Dietary Nitrate SupplementationNIMMINCT05579262
Evaluating the Metabolic Effects of Dietary Nitrate Supplementation
A study testing Beetroot juice in people with Dietary Nitrate Supplementation, run by Institute for Human Development and Potential (IHDP), Singapore at 1 site in Singapore.
Trial summary
Dietary nitrate is found to enhance muscle fatty acid oxidation/glucose uptake and increase mitochondrial biogenesis, which in turn, aid in the prevention and management of metabolic diseases. Read more about this study
- Who is it for?
- Ages 40 to 65 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Dietary Nitrate Supplementation
- What is being tested?
- Beetroot juice
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteSingapore
- Study dates
- 8 Jul 2022to 4 Apr 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 65 years
- Men only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Males aged 40 - 65 years old, residing in Singapore
- Body mass index (BMI) 23 - 30 kg/m2
- Glucose metabolism: a. Normal group with having FPG < 5.6 mmol/L and HbA1c < 5.7, b. Pre-diabetes group FPG 5.6 to 6.9 mmol/L, and HbA1c < 6.5 %.
- Willing to refrain from using oral mouth wash during study participation
- Willing to adhere to study protocol
Who cannot join
- Any current diagnosis or history of cardiovascular, hepatic, renal, metabolic (e.g. diabetes), gastrointestinal diseases, psychiatric disorders or diseases having impact on the study
- Suffering from current oral health conditions such as gum diseases, oral cancer or mouth injury
- Having medication and/or supplements which are known to influence glucose and insulin and muscle mitochondrial metabolism (e.g. Vitamin A, B, C and D, peroral corticosteroids)
- Having medication for oral health conditions in the last 4 weeks and/or using oral mouth wash (e.g Listerine) in the last 2 weeks
- Uncontrolled hypertension (blood pressure > 160/100 mmHg)
- Current smoker or excessive alcohol intake (>4 standard drinks per day)
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- Known allergy/intolerance to beetroot family (eg: beetroot, spinach)
- Undergoing weight loss diet and/or programs
- Having contraindications for MRI e.g. metallic implants such as cardiac pacemaker
- Receiving antibiotics or suffering from diarrhoea in the last 4 weeks
- Consuming supplement(s) which contains nitrate
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Evaluating the Metabolic Effects of Dietary NItrate Supplementation for Improving Skeletal Muscle Mitochondrial Function, Insulin Sensitivity, Insulin Secretion, Body Fat Composition and Overall Health
Dietary nitrate is found to enhance muscle fatty acid oxidation/glucose uptake and increase mitochondrial biogenesis, which in turn, aid in the prevention and management of metabolic diseases. In recent years, inorganic nitrate supplementation is clinically emerging as a therapeutic strategy for possible treatment and management of metabolic diseases and cardiometabolic disorders. This is mostly explored in healthy/obese subjects, for improving blood pressure, endothelial function, insulin response and vascular effects. However, the metabolic effects of dietary nitrate for improving skeletal muscle glucose/lipid metabolism, muscle mitochondrial metabolism, muscle blood flow and body fat composition are not comprehensively studied in diabetic/pre-diabetic subjects. Hence, this study aims to evaluate the therapeutic efficacy of a natural nitrate supplement (beetroot juice) for improving overall metabolic health in obese pre-diabetic and non-diabetic subjects.
Read the detailed description
Skeletal muscle plays a key role in glucose and energy homeostasis and is involved in metabolizing a substantial proportion of glucose through glucose oxidation as well as through non-oxidative pathways. Skeletal muscle insulin resistance is one of the key driving factors associated with the pathophysiology of type 2 diabetes (T2D) and muscle dysfunction. Further, mitochondrial dysfunction is implicated in the pathogenesis of insulin resistance, insulin secretion and T2D. Enhancement of muscle fatty acid oxidation/glucose uptake along with increased mitochondrial biogenesis using natural supplements is an emerging strategy for preventing and managing metabolic diseases. One such natural supplements is nitrate (NO3). The oral microbiome plays a prominent role in the bioactivation of dietary nitrate (NO3) to nitrite (NO2), which is further reduced to nitric oxide (NO) in the gastrointestinal tract to maintain NO homeostasis and vascular health. NO is an important physiological signaling molecule and is involved in the modulation of skeletal muscle functions including regulation of blood flow (hemodynamic effect), muscle contractility, glucose, calcium homeostasis, mitochondrial respiration and biogenesis.
