By Richard J Johnson, MD

Fructose—a common type of sugar in our diets—has been shown to trigger aspects of the foraging response.

When a fasting animal runs out of fat, it must wake from its sleep or leave its nest and start foraging for food.

If it does not find food, it will die—this is a desperate situation—so the animal must be willing to enter new and unfamiliar areas in its search, which places it at risk from predators.

Accordingly, it must be able to rapidly assess its environment, make fast decisions, and move quickly. 

There is no time for prolonged deliberation; the animal must be impulsive, for the longer it remains in an unfamiliar area, the more danger it is in.

The animal cannot be timid, and if it runs into a predator, it may have to defend itself. Similarly, if the animal sees prey, it must attack even if there is a chance the prey might win.

This cluster of behaviors—impulsivity, exploratory behavior, rapid decision-making, novelty-seeking, and risk-taking—is collectively referred to as the foraging response. 

For example, a clinical study that compared the effects of drinking fructose versus glucose in healthy volunteers showed via MRI that, in comparison to glucose, fructose intake was associated with more immediate hunger and greater desire for high-calorie foods.

Moreover, the area of the brain that controls willpower (that is, the prefrontal cortex) showed a decrease in electrical activity consistent with increased risk of giving in to temptation, decreased ability to say no, and a general decrease in willpower. These changes suggest fructose increases impulsivity, novelty-seeking, and risk-taking behaviors.

Foraging Behavior Research

Fructose metabolism results in the formation of uric acid, and there is evidence that uric acid stimulates the foraging response. For example, when blood uric acid levels are raised in laboratory rats, the animals initially become hyperactive.

A study performed by Angelina Sutin at Florida State University reported that mice with high uric acid levels show stronger foraging behavior, including roaming over a greater area, being more excitable with spontaneous jumping, interacting more with novel objects presented to them, and showing more exploratory activity. 

Another study, led by Roy Cutler at the National Institutes of Health, confirmed that mice with high uric acid levels roamed much more widely over an open field than mice with normal levels, and showed more exploratory behavior.

They also found that mice with higher uric acid levels had greater endurance on running wheels. However, while uric acid likely benefits endurance in the short-term as part of the foraging response, over time the negative effects of high uric acid appear to trump these effects.

Sutin’s research group also evaluated the relationship of blood uric acid levels with personality traits in humans, based on two different community studies. Again, a higher uric acid level was associated with characteristics of foraging behavior, including impulsivity, novelty-seeking, risk-taking, and decreased ability to deliberate (think before acting).

Many of these behaviors can be viewed, in some respects, as admirable. They are the same behaviors we use to characterize explorers, astronauts, and others willing to take great personal risks for potentially greater reward, both for themselves and for humankind. People with foraging personality types are the ones who break new ground, make scientific discoveries, start new industries, and open our world to new ideas. 

Yet there is only a fine line separating the successful foraging response of the bold adventurer who guides us through perilous situations and the individual diagnosed with disorders such as attention deficit/hyperactivity disorder (ADHD), bipolar disorder, or mania due to impulsive, hyperactive, manic, and/or aggressive behavior. 

Fructose Role in Attention Deficit/Hyperactivity Disorder 

Attention deficit/hyperactivity disorder refers to a behavioral disorder in which an individual— child or adult—manifests behaviors such as fidgeting, inability to stay still, and excessive talking (hyperactivity) coupled with impulsivity, getting distracted easily, inattentiveness, and inability to focus or complete tasks (attention deficit). ADHD can affect school performance and the ability to sustain a job and is also associated with increased risk of addiction. 

Today, ADHD is extremely common. As of 2011, ADHD is reported to affect one in five high school boys and one in ten high school girls. Among children age four to seventeen, 11 percent have received the diagnosis. The condition often does not resolve with age, and many adults also show characteristics of ADHD.  One survey found that one-third of households have someone in the family with ADHD.

Many factors likely play a role in causing ADHD, but I believe excessive intake of fructose may be an important one.  For one thing, the prevalence of ADHD has increased dramatically in the last decades, in parallel with rising intake of sugar and high fructose corn syrup—in fact, the frequency of ADHD is higher among people who are overweight or obese. A study of dietary patterns in seventeen different countries also found that impulsivity disorders such as ADHD, as well as anxiety and substance use disorders, are greatest in countries with high sugar intake.

Within-country studies also show that individuals with the highest sugar intake commonly have behavioral issues consistent with ADHD. For example, a study of tenth graders from Oslo, Norway, found that 50 percent of the boys and 20 percent of the girls drank at least one soft drink daily, and 10 percent of the boys drank four a day or more.

