Sweet and Rusty: the link between sugar, glycation and joint health

red meat with cooking plate

What do rusty cars and squeaky knees have in common?

As embarrassing as it is to admit, I only have a passing knowledge of the inner workings of an automobile. I’m sad to say that my father will be the last generation of Bakers that can easily change the oil in his car. If my sons, or daughters learn, it won’t be from dear old dad. Likely they’ll be shuttled about by Uber-esque driverless cars whilst staring at their phones anyway.

Even with my meager understanding of vehicle repair, I know that when I see a rusted out clunker sitting out in front of some farmers barn, that it’s not likely to even run, much less be a high performance racing machine.

As an orthopedic surgeon and lifelong athlete I do, however, have a fair amount of knowledge about the workings of the human musculoskeletal system and have definitely seen my share of rusted out human clunkers.

We all start out showroom fresh with brand new parts and way low mileage. But then with time, accidents and rusting occurs even among the most meticulous of owners. Short of the “here hold my beer and watch this!” type of stupidity, accidents are often just that and are unavoidable. Broken bones, torn ligaments or tendons are always just one bad fall away.

Like the Tin Man from from the Wizard of Oz, do we see oxidized metal causing people to grind and squeak. Well not normally, unless you count some poorly placed squeaky ceramic hip replacements. What I am referring to is the accumulation of the so called AGEs (Advanced Glycation End-Products).

You can think of AGEs that accumulate in humans somewhat like the rust building up on a car; a certain amount is normal but poor maintenance speeds it up

The similarities between glycation and rust

These advanced glycation end-products are the result of the non-enzymatic attachment of sugar molecules to other structures. Fortunately, this is only known to occur with proteins, fats and nucleic acids (the ACGT letters of the DNA code). Unfortunately, that pretty much covers the entire human body, unless you’re a lifelong vegan, then perhaps some of your tissues may have been converted to chlorophyll.

These molecules that result from glycation have been postulated to be crucial to the aging process and are certainly found in association with a whole slew of diseases, most notably diabetes and its plethora of complications. What is not so commonly discussed are their role in musculoskeletal disease.

But first it is helpful to consider where these products of glycation come from in the first place. The name provides a fairly decent clue with the word “Glycation” referring to some kind of business with sugar. Sugar is certainly taking its lumps (pun intended) these days and I’m certainly going to add to it. We can consider two sources of AGEs to which our bodies are exposed. Exogenous AGEs, which are the ones we eat, and the endogenous ones which we form ourselves. Of the two, the endogenous are more likely to cause the most trouble.

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In 1912 the French chemist Louis-Camille Maillard [1], described the non-enzymatic interaction that occurs between sugars and amino acids we can all see by the browning or caramelization of certain foods as they are cooked. When we eat a well seared steak or a crispy piece of toast we are unwittingly ingesting a certain amount of these unfriendly molecular products resulting from glycation. Fortunately for us, digestion tends to likely render much of them relatively impotent. Not surprisingly, cigarette smoking also is known to result in AGE formation. Likely one of the reasons cigarette smokers often tend to wrinkle prematurely.

Seeing glycation in the body, first-hand

As someone who has peered inside of thousands of knees and shoulders I can tell you that a slow low temperature caramelization of your tissues is definitely occurring. The beautiful, pristine, shiny white cartilage of youth is later replaced with a dull and yellowed facsimile which is prone to tear and crumble away. The same things are occurring with ligaments, tendons and the like.

If the molecular products of glycation are contributing to this process, is there anything that can be done to prevent it from occurring or perhaps even reverse some of its damage?

If we look at the endogenously produced AGEs we can see that the preponderance of their formation is a result of glucose and especially fructose metabolism, pathways we hit hard by over consuming glucose and fructose in our Western diets [2].

The more we run these sugars through our system, the more we start to toast our little internal marshmallows. In my business, I believe that equates to pain, injury susceptibility, and eventually chronically destroyed tissues. Unfortunately, this has been woefully understudied up to this point. It is clear that the molecular products resulting from glycation demonstrably interfere with both collagen structure and function. Collagen makes up a significant percentage of our joints and connective tissues. It is not a great leap to postulate that disrupted collagen can lead to the above described problems.

Is there a way to limit our exposure to sugar metabolism?

Well, as crazy as it sounds, eating less of it is actually a pretty good strategy.

