Evaluating the Metabolic Effects of Dietary Nitrate Supplementation

NCT05579262 | Completed

• 1 other identifier: 2022/00194
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Dietary Nitrate Supplementation

Keywords

Beetroot; Nitrate; Supplementation; NO3; Mitochondria; Insulin; Metabolic; Fat; Skeletal; Muscle

Outcome Measures

Primary Outcomes (4)

• 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.

  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.

  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.

  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.

  Baseline, Week 16

Secondary Outcomes (9)

• Ectopic fat metabolism

  Baseline, Week 8, Week 16

• Body fat composition

  Baseline, Week 8, Week 16

• Measure of quality of life

  Baseline, Week 16

• Measure of anxiety (if any)

  Baseline, Week 16

• Measure of depression (if any)

  Baseline, Week 16

Study Arms (2)

Normal

EXPERIMENTAL

Subjects will consume 140mL of beetroot juice per day (800mg NO3/day), taken twice a day (70mL) in the afternoon and evening.

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.

Dietary Supplement: Beetroot juice

Interventions

Beetroot juice DIETARY_SUPPLEMENT

Single-centre, two-arm study involving 16 weeks of beetroot juice supplementation

Normal; Pre-diabetic

Eligibility Criteria

• Age: 40 Years - 65 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• Institute for Human Development and Potential (IHDP), Singapore: lead

Study Sites (1)

Singapore Institute for Clinical Sciences

Singapore, Singapore

Location

MeSH Terms

Conditions

Insulin Resistance; Platelet Glycoprotein IV Deficiency

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Yaligar Jadegoud, PhD

  Institute for Human Development and Potential (IHDP), Singapore

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 24, 2022
• First Posted: October 13, 2022
• Study Start: July 8, 2022
• Primary Completion: April 4, 2023
• Study Completion: April 4, 2023
• Last Updated: September 11, 2023

Record last verified: 2023-09

Locations

SG (1)