The use of dietary NO3 supplementation has been explored in the literature for mainly improving blood pressure, endothelial function, insulin response, and vascular effects in healthy/obese subjects. However, the metabolic effects of dietary NO3 for improving skeletal muscle glucose/lipid metabolism, muscle mitochondrial energetics, muscle blood flow, and body fat composition are not well studied in diabetic/pre-diabetic subjects.
In view of the potential health benefits of NO3/NO, this study plans to evaluate the therapeutic efficacy of a natural supplement, beetroot juice (rich in NO3) for improving the skeletal muscle mitochondrial function, muscle energetics, insulin sensitivity/glucose homeostasis, body fat composition and overall metabolism in middle aged (40 - 65 years) healthy and pre-diabetic male subjects. This would be the very first pilot study in the domain of metabolic diseases to evaluate the overall metabolic health of both obese pre-diabetic and non-diabetic male subjects using an advanced and comprehensive multi-model metabolic imaging approach.
- Conditions
- Dietary Nitrate Supplementation
- Being tested
- Beetroot juice
- Keywords
- Beetroot, Nitrate, Supplementation, NO3, Mitochondria, Insulin, Metabolic, Fat, Skeletal, Muscle
- Medical subject headings
- Insulin Resistance, Platelet Glycoprotein IV Deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Beetroot juiceDietary supplement
Single-centre, two-arm study involving 16 weeks of beetroot juice supplementation
| Study group | Role | What they receive |
|---|---|---|
| Normal | Experimental | Subjects will consume 140mL of beetroot juice per day (800mg NO3/day), taken twice a day (70mL) in the afternoon and evening. Receives: Dietary Supplement: Beetroot juice |
| Pre-diabetic | Experimental | Subjects will consume 140mL of beetroot juice per day (800mg NO3/day), taken twice a day (70mL) in the afternoon and evening. Receives: Dietary Supplement: Beetroot juice |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in skeletal muscle mitochondrial oxidative capacity
Primary outcome involves the measure of muscle mitochondrial capacity (mVO2max) as recovery rate constant (min-1) by near-infrared spectroscopy (NIRS). The muscle's oxidative capacity in handling the lipid/glucose fuel substrates will be studied by measuring the mitochondrial oxidative capacity by NIRS.
Measured: Baseline, Week 8, Week 16
Changes in skeletal muscle fuel rating
Primary outcome involves the measure of muscle fuel rating (i.e. muscle energy status) by ultrasound imaging. Ultrasound imaging will be performed in various skeletal muscle compartments. Complementary to NIRS data, the muscle fuel rating, i.e. the muscle's capacity to store and utilize fuel changes over time in response to interventions will be measured.
Measured: Baseline, Week 8, Week 16
Changes in insulin sensitivity in response to beetroot juice consumption via blood glucose measurements
The blood glucose (mmol/L) contents will be measured at week 0 and after 16 weeks of beetroot juice consumption. Changes in concentrations of blood glucose will be measured by the IVGTT for evaluating the insulin secretion/sensitivity in response to glucose stimulation. This data will be helpful for interpreting the first phase of insulin response and changes in insulin sensitivity.
Measured: Baseline, Week 16
Changes in insulin sensitivity in response to beetroot juice consumption via blood insulin measurements
The insulin (mU/L) contents will be measured at week 0 and after 16 weeks of beetroot juice consumption. Changes in concentrations of blood insulin will be measured by the IVGTT for evaluating the insulin secretion/sensitivity in response to glucose stimulation. This data will be helpful for interpreting the first phase of insulin response and changes in insulin sensitivity.
