Lack of studies on small doses of chlorine dioxide as treatment for diseases

Question

While ingesting high doses of chlorine dioxide are toxic to humans, this is not the case for smaller doses. Ingesting, for example, 30 mg per day for a few days would probably not result in serious adverse events. I conclude this from the NOAEL value of the EPA. This value is 3 mg/kg per day, so 210 mg for a person of 70kg.

Considering that many people actually believe that ingesting chlorine dioxide can treat various diseases (see for example the Wikipedia page), why has there not been any research on this?

A few remarks:

• Of course, I am aware of MMS, which contains ridiculously high concentrations of chlorine dioxide. This question is not about MMS, but it is about ingesting much lower concentrations.
• I have searched the internet for approximately half an hour and found not even a single reliable study on chlorine dioxide for the treatment of any disease. Please tell me if I am wrong and if there are reliable studies on this topic.

Answer 1

You are quite wrong that no-one has looked at efficacy of ClO₂.

There have been numerous studies on this topic as listed in PubMed (1552 according to them, though lots of these will be about disinfection of surfaces etc or activity in non-human species), with everything from COVID-19 (e.g. this one¹), to bacterial infections and fungal infections being examined.

Generally the uses examined have been as a surface cleaner, such as a mouthwash or a sanitizing wipe. There is limited use for it in situations other than these because of the nature of the chemical.

So far, no-one has found any efficacy for ingestion of these compounds because, and it's not a surprising conclusion... they don't work. Basically what happens once ingested is that the chemical acts as an oxidizer, reacting with whatever is available to be oxidized, be it lipids, proteins, etc. In the case of a viral infection while there are high loads of virus in the body, these are still vastly dwarfed by the biological compounds from the body, so the molecules of ClO₂ are much much more likely to hit a cell, mucus, etc from the body than they are an infecting organism.

As this² article states:

It is necessary to understand the mechanism of action of oxidizing agents, such as chlorine dioxide and sodium chlorite. As mentioned previously, these substances serve as disinfectants due to their oxidizing properties. This means they can oxidize other compounds via an oxidation–reduction reaction [24]. Ultimately, chemical reactions will induce disruption of protein synthesis and outer membrane permeability due to rapid efflux of potassium ion, leading to the destruction of the transmembrane ionic gradient [25, 26]. This effect is not specific to a particular organism; human cells, like other microorganisms, are also affected [27].

To put it into some perspective, I've added the below.

The webcomic XKCD gave a reasonable explanation of how abundant viruses are in their What-if? series. Basically what it boils down to is that in the natural state you have about 10¹² (a thousand billion) virions in you all the time. These are mostly bacteriophages, so only infect bacteria. However, if you gathered these 10¹² virions from all the people on the planet, they would still only make up about 10 40-gallon (10 x 150 litre) barrels in volume. That's the equivalent of a box 1 metre width x 1 m height x 1.5 m (3.3 x 3.3 x 5 feet) long in total.

I did a back-of-the-envelope calculation on how much that would be in volume per person. Assuming 1500 l (10 x 150 l) and 8 billion (7.96 billion actually) people on the planet, it works out to be about 0.2 microlitres (actually 0.1875) per person. That's a drop so small that it is hard to measure, but because I work in a lab I can, so I did and took a photo (excuse the blurriness, it's hard to focus at that range/scale with a cell-phone camera):

That's a centimetre ruler, each small division is 1 millimetre. The blue drop is 0.2 microlitres. So, if you compare that volume (~0.2 ul) to the volume of a human body, you can see why the ClO₂ molecules would be massively more likely to interact with a human tissue component than the virus itself, and hence why ingestion certainly doesn't work.

Now, you might be thinking, "But what about COVID infection, that's not a normal state" - well, this paper³ estimates about 10¹¹ RNA copies per person per infection - lets assume that's the number of virions (it's not - many more RNA produced than virions, but for calculation's sake...) that's still only one tenth of the 10¹² virions normally present i.e. 1.1 x10¹² instead of 1.0 x10¹² particles, so it doesn't change the amount/volume meaningfully!

References:

1. Travis BJ, Elste J, Gao F, Joo BY, Cuevas-Nunez M, Kohlmeir E, Tiwari V, Mitchell JC. Significance of chlorine dioxide-based oral rinses in preventing SARS-CoV-2 cell entry. Oral Dis. 2022 Jul 16. doi: 10.1111/odi.14319. Epub ahead of print. PMID: 35841377.

2. Arellano-Gutiérrez G, Aldana-Zaragoza EH, Pérez-Fabián A. Intestinal perforation associated with chlorine dioxide ingestion: an adult chronic consumer during COVID-19 pandemic. Clin J Gastroenterol. 2021 Dec;14(6):1655-1660. doi: 10.1007/s12328-021-01527-y. Epub 2021 Oct 18. PMID: 34664196; PMCID: PMC8522852.

3. Sender R, Bar-On YM, Gleizer S, Bernsthein B, Flamholz A, Phillips R, Milo R. The total number and mass of SARS-CoV-2 virions. medRxiv [Preprint]. 2021 Apr 5:2020.11.16.20232009. doi: 10.1101/2020.11.16.20232009. Update in: Proc Natl Acad Sci U S A. 2021 Jun 22;118(25): PMID: 33236021; PMCID: PMC7685332.