The History and Therapeutic Mechanisms Of Chlorine Dioxide

Chlorine dioxide was discovered over 200 years ago. It's use has steadily expanded into many industries and therapeutic applications despite a near global regulatory blockade on clinical research.

I believe that my writings on chlorine dioxide are the most important (and the most dangerous) work I have yet done on Substack. Although several experts have written extensively on this topic previously (here, here, and here), this similar effort of mine simply results from my wish to become as knowledgeable as possible about this critically important therapeutic (there is no better way to do so than personally researching and writing about a topic).

This is the 3rd in my ongoing series of posts. In the first two I presented the political context in which chlorine dioxide has been attacked during Covid (“Trump’s Bleach Conference”) and in the 2nd post I detailed the success achieved by Bolivia’s national chlorine dioxide program against Covid.

In this post I will review its discovery, chemical properties, industrial applications, and therapeutic mechanisms. Upcoming posts will cover the history of the attacks faced by the pioneering researchers and practitioners, followed by a review of the safety studies of oral ingestion and a compilation of studies showing efficacy in a number of diseases. Be sure to subscribe so as not to miss out on these critical upcoming posts.

Ultimately, what me and my growing network of clinical and scientific experts of this therapeutic compound want to achieve, is for the FDA (and the copycat regulatory agencies worldwide) to lift its restrictions on performing clinical research trials of chlorine dioxide in human diseases. If anyone from MAHA is reading this right now (and I know some are), please add chlorine dioxide (and DMSO) to the list of therapies currently being suppressed by the FDA that need to be reversed (RFK Jr listed more than a dozen other such therapies in the below recent tweet):

Note that, in the below, many (but not all) references were found from the superlative theuniversalantidote.com’s website, from their “interactive reference guidebook” document.

Chlorine Dioxide - What It is, What It Isn’t

Chlorine Dioxide is a small, volatile and strong molecule consisting of 1 chlorine atom and 2 oxygen atoms.

• It is a gas at normal temperatures and pressures.

• Yellowish/green color and has an odor similar to that of chlorine.

• Denser than air and is water soluble at standard temperatures and pressures up to 2500ppm.

• Explosive in air at concentrations >10%. It is therefore normally generated in-situ (on-site) within an aqueous solution at <0.3%

• Chlorine dioxide is a biocide. This means it kills all bacteria, viruses, and fungus on contact through a process of oxidization.

Chlorine dioxide was initially discovered in 1814 by Sir Humphrey Davy and was commercially produced in 1940 as a bleaching agent. It is labeled as a strong oxidizing agent, microbicide, and antiseptic. Based on these references here and here, chlorine dioxide is also known to have the ability to “neutralize various toxins, pesticides, herbicides, and pharmaceuticals contaminating drinking water.”

As an added bonus, it can do all of that without producing any harmful organic compounds as occurs with nearly all other disinfectants (like bleach - which contrary to FDA “warnings,” chlorine dioxide certainly is not).

Chlorine dioxide is more effective as a disinfectant than chlorine in most circumstances against waterborne pathogenic agents such as viruses, bacteria, and protozoa – including the cysts of Giardia and the oocysts of Cryptosporidium.

Chlorine dioxide has been extensively studied within multiple fields (commercial, industrial, healthcare) and by multiple entities including: EPA, HHS, USDA, CDC, NIH, NASA, DOD, independent laboratories, and universities worldwide.

Chlorine dioxide is registered as a sterilizer and biocide and is used to sterilize medical facilities and laboratories including BSL-3 and BSL-4 labs which handle the world's most deadly pathogens. It was used to decontaminate the Senate offices in 2001 after the anthrax attack, and was also used in Ebola hot spots.

From this systematic review paper on chlorine dioxide as a disinfectant:

Different chemical structures with properties of disinfectants have been identified. These chemical structures include alcohol, aldehydes, anilides, biguanides, bisphenols, diamidines, halogen-releasing agents, halophenols, heavy metal derivatives, peroxygens, quaternary ammonium compounds, phenols, and cresols. However, each disinfectant attacks different target areas of the micro-organisms. Disinfectants can be divided into two broad groups: oxidizing and non-oxidizing disinfectants. Disinfectants containing halogens such as chlorine, iodine, and oxygen releasing materials are called oxidizing disinfectants, while disinfectants that bond to structures such as quaternary ammonium compounds and amphoterics are known as non-oxidizing disinfectants.

