Fructose and Cardiometabolic Health: What the Evidence From Sugar-Sweetened Beverages Tells Us

Abstract

Recent attention has focused on fructose as having a unique role in the pathogenesis of cardiometabolic diseases. However, because we rarely consume fructose in isolation, the major source of fructose in the diet comes from fructose-containing sugars, sucrose and high fructose corn syrup, in sugar-sweetened beverages and foods. Intake of sugar-sweetened beverages has been consistently linked to increased risk of obesity, type 2 diabetes, and cardiovascular disease in various populations. Putative underlying mechanisms include incomplete compensation for liquid calories, adverse glycemic effects, and increased hepatic metabolism of fructose leading to de novo lipogenesis, production of uric acid, and accumulation of visceral and ectopic fat. In this review we summarize the epidemiological and clinical trial evidence evaluating added sugars, especially sugar-sweetened beverages, and the risk of obesity, diabetes, and cardiovascular disease and address potential biological mechanisms with an emphasis on fructose physiology. We also discuss strategies to reduce intake of fructose-containing beverages.

Keywords: cardiometabolic diseases; diabetes; fructose; obesity.

Figure 1. Fructose metabolism in liver cells

Fructose metabolism (grey arrows) differs from glucose (black arrows) due to 1) a nearly complete hepatic extraction and 2) different enzyme and reactions for its initial metabolic steps. Fructose taken up by the liver can be oxidized to CO₂ and then converted into lactate and glucose; glucose and lactate are subsequently either released into the circulation for extrahepatic metabolism or converted into hepatic glycogen or fat. The massive uptake and phosphorylation of fructose in the liver can lead to a large degradation of ATP to AMP and uric acid. From: Physiol Rev 90: 23–46, 2010; doi:10.1152/physrev.00019.2009.

Figure 2. Central Illustration: Fructose and Cardiometabolic Health: Sugar-Sweetened Beverages

Putative biological mechanisms linking excess sucrose and HFCS intake from sugar sweetened beverages to the development of obesity, gout, diabetes and cardiovascular disease. Excess calories, incomplete compensation for liquid calories and high glycemic load lead to obesity. Increased diabetes and cardiovascular disease risk also occur independent of weight through adverse glycemic effects and increased fructose metabolism in the liver. Excess fructose ingestion promotes hepatic uric acid production, de novo lipogenesis, accumulation of visceral adiposity and ecopic fat, which ultimately increase diabetes and cardiovascular disease risk. HFCS, high fructose corn syrup.