Friday, March 06, 2009

Fructose, Glucose and Cholesterol

This paper came my way via Eddie Vos, through a discussion in the THINCS group.

OK, what's going on in the paper? It's the metabolic ward study to end all metabolic ward studies. Routine criminals who volunteered to live in a "food proof" prison and to eat a diet based on pure chemicals. This is a prison within a prison:

"The described study was conducted in an especially isolated wing of the California Medical Facility (CMF), a state institution for adult male felons. The isolated area included large indoor recreation, lounge, and shower areas, and 24 individual cells, and was so located as to prevent completely the passage of any food through or near the area."

And what yummy food did the inmates receive?

"These diets were unique in that a) their essential and nonessential nitrogen source was provided exclusively in the form of optically pure L-amino acids and b) they were administered as single, crystal clear aqueous solutions that were nutritionally complete in themselves. In essence, the diets were composed of balanced (but varying) proportions of L-amino acids, the required water-soluble and fat soluble vitamins, the pertinent mineral salts, glucose or other simple sugars as the source of carbohydrate, and ethyl linoleate as the source of essential fat."

Apparently the various versions of the diet all tasted disgusting, for want of a better word.

Apart from the interest of human experiments along these lines, there were a few other tweaks they applied. First we have to note that these diets were essentially ultra low fat diets, the same family as the diets used by McDougal and co. There is not a grain of white rice which does not end up as blood glucose. If you eat brown rice there is a split between the fibre and the minerals it is depriving you of (you know where they get flushed) and the starch, which ends up as blood glucose. So these are seriously low fat, high carbohydrate diets.

What happens when you feed an elemental diet based on glucose alone as its calorie source? Blood cholesterol drops, from a normal value found in a non statinated male of 227mg/dl (while eating 1970s style prison food), to a cardiologic near Nirvana of 160mg/dl. Replacing 25% of the glucose with sucrose produces a rise in cholesterol to 208mg/dl. Removing the sucrose and going back to pure glucose drops the cholesterol level back down to 151mg/dl.

Is that good or bad? You need to remember the old adage that the best cholesterol level is one that has not been measured. But what is happening probably goes back to that short section of the ApoB100 protein which glycates particularly easily, discussed here. I think it is worth pointing out again that fructose should never penetrate in to the systemic circulation, so its whole body damage should be indirect. It probably does this through the induction of hepatic insulin resistance. Fructose has to be metabolised immediately and the end result is raised intracellular hepatic triglycerides. We've seen before that a decent supply of intra cellular lipid makes a cell say no to glucose and that it does this by exhibiting insulin resistance. The liver normally stores glucose in response to insulin. Rendering it insulin resistant would logically stop it storing glucose and pour the stuff out in to the systemic circulation...

That's the basis of this post and it needs bearing in mind when we look at cholesterol variation and heart disease with a given population. But there's an aside first that really creased me up...

A quick pubmed looking for a reference to fructose and insulin resistance (there are hundreds) produced this gem, hot out of cyberpublishing a few days ago.

The group used an antisense oligonucleotide, which is a short section of DNA, RNA or a similar synthetic drug which specifically blocks the activity of a corresponding section of messenger RNA, which means the the relevant gene no longer gets successfully transcribed. By doing this they turned off lipid synthesis in the liver in response to fructose. No hepatic insulin resistance despite fructose intake: Wow!!!!!!!!!! Take this drug and you too can drink Pepsi Max without turning your liver in to foie gras. What else does it do? Oh, it lowers insulin resistance, whole body! Superb, give me some.

Oh oh, it's your butt which soaks up the plasma glucose... As they say of their own technique, it resulted in:

"increased insulin-stimulated whole-body glucose disposal due to a threefold increase in glucose uptake in white adipose tissue"

Translation: "our wonder drug makes you fat".

It is also described as a potential "treatment of NAFLD, hypertriglyceridemia, and insulin resistance associated with increased de novo lipogenesis", I would add "by making you fat". I'd also add that this de novo lipogenesis can easily be avoided by avoiding the fructose in the first place.

What is not remotely obvious from the abstract is: Where does the fructose go to, if it's not used to converted your liver to foie gras?

I guess it's either going to glycosylate your liver (sounds great for longevity) or spill in to your systemic circulation, where it can glycosylate whatever it come in to contact with.... Or it might just overload each liver cell with more pyruvate than it knows what to do with. Now there's grist for the mill of unintended consequences!

