Evidence-Based Research

Chlorhexidine (CHX), Cetylpyridinium Chloride (CPC), sodium hypochlorite (NaOCl), and iodine-based antiseptics are effective but come with well-documented downsides—ranging from cytotoxicity (tissue damage, irritation, delayed healing) to tooth staining, and in CHX’s case, risks of microbial resistance and even anaphylaxis.

Our prediction*: Hypochlorous acid (HOCl)–based solutions will become the new gold standard—thanks to HOCl’s natural presence in the body and its uniquely broad benefits: high antimicrobial efficacy, low toxicity, itch-relieving (antipruritic), cell-supportive, and anti-inflammatory effects.

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1. Block et al. (2020)

Hypochlorous Acid: A Review. Journal of Oral and Maxillofacial Surgery

  • Summary: This comprehensive review synthesizes existing research on hypochlorous acid (HOCl), highlighting its broad-spectrum antimicrobial properties against bacteria, viruses, and fungi. It details HOCl's safety profile, noting its natural presence in the immune system and minimal toxicity. The review explores its diverse applications in healthcare, including wound care, disinfection, and particularly its growing relevance in oral and maxillofacial surgery due to its efficacy and biocompatibility.

2. Hsieh et al. (2020)

In Vivo Toxicity, Antimicrobial Properties for Electrolyzed Oxidizing (EO) Water Mouthwashes

  • Summary: This study conducted an in vivo evaluation of electrolyzed oxidizing water (EO, aka HOCl) and chlorhexidine (CHX) mouthwashes, assessing both their toxicity and antimicrobial properties. 0.2% CHX showed a bacterial reduction rate of 87.5% and an embryo toxicity mortality rate of 66.7 ± 26.2%, at a soaking time of 0.5 min. Both 0.0125% and 0.0250% HOCl rinses showed >99.9% S. mutans antimicrobial efficacy within 0.5 min, with zero mortality rate.
  • Notes: Despite evidence of anaphylactic risks, staining, cytotoxicity, wound healing impairment, and potential for resistance, chlorhexidine is still considered the gold standard by many clinicians. 
  • Hypochlorous acid at appropriate concentrations, on the other hand, has repeatedly been shown to have exceptional safety and effectiveness, without CHX’s drawbacks.

3. Sanon et al. (2025)

Hypochlorous acid as a potential cavity conditioner for caries-affected dentin

  • Summary: This study explores the novel application of hypochlorous acid (HOCl) as a conditioning agent for caries-affected dentin (CAD). This study showed HOCl (at 50ppm, or 1:3 dilution equivalent of Aloeha Rx Rinse’s 150ppm) pretreatment significantly enhanced the microtensile bond strength of CAD (from 25.6 ± 4.3 to 35.8 ± 7.2, p < 0.001), demonstrated significant antibacterial efficacy against S. mutans, while maintaining compatibility with dental pulp cells. HOCl shows promise as a dentin conditioner, offering enhanced bond performance to CAD with improved bond durability, while providing antibacterial benefits and maintaining biocompatibility.

4. Plata et al. (2018)

Hypochlorous Acid as a Potential Postsurgical Antimicrobial Agent in Periodontitis: A Randomized, Controlled, Non-Inferiority Trial

  • Summary: This study compared the effectiveness of two post-surgical antimicrobial protocols after Open Flap Debridement (OFD) over 7, 21, and 90 days: (A) HOCl (500 ppm then 250 ppm) and (B) CHX (0.2%/0.12%), both without brushing during the first 21 days. Outcomes measured included plaque index (PI), gingival index (GI), pocket depth (PD), clinical attachment level (CAL), and bacterial recolonization. HOCl was found to be non-inferior to CHX in reducing plaque and inflammation and showed fewer adverse effects. By day 90, HOCl produced significantly greater CAL gains (>3 mm), likely due to its antimicrobial, anti-inflammatory, and cell-proliferative effects. Notably, 31% of HOCl users reported whiter teeth, while 68% of CHX users experienced tooth staining. Although the study used higher concentrations (250–500 ppm), research suggests that lower doses (5–150 ppm) provide comparable clinical benefits with better taste, less irritation, and higher patient compliance.