Measured: Baseline, Week 16
Secondary outcomes (9)
Ectopic fat metabolism
Fat content (in percentage) in ectopic organs including the liver pancreas, abdomen, and skeletal muscle will be measured by magnetic resonance imaging (MRI)/magnetic resonance spectroscopy (MRS). Assessment of changes in fat content will help us in evaluating the body fat metabolism and body fat composition in these organs in response to intervention.
Measured: Baseline, Week 8, Week 16
Body fat composition
Body fat percentage will be assessed using Bioelectrical Impedance Analysis (BIA). Assessment of changes in fat percentage will help us in evaluating the body fat composition in response to intervention.
Measured: Baseline, Week 8, Week 16
Measure of quality of life
Assessed by the 36-Item Short Form Survey (SF-36).
SF-36 questionnaires consists of eight scales yielding two summary measures including physical (physical role, bodily pain, and general health) and mental health (vitality, social functioning, role-emotional, and mental health). Higher scores indicate better health status, and a mean score of 50 has been articulated as a normative value for all scales.
Measured: Baseline, Week 16
Measure of anxiety (if any)
Assessed by State-Trait Anxiety Inventory (STAI).
The STAI is a psychological inventory consisting of 40 self-report items on a 4-point Likert scale. The state and trait anxiety levels will be interpreted based on the STAI score, the score range from 20-80, with a higher STAI score indicating higher levels of anxiety.
Measured: Baseline, Week 16
Measure of depression (if any)
Assessed by Beck Depression Inventory-II (BDI).
The BDI is an inventory consisting of 21 self-report items with a score value of 0-3 for each question. The total score ranges from 0-63, with higher BDI score indicating higher levels of depression.
Measured: Baseline, Week 16
Measure of food frequency
For assessment of levels of nitrate consumed in usual diet
Measured: Baseline, Week 16
Measure of resting energy expenditure
Indirect calorimetry will be used to measure resting energy expenditure
Measured: Baseline, Week 8, Week 16
Oral microbiome assessment
The dorsum surface of the tongue is rich nitrate-reducing bacteria and beetroot juice consumption alters the salivary microbiome. The oral microbiome 16S rRNA gene amplification will be assessed from oral swab sample. The relative abundance of the complete oral microbiome including Rothia, Actinomyces, Prevotella, Neisseria, Veillonella, Proteobacteria and Corynebacterium and Propionibacterium will be assessed. This data will help investigators to understand the effect of beetroot juice consumption in improving the oral microbiome.
Measured: Baseline, Week 8, Week 16
Gut microbiome assessment
Beetroot juice consumption alters the gut microbiota and thereby improves the systemic metabolism. Stool sample will be analyzed by 16S rRNA generic characterization and metagenomics analysis.