Oxidizing agents like chlorine dioxide are chemical compounds that accept electrons from “electron donors.” This is important because relative to chlorine dioxide, all pathogens (disease causing organisms or substances) are electron donors.

So what happens to chlorine dioxide after it reacts and oxidizes the pathogens? In aqueous systems, chlorine dioxide eventually decomposes into generally safe byproducts that naturally occur in our environment, i.e. chloride ions (like in table salt), oxygen (O₂), and other non-toxic residues.

From Chat GPT when asked to contrast chlorine dioxide with bleach:

Chlorine dioxide and bleach (sodium hypochlorite) are both powerful oxidizing agents commonly used as disinfectants, but they differ significantly in their chemical structure, mechanism of action, and applications. Here's how they compare:

1. Chemical Composition

• Chlorine Dioxide (ClO₂): A gas at room temperature, typically dissolved in water for use. It is a single molecule composed of one chlorine atom and two oxygen atoms.

• Bleach (Sodium Hypochlorite, NaOCl): A liquid solution containing sodium hypochlorite as the active ingredient, along with water and small amounts of other chemicals.

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2. Mechanism of Action

• Chlorine Dioxide: Kills microorganisms by disrupting their metabolic processes and breaking down cell membranes and proteins. It primarily reacts with organic matter through oxidation.

• Bleach: Also acts as an oxidizer, generating hypochlorous acid (HOCl) in water, which destroys bacteria and viruses by disrupting their enzymes and proteins.

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3. By-products

• Chlorine Dioxide: Produces fewer harmful by-products, primarily chlorite and chlorate ions (initially), which are less persistent in water systems compared to bleach by-products.

• Bleach: Can produce potentially harmful chlorinated organic compounds (e.g., trihalomethanes and chloramines), especially when reacting with organic matter in water. (Editorial note: this is extremely important, trihalomethanes are suspected carcinogenic disinfection by-products^[ associated with chlorination of naturally occurring organics in raw water.

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4. Effectiveness

• Chlorine Dioxide: Remains effective over a wide pH range (4–10) and is less affected by the presence of organic matter, making it suitable for challenging disinfection tasks.

• Bleach: Its efficacy decreases significantly outside a pH range of 6–8 and in the presence of organic matter.

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5. Applications

• Chlorine Dioxide:

  • Water treatment (municipal, industrial, and potable water systems).

  • Food and beverage sanitation.

  • Medical disinfection and biofilm removal.

• Bleach:

  • Household cleaning and laundry.

  • Pool and spa disinfection.

  • Surface disinfection in healthcare and other settings.

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6. Safety and Stability

• Chlorine Dioxide: Typically generated on-site because it is unstable as a concentrated gas and can decompose explosively. However, it is considered safer for certain applications due to fewer toxic by-products.

• Bleach: Stable in liquid form but degrades over time, particularly when exposed to light and heat. It has a strong, recognizable smell and can be irritating to skin and respiratory systems.

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7. Odor and Residue

• Chlorine Dioxide: Has a less pronounced odor and does not leave a strong chemical residue or taste in treated water.

• Bleach: Has a strong chlorine smell and can leave noticeable chemical residues.

Summary:

While both are effective disinfectants, chlorine dioxide is often preferred for applications requiring minimal by-products and effectiveness in diverse conditions, whereas bleach is more common for general-purpose household and industrial disinfection.

TIMELINE OF ITS ADOPTION ACROSS INDUSTRIES

Taken from pioneer Jim Humble’s website, here I provide a short paraphrased history of its use in industry where I also dug up the references:

1811: Chlorine dioxide is discovered by Sir Humphrey Davy, when he adds sulfuric acid (H2SO4) to potassium chlorate (KClO3). In the early 1900’s it was recognized as an antimicrobial biocide and became known for its disinfectant properties.

1930’s: Due to concerns about the logistics of safely transporting the gas, sodium chlorite began to be manufactured as a relatively safe precursor chemical, and the industries using chlorine dioxide would then generate the gas onsite as needed. Because of chlorine dioxide’s solubility in water, it starts being used as a water treatment.

