Metformin has some intriguing effects on fructose metabolism hinting that reducing fructose spikes should be a priority if you’re metabolically challenged

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How metformin works to “fix” type 2 diabetes

Metformin has some intriguing effects on fructose metabolism hinting that reducing fructose spikes should be a priority if you’re metabolically challenged

If you’re taking meds to manage your type 2 diabetes/pre-diabetes, there is a very good chance you’re taking metformin. Of course METFORMIN is not what will be on your pill box, this is the generic name of the drug, the pill box you have will reflect the trade name – there are lots of options.

Here is a list of some of the medications that contain metformin

Carbophage, Riomet, Fortamet, Glumetza, Obimet, Gluformin, Dianben, Diabex, Diaformin, Siofor, Metfogamma and Glifor

Now metformin is not the only oral hypoglycaemic drug on the market, but currently metformin is THE DRUG of choice, although this might be changing.  In metformin’s favour :

It’s relatively safe and CHEAP.

It’s been around for years. In fact,  it has proved so useful in type 2 diabetics, it has acquired a fan club looking to extend it’s prescription to a number of pathologies and some  healthy peeps take it  to try to  cheat FATHER TIME.

So how does metformin work ?

Believe it or not, despite being around for years and being a key component of the anti-diabetes toolkit, it’s still a bit of a mystery. Pharmacology textbooks attribute it’s magic to metformin’s ability to inhibit complex 1 inside the mitochondria.  Translated into plain English…………..

It “breaks” the little furnaces that provide cells with the energy they need TO DO THINGS.

And this triggers and energy crisis inside the cell, spearheaded by the enzyme known as AMP kinase, the body scrambles to fix the problem and somehow ………….. everyone lives happily ever after.

Now part of the happily ever after involves the liver producing less glucose.

There are some holes in the theory…..

Breaking the broken

The most notable being one of the primary problems, if not THE PRIMARY problem  in someone with type 2 diabetes is  fuel is NOT BEING BURNED.

This is why everything runs high

• Sugar
• LDL cholesterol
• Triglycerides
• Free fatty acids
• Branched chain amino acids

So the idea that metformin  BREAKS  the broken and this fixes the problem is a little hard to swallow.

NOTE : The thinking is that  BURNING less has benefits because it lowers oxidative stress.

Mmm….

It doesn’t take a rocket scientist to work out, this cannot be the whole story.

So what is the story and why do we need to figure it out ?

Metformin leading the way

The biggest benefit of unpacking what metformin is doing is “we” would be one step closer to figuring out what is really going wrong in type 2 diabetes/insulin resistance and be better able to treat people suffering from this affliction, but more importantly stop others from sliding into this devastating BODY CHEMISTRY pattern.

I think there has been a break through on the how metformin lowers blood sugar levels front.

Fructose natural yet dangerous

And the story is related fructose…..

A natural sugar  (it is the sugar that occurs in fruit) that  has been “perverted” by technology to become a major component of ultra-processed foods where it appears as high fructose corn syrup.

So let’s dive in.

Mice doing metformin

The team of American  researchers treated 18 week old  “ordinary”  mice with “ORAL” metformin for 2 weeks.

NOTE : The mice in the study were not fat and diabetic.

I’ve put the ORAL in inverted commas, because  the mice did not simply swallow their meds with breakfast, getting the metformin in was a “procedure”.  The official term for what was done was gavage. It involves forcibly delivering the drug to the stomach.  Not a pleasant experience all round, but very necessary, because the research team wanted to study what metformin was doing in the intestine.

Thanks to previous research they had a hunch that this was very important.

Metformin does magic

Despite the fact that the mice were not diabetic the metformin treated mice showed improvements in their glucose tolerance.

Fasting glycemia levels after 2 weeks of treatment of healthy mice with metformin. 2023 Wenxin Tong et al.

Go metformin !

Gut feelings and reactions

Following the 2 week treatment with a dose of metformin designed to mimic the plasma levels seen in humans, they  TOOK a look at what had happened in the intestinal tissue.  Specifically they explored the chemicals related to fructose metabolism.

Fructose enters enterocytes (the cells lining the gut) via a different gate from glucose.

