Phase I Clinical Trial Investigating the Effects of Caffeine Citrate on Serum Vascular Adhesion Protein -1 (VAP-1) Levels in Healthy Volunteers.

Worldwide, liver related morbidity and mortality continue to rise. It is the 5th commonest cause of death in the UK. Liver damage consists of two main components - a) damage to the cells of the liver, called hepatocytes, meaning the liver cannot function properly leading to jaundice (yellow appearance of the skin and/or eyes) and liver failure and b) scarring of the liver, called Cirrhosis, leading to impaired function and inadequate blood flow through the liver with potential to develop into cancer. Manifestations of this state include ascites (fluid in the tummy) and varices (swollen blood vessels in the food pipe). Liver transplant is currently the only curative treatment for end stage chronic liver disease. Unfortunately its high demand has not been matched by an equivalent rise in liver donations and even when a transplant has occurred there are numerous lifestyle effects such as immunosuppression and kidney impairment thus outcome remains poor for many patients. Coffee has been shown to have mortality benefit in humans and drinking two to three cups a day was associated with a 40% reduced risk of developing cirrhosis, particularly alcohol related; and higher the more cups consumed. Previous work has demonstrated coffee reduces the level of fibrosis in the liver by interrupting signalling pathways, blocking the effects of special products, called cytokines, and reducing accumulation of iron. The investigators' hypothesis is that given the potential for caffeine to be used as a treatment in SSAO activity associated diseases it is important to see if the activity of SSAO can be blocked in healthy humans too. The Investigators' aim to examine the effect of caffeine on circulating VAP-1 levels in large numbers of healthy volunteers to assess its potential as an attractive therapeutic target in view of its low toxicity and widespread availability.