How Sugar Leads to Toxic Glycation

By Michael A. Smith, MD

We’ve all heard it many times by now - the consumption of refined sugar is killing people.

And it’s true. As a matter of fact, I often refer to sugar as the “American diet culprit” — a statement that I stand behind 100%.

But how exactly is sugar harming us? Or let me ask it this way: What is sugar really doing to our cells and tissues that is so very harmful?

Below, we’ll answer this by investigating the pathological reaction involving sugar. We’ll also explain how you can prevent it from happening to you, naturally.

Sugar Reacts to Cause Dangerous Glycation

First off, sugar is very reactive … chemically speaking. It readily combines, or reacts, with cell-surface proteins and fats. This reaction is called glycation and it’s not a good thing at all.

Every molecule of protein and fat in your body has a distinct structure and form. If the structure or form is changed, even just slightly, the result can be complete dysfunction of the protein or fat.

We call this the “structure-function” relationship of molecules. The need for a specific structure to perform a function can easily be envisioned if we think about the way a key has to fit into a lock.

In fact, the “lock and key” model in biochemistry is used to describe the need for a perfect match between a protein enzyme and its binding site. In another example, think about it on a more grand scale.

Look at your hand. It has a very detailed and specific structure to it. Crushing your hand in an industrial accident and breaking all of your fingers, changes your hand’s structure.

In a “crushed” form, your hand cannot function as a hand. Your hand has lost its “structure-function” relationship.

Sugar Destroys Structure-Function Relationships

The same is true for proteins and fats on the surface of your cells. When sugar reacts with a surface protein, say a receptor for a hormone, it changes the receptor’s structure and ultimately its function as a specific hormone receptor.

What does this mean to the cell? Well, the hormone, which carries a specific message for the cell, can no longer pass on its message. And keep in mind that the hormonal message could very well be essential for the cell’s function and survival. And that’s just one example.

Destroying the structure of a cell-surface protein or fat through glycation will destroy its function. The cell membrane becomes damaged and the cell dysfunctions. This inevitably is followed by tissue damage, organ failure, and organism death.

Bottom-line: Too much sugar undergoes a dangerous reaction called glycation. So let’s take a look at some ways of preventing it.

Carnosine Sacrifices Itself to Protect Your Cells

Carnosine is a unique small protein, called a dipeptide, which can interfere with the glycation process.1,2 It probably protects against glycation in two ways.

First, it may, in a sense, “sacrifice itself.” Instead of sugar reacting to critical cell proteins, it will attack supplemented carnosine instead. I like to call it the glycation martyr.

Secondly, carnosine seems to have an ability to help “unfold” (return to normal) the structure of glycated proteins. In a laboratory study, researchers showed that glycated alpha-crystallin (a protein) unfolded and returned to normal structure after carnosine was added.1

Supplementing with 1 gram a day of carnosine may help people with sugar issues reduce the amount of glycation their cells and tissues experience.

Benfotiamine Manages Normal Sugar Reactions

Another way to prevent glycation is to make sure sugar undergoes normal metabolism — meaning it’s used properly for energy or safely stored away for later use. This is where benfotiamine comes into play — a fat soluble form of vitamin B1. It can help ensure sugar is correctly metabolized.3

Benfotiamine is a co-factor for the enzyme transketolase — which is critical to blood sugar metabolism. In a landmark study, it boosted healthy transketolase activity in cell cultures. The result was activated glucose metabolism, resulting in healthy blood sugar levels and less sugar available for glycation reactions.3

The researchers concluded that benfotiamine could help inhibit advanced glycation reactions, maintain healthy endothelial, retinal, kidney and nerve cell function.

Special Forms of B6 Inhibit Glycation

Sub-forms of vitamin B6, like pyridoxamine and pyridoxal-5’-phosphate, have been shown to protect critical cellular fats and proteins against glycation reactions.4

They probably work similar to benfotiamine by helping our cells manage sugar better and stopping glycation early on, before too much damage occurs. In any case, research has clearly shown that supplementing with them can minimize glycation reactions.

A team of biochemists at the University of South Carolina, for instance, were able to show that these sub-forms of B6 trap reactive metabolites formed during the initiation of glycation. They then chaperone them harmlessly into the urine before too much damage occurs.5

Sugar – How Sweet It Isn’t

So here’s the takeaway: Sugar is not a sweet, innocent compound. It’s highly reactive and can cause great structural damage to critical proteins and fats. Once structurally damaged, these proteins and fats cannot function properly.

So what can you do to protect yourself? First, start off by eating less sugar. Then, also consider supplementing with the triad of anti-glycation nutrients mentioned above — carnosine, benfotiamine and special forms of vitamin B6.


  1. Arch Biochem Biophys. 2004 Jul 1;427(1):110-5.
  2. Exp Gerontol. 2009 Apr;44(4):237-42.
  3. Nature Med. 2003 Mar;9(3):294-9.
  4. J Lipid Res. 2006 May; 47(5): 964-74.
  5. J Biol Chem. 2003 Oct 24;278(43):42012-9.


Jennifer said...

I was a bit hesitant to read this article because I love my sweets. But after just a few sentences I knew I would be able to gain quite a bit of knowledge and understand. I am wondering if you can acquire carnosine from your local health food store, that it something I am interested in trying. I'll also think twice before heading down the candy isle. Thanks for the information.

Anonymous said...

I am curious about the dipeptide Carnosine. I understand that Carnosine declines in the aging population. Promising data on longevity & antiglycation properties are frequently mentioned in science literature.
It is also well known that the common inexpensive athletic supplement Beta Alanine can elevate carnosine in human subjects. Carnosine is a dipeptide synthesised in the human body from Histidine & Beta alanine. Histidine is generally in plentiful supply (from diet) hence it’s the Beta alanine that is rate limiting factor. There seems some mention in literature that carnosine is broken down into its 2 constituents during digestion anyway, then reassembled. There is some mention that carnosine can in trace be absorbed intact. There is some mention that supplementing beta alanine alone does not confer benefit. My question is. Is there a definitive answer yet available on the above?
Incidentally I actually take both Carnosine & beta alanine in supplement form.
And thankyou ! – You have been a go to Site for common sense & inspiration for many years.

Steve Waner said...

Sugar is the main culprit of certain diseases like diabetes. It is not wrong to consume sugar but we should do it in moderation, but if we can thoroughly avoid it, the better for us. If we love sweets, we might consider certain fruits, most fruits are sweet by nature and at the same time, we can gain a lot of good benefits. We might consider honey as a sweetener also.

LifeExtension said...

Jennifer - Sweets are definitely hard to resist. Carnosine is something you could typically find in your local health food store.

LifeExtension said...

Steve Waner - Good advice! A little sugar definitely goes a long way. :)

LifeExtension said...

Anonymous - Good question! Orally ingested carnosine can be broken down into beta-alanine and L-histidine in the liver. It can also be absorbed whole into the bloodstream and be transported to different body tissues.

Randi said...

Is their a supplement that has these three things in it?

LifeExtension said...

Randi - Yes, actually. :-)

Anonymous said...

I try to limited my sugar intake as much as possible. I don't always succeed, but... I do try. Staying away from soda is a BIG plus!!! ;-)

Life Extension said...

Anonymous- Indeed! Glad to hear that you are limiting your sugar intake as much as possible! :-)

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