Health outcomes of a high fructose intake: the importance of physical activity

J Physiol 597.14 (2019) pp 3561–3571

Luc Tappy and Robin Rosset

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  • 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
  • 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.