, glutathione, glutathione reductase,
glutathione-S-transferase, peroxiredoxin, thioredoxin,
glutaredoxin, plasmoredoxin, thioredoxin reductase,
falcipain and ornithine decarboxylase.
HEME IS AN OXIDANT SENSITIZER
Of particular relevance to treating malaria is the fact that
Plasmodial trophozoites living inside red blood cells must
digest hemoglobin as their preferred protein source. They
accomplish this by ingesting hemoglobin into an organelle
known as the "acid food vacuole". Incidently, the high
concentration of acid in this organelle could serve as an
additional site of conversion of chlorite (ClO2-) to the more
active chlorine dioxide (ClO2) right inside the parasite.
Furthermore, Plasmodia consume 50 to 100 times more glucose
than noninfected red blood cells most of which is metabolized
to lactic acid a known activator of chlorite.
Next falcipain a hemoglobin digesting enzyme hydrolyzes
hemoglobin protein to release its nutritional amino acids.
A necessary byproduct of this digestion is the release
of 4 heme molecules from each hemoglobin molecule digested.
Free heme (also known as ferriprotoporphyrin IX) is redox
active and can react with ambient oxygen (O2), an abundance
of which is always present in red blood cells. This produces
superoxide radical (*OO-), hydrogen peroxide (H2O2) and
other reactive oxidant toxic species (ROTS). These can
rapidly poison the parasite internally. To protect themselves
against this dangerous side-effect of eating blood protein,
Plasmodia must maintain a high reductant capacity
(an abundance of reduced thiols and NADPH) to quench these
ROTS. This is their main mechanism of antioxidant defense.
Plasmodia must also rapidly and continuously eliminate heme,
which is accomplished by two methods. Firstly, heme is
polymerized producing hemozoin. Secondly, heme is metabolized
in a detoxification process that requires reduced glutathione
(GSH). Therefore any method (especially exposure to oxidants)
which limits the availability of reduced glutathione (GSH)
will cause a toxic build up of heme and of ROTS inside the
parasite cells. Sodium chlorite and chlorine dioxide (the
exact agents present in Mr. Humble's treatment) readily
oxidize glutathione. Therefore, a rapid killing of Plasmodia
upon taking acidified sodium chlorite orally should be
OVERCOMING ANTIBIOTIC RESISTANCE WITH OXIDATION
Now the issue of resistance of Plasmodium species to commonly
used antiprotozoal antibiotics must be addressed. Quinine,
chloroquine, mefloquine, quinacrine, amodiaquine, primaquine
and other quinoline-like antibiotics all work by blocking the
heme detoxifying system inside the trophozoites. Many
Plasmodial strains against which quinolines have repeatedly
been used have found ways to adapt to these drugs and to
acquire resistance. Research into the mechanisms of resistance
has found that often resistance is accomplished by a meere
upregulation of glutathione production and utilization.
Consequently oxidizing or otherwise depleting glutathione
inside the parasite usually restores sensitivity to the
quinoline antibiotics. Therefore, protocols combining the use
of oxidants with quinolines are under developement and already
showing signs of success. In this context let us consider that
no amount of intraplasmodial glutathione (GSH) could ever
resist exposure to a suffient dose of chlorine dioxide (ClO2).
Note that each molecule of ClO2 can disable 1 to 5 molecules
of glutathione depending on the reaction mechanism.
2(GSH) + 2(ClO2) -> 1(GSSG) + 2(H+) + 2(ClO2-)
or 10(GSH) + 2(ClO2) -> 5(GSSG) + 2(H+) + 2(Cl-) + 4(H2O)
Acidified sodium chlorite could provide a powerful new
opportunity to improve or to restore sensitivity to quinolines
by virtue of its oxidative power. However, quinolines contain
secondary or tertiary amino groups which react with chlorine
dioxide in such a way that both could destroy each other.
Some possible strategies to resolve this incompatibility are
Similar problems apply to methylene blue and many other drugs
if they have an unoxidized sulfur atom, a phenol group,
a secondary amine or a tertiary amine. Such are also very
reactive with the chlorine dioxide component.
- Acidified sodium chlorite could be used as
explained above only as a solo therapy.
- Quinoline administration could be withheld
until after the acidified sodium chorite has
completed its action.
