Oral Probiotic Effect on Dietary Nitrate to Plasma Nitrite Production
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Sponsor
- Wake Forest University
- Enrollment
- 20
- Locations
- 2
- Primary Endpoint
- Dietary Nitrate Conversion to Plasma Nitrite
Study Overview
Brief Summary
Nitric Oxide (NO) is an important molecule that is produced naturally in the body and that helps maintain healthy blood flow. Low availability of NO contributes to many diseases while administration of NO is therapeutic.
In addition to being made naturally in the body, NO can be obtained through the diet via the Nitrate-Nitrite-NO cycle. Nitrate, which is abundant in green leafy vegetables and beetroot juice, is partially converted to nitrite by oral bacteria. The nitrate and nitrite are taken up into the blood and nitrite is converted into NO. Remaining nitrate in the blood is taken back up into the mouth by salivary glands and the cycle continues. Emerging studies suggest that the Nitrate-Nitrite-NO cycle may contribute to cardiovascular health. In addition, there have been many studies where dietary nitrate is given to increase NO and treat various conditions.
The current study rests on the premise that the quality of the oral microbiome plays a major role in the Nitrate-Nitrite-NO cycle and hence cardiovascular health and the efficacy of dietary nitrate interventions. Investigators have begun to identify oral bacterial species that are effective nitrite producers as well as though that are nitrite depleters (those that interfere with nitrite production from nitrate).
In laboratory experiments, certain bacterial species have been shown to block nitrate to nitrite conversion by other oral bacteria. These nitrite depleting species are found in a commercially available oral probiotic designed to improve oral health. The purpose of this study is to examine if use of the probiotic negatively affects the Nitrate-Nitrite-NO cycle. Nitrate to Nitrite conversion will be assessed by measuring plasma levels of nitrite before and after consumption of nitrate-rich beetroot juice. Dietary nitrate to plasma nitrite conversion will assessed at baseline and after one week of consumption of the probiotic or a placebo (follow-up). The primary hypothesis of this study is that participants that consume the probiotic will have lower nitrate to nitrite conversion at follow-up compared to baseline and that there will be no significant change in nitrate to nitrite conversion between baseline and follow-up for participants who consume the placebo.
While this study does not aim to treat any specific disease, it is intended to elucidate a basic physiological function that may be relevant to cardiovascular health and certain NO-based therapeutics.
Detailed Description
Background
Nitric oxide (NO) plays critical roles in a myriad of cellular and molecular mechanisms regulating physiology and function of various organs and systems.1,2 Low NO bioavailability contributes to pathology in multiple diseases including hemolytic anemias,3 malaria,4,5 transfusion of older stored blood,6,7 chronic heart failure,8 atherosclerosis,9 and diabetes.10 Recent reports suggest that the oral microbiome is linked with regulating NO homeostasis through the action of certain bacteria that have an ability to reduce nitrate to nitrite.11-15 Nitrite is then further reduced to NO through a variety of mechanisms in different tissues.16,17 Plasma nitrate is taken up back into the oral cavity by salivary glands so that the nitrate-nitrite-NO cycle provides sustained increases in NO bioavailability. Many clinical studies have used dietary nitrate as a source of NO through nitrite conversion.18-24 However, there is substantial variability in the clinical outcomes due to dietary nitrate intake and this is reflected in variability in the amount of nitrate converted to plasma nitrite.13,24-29 30. The variability and hence a large overall limitation in efficacy of dietary nitrate based treatments has been attributed to the capacity of the oral microbiome to reduce nitrate to nitrite.24-27 Preliminary work has begun to identify bacterial strains that are efficient nitrate to nitrite converters as well as those that actually inhibit nitrate to nitrite conversion.31,32 The efficiency of the nitrate-nitrite-NO cycle and the role of oral bacteria may contribute to normal health.11 Thus, understanding the variability in nitrate to nitrite conversion and aspects of the oral microbiome could lead to improvements in normal cardiovascular health. In addition, in order to maximize benefits from dietary nitrate interventions, we need to understand factors of the oral microbiome that affect nitrate to nitrite conversion. The investigators have recently discovered that several species of Lactobacillus produce a metabolite that blunts nitrate to nitrite conversion by other oral bacteria in vitro. Several of these Lactobacillus species are the main component of a commercially available oral probiotic, https://www.amazon.com/Dental-Probiotics-Breath-Gingivitis-Throat/dp/B096SZSFFS
Purpose
The purpose of this study is to determine if Lactobacillus will blunt dietary nitrate to plasma nitrite conversion.
The investigators hypothesize that the presence of oral Lactobacillus will blunt the conversion of dietary nitrate to plasma nitrite and will test this by comparing the conversion before and after use of this probiotic.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Basic Science
- Masking
- Single (Participant)
Masking Description
Participants will not know which group they are in. The lozenges will be distributed in unmarked bottles
Eligibility Criteria
- Ages
- 18 Years to 70 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Healthy adult volunteers ages 18-70
Exclusion Criteria
- •Individuals with a history of difficult blood draws. More than 2 blood draws in one week; on anti-coagulant or anti-platelet therapy (e.g. aspirin, Coumadin, etc.); known pregnancy; in police custody or a prisoner; common illness within 2 weeks of potential enrollment. The cumulative volume of blood drawn from a healthy adult over the prior eight-week period would exceed 550 ml including the current draw.
- •In addition, individuals uncomfortable spitting into a tube, dry mouth (xerostomia) or dry eyes, Patients suffering from autoimmune diseases such as Sjogren's syndrome, rheumatoid arthritis, systemic lupus erythematosus, or progressive systemic sclerosis, since individuals with these autoimmune inflammatory diseases exhibit persistent xerostomia, individuals with active caries diagnosis or history of periodontitis
Outcomes
Primary Outcomes
Dietary Nitrate Conversion to Plasma Nitrite
Time Frame: The two visits will be 8 days apart.
The main outcome is the plasma nitrite level 2.5 after consuming Beet Juice minus the plasma nitrite level prior to drinking beet juice. Blood will be collected prior to drinking one Beet it Sport shot and 2.5 hours after drinking the shot. Plasma nitrite will be measured from these blood draws. This outcome will be measured at two visits: baseline and followup (day 8) and the increase in plasma nitrite at the two visits will be compared. Between the two visits the participants will consume the Probiotic or Placebo for 7 days.
Secondary Outcomes
- Percentage Lactobacillus(The two visits will be 8 days apart.)