Mouthwashes represent a huge business in the oral care industry, and a great deal is still not known about their effects on the human body and in particular the oral cavity.
Topic 1 – Antimicrobial Mouthwashes: An Overview of Mechanisms and What We Still Need to Know?1,2
Authors: Zoe Brookes, Colman McGrath, Michael McCillough
Mouthwashes are widely available over-the counter (OTC) or via prescriptions from dental practitioners. These OTC products range from cetylpyridinium chloride (CPC) to essential oils(OE’s) to assorted quatenary compounds to povidone iodine.
Some mouthwashes kill pathogenic bacteria (bacteriocidal), while others prevent bacterial growth (bacteriostatic). Each has positive and negative attributes.
By far chlorhexidene gluconate (CHX) is considered the most effective for reducing plaque and gingivitis. Many antiseptic mouthwashes appear to be less effective with severe gum disease. This may be due with their inability to reach pocket depths harboring anaerobic bacteria. It is important to understand mouthwashes should be a part of complete dental treatment.
Chlorhexidene gluconate is generally prescribed by dental practitioners. It possesses excellent antimicrobial properties against all bacteria, fungi and a limited number of viruses (enveloped). It is recommended for short term use (up to one month). Evidence is also emerging about antimicrobial resistance.
Hydrogen peroxide is a widely employed mouthwash due to its strong oxidizing properties, by releasing oxygen free radicals that disrupt cell walls. It has shown effectiveness at reducing plaque and gingivitis.
Cetylpyridinium chloride (CPC) a quatenary compound is a widely used mouthwash ingredient. CPC destroys pathogenic bacteria by penetrating cell membranes.
Povidone iodine may be in some mouthwashes, but it generally is used as a gargle. If swallowed it could cause adverse reaction in thyroid function and anaphylactic allergic reaction with people allergic to iodine.
Essential oils are extracted from plants and demonstrate good antibacterial, antifungal and antioxidant properties with low toxicity. Typical oils include peppermint, menthol, eucalyptus and thymol. Some EO mouthwashes can contain up to 26% alcohol which can contribute to dry mouth and mucosal ulcerative disease.
Alcohol has been used for centuries due to its potent antimicrobial properties. Alcohol’s link to oral cancer has resulted in many mouthwashes eliminating its use.
The above described compounds exhibit good antibacterial properties, some antiviral and antifungal properties. What is not known is the effect on the oral microbiome which is not well understood.
It is interesting to note that hypochlorous acid, while not part of this article has not been studied to any degree for its use in mouthwashes. It has been known for over 200 years and is used in wound treatment and possesses excellent antimicrobial properties with a high safety profile.
Topic 2 – Mouthwashes Effects on the Oral Microbiome: Are They Good, Bad or Balanced 3,4
Authors: Zoe Brookes, Leanne Teoh, Fabian Ciep, Purnina Kumar
It is a known fact the oral cavity is a well studied ecosystem of the human body. It is a complex mix of anaerobic bacteria, fungi,viruses and protozoa. They exist on all surfaces of the oral cavity. The predominance of antibacterial studies have been in vitro, with single species.
Chlorhexidene has a potent bactericidal effect on single species and multispecies cultures containing Streptococcus mitis, Fusobacterium nucleatum, Pophrymonas gingivalis and Aggregatibacter actinomycetemcomitans. Chlorihexidene also decreases bacterial diversity and vitality in saliva and on the tongue. Chlorhexidene mouthwashes reduce plaque and gingivitis and may be used as an adjunct in to manage peridontal disease in certain countries, it has also demonstrated in healthy individuals that certain species, namely Veillonella, Actinomyces, Haemophilus, Rothia and Neisseria, are also inhibited. These health-associated oral bacteria in saliva perform the important function of reducing dietary nitrates to nitrite, contributing to the maintenance of cardiovascular health via the release of nitric oxide.