- Patients already preloaded with a quinoline
could stop this, wait a suitable period of time
for this to wash out, then administer the
acidified sodium chlorite.
- The quinoline could remain in use and while
the less active sodium chlorite is administered
without acid. This should retain plenty of oxidant
effectiveness without destroying any quinoline or
wasting too much oxidant.
- Switch from a quinoline to an endoperoxide
(such as artemisinin) or to a quinone (such as
atovaquone) before using acidified sodium chlorite,
as these may be less sensitive toward destruction
by chlorine dioxide.
REDUCTANT RECOVERY SYSTEMS
Living things possess a recovery system to rescue oxidized
sulfur compounds. It operates through donation of hydrogen
atoms to these compounds and thereby restores their original
condition as thiols.
2 [H] + (GSSG) -> 2(GSH)
This system is known as the hexose monophophate shunt.
A key player in this system is the enzyme glucose-6-phosphate-
dehydrogenase (G6PDH). Patients with a genetic defect of G6PDH,
known as glucose-6-phosphate-dehydrogenase deficiency disease,
are especially sensitive to oxidants and to prooxidant drugs.
However, this genetic disease has a benefit in that such
individuals are naturally resistant to malaria. They can still
catch malaria, but it is much less severe in them, since they
permanently lack the enzyme necessary to assist the parasite
in reactivating glutathione and other oxidized thiols.
Chlorine dioxide (ClO2) has been shown to oxidize and denature
G6PDH by reaction with tyrosine and tryptophan residues inside
the enzyme. Furthermore, G6PDH is sensitive to inhibition by
sodium chlorate (NaClO3), another member of the chlorine oxide
family of compounds. Sodium chlorate (NaClO3) is a trace
ingredient present in Jim Humble's antimalarial solution.
Some sodium chlorate (NaClO3) should also be produced in vivo
by a slow reaction of chlorine dioxide (ClO2) with water under
2(ClO2) + 2(OH-) -> (ClO2-) + (ClO3-) + H2O
The Plasmodia may attempt to restore any thiols (RSH) lost to oxidation.
However, this becomes more difficult as G6PDH is inhibited by chlorine
dioxide (ClO2) or by chlorate (ClO3-).
While most available literature refers to redox imbalances
causing depletion of necessary thiols. Other mechanisms
of toxicity of the oxides of chlorine against Plasmodia
should also be considered. Oxides of chlorine are generally
rapidly reactive with ferrous iron (Fe++) converting it to
ferric (Fe+++). This explains why in cases of overdosed
exposures to oxides of chlorine such as sodium chlorite
(NaClO2) there was a notable rise in methemoglobin levels.
Methemoglobin is a metabolically inactive form of hemoglobin
in which its ferrous iron (Fe++) cofactor has been oxidized
to ferric (Fe+++). In living things including parasites iron
is a necessary cofactor for many enzymes. Thus it is
reasonable to expect that any damage to Plasmodia caused
by oxides of chlorine is compounded by conversion of ferrous
(Fe++) cofactors to ferric (Fe+++) or other alterations of
iron compounds. Superoxide dismutase (SOD) inside Plasmodial
cells also utilizes iron in its active center. Chlorine dioxide
also oxidizes manganese.
Other metabolites necessary for survival and growth in tumors,
bacteria and parasites are the polyamines. Plasmodia quit
growing and die, when polyamines are lacking, or when their
functions are blocked. Polyamines are also sensitive to
oxidation and can be eliminated by strong oxidants. When
oxidized, polyamines are converted to aldehydes, which are
deadly to parasites and to tumors. Chlorine dioxide (ClO2)
is known to be especially reactive against secondary amines.
This includes spermine and spermidine the two main
biologically important polyamines. Thus any procedure,
which is successful to oxidize both thiols and polyamines
does quadruple damage to the pathogen:
1) oxidation of the thiol ornithine decarboxylase
inhibits polyamine synthesis;
2) oxidation of the thiol S-adenosyl-L-methionine decarboxylase
also inhibits polyamine synthesis;
3) oxidation of the secondary amines spermidine and spermine
depletes polyamine supplies;
4) the products of polyamine oxidation are toxic aldehydes.
