Uric acid is a metabolic end-product of purine metabolism and has been recently incriminated in a number of chronic disease states, including hypertension, metabolic syndrome, diabetes, non-alcoholic fatty liver disease, and chronic kidney disease.
Several experimental and clinical studies support uric acid as a contributory causal factor in these conditions. Here we discuss some of the major mechanisms linking uric acid to cardiovascular diseases.
Hypertension has been linked to inflammation of the kidneys. This low-grade inflammation in the kidneys is due to T-cells and macrophages. This inflammation tends to be in the main part of the kidney where the tubules are and around the little blood vessels. An inflamed kidney has difficulty excreting salt. This is because of reduced blood flow to the organ which leads to salt retention.
So what is causing this inflammation? Many things can, including some vasoconstricting drugs and activation of the renin-angiotensin system, but it has also been discovered that uric acid leads to kidney inflammation.
Dr. Rick Johnson has run multiple studies to support the role of uric acid in hypertension. This study showed that adolescents with newly diagnosed hypertension were likely to have high uric acid levels. Another study showed that inducing mice with uric acid led to mitochondrial dysfunction and decreased intracellular ATP production. Uric acid inside the cell causes oxidative stress to the mitochondria, which are really important in ATP production. Finally, he randomized adolescents with high blood pressure into two groups. One group took a drug to lower uric acid (allopurinol) and the other had no treatment. The results of this study showed that 90% normalized their blood pressure when their uric acid levels were lowered.
Uric acid is also raising blood pressure directly through effects on blood vessels by inhibiting nitric oxide; it will stimulate oxidative stress. Specifically, uric acid will reduce endothelial nitric oxide by binding to it.
In this image, we are focussing on sodium retention and hypertension. Excess fructose, the sugar in fruits leads to uric acid production. While this pathway was great for our ancestors who dealt with food shortages, it is not ideal for the population that has an abundance of highly processed foods available at all times.
“But the problem is that the body can make fructose. And it turns out that the favorite way it makes fructose is through high glucose levels.” – Rick Johnson
A high sugar diet leads to increased production of fructose and an increase of uric acid. In this study, excessive fructose intake induced the features of metabolic syndrome in healthy adult men through uric acid. And this study shows Increased fructose is associated with elevated blood pressure.
Salt raises blood pressure and stimulates the endogenous production of fructose; as the salt concentration in the blood goes up, it activates the polyol pathway and turns on this enzyme (aldose reductase) to make fructose which converts glucose to fructose.
What can we do with this information?
As discussed, allopurinol can have a great effect on uric acid if all else fails, but there are plenty of lifestyle modifications that should be attempted before initiating pharmaceutical interventions.
Eating less processed foods, which are high in salt and sugar is the most effective way to lower uric acid. Avoiding added sugars prevents glucose from converting to fructose. A whole-food approach, with carbohydrate consciousness, will work better than any pharmaceutical in this space. Coupling this with exercise, a minimum of 150 minutes at moderate intensity every week, will lower uric acid and help to reverse metabolic disease.