Hydrogen peroxide in vivo reduced gingivitis and bleeding scores. It demonstrated low effectiveness on on Streptococcus mutans. No studies exist on the effect on the oral microbiome.
Povidone iodine is an effective antimicrobial against many pathogenic bacteria. A great deal more research is needed to study the effect on the oral microbiome.
Essential oils demonstrate reduction of plaque and bleeding scores when used in combination with brushing. The effect on the oral microbiome in vivo has not been investigated.
Sodium fluoride is generally used to reverse caries. No studies have been run to determine effect on oral microbiome.
Probiotics effective use as a mouthwash has been limited. There have been tests in patients which indicate reduced plaque and bleeding scores. Little evidence exists on their effectiveness and the oral microbiome.
Propolis is made from a waxy substance used by bees. It has demonstrated the ability to lower plaque and bleeding scores. No evidence is available on the oral microbiome.
Fungi exist in the oral microbiome. There are mixed results relating oral biofilms. In some studies CHX appears to inhibit sngle species biofilms containing C. albicans and S. Mutans. In others alcohol free mouthwashes (CHX, sodium flouride, essential oils, CPC and triclosan) failed to impair the ability of C. albicans to form biofilms.
Viruses and the oral microbiome (virome) The human oral microbiome is home to both RNA and DNA viruses. A recent study showed that anti-septic mouthwashes containing QAC’s, such as benzalkonium chloride had virtually no virucidal effects to MS2 bacteriophages in vitro.
In vivo however, a recent review reported CHX had some virucidal effects against HSV1 and IAV, but moderate to no efficacy against HCoV and Sars-Co-V2.
Antimicrobial resistance (resistome): This topic is becoming more prevalent, CHX has shown lower virucidal activity as did hydrogen peroxide.
CHX: There are two predominant mechanisms conferring resistance. The first is multidrug efflux pumps which allows the microorganism to export chlorhexidene and other antibiotics from the cytoplasm and out of the cell. The second mechanism is cell membrane changes that prevent chlorihexidene from binding to the target site. The earliest evidence for antimicrobial resistance in bacteria came in the early 70’s.
QAC’s: Multiple mechanisms explain development of resistance to QAC’s such as benzalkonium chloride and CPC. Current literature is ambivalent on the clinical significance of developing resistance to chlorhexidene and QAC’s. It is unclear whether the oral cavity is a potential reservoir for horizontal gene transfer that will increase resistance to both QAC’s and chlorhexidene.
While not mentioned by the authors, Hypochlorous acid is widely used in wound care and is known for its potent antibacterial, antifungal and antiviral properties while not harming healthy species. It is produced in the human body by neutrophills in white blood cells.
Topic 3 – The Effects of Antimicrobial Mouthwashes in Systemic Diseases: What is the Evidence5
Authors: Mohammed S. Alrashdan, Jair Carniero Leao, Amazon Doble, Michael McCullough, Stephen Porter
Limited data becoming available indicate mouthwashes have the potential to increase the risk of or worsen common systemic disorders. The bulk of the evidence involves CHX. Because conventional mouthwashes can’t discriminate between good and bad bacteria, they can contribute to microbial dysbiosis.
The production of NO from nitrate-nitrite reduction is critical to cardiovascular health. A number of reports suggest antimicrobial mouthwashes may directly worsen CVD.
CHX in particular has found to cause a shift in the oral microbiome. A 3-year study found daily use of mouthwashes represents an independent risk factor for development of prediabetes/diabetic mellitus and hypertension. Use of .12% CHX may destroy more than 90% of oral nitrate -reducing bacteria.
Alcohol consumption is a known risk factor for potentially malignant disease of oral mucosa. There seems to be some evidence that long term use of alcohol containing mouthwashes could contribute to a risk of oral cancer. There is some evidence that antimicrobials in general may cause harm to systemic health, most relating to CVD.
It is worth mentioning , although not part of this paper, HOCL is naturally produced by the body, thereby precluding any negative effect to human systemic health.
