J Physiol 597.14 (2019) pp 3561–3571
Luc Tappy and Robin Rosset
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
- 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.
of the aforementioned effects can be prevented when high fructose intake
is associated with increased levels of physical activity.
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.
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.
total energy output is low, however, the mismatch between fructose input
and energy output forces the diversion of some fructose into lipids.
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.
is also evidence that, during exercise, fructose carbons are efficiently
transferred to skeletal muscle as glucose and lactate to be used for
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.