Purines are essential to many life processes. These molecules
have a double ring structure. The rings are heterocyclic
being composed of both carbon and nitrogen. The nitrogen atoms
are vulnerable to reaction with chlorine dioxide. Examples of
important biologic purines are xanthine, hypoxanthine,
inosine, guanine and adenine. Guanine and adenine are
essential components of DNA and RNA necessary for all genetic
functions and for all protein syntheses. Adenine is an
essential component of the cofactors NADH, NADPH, FAD and ATP,
necessary for many metabolic functions including oxidation-
reduction and energy metabolism. Any purines lost by chlorine
dioxide exposure can be readily replaced by host cells.
Plasmodia and other apicomplexae are uniquely vulnerable to
purine deficiency as they lack the enzymes necessary to produce
purines for themselves. Instead these must be scavenged from
host cells and imported across the plasma membranes of the
parasite cells. Drugs are under development to inhibit purine
utilization by Plasmodia and are already showing signs of
success. Temporarily destroying some of the purines in the
blood as should occur upon brief exposure to chlorine dioxide
in vivo is probably an additional stress that Plasmodia cannot
Chlorine dioxide (ClO2) is highly reactive with thiols,
phenols, secondary amines and tertiary amines. Therefore,
proteins composed of amino acids which present these
reactive groups are vulnerable to oxidation by this agent.
Proteins which present residue(s) of the amino acid L-cysteine
are discussed above under TARGETING THIOLS. L-tyrosine
presents a phenol group and is therefore similarly vulnerable.
L-tryptophan and L-histidine present secondary amino groups
which are also especially reactive with chlorine dioxide.
A remaining concern is safety. So far, at least anecdotally,
the dosages of chlorine oxides as administered orally per
Jim Humble's protocol have produced no definite toxicity.
Some have taken this as often as 1 to 3 times weekly and
on the surface seem to suffer no ill effects. To be certain
if this is safe more research is warranted for such long
term or repeated use. The concern is that too much or too
frequent administration of oxidants could excessively
deplete the body's reductants and promote oxidative stress.
One useful way to monitor this may be to periodically check
methemoglobin levels in frequent users. Sodium chlorite,
as found in municipal water supplies after disinfection
by chorine dioxide, has been studied and proven safe.
Animal studies using much higher oral or topical doses have
proven relatively safe. In a suicide attempt 10g of sodium
chlorite taken orally caused refractory methemoglobinemia
and nearly fatal kidney failure and refractory
methemoglobinemia. Inhalation or aerosol exposure to chlorine
dioxide gas is highly irritating and generally not
recommended. Special precautions must be employed
in cases of glucose-6-phosphate-dehydrogenase deficiency
disease, as these patients are especially sensitive to oxidants
of all kinds. Nevertheless, oral acidified sodium chlorite
solutions might even be found safe and effective in them,
but probably will need to be administered at lower doses.
It is hoped that this overview will spark a flurry of interest,
and stimulate more research into the use of acidified sodium
chlorite in the treatment of malaria. The above appreciated
observations need to be proven more rigorously and published.
The biochemistry most likely involved suggests that other
members of the phylum Apicomplexa should also be sensitive to
this treatment. This phylum includes: Plasmodium, Babesia,
Toxoplasma, Cryptosporidium, Eimeria, Theileria, Sarcocystis,
Cyclospora, Isospora and Neospora. These pathogens are
responsible for widespread diseases in humans, pets and cattle.
Other thiol dependent parasites should also be susceptible
to acidified sodium chlorite. For example Trypanosoma and
Leishmania extensively utilize and cannot survive without the
cofactor known as trypanothione. Each molecule of trypanothione
presents 2 sulfur atoms and 5 secondary amino groups all of
which are vulnerable to oxidative destruction from chlorine
Chlorine dioxide has been proven to be cidal to almost all
known infectious agents in vitro using remarkably low
concentrations. This includes parasites, fungi, bacteria and
viruses. The experiences noted above imply that this compound
is tolerable orally at effective concentrations. Therefore
extensive research is warranted to determine if acidified
sodium chlorite is effective in treating other infections.
We may be on the verge of discovering the most potent and
broad spectrum antimicrobial agent yet known. Special thanks
go to Jim Humble for his willingness to share his discovery
with the world.
by Thomas Lee Hesselink, MD
References are available upon request.