Fructose and Uric Acid as Drivers of a Hyperactive Foraging Response: A Clue to Behavioral Disorders Associated with Impulsivity or Mania?

Several behavioral disorders, including attention deficit hyperactivity disorder (ADHD), bipolar disorder, and aggressive behaviors are linked with sugar intake and obesity. The reason(s) for this association has been unclear. Here we present a hypothesis supporting a role for fructose, a component of sugar and high fructose corn syrup (HFCS), and uric acid (a fructose metabolite), in increasing the risk for these behavioral disorders. Recent studies have shown that the reason fructose intake is strongly associated with development of metabolic syndrome is that fructose intake activates an evolutionary-based survival pathway that stimulates foraging behavior and the storage of energy as fat. While modest intake may aid animals that would like to store fat as a protective response from food shortage or starvation, we propose that high intake of sugar and HFCS causes a hyperactive foraging response that stimulates craving, impulsivity, risk taking and aggression that increases the risk for ADHD, bipolar disease and aggressive behavior. High glycemic carbohydrates and salty foods may also contribute as they can be converted to fructose in the body. Some studies suggest uric acid produced during fructose metabolism may mediate some of these effects. Chronic stimulation of the pathway could lead to desensitization of hedonic responses and induce depression. In conclusion, a hyperactive foraging response driven by high glycemic carbohydrates and sugars may contribute to affective disorders.