Few modern studies have compared the long-term effects of glucose, fructose, and starch under physiologically relevant condition, and such research should assume high priority. The available evidence suggests 3 key points. First, fructose in its primary natural form (whole fruit) is not associated with adverse effects up to the limits of human consumption. Second, excessive intake of refined sugar plays a significant role in the epidemics of obesity and related diseases, in part because large amounts of rapidly absorbed fructose can overwhelm hepatic biochemical pathways. Third, rapidly absorbed forms of glucose—present in both sugar and high glycemic index starch—also contribute importantly to these diseases, especially considering their much greater caloric contribution to typical diets than fructose. Therefore, the recommendation to replace fructose with glucose lacks an evidence basis. Rather, public health efforts should focus on reducing intakes of all highly processed carbohydrates, not just refined sugar./.../