Can you prevent a knee replacement just by omitting sugar and starches from your diet?

In my view, perhaps. The longer I am involved in this the the more I see an undeniable connection between metabolic disease and orthopedic issues.

Two major ways to limit excessive AGEs build up is to avoid sugar and smoking

One of the comments I often hear from people that have gone on low-carb diets is that musculoskeletal pain lessens or completely resolves (a small subset will however report the opposite, which I believe may be related to a temporary relative decrease in uric acid excretion due to competition with increasing urinary ketones).

It is also interesting to note that many, if not most, report these improvements prior to or in the absence of significant weight loss. To me this certainly has several implications regarding the causes of musculoskeletal pain. I was always perplexed by the fact that one person could have an X-ray that looked like a rabid dog had chewed on their knee joint and yet have relatively minor pain versus another patient whose x-rays would be almost perfect and yet would have unremitting and debilitating pain.

My current belief is that metabolic health plays a significant role here and likely can potentially explain the difference. It’s is also interesting to note that if the second patient goes on to have a knee replacement (after exhausting all other options) he or she will be at much higher risk for continued postoperative chronic knee pain. Again I think this has to do with failure to address a metabolic component of the joint disease.

Turning back time on glycation

Can you reverse the effects of glycation?

This remains to be proven but I suspect that it is highly plausible. We do know that collagen does turn over with time and we also know that AGEs can slow but not likely stop this process [3]. There are pathways by which the molecular products of glycation can be cleared. One of the more important is via a glutathione dependent system [4].

The problem is that if the tissues are turning over in an environment where AGEs are continually being formed via sugar metabolism then it is unlikely to allow for much improvement. If tissue turnover occurs in a relatively AGE-free environment then we might have a shot.

Can you fix a completely destroyed joint or a completely torn tendon via diet?

I wouldn’t hold my breath but you might certainly improve the recovery process. Additionally, it is also of interest to note that the production of glutathione, which helps to clear molecular products of glycation, is up regulated via low-carb diet or even lower-carb ketogenic diets. Well-formulated versions of these diets are great for normalizing insulin signaling which is an important way to moderate methylglyoxal levels that induce the formation of AGEs [5].

My personal experience has taught me that the less sugar and carbohydrates I consume, the better my joints and tendons feel. Hopefully, I will keep this 1967 model out of the junkyard in the fast lane for many years to come!

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Written by Shawn Baker M.D. (@ShawnBakerMD on Twitter)

We at Break Nutrition are proud to introduce you to Doctor Shawn Baker, an orthopedic surgeon working in Texas. He has done excellent medical work with the US military, has an outstanding personal fitness practice and continually explores the science of nutrition that translates to cutting-edge advice to his patients. We hope to bring you more of his valuable insights about patient care and how his knowledge of nutrition enables him to excel in his profession.

3 comments On Sweet and Rusty: the link between sugar, glycation and joint health

  • Excellent post, doctor. My (totally uneducated) guess is that if your diet is rich in chondroitin, vitamin C, glycine, and other rebuilding substances, and if the cartilage is still in one piece, and you are not too old, eventually the cartilage will be rebuilt properly. In my experience, a soccer hip injury from 1994 which made my hip sensitive for about 13 years after, solved itself, but when I eat too many tomatoes it flares up (a pound, which happens to those who have large gardens in summer). Sugar may not be the whole story.

  • Hi glib,

    I agree that sugar isn’t the whole story. It seems that certain plant compounds can also negatively affect joints when the immune system perceives them as a threat. However, I’d maintain that on a population level sugar is probably the single biggest culprit (and if not that, quite substantial).

  • The name, “glycation,” indicates the addition of sugar groups to proteins, such as occurs in diabetes and old age, but when tested in a controlled experiment, lipid peroxidation of polyunsaturated fatty acids produces the protein damage about 23 times faster than the simple sugars do (Fu, et al., 1996). And the oxidation of fats rather than glucose means that the proteins won’t have as much protective carbon dioxide combined with their reactive nitrogen atoms, so the real difference in the organism is likely to be greater than that seen by Fu, et al.

    These products of lipid peroxidation, HNE, MDA, acrolein, glyoxal, and other highly reactive aldehydes, damage the mitochondria, reducing the ability to oxidize sugar, and to produce energy and protective carbon dioxide.

    http://raypeat.com/articles/articles/glycemia.shtml

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