Nitrate Mouthwash for Oral Microbiome

Overseen By Leigha Rock

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Dalhousie University

Must not be taking: Antibiotics, Probiotics, Antimicrobials

Disqualifiers: Uncontrolled diseases, Oral conditions, others

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 2 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether a mouthwash with nitrates (from beetroot) can alter oral bacteria. Researchers aim to determine if this nitrate mouthwash also impacts blood pressure and nitric oxide levels in saliva. Participants will use either the nitrate mouthwash or a regular water rinse daily for two weeks. This trial suits individuals aged 18 to 40 with mild conditions like asthma or type 1 diabetes, who do not have serious oral or systemic health issues. As an unphased trial, it offers a unique opportunity to contribute to scientific understanding and potentially enhance oral and systemic health.

Will I have to stop taking my current medications?

The trial requires that you stop taking prescription medications, antibiotics, probiotics, or antimicrobial mouthrinses to participate.

What prior data suggests that this nitrate mouthwash is safe for use?

Research shows that using a mouthwash rich in nitrates, such as those made from beetroot, is generally safe. Some studies have examined beetroot juice, which is high in nitrates and has been used to help manage blood pressure, suggesting it has been used without major problems.

Increasing nitrates, like those in beetroot juice, can alter the bacteria in the mouth, and these changes are usually well-tolerated. However, one study found that higher nitrate intake might cause a rise in blood pressure, so awareness of this possible side effect is important.

Overall, treatments with nitrates, especially from beetroot, have been used safely in the past. However, as with any treatment, some side effects, such as changes in blood pressure, might occur. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the nitrate mouthwash treatment because it introduces a unique approach to supporting oral health by utilizing beet root-derived nitrates. Unlike traditional mouthwashes that primarily focus on killing bacteria through antiseptic agents, this treatment leverages the natural conversion of nitrates into nitric oxide by the oral microbiome, which can promote beneficial bacteria and improve oral health. Additionally, its simple delivery method—swishing and expectorating a nitrate solution—offers an easy and non-invasive way to potentially enhance oral health within just 14 days.

What evidence suggests that this nitrate mouthwash is effective for changing the oral microbiome?

This trial will compare a Nitrate Mouth Rinse with a Water Mouth Rinse. Research has shown that a mouthwash rich in nitrates can alter the types of bacteria in the mouth. One study found that beetroot juice, high in nitrates, increased beneficial bacteria and reduced harmful ones. Another study demonstrated that nitrates can enhance heart health in older adults by altering oral bacteria. Additionally, beetroot juice lowered blood pressure in both young and older adults. These findings suggest that a nitrate mouthwash might improve oral health and help lower blood pressure by modifying oral bacteria. ^{6 7 8 9 10}

Who Is on the Research Team?

Leigha Rock

Principal Investigator

Dalhousie University

Are You a Good Fit for This Trial?

This trial is for individuals interested in the effects of a nitrate-rich mouth rinse on their oral microbiome. Participants should maintain normal oral hygiene during the study and use either water or the provided mouth rinse daily for two weeks.

Inclusion Criteria

I do not have any uncontrolled illnesses.

Participants with mild chronic conditions such as asthma and type 1 diabetes mellitus

Exclusion Criteria

I am under 18 years old.

I am currently taking antibiotics, probiotics, or using antimicrobial mouthrinses.

I have current mouth or gum issues, including cold sores or cavities.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants use either a nitrate-rich or water mouth rinse once daily for 2 weeks

2 weeks

Daily self-administration

Follow-up

Participants are monitored for changes in the oral microbiome, blood pressure, and salivary nitric oxide levels

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Beet Root

Trial Overview

The study tests if using a beetroot-based, nitrate-rich mouth rinse once daily changes the makeup of bacteria in your mouth compared to rinsing with water. It also looks at blood pressure and saliva's nitric oxide levels as secondary outcomes.

How Is the Trial Designed?

Group I: Nitrate Mouth Rinse Experimental Treatment 1 Intervention

Nitrate suspension with approximately 50-100mg nitrates formulated with water swished in mouth for 30 seconds and then expectorated once daily for 14 consecutive days.

Group II: Water Mouth Rinse Placebo Group 1 Intervention

Water mouth rinse swished in mouth for 30 seconds and then expectorated once daily for 14 consecutive days.

Beet Root is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Beetroot Juice for:

• Dietary Supplement
• Blood Pressure Support

Approved in European Union as Beet Root Supplement for:

• Food Supplement
• Cardiovascular Health

Approved in Canada as Dietary Nitrate for:

• Natural Health Product
• Blood Pressure Regulation

Who Is Running the Clinical Trial?

Dalhousie University

Lead Sponsor

Trials

177

Recruited

402,000+

Published Research Related to This Trial

A study isolated 62 bacteria from the mouths of healthy donors, identifying 53 as nitrate-reducing, which could help improve oral health and increase systemic nitric oxide levels, potentially benefiting conditions like hypertension and diabetes.

The research found that certain Rothia species not only effectively reduce nitrate but also do so better at an acidic pH, suggesting that these bacteria could be used as probiotics to enhance oral nitrate-reduction capacity and improve overall health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isolation and Characterization of Nitrate-Reducing Bacteria as Potential Probiotics for Oral and Systemic Health. Rosier, BT., Moya-Gonzalvez, EM., Corell-Escuin, P., et al.[2023]

In newborn infants, the conversion of nitrate to nitrite in saliva is significantly lower than in adults, with no measurable bacterial activity in the first two weeks of life, which may limit the protective effects of nitrite in their gastrointestinal tract.