5. Hiebert et al. (2016)

Post-Debridement Effects on Tissue Bacterial Wound Counts of HOCl vs Saline in Chronic Wounds

  • Summary: This study compared the post-debridement effects of hypochlorous acid (HOCl) versus saline solution on bacterial counts in chronic wound tissues. Wound antiseptics have been useful as wound irrigants, but some such as Dakin's solution and chlorhexidine have been reported to be cytotoxic. Hypochlorous acid has been demonstrated to be noncytotoxic, so was chosen as an irrigant in this study. The research aimed to determine if HOCl irrigation could significantly reduce the bacterial burden in difficult-to-heal wounds after initial debridement. 7 days post-irrigation, despite the fact that clinically the wounds in both groups appeared ready for closure, patients irrigated with saline had an increased bioburden, and more than 80% of the wound closures were unsuccessful. Ultrasound debridement with Hypochlorous acid irrigation reduced bacterial growth in chronic open wounds more efficiently than saline alone. Postoperative wound closure outcomes suggest a remarkable reduction in wound complications after wound debridement using hypochlorous acid irrigation with ultrasound versus saline alone.

6. Chen et al. (2016)

Effectiveness of Hypochlorous Acid to Reduce the Biofilms on Titanium Alloy Surfaces

  • Summary: This research evaluated the efficacy of HOCl in reducing bacterial biofilms formed on titanium alloy surfaces (dental implants and prosthetics). The study demonstrated HOCl's potent ability to disrupt and eliminate tenacious biofilms. The antibacterial ability of HOCl against the four strains was volume-dependent. Notably, the 4:1 volume ratio of HOCl to bacterial solution completely killed the bacteria. This result was similar to the effectiveness of 1.3% NaOCl and 0.2% CHX at a 1:1 volume ratio with a 30 s treatment time. Additionally, HOCl significantly lowered the LPS concentration of P. gingivalis when compared with 1.3% NaOCl and .2% CHX. This highlights HOCl's potential as an effective agent for cleaning and decontaminating implant surfaces, which is crucial for addressing peri-implantitis.
  • Notes:  HOCl’s neutral charge allows it to target negatively-charged pathogens and inflammatory LPS endotoxins at ~100x lower concentrations than NaOCl (bleach), which is repelled due to its negative charge. Volume of HOCl irrigation needs to be adequately proportional to bacterial load, 4:1 in this case, to maintain effectiveness at low concentrations.

7. Kim (2016)

Development of a mouthwash alternative using a low-level hypochlorous acid solution and its application to oral health

  • Summary: Bacteria suspensions were treated with the low-level hypochlorous acid solution (5ppm) or non-treated saline controls for 1 min and then serially plated on appropriate bacterial culture plates. Results showed a 99.99-99.99999% bactericidal activity for all strains including four anaerobic bacteria (P. gingivalls, P. intermedius, P. nigrescens, F. nucleatum) responsible for periodontitis and five facultative anaerobic bacteria (S. mutans, S. sobrinus, S. godonii, S. oralis, S. salivarius) associated with cavity development. The authors concluded that low-level hypochlorous acid solution has the potential to replace alcohol-containing mouthwash.

8. Dipali et al. (2019)

A comparative clinicomicrobiological study to evaluate efficacy of superoxide solution with povidone-iodine irrigation in chronic periodontitis patients

  • Summary: The present study aimed to compare superoxide solution (OXUM, 60ppm HOCl) with povidone-iodine (PI, Betadine) by means of clinical parameters and microbiologically by colony-forming units. Even though the outcome of mechanical debridement usually satisfies in terms of reduction in probing depth and bleeding on probing, difficulties reaching the bottom of the pocket can lead to its failure. As a consequence, supplementary treatment becomes inevitable. Furthermore, some microbiota simply cannot be mechanically eradicated. Method: SRP + 5-10min irrigation (10ml syringe/metallic cannula). The results show that HOCl irrigation is better than Betadine irrigation. The mean probing pocket depth (PPD) at baseline and 30 days was observed to be 1.716 ± 0.351 and 0.683 ± 0.274, respectively, for HOCl group and 1.700 ± 0.380 and 1.00 ± 0.00, respectively, for PI group. The mean gingival sulcus bleeding scores at baseline and 30 days were observed to be 1.726 ± 0.351 and 0.603 ± 0.274, respectively, for HOCl and 1.700 ± 0.380 and 1.25 ± 0.00, respectively, for PI. There was a statistically significant reduction in colony-forming units in HOCL group after 1 month as compared to PI group. These results suggest the effective usage of HOCl irrigation could aid in the treatment of periodontal disease. It proved to be a more effective treatment modality than SRP alone.
  • Notes: Despite manufacturer claims, many iORinse (molecular iodine) reviewers mention staining and burning.

