Sunday, October 31, 2010

Hepatic extraction of fructose

EDIT on 2nd March 2011. This post is incorrect! I'll leave it up as a reminder to myself to check all facts, even when net access is very limited. The pancreas monitors enteric glucose hormonally, not by direct access to the portal vein blood flow. It gets as much or as little fructose exposure as any organ than the liver. Mea culpa. The links are good, so the post has some use still. Thanks to Kurt for catching this one for me. END EDIT

OK, still no posting except for this brief note which is only delivered because the clocks changed, Daniel had a disturbed night and we both have been wake for several hours. Another heavy clinical week to come as of tomorrow... I publish the non-viagra comments on older posts by a brief mouse click but still don't get time to comment back and that will probably apply to this post too. That's just how it is at the moment. Tee hee, probably means there are a ton(ne) of typos in this post too!

Over the last few months I've tried to keep up with my favourite blogs (difficult because work blocks access to all blogs). Many people commented on the fructose and cancer article via Reuters. I'd just like to stick a few observations down about it and about hepatic fructose extraction.

Don over at Primal Wisdom has a nice post discussing the subject and its possible implications. But does fructose feed cancer in vivo? Does it even get to any cancer cells outside the liver and gut?

This led to a follow on post about hepatic fructose extraction, with a nice paper from Japan in Diabetes Care cited. It's unfortunate that ref 11 and ref 13 from this article are both unavailable, even in abstract form. One title specifies investigation of splanchnic blood levels of fructose, which is a very vague term but might include portal vein from gut to liver and might just, if we were lucky, include hepatic vein concentrations, which would allow us to see hepatic extraction rate and systemic penetration.

This would be nice as the second reference's title only seems to specify the role of the liver in the mop-up following intravenous fructose administration. Obviously intravenous fructose bypasses hepatic extraction, so it might not say too much about dietary fructose penetration in to the systemic circulation.

When we look at the micro molar concentrations of fructose (as opposed to milli molar for glucose) in serum as measured in DC article we are looking at venous samples. If the fructose in these samples has come from the diet in the gut it will have been fructose extracted by the liver, then pumped around the body, been fructose extracted by the tissues and only then finally arrived at the sampling needle. It looks like an open question how much fructose comes past the liver and hits the tissues themselves, to feed cancer cells.

You might get more information by measuring the arterial concentration of fructose, as opposed to the venous concentration. Arterial concentration is the hepatic vein fructose diluted in the the full venous return/cardiac output. This would give an indication of hepatic fructose passage without the complication of tissue extraction. But you can't have what's not in the paper and arterial blood samples are a little harder to obtain than venous samples!

EDIT: Cynthia found the abstract to the rat paper. Hepatic extraction is around 50-70%, this dilutes in the venous return but there is still a significant surge through the systemic circulation. This is particularly interesting as humans do metabolise fructose in their muscles, which might just have something to do with systemic as well as hepatic insulin resistance from fructose. I wish I had the time to follow these leads. Abstract text in the first comment. Ta Cynthia. END EDIT

The DC paper does suggest, among several explanations, that the higher venous fructose in diabetics might come from glucose via the polyol pathway. Glucose to sorbitol, sorbitol to fructose. This endogenously generated fructose then drops in to the venous system and gets sampled before going off to liver and/or muscles for metabolism.

So there are a lot of "if"s, "but"s and "maybe"s.

However, the cancer feeding effect of fructose was noted in pancreatic cells. Pancreatic cells sit in the portal vein to monitor gut glucose absorption. They also get hit by the full load of fructose arriving after a couple of cans of soda. It doesn't matter how much fructose the liver extracts if you happen to be a pancreatic cell sitting in the portal blood flow.

You get nuked.

If you are a pancreatic cancer cell you get fed.


BTW NAFLD has it's parallel in non alcoholic fatty pancreatic disease. Both go from normal through fatty infiltration to chronic inflammation to scarring to neoplasia. Both organs sit in the portal venous drainage from the gut. Another few posts there but...


Drs. Cynthia and David said...

Been missing your posts. Here's the abstract for no. 11:
The concentrations of fructose, glucose and lactate were measured in the hepatic portal vein, hepatic vein and systemic aorta of fed and fasting rats given a large meal of fructose by gastric intubation. The maximum concentration of fructose found in portal vein blood was within the range 20–40 mg/100 ml. The corresponding range in the systemic circulation was 2–6 mg/100 ml. A fractional hepatic fructose uptake of 54.9% and 71.5% was found in fed and fasting rats, respectively. Little fructose was removed by extrahepatic tissues. Fructose feeding lowered the concentration of glucose in the hepatic vein of fed animals but did not alter glucose concentrations in any other vessels sampled in fed or fasting rats. The absorption of fructose raised blood lactate concentrations in all vessels sampled of both fed and fasting animals. It is suggested that this effect is due to reduction in hepatic uptake of lactate. Fructose feeding did not increase lactate production by the intestine, neither was there any evidence of significant intestinal conversion of fructose to glucose.

Interesting point about fructose reducing liver lactate uptake. Wonder if that has any effect on athletic performance?


Peter said...

Thanks Cynthia, edit in place. The Tour de Francers certainly use fructose...

All the best


Dave Lull said...

