Molecular iodine offers new hope to periodontal patients: How does it compare to chlorhexidine? - Oral Health Group (2025)

Molecular iodine offers new hope to periodontal patients: How does it compare to chlorhexidine? - Oral Health Group (1)

Chlorhexidine gluconate (CHX) was first introduced into clinical practice in 1954.1In its more than 70 years of clinical use, it has become a standard of care in infection control, globally. CHX oral rinse has earned the American Dental Association’s Seal of Acceptance and has been a valuable adjunct in the control of periodontal disease for decades. But has it outlived its usefulness? Let’s compare the features and benefits of CHX to a current state-of the-art antiseptic agent, molecular iodine (I2), that is currently being introduced into Canada so that you can answer that question.

Just because an antiseptic agent has earned prominence as a standard of care, doesn’t mean that it will always retain that distinction. For example, during the 1930’s and early 1940’s, sulfa drugs were considered the standard of care as antibiotic agents. With the large-scale introduction of penicillin in 1945, sulfa was no longer considered the antibiotic of choice.2Consider your own practice today. When was the last time you prescribed sulfa for an infection?

So, how do CHX and I2really compare in parameters that are important to our patients and to our practices? Let’s first look at their relative antimicrobial efficacy.

CHX has excellent biocidal activity against periodontal bacteria, but I2is considerably more effective. In Table 1, seven of the most commonly used professional periodontal rinses were compared for their biocidal efficacy against two key periodontal pathogens (Fusobacterium nucleatum and Prevotella intermedia). At 30 seconds exposure time, I2was the only rinse found to be fully effective. It was 28 times more effective than CHX against Fusobacterium and 730 times more effective than CHX against Prevotella. It was also far more effective than every other rinse tested. This is no small feat, since all the testing was done in the presence of fresh, human whole saliva, which neutralizes most antiseptic rinses.3

Table 1

Log reduction at 30 seconds
Antiseptic rinseFusobacterium nucleatumPrevotella intermedia
ioRinse Ultra (100 ppm I2)6.0 –complete inactivation6.0 –complete inactivation
Chlorhexidine gluconate 0.12%4.8 –28x less effective3.3 –730x less effective
Cetylpyridinium chloride 0.07%0.2 –820.000x less effective5.3 –7x less effective
Chlorine dioxide0.71 –361.000x less effective3.9 –190x less effective
Povidone iodine 10%1.8 –28.000x less effective1.3 –73.000x less effective
Hydrogen peroxide0.4 –640.000x less effective0.52 –532.000x less effective
Stabilized chlorine dioxide0.04 –964.000x less effective0 –no biocidal activity

We are not just concerned about periodontal bacteria. How effective are CHX and I2against cariogenic bacteria? Table 2 shows the relative biocidal efficacy of CHX and I2against Strep mutans, a principal caries-causing pathogen. Within 15 seconds, I2completely destroyed all bacteria present with a 6+ log reduction. CHX achieved a 0.18 log reduction against Strep mutans in the same time frame. That 0.18 log reduction by CHX is the equivalent of starting with 1 million viable Strep mutans bacteria, exposing it to CHX for 15 seconds, and having 810,000 viable bacteria remain unscathed.4

Table 2

Molecular lodine (Iz)Chlorhexidine Gluconate
MicroorganismStrengthLog ReductionTimeStrengthLog ReductionTime
Strep mutans100 ppm4.0
complete inactivation
30 sec.0.12%0.1915 sec.

Let’s turn to viruses. How effective are CHX and I2against important viruses? Table 3 helps to answer that question. Four different rinses were evaluated for their efficacy against SARS Co V-2. The testing was conducted at the Institute for Antiviral Research at Utah State University. Only one rinse was fully effective, a molecular iodine rinse. It was fully effective at just 30 seconds exposure time. None of the other rinses, including CHX were fully effective. Not at 30 seconds and not even when the exposure time was doubled to 60 seconds.5

Table 3

Sars Co V-2 Log ReductionSars Co V-2 Log Reduction
Oral Rinse30 Seconds60 SecondsObserved Cytotoxicity
1.5% hydrogen peroxide<1.0<1.01/10,1/100, 1/1000 dilutions
0.2% povidone iodine2.03.0none
0.12% chlorhexidine gluconate<1.01.01/10,1/100 dilutions
Molecular iodine formula 100-S>3.6
Complete
inactivation
>3.6
Complete
inactivation
none

Let’s try another virus. Rhinovirus is a common upper respiratory virus responsible for most cases of viral pharyngitis. It is a difficult-to-kill non-enveloped virus. Table 4 compares the antiviral efficacy of CHX to I2against Rhinovirus. Within 30 seconds, I2completely destroys Rhinovirus. In that same time frame, CHX has no biocidal efficacy, at all.6

Table 4

Molecular lodine (I2)Chlorhexidine Gluconate
MicroorganismStrengthLog ReductionTimeStrengthLog ReductionTime
Rhinovirus25 ppm4.0
complete inactivation
30 sec.0.12%0.030 sec.