Back to the real world:

A fructose intake of 12% of your calories makes your metabolism unhappy enough that it has evolved a technique to increase cholesterol levels under these rather rare (until recent times) conditions. It probably has knock on effects through hepatic insulin resistance resulting in hyperglycaemia and all of the damage that this leads to.

While some fructose is perfectly OK (I too eat home grown fruit in season and a certain amount of sucrose) I suspect a large amount is not OK.

Under highly defined conditions, fructose raises your total cholesterol level.


EDIT: Sue has pointed out, off blog, that the other reason for a fall in cholesterol is due to minimal production of triglycerides. If glucose is being consumed within the ability of the liver to store it as glycogen there is no reason to convert it to fat and so there is no fat to export as triglycerides. Fructose immediately converts to fat and any fat produced in excess of the needs of the liver will be shipped out as LDL precursor particles, raising both LDL and TC.

Both mechanisms are fructose related but not fructose specific. The average trigs were 93mg/dl but the study did not split anything other than TC by the sucrose/fructose periods early in 19 weeks of the initial part of the diet. The volunteers remained pretty well weight stable throughout, as far as I can see.

So you have a choice of two mechanisms, there may be more, but the association still seems to hold that TC is a marker of fructose intake, with a number of confounders once you get off of chemical diets. BTW the TC went back to a normal >200mg/dl on return to normal food. Or uless you have a TC like mine (and a few other folks), which is a law unto itself.


L said...

For the thick:

The best things in life are free. Fruit is expensive. Therefore, compared to it, fatty meat is the bestest thing in life.

Has anyone else observed that blueberry cake donghnuts taste more like blueberries than actual blueberries? Had one the other day. Could have ate a dozen. Fortunately vanity is one of my strongest virtues. Whatever it is, if it's sweet DO NOT CONSUME!

L said...

I just thought of something. My logic does not work using a bag of white sugar (dirt cheap). So it won't convince everyone.


Peter said...

L, living on carbs is frighteningly cheap, but you can get pretty low cost by careful choices of fats. Trying to afford or stomach 3000kcal/day of spinach is not a pleasant thought, either financially or digestively. I can see the way you are thinking.


chlOe said...

Totally makes sense.
Just like when doctors put diabetics on insulin - they gain weight - so then the doctors tell them they should stop eating fat and put them on a diet of skim milk, orange juice, fruit and grains, and very little calories no less. Way to fight insulin resistance.

homertobias said...


Hope you got a chance to look up melamed's article. Also there is an excellent series of lectures on Vitamin D on youtube from UCSD (UCTV) (Cedric Garland, Frank Garland, Donald Trump, David Sane) for anyone who ia interested. These are all the vitamin D heavy hitter researchers.

Captain Mikee said...

I saw this article recently:

The author claims the "fructose" found in fruit is actually "levulose," which is chemically different. However, the author seemed like they might be a bit chemically challenged. I'd never heard of levulose. Can you explain the difference?

Peter said...

Hi Captain Mikee,

I noticed he didn't give the chemical formulae of these two distinct chemicals. He notes that many people make the mistake of thinking they are the same, I'm one of those people!

A glass of gently squeezed, still living orange juice, handled with love and cherished when consumed will fry your liver like any other form of sucrose. You could believe that the gift of antioxidants from the orange plant would stop the fatty changes in your liver, or you could pour the orange juice (lovingly, it's still alive) down the loo.

Then I'd flush it.

As an aside I remember reading Mike Adams, the originator of Natural News, on Dr Garemo's PhD.

I blogged on the same PhD here.

The abstract is here and the full text here.

You need table 3 and scroll down to the SFA line.

Mike Adams "forgot" to mention that the slimmest children ate the most SATURATED, predominantly animal derived, fat. He didn't lie, but I'd not rely on him for health advice. But then I've got doner kebab wedged between my teeth right now. Time to floss.


Peter said...

Hi Homertobias,

Not had time to I'm afraid. I'm a fairly secure vit D taker and, as you point out, there are people for whom its promotion is a major aspect of their route to health. I'm currently overdosed and have backed off, so I'm quite willing to let others make their own decisions. The links are welcome but the main mpg I want to listen to at the moment is the interview with the GP (Dr Dahlqvist) at the centre of the current diabetes revolution in Sweden, available on Jimmy Moore's site, and that's been waiting for weeks to be listened to...


Captain Mikee said...

Thanks, Peter. You confirmed my suspicions. I just read "Sugar Blues" by William Dufty and it was disappointingly full of similar errors.