Title: Role human liver assimilation intravenously administered fructose

Description: In 5 normal unanesthetized human subjects, the role of the liver in the metabolism of intraven. administered fructose was investigated by the hepatic vein catheterization technic. The following conclusions were drawn from the data obtained: (a) The removal of fructose by the splanchnic bed accounted for 32 to 48% of fructose infused. (b) During the fructose infusion the liver produced lactic and pyruvic acids which represented 20 to 50% of the fructose removed by the splanchnic bed. (c) The fate of the infused fructose was calculated as follows: removed by splanchnic bed, 32 to 48%, excreted in the urine, less than 4%, distributed in total body water, 36 to 49%, unaccounted for, 0. to 30%. In 4 anesthetized subjects undergoing upper abdominal operations, simultaneous sampling of aortic, superior mesenteric venous and peripheral venous blood showed that the splanchnic bed, exclusive of the liver, plays a minor, but not insignificant, role in the uptake of fructose, but does not contribute to the production of lactic and pyruvic acids.

blogblog said...

I'm sure Big Pharma is already developing a very expensive drug to block fructose uptake as we speak.

It is worth noting that cancers were non-existent amongst traditional Inuits eating fructose-free diets.

blogblog said...

I should have read the article first. It seems Big Pharma are already working on such a drug. I think it would be easier just to stop drinking the sugar water.

gooley said...

Interesting -- and annoying -- that the Reuters article mentions the high-fructose corn syrup ubiquitous as a sweetener in the US, but does not mention that sucrose is almost as good a source of fructose (HFCS is 55% fructose and sucrose about half). By omission they imply that sucrose isn't harmful.

blogblog said...

The most important point is that the equal amounts of glucose in sucrose and HFCS greatly increase fructose absorption. It would probably be better just to use half as much fructose (and a neutral bulking agent like methycellulose) instead of sucrose or HFCS in soda.

Owen said...

Anyone have an idea as to what's going on in this study Chris Masterjohn wrote about that shows fructose in honey to have less detrimental effects than other forms of fructose?

Here's his post about it on The Daily Lipid:

Could it simply be, as blogblog says, that honey has a higher proportion of fructose to glucose, so it tastes sweeter and less is absorbed. But then I would think that honey users would tend to experience more acute fructose intolerance (in the bathroom I mean) than you hear about, if malabsorbtion was an issue...

blogblog said...

Hi Owen, the body gradually becomes more efficient at transporting fructose across the gut as the dosage increases. The dose tolerance typically varies from 5-50g/day

blogblog said...

Honey is basically HFCS with some natural colours and flavours. It has a 1.15x as much fructose as glucose.

Anonymous said...

Honey is supposedly less detrimental because it has antibacterial properties. It's also full of salicylates. Things would be so much simpler if we just produced a pentase.

blogblog said...

The antibacterial properties of honey only work when it is applied topically. This is mostly due to reducing water activity. Similar result can be obtained using sugar syrups.

Allan Folz said...

Interesting about the pancreatic cancer. I wonder has anyone asked pancreatic cancer patients what their soda intake used to be?

Might that cut to the chase?

Unknown said...

Over the last few months I've tried to keep up with my favourite blogs (difficult because work blocks access to all blogs).

Use free logmein to access your home computer and surf the "forbidden" blogs from there.

blogblog said...

"Interesting point about fructose reducing liver lactate uptake. Wonder if that has any effect on athletic performance?"

Sports drinks always use glucose rather than sucrose as a carbohydrate source.

Steve said...

I think the point the Dr's where making was how does an already fructose damaged liver affect athletic performance due to reduced lactate uptake.
While many sports drinks are soley glucuse, there are also many examples that use both (or just sucrose in Australia), or just eating fruit as part of training/recovory/pre or post workout...?
What does that say about Phelps and his 'junk food' training diet, could he have done better considering his lactate oriented events?
Though the difference between calorie excess or restriction plays a large part in fructoses effects

Stipetic said...

If you could touch on fructose metabolism as it relates to the source (D- versus L-fructose), this might be helpful to many. Thanks.

karl said...

We have known from experiments during the Apollo program that fructose causes triglycerides to skyrocket. There is also the effect of backing up the liver with chronic fructose containing sugars to the point that blood fructose levels rise. The ability of fructose to form AGE is about 10 times that of glucose.

Cancers use a fermentation type of metabolism, thus high glucose levels aid in the speed of growth and give out immune systems less time to deal with the cancers before they are large enough to suppress the immune response. I would suspect that fructose and glucose levels are correlated and would confound causation of cancers.

I think there is evidence that fructose does increase oxLDL - and the inflammation cascade caused by oxLDL might be cancer causing.

I'm assuming you have seen Dr. Lustig's lecture here:

You might also be interested in this:

blogblog said...

athletes like Phelps have to live on high carbohydrate junk just to maintain their weight. There is simply no other viable option to get 12,000KCal/day.

It is probably impossible to eat a 12,000/day regularly on a VLC. You would need to eat well over 1kg of fat and 500g of protein. You would almost certainly suffer from chronic diarrhoea and acidosis.

4000KCal/day is probably the realistic long term upper limit on a VLC diet.

You must also remember that the physical activity levels of HGs are only around 1/4 to 1/3 of professional athletes.