1944: First commercial application. Used as a biocide/taste and odor control agent in domestic water at Niagara Falls in the USA.

1950’s: Increasing use of chlorine dioxide in water treatment plants and swimming pools in the U.S.A. Likewise it is discovered that chlorine dioxide destroys biofilm, the algal slime that collects in cooling towers, among other places and harbors harmful bacteria. Chlorine bleach by contrast cannot kill biofilm.

1956: Brussels, Belgium, switches to chlorine dioxide from chlorine for its drinking water disinfection operations. This marks the first large scale use of chlorine dioxide for potable water treatment.

1967: The Environmental Protection Agency (EPA) of the United States first registers chlorine dioxide as a disinfectant and sanitizer. The registration is for chlorine dioxide in the liquid form. Indicated uses include food processing (!), handling and storage plants, bottling plants, washing fruit and vegetables (!), sanitizing water, controlling odors, and treating medical wastes.

1970’s: The EPA begins recommending using chlorine dioxide instead of chlorine bleach to treat water. Hundreds of municipal water systems successfully convert to chlorine dioxide. This happens across the United States and Europe; more so for the latter. The conversion is catalyzed by a safer environmental profile of chlorine dioxide over chlorine, because chlorine dioxide does not produce any harmful byproducts, as does chlorine bleach.

1977: Three thousand municipal water systems achieve biological control using chlorine dioxide (EPA document here)

1980’s: Chlorine dioxide gradually replaces chlorine in many industries – in the pulp and paper industry as a bleaching agent, in industrial water treatment as a biocide and as an odor control agent, in food processing as a sanitizer.

1983: The EPA recommends chlorine dioxide as a solution for the problem of trihalomethanes (THMs). When chlorine is used to disinfect water and make it potable (chlorination), THMs are produced as a by-product. THMs have been linked to cancer (i.e., they are carcinogenic). Chlorine dioxide does not produce THMs.

1988: The EPA registers chlorine dioxide as a sterilizer. This means chlorine dioxide is both safe and effective to use in hospitals, healthcare facilities, and laboratories.

1990: Use of chlorine dioxide as a disinfectant, sanitizer and sterilizer grows across many industries and countries. Some of the industries are the beverage industry, fruit and vegetable processing plants, pulp and paper industries, and industrial waste treatment sites. These industries are spread across the United States, the United Kingdom and Europe.

2001: The Federal Emergency Management Agency (FEMA) and other government agencies use chlorine dioxide to decontaminate buildings contaminated with Anthrax. The chlorine dioxide was completely effective against the tiny Anthrax spores. The buildings, walls and furnishings suffered no damage from the treatment.

2005: FEMA again uses chlorine dioxide. It is used to eradicate mold infestations in homes damaged by the flood waters from Hurricane Katrina. After a 12-hour treatment, a New Orleans restaurant is able to banish all mold inside without rebuilding.

2010: The United States Food and Drug Administration issue a warning on using the chlorine dioxide formulation called Miracle Mineral Solution (MMS - made by combining sodium chlorite with hydrochloric acid) and pioneered by Jim Humble in his numerous treatment protocols. The FDA repeatedly describes it as industrial bleach while at the same time approving chlorine dioxide for use in mouthwashes, toothpastes, and as a food service disinfectant, citing it as being a better alternative than chlorine.

2014: The Centers for Disease Control (CDC) registers ProKure V and PERFORMACIDE® as disinfectants against the Ebola virus. Both contain chlorine dioxide. ProKure V claims it “begins to kill pathogens in a matter of seconds, whereas other commonly used, more traditional disinfectants take minutes. The rapid speed in which ProKure V kills pathogens makes it a product of choice for helping contain infectious-disease outbreaks and keeping public facilities cleaner and safer for everyone.” Chlorine dioxide is a potent virucide.”

EFFICACY AND SAFETY AS A BIOCIDE

Chlorine dioxide is one of, if not the fastest known and “complete spectrum” disinfectants, killing all forms of bacteria (aerobic, anaerobic, gram positive and negative), viruses, fungi and yeast, typically within a minute of contact, (spores a little longer), and notably without damage to animal cells, or even tissue culture cells.

