Recent studies suggest that specific types of macronutrients in the diet may have selective effects on nutrient absorption, insulin sensitivity, and lipid metabolism. Elucidation of the metabolic impact of specific dietary components may well result in improved efficacy of lifestyle approaches to reduce obesity and metabolic diseases. Despite similar fructose consumption, the phenotype of co-morbidities is different between African Americans and Latinos. Latino and Caucasian children manifest worsened dyslipidemia and non-alcoholic fatty liver disease (NAFLD), while African American children manifest worsened insulin resistance and hypertension. We have also documented in adults that a reduction in de novo lipogenesis (DNL; production of new lipids) in the liver and liver fat content, and improvement in hepatic insulin sensitivity were achieved by substitution of complex carbohydrate for fructose; but these changes appeared less dramatic in African American compared to Latino or Caucasian subjects. These divergent findings suggest ethnic and race-specific differences of fructose metabolism and disposition.