The presence of oral nitrate-reducing bacteria in infants does not translate to effective nitrite production, potentially contributing to their increased vulnerability to hypoxic stress and gastrointestinal issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nitrate reductase activity of bacteria in saliva of term and preterm infants. Kanady, JA., Aruni, AW., Ninnis, JR., et al.[2021]

Beetroot (Beta vulgaris L.) contains various bioactive compounds, such as dietary fiber, betalains, and phenolics, which have been shown to positively influence gut microbiota and promote gastrointestinal health.

These compounds can enhance the growth of beneficial gut bacteria, increase the production of short-chain fatty acids, and exhibit antioxidant and anti-inflammatory properties, making beetroot a valuable addition to a healthy diet and functional food products.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review on bioactive compounds of beet (Beta vulgaris L. subsp. vulgaris) with special emphasis on their beneficial effects on gut microbiota and gastrointestinal health. de Oliveira, SPA., do Nascimento, HMA., Sampaio, KB., et al.[2021]

The study found that using an antiseptic mouthwash in rats significantly reduced the number of beneficial nitrate-reducing bacteria in the mouth, which in turn decreased the levels of bioactive nitric oxide and nitrite in the body.

As a result of the reduced bacteria, the protective effects of dietary nitrate on gastric mucosal defense were lost, and the expected decrease in blood pressure from nitrate supplementation was also eliminated, highlighting the importance of oral bacteria in cardiovascular and gastrointestinal health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gastroprotective and blood pressure lowering effects of dietary nitrate are abolished by an antiseptic mouthwash. Petersson, J., Carlström, M., Schreiber, O., et al.[2016]

A diet high in nitrate and amines significantly increases the formation of carcinogenic nitrosamines, as shown by increased urinary and salivary levels in 12 volunteers consuming such foods.

Using an antibacterial mouthwash containing chlorhexidine effectively reduces salivary nitrite levels and urinary excretion of certain nitrosamines, suggesting it may help inhibit the formation of these harmful compounds.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Formation of nitrosamines during consumption of nitrate- and amine-rich foods, and the influence of the use of mouthwashes. van Maanen, JM., Pachen, DM., Dallinga, JW., et al.[2022]

This study found significant biological variability in the levels of nitric oxide (NO) markers (nitrate and nitrite) in both plasma and saliva after consuming nitrate-rich beetroot juice, indicating that individual responses can vary widely.

The research established critical difference thresholds for NO markers, which are essential for determining whether changes in these markers after dietary nitrate supplementation are meaningful, helping to clarify the mixed evidence surrounding the effects of dietary nitrate on exercise performance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Variability in nitrate-reducing oral bacteria and nitric oxide metabolites in biological fluids following dietary nitrate administration: An assessment of the critical difference. Liddle, L., Burleigh, MC., Monaghan, C., et al.[2019]

A nitrate-rich diet, specifically through a daily intake of 200 mg from a lettuce juice beverage, significantly reduced gingival inflammation in 37 periodontal patients over a 2-week period.

This dietary intervention led to notable changes in the subgingival microbiome, including an increase in beneficial bacteria like Rothia and Neisseria, while the control group showed no significant microbial changes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nitrate-rich diet alters the composition of the oral microbiota in periodontal recall patients. Jockel-Schneider, Y., Schlagenhauf, U., Stölzel, P., et al.[2022]

Freeze-dried red beet root (FDBR) and freeze-dried red beet stem and leaves (FDBSL) significantly increased beneficial bacteria like Lactobacillus and Bifidobacterium while decreasing harmful bacteria during 48 hours of in vitro colonic fermentation.

Both FDBR and FDBSL enhanced the metabolic activity of human colonic microbiota, leading to lower pH levels and increased production of short-chain fatty acids, suggesting their potential as effective prebiotic ingredients for gut health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Investigating the effects of conventional and unconventional edible parts of red beet (Beta vulgaris L.) on target bacterial groups and metabolic activity of human colonic microbiota to produce novel and sustainable prebiotic ingredients. de Oliveira, SPA., de Albuquerque, TMR., Massa, NML., et al.[2023]

Consuming 50 ml of nitrate-rich beetroot juice daily for two weeks did not affect bacterial lactate production or the pH levels in saliva and oral biofilm, indicating no caries-preventive properties.

Despite the accumulation of nitrate and nitrite in saliva after beetroot juice consumption, the study found no significant antibacterial effects against cariogenic bacteria under the tested conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of Consumption of Nitrate-rich Beetroot Juice on Lactate Production in Saliva and Oral Biofilm - A Clinical Trial. Sterzenbach, T., Hannig, C., Hertel, S.[2023]

Chlorhexidine mouthwash significantly inhibits the presence of nitrate-reducing bacteria, specifically Veillonella dispar, which could impact the body's ability to convert dietary nitrate into beneficial nitrite and nitric oxide.

In contrast, essential oil and povidone-iodine mouthwashes showed little effect on salivary nitrate/nitrite levels and the activity of nitrate-reducing bacteria, suggesting they may be safer options for maintaining oral nitrate-reducing activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of essential oil, povidone-iodine, and chlorhexidine mouthwash on salivary nitrate/nitrite and nitrate-reducing bacteria. Mitsui, T., Harasawa, R.[2018]

A 14-day study on healthy adults showed that consuming red beetroot juice led to temporary changes in gut bacteria, including an increase in beneficial Akkermansia muciniphila and a decrease in Bacteroides fragilis after just 3 days.

The presence of betacyanins from beetroot in stool was linked to positive changes in certain gut bacteria and an increase in butyric acid, suggesting that red beetroot may promote both gut health and overall well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of two-week red beetroot juice consumption on modulation of gut microbiota in healthy human volunteers - A pilot study. Wang, Y., Do, T., Marshall, LJ., et al.[2023]

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