Measured: Baseline, Week 16
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Oct 2022
- Study start8 Jul 2022
- Primary completion4 Apr 2023
- Study completion4 Apr 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Dietary Nitrate SupplementationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Institute for Human Development and Potential (IHDP), Singapore
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Yaligar Jadegoud, Institute for Human Development and Potential (IHDP), Singapore
- Investigators
- Yaligar Jadegoud, PhD, Principal investigator, Institute for Human Development and Potential (IHDP), Singapore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05579262
- Sponsor's protocol ID
- 2022/00194
- Acronym
- NIMMI
- Status last verified
- Sep 2023
- First submitted
- 24 Jun 2022
- Last updated
- 11 Sep 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluating the Metabolic Effects of Dietary NItrate Supplementation for Improving Skeletal Muscle Mitochondrial Function, Insulin Sensitivity, Insulin Secretion, Body Fat Composition and Overall Health
- ClinicalTrials.gov ID
- NCT05579262
- Acronym / sponsor ID
- NIMMI / 2022/00194
- Conditions
- Dietary Nitrate Supplementation
- Keywords
- Beetroot, Nitrate, Supplementation, NO3, Mitochondria, Insulin, Metabolic, Fat
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Institute for Human Development and Potential (IHDP), SingaporeUniversity, hospital or other
- Study start
- 8 Jul 2022 (actual)
- Primary completion
- 4 Apr 2023 (actual)
- Study completion
- 4 Apr 2023 (actual)
- First posted
- 13 Oct 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Dietary nitrate is found to enhance muscle fatty acid oxidation/glucose uptake and increase mitochondrial biogenesis, which in turn, aid in the prevention and management of metabolic diseases. In recent years, inorganic nitrate supplementation is clinically emerging as a therapeutic strategy for possible treatment and management of metabolic diseases and cardiometabolic disorders. This is mostly explored in healthy/obese subjects, for improving blood pressure, endothelial function, insulin response and vascular effects. However, the metabolic effects of dietary nitrate for improving skeletal muscle glucose/lipid metabolism, muscle mitochondrial metabolism, muscle blood flow and body fat composition are not comprehensively studied in diabetic/pre-diabetic subjects. Hence, this study aims to evaluate the therapeutic efficacy of a natural nitrate supplement (beetroot juice) for improving overall metabolic health in obese pre-diabetic and non-diabetic subjects.
Detailed description
Skeletal muscle plays a key role in glucose and energy homeostasis and is involved in metabolizing a substantial proportion of glucose through glucose oxidation as well as through non-oxidative pathways. Skeletal muscle insulin resistance is one of the key driving factors associated with the pathophysiology of type 2 diabetes (T2D) and muscle dysfunction. Further, mitochondrial dysfunction is implicated in the pathogenesis of insulin resistance, insulin secretion and T2D. Enhancement of muscle fatty acid oxidation/glucose uptake along with increased mitochondrial biogenesis using natural supplements is an emerging strategy for preventing and managing metabolic diseases. One such natural supplements is nitrate (NO3). The oral microbiome plays a prominent role in the bioactivation of dietary nitrate (NO3) to nitrite (NO2), which is further reduced to nitric oxide (NO) in the gastrointestinal tract to maintain NO homeostasis and vascular health. NO is an important physiological signaling molecule and is involved in the modulation of skeletal muscle functions including regulation of blood flow (hemodynamic effect), muscle contractility, glucose, calcium homeostasis, mitochondrial respiration and biogenesis.
The use of dietary NO3 supplementation has been explored in the literature for mainly improving blood pressure, endothelial function, insulin response, and vascular effects in healthy/obese subjects. However, the metabolic effects of dietary NO3 for improving skeletal muscle glucose/lipid metabolism, muscle mitochondrial energetics, muscle blood flow, and body fat composition are not well studied in diabetic/pre-diabetic subjects.
In view of the potential health benefits of NO3/NO, this study plans to evaluate the therapeutic efficacy of a natural supplement, beetroot juice (rich in NO3) for improving the skeletal muscle mitochondrial function, muscle energetics, insulin sensitivity/glucose homeostasis, body fat composition and overall metabolism in middle aged (40 - 65 years) healthy and pre-diabetic male subjects. This would be the very first pilot study in the domain of metabolic diseases to evaluate the overall metabolic health of both obese pre-diabetic and non-diabetic male subjects using an advanced and comprehensive multi-model metabolic imaging approach.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Normal | Experimental | Dietary Supplement: Beetroot juiceSubjects will consume 140mL of beetroot juice per day (800mg NO3/day), taken twice a day (70mL) in the afternoon and evening. |
| Pre-diabetic | Experimental | Dietary Supplement: Beetroot juiceSubjects will consume 140mL of beetroot juice per day (800mg NO3/day), taken twice a day (70mL) in the afternoon and evening. |
Who may qualify
- Ages
- 40 to 65 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Males aged 40 - 65 years old, residing in Singapore
- Body mass index (BMI) 23 - 30 kg/m2
- Glucose metabolism: a. Normal group with having FPG < 5.6 mmol/L and HbA1c < 5.7, b. Pre-diabetes group FPG 5.6 to 6.9 mmol/L, and HbA1c < 6.5 %.
