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I am Dr Luc Tappy, a physician and professor of physiology at the University of Lausanne in Switzerland. I took part in a symposium at the 51st European Association for the Study of Diabetes annual meeting[1] devoted to fructose and its potential deleterious effect. I had to address the question: Is fructose dangerous?

What Happens When You Eat Fructose?

But first, before attempting to answer this question, what is special about fructose? You have to remember that we eat about 50% of all energy as carbohydrates, which are composed of starch—a complex carbohydrate—and sugars. Starch should be the major part of our dietary carbohydrates. Once starch is digested, it is split into glucose molecules and absorbed into the blood as glucose.

The most common sugar is sucrose, a dimer of glucose and fructose. When one eats sucrose, it is split into glucose and fructose, both of which are absorbed into the blood.

All of an organism's cells can use glucose directly as an energy substrate, and most cells can also use fatty acids. But apart from glucose and fatty acids, most cells cannot use other energy substrates because they don't express the enzyme required for their metabolism.

In this case, the liver serves as a preprocessing organ that will convert this nutrient into glucose and fat. So, what happens when you eat fructose is that it gets metabolized in a two-step process. First, it will be converted into glucose or fat or both in the liver. Second, the liver will release glucose or fat in the blood to be used by other cells.

Does Fructose Lead to Weight Gain?

Now, does fructose—or does sugar—make you fat? The answer is difficult to address.

Obviously, you will become fat when your energy intake exceeds your energy expenditure. Fructose does not change your energy expenditure. So, if it does make you fat, it is because it makes you eat more. That's most likely not a metabolic effect but due to the hedonic properties of fructose. Fructose is a sugar, has a sweet taste, makes food palatable, and may lead to overeating.

Now, what evidence is there that fructose actually contributes to making you fat? There are many studies[2,3,4,5,6] that have looked at the relationship between sugar consumption or fructose consumption—or, more specifically, drinking sugar-sweetened beverages—and weight gain. All agree that sugar consumption is associated with weight gain over time. That does not mean that there is a causal effect, but the association is there.

Fructose and Insulin Resistance

Now, we may also consider the possibility that, independently of weight gain or energy balance, fructose may have deleterious metabolic effects. The first question we may ask is whether fructose would cause insulin resistance; and, if so, whether that insulin resistance, in the long term, would lead to the development of diabetes.

Insulin acts in several organs. To regulate glucose, it acts mainly in the liver and skeletal muscles. The effect of insulin in the liver is to inhibit glucose production. In normal subjects, you can see that after 4 or 5 days on a high-fructose diet, this effect is blunted, meaning there is some degree of hepatic insulin resistance. This insulin resistance is pretty mild and comes without any changes in blood glucose or insulin concentrations.

When you look at muscle insulin resistance—which is the hallmark of type 2 diabetes—you observe that even if you work with people with a high-fructose diet for up to 4 weeks, you don't have insulin resistance. That suggests that fructose is not directly involved in insulin resistance[7] but may be involved only when it is associated with weight gain.

Fructose, Lipid Metabolism, and CV Disease

The last questions would be: Does fructose alter lipid metabolism; and, if so, does it cause cardiovascular disorders through alteration of lipid metabolism?

These questions are the easiest to address because it has been known for at least 30 years that a high-fructose diet, or a high sugar-diet, increases blood triglyceride concentration. It increases fasting and postprandial triglyceride concentration. Many studies have shown that.[8,9,10]

We know from other studies that high blood triglyceride concentration can be a risk factor for the development of cardiovascular diseases. It makes us fear that a high-fructose diet may be a risk factor for cardiovascular diseases as well.

Finally, one more thing that we have recognized for over 20 years is that obesity and insulin resistance are strongly associated with fat accumulation in the liver, known as non-alcoholic fatty liver disease. What we have observed is that in healthy subjects fed with a high-fructose diet, there will be a doubling or tripling of intrahepatic fat within a few days.

There is clearly a concern that a high-fructose diet may favor the development of non-alcoholic fatty liver disease and possibly of metabolic disorders in the long term.

Conclusion

Sugar certainly plays a role in the development of obesity because, at least in Western countries, it's an important part of our diet. It has hedonic properties that favor overfeeding. In addition, it may have specific effects—mainly related to lipid metabolism—that may increase the risk for cardiovascular diseases in the long term.

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