At high intake, fructose is more harmful than glucose: it raises triglycerides, abdominal fat, liver fat and uric acid to a greater degree. Compared with regular sugar (sucrose, which is half fructose), however, the difference at moderate doses has not been clearly demonstrated in humans. The form of consumption (drinking versus eating) appears to be at least as important as the type of sugar.
Fructose and regular sugar (sucrose) are closely related: sucrose is half fructose and half glucose. The key difference lies in how the body processes them. Glucose is taken up by virtually all cells in the body, whereas fructose is processed almost entirely by the liver. There, the liver can convert fructose into fat, triglycerides and uric acid. Randomised trials show that fructose, compared with glucose, leads to higher triglycerides, more abdominal fat, more fat in the muscles and more liver fat. Glucose does not do this to the same extent1.
At chronically high doses, fructose is clearly harmful in animal models: it causes insulin resistance, obesity, type 2 diabetes and high blood pressure. In humans the evidence is less convincing, but disturbed blood lipids (dyslipidaemia) and reduced hepatic insulin sensitivity have also been demonstrated at high intake levels. At moderate doses there is no consistent evidence of direct harm in humans2.
A specific risk of fructose is an increase in uric acid in the blood. When processing fructose, the liver consumes ATP (the energy molecule), which produces uric acid as a by-product. In men this is associated with an increased risk of gout1,3. This risk is smaller with regular sugar and virtually absent with pure glucose.
In animal models, fructose also promotes the development of non-alcoholic fatty liver disease (NAFLD). Whether this translates directly to humans remains uncertain due to the limitations of animal models4. Mouse studies have also shown that the form in which sugar is consumed, drinking versus eating, matters more than the type of sugar: liquid sugar led to greater calorie intake and more liver fat accumulation than the same amount of solid sugar5. This is relevant because both fructose and regular sugar are commonly found in soft drinks.
For the comparison of high-fructose corn syrup (HFCS, the widely used sweetener in soft drinks) with regular sugar, there is no direct evidence that HFCS has more severe metabolic consequences than sucrose. Both contain similar ratios of fructose and glucose2. The epidemiological association between sugar-sweetened beverages in general and higher body weight, cardiovascular disease and metabolic disorders has been demonstrated for both types2,1. Finally, there is an interesting nuance for people with type 2 diabetes: fructose produces a smaller blood glucose spike directly after a meal than regular sugar or HFCS. However, measured over three hours, the total difference is not statistically significant, so this advantage is limited6.
All claims are based on one review article (PMID 20086073), supplemented by several experimental and clinical studies (PMID 23493538, 3891268, 25010715, 34359974, 7443098). Most of the human evidence is moderate in strength; strong evidence comes almost exclusively from animal models.