Metabolic syndrome and diabetes are main health problems of modern life in the twenty-first century. Alarming ratios of global prevalence lead to conduct more and more researches about etiological factors and pathogenesis. Disease mechanism is elementary for advancing more efficient and practicable treatment methods. Concurrent increase in both fructose consumption with Western diet and metabolic syndrome has revealed fructose hypothesis that suggests fructose as one of etiological factor of metabolic syndrome (insulin resistance, central obesity, hypertension, etc.). Recent studies have increasingly lightened the unknowns about role of fructose on pathogenesis. This review discusses fructose hypothesis by exploring current studies and their results in wide perspective. Potential mechanisms covering low-grade inflammation or de novo lipogenesis, etc., in the development of insulin resistance and obesity are explained. Clinical trials have revealed connection of fructose-induced hyperuricemia with insulin resistance and chronic inflammatory state leading to hepatosteatosis or obesity. Further, novel hypothesizes suggesting role of fructose-induced modifications in epigenetics, gut microbiota and oxidative stress on disease pathogenesis are reviewed based on recent clinical trials. More innovative theories including fructose-induced malignancy; decreased satiety feeling, and unfavorable bone health are argued covering fructose-induced neurotransmitter changes in central nervous system, more aggressive malignancy phenotype and impaired calcium absorption.
Keywords: Cardiovascular disease; Fructose; Hypertension; Kidney disease; Obesity.