What about fructose - does it convert to glucose or not?

[amwassil]

I think we may need to reassess our understanding of the metabolism of fructose.

PDF: https://www.cell.com/cell-metabolism/pdf/S1550-4131(17)30729-5.pdf
HTML: http://tiny.cc/uncgcz

Summary

Excessive consumption of sweets is a risk factor for metabolic syndrome. A major chemical feature of sweets is fructose. Despite strong ties between fructose and disease, the metabolic fate of fructose in mammals remains incompletely understood. Here we use isotope tracing and mass spectrometry to track the fate of glucose and fructose carbons in vivo , finding that dietary fructose is cleared by the small intestine. Clearance requires the fructose-phosphorylating enzyme ketohexokinase. Low doses of fructose are ∼90% cleared by the intestine, with only trace fructose but extensive fructose-derived glucose, lactate, and glycerate found in the portal blood. High doses of fructose (≥1 g/kg) overwhelm intestinal fructose absorption and clearance, resulting in fructose reaching both the liver and colonic microbiota. Intestinal fructose clearance is augmented both by prior exposure to fructose and by feeding. We propose that the small intestine shields the liver from otherwise toxic fructose exposure.
(Emphasis mine.)

Discussion

…We were surprised to find that, upon oral administration of labeled fructose, F1P accumulates much more in the small intestine than in the liver. This motivated us to sample blood from the portal vein, which connects the small intestine to the liver. In the portal vein, we observed that most dietary fructose has already been converted into glucose and various organic acids (lactate, glycerate, TCA intermediates, and amino acids).
… Our observation of fructose conversion to glucose by the small intestine echo results of Ockerman and Lundborg (1965), who obtained evidence for similar conversion in humans based on detecting increased glucose levels in a mesenteric vein after intraduodenal injection of fructose. Thus, intestinal clearance of dietary fructose by the small intestine may be a general feature of mammalian metabolism (Ockerman and Lundborg, 1965, Bismut et al., 1993).
(Emphasis mine.)

So, all carbs become glucose. Right? Well, OK, technically ethanol is a carb that doesn’t. Then again I await the “isotope tracing and mass spectrometry to track the fate of ethanol”. There might be a surprise or two there.

Let the games begin!

[amwassil]

The OP article was provided by https://www.cell.com/, which appears to be an excellent source for studies including metabolism related.

[KidKeto]

This is an awesome thread. I can’t come to a conclusion of what happens in the end to the fructose we consume from fruits. Specifically in muscle glycogen pathways?

[ctviggen]

I always thought fructose went to your liver, which was the problem. See this:

Abundance of fructose not good for the liver, heart - Harvard Health

The entry of fructose into the liver kicks off a series of complex chemical transformations. (You can see a diagram of these at health.harvard.edu/172.) One remarkable change is that the liver uses fructose, a carbohydrate, to create fat. This process is called lipogenesis. Give the liver enough fructose, and tiny fat droplets begin to accumulate in liver cells (see figure). This buildup is called nonalcoholic fatty liver disease, because it looks just like what happens in the livers of people who drink too much alcohol.

[PaulL]

Fructose metabolism features heavily in this lecture:

[ctviggen]

High doses of fructose (≥1 g/kg)

Although this is a very high level of fructose. An entire pint of Ben & Jerry’s has less than this in fructose (since table sugar = glucose + fructose, I’d have to take the time to calculate exactly how much fructose, but it’s less than the limits above). That seems a bit high compared to what others say, so maybe Michael’s post does change things.

[amwassil]

In light of the study you link, I think it’s a good guess, then, that per the study I linked in the OP:

We propose that the small intestine shields the liver from otherwise toxic fructose exposure."

[SomeGuy]

@amwassil I admire your tenacity

Still, I’m not yet sold on your “all carbs become glucose” claim as repeated above.

Even the citations you’ve provided state that fructose is converted into a number of things besides glucose. And so, repeating the claim that all carbs become glucose remains a non sequitur.

But with this thread you’ve shifted the argument with a new title, asking whether fructose “converts to glucose or not?” Well, okay, that’s a different question than whether all carbs become glucose.

If you’ll please clarify the specific position you’re taking and refrain from offering citations that refute whatever that position is, I’d welcome the chance to digest and attempt a reply.

Warm regards!

[amwassil]

Hey, Joey! Here’s what I’m claiming.

All carbs eventually become glucose (current sole exception is ethanol*).

