What Does the Research Say About Hypochlorous Acid Mouthwash?

What Is the Research Foundation Behind HOCl?

HOCl is not new to antimicrobial research. It is produced by the body's immune system as part of its natural defense against microorganisms.^[1] Researchers have studied this antimicrobial chemistry for decades, including how HOCl damages important components of microbial cells and reduces their ability to survive.^[1][2]

That research has translated into practical use across healthcare, wound care, food safety, sanitation and disinfection. One familiar example came during the COVID-19 pandemic: HOCl was the active ingredient in EPA-registered disinfectants included on List N, the EPA's list of products that met its criteria for use against SARS-CoV-2.^[3]

Research has evaluated HOCl activity against bacteria, viruses and fungi.^[2] Its use across these different settings helps demonstrate that HOCl's antimicrobial role extends well beyond oral care. This broader body of evidence provides the scientific foundation; oral-care research then helps determine what those antimicrobial properties mean when HOCl is used in the mouth.

How Is HOCl Used and Studied in Dentistry?

HOCl has an established history in dentistry that extends beyond mouthwash. Dental professionals have used HOCl and on-site electrolyzed-water systems to produce antimicrobial solutions for use within dental practices, while researchers have evaluated the chemistry across a much wider range of dental applications.^[4][5]

How Is HOCl Used in Dental Practices?

One notable part of HOCl's history in dentistry is point-of-use generation. Dental practices can use electrolyzed-water systems to generate antimicrobial solutions on site for applications such as dental-unit waterlines, treatment areas, irrigation and rinsing.^[4][5]

There is a practical reason for generating these solutions close to when they are needed: HOCl-containing solutions can lose available chlorine—and therefore antimicrobial strength—depending on time and storage conditions.^[5][6] In a 2023 review of dental research, 72% of studies evaluating a single electrolyzed-water formulation used solution generated at the point of use, compared with 24% using bottled ready-to-use solutions.^[5]

More recent dental research continues to examine this issue. A 2024 study focused specifically on the storage stability of neutral electrolyzed water containing HOCl for intraoral use, reinforcing the importance of concentration, storage conditions and maintaining the intended properties of the solution.^[6]

What Has Dental Research Studied?

Dental research involving HOCl and related electrolyzed solutions extends across both patient care and infection control. Studies have evaluated:

• mouthrinses and oral bacteria, including changes in salivary bacterial levels;
• plaque, oral biofilms and periodontal care, including bacterial recolonization following periodontal treatment;
• irrigation during periodontal, surgical and root-canal procedures;
• dental-unit waterlines and control of microbial contamination;
• oral tissues and how different formulations interact with cells and tissues; and
• dental materials, including compatibility with materials used in dental care.

The breadth is substantial. By 2023, a scoping review had identified 114 peer-reviewed studies of electrolyzed oxidizing water in dental healthcare, including 25 clinical studies.^[5] Research has continued since that review, including newer human oral studies and research examining HOCl formulations for periodontal and intraoral applications.^[6][7][8]

This broader dental literature does not mean there are 114 studies of HOCl mouthwash. Formulations and applications vary. Instead, it shows that HOCl-related antimicrobial chemistry has been investigated across dentistry for years. The research specific to HOCl mouthwash is narrower—and that is where the evidence becomes most relevant to everyday oral rinsing.

What Does Clinical Research Show About HOCl Mouthwash?

Clinical studies have evaluated HOCl mouthwash across several oral-health measures, including bacterial levels, plaque, periodontal bacteria, gum health and how long antimicrobial activity persists after rinsing.

Oral Bacteria

The clearest direct evidence involves bacterial reduction. In a 2023 randomized clinical trial involving patients with periodontal disease, 100 ppm HOCl mouthwash significantly reduced total salivary bacterial counts after rinsing.^[7] This demonstrates antimicrobial activity in people using HOCl as an oral rinse—not simply activity measured under laboratory conditions.

Plaque and Periodontal Health

Researchers have also studied HOCl in patients receiving periodontal treatment. In a randomized clinical trial following periodontal surgery, researchers evaluated plaque, gingival health, pocket depth, clinical attachment and the return of periodontal bacteria over a 90-day period.^[8]

The HOCl protocol reduced plaque and gingival index scores and limited recolonization of several periodontal bacteria following treatment.^[8] Because these patients had undergone periodontal surgery and used specific HOCl concentrations and protocols, the findings should not be interpreted as evidence that everyday HOCl mouthwash treats periodontal disease. They do, however, extend the clinical evidence beyond short-term bacterial reduction.

Oral Biofilms

Dental plaque is more than free-floating bacteria. It is a structured biofilm—a community of microorganisms attached to surfaces in the mouth. Laboratory researchers have therefore studied whether HOCl can act against these more complex microbial communities.

HOCl demonstrated antimicrobial activity against multispecies oral biofilms containing bacteria associated with both above- and below-gumline communities.^[9] This provides supporting laboratory evidence for HOCl's antimicrobial activity against organized oral biofilms, but it does not by itself establish a clinical outcome in people.

