Friday, August 20, 2010

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 (1820)."

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."


LeonRover said...


I looked at at the full study and found out about 1,5-AG (anhydro-glucitol), a marker for hyperglycemia above 180.

Good stuff!

kellgy said...

Fantastic find, and I have to say the information developing around sugars, including fructose, should bring to the surface improved treatments for diabetes and other debilitating diseases. At least one can hope.

LeenaS said...

Very interesting article, thanks.

However, I have two further questions:
- In what formation glucose is in the blood stream, when it is not as a free aldehyde?
- Since fructose is more reactive of the two, how big a proportion of is will end up circulating as a free aldehyde? While being less compatible with mammal metabolism, fructose still still a sugar, with normal sugar chemistry in a watery solvent (blood)?

With regards,

Peter said...

Hi Don,

It's also possible that a significant amount of fructose is formed by the polyol pathway through aldose reductase and sorbitol dehydrogenase. I have an observational paper correlating plasma fructose with diabetic retinopathy. They discussed this pathway as an explanation. Of course it might be fructose is a marker of activation of the polyol pathway not directly toxic to the retina itself... Of course direct fructose toxicity is an equally appealing explanation!


Helen said...

Hi Don,

This is interesting - and yet you still eat fruit? I remember your March 31 post defending low levels of fructose from fruit in a healthy diet. I found it reassuring. Do you still go by that?

Don said...

Hi Helen,

Yes, I still eat fruit. I don't think you can easily overload the liver system of fructose metabolism with moderate fruit intake.


I added myself to follow your blog. You are more than welcome to visit mine and become a follower if you want to.

God Bless You ~Ron

Valtsu said...

Just wondering...

In the comments of your post "Fructose Fact vs. Fiction" Ryan mentioned that there are two different fructose enantiomers, and L-fructose isn't quite natural. Maybe that synthetic L-form is the one that liver can't handle well, and natural sugars in fruits aren't so carsinogenic?

Hmm, I think it may be quite hard to find an answer to my question :S

Carlos Monteiro said...

Hi Don,
Studies have shown that the ingestion of glucose, fructose and other sugars may have the effect of raise blood lactic acid with this increase being most marked and lasting longest after fructose. Other studies have demonstrated that high-carbohydrate diets, including fructose, may keep the sympathetic nervous system overactive, leading in our view to raised levels of lactic acid in blood.
According Otto Warburg the malignant tumors frequently exhibit an increase in "anaerobic glycolysis" a process whereby glucose is used by cancer cells as a fuel with lactic acid as an anaerobic byproduct -- compared to normal tissues.
For references please read:
1. Carlos ETB Monteiro, Acidic environment evoked by chronic stress: A novel mechanism to explain atherogenesis. Available from Infarct Combat Project, January 28, 2008 at
2. Digitalis: The Insulin for Cancer? at
3. New Evidences: Acidity Theory of Atherosclerosis at