What I am not claiming is that every single atom of every single carbohydrate molecule ultimately ends up in a glucose molecule. I’m also not claiming that other by-products of the overall process are not also produced along the way.

You seem to think that if every single atom of every single molecule does not turn into glucose that my claim is false. IMHO that’s nonsense. Metabolism, as you have admitted repeatedly, is not simple.

Do you think it false to claim all wood burns because some hard woods will not burn completely if the fire does not get above a certain temperature?

Re my citation above. I think the following statements confirm my claim: “Low doses of fructose are ∼90% cleared by the intestine, with only trace fructose but extensive fructose-derived glucose, lactate, and glycerate found in the portal blood.” and; “In the portal vein, we observed that most dietary fructose has already been converted into glucose and various organic acids”.

If you assert these quotes invalidate my claim please say why so, if it’s something different from what I said above.

*The reason being it’s already pure fuel more easily utilized than glucose. So why convert it into glucose just to make it less efficient? So I think it’s been evolutionarily selected as is. Or maybe it’s just a fluke.

[amwassil]

Besides all that.

All carbs become glucose the only difference between them is how long they take to do so.

… is a catchy, accurate and effective response to the phony claim that there are ‘good’ carbs that we should eat and ‘bad’ carbs we should not. A carb is a carb… the only difference is a couple hours.

[amwassil]

This covers the conventional explanation of fructose metabolism. That is that fructose is metabolized primarily in the liver and the primary result is fat. I include it for reference and comparison purposes.

http://watcut.uwaterloo.ca/webnotes/Metabolism/OtherSugars.html

[SomeGuy]

@amwassil I’m afraid we’re reaching the point where we’re repeating ourselves. The facts are what they are, my friend. Tapping out.

[amwassil]

Fructose in perspective

Overview of the major aspects of hepatic metabolism of glucose and fructose. Key points emphasized in the text: the two sugars converge at the level of the triose-phosphates (dihydroxyacetone-phosphate (DHAP) and glyceraldehyde-3-P (Ga-3-P)). Conversion of fructose to the triose-phosphates is unidirectional but fructose-1-phosphate is a positive effector of glucokinase and regulates glycogen synthesis by activating the synthase and inhibiting phosphorylase. The last effect may be different between species. Light blue arrows show the path of gluconeogenesis from fructose leading to glucose-6-P which, in turn, can produce glucose or be incorporated into glycogen.

[amwassil]

copyright © 1996-2019 the medical biochemistry page, LLC

… Under normal dietary intake the majority of the ingested fructose is metabolized by the enterocytes of the small intestine primarily to glucose which is then delivered to the systemic circulation. In addition to glucose, the carbon atoms from dietary fructose are converted, by intestinal enterocytes, into several other metabolites including glycerate, glutamate, glutamine, alanine, ornithine, and citrulline.
However, diets containing large amounts of sucrose, high fructose corn syrup, or fructose alone, overwhelm the ability of the small intestine to metabolize it all and under these conditions a significant amount of fructose is then metabolized by the liver and to a lesser extent by other organs such as skeletal muscle.

Link

[PaulL]

Re my citation above. I think the following statements confirm my claim:

In mice, sure. But existing isotopic trader studies in human beings suggest not.

[David_Stilley]

A carb is a carb… the only difference is a couple hours.

This is wrong Michael. Complex and simple carbohydrates have different insulin responses. Simple carbs cause a huge quick spike of insulin, complex carbs cause a slower spike and lower level of insulin spread over time. And fructose doesn’t spike insulin. Sugar rush compared to eating a potato.

[KidKeto]

Assume I have 6oz of raspberries. Under maintenance calories and inside an eating window (meal was had a few hours before) would 7 grams of fructose turn into fat or is it only the case with high doses?

[atomicspacebunny]

Some additional information, this subject is more complex than I ever realized?

[1] Fructolysis: Fructose is metabolized almost completely in the liver in humans, and is directed toward replenishment of liver glycogen and triglyceride synthesis, while much of dietary glucose passes through the liver and goes to skeletal muscle, where it is metabolized to CO2, H2O and ATP, and to fat cells where it is metabolized.…More

[2] Dietary Glucose: “…When the stomach digests food, the carbohydrate (sugars and starches) in the food breaks down into another type of sugar, called glucose. The stomach and small intestines absorb the glucose and then release it into the bloodstream. Without insulin, glucose stays in the bloodstream, keeping blood sugar levels high. …” …More

