Evaluating the Metabolic Effects of Dietary Nitrate Supplementation
Condition: Dietary Nitrate Supplementation
Study type: Interventional

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.
    

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.
    

Intervention name(s): Beetroot juice
Intervention type(s): Dietary Supplement
Intervention description(s): Single-centre, two-arm study involving 16 weeks of beetroot juice supplementation
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Beetroot; Nitrate; Supplementation; NO3; Mitochondria; Insulin; Metabolic; Fat; Skeletal; Muscle