The link between fructose consumption and incidence of metabolic syndrome

A recent article in the Guardian (Mon 21st Oct) reports on “Fructose: the poison index” in which they present arguments and an outrage at the recent EU ruling to not only substitute sucrose with fructose in sweetened drinks and food products but also allow health claims by food companies for using fructose in these products. This decision was made on the advice of the European Food Safety Authority (Efsa), on the grounds that fructose has a lower glycaemic index and as such does not cause as high and rapid rise in blood sugar levels as sucrose or glucose.

However, the science behind the ruling is actually more nuanced than presented: substituting sucrose for fructose may benefit some people at the cost of harming others. I’ll explain the evidence below.

Sucrose vs. Fructose: Examining the Evidence

Fructose is a fruit sugar found in many common foods like honey, raisins, bananas, crab and similar healthy foods; however, in its pure synthetic form it is derived from sugar cane, corn or sugar beets. The increased use of high-fructose corn syrup by the food industry (in most drinks, yoghurts, bakery products, cereals) has been associated with increased obesity and diabetes epidemics in the Western countries. Fructose intake from added sugars has also been implicated as a cause of the metabolic syndrome and non-alcoholic fatty liver disease, cardiovascular disease, cancer and others. Human studies investigating the effects of glucose versus fructose on metabolism are numerous. For example, in one study that assessed the relative effects of glucose versus fructose consumption, provided in the form of sweetened drinks, in overweight and obese subjects found that although both study groups exhibited similar weight gain during the study, visceral fat mass (belly fat) was significantly increased only in subjects consuming fructose-sweetened drinks. Also many other lipid and glucose measurements such as cholesterol, glucose and insulin were only increased in the fructose-consuming group.

KL Stanhope, et al. (2009). Consuming fructose-sweetened, not glucose-sweetened, beverages increases visceral adiposity and lipids and decreases insulin sensitivity in overweight/obese humans. Journal of Clinical Investigation, 119(5):1322-34. doi: 10.1172/JCI37385.

There was also a recent presentation by an addiction expert Francesco Leri at the 2013 Canadian Neuroscience Meeting which suggested that high-fructose corn syrup can also cause behavioural reactions similar to those produced by drugs of abuse such as cocaine.

The article referred to in the Guardian coverage correctly cites one of the most well known cancer researchers Dr. Lewis Cantley and his recent Nature News and Views article called “Metabolic syndrome: F stands for Fructose and Fat”. This article reports on the two recent studies performed to investigate directly the role of fructose in metabolic syndrome and obesity. Both studies use mouse models that are not able to metabolize fructose and support the notion that diets high in fructose could cause excess fat accumulation in the liver, leading to the liver disorders, fatty liver disease, steatohepatitis and, ultimately, cirrhosis.

Lyssiotis CA, Cantley LC. (2013). Metabolic syndrome: F stands for fructose and fat. Nature, 502(7470):181-2. doi: 10.1038/502181a

In the first study, wild-type (normal) or fructokinase knockout mice (mice genetically altered to be unable to metabolize fructose) were fed a low-fat, high-fat, or high-fat and high-sucrose diet for 4 months (3). Both wild-type and fructokinase knockout mice developed obesity with mild liver damage on a high-fat diet compared to a low-fat diet, which is not surprising considering that we know that diets rich in fat are not good for us. However, in contrast, wild-type mice fed a high-fat and high-sucrose diet developed more severe hepatic steatosis and liver fibrosis (severe liver damage), whilst the mice lacking the gene for fructokinase did not. This led the researchers to conclude that high-fat and high-sucrose diet did have negative effects on lipid accumulation in the liver and liver damage and that there was a key role for fructose (obtained from sucrose) in the development of fatty liver and non-alcoholic liver damage.

Ishimoto T, et al. (2013). High fat and high sucrose (western) diet induce steatohepatitis that is dependent on fructokinase. Hepatology, in press. doi: 10.1002/hep.26594

The second study took the advantage of the fact that high serum glucose levels lead to an increase in fructose generation in the liver. They were able to show that the mice that are unable to metabolize fructose were completely protected from an increase in food intake and body weight, obesity and fatty liver that occurred in normal wild type animals, after exposure to 10% glucose for 4 months (4).

Lanaspa MA, et al. (2013). Endogenous fructose production and metabolism in the liver contributes to the development of metabolic syndrome. Nature Communications, 4:2434. doi: 10.1038/ncomms3434

What did the European Food Safety Authority (Efsa) say about replacing sucrose and glucose with fructose?

The Efsa Panel stated that they

“…took into account that the few intervention studies in healthy and type 2 diabetic subjects provided to them showed a consistent significant reduction in post-prandial glycaemic responses, without disproportionally increasing post-prandial insulinaemic responses, following fructose consumption in foods or beverages compared with sucrose and glucose, and that the mechanism by which fructose (in place of sucrose or glucose) in food or beverages could exert the claimed effect is well established.”

In other words, Efsa made their decision based on a few studies using healthy subjects and those with type 2 diabetes, which suggested that following fructose consumption in foods and drinks (instead of sucrose or glucose) there was a significant decrease in glucose levels after a meal, without the side-effect of increased insulin levels, They concluded that, in light of these findings, the fructose benefit was evident.

However, just a couple of paragraphs later, they also put in a claim that these beneficial effects would be in those individuals who wish to reduce the high rise in glucose levels after a meal and that they are aware that consumption of fructose could lead to metabolic complications such as obesity and insulin resistance (one of the characteristics of type 2 diabetes).

“The target population is individuals who wish to reduce their post-prandial glycaemic responses. The Panel notes that high intakes of fructose may lead to metabolic complications such as dyslipidaemia, insulin resistance and increased visceral adiposity.”

It is not clear, however, how they will ensure that consumers are informed that increased fructose consumption in people who are overweight, obese or with any metabolic problems (such as type 2 diabetes, high blood pressure) may have the opposite effects.

How does the reporting compare to the evidence?

The studies cited by the Guardian join numerous previous publications and scientific studies in humans, rodents and cell culture models that suggest that fructose has negative effects and may be a contributing factor towards development of metabolic diseases. Thus, the Guardian article is correct in their report of many known negative effects of fructose consumption in our diet and the outrage at its labeling as a “health food”.