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Resolving the paradox of iodine - an essential biomolecule 2 of 4

Diluting iodine solutions debunk the I2 toxicity belief


Molecular iodine is not easily studied in clinical settings due to its instability in aqueous solution. To circumvent this problem, complexing agents and other iodine species have been used to stabilize I2.

As a result of not being able to adequately study molecular iodine, the scientific community has arbitrarily linked negative traits to I2, even though they should be attributed to the complex and diverse iodine solution.

Food for thought:

Is the difficulty encountered when studying molecular iodine adequate reason to "assume" it is the cause of the negative traits in iodine formulations that contain multiple iodine species?

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Resolving the paradox of iodine - an essential biomolecule 1 of 4

Imprecise definition of Iodine is a major challenge to clinical application.


The broad medical community considers the term iodine as any of many different topical antiseptics that stain the skin. Among chemists, the use of this term is a long-standing abuse of iodine’s nomenclature which generalizes every iodine species as “iodine”. This nomenclature generalization masks the complexity of iodine chemistry within the medical community and contributes to some avoidable adverse effects for patients.

Food for thought:

The lack of addressing specific iodine components makes it difficult to correct misconceptions and leads to miseducation surrounding iodine’s properties of staining, toxicity, and biocidal activity.

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Molecular iodine is not responsible for cytotoxicity in iodophors

Molecular iodine is not responsible
for cytotoxicity in iodophors


The aims of the investigation were to:

  • Compare the staining properties of the I2 species versus those species of iodine that comprise the overwhelming majority of iodine found in topical disinfectants.
  • Demonstrate that the concentrations of I2 used by health care workers in diluted Povidone Iodine used to reduce SARS-CoV-2 in the nasal cavity are not cytotoxic.
  • Determine if high concentrations of I2 can be delivered beyond the stratum corneum into the hypodermis of skin which could provide a mechanistic rationale for I2 out-gassing first reported by Gottardi.
Key takeaways:
  • Concentrations of I2 (7800 ppm) that are 1500 times higher than that found in Povidone Iodine can be applied to skin without irritation and staining.
  • I2 is not cytotoxic at concentrations more than 100 times higher than that found in Povidone Iodine and does not materially contribute to staining of skin at concentrations found in Lugol’s solution (ca 170 ppm).
  • I2 delivered topically will reach the hypodermis tissue and release through the skin over time.
Why is this manuscript important:
  • It disproves the long-held belief that I2 is responsible for toxicity and staining associated with Povidone Iodine, Lugol’s Solution and iodine tinctures.
  • It demonstrates that I2 is absorbed through all skin layers and partitions into regions of unsaturated lipid (fat) in the hypodermis. The hypodermis tissue becomes a material that releases I2 through all layers of the skin over time.
Food for thought:
Inclusion of I2 as an active biocide in a topical composition may provide the benefits observed with other topical antiseptic disinfectants and have the potential to:
  •   - Treat infectious diseases.
  •   - Act as an anti-inflammatory.
  •   - Stimulate wound healing.


Citation:
Freeman C, Duan E, Kessler J, Molecular iodine is not responsible for cytotoxicity in iodophors, Journal of Hospital Infection, https://doi.org/10.1016/j.jhin.2022.01.015.

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The Effect of Supraphysiologic Levels of Iodine on Patients with Cyclic Mastalgia

The Effect of Supraphysiologic Levels of Iodine on Patients with Cyclic Mastalgia


This study determined the specific dose of iodine that produces the largest decrease in breast pain severity, as well as the safety of iodine as a treatment for breast pain.



What was shown:
  • Molecular Iodine was the active iodine agent used to treat chronic cyclic breast pain in women of childbearing ages in Phase I, II and III trials conducted in the United States.
  • The novel iodine tablet consisted of two food additives that formed Molecular Iodine in the stomach when dissolved in gastric fluid.
  • The safety of iodine as a treatment for breast pain was demonstrated at daily doses of 1.5, 3.0 and 6.0 mg/day.
  • In this phase II study, the reduction in self-reported breast pain was proportion to the daily dose of I2.
Food for thought:

A tablet form of iodine created Molecular Iodine in the stomach after which it could be absorbed by the body, and in the study case, used to alleviate pain.

Citation:
Kessler JH. Breast J. 2004 Jul-Aug;10(4):328-36.
doi: 10.1111/j.1075-122X.2004.21341.x. PMID: 15239792.