L said...


I agree. High carb diets can be cheap. But when I think of carbs I'm supposed to eat it's fresh, organic micro greens and brightly colored stuff. Those aint. Red and yellow bell peppers. WTF? Arm and leg. And yes, be careful in the meat aisle, kobe beef, fancy hams from spain and italy---out of the question. good ole grain fed walmart beef will suffice. Unless you have a super sensitive pallete the trace amounts of feces in the ground stuff should not be problematic. think hormesis. Let me warn state side readers: fancy steaks purchased through the mail----garbage! Not really. They taste fine but the cost is not justified. If you get the catalog in the mail, chuck it immediately. No temptation. Why do we fall prey to thinking if it costs a lot it must good? I'll bet I could piss in a tinted bottle, slap on an elegantly scripted label--"Urinilini de Luigi" and find somebody who drives a mercedes to drink it, say it was divine and refreshing, and desperately ask where they can get it. Unzip.

TedHutchinson said...

Direct links to the Vit D videos mentioned earlier
Vitamin D videos from Grassrootshealth

May I suggest the Holick lecture,Vitamin D and Prevention of Chronic Diseases, may not be to everyone's taste.

These pdf's have the slides used in the above presentations. Most of the readers here will be able to follow the argument from these and then decide if they want to hear exactly what was said.

Thackray said...

Hi Peter!

I had an exchange of emails with Eddie Vos back in Nov of 2007. I was curious about his support of canola oil. He cited the work of Stephan Cunnane who argues that ALA is the only “truly” essential fatty acid.

From a human nutrition standpoint I had always thought that ALA was just a precursor to EPA and maybe a little bit of DHA. As a result, I take Blue Ice High Vitamin Cod Liver Oil and Krill oil for my EPA and DHA and avoid the ALA oils like canola, soy bean and flax. I could never establish if there is a clear need for ALA itself - Eddie seemed to think that there was.

I think there are also some politics involved here as canola oil represents a cheap and readily available source of Omega 3 and several studies have shown a health benefit from adding canola oil. Governments are far more likely to push canola oil over fish oil.

I miss the days when the Thincs discussions were published on the Thincs site. How come they stopped doing that?

Philip Thackray

Peter said...

Hi Phillip,

Yes, Eddie Vos is still very pro canola, as far as I can see largely based on the Lyon study. But he also can see nothing wrong with fruit, so we must all have our own perspective. Personally I can no more see where we would have obtained linseed oil (before the advent of varnish) than we could have obtained an ad lib supply of Golden Delicious and 6" diameter oranges as HGs.

But if you are going to eat a "healthy diet" based around fruit and starches, using ALA as a pharmaceutical anti arrhythmic is a lot better than dying of VF in the aftermath of a minor coronary brought on by fructose...

I tried to help Melchior Meijer get some of the THINCS discussions up on to Uffe's website, but the process is time consuming and neither he nor I made any progress (this was before Christmas!) and my free time is just about to disappear completely from what I can see. He's in no better a situation, time wise. The process is labour intensive and the threads never begin and end neatly. The cardiological concept of the blocked pipe is currently a very long and on going thread and anyone who imagines an explanation this simple fits the facts is going to be very disappointed. Currently I have no idea of what process actually causes a heart attack! I think hyperglycaemia is central but that in no way is enough....

Anyway, I should be getting plans ready for Building Regulations approval on the new bathroom and loo. Just a few more replies...

BTW, steady 9 eggs per day at the moment. Great eggs. Three each per day with a top up to 6-9 each using Sainsburys economy free rangers. Doing well!


Unknown said...

Fructose is not completely absorbed by the gut, the tolerance level differs between individuals. Some people cannot tolerate even the smallest amounts. Hydrogen breath tests can verify if you have fructose malabsorption. The free fructose passes into the lower bowel and causes havoc with fermenting bacteria - not pleasant! Although from your post it seems the fructose that is absorbed is the problem ... anyway, my focus is more on digestion - but I thought I would add my twopenny as I just found your blog, which I think is great :) Nice work. Living the high fat way for my digestive health - and I couldn't be healthier.

Peter said...

Hi Lisa,

Yes, intestinal dysbiosis is a feature of fructose malabsorption and is a common trigger for IBS (, along wth starches, fibre and an unlucky HLA subtype. There was once a trend to use intravenous fructose as a critical care caloric source. Here fructose intolerance = acute death. They don't do that nowadays!