# The Effects of Nitrate on Brown Fat Fraction and Activation in Older Adults With Type 2 Diabetes: A Randomised, Double‐Blind and Placebo‐Controlled Crossover Trial

## TL;DR

This study tested if nitrate from beetroot juice could activate brown fat in older adults with type 2 diabetes, but found no significant effect.

## Contribution

A randomized, placebo-controlled trial investigating nitrate's effect on brown adipose tissue in type 2 diabetes patients.

## Key findings

- Nitrate supplementation increased plasma nitrate and nitrite levels significantly.
- No significant changes in brown adipose tissue fat fraction or activation were observed.
- Cooling reduced mean skin temperature but did not enhance BAT activation with nitrate.

## Abstract

Type 2 diabetes mellitus (T2DM) is a metabolic disease characterised by chronic hyperglycaemia, whereas obesity is a major risk factor which increases morbidity and mortality. Treatments that alter white adipose tissue to express a metabolically active brown adipose phenotype in rats may offer adjunct treatment in people with T2DM. To investigate whether inorganic nitrate supplementation from beetroot juice (BJ) alters brown adipose tissue (BAT) fat fraction and activation in humans. Thirteen older adults with T2DM (glycated haemoglobin [HbA1c]: 58 ± 13 mmol·mol−1 and body mass index: 29.1 ± 3.1 kg·m−2) completed a double‐blind, randomised, balanced and placebo‐controlled crossover study. Outcome measures (including BAT fat fraction; activation; plasma [nitrate] and [nitrite]) were assessed before and after 14‐day of 140 mL·day−1 BJ containing inorganic nitrate (∼12.4 mmol·L1) or a placebo (∼0.1 mmol·L1). Magnetic resonance imaging (MRI) and infrared thermography (IRT) were performed to image supraclavicular BAT following a rested cooling protocol, consisting of 60‐min exposure via a cold water (8.1 ± 1.2°C) perfused jacket. Respiratory parameters, including respiratory exchange ratio [RER] and mean skin temperature, were measured during the cooling protocol to confirm participants were not shivering. BJ significantly increased venous plasma [nitrate] and [nitrite] versus placebo (p < 0.001) but did not affect BAT fat fraction (p = 0.650) or activation (p = 0.152). Cooling significantly reduced mean skin temperature in BJ (−0.8 ± 0.7°C) and placebo (−0.6 ± 0.6°C) (p < 0.001) and RER remained representative of nonshivering thermogenesis throughout (0.88 ± 0.05 a.u.). 14‐day of nitrate supplementation did not increase BAT fat fraction or activation in older adults with T2DM.

This trial investigated nitrate supplementation on brown adipose tissue fat fraction and activation in adults with type 2 diabetesNitrate supplementation increased plasma [nitrite], whereas a water‐perfused jacket reduced mean skin temperature to investigate brown fat activation via coolingNitrate supplementation did not increase BAT fat fraction or activationPossible explanations for the lack of effect include; adiposity, insufficient cooling periods, lack of efficacy of nitrate and hypoglycaemic agents stimulating BAT

This trial investigated nitrate supplementation on brown adipose tissue fat fraction and activation in adults with type 2 diabetes

Nitrate supplementation increased plasma [nitrite], whereas a water‐perfused jacket reduced mean skin temperature to investigate brown fat activation via cooling

Nitrate supplementation did not increase BAT fat fraction or activation

Possible explanations for the lack of effect include; adiposity, insufficient cooling periods, lack of efficacy of nitrate and hypoglycaemic agents stimulating BAT