In this mouse study (know that mice are more sensitive than humans to toxicities for many but not all compounds), they found that at concentrations between 5 and 20 ppm (this concentration becomes highly relevant in a later post when I discuss safety of oral treatment dose concentrations), chlorine dioxide killed almost all of the bacteria and fungi present while no damage to lung cells, eyes, or other organs was observed, even when 40ppm was added to their drinking water sub-chronically. The study concluded “chlorine dioxide showed favorable disinfection activity and a higher safety profile tendency than in previous reports.”

This is a very short list of papers showing in vitro and/or in vivo (animals) efficacy against a number of viruses and bacteria (more on this in a later post).

Typhoid, Norovirus, Hepatitis C virus, HPV, HIV, Influenza A Virus, E.Coli, Listeria, Rotavirus, Mycobacterium Avium, Hepatitis A Virus, staph aureus, also hospital pathogens like Acinetobacter baumannii, Escherichia coli, Enterococcus faecalis, Mycobacterium smegmatis, and Staphylococcus aureus.

Moving away from in vitro data in order to show that it can cure infectious disease in animals (in vivo study), in a randomized controlled trial from 2008 they exposed 10 mice to aerosolized influenza A and aerosolized chlorine dioxide at (0.03 ppm) simultaneously for 15 minutes. A control group of 10 mice were exposed to only the aerosolized influenza A for 15 minutes. Sixteen days after exposure, none of the mice exposed to the chlorine dioxide influenza A group had died, but 7 out of 10 mice in the influenza only control group died. That is a 70% fatality for the mice that did not receive aerosolized chlorine dioxide. Did you catch that? Extremely low doses of chlorine dioxide protected 100% of those mice from influenza.

Moving past in vitro and in vivo trials, in a later post I will review the efficacy of chlorine dioxide in the treatment of infectious and other diseases in humans. There I will provide a compilation of all published human clinical trials and studies (which are artificially few due to the suppression of clinical research using chlorine dioxide.

A comprehensive list of all organisms it has been studied and shown efficacy against is beyond the scope of this post, however, know that in a 2010 study, concentrations ranging from 1 to 100 ppm inactivated ≥ 99.9% of the viruses with a 15 sec treatment. The antiviral activity of CD was approximately 10 times higher than that of sodium hypochlorite which is standard bleach.

NASA actually referred to chlorine dioxide as “A Universal Antidote” back in 1988 (p.118 from this Annual Report), where these statements appear:

1. The special properties of the Alcidem formulation, which has been approved by U.S. regulatory authorities, enable it to destroy mold and fungus, as well as bacteria and viruses, with minimal harm to humans, animals or plants

2. NERAC conducted a computer search of more than a dozen databases and uncovered scores of applications, among them treatment of viral, fungal and bacterial infections in animals; treatment of human skin diseases; disinfection and sterilization of medical facilities;

3. The University of Connecticut Medical School is studying the effects of the Alcide compound on human wound healing and scar tissue suppression.

4. At Israel's Hebrew University Dental School, trials are in progress on a plaque reducing mouthwash and in England researchers are meeting success in human clinical trials of treating herpes and other sexually transmitted diseases.

I cannot over emphasize the importance of the above NASA document from 1988. In it, they admit that it treats a broad range of infections in animals, aids in wound healing (I have a lot on that later), and was having success in treating herpes and other STD’s. Never forget this when you read statements from regulatory agencies across the world where they repeatedly warn that it is a “toxic bleach,” “bleach like substance,” and is “dangerous for ingestion.” Absurd.

Also take note of the fact that NASA never refers to it again in such a positive way. The next mention by NASA was in 1991 when referring to its use in the space shuttle where they caution of the risk of developing hemolytic anemia and disturbing thyroid function (such risks are negligible to non-existent in clinical practice).

Therapeutic Mechanisms Of Action

• Anti-bacterial mechanisms: chlorine dioxide interacts intricately with sulfur-containing compounds that are abundantly found in various bacteria. This interaction disrupts the metabolic processes of these microorganisms, effectively inhibiting their reproduction and growth. Remarkably, at lower concentrations of 0.25 mg/L, CD can eradicate 99% of E. coli (15,000 cells/mL) within a mere 15 seconds.