- Willing to refrain from using oral mouth wash during study participation
- Willing to adhere to study protocol
Key exclusion criteria (11 listed)
- Any current diagnosis or history of cardiovascular, hepatic, renal, metabolic (e.g. diabetes), gastrointestinal diseases, psychiatric disorders or diseases having impact on the study
- Suffering from current oral health conditions such as gum diseases, oral cancer or mouth injury
- Having medication and/or supplements which are known to influence glucose and insulin and muscle mitochondrial metabolism (e.g. Vitamin A, B, C and D, peroral corticosteroids)
- Having medication for oral health conditions in the last 4 weeks and/or using oral mouth wash (e.g Listerine) in the last 2 weeks
- Uncontrolled hypertension (blood pressure > 160/100 mmHg)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Beetroot juiceSingle-centre, two-arm study involving 16 weeks of beetroot juice supplementation | Dietary supplement | Normal, Pre-diabetic |
Primary outcome
Changes in skeletal muscle mitochondrial oxidative capacity
Time frame: Baseline, Week 8, Week 16
Primary outcome involves the measure of muscle mitochondrial capacity (mVO2max) as recovery rate constant (min-1) by near-infrared spectroscopy (NIRS). The muscle's oxidative capacity in handling the lipid/glucose fuel substrates will be studied by measuring the mitochondrial oxidative capacity by NIRS.
Changes in skeletal muscle fuel rating
Time frame: Baseline, Week 8, Week 16
Primary outcome involves the measure of muscle fuel rating (i.e. muscle energy status) by ultrasound imaging. Ultrasound imaging will be performed in various skeletal muscle compartments. Complementary to NIRS data, the muscle fuel rating, i.e. the muscle's capacity to store and utilize fuel changes over time in response to interventions will be measured.
Changes in insulin sensitivity in response to beetroot juice consumption via blood glucose measurements
Time frame: Baseline, Week 16
The blood glucose (mmol/L) contents will be measured at week 0 and after 16 weeks of beetroot juice consumption. Changes in concentrations of blood glucose will be measured by the IVGTT for evaluating the insulin secretion/sensitivity in response to glucose stimulation. This data will be helpful for interpreting the first phase of insulin response and changes in insulin sensitivity.
Changes in insulin sensitivity in response to beetroot juice consumption via blood insulin measurements
Time frame: Baseline, Week 16
The insulin (mU/L) contents will be measured at week 0 and after 16 weeks of beetroot juice consumption. Changes in concentrations of blood insulin will be measured by the IVGTT for evaluating the insulin secretion/sensitivity in response to glucose stimulation. This data will be helpful for interpreting the first phase of insulin response and changes in insulin sensitivity.
9 secondary outcomes
Ectopic fat metabolism
Time frame: Baseline, Week 8, Week 16
Body fat composition
Time frame: Baseline, Week 8, Week 16
Measure of quality of life
Time frame: Baseline, Week 16
Measure of anxiety (if any)
Time frame: Baseline, Week 16
Measure of depression (if any)
Time frame: Baseline, Week 16
Measure of food frequency
Time frame: Baseline, Week 16
Measure of resting energy expenditure
Time frame: Baseline, Week 8, Week 16
Oral microbiome assessment
Time frame: Baseline, Week 8, Week 16
Gut microbiome assessment
Time frame: Baseline, Week 16
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Sep 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yaligar Jadegoud, PhD principal investigator
Institute for Human Development and Potential (IHDP), Singapore
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Beetroot juice in people with Dietary Nitrate Supplementation, run by Institute for Human Development and Potential (IHDP), Singapore at 1 site in Singapore.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in skeletal muscle mitochondrial oxidative capacity (time frame: Baseline, Week 8, Week 16). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Sep 2023.