Topic 4 – Effective of Mouthwashes in Managing Oral Diseases and Conditions6
Authors : Colman McGrath, Janet Clarkson, Ann-Marie Glenny, Laurence J. Walsh, Fang Hua
CHX has been shown to reduce dental plaque in conjunction with mechanical oral hygiene. CHX has been advocated as an anticaries agent due to its ability to reduce Streptococcus mutans levels. Some evidence exists that CHX use pre and post extraction may reduce the risk of dry socket.
Flouride mouthwashes have long been advocated for oral health, especially for their role in preventing dental caries.
Essential oils: A systemic review evaluating the efficacy of EO’s, indicate they are more effective for reduction of plaque versus a placebo. In regard to dental caries ,a bulk of the evidence relates to in vitro evaluation of Streptococcus mutans.
Essential oils have been shown to manage halitosis. It has been suggested they may have antiviral properties, indicating use as a preprocedural rinse.
Cetypyridinium chloride: Recent reviews claimed that CPC was effective in plaque and gingival inflammatory control at interproximal sites. Other studies indicate that CPC mouthwashes have significantly reduced plaque index scores. There is no evidence for in vivo effect reduction of dental caries.
Povidone iodine: PVP-I is a broad spectrum antiseptic used widely in wound care. It has a wide range of effectiveness against microorganisms, ranging from bacteria, viruses, fungi and protozoa. A study revealed a small additional benefit in a non-surgical periodontal therapy.
It has not been shown to consistently reduce plaque accumulations. There is no hard evidence it can provide anticariogenic protection.
While not covered in this supplement, HOCL could be a potentially effective mouthwash, demonstrating its ability to elimanate pathogenic organisms including bacteria, viruses, fungi and protozoa.
Topic 5 – Mouthwashes: Alternatives and Future Directions7,8
Authors: Brett Duane, Tami Yap, Prasanna Neelakantan, Robert Anthonappa, Raul Boscos, Colman mcGrath, Michael McCullough, Zoe Brookes
There are a number of “alternative” or natural mouthwashes, along with newly emerging products of the future. Naturopathic products use the body’s natural healing ability. Probiotic bacteria and propolis are available in health food stores. Natural mouthwashes include red ginseng, aloe, fennel, activated charcoal and lemon extract. There is very little long term data and clinical studies comparing the efficiency of natural versus conventional mouthwashes. There is little conclusive evidence of natural mouthwashes effectiveness versus conventional or placebo in controlling plaque or gingival inflammation and enamel demineralization.
When considering natural mouthwashes one should think about HOCl, although not part of this supplement. You cannot get more natural than HOCL.
Topic 6 – Mouthwashes: Implications for Practice
Authors: Zoe L.S. Brookes, Michael McCullough, Purnima Kumar, Colman McGrath
Based on moderate evidence for clinical effectiveness, most guidelines suggest fluoride for managing dental caries and CHX for managing peridontal diseases. There is a general consensus that CHX, cetylpyridinium chloride and essential oils have displayed clinical effectiveness by reducing plaque and gingivitis The bulk of results are for CHX. On the other hand emerging evidence that frequent use of antimicrobial mouthwashes may cause dysbiosis of the oral microbiome..This evidence suggests it may be prudent to avoid antimicrobial mouthwashes for healthy individuals.
The American dental Association has a dichotomous approach as to cosmetic or therapeutic use of mouthwashes based on the absence of a chemically active agent. Basically cosmetic products lack bacteriacidal or bacteriostatic properties. Essential oil containing antimicrobial mouthwashes are recognized for having clinical efficiency against plaque and gingivitis. Therapeutic mouthwashes such as cetylpyridinium chloride, CHX, hydrogen peroxide and fluoride are generally dispensed by prescription and indicated for short term use.
Practitioners should alongside national guidelines and best evidence consider the balance between emerging bacterial resistance, systemic health issues and environmental contamination versus use of mouthwashes. Use of products should be considered on an individual basis. Since antimicrobials on their own have limited effectiveness on peridontal disease, it may be they are not recommended.
