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

Purpose of review— The effects of dietary sugar on risk factors and processes associated with metabolic disease remains 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 risk factors for cardiovascular disease (CVD) 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 non-calorically 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, CVD and 2 diabetes. evidence that sugar consumption is associated with metabolic disease. consuming excess with an libitum TG content, as previous an overfeeding to energy-balanced diets corroborate our previous observation that fructose consumption can increase visceral adiposity to sugar-sweetened beverage consumption impairs lipid metabolism promotes randomized This paper is important for demonstrating that a moderate dose of sucrose promotes a more adverse lipid profile in as little as 3 weeks. The results in this are important in that they demonstrate a moderate dose of fructose affects hepatic insulin sensitivity in as little as 3 weeks, and they also corroborate our previous suggestion that fructose induces hepatic insulin resistance prior to whole body insulin resistance (Stanhope, Curr Opin Lipidol, 2008). of of HFCS sweetened (>24 h) on risk factors. Lipid risk factors for CVD (LDL, ApoB and sdLDL) were elevated within 2 weeks of consuming fructose- or HFCS-sweetened beverages in (18-40 year and for variations in and physical activity, in the clinical center for 48 hour prior to the baseline and 2-week intervention blood collections that were analyzed for lipid outcomes. The results of this suggest that fructose may promote liver lipid accumulation both directly, via DNL, and indirectly, via DNL-induced inhibition of fatty acid This is the first study to measure and compare the 24-h uric acid profile following sustained consumption of fructose and glucose. The finding suggests that changes of 24-h uric acid exposure, which were markedly increased by only fructose, The results from this study suggest the possibility that prolonged consumption of fructose may contribute to the development of metabolic syndrome via induction of specific proinflammatory and prothrombotic mediators. The results from this suggest that may be more sensitive to the lipogenic effects fructose consumption without NAFLD. This blinded and randomized 18-month intervention comparing the effects of consuming one daily serving of SSB containing 104 kcals with one serving of non-caloric sweetened beverage in 641 children provides strong evidence that SSB promotes weight gain in children. It also suggests that strategies that target reduction of SSB consumption in children may be effective in lowering the prevalence of pediatric overweight and obesity. This study demonstrates that the metabolism of fructose through fructokinase C is necessary to generate adverse metabolic effects. It also demonstrates that when fructose flux through fructokinase C is increased due to knockout of fructokinase A, adverse metabolic effects of fructose exacerbated. suggests that ChREBP is involved The results of this study suggests that endoplasmic reticulum stress is associated with upregulation of DNL, rather than resulting from hepatic steatosis or insulin resistance. Thus, This provides evidence that SSB and high uric acid levels interact to produce more adverse effects in rats than either SSB or high uric acid levels alone. While these are important mechanistic results, they have potential clinical implications for hyperuricemic