Wednesday, October 7, 2009

Fats and AGEs: PUFAs Are Even Worse than Fructose

Olive oil is mostly monounsaturated fat.
Olive oil is mostly monounsaturated fat. (Photo by Splat Worldwide)

While the exact role AGEs play in aging is still unclear, it seems that reducing their accumulation in the body is a useful goal. And if for no other reason, how about being superficial: liver spots, for example, are a visible sign of AGEs in the skin. If you want to look youthful, glycation is not the way to go.

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 and a 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):

AGE formation from glucose and lipids
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?

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13 kommenttia:

Aaron October 7, 2009 at 8:09 PM  

Nice post! We're thinking on similar wavelengths. I've been too lazy to find any studies proving that PUFAs are the #1 problem and you show even more evidence of that. (I'm always lazy in finding studies to back me up, I could get more credit if I would just spend the time)-- I also share you sentiment that exogenous AGEs play less of a role in pathogenesis than endogenous AGEs.

We need to figure the threshold for where polyunsaturate intake should be-- It's entirely possible that when you keep omega 6 way down, our need for omega 3 content goes way down. In face-- stephan at whole food source showed the benefit in keeping it at 4% of calories or less.

Most people have so much omega 6 in their tissues though that they'd benefit from omega 3 consumption. Even when they are trying to lose weight they liberate omega 6 so they could use the balancing effect of omega 3.

JLL October 7, 2009 at 9:12 PM  


I agree that high levels of omega-3 are probably not needed, provided that omega-6 intake is low. I'm even beginning to be a little skeptical of fish oil (even though it does have many benefits too).

Aaron October 8, 2009 at 4:12 AM  

fish oil and omega 3 requirements are interesting--

First, do other primates seem to suffer from their lack of omega 3? How many polyunsaturated acids are going to escape consumption from the bacteria in their multiple stomachs? <---- answer, not much!

Human males don't seem to convert ALA to DHA much at all-- but then again, researchers have only looked at tissues- and not what is going on in the brain(because most people don't agree to brain biopsies.

Most longevity studies do not show benefits to incorporating more DHA into tissues -- even the heart. So even if you lower the change of some type of heart problem-- you really aren't living that much longer.

Lastly, do we really need DHA to keep our brains or eyes healthy? I know they have DHA in their tissues- but can they maintain their stores without outside intake. Given the amount of fat in our brains-- and the fact that it would have to have a high turnover rate-- I just don't see how we need to consume DHA to maintain our brain at all-- in fact, I think I remember reading that their is an increase in polyunsaturates in the brains of people who have alzheimers.

The question is: how low should we go? Do we really need polyunsaturates?

JLL -- besides balancing inflammation, have polyunsaturates proven any beneficial qualities? I have heard of faster wound healing with higher intakes-- but I just don't see how

Also, what about UDO erasmus-- he consumes tons of polys-- and talks about all kinds of beneficial effects- I just don't see how he could be totally wrong.

JLL October 9, 2009 at 7:29 PM  


There seems to be a lot of debate over whether diets deficient in omega-3 cause problems or not. I haven't had time to really dig into it yet, but I plan to do so.

We do know that humans can synthesize Mead acid (an omega-9 fatty acid) when EPA/DHA consumption is extremely low. Some people say this is a good thing, others say it's bad (see Ray Peat vs. Mary Enig, for example).

Definitely looks like no benefit from increased DHA in tissues -- quite the opposite. Some people consider lower cholesterol from PUFAs a good thing, but I don't. There's also some studies showing improved mental performance from EPA & DHA (at least in rodents), but I wonder whether this is a short-term benefit with possible long-term harm.

Never heard of Udo Erasmus, before. Will check him out, though.


Anonymous October 9, 2009 at 11:03 PM  

I'm late, but in re: wound healing: there is evidence that day length has an adverse effect if sleep is reduced in accordance with seasonal changes at high latitudes. Check data on injured polar workers.

Coconut fatty acid applied to some sorts of wounds (atopic dermatitis) will re-establish the acid mantle of the skin and bring about healing. This is good for other skin problems such as rosacea and eczema.

Cocoa butter is also good for protecting wounds while they heal and reduces scar formation.

As an aside: all of the 'liver spots' on the dorsal surfaces of my hands are due to burns from splattering oil or touching the edges of the oven etc. They shrink with time but remain as flattened melanotic scars. A life lived; not a liver spotted. :)

g kadar


Aaron October 10, 2009 at 2:42 AM  

I still wonder why our body takes the precursor ALA and turns it to DPA and others if this was really a destructive process. Same thing was the conversion of LA.

If polyunsaturates were just straight up toxic-- wouldn't we just leave them alone or try to oxidize them? Why would our bodies elongate them even further?

I'm actually doing a month long experiment myself to see if taking 2 tbsps of UDOs choice oil (udo erasmas) gives me any beneficial effects. I hope you get a chance to check out his site-- or even his book for that matter. I've known about him for a while-- as well as ray peat-- but i really can't resolve the polyunsaturate issue-- I do know that keeping omega 6 low though is beneficial.

Also, if you are not already familiar with him-- check out he is the self-experimental king