What about their effectiveness against fungi? Table 5 compares the relative efficacy of a 300 ppm molecular iodine solution to a solution consisting of 2% CHX and 70% isopropyl alcohol. Both the molecular iodine solution and the CHX/alcohol solution were tested against Aspergillus brasiliensis, one of the most resilient fungi known. The I2solution completely inactivated the fungus within 15 minutes. The CHX/alcohol solution took one full hour to achieve the same result.6

Table 5

Antiseptic AgentTime Required for Complete Inactivation
of Aspergillus brasiliensis
CHX 2.0% (17x stronger than 0.12% CHX oral rinse) + Isopropyl Alcohol 70%60 minutes
Molecular Iodine (300 ppm)15 minutes

What about safety? Which product is safer to use? Iodine is an essential nutrient required in the diets of humans to avoid iodine deficiency diseases.7That’s why our salt is iodized. Iodizing salt is an inexpensive public health measure to help us avoid iodine deficiency diseases (including birth defects and mental retardation).7

Not only does I2have an excellent safety profile, but it is, perhaps, the most effective antimicrobial agent for human use as well as being amongst the safest to use. It can be used safely, each and every day by patients, literally for the rest of their lives.

Table 6

AntibioticChange in number of resistant perio patients
Year 2000 >> Year 2020
Clindamycin16x greater
Amoxicillin28x greater

CHX, unfortunately has serious health concerns. It is a potential carcinogen. Every bottle of CHX oral rinse sold in the U.S. is required by FDA to include a safety data sheet which states that it “may cause cancer”(Fig. 1). It is categorized by FDA as a class 1A carcinogen, meaning that the evidence supporting that classification is based on actual human data.8

Fig. 1

Molecular iodine offers new hope to periodontal patients: How does it compare to chlorhexidine? - Oral Health Group (2)

FDA has also issued a safety warning for CHX in response to a rising number of allergic reactions.9These reactions can be so severe that life threatening anaphylactic shock from the use of CHX has been reported on multiple occasions.10CHX also allows bacterial resistance to develop. The medical literature is replete with references to bacterial resistance development associated with CHX use.11The rapid increase in patients becoming resistant to antimicrobial agents has become alarming. In a study conducted at Temple University Dental School, it has been shown that within the 20-year time span ending in 2020, 16 times as many periodontal patients became resistant to Clindamycin at the end of the study as compared to the beginning and 28 times as many patients became resistant to Amoxicillin.12

Iodine does not cause microbial resistance.13Nowhere in the medical literature is there any evidence of microbial resistance development to iodine. Because of safety concerns CHX is only indicated for short-term, episodic use, not to exceed two weeks.14Because CHX is not effective against certain resilient bacteria, FDA has also issued multiple recalls for CHX because of microbial contamination by bacteria living within the CHX rinse bottles.15,16

Antimicrobial efficacy and product safety are critically important attributes of our antiseptic agents, but there are other important product characteristics that can spell the difference between treatment failure and treatment success. Table 7 shows important product characteristics for both CHX and I2oral rinses. CHX interferes with both soft tissue repair and bony regrowth because of its inhibitory activity against fibroblasts and osteoblasts.17Periodontal pocket depth reduction and clinical attachment gain are impeded by this inhibitory activity. Unlike povidone iodine and chlorhexidine gluconate, molecular iodine rinses do not stain.18It has been shown that CHX degrades the biocompatibility of titanium surfaces. It is therefore contraindicated for use with titanium implants because implants that are no longer biocompatible, cause local tissue reaction leading to peri-implant mucositis and also peri-implantitis.19

Table 7: Product Characteristics of CHX and I2 Oral Rinses

CharacteristicCHX Oral RinseI2Oral Rinse
FDA safety warning issuedYesNo
FDA recalls for microbial contaminationYesNo
Inhibits fibroblast proliferationYesNo
Inhibits osteoblastic activityYesNo
Stained teeth and tongueYesNo
Promotes dental calculus buildupYesNo
Alters tasteYesNo
Use limited to short term onlyYesNo
Allows microbial resistance developmentYesNo
Compromises implant biocompatibilityYesNo

A molecular iodine oral rinse checks all the boxes in being as nearly perfect as an antiseptic rinse can be. Because molecular iodine has such broad-spectrum activity, wouldn’t it be expected to destroy nitric oxide-producing bacteria in the mouth, as well? Wouldn’t a lower nitric oxide level then lead to negative changes in vaso-activity and ultimately heart disease? The answer may surprise you.

