A new, preliminary imaging study that compares the effects of fructose and glucose on the brain has found differences that may explain why diets high in fructose may be behind the obesity epidemic.

Upon examining brain magnetic resonance imaging (MRI) scans of adult volunteers, first study author Kathleen A. Page of Yale University School of Medicine in the US, and colleagues, found ingestion of glucose but not fructose reduced blood flow and brain activity in regions of the brain that regulate appetite, and ingestion of glucose but not fructose, led to higher levels of hormones that produce feelings of fullness and satiety.

They write about their findings in a paper published online in JAMA on 2 January.

Fructose in Diet

In the average western diet, fructose comes from two sources: as a natural compound in fruit, and as an added ingredient of processed foods.

Food companies use fructose because it is sweeter than glucose and helps to stabilize processed foods.

The main source of fructose in processed foods in the US is high fructose corn syrup, which is also used to improve the appearance of baked goods because it produces a more consistent browning.

There is currently a debate about whether high fructose corn syrup is driving the obesity epidemic, which is likely to become more heated since the publication in 2012 of an extensive review in the International Journal of Obesity that found no evidence that consumption of high fructose corn syrup is to blame for the obesity crisis in the US.

There are also concerns about links with type 2 diabetes. A more recent study by the University of Oxford and the University of Southern California suggests countries that use large amounts of high fructose corn syrup in their food may be helping to fuel the global epidemic of type 2 diabetes.

An author of that study, Stanley Ulijaszek, Director of the Institute of Social and Cultural Anthropology at the University of Oxford, commented on the difference between consumption of naturally occuring fructose in fruit and artificially introduced fructose as in processed foods. He said:

"... fructose in an apple is probably released slowly because of the fibre within the apple and because the fructose is inside the cells of the apple."

The Study

In their background information, Page and colleagues write how evidence from animal studies suggests that "fructose possibly increases food-seeking behavior and increases food intake", and that "fructose ingestion produces smaller increases in circulating satiety hormones compared with glucose ingestion". But it was not clear how the brain regions that lie behind such changes are affected in humans.

So, for this preliminary investigation into what neurophysiological factors might explain potential links between fructose consumption and weight gain, they recruited 20 healthy, normal weight adults who underwent two sessions of MRI so the researchers could examine changes in blood flow in certain parts of the brain.

The researchers were mainly interested in changes in hypothalamic regional cerebral blood flow (CBF) after glucose or fructose ingestion.

The two sessions of MRI were several weeks apart. The scans were taken before and after ingestion of glucose or fructose.

The Results

The results showed a significantly greater reduction in hypothalamic CBF after ingestion of glucose compared with ingestion of fructose.

"Glucose but not fructose ingestion reduced the activation of the hypothalamus, insula, and striatum - brain regions that regulate appetite, motivation, and reward processing; glucose ingestion also increased functional connections between the hypothalamic-striatal network and increased satiety," write the researchers.

Senior author Robert Sherwin, a professor of medicine at Yale, said in a telephone interview reported by Bloomberg that the results suggest the brain appears to respond differently to glucose than to fructose.

Glucose is a fuel that the body needs. When there isn't enough, it activates cells to get the body to eat more glucose. When the body's levels of glucose rise again, the brain turns those cells off.

What this study appears to show is that fructose does not have this effect: it doesn't turn the cells off.

"If you don't turn off the areas of the brain that are driving you to eat, you have a tendency to eat more than you would," says Sherwin.

He and his colleagues also note that:

"The disparate responses to fructose were associated with reduced systemic levels of the satiety-signaling hormone insulin and were not likely attributable to an inability of fructose to cross the blood-brain barrier into the hypothalamus or to a lack of hypothalamic expression of genes necessary for fructose metabolism."

They conclude:

"In a series of exploratory analyses, consumption of fructose compared with glucose resulted in a distinct pattern of regional CBF and a smaller increase in systemic glucose, insulin, and glucagon-like polypeptide 1 levels."

Expert Comments

In an accompanying editorial, Jonathan Q. Purnell and Damien A. Fair of Oregon Health & Science University, say the study supports the idea that when fructose enters the human brain, it changes the neurobiological pathways that control appetite in a way that makes you want to eat more.

They suggest the study adds to the mounting evidence, from "epidemiologic, metabolic feeding, and animal studies", that show:

"... advances in food processing and economic forces leading to increased intake of added sugar and accompanying fructose in U.S. society are indeed extending the supersizing concept to the population's collective waistlines".

Purnell suggests people should cook more meals at home and limit their intake of processed foods containing fructose and high-fructose corn syrup.

He also advises drinking less sugar-sweetened beverages. You don't have to cut them out altogether, but just control how much and how often you drink them, he says in an interview reported by the Associated Press.

Written by Catharine Paddock PhD