The gate that fructose uses is the GLUT5 gate, once inside the enzyme fructose kinase quickly throws a phosphate on to make sure the fructose doesn’t “change it’s mind” and escape.  This process creates a chemical called fructose-1-phosphate.  The figure below shows the relative quantity of  fructose-1-phosphate  in the intestine following short term  metformin treatment.

The relative quantity of fructose 1-phosphate in intestinal tissue following short term treatment with metformin. 2023 Wenxin Tong et al.

Suggesting the fructose was not making it inside.

So what ?

Fructose free zone

Under normal circumstances the fructose that is taken up by enterocytes is turned into glucose.  When the team tested intestinal glucose production it was significantly lower.

Relative glucose levels in the intestinal tissue following short term treatment with metformin 2023 Wenxin Tong et al.

And…………… this quite possibly is the MAGIC of metformin.

Too little insulin is relative

What is not always appreciated when someone is battling to control their sugar levels is a big part of the problem is there is TOO MUCH SUGAR. There is the sugar coming WITH DINNER on top of the sugar the body is producing to ensure the brain and other delicate bits are adequately fuelled.

Insulin is meant to turn off endogenous insulin production.

When you’re insulin resistant – insulin fails to put a lid on this sugar production.

NOTE : This is why low carb diets are so helpful, less sugar coming in means the insulin that is around is not scrambling to handle all the EXTRA SUGAR.

Metformin stops glucose production

Not in the liver,  but in the intestine.

Of course, this begs the question,  what happens to the fructose that the enterocytes pass on  ?

One possibility is it ends up in the liver, which would not be a good thing because thanks to fructose chemistry, it could be turned into fat and cause the liver a whole lot of unhappiness. This is what happens when you drink sugar laden beverages.  Click here to learn more.

The fructose escapes and gets up to all sorts of mischief.

Metformin protects the liver too

The good news – it didn’t.   No surprises here, if it didn’t metformin would NOT be the drug of choice for type 2 diabetes. Lol !

Relative levels of fructose and it’s metabolic product in portal vein and liver. © 2023 Wenxin Tong et al

So the fructose just keeps on moving through…………..to become the colon’s problem.

Bacterial tea party

Arriving on the menu of the hoards of bacteria living in the colon.  Now the taste for fructose is an acquired taste.  So initially, the unabsorbed fructose can make for unpleasant tummy rumbles, something that often happens when people first start taking metformin.

But there are species of bacteria THAT LOVE IT.

Adjustments are made in who is who in the zoo and life goes on.

Metformin is an acquired taste

This probably explains why the vast majority of people (75 %) experience gastrointestinal side effects such as diarrheoa, nausea, vomiting, abdominal discomfort and flatulence, when the first start taking metformin.

It’s caused by the excess unabsorbed fructose in the colon.

Disrupting the water pumps.

Those who push through the tummy upsets …………. find the problem subsides as the gut flora adapts to the change in food sources.

The hero and the villain

This research implicates fructose in the pathology of metabolic disturbances.  It’s not a new idea…

And it’s probably not as simple as…. FRUCTOSE causes METABOLIC DISEASE !

My guess is it’s SOMETHING goes wrong in the intestine, based on the fact that bariatric surgery that “cures” type 2 diabetes almost ALWAYS “messes” with the jejunum (the middle part of the small intestine).

You should view intestinal fructose as THE ENEMEY

Based on this finding – too much fructose, in the intestine,  is clearly not healthful.   And if you are metabolically challenged, it would probably be prudent to minimize fructose spikes in the intestine.

Fortunately this is not so hard to do.

• If you are diabetic do not use fructose as your sugar substitute.
• Cut back on your consumption of highly processed foods : high fructose corn syrup is often an ingredient
• Don’t drink your fructose ESPECIALLY on an empty stomach.

NOTE  : Fructose is not just found in the “BAD” sugar laden beverages, it pops up in the “GOOD” sugar laden beverages too. Think orange juice and smoothies.

The final suggestion and maybe a bit more controversial opt for more VEGETABLES and less FRUIT in your regular day to day diet.  Natural fructose is still FRUCTOSE so treat it accordingly.  If you want to learn more about the biology of fructose ?   Click through to the fructose library page on BETTER BODY CHEMISTRY blog.

Further reading

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