Effects of fructose-containing sweeteners on fructose intestinal, hepatic, and oral bioavailability in dual-catheterized rats

Abstract

Objective: Fructose is commonplace in Western diets and is consumed primarily through added sugars as sucrose or high fructose corn syrup. High consumption of fructose has been linked to the development of metabolic disorders, such as cardiovascular diseases. The majority of the harmful effects of fructose can be traced to its uncontrolled and rapid metabolism, primarily within the liver. It has been speculated that the formulation of fructose-containing sweeteners can have varying impacts on its adverse effects. Unfortunately, there is limited data supporting this hypothesis. The objective of this study was to examine the impact of different fructose-containing sweeteners on the intestinal, hepatic, and oral bioavailability of fructose.

Methods: Portal and femoral vein catheters were surgically implanted in male Wistar rats. Animals were gavaged with a 1 g/kg carbohydrate solution consisting of fructose, 45% glucose/55% fructose, sucrose, glucose, or water. Blood samples were then collected from the portal and systemic circulation. Fructose levels were measured and pharmacokinetic parameters were calculated.

Results: Compared to animals that were gavaged with 45% glucose/55% fructose or sucrose, fructose-gavaged animals had a 40% greater fructose area under the curve and a 15% greater change in maximum fructose concentration in the portal circulation. In the systemic circulation of fructose-gavaged animals, the fructose area under the curve was 17% and 24% higher and the change in the maximum fructose concentration was 15% and 30% higher than the animals that received 45% glucose/55% fructose or sucrose, respectively. After the oral administration of fructose, 45% glucose/55% fructose, and sucrose, the bioavailability of fructose was as follows: intestinal availability was 0.62, 0.53 and 0.57; hepatic availability was 0.33, 0.45 and 0.45; and oral bioavailability was 0.19, 0.23 and 0.24, respectively.

Conclusions: Our studies show that the co-ingestion of glucose did not enhance fructose absorption, rather, it decreased fructose metabolism in the liver. The intestinal, hepatic, and oral bioavailability of fructose was similar between 45% glucose/55% fructose and sucrose.

Fig 1. Fructose intestinal, hepatic, and oral bioavailability.

F_a x F_g = intestinal availability or fructose absorption. F_h = hepatic availability. F = oral bioavailability.

Fig 2. Fructose serum concentration versus time profiles after oral administration of sugar-sweetened solutions.

A) Fructose concentrations in the portal vein over 6-hr. B) Fructose concentrations in the systemic circulation (femoral vein) over 6-hr. Wistar rats were gavaged with 1 mL of the following solutions: (C) Fructose, (D) 45/55 Glucose/Fructose, (E) Sucrose, (F) Glucose, and (G) Water. Portal serum concentrations are shown as closed symbols. Systemic serum concentrations are shown as open symbols. Data represents the mean ± standard deviation.

Fig 3. Effects of sugar-sweetened solutions after oral administration on fructose pharmacokinetic parameters.

(A) Portal fructose area under the curve (AUC_pv) (B), systemic fructose area under the curve (AUC_sys), (C) normalized portal fructose area under the curve (AUC_pv/D), (D) normalized systemic fructose area under the curve (AUC_sys/D), (E) adjusted portal fructose maximal concentration (AdjC_{max_pv}), (F) adjusted systemic fructose maximal concentration (AdjC_{max_sys}), (G) normalized adjusted portal fructose maximal concentration (AdjC_{max_pv}/D), (H) normalized adjusted systemic fructose maximal concentration (AdjC_{max_sys}/D), (I) portal fructose half-life (T_{1/2_pv}), and, (J) systemic fructose half-life (T_{1/2_sys}). 45/55 G/F = 45% glucose/55% fructose. P-value: * < 0.05, ** < 0.01, and *** < 0.001.

Fig 4

Effects of sugar-sweetened solutions after oral administration on (A) intestinal fructose bioavailability (F_a x F_g), (B) hepatic fructose bioavailability (F_h), and (C) systemic fructose bioavailability (F). 45/55 G/F = 45% glucose/55% fructose. P-value: * < 0.05, ** < 0.01, and *** < 0.001.