The metabolic toll of sweetness: fructose and the global rise in childhood health risks. A critical review

As the global rise in pediatric metabolic dysfunction con­ti­nues, mounting evidence implicates excessive intake of added sugars – particularly fructose – as a primary me­ta­bo­lic disruptor. This critical review examines the metabolic im­pact of high fructose intake during childhood, drawing from current findings in nutritional biochemistry, pediatric en­do­cri­no­logy and public health. Unlike glucose, fructose is primarily metabolized in the liver, where it bypasses key regulatory steps of glycolysis, leading to unregulated phos­pho­ry­la­tion by ketohexokinase C (KHK-C). This drives rapid ATP depletion and uric acid production, initiating mi­to­chon­drial dysfunction, oxidative stress and de novo li­po­ge­ne­sis. These processes contribute to the early onset of metabolic syndrome, serving as initiating mechanisms for the development of insulin resistance, visceral adiposity, he­pa­tic steatosis and metabolic dysfunction – associated stea­to­tic liver disease (MASLD). Furthermore, fructose me­ta­bo­lism promotes systemic inflammation through immune ac­ti­va­tion, oxidative stress and gut microbiota disruption, fac­tors that amplify the metabolic dysfunction and the long-term disease risk. Fructose has also been implicated in neu­ro­in­flam­ma­tory pathways, altered appetite regulation and intestinal barrier impairment. This review underscores the need for early intervention strategies, including sugar ta­xa­tion, improved food labeling, nutritional education and clinical counseling. Reducing pediatric fructose ex­po­sure represents a critical, equity-driven priority for mi­ti­ga­ting long-term metabolic risks and for promoting po­pu­la­tion health.