• Anti-fungal mechanisms: causes significant damage to fungal cell membranes. This damage leads to the leakage of intracellular components such as potassium ions (K⁺) and adenosine triphosphate (ATP), suggesting that ClO₂ disrupts membrane integrity.

• Anti-viral mechanisms: ClO₂ inactivates viruses by oxidizing specific amino acids, such as cysteine, methionine, tyrosine, and tryptophan, in viral proteins. This oxidative modification leads to protein denaturation, impairing the virus's ability to infect host cells. ClO₂ reacts with viral components, including proteins and genetic material. These reactions compromise the virus's structural integrity and functionality, leading to its inactivation. In its gaseous state, ClO₂ can penetrate the outer shells of encapsulated viruses, leading to their inactivation.

In this post, Andreas Kalcker describes the “dual properties” of CDS:

It possesses the unique ability to effectively oxidize pathogens that exhibit an oxidation-reduction potential (ORP) lower than its own ORP of 0.95V. This means that it can target and neutralize various harmful microorganisms, including bacteria, viruses, and fungi, by disrupting their cellular processes and ultimately leading to their demise.

At the same time, CDS also functions as a powerful reducing agent, as it can interact with and reduce harmful free radicals that have higher ORPs—such as hydroxyl radicals (OH-) which possess an ORP of 2.8V. In this process, chlorine dioxide transforms these detrimental radicals into harmless water molecules. This dual functionality is particularly important in the context of therapeutic applications, as it allows CDS to both eliminate harmful agents while simultaneously protecting healthy cells from oxidative stress.

From this masterful review article in the University of Guadelajara journal on mechanisms of chlorine dioxide, they report even more broadly systemic therapeutic mechanisms:

• low concentrations of ClO2 can protect erythrocytes (red blood cells) from oxidative stress while inhibiting myeloperoxidase (MPO)-mediated excessive hypochlorous acid (HClO) production, thus reversing inflammatory responses and macrophage activation.

• increases the expression of heme-oxygenase (HO-1), protects cells from death caused by hydrogen peroxide (H2O2), enhances the expression and activities of antioxidant enzymes, such as superoxide dismutase, catalase and glutathione peroxidase, and contributes to the resolution of the inflammatory process.

• It promotes apoptosis (programmed cell death) in neutrophils, which helps resolve inflammation effectively

• It has demonstrated anti-inflammatory responses by inhibiting macrophage activation in humans, thus reducing inflammation

• Here it is important to review the different types and functions of macrophages (our immune system’s first line of defense against toxins and pathogens) :

  Monocytes are bone marrow derived precursors of tissue macrophages that are critical effectors of wound healing, clearance of bacteria and cellular debris and induction and resolution of inflammation. Macrophages that are associated with classical inflammation are termed M1 and those cells produce factors such as TNF-α, IL-1 and other proinflammatory factors. Macrophages that are associated with reversal of inflammation and suppression of immune responses are termed M2. In the context of ALS pathogenesis, the M2 macrophage phenotype within the spinal cord is associated with normal function, whereas the appearance of new M1 type macrophages within the spinal cord is associated with disease progression.

  These data suggest that systemic macrophage associated inflammation may play a significant role in ALS disease progression.“ In this study of a chlorine dioxide precursor in ALS, they report “these mechanisms of downregulation transform inflammatory monocytes/macrophages from a proinflammatory to a basal phagocytic (wound healing) state.”

  I will cover the studies showing improved survival and function in ALS patients in a later post.

• taurine-chloramine is a product of activated neutrophils and represents the most relevant functional product formed under the influence of chlorine dioxide. This molecule activates nuclear factor erythroid 2 (Nrf2), (this transcription factor regulates the inducible expression of numerous genes for detoxifying and antioxidant enzymes), and inhibits production of pro-inflammatory cytokines.

• In a study of a different precursor, they report, “Of importance, a single dose of NP001 (a patented formulation of chlorite) caused a dose-dependent reduction in downregulation of CD16-expressing inflammatory macrophages in blood.”

• In this study, they found that the above WF10 (another patented formulation) exerts potent immune-modulatory effects through generating endogenous oxidative compounds such as taurine chloramine. Proliferation and IL-2 production of anti-CD3 stimulated PBMC were inhibited by WF10, as was the nuclear translocation of the transcription factor NFATc.