[3] Dietary Sucrose: Sucrose is digested rapidly, but has a relatively low glycemic index due to its content of fructose, which has a minimal effect on blood glucose. As with other sugars, sucrose is digested into its components via the enzyme sucrase to glucose (blood sugar) and fructose. …” …More

[4] High Fructose Corn Syrup: “…The proportion of fructose to glucose in both HFCS 42 and HFCS 55 is similar to that of sucrose. The primary differences between sucrose and the common forms of HFCS are:

• HFCS contains water.
• In sucrose, a chemical bond joins the glucose and fructose. Once one eats, stomach acid and gut enzymes rapidly break down this chemical bond.
• In HFCS, no chemical bond joins the glucose and fructose. …” …More

[5] Endogenous Fructose Production Contributes To Metabolic Syndrome (yes it can happen? how strange?)

[6] Fructose Malabsorption and Intolerance: Effects of Fructose with and without Simultaneous Glucose Ingestion

[7] “…The researchers at Yale reported in the journal, JCI Insight, that the brain uses the polyol pathway to produce fructose in the brain. Unlike glucose, which can be metabolised throughout the body, fructose is normally metabolised almost completely in the liver and also in semen where it produces energy for sperm. …” …More

image link

[8] What is “FREE SUGAR?” “…Fructose is found in fruit (and a small amount in vegetables) but there is a big difference when we eat it in fruit as opposed to it being a ‘free sugar’. Fructose in fruit is encased in fibre which hugely affects its metabolism in our bodies. The fibre helps to slow down the absorption and so it doesn’t get fast, direct access to the liver like it does when it is ‘free’. As I experienced, when it is able to access the liver very quickly, there is no regulation process for it (because it was so rare in nature when we were evolving) so it rapidly gets turned into fat. (SO IT RAPIDLY GETS TURNED INTO FAT: in-case you missed that?) This process is greatly effected and halted when the fructose is absorbed with the fibre of the fruit. …” …More

[9] “…So, fiber is a good thing for people with diabetes. …Insoluble fiber keeps your digestive tract working well. Whole wheat bran is an example of this type of fiber. Soluble fiber can help lower your cholesterol level and improve blood glucose control if eaten in large amounts. …More

Note: Who can constantly eat large amounts of insoluble or soluble fiber and be consistent with it? Soluble fiber with every meal you would eat in the context of a SAD diet? Personally I’ve seen people try, but being persistent with it? NO! And damage your intestinal tract (leaky gut) in the process of eating insoluble fiber?

[amwassil]

This is wrong Michael. Complex and simple carbohydrates have different insulin responses. Simple carbs cause a huge quick spike of insulin, complex carbs cause a slower spike and lower level of insulin spread over time. And fructose doesn’t spike insulin. Sugar rush compared to eating a potato.

That’s why we tell all newbies to “eat sub-20 grams of monosaccharide bad carbs, but it’s AOK to eat disaccharide and polysaccharide good carbs because they cause a slower spike in glucose and a lower level of insulin spread over a couple hours longer”.

Oh, wait…

We actually tell newbies to “eat sub-20 grams of all carbs”. We even debate the wisdom of whether it should be total or net.

If there’s such a big difference between the bad simple and the good complex carbs, why do we make it so difficult for so many newbies? Why don’t we just tell them that potatoes and rice and bread and pasta and whatever their fave complex carb food is OK. Just give up the pop tarts and the donuts and stop putting sugar in coffee?

We know those big differences you list between simple and complex carbs amount to slightly different total glucose and insulin loads over a slightly different time span. That’s it. A carb is still a carb and the distinction between ‘good’ and ‘bad’ is irrelevant. Unless you’re eating SAD and consuming several hundred grams of carbs per day where it might alter the onset of obesity, CVD and T2D by a few years. If you’re eating ketogenic, it’s doodly squat.

The best advice is to make carbs, any/all carbs, a miniscule, minimal, incidental part of the ketogenic diet, the free-riders of fat and protein foods. Gluconeogenesis makes all the glucose we need. There is absolutely no requirement to eat sugar to get it. Eating sugar in any more than incidental amounts brings with it a host of metabolic risks all of which are easily avoided by not eating it in the first place. Not by pretending that ‘complex’ carbs are significantly different from and/or ‘better’ than ‘simple’ carbs.

IMHO.

[David_Stilley]

I’m not arguing for healthy carbs, just that they have different insulin responses. A higher spike is more badder!

You can’t believe sucking on hard candy is the same as having a bowl of broccoli…