9. Akama et al (2022)

Applicability of neutral electrolyzed water for cleaning contaminated fixed orthodontic appliances 

  • Summary: This research explored the effectiveness and applicability of neutral electrolyzed water (HOCl) for cleaning fixed orthodontic appliances contaminated with bacteria and plaque. The findings suggest that HOCL (at 30ppm, or 1:5 dilution of Aloeha Rx Rinse) is a viable and effective oral irrigation solution for maintaining the hygiene of orthodontic patients.
  • Notes: Ortho patients may benefit from using Aloeha Rx Rinse in their water flosser at a dilution of 1:2 to 1:5 (30ppm).

10. Yeh et al. (2023)

Effects of HOCl mouthwash on salivary bacteria in patients with periodontal disease: RCT

  • Summary: This randomized controlled trial (RCT) investigated the impact of HOCl mouthwash on salivary bacterial populations in individuals with periodontal disease. The study aimed to assess if regular use of HOCl mouthwash could reduce the bacterial load associated with periodontitis. Findings suggested that HOCl mouthwash effectively reduced pathogenic bacteria in saliva, indicating its potential as an adjunctive therapy for managing periodontal disease.

10. Delcanale et al. (2022)

Effects of stabilized hypochlorous acid on oral biofilm bacteria

  • Summary: This study focused on the effects of HOCl formulations on complex bacterial oral biofilms. The research investigated HOCl's ability to penetrate and disrupt these protective biofilm structures and reduce the viability of embedded bacteria. Low concentrations of HOCl (5 ppm, or 1:30 dilution of Aloeha Rx Rinse equivalent) significantly reduced viability in multi-species biofilms representing supra- and sub-gingival oral communities after 5 min, without causing erosion of HA surfaces. The findings indicate the potential of stabilized HOCl products for effective biofilm management in oral hygiene.
  • Notes: High-risk patients may benefit from using HOCl spray after meals (most biofilm creation) or with extended contact time (under removable oral appliances - aligners, retainers, dentures).

11. Stough MD (2023)

Topical Stabilized Super-Oxidized Hypochlorous Acid for Wound Healing in Hair Restoration Surgery: A Real-Time Usage-Controlled Trial Evaluating Safety, Efficacy, and Tolerability

  • Summary: Objective: Assess the perceived efficacy of stabilized, super-oxidized hypochlorous acid (HOCl) in hair transplant surgical procedures intraoperative and postoperative. Stabilized, super-oxidized hypochlorous acid (HOCl) is highly effective against bacterial, fungal, and viral microorganisms. In addition, topical HOCl will increase tissue oxygenation of wound sites to aid in healing. This molecule represents an ideal agent for intraoperative and postoperative use in hair restoration procedures that involve thousands of small wounds. Surgeons were provided a 500 mL trigger spray bottle of HOCl spray liquid for use prior to and throughout the surgical procedure. Patients were provided with a ten-day supply of HOCl for postoperative care. Statistical analysis found 56% had significant reduction in the amount of erythema compared to their current wound healing regimen. More than half of the patients (54%) had significant improvement of pruritus. There were no incidences of donor or recipient tissue necrosis. Topical, stabilized hypochlorous spray represents a major advance in wound cleansing and healing and offers the theoretical benefits of reducing tissue necrosis through oxygenation.

