Adverse metabolic effects of dietary fructose: results from the recent epidemiological, clinical, and mechanistic studies

Abstract

Purpose of review: The effects of dietary sugar on risk factors and the processes associated with metabolic disease remain a controversial topic, with recent reviews of the available evidence arriving at widely discrepant conclusions.

Recent findings: There are many recently published epidemiological studies that provide evidence that sugar consumption is associated with metabolic disease. Three recent clinical studies, which investigated the effects of consuming relevant doses of sucrose or high-fructose corn syrup along with ad libitum diets, provide evidence that consumption of these sugars increase the risk factors for cardiovascular disease and metabolic syndrome. Mechanistic studies suggest that these effects result from the rapid hepatic metabolism of fructose catalyzed by fructokinase C, which generates substrate for de novo lipogenesis and leads to increased uric acid levels. Recent clinical studies investigating the effects of consuming less sugar, via educational interventions or by substitution of sugar-sweetened beverages for noncalorically sweetened beverages, provide evidence that such strategies have beneficial effects on risk factors for metabolic disease or on BMI in children.

Summary: The accumulating epidemiological evidence, direct clinical evidence, and the evidence suggesting plausible mechanisms support a role for sugar in the epidemics of metabolic syndrome, cardiovascular disease, and type 2 diabetes.

Figure 1. Effect of body weight gain on the changes of fasting cholesterol, LDL and apoB in subjects consuming sugar

Changes in fasting lipid outcomes in subjects who gained and did not gain body weight while consuming 25%E HFCS-, fructose-, or glucose-sweetened beverages for 2 weeks with ad libitum diets (*P < 0.05, **P < 0.01; 2 week vs baseline).

Figure 2. Two mechanisms by which sugar increases metabolic risk

Consumption of sugar increases risk for metabolic disease via the direct effects of fructose on lipid and carbohydrate metabolism. Consumption of sugar may also promote body weight gain. The increased body weight/adiposity further increases risk for metabolic disease. Thus consumption of sugar increases risk for metabolic disease both directly and via effects to promote weight gain.