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Article Fructose metabolism in humans-what isotopic tracer studies t...

Dear Andy,

In addition to the above cited excellent review (Sun and Empie 2012), I hope to help by giving a view on the topic. Fructose metabolism during exercise indeed remains questionable. However, the current best (and perhaps only) evidence remains the findings from the Ahlborg and Björkman 1990 work (see first link below).

In this experiment, they used a fructose infusion directly in the systemic circulation (bypassing splanchnic organs) and investigated fructose metabolism by arteriovenous catheterization in muscle and splanchnic beds during exercise and recovery. Muscle tissue (active and resting) was responsible for approx. 50% of fructose metabolism, with the splanchnic region (i.e. mainly the liver and kidneys) removing the other half.

Importantly, a couple of factors suggest that this 50% fructose being metabolized in muscle to be kind of a maximum value unlikely to be reached under normal conditions (i.e. with an oral load).

First, there is a competition between plasma glucose and fructose for access to muscle hexokinase (performing glu->glu-6p or fru->fru6p). Normally, glucose concentration is ten-fold higher than fructose in plasma (typically below 0.6 mmol/L after quite high oral fructose loads -see second link-) and hence more glucose is susceptible to be metabolized by hexokinase.

Second, and related, that competition also depends on the affinities of muscle hexokinase for both substrates, with the affinity for glucose being also higher than that for fructose (Km glucose > Km fructose). Altogether, both factors suggest that the plasma fructose of 4-5 mmol/L in that experiment strongly favored muscle fructose metabolism, and that muscle disposal would be lower under physiological concentrations (Ahlborg and Björkman 1990 mention this in their discussion).

Third, fructose having followed an oral route is considered to be almost entirely extracted by splanchnic organs (gut+liver may collectively extract close to 90% fructose). This is classically explained by the high affinity of fructokinase, a specialized enzyme only expressed in splanchnic organs (performing fru->fru-1p) and fructose would therefore hardly never reach the circulation as fructose, but rather be presented to muscle as newly formed lactate and glucose. Obviously, the use of a systemic infusion also bypassed this step, and still in that case this resulted in 50% fructose disposal being splanchnic (i.e. a "minimum" value).

Altogether and under normal conditions, oral fructose seems then very likely to be primarily metabolized in splanchnic organs (and hence the fru->fru-1p pathway being privileged), also during exercise, with important effects on glucose and lactate metabolisms (see third link).

Hoping to have helped, feel free to complement :)

Best,

Robin Rosset

PhD student - Luc Tappy's group

University of Lausanne, Switzerland

https://www.ncbi.nlm.nih.gov/pubmed/2262441

https://www.ncbi.nlm.nih.gov/pubmed/25100436

https://www.ncbi.nlm.nih.gov/pubmed/20826630