The extra-splanchnic fructose escape after ingestion of a fructose-glucose drink: An exploratory study in healthy humans using a dual fructose isotope method

Abstract

Background & aims: The presence of specific fructose transporters and fructose metabolizing enzymes has now been demonstrated in the skeletal muscle, brain, heart, adipose tissue and many other tissues. This suggests that fructose may be directly metabolized and play physiological or pathophysiological roles in extra-splanchnic tissues. Yet, the proportion of ingested fructose reaching the systemic circulation is generally not measured. This study aimed to assess the amount of oral fructose escaping first-pass splanchnic extraction after ingestion of a fructose-glucose drink using a dual oral-intravenous fructose isotope method.

Methods: Nine healthy volunteers were studied over 2 h before and 4 h after ingestion of a drink containing 30.4 ± 1.0 g of glucose (mean ± SEM) and 30.4 ± 1.0 g of fructose labelled with 1% [U-¹³C₆]-fructose. A 75%-unlabeled fructose and 25%-[6,6-²H₂]-fructose solution was continuously infused (100 μg kg^-1 min^-1) over the 6 h period. Total systemic, oral and endogenous fructose fluxes were calculated from plasma fructose concentrations and isotopic enrichments. The fraction of fructose escaping first-pass splanchnic extraction was calculated assuming a complete intestinal absorption of the fructose drink.

Results: Fasting plasma fructose concentration before tracer infusion was 17.9 ± 0.6 μmol.L^-1. Fasting endogenous fructose production detected by tracer dilution analysis was 55.3 ± 3.8 μg kg^-1min^-1. Over the 4 h post drink ingestion, 4.4 ± 0.2 g of ingested fructose (i.e. 14.5 ± 0.8%) escaped first-pass splanchnic extraction and reached the systemic circulation. Endogenous fructose production significantly increased to a maximum of 165.4 ± 10.7 μg kg^-1·min^-1 60 min after drink ingestion (p < 0.001).

Conclusions: These data indicate that a non-negligible fraction of fructose is able to escape splanchnic extraction and circulate in the periphery. The metabolic effects of direct fructose metabolism in extra-splanchnic tissues, and their relationship with metabolic diseases, remain to be evaluated. Our results also open new research perspectives regarding the physiological role of endogenous fructose production.

Keywords: Fructose metabolism; Human physiology; Isotope tracers.