J Physiol 597.14 (2019) pp 3561–3571
Luc Tappy and Robin Rosset
- To draft an overview of fructose metabolism, focusing on its potential detrimental effects for health on one hand, and on its potential beneficial effects during exercise on the other, and to propose a simple model to account for the interactions of dietary fructose intake and physical activity on fructose-related cardio-metabolic risk factors.
- Fructose metabolism is generally held to occur essentially in cells of the small bowel, the liver, and the kidneys expressing fructolytic enzymes (fructokinase, aldolase B and a triokinase).
- In these cells, fructose uptake and fructolysis are unregulated processes, resulting in the generation of intracellular triose phosphates proportionate to fructose intake. Triose phosphates are then processed into lactate, glucose and fatty acids to serve as metabolic substrates in other cells of the body.
- With small oral loads, fructose is mainly metabolized in the small bowel, while with larger loads fructose reaches the portal circulation and is largely extracted by the liver. A small portion, however, escapes liver extraction and is metabolized either in the kidneys or in other tissues through yet unspecified pathways.
- In sedentary subjects, consumption of a fructose-rich diet for several days stimulates hepatic de novo lipogenesis, increases intrahepatic fat and blood triglyceride concentrations, and impairs insulin effects on hepatic glucose production.
- No methodology was reported in this review.
- All of the aforementioned effects can be prevented when high fructose intake is associated with increased levels of physical activity.
- In conditions of low fructose intake, available data suggest that fructose is primarily metabolized in the gut and, to a lesser extent, in the liver. Fructose metabolized in these organs then recirculates as glucose and lactate intermediates to be distributed to the periphery.
- With increasing fructose intake, intestinal fructose metabolism becomes saturated and fructose is mostly extracted by the liver where it is converted into metabolic intermediates. When total energy output is high, fructose conversion into glucose and lactate remains the preferred, most energy-efficient disposal routes as both intermediates can provide energy to working muscle.
- When total energy output is low, however, the mismatch between fructose input and energy output forces the diversion of some fructose into lipids.
- According to the proposed model, fructose’s deleterious effects on health would only appear in conditions of chronically high fructose intake associated with low physical activity.
- There is also evidence that, during exercise, fructose carbons are efficiently transferred to skeletal muscle as glucose and lactate to be used for energy production.
- Glucose and lactate formed from fructose can also contribute to the re-synthesis of muscle glycogen after exercise.
- The authors therefore propose that the deleterious health effects of fructose are tightly related to an imbalance between fructose energy intake on one hand, and whole-body energy output related to a low physical activity on the other hand.
- The modern human lifestyle is associated with readily available foods and a low physical activity, and hence with a lower need of nutrients targeted for physical activity such as fructose. This imbalance may possibly explain the risks of adverse effects related to current fructose consumption.