Health Implications of Fructose Consumption in Humans

Abstract

Fructose is a component of natural (sucrose) or industrial (high-fructose corn syrup) sugars. It has a caloric content similar to glucose and a higher sweetening power. All cells of the human body can use glucose as an energy substrate, and most can also use fatty acids. In contrast, most cells cannot use directly fructose, and this substrate needs first to be converted into lactate, glucose, or fatty acids in the gut, liver, and kidneys. Cells of these three organ express a set of fructolytic enzymes: fructokinase, aldolase B, and triokinase which convert fructose into two triose phosphate. Since there is no negative feedback on the activity of these fructolytic enzymes, the ingested fructose is almost completely and immediately metabolized in the gut and the liver. When a large amount of fructose is ingested, splanchnic organs are faced with an overproduction of triose phosphate, which they first release into the systemic circulation as lactate and glucose. When these pathways become saturated, fructose is converted into fatty acids through de novo lipogenesis, and newly synthetized fatty acids are either secreted into the blood as very low density lipoproteins – triglycerides – or temporarily stored as intrahepatic triglycerides. The metabolic fate of ingested fructose is dependent on whole body energy output. In resting conditions, glucose and lactate oxidation are limited by the low whole body energy expenditure, and excess fructose intake leads to a moderate increase in splanchnic glucose output to increased fasting and postprandial blood triglyceride concentration and to increased intrahepatic fat concentrations. During exercise, whole body energy output is high; fructose and glucose and lactate synthetized from glucose are essentially oxidized in skeletal muscle.