High fructose intake is associated with a number of metabolic disturbances. Elevated fructose levels cause rapid dephosphorylation of ATP in the liver, which increases levels of AMP deaminase and subsequent increases in uric acid production. Elevated uric acid levels are associated with increased risks for hypertension, gout, and renal impairment.
Although renal impairment itself appears to increase risk for elevated uric acid concentrations through decreased excretion, the effect of uric acid on metabolic syndrome begs the question of whether a causative effect exists between uric acid and subsequent renal impairment.
Recent animal models have shown that rats fed a high fructose diet and treated with allopurinol or benzbromarone did not develop hyperinsulinism, hypertension, hyperlipidemia, and excess bodyweight gain, whereas rats fed the same diet but not treated with allopurinol developed all of the aforementioned ailments (Am J Physiol Renal Physiol 2006;290:F625-631). These results would tend to indicate that elevated uric acid is a potential propagator of metabolic syndrome.
Uric acid mechanisms
Uric acid appears to reduce nitric oxide synthesis, an important regulator of blood pressure through endothelial vasodilation (Hypertension 2001;38:1101-1106). In addition, there appear to be stimulatory effects of uric acid on the renin-angiotensin system. A recent study found that in hypertensive adolescents, a reduction in uric acid levels normalized blood pressure (BP) in 66% of the participants compared with controls (JAMA 2008;300:924-932).
Furthermore, a two-week intervention with a high fructose diet led to increases in BP in 74 overweight subjects (Int J Obes 2010;34:454-461). These results were reversed after uric acid reducing agents were administered.
Fructose and CKD
Associations between chronic kidney disease (CKD) and elevated uric acid levels have been well established (Semin Arthritis Rheum 2013;42:551-561.
As stated previously, reduced ability to excrete uric acid may be one factor. It is important to note that genetic polymorphisms in renal uric acid excretion receptors can influence uric acid levels in individuals; those with improved uric acid clearance show a reduced response to OFTT on uric acid levels (Ann Rheum Dis 2013; published online ahead of print).
A recent intervention with an oral fructose load found a number of metabolic disturbances in CKD patients (Metabolism 2013; published online ahead of print). A 70 g oral fructose tolerance test found significant increases in uric acid levels in both renal transplant recipients (RTR) and non-RTR CKD subjects. Total cholesterol, LDL, HDL, and triglyceride levels increased significantly in the non-RTR CKD subjects, whereas the RTR subjects demonstrated increases in triglyceride values and decreases in total cholesterol, LDL, and HDL values.
Additionally, dialysis patients have been shown to have a reduced ability to clear both uric acid and fructose metabolites. Investigators found that hemodialysis patients’ uric acid levels remained elevated up to 240 minutes after ingestion of 190 mL cream and 75 g sucrose, whereas values peaked at 60 minutes in healthy controls (Scand J Clin Lab Invest 2013;73:154-160).
Of note, values were measured up to 240 minutes after ingestion. They remained elevated up to that point and still had not begun to decrease at the conclusion of measurements. These studies indicate that fructose is an important target for reduction in renal patients to decrease uric acid levels.
Foods high in fructose
When attempting to reduce fructose intake in the diet, the type of food and the portion must be considered. Most fructose sources generally have a varying content of fructose and glucose that approximate a 50/50 ratio and generally deviate within 10%.
The most notable source of fructose in modern diets is from high fructose corn syrup and sucrose. High fructose corn syrup may range in fructose content depending on production, but generally it contains 55% fructose. Sucrose is quickly converted in the body to its constituent sugars, thus effectively providing a 50% fructose content. Fruit sources and honey also contain a varying content of fructose and glucose that generally vary close to a 50/50 ratio with a 10% variation (assuming sucrose content is also a 50/50 ratio of glucose to fructose).
Reducing intake of added syrups and sugars in the diet is the most powerful method to reduce fructose intake. Sweetened beverages often provide the largest fructose dose in the general population. Fruit in its natural form can be an appropriate food when proper portions are considered, but the intakes of fruit juices or dried fruits can easily provide high sources of fructose through excessive portion intake.
Focusing one’s carbohydrate intake primarily on glucose sources, namely starches, would appear to be most beneficial in controlling fructose intake. In renal patients without elevated potassium, tubers such as potatoes and yams would appear to be an ideal source of carbohydrates due to their low fructose content and positive effect on potential renal acid load.