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Control of the amount of free molecular iodine in iodine germicides

Control of the amount of free molecular iodine in iodine germicides


This study was performed to establish the main aspects of iodine chemistry, bactericidal efficacy and toxicity of enzyme-based iodine germicides using horseradish peroxidase.

What was shown:

  • Real time measurement of the conversion of iodide into free molecular iodine.
  • Use of Gottardi's [contributing author] potentiometric method to dynamically monitor free molecular iodine.
  • The enzyme-based composition catalyzes the regeneration of iodine. Molecular iodine was regenerated in response to a bioburden which enabled persistent biocidal activity.
  • The naturally occurring biocidal iodine species (molecular iodine) was shown to be available and active for sustained periods of time.
  • The biocidal efficacy of such compositions was proportional to the concentration of free molecular iodine.
  • An effective germicide containing a high level of molecular iodine need not be irritating or toxic.
Food for thought:
The ability to regenerate a natural biocide that is neither irritating nor toxic is available today for integration into products where disinfection is a key aspect.

Citation:
Hickey J, Panicucci R, Duan Y, Dinehart K, Murphy J, Kessler J, Gottardi W. J Pharm Pharmacol. 1997 Dec;49(12):1195-9.
DOI: 10.1111/j.2042-7158.1997.tb06069. PMID: 9466342.

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Properties of an enzyme-based low level iodine disinfectant

Properties of an enzyme-based low level iodine disinfectant


This study documents an enzyme-based iodine (EBI) disinfectant that continuously generates free molecular iodine (I2) in a controlled fashion and evaluates the EBI for use in disinfecting flexible fiberoptic endoscopes (FFEs).

What was shown:

  • A unique feature of the EBI-solution is its ability to generate I2 at a defined rate over a day.
  • The generation of I2 can be controlled and tailored for specific application use
  • Five different flexible fiber scopes were processed (disinfected). No organism was recovered from internal or external sampling sites from 15 trials.
  • Acute dermal, acute ocular, acute oral and acute inhalation toxicity testing on animals resulted in a toxicity score of zero in all instances.
  • Bacteria, mycobacteria and viruses (including HIV-1 and Polio) were inactivated at a rate equivalent to 2% Glutaraldehyde.
  • The EBI-solution passed the AOAC sporicidal assay at 24 hours.
  • Gottardi's [contributing author] potentiometric method was used to dynamically monitor I2.
Food for thought:
It is possible to control the regeneration of free molecular iodine (a natural biocide). Using free molecular iodine as the biocidal agent, an alternative disinfectant to Glutaraldehyde can be created that is as effective and has a more desirable safety profile.

Citation:
Y Duan 1, K Dinehart, J Hickey, R Panicucci, J Kessler, W Gottardi
Properties of an enzyme-based low level iodine disinfectant
J Hosp Infect. 1999 Nov;43(3):219-29. DOI: 10.1053/jhin.1999.0249. PMID: 10582189.

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Molecular Iodine In, On and Above the Skin

Molecular Iodine - In, On and Above the Skin


Molecular iodine (I2) is an ingredient in all I2PURE formulations. The I2 is absorbed into the Epidermis, the Dermis and down to the Subcutaneous Tissue. The I2 converts to a colorless, odorless gas which is released through the skin. For 6+ hours pathogens which come in contact with the I2 gas (in, on or above the skin) are killed.

Food for thought:

Molecular Iodine can be included as an ingredient in hand lotion. Once absorbed into the skin, the I2 becomes a gas and is released through the skin. It cannot be washed off.

Pathogens coming in contact with the gas in, on and above the skin are killed for 6+ hours.

How does this compare to hand sanitizers that wash off?



Citation: Base Image Attribution.

The Dawn of Molecular Iodine

The Origin Story of Molecular Iodine


DID YOU KNOW ... iodine along with other essential elements trace their origin stories back 10 billion years when a dying star went supernova. That massive explosion set off a nucleosynthesis – a process by which new atomic nuclei are formed by the collapse of a star. As the supernova dissipated, its dust formed the earth about 5 billion years ago. Iodine on the earth is a component of nuclear ash!  How cool is that!

Food for Thought:

  • When looking at iodine from an evolutionary perspective, it may be the most ancient antioxidant available.
  • On earth, iodine is the 61st rarest essential element although it is found in almost every environment.
  • On earth’s terra firma, iodine is scarce due to it having been washed to the sea over the past hundreds of millions of years. Although found in fresh and saltwater, sea water has approximately 200 times more iodine.

Citation:
Venturi S. 2011. Evolutionary significance of iodine. Current Chemical Biology, 5(3), 155–162. DOI:10.2174/2212796811105030155