Caries: Clinical evidence using fluoride containing mouthwashes demonstrate its anticariogenic effect , supported by remineralization properties. There is a lack of high quality evidence as to the effectiveness of fluoride to bacteriacidal action in vivo or effect on oral microbiome.
Most effective antimicrobial mouthwashes seem to “kill” bacteria in the oral cavity, due to fatal destruction of the bacterial cell membrane. There has also been a study on the virucidal effects of mouthwashes, including Covid-19 and other emerging respiratory pathogens, but the antiviral effects of mouthwashes in vivo remain uncertain.
Clinical evidence indicates that in combination with oral hygiene and mechanical plaque removal, mouthwashes reduce plaque and gingivitis. This supplement tends to reinforce the opinion that antimicrobial mouthwashes are not effective as the sole agent in managing peridontal disease.
The report advises that mouthwashes should be used short term (2-4 weeks), to manage mild to moderate peridontal diseases. Generally CHX and essential oil-containing products are recommended for gum disease based on the amount of evidence supporting their use. In general, patients with good peridontal health and low caries should not use mouthwashes due to possible allergic reactions and dysbiosis of the oral microbiome.
Although not mentioned by the authors in this supplement, it might be prudent for dental practitioners to follow research regarding the use of HOCL in the oral cavity for a number of conditions. 
Oral Health welcomes this original article.
References
- Hypochlorous acid identified by Humphrey Davy in 1811 and isloated by Michael Faraday in 1823. Wikipedia
- Michael H. Gold MD,FAAD, Anneke Andriessen PhD, Ashish C. Bhatia MD FAAD, Patrick Ritter Jr. MD FAAD, Suneel Chilukuri MD,FAAD, FACMS, Topical stabilized hypochlorous acid: The future gold standard for wound care and scar management in dermatologic and plastic surgery procedures Journal of cosmetic Dermatology 06 January 2020
- Serhan Sakarya, Necati Gunay, Meltem Karakulak, Barcin Ozturk, Bulent Ertugred. Hypochlorous acid: An ideal wound care agent with powerful micrbiocidal, antibiofilm and wound healing potency. Wounds 2014 Dec. 26 (12) 342-50
- Ulfig A., Leichert L.. The effects of neutrophil generated hypochlorous acid on host pathogens, Cellular and Molecular Life science 2021 Ja. 7892) 385-414
- Dirk Boecker, Zhentian Zhang, Roland Breves, Felix Herth, Axel Kramer, Clemens Bulitta, Antimicrobial efficacy: mode of action and in vivo use of hypochlorous acid (HOCL) for prevention or therapeutic support of infections GMS Hygiene and Infection Control March 27.2023
- 6) Yu-Rin Kim, Seoul- Hee Nam, Comparison of the preventive of slightly acidic HOCL mouthwash and CHX mouthwash for oral diseases Biomedical Research 2018; 29(8) 1718-1723
- Kento Tazawa, Rutaja Jadhav, Marianne Moffei Azuma, Christopher Fenno, Hajime Sasaki, Hypochlorous acid inactivates oral pathogens and a sars CoV-2 surrogate BMC Oral Health 2023:23:111
- Olivia Aherna, Roberto Ortiz,, Magnus M. Fazli and Julia R. Davies Effects of stabilized hypochlorous acid on oral biofilm bacteria BMC Oral Health 92022) 22: 415
About the Author:
Dr. Janice Goodman received her MSc in Oral Medicine/Orofacial pain from USC in 2015 after practicing general dentistry for 36 years in downtown Toronto, Canada. She is an editorial Board member of Oral Health Dental Journal and the AAPMD. Diplomate of the American Academy of Cranialfacial pain as well as American Board of Cranialfacial Dental Sleep Medicine. Her focus is functional dentistry based. She can be reached at jangoodman@rogers.com
