Evaluating the Metabolic Effects of Dietary NItrate Supplementation for Improving Skeletal Muscle Mitochondrial Function, Insulin Sensitivity, Insulin Secretion, Body Fat Composition and Overall Health
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Changes in skeletal muscle mitochondrial oxidative capacity
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 40 Years 至 65 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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
结局指标
主要结局
Changes in skeletal muscle mitochondrial oxidative capacity
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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.
次要结局
- Measure of resting energy expenditure(Baseline, Week 8, Week 16)
- Measure of depression (if any)(Baseline, Week 16)
- Gut microbiome assessment(Baseline, Week 16)
- Measure of quality of life(Baseline, Week 16)
- Measure of anxiety (if any)(Baseline, Week 16)
- Oral microbiome assessment(Baseline, Week 8, Week 16)
- Measure of food frequency(Baseline, Week 16)
- Ectopic fat metabolism(Baseline, Week 8, Week 16)
- Body fat composition(Baseline, Week 8, Week 16)
研究者
Yaligar Jadegoud
Principal Investigator
Institute for Human Development and Potential (IHDP), Singapore