Initial fructose metabolism is thought to occur primarily in the liver. However Jang et al. (2018) demonstrate that in mice, it is the small intestine that is the primary site of fructose metabolism. This raises important questions about fructose and its metabolism in humans, as this will have implications for both health and sports.

Some global health guidelines are calling in recent years for reductions in fructose consumption (especially that added to ultra-processed products such as HFCS or simply by high sucrose consumption) as fructose has been identified as a primary candidate responsible for health problems. High fructose intake can stimulate endogenous glucose production and lipid synthesis, which can therefore increase fasting and postprandial blood glucose and triglyceride concentrations.

Jang et al. (2018) reveal that fructose is initially metabolized by the small intestine in mice (by 90%). The major pathways of fructose metabolism include conversion to glucose and conversion to lactate. Thus, in mice, dietary fructose intake is metabolized primarily by the small intestine, exposing the liver primarily to glucose and lactate.

In humans, even though having much less small intestine than mice in proportion to size, plasma glucose concentrations are known to remain very low in plasma after fructose consumption, even when consumed in large amounts. This is because much of the fructose is metabolized in the liver in humans.

On the other hand, the presence of specific fructose transporters and fructose metabolizing enzymes in skeletal muscle, brain, heart, adipose tissue and many other tissues has now been demonstrated. This suggests that fructose can be directly metabolized and play physiological or pathophysiological roles in extra-skeletal tissues. The fact that fructose can be directly metabolized in muscle tissue has important implications, especially in the sporting arena. However, tissues such as skeletal muscle have a low capacity for fructose metabolism, since the capacity for fructose uptake in this tissue is low (about 8 times less in relation to glucose), therefore, between the fact that little fructose reaches the muscle, due to the high splanchnic “sequestration” that this presents and this added to the low uptake of fructose by muscle tissue, the influence of this during exercise is not known.

The proportion of ingested fructose that reaches the systemic circulation is generally not measured. The aim of a recent study (Francey et al 2018) was to assess the amount of oral fructose that escaped first-pass splanchnic sequestration after ingestion of a fructose-glucose beverage.

The results indicated that a non-negligible fraction of fructose may escape splanchnic sequestration and circulate in the periphery, more than previously thought (15% approx), which may be a starting point for further investigation and perhaps rethinking some sports nutritional strategies in this regard.

On the other hand, the metabolic effects of direct fructose metabolism in extra-splastic tissues, and its relationship with metabolic diseases, have not yet been evaluated. It is noteworthy that high fructose diets can only negatively affect metabolism during positive energy balances (overfeeding) and chronically in sedentary subjects, something not remarkable in athletic subjects, which is another sign that the context and profile of the subject is key and must be taken into account before making general statements to the population. In fact, only modest amounts of exercise seem to be sufficient to counteract many negative effects of fructose, i.e. to have a high energy flow (Egli et al., 2013).

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