Fructose metabolism

Toxic effects of fructose metabolism

Pawel Malczewski
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Fructose and glucose are the most commonly consumed simple sugars. They have the same amount of calories per gram, but differ greatly in the way they are broken down. (1)Vos MB, Lavine JE. Dietary fructose in nonalcoholic fatty liver disease. AASLD. Hepatology. Volume 57, Issue 6 June 2013 Pages 2525–2531. Available here. (2)Bray GA. How bad is fructose? Am J Clin Nutr October 2007. Vol. 86 no. 4 895-896. Available here.

As a result of sugar breakdown, harmful substances are formed in varied quantities depending on the sugar that is metabolized and its quantity.

Fructose metabolism produces not only a higher amount of harmful substances than glucose, but some of the most harmful ones are produced by fructose and not by glucose metabolism.

Please note that the harmful effects of fructose metabolism refer to high sugar diets consisting of sweetened beverages, fruit juices, and other products with added sugars.

Although fruit contain sugars, fructose from obtained from consumption of moderate amounts of whole fruit as a part of a balanced diet is well handled by the liver and doesn’t produce the harmful effects. On the contrary, consumption of moderate amounts of fruit has been shown to improve cardiovascular health.

It is all in numbers

While glucose is mostly used by the cells in the body for energy production and storage, fructose is mostly metabolized in the liver.

This means that much higher amounts of fructose go through the liver metabolic processes producing more of these substances.

Products of fructose metabolism

Energy production
Some of the fructose is converted to energy (ATP), which is essential for the cells to perform their day to day functions.

Uric acid production
Fructose metabolism produces uric acid. Uric acid blocks the enzyme that produces nitric oxide, responsible for lowering blood pressure. In other words, high amounts of dietary fructose lead to an increase in blood pressure.

Increased amount of uric acid also causes gout.

Fat production
Some fructose is converted by the liver cells’ mitochondria to a substance called citrate which is used for lipid production.

Since most of the consumed fructose goes through the liver cells, the amount of citrate produced and released from mitochondria is quite high and certainly higher than in the case of glucose metabolism. Some of the citrate is then converted to free fatty acids, which are released from the liver to circulation and absorbed by the muscle cells, causing muscle insulin resistance. Some of the citrate-generated fats, called lipid droplets, will remain in the liver.

Frequent production of high amounts of lipid droplets lead to a non-alcoholic fatty liver disease.Another fructose metabolism by-product is Xylulose-5-phosphate. It stimulates the fat making enzymes.

An overload of citrate released from mitochondria, and the abundance of the fat-making enzymes produce much higher amounts of VLDL amounts than in the glucose metabolism.

Since high lipid contents lead to liver disease, for self-preservation the liver releases the excess lipids to the bloodstream causing dyslipidemia.

Pro-Inflammatory substances
The by-products of fructose metabolism in the liver cells forms a substance called JNK1, responsible for inflammation and liver insulin resistance.

References   [ + ]

1. Vos MB, Lavine JE. Dietary fructose in nonalcoholic fatty liver disease. AASLD. Hepatology. Volume 57, Issue 6 June 2013 Pages 2525–2531. Available here.
2. Bray GA. How bad is fructose? Am J Clin Nutr October 2007. Vol. 86 no. 4 895-896. Available here.