Uric acid is almost always mentioned in the context of gout, an inflammatory type of arthritis that results from excessive uric acid in the blood. It may be surprising, then, that it has also been linked with a vastly different type of disease: bipolar disorder. Elevated uric acid has been observed in patients with acute mania, and reducing uric acid improves symptoms. New evidence supports its potential as a treatment target.

Uric acid is a by-product of the breakdown of compounds called purines, found in many foods and manufactured by the body. High levels of uric acid can indicate that these compounds, such as the neurotransmitter adenosine, are being broken down too readily in the body. “Adenosine might play a key role in neurotransmission and neuromodulation, having sedative, anticonvulsant and antiaggressive effects,” says physician Francesco Bartoli, a researcher at the University of Milano-Bicocca in Italy. Bartoli's new study, published in May in the Journal of Psychosomatic Research, examined uric acid levels in 176 patients with bipolar disorder or another severe mental illness and 89 healthy controls. The results show that bipolar disorder was the only diagnosis significantly linked with levels of uric acid. Excess uric acid was found to be linked to male gender, metabolic syndrome, waist size and triglyceride levels.

Beyond the too rapid breakdown of adenosine, other potential explanations for increased uric acid include the metabolic abnormalities often present in people with bipolar disorder and frequent consumption of purine-rich foods and drinks, such as liver, legumes, anchovies and alcohol. Fructose consumption can also be a problem because the sugar inhibits uric acid excretion. Dietary interventions may reduce levels, but medication is typically required if dietary changes are insufficient.

The uric acid link points to novel treatments for mania. In a double-blind, randomized controlled trial reported in 2014, researchers in Iran and Switzerland investigated the efficacy of allopurinol, a gout medication that reduces levels of uric acid, in 50 patients with bipolar disorder during acute mania. During a period of four weeks, subjects received the mood stabilizer sodium valproate—a standard treatment—plus either allopurinol or a placebo. In the allopurinol group, there was a significant reduction in uric acid levels and mania symptoms, and rates of remission were 23 times higher.

In the future, doctors may find it useful to help bipolar patients modify their diet, says study co-author Serge Brand, a research psychologist at the University of Basel in Switzerland: “This approach is timely and is part of the broader research focusing on the so-called gut-brain axis.”