Fats and AGEs: PUFAs Are Even Worse than Fructose

The question of how to avoid AGEs has proven to be more difficult than one might think, however. If it was merely a matter of reducing the formation of advanced glycation end-products during cooking, we could just cook our foods at lower heat and use water instead of frying at high temperatures. But as we’ve seen, the AGEs we get directly from food may not be as important as the AGEs that form inside our body as a result of internal glycation.

The term ‘advanced glycation end-product’ is somewhat misleading in the sense that they are not formed only by glycation, which refers to glucose molecules binding to protein or lipid molecules, but also by fructation, which is essentially the same thing but this time with fructose. In fact, fructose is much more prone to form these products than glucose. Since there’s no such term as ‘advanced fructation end-product’, they’re also referred to as AGEs (other sugars like galactose go through a similar process too; more on that in another post).

To complicate this further, similar products are also formed during cooking when fats alone are exposed to high heat and air. This process is known as lipid peroxidation. The end results of lipid peroxidation are referred to as either AGEs or ALEs, short for advanced lipoxidation end-products. For the sake of simplicity, I will refer to all of them as AGEs, unless the difference is important.

So we now have several different ways to accumulate AGEs: eating cooked foods that contain sugars heated with protein or fats, eating uncooked foods that contain sugars, or eating oxidized fats. And, like glycation, lipid peroxidation can also happen endogenously. That is, even if the fats you eat do not contain any AGEs, they can still form AGEs inside the body if they are unstable and prone to oxidation.

The bad news is that not only does lipid peroxidation lead to AGEs, it appears to do so more rapidly than glycation does. CML, a product of the oxidative degradation of glycated protein anda common measure of AGE levels, is actually formed through the oxidation of arachidonic acid in much higher quantities than from glycation (link). CML is a handy way to compare things, because it can be formed through glycation, fructation or lipid peroxidation.

The reason you should keep your fish oil and flax seed oil in the fridge is precisely because they, like other highly unsaturated fats, are easily oxidized (link). Cooking with these oils is a really bad idea. Through lipid peroxidation, polyunsaturated fats or PUFAs are more prone to form AGEs. Below is a comparison of CML formation from three different fatty acids and glucose (link):

The left graph shows that arachidonic acid forms CML at about twice the rate as linoleic acid. The formation of CML from oleic acid is close to zero. Compared to glucose in the right graph, the two PUFAs here are at least 10 times as prone to AGE formation – very much like fructose, except that if you look at the fructose graphs, the 10-fold increase is not seen as early as it is in these graphs.

The explanation for the differences is that lipid peroxidation increases exponentially as a function of the number of double bonds (link), i.e. the degree of unsaturation. Arachidonic acid is a 20-carbon chain PUFA with four double bonds and linoleic acid is an 18-carbon chain PUFA with two double bonds. Oleic acid, like all MUFAs, has one double bond. Note that this equation makes the omega-3 fatty acids DHA and EPA (with their 6 and 5 double bonds, respectively) the worst offenders.

So oils high in PUFAs seem to have the ability to raise the AGE burden much more than glucose, or even fructose. This could potentially explain some of the differences in AGE levels between omnivores and vegetarians – maybe vegetarians eat more vegetable oils than omnivores, since glucose and fructose intakes alone are insufficient to explain the results. The authors of the paper state:

Oxidation of fatty acid is clearly a more efficient source of CML, despite the fact that the glucose is in solution throughout the course of the experiment, while the PUFA are only progressively solubilized. Further, after 6 days of incubation, a large fraction of the arachidonate was oxidized based on its solubilization in the aqueous phase, while less than 2% of the glucose is oxidized during this same time period.

In the same study, arachidonic acid produced more than 10 times the amount glyoxal than it did CML. Glyoxal is another inflammatory compound, which in food is created by heating unstable (i.e. polyunsaturated) oils to high temperatures but which, again, can also be formed inside the body. Some of this glyoxal goes on to form AGEs, but the rest that doesn’t isn’t exactly life elixir either.

Unfortunately, the problems don’t end with CML. Polyunsaturated fats also quite easily form other AGEs, such as malondialdehydelysine (MDA-lys) and carboxyethyllysine (CEL). Indeed, rats fed a diet high in PUFAs have over twice the level of MDA-lys in their brains compared to rats fed a diet high insaturated fat diet (link). Their levels of CEL and CML in the brain and MDA-lys in the liver are also significantly higher (although CEL and CML are lower in the liver). Unsurprisingly, MDA and CML deposits in the brain are implicated in Alzheimer’s disease (link).

As I mentioned before, simply avoiding cooking with oils rich in PUFAs is probably not enough, because exposing them to high heat and air in the frying pan isn’t the only thing that causes them to form AGEs. Reactive species such as radicals, transition metals, other electrophiles, and enzymes can also cause their oxidation inside the body (link).

In fact, it’s not certain based on the studies mentioned here just how bad food-derived ALEs are. Perhaps ALEs from food are less important than ALEs formed endogenously. Endogenous AGEs certainly appear to play a bigger role than exogenous AGEs, although consuming excess amounts of AGEs is probably not a good idea either.

Personally, I’m trying to limit both endogenous and exogenous AGEs and ALEs by avoiding cooking at high temperatures and using saturated fats for frying. Stay tuned for more posts on the issue. Meanwhile, see these posts on glycation and fats:

AGE Content of Foods
The 7 Types of Aging Damage That End up Killing You
Green Tea Reduces the Formation of AGEs
Should Saturated Fat Be Avoided in Low-Carb Diets?