Yes, molecular iodine will destroy nitric oxide-producing bacteria along with pathogenic bacteria, but the limited production of nitric oxide produced in the mouth has only a negligible effect, if any, on vaso-activity. A joint study by John Hopkins School of Medicine and the University of Virginia Medical School demonstrate conclusively that the key production of nitric oxide involved in vaso-regulation is located in and around the blood vessels themselves, not in the mouth. They also point out that nitric oxide is produced almost everywhere in the body (skin, skeletal muscle, nose and sinuses, liver, blood cells, epithelial cells, nerves and all throughout the alimentary canal)(Fig. 2).

Fig. 2

Molecular iodine offers new hope to periodontal patients: How does it compare to chlorhexidine? - Oral Health Group (3)

What about dysbiosis of the oral microbiome? Wouldn’t inactivation of commensal bacteria by a powerful antiseptic rinse lead to dysbiosis? The mouth is never sterilized with the use of an antiseptic rinse. Residual, viable microbes, with the help of microbes from the nose, the throat, and the air we breathe, rapidly repopulate. It is postulated that repopulation of gram-positive, aerobic bacteria occurs more quickly and completely than does repopulation of anaerobic, pathogenic bacteria.24It is the rapid repopulation of these aerobic bacteria that crowds out the anaerobes, establishing a new microbiome favoring commensal bacteria.

We should also not lose sight of the fact that controlling periodontal disease is critical in helping to control heart disease. Periodontal disease has reached epidemic proportions, and the most effective antiseptic agents are required to help us control periodontal disease.24

In a recent landmark study reported in the British Dental Journal, 100,000 patients were stratified into 3 groups depending on the level of their daily, at-home oral hygiene (poor at-home oral hygiene, moderate at-home oral hygiene and best at-home oral hygiene). These patients were followed for almost 19 years, tracking the number of deaths attributable to cardiovascular disease that occurred in each group. The most significant finding was that 4 times as many patients died from cardiovascular disease in the poor periodontal health group than did in the best periodontal health group.

Is molecular iodine a newly discovered molecule? Oddly, molecular iodine or I2has been around as long as iodine has been around. Early Chinese physicians provided the first recorded evidence of therapeutic benefit of using iodine-rich substances more than 5,600 years ago. They formulated pastes of ground up seaweed and sea urchins, applying these pastes to the necks of patients who had goiters (enlarged thyroid glands)20. Although they were successful in shrinking the size of many of these goiters, they had no idea that the active agent in these pastes was iodine. It wasn’t until 1814 that the French researcher, Courtois identified iodine as an element.21

Figure 4 shows two schematic diagrams. The schematic on the left represents 10% povidone iodine. It contains approximately 31,600 ppm of total iodine. Of all the different species of iodine in povidone iodine, only one species is biocidal and actually kills germs. That species is molecular iodine (I2)6and it is only present in povidone iodine at trace levels (2-3 ppm).6As almost unimaginable as it may be, those 2-3 ppm of I2account for all of povidone iodine’s germicidal activity. The schematic on the right side of Figure 2 shows a high-level molecular iodine solution containing 300 ppm I2. Only trace levels of other iodine species are present in this high-level iodine solution, so it does not stain.18

Fig. 3

Molecular iodine offers new hope to periodontal patients: How does it compare to chlorhexidine? - Oral Health Group (4)

Fig. 4

Molecular iodine offers new hope to periodontal patients: How does it compare to chlorhexidine? - Oral Health Group (5)

For decades, researchers have tried unsuccessfully to develop high level molecular iodine solutions while suppressing other iodine species which are toxic and staining. I2is unstable and quickly morphs into other forms of iodine which are not biocidal.22So even if it was possible to add I2to povidone iodine, it wouldn’t stay as I2but would rapidly change into other non-biocidal species of iodine.

