Uric Acid: A Major Player in the Metabolic Syndrome Save

An open source, free read from the European Journal of Internal Medicine discusses how uric acid has evolved from the toxic cause of gout and nephrolithiasis and evolved, by way of science, into a pleiotropic recidivist in the evolution of obesity, diabetes, insulin resistance, renal disease, hypertension, fatty liver, and cardiovascular disease. While once considered epiphenomenal to these disorders, research suggests that uric acid may orchestrate the many comorbid hats it wears.

Below we have exerpted some of the major mechanisms linking uric acid to metabolic and cardiovascular diseases. In the end, hyperuricemia may turn out to be one of the most important modifiable risk factors for metabolic and cardiovascular diseases.

Uric acid and metabolic syndrome

Uric acid, and hyperuricemia, has been closely linked with may of the components of the metabolic syndrome, which is largely a consequence of excessive fat storage. Thereby leadign to obesity, fatty liver, insulin resistance and hypertension.  It appears that uric acid promotes fat accumulate via adenosine monophosphate (AMP) deaminase.

Uric acid and hypertension

Does hyperuricemia lead to renal disease with hypertension as a by product or does hyperuricemia independently contribute to HTN?  Asymptomatic hyperuricemia is associated with and predicts the development of hypertension. Animal models that accumulate uric acid develop hypertension. The belief is that chronic hyperuricemia induces microvascular and inflammatory changes in the kidney and enhanced sensitivity to the effects of salt.  There have been mixed results with studies designed to lower uric acid in an attempt to improve blood pressure, including in studies in pre-hypertensive obese and hypertensive adolescents, hypertensive children on an angiotensin converting enzyme inhibitor, adults with asymptomatic hyperuricemia, older hypertensive adults , gout patients, obese prehypertensive adults, etc. Some studies have shown that uric acid may be a remediable risk factor in subjects with hypertension.

Uric acid and diabetes

Hyperuricemia has been linked with diabetes since the 1800s and was associated with metabolic syndrome by the early 1920s. There is strong evidence that hyperuricemia is both present and predicts the development of insulin resistance and type 2 diabetes. There are studies showing insulin resistance in metabolic syndrome can be improved by lowering serum uric acid. Reducing uric acid can improve circulating adiponectin levels and insulin resistance in mice with metabolic syndrome.

Uric acid and fat storage (adipose and liver)

Hyperuricemia has been linked to the development of obesity and fatty liver.

Diet and uric acid 

Excess uric acid can be induced by high purine foods (such as beer) and by fructose, high fat diets and purine-rich foods are recognized as risk factors for metabolic syndrome. Clinical studies have shown that fructose can raise serum uric acid and induce features of metabolic syndrome.

Uric acid and cardiovascular disease

Uric acid has been associated with cardiovascular disease and an increased risk of CV event. There are now some early trials showing that lowering uric acid improves carotid intimal thickness, angina, left ventricular hypertrophy, arterial stiffness and cardiovascular events in subjects with and without chronic kidney disease.

The authors concluded by writing, "While uric acid was once the lonely dinner conversation for those suffering from gout or kidney stones, it is now being evaluated as a potential master conductor in the worldwide symphony of obesity, diabetes, and cardiorenal disease. However, at this time, it is still premature to lower uric acid as a means for reducing metabolic and cardiovascular disease. They call for more large-scale studies to determine if urate lowering therapies may improve or prevent hypertension, insulin resistance, obesity, fatty liver, and cardiovascular disease.