Challenging the Fructose Hypothesis: New Perspectives on Fructose Consumption and Metabolism123

The field of sugar metabolism, and fructose metabolism in particular, has experienced a resurgence of interest in the past decade. The "fructose hypothesis" alleges that the fructose component common to all major caloric sweeteners (sucrose, high-fructose corn syrup, honey, and fruit juice concentrates) plays a unique and causative role in the increasing rates of cardiovascular disease, hypertension, diabetes, cancer, and nonalcoholic fatty liver disease. This review challenges the fructose hypothesis by comparing normal U.S. levels and patterns of fructose intake with contemporary experimental models and looking for substantive cause-and-effect evidence from real-world diets. It is concluded that 1) fructose intake at normal population levels and patterns does not cause biochemical outcomes substantially different from other dietary sugars and 2) extreme experimental models that feature hyperdosing or significantly alter the usual dietary glucose-to-fructose ratio are not predictive of typical human outcomes or useful to public health policymakers. It is recommended that granting agencies and journal editors require more physiologically relevant experimental designs and clinically important outcomes for fructose research.