• In another study of the NP001 proprietary formulation of pH stabilized, purified chlorite, they found that in the presence of heme-associated iron, presumably from the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex on the surface of phagocytic cells, it is converted from a prodrug through a hypochlorite intermediate, to an intracellular form of taurine chloramine (TauCl). TauCl is a long-lived effector molecule within macrophages that down-regulates NF-kB expression and inhibits production of pro-inflammatory cytokines in part through activation of heme oxygenase-1 (HO-1). A phase 1 controlled trial of NP001 in patients with ALS demonstrated the safety, tolerability, and dose dependent down-regulation of monocyte activation.

More therapeutic mechanisms:

Taken from this Andreas Kalcker substack post, he describes the effects of chlorine dioxide solution (CDS) using venous blood gas analysis:

• The blood pH became more alkaline, indicating a reduction in acidity and an increase in basicity.

• Blood oxygen levels increased, suggesting enhanced oxygenation throughout the body.

• The concentration of carbon dioxide (CO₂) in blood decreased, implying effective CO₂ elimination via respiration.

• There was an observable improvement in acid-base balance, particularly in base deficit, reflecting better pH regulation within the body, essentially reducing metabolic acidity, frequently a fundamental factor in numerous modern diseases

• Blood glucose levels normalized, with reductions in hyperglycemia noted in other cases.

• A significant decrease in blood lactic acid levels was observed, indicating improved removal of metabolic waste products.

Based on the above and considering the molecular composition of chlorine dioxide (two atoms of oxygen), Kalker argues in his mechanisms of action post here (where I paraphrase for brevity:

"chlorine dioxide transports oxygen to all parts of the body where water is present. The bound oxygen dissociates in the presence of excess protons in areas of disease (like spike protein). The released oxygen optimizes the saturation of hemoglobin in the red blood cell and thus improves oxygen delivery to the most acidic cells and their compromised mitochondria first, while the chlorine ion (not chloride) eliminates pathogens or acidic toxins and restores pH balance. This improvement in cellular oxygenation is thought to be yet another positive therapeutic mechanism for reversing disease.

Images depicting the effects of CDS on blood on a Nikon Phase contrast Microscope:

Effects of CDS in Human Blood under phase contrast microscope

In these phase contrast microscopy images above, the impact of CDS on small red blood cells is clearly visible. Initially, the cells were highly agglutinated and oxygen-deprived. Following the infusion of CDS at a maximum concentration of 3000 ppm from the left side, immediate signs of oxygenation can be observed. After a mere 12 minutes, all blood cells exhibit optimal oxygenation levels.

**As a pulmonologist, I don’t know how you can “see” improved oxygenation, although it can be inferred by the dramatic increase in the exposed surface area of each blood cell as they de-aggregate.

Overall, studies and treatment experiences reveal that treatment with chlorine dioxide:

1. is broadly antimicrobial against nearly all infectious pathogens

2. reduces inflammation

3. prevents scarring

4. aids in wound healing

5. is non-toxic when orally ingested (in appropriate concentrations)

6. reduces oral plaque

7. treats oral atrophic candidiasis

8. is a potent deodorizer

9. has in-vitro anti-cancer cell effects, stimulates an in-vivo anti-cancer cell immune response and is also effective when injected intra-tumorally, or via a combination of oral, enema, and IV administration.

This combination of properties is not found in any other compound. The therapeutic uses for chlorine dioxide are endless. And therein lies the problem. Stay tuned for my upcoming post which compiles the studies and trials in a diverse set of human diseases.

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** Please know that I am not recommending that anyone use chlorine dioxide orally given it is not FDA approved for oral ingestion in any medical condition, nor has it been approved by any foreign regulatory agency, nor is it classified as a food supplement. What I am trying to do is amass the critical information needed to petition the “new” FDA (and other regulatory agencies worldwide) to remove their restriction on performing human subjects research with orally ingested chlorine dioxide.

If this post whet your appetite for learning more about chlorine dioxide and you appreciate the time and effort I put into researching and writing my posts, please consider a paid subscription. My next posts will contain more detailed and referenced information on the safety and efficacy of oral, topical, and IV administration

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