Uric acid is a nitrogen containing substance that is generated during the breakdown of tissues, such as from DNA and RNA. It is also produced during the metabolism of some foods, especially sugar, alcohol, and red meats. Most of us who have heard of uric acid know it because it is the cause of gout. Gout is a type of arthritis that typically affects middle-age men and causes painful swelling of their joints, especially the big toe. People with gout tend to have high uric acid levels in their blood, and when it gets too high it can precipitate into crystals that deposit in the joints. These crystals are quite inflammatory, and cause redness and pain. Each episode may last up to a week or more, and during that time it can be very difficult to walk.
It had been known for hundreds of years that individuals with gout have a much higher frequency of obesity, diabetes, high blood pressure, fatty liver, and kidney disease. Indeed, they also have a much higher risk for heart disease. For years this relationship was thought to be due to the fact that obesity and diabetes may predispose to high uric acid levels. However, studies have consistently shown that a high uric acid level precedes the development of these conditions. This has led many to realize that uric acid cannot simply reflect the presence of these conditions, because it precedes them.
Our experimental studies have shown that the uric acid is playing a role in causing these conditions. However, it is not the uric acid in the blood that is responsible for these effects. Rather it is the uric acid inside the cell that is important, and the uric acid works by causing oxidative stress to the mitochondria. The observation that it is the intracellular uric acid that is driving the metabolic effects is important, as not always to the blood uric acid concentrations correlates with intracellular levels.
While intracellular uric acid levels drive many features of the metabolic syndrome, there are other components of the switch that are also important, and blocking uric acid only partially improves the metabolic syndrome. A more effective way for blocking the switch is to inhibit fructose metabolism completely or by restricting foods that activate the switch.