Duration of Antimicrobial Activity

Researchers have also examined substantivity—how long antimicrobial activity continues after rinsing. In a randomized clinical trial, HOCl reduced salivary bacterial viability immediately after use, but the effect was not sustained over time under the conditions tested.^[10] Chlorhexidine produced longer-lasting antimicrobial activity in the same study, a difference examined further below.

Tolerability and Reported Side Effects

Research on HOCl mouthwash tolerability is limited. The available clinical data come from relatively small study groups, and the HOCl rinses evaluated for tolerability were tested at higher concentrations of 250 to 500 ppm. Some participants were also periodontal patients following surgery rather than people using mouthwash for routine daily oral care.^[8][10]

Within these studies, participants using HOCl reported effects including unpleasant taste and temporary dryness.^[8][10] Both trials directly compared HOCl with chlorhexidine, allowing researchers to evaluate tolerability alongside antimicrobial performance, although the small study groups limit broader conclusions.

Overall, these studies provide some insight into short-term tolerability but are not enough to establish how HOCl mouthwash will be tolerated across different formulations, concentrations or long-term daily use. A separate randomized clinical study demonstrated bacterial reduction with 100 ppm HOCl, but tolerability was not directly evaluated as an outcome.^[7]

Taken together, the research provides the strongest direct evidence for short-term reduction of oral bacteria, with additional clinical and laboratory evidence involving plaque, periodontal bacteria, gingival measures and oral biofilms.

What Does Research Show About 100 ppm HOCl?

100 ppm HOCl has been evaluated directly as a mouthwash in randomized human clinical research. In a 2023 study, patients with periodontal disease rinsed with 100 ppm (0.01%) HOCl. Researchers found a significant reduction in total salivary bacterial counts after rinsing.^[7] The study focused on antimicrobial activity and did not directly evaluate tolerability.

Other clinical studies have evaluated HOCl oral rinses at higher concentrations, including 250 and 500 ppm, while examining plaque, periodontal bacteria, antimicrobial persistence and tolerability.^[8][10]

Higher ppm does not automatically mean a better mouthwash. These studies used different formulations, concentrations, protocols and patient populations. They were not designed to establish a universal dose-response relationship or determine one ideal HOCl concentration for oral care.

Concentration is only one part of an HOCl formulation. pH, stability, contact time and how the solution is used can also influence antimicrobial performance.^[4][5] Research findings are therefore most meaningful when the complete formulation and study conditions are considered.

River Refresh Oral Rinse is formulated at 100 ppm HOCl, the same HOCl concentration evaluated in the 2023 clinical study.^[7] The study evaluated 100 ppm HOCl—not River Refresh. Its findings provide relevant research context for the concentration but should not be interpreted as clinical testing or validation of the River Refresh formulation.

How Does HOCl Compare With Chlorhexidine Mouthrinses?

Chlorhexidine is a prescription antimicrobial mouthrinse used to treat gingivitis in the United States, while HOCl oral rinses are available over the counter. In a randomized clinical trial, both HOCl and chlorhexidine reduced salivary bacteria immediately after rinsing, although chlorhexidine produced a greater initial reduction and longer-lasting antimicrobial activity.^[10]

A separate periodontal-surgery trial found the HOCl protocol was non-inferior to chlorhexidine for plaque reduction—meaning it met the study's criteria for performing no worse than chlorhexidine for that specific outcome.^[8]

The research does not establish either rinse as universally superior. Chlorhexidine's longer-lasting antimicrobial activity can be useful for therapeutic treatment, while tooth staining and changes in taste are recognized considerations with continued use.^[10][11] HOCl has demonstrated antimicrobial activity but has different persistence, concentrations and study protocols depending on how it is used.

What Does the Research Not Yet Establish?

Research supports the antimicrobial activity of HOCl and provides growing clinical evidence for its use as an oral rinse. However, current research does not yet establish:

• Long-term daily-use outcomes from continuous use of HOCl mouthwash;
• one ideal HOCl concentration for oral rinsing across different uses and populations;
• prevention or treatment of specific oral diseases based on bacterial reduction alone; or
• equivalent results across HOCl formulations, since studies have used different concentrations, formulations, contact times and protocols.

These limitations do not negate the findings that have been demonstrated. Human studies have shown antimicrobial activity with HOCl mouthrinses, including at 100 ppm, while periodontal and comparative trials provide additional evidence involving plaque and periodontal bacteria. They define where the evidence is strongest—and where further clinical research is still needed.

Related Oral Care Articles

• Hypochlorous Acid for Oral Care: Uses, Safety, and Fresh Breath
• Does Hypochlorous Acid Mouthwash Help With Bad Breath?
• Is Hypochlorous Acid Mouthwash Safe for Daily Use?
• Hypochlorous Acid Mouthwash vs. Alcohol-Based Mouthwash: What's the Difference?
• How Can Hypochlorous Acid Mouthwash Support Gum Health?
• Why Do ppm and pH Matter in Hypochlorous Acid Mouthwash?
• How to Use Hypochlorous Acid Oral Rinse