beta-D-fructose

Acute consumption of fructose or high fructose corn syrup is essentially non-toxic. Chronic, excess fructose consumption has been shown to be a cause (or indirect cause) of gout, insulin resistance, hypertension, obesity, fatty liver disease, elevated LDL cholesterol and elevated triglycerides, leading to metabolic syndrome. In Wistar rats, a laboratory model of diabetes, 10% fructose feeding as opposed to 10% glucose feeding was found to increase blood triglyceride levels by 86%, whereas the same amount of glucose had no effect on triglycerides. A 2008 study found a substantial risk of incident gout associated with the consumption of fructose or fructose-rich foods. It is suspected that the fructose found in soft drinks (e.g., carbonated beverages) and other sweetened drinks is the primary reason for this increased incidence.

Fructose is distinct from other sugars in its ability to cause intracellular ATP depletion, nucleotide turnover, and the generation of uric acid. Uric acid is generated via fructose due to its rapid phosphorylation (to fructose-1-phosphate) in the liver, leading to a rapid drop in free phosphate and ATP. This drop in ATP leads to the stimulation of adenosine monophosphate (AMP) deaminase which deaminates AMP to produce IMP, which is subsequently converted to uric acid (A15346). Uric acid is normally an anti-oxidant but without sufficient amounts of ascorbic acid (vitamin C) present in the plasma, it functions as a pro-oxidant. Because many soft drinks and foods that are sweetened with high fructose corn syrup do not contain vitamin C, the resulting uric acid can lead to a number of harmful effects, including gout, chronic inflammation, hypertension, increased adiposity, fatty liver disease and obesity (A15346). Many studies have shown that elevated uric acid levels are associated with several metabolic and cardiovascular conditions, including diabetes and coronary artery disease (A15346). Elevated serum uric acid has also been shown to be the most reliable predictor for the development of hypertension and incident renal disease (A15347) as well as fatty liver disease (A15348). Fructose-induced uric acid generation also causes mitochondrial oxidative stress that stimulates fat accumulation independent of excessive caloric intake (A15349). Several studies have demonstrated that oxidative stress is one of the earliest phenomena observed in vascular, renal, liver cells and adipocytes exposed to uric acid (A15347). High fructose consumption is also associated with more severe depletion of liver ATP, which may impair liver "energy balance”. High-fructose beverages have also been shown to lead to lower circulating insulin and leptin levels, and higher ghrelin levels. Since leptin and insulin decrease appetite and ghrelin increases appetite, some researchers suspect that eating large amounts of fructose increases the likelihood of weight gain.

Consuming more than 100 g a day of pure fructose may lead to a modest but statistically significant rise in body weight of 0.44 kg a week. Consuming 100 g or more of fructose a day also significantly increases fasting levels of serum triglycerides. LD50: 15000 mg/kg (intravenous, rabbit)

Free fructose is absorbed directly by the intestine. When fructose is consumed in the form of sucrose, it is digested (broken down) and then absorbed as free fructose. Fructose absorption occurs on the mucosal membrane via facilitated transport involving GLUT5 and GLUT2 transport proteins. Fructose is phosphorylated in the liver by fructokinase (Km= 0.5 mM). Fructokinase initially produces fructose 1-phosphate, which is split by aldolase B to produce the trioses dihydroxyacetone phosphate (DHAP) and glyceraldehyde. DHAP is then converted to glycerol-3-phophate which stimulates production of triglycerides. Nearly half (45%) of all pure fructose consumed is used up within 3-6 hours by the body for energy. If fructose is consumed with glucose (as it typically is in nature), up to 66% of it is used for energy within the same time frame. Roughly a third (29%) to a half (54%) of all fructose consumed is converted to glucose. Less than 1% of fructose appears to be directly converted to triglycerides.