12. Bhatia et. al (2018)

Optimizing Wound Healing for Cosmetic and Medical Dermatologic Procedures

  • Summary: This Practical Derm article examines the use of physiologically balanced, slightly acidic solution HOCl for enhancing wound healing and reducing infection risk post-dermal procedures. It highlights HOCl’s rapid antimicrobial action, sealing properties that protect treated skin, and its role in minimizing inflammation and supporting tissue restoration. Clinically, it demonstrates broad-spectrum pathogen reduction, biofilm disruption, and favorable tolerability—without cytotoxicity or irritation—making it a valuable prophylactic aid and adjunct in cosmetic or surgical care.

13. Rathakrishnan et. al (2016)

To Evaluate the Efficacy of an Innovative Irrigant on Smear Layer Removal - SEM Analysis

  • Summary: The aim of this study was to find a viable alternative irrigant, which is easily available with less erosion and clinically acceptable smear layer removal by comparing the efficacy of EDTA and commercially available super-oxidized water, named OXUM (60ppm HOCl), as a final rinse on smear layer removal and erosion in relation to coronal, middle and apical thirds of radicular dentin using Scanning Electron Microscope (SEM) analysis. The final irrigation (5 ml) sequence was as follows: Group I- 17% EDTA, Group II - OXUM, and Group III - 0.9% saline (control) for one minute. The 60ppm HOCl group showed significantly less dentine erosion when compared to EDTA, and proved to be equally effective in smear layer removal.


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Conventional Mouthwash Comparison

1. Maezono et al. (2024)

Effects of Sodium Hypochlorite Concentration and Application Time on Bacteria in an Ex-Vivo Polymicrobial Biofilm Model

  • Summary: Biofilms were exposed to 0.1%–2% sodium hypochlorite (NaOCl) for 1–3 minutes. Only concentrations of 0.5% and above (Dakin’s solution or stronger) significantly reduced bacterial load compared to sterile water. While 0.2% NaOCl (as found in products like CTX) has been validated in some studies, its efficacy is questionable in short contact times due to biofilm resistance and the chemical profile at pH 10: ~7 ppm HOCl vs. ~2000 ppm OCl⁻. OCl⁻, the dominant species at this pH, is cytotoxic, 100× less effective than HOCl, and repelled by negatively charged bacterial membranes and inflammatory LPS endotoxins.
  • In contrast, ALOEHA RX (<$27/500ml) delivers 150 ppm of >99% pure HOCl at a tissue-friendly pH 6.5–7.2, ensuring minimal toxicity and significantly improved cost-efficiency versus CTX ($40/351ml, or $57/500ml equivalent).

2. Tsai et al. (2025)

“Selective Antimicrobial Effects of an Herbal Compound Rinse Against Multi-Species Oral Biofilms”

3. Weller et al. (2024)

Antimicrobial Cetylpyridinium Chloride (CPC) Causes Functional Inhibition of Mitochondria

  • Summary: This study investigates the cytotoxicity of cetylpyridinium chloride (CPC), a common antimicrobial agent found in mouthwashes (CPC containing versions of Listerine, Therabreath, generic rinses). This work reveals CPC as a mitotoxicant despite widespread use. Typical CPC exposure causes mitochondrial defects within 60 minutes and inhibits ATP production in primary human keratinocytes, fibroblasts, and mast cells.
  • Notes: Mouthwash is often partially swallowed, and sometimes inhaled when used as a breath spray (Crest Mist w/CPC). Why are we exposing ourselves to potentially petroleum-based quaternary ammonium compounds (QAC), and a myriad of other chemicals (artificial colors, flavors, PEGs, petrochemicals) to address bad breath when there’s a natural and effective alternative? 

At $5 for .5 oz Crest CPC Spray, or $9 for 1 oz Closys breath spray, that’s a 16.9 oz equivalent of $169 and $152, respectively.

Aloeha Rx’s [Supercharged] Oral Rinse 16.9 oz is <$27 (<$1.60/oz), includes a refillable 1 oz glass spray bottle, degrades to salt + water, and has multipurpose capabilities!


*Disclaimer: We make no medical claims - just informed decisions. This information simply shares the compelling evidence that guided our choice of ingredients—selected with care for the well-being of our patients and the quality of our products.