Beneficial Effects of Inorganic Nitrates in Liver Steatosis

• Research type

  Research Study

• Full title

  Beneficial Effects of Inorganic Nitrates in Liver Steatosis

• IRAS ID

  213037

• Contact name

  Michele Vacca

• Contact email

  mv400@medschl.cam.ac.uk

• Sponsor organisation

  Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge

• Duration of Study in the UK

  0 years, 9 months, 20 days

• Research summary

  The Metabolic Syndrome (MetS) is a cluster of cardiovascular risk factors (obesity, hypertension, insulin resistance, and dyslipidaemia) associated with inflammation, pro-thrombotic state and non-alcoholic fatty liver disease (NAFLD)/steatohepatitis (NASH). Neither pharmacological approaches nor diet/exercise (due to low long-term compliance) have proven to be efficient in preventing/treating obesity and its comorbidities; new approaches are thus needed. Here we propose to nutritionally modulate nitric oxide (NO) signalling to revert the effects of the MetS pathophysiology. In rodents, nutritional supplementation with inorganic nitrate reduces weight and visceral fat,
  improves glucose metabolism, and promotes fat burning in organs such as skeletal muscle and adipose tissue. Nitrate-rich vegetables and extracts thus have potential as therapeutic interventions for MetS and NAFLD/NASH. In fact, NAFLD results from excessive storage of lipids, where the capability of the hepatocytes to store, burn and process the lipids is exceeded. Increasing fat burning in the liver has been proposed as a promising strategy for NAFLD management. Our preliminary pre-clinical results show that inorganic nitrate promotes metabolic health and interferes with the mechanisms leading to NASH (i.e. fat accumulation, inflammation) through a mechanism of enhanced fat burning.
  This double-blind double-arm crossover nutritional intervention aims to confirm the short-term (4 weeks) effect of beetroot juice (rich in nitrates; vs. Placebo – beetroot juice deliberately depleted of nitrates) on the metabolic function of patients with MetS/NASH. The clinical assessment of the metabolic function and liver damage will be complemented with state of the art nutrigenomic approaches (to study genes, circulating metabolites and lipids) to understand the mechanisms underlying the effects of inorganic nitrates on metabolic homeostasis and inflammation.

• REC name

  East of England - Cambridge Central Research Ethics Committee

• REC reference

  17/EE/0002

• Date of REC Opinion

  8 May 2017

• REC opinion

  Further Information Favourable Opinion