In 2016, after 3 years of painstaking research focused on this very problem, Iotech International, a Florida-based medical technology company, developed the breakthrough technology that has ushered in a new generation of stable, high level molecular iodine oral care products which have been patented globally and have a useful shelf life of 2 years.23

These products are already successfully being used in thousands of dental offices in the U.S. and are now being introduced into Canada through Henry Schein-Canada. You should now be able to answer the question, “How does molecular iodine compare to chlorhexidine?” Perhaps a more important question to ask yourself is “If molecular iodine oral rinse is available, why am I still using chlorhexidine?”.Molecular iodine offers new hope to periodontal patients: How does it compare to chlorhexidine? - Oral Health Group (6)

Oral Health welcomes this original article.

Disclaimer:The author Dr. Herb Moskowitz is the Chairman and Co-Founder of ioTech International, a developer and manufacturer of molecular iodine oral care products.

References

  1. FIScT, T. S. P. C. (2024, April 21). Skin deep: Chlorhexidine – history and efficacy. https://www.linkedin.com/pulse/skin-deep-chlorhexidine-history-efficacy-tim-r9g8e/
  2. History of antibiotic development – Antibiotics – ReAct. (2024, September 17). ReAct. https://www.reactgroup.org/toolbox/understand/antibiotics/development-of-antibiotics-as-medicines/
  3. Keena, T. (2023, May 5). The need for objective, evidence-based efficacy testing of Oral Rinses. Registered Dental Hygienists. https://www.rdhmag.com/patient-care/home-care/article/14291458/the-need-for-objective-evidence-based-efficacy-testing-of-oral-rinses
  4. BioScience Laboratories, Bozeman, Montana: Antimicrobial Efficacy comparison of Oral Rinses Against Strep Mutans, April 2024
  5. Moskowitz, H., & Mendenhall, M. (2019). Comparative Analysis of Antiviral Efficacy of Four Different Mouthwashes against Severe Acute Respiratory Syndrome Coronavirus 2: An In Vitro Study. International Journal of Experimental Dental Science, 9(1), 1–3. https://doi.org/10.5005/jp-journals-10029-1209
  6. Moskowitz, H. (2019, July 1). CHX: We don’t like it! why are we still using it? Registered Dental Hygienists. https://www.rdhmag.com/career-profession/article/14036891/chx-we-dont-like-it-why-are-we-still-using-it
  7. Office of Dietary Supplements – iodine. (n.d.). https://ods.od.nih.gov/factsheets/Iodine-HealthProfessional/
  8. Darby Dental Supply. (n.d.). Safety Data Sheet: Chlorhexidine gluconate 0.12%. Retrieved January 15, 2025, from https://chemmanagement.ehs.com/9/60BBBCFA-FE39-4844-A79D-86123E2EAD1B/pdf/MSZ873
  9. U.S. Food and Drug Administration. (2017, February 2). FDA drug safety communication: FDA warns about rare but serious allergic reactions with skin antiseptic products. Retrieved January 15, 2025, from https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-warns-about-rare-serious-allergic-reactions-skin-antiseptic#:~:text=Stop%20using%20the%20product%20containing,to%20other%20more%20serious%20symptoms
  10. Weng, M., Zhu, M., Chen, W., Miao, C., Fudan University Shanghai Cancer Center, & Shanghai Medical College, Fudan University. (n.d.). Life-threatening anaphylactic shock due to chlorhexidine on the central venous catheter: a case series. In Int J Clin Exp Med (Vol. 7, Issue 12, pp. 5930–5936). https://e-century.us/files/ijcem/7/12/ijcem0002887.pdf
  11. Wand, M. E., Bock, L. J., Bonney, L. C., & Sutton, J. M. (2016). Mechanisms of Increased Resistance to Chlorhexidine and Cross-Resistance to Colistin following Exposure of Klebsiella pneumoniae Clinical Isolates to Chlorhexidine. Antimicrobial Agents and Chemotherapy, 61(1). https://doi.org/10.1128/aac.01162-16
  12. Rams, T. E., Sautter, J. D., & van Winkelhoff, A. J. (2023). Emergence of Antibiotic-Resistant Porphyromonas gingivalis in United States Periodontitis Patients. Antibiotics (Basel, Switzerland), 12(11), 1584. https://doi.org/10.3390/antibiotics12111584
