Fructose Feeds Cancer Follow-up: Is all fructose metabolized in the liver?

In response to my posting entitled Fructose Feeds Cancer, which referred to the Reuters story entitled Cancer Cells Slurp Up Fructose, some commenters on my blog and other bloggers have stated that fructose gets metabolized by the liver so doesn't make it into the blood stream and couldn't promote cancer anywhere but in the liver. 

I dissented and today took a moment to search for studies measuring fructose concentrations in the blood.  My first find was Increased Fructose Concentrations in Blood and Urine in Patients With Diabetes published in Diabetes Care.  From the abstract:

"Serum fructose concentrations in patients with diabetes (12.0 ± 3.8 μmol/l) were significantly higher than those in healthy subjects (8.1 ± 1.0 μmol/l, P < 0.001) and nondiabetic patients (7.7 ± 1.6 μmol/l, P < 0.001), and daily urinary fructose excretion was significantly greater in patients with diabetes (127.8 ± 106.7 μmol/day) than in nondiabetic patients (37.7 ± 23.0 μmol/day, P < 0.001)."

So there you have it.  Non-diabetics, healthy subjects, and diabetics all have fructose in serum, with the diabetics carrying an average of about 50% more fructose in serum than healthy subjects. 

If you read the full text, you will learn that inadequate technology once made detection of fructose in serum difficult, and the authors of this study overcame that limitation.  You will also see this discussion of several mechanisms which might explain increased fructose in serum of diabetics:

"First, impaired fructose metabolism in the liver might play an important role, given that several studies have shown that the liver metabolizes at least half of all fructose (11,13). Second, the transport system for fructose might be disrupted. Fructose is transported into the liver, at least in part, by the same system as glucose and galactose (14,15). In adipocytes, fructose can enter by at least two different carriers. Hajduch et al. (16) reported that GLUT5 was responsible for mediating ∼80% of the total cellular fructose uptake, whereas the remaining 20% was cytochalasin B-sensitive, which most likely reflects transport via GLUT1 and/or GLUT4. Third, the polyol pathway might play a role in the increment of serum and urinary fructose concentrations. This pathway reportedly contributes to increased fructose concentrations in many tissues of patients with diabetes (17) and diabetic animals (18–20)."

Notice that the authors say "the liver metabolizes at least half of all fructose,"  not "the liver metabolizes all of ingested fructose."  Also, they cite four studies that found increased fructose concentrations in "many tissues" of diabetic humans and animals.  To get to those tissues it had to go through the blood from the gut.  These findings clearly indicate that the development of diabetes involves a rise in serum and tissue levels of fructose, providing fuel for cancer proliferation in affected tissues.  And we don't have to eat an diet of 100% fructose to get this result.  

Some might scoff at the micromolar concentrations but the authors also point out that fructose is so much more reactive than glucose that it has comparable pathological effects even at these very low concentrations:

"Although glucose circulates in millimole concentrations, only ∼1/1,000 molecules circulates as a free aldehyde and can therefore participate in glycation reactions. Fructose, although circulating in micromole concentrations, is much more reactive in this regard and, therefore, may be comparable to glucose in terms of mediating pathology through nonenzymatic reactions and downstream processes."