When they were evaluated for hyperactivity and conduct problems, there was a direct relationship between such problems and drinking one or more sodas a day. Furthermore, children and adults with ADHD both have been reported to have higher uric acid levels. 

In one study of children between three and five years old, higher blood uric acid levels correlated with greater hyperactivity, shorter attention span, and less anger control. In 2019, a French research group led by psychologist Charlotte Van den Driessche noted that individuals with ADHD do not simply show hyperactivity and impulsivity, but also show exploratory behavior whereby they can make rapid assessments consistent with what is required for successful foraging. 

This observation led her group to suggest that ADHD might itself be a manifestation of foraging behavior, as hyperactivity, exploratory behavior, and rapid assessment would all be useful behaviors in settings where food was scarce.

The idea that sugar is related to hyperactivity isn’t new. Most parents and schoolteachers have been attributing children’s hyperactive behavior to sugar consumption for decades. One study reported that 80 percent of elementary teachers believed sugar caused hyperactivity, and 40 percent thought that sugar had a role in causing ADHD.

Many of you have probably witnessed children becoming hyperactive and manic within minutes of eating Halloween candy (being on a “sugar high”), only to suddenly lose all their energy and “crash” an hour later. 

A recent study of Hispanic adolescents appeared to confirm this belief. In this study, children were given a high-sugar, low-fiber meal, and on a separate occasion a low-sugar, high-fiber meal. After the high-sugar meal, the children’s activity increased markedly during the first three hours, then slowed down to below-normal levels. In contrast, after eating the low-sugar meal, their activity remained the same throughout the observation period.

Yet the medical literature calls a causal relationship between sugar and hyperactivity a myth. The reason is that a series of research studies, performed on children in the 1980s and early 1990s, could not demonstrate that sugar had any effect on hyperactivity or related behavioral issues.  Most of these studies gave children sugar for a short period (from a single dose up to a daily dose for two or three weeks) and compared it to the effects of artificial sweeteners, such as aspartame or saccharin.

I believe these studies have several problems proving that sugar and hyperactivity are unrelated. First, they did not measure variations in uric acid levels. Our work suggests that the way fructose causes hyperactivity is by increasing uric acid. The rise typically occurs in the first hour after you eat fructose, which correlates with when the hyperactivity is commonly observed.

However, the amount of uric acid produced can vary dramatically with how much sugar is eaten, how rapidly it is ingested, and whether the subject is accustomed to eating a lot of sugar. Furthermore, with long-term sugar intake, baseline uric acid levels remain high all day long, and so the normally acute change in uric acid in response to eating sugar is blunted. When this happens, a child (or adult) might have characteristics of hyperactivity or ADHD, but no longer show significant worsening of these symptoms after eating sugar. 

Since none of these prior studies measured the uric acid following sugar intake, they are hard to interpret. A second problem is that these studies gave the children sucrose.  As many know, sucrose contains both fructose and glucose. Although fructose causes foraging behavior, glucose does the opposite: it quells hunger and increases activity in the brain associated with enhanced willpower.

While fructose-associated effects typically dominate the outcome when both fructose and glucose are given together, as in sucrose or high fructose corn syrup, studies investigating the ability of sugar to cause ADHD should test not only table sugar, but also fructose alone, glucose alone, and a low-glycemic carbohydrate. 

Finally, most of the studies that failed to document sugar-induced hyperactivity compared diets high in sugar with diets containing an artificial sweetener rather than low-sugar diets. Artificial sweeteners may not be the right comparison, as these substances also stimulate a pleasure response in the brain but do not provide calories, and there is some evidence that this may cause dissatisfaction and agitation.  

Theoretically, agitation could mimic some signs associated with ADHD, like ability to concentrate or stay still, making it difficult to show differences between the two groups even if sucrose were causing signs of ADHD. I admit, some of the evidence that high intake of fructose-containing sugars contributes to ADHD is based on associations, and we do need more direct clinical proof. Nevertheless, there are good reasons to suspect that fructose may play a role.

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Richard Johnson, MD, is a Professor of Medicine at the University of Colorado and is a clinician, educator, and researcher. He is board certified in internal medicine, infectious diseases, and kidney disease and is the founding editor of Comprehensive Clinical Nephrology. For more than 20 years, he has led research on the cause of obesity and diabetes, with special interest in the role of sugar (especially fructose) and uric acid. His research has been highly cited, published in top medical journals, and supported by grants from the National Institutes of Health. He is the author of The Sugar Fix and The Fat Switch. Currently, Johnson lives in Colorado with his wife, kids, and two rambunctious puppies. Learn more at https://drrichardjohnson.com/

Well Being Journal adapted this excerpt from Nature Wants Us to Be Fat by Richard Johnson, MD, copyright 2022, used with permission from BenBella Books https://benbellabooks.com/