  13. Lanker Klossner, B., Widmer, H. R., & Frey, F. (1997). Nondevelopment of resistance by bacteria during hospital use of povidone-iodine. Dermatology (Basel, Switzerland), 195 Suppl 2, 10–13. https://doi.org/10.1159/000246024
  14. Martino, R., DDS. (2022, July 13). Revealing the truth about chlorhexidine, and a better alternative. Decisions in Dentistry. https://decisionsindentistry.com/article/revealing-the-truth-about-chlorhexidine-and-a-better-alternative/#:~:text=Noted%20for%20its%20high%20potential,or%20other%20solution%20than%20CHX.
  15. The Food and Drug Administration (FDA) recalls Paroex Chlorhexidine Gluconate Oral Rinse USP, 0.12% by Sunstar Americas. (2021, January 11). Constituent. https://www.agd.org/constituent/news/2021/01/11/the-food-and-drug-administration-(fda)-recalls-paroex-chlorhexidine-gluconate-oral-rinse-usp-0.12-by-sunstar-americas
  16. U.S. Food and Drug Administration. (2023, March 7). Lohxa, LLC issues voluntary nationwide recall of chlorhexidine gluconate oral rinse USP, 0.12% due to microbial contamination. Retrieved January 15, 2025, from https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/lohxa-llc-issues-voluntary-nationwide-recall-chlorhexidine-gluconate-oral-rinse-usp-012-due#:~:text=0.12%25%20Alcohol%20free-,Company%20Announcement,repackaged%20from%20Sunstar%20Americas%20Inc.
  17. Liu, J. X., Werner, J., Kirsch, T., Zuckerman, J. D., & Virk, M. S. (2018). Cytotoxicity evaluation of chlorhexidine gluconate on human fibroblasts, myoblasts, and osteoblasts. Journal of bone and joint infection, 3(4), 165–172. https://doi.org/10.7150/jbji.26355
  18. Riad, A., Yilmaz, G., & Boccuzzi, M. (2020). Molecular iodine. British dental journal, 229(5), 265–266. https://doi.org/10.1038/s41415-020-2127-0
  19. Kotsakis, G. A., Lan, C., Barbosa, J., Lill, K., Chen, R., Rudney, J., & Aparicio, C. (2016). Antimicrobial Agents Used in the Treatment of Peri-Implantitis Alter the Physicochemistry and Cytocompatibility of Titanium Surfaces. Journal of periodontology, 87(7), 809–819. https://doi.org/10.1902/jop.2016.150684
  20. Lee, Chen-Hsena,b,c,e,*; Chiu, Jen-Hweyb,c,d. Goiter disease in traditional Chinese medicine: Modern insight into ancient wisdom. Journal of the Chinese Medical Association 84(6):p 577-579, June 2021. | DOI: 10.1097/JCMA.0000000000000547
  21. Metrangolo, P., & Resnati, G. (2011). Tracing iodine. Nature Chemistry, 3(3), 260. https://doi.org/10.1038/nchem.998
  22. Blasi C. (2021). Iodine mouthwashes as deterrents against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Infection control and hospital epidemiology, 42(12), 1541–1542. https://doi.org/10.1017/ice.2020.1356
  23. Liquid gold. (2024, June 30). Incisal Edge – Strategies to Accelerate Success, p 14-16 https://www.incisaledgemagazine.com/mag/article/liquid-gold/
  24. Moskowitz, H. (2024) Oral Rinses: What’s Safe? What’s Effective? Dental CE Academy. https://www.dentalceacademy.com/iotech-international-on-demand-webi

About the authors

Molecular iodine offers new hope to periodontal patients: How does it compare to chlorhexidine? - Oral Health Group (7)

Dr. Herb Moskowitzis the Chairman and Co-Founder of ioTech International. He is the co-author of ioTech’s U.S. patent and global patent applications. He has also practiced clinical dentistry for more than 25 years and is a graduate of the University of Tennessee Dental School. He also has a financial interest in ioTech International, a developer and manufacturer of molecular iodine oral care products.

Molecular iodine offers new hope to periodontal patients: How does it compare to chlorhexidine? - Oral Health Group (8)

Dr. Janice Goodmanis a member of the Oral Health Dental Journal Editorial Board. She graduated from UofT in 1979 and USC in 2015.She has practiced functional dentistry in Toronto for over 40 years. She has a financial interest in ioTech International, a developer and manufacturer of molecular iodine oral care products.

Molecular iodine offers new hope to periodontal patients: How does it compare to chlorhexidine? - Oral Health Group (2025)
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