Eucalyptus Inhibits Postprandial Hyperfructosemia 209 fructose as an internal standard [14]. By using this method, we found that the fasting SFCs in the samples derived from the cardiac (Study 1) and peripheral blood (Study 2) of rats were approximately 20 μmol/L at the baseline and nearly equaled previously reported fasting SFCs in humans [14, 22]. After oral sucrose administration, the SFC in the portal samples in the control group rapidly increased. In our study, ELE suppressed the increase in the SFC after sucrose admin- istration (Fig. 1A). The changes in the SFCs in the cardiac samples (Fig. 1B) were consistent with the changes in the portal samples (Fig. 1A); ELE also suppressed the elevation in the postprandial fructose concentrations in the cardiac samples. Since the SFCs in the portal and cardiac samples were highly correlated (Fig. 2), it was possible to evaluate the suppressive effect of ELE on the increase in postprandial blood fructose concentrations by using cardiac blood, which can be collected in large amounts (>1 mL). The increase in the peripheral SFCs in the ELE group was significantly lower than that in the control group (Fig. 3). Thus, the suppressive effect of ELE can also be evaluated by sampling peripheral blood. In contrast, the changes in the serum glucose concentrations in the cardiac and portal samples did not differ between the ELE and control groups during the 60-min oral sucrose-tolerance test (Fig. 1C and D). A previous study has reported that ELE does not inhibit intestinal glucose absorption in rats, and that it inhibits sucrase activity in vitro to a lower extent than other inhibitors such as (+)-catechin and (−)-epigallocatechin 3-O-gallate [13]. These results reinforce the hypothesis [13] that ELE specifically inhibits fructose absorption in the intestine. However, the possibility that ELE only delays fructose absorption in the intestine and has little effect on the total amount of absorbed fructose cannot be ruled out because we did not examine the area under the blood concentration-time curve of fructose in this study. Fructose transported to the liver is rapidly metabolized because the metabolic pathway involved bypasses the main rate-controlling step in glycolysis, which is catalyzed by 6- phosphofructokinase [23]. Consequently, the postprandial fructose concentrations in the peripheral blood are lower than the glucose concentrations [18, 19]. In the control group, the increase in the postprandial SFC in the peripheral samples (Fig. 3) was much lower than that in the portal samples (Fig. 1A). Therefore, we inferred that the liver actively metabolizes fructose. Further, we found that in the control group, the administration of sucrose at a dose of 2 g/kg body weight increased the peripheral SFC to more than 7-fold the fasting concentration. In human subjects, the SFC after the administration of fructose at a dose of 0.75 g/kg body weight has been reported to be approxi- mately 600 μmol/L [21]. In a previous study, we reported the case of a patient who had an SFC of 517 μmol/L because of excessive daily and long-term consumption of soft drinks Vol. 46, No. 3, 2010 [9]. It appears that a large amount of free fructose is released in the systemic circulation by the liver, without being metabolized. SFCs can significantly affect protein glycation [24] because fructose is more reactive than glucose in the Maillard reaction by at least 1 order of magnitude [25, 26]. Clinical and rodent studies have shown that dietary fructose consumption increases fructated advanced glycation end- products (AGEs) in serum and various tissues [27–29]. ELE may prevent such glycation by lowering postprandial eleva- tion of blood fructose concentration. The active ingredients of ELE have not yet been identified. Various components have been isolated from ELE such as hydrolyzable tannins [30–32], flavonol glycosides [32, 33], β-diketones [34], and phloroglucinol derivatives [35, 36]. ELE was solubilized in water and subjected to extraction with diethyl ether, ethyl acetate and n-butanol; the n-butanol extract inhibited intestinal fructose absorption (data not shown). We speculate that the active component(s) of ELE are not β-diketones because these compounds were not identified in our n-butanol extract. Further investigation is required to identify the substance(s) in ELE that inhibit intestinal fructose absorption. In conclusion, ELE can potentially prevent and treat disorders induced by excessive fructose intake. Further, the suppressive effect of ELE on the increase in postprandial blood fructose concentrations may be evaluated in human subjects by using peripheral blood samples. Acknowledgments A part of this research was supported by the research and development support program for regional revitalization in the food industry sector from the Ministry of Agriculture, Forestry and Fisheries, Japan. The other expenditure came from Nagaoka Perfumery Co. Ltd. Abbreviations HFCS, high-fructose corn syrup; ELE, eucalyptus leaf extract; SFC, serum fructose concentration; GC/MS, gas chromatography/mass spectrometry; HPLC, high-performance liquid chromatography; AGE, advanced glycation end-product. References [1] Havel, P.J.: Dietary Fructose: Implications for dysregulation of energy homeostasis and lipid/carbohydrate metabolism. Nutr. Rev., 63, 133–157, 2005. [2] Johnson, R.J., Segal, M.S., Sautin, Y., Nakagawa, T., Feig, D.I., Kang, D.H., Gersch, MS., and Sánchez-Lozada, L.G.: Potential role of sugar (fructose) in the epidemic of hyper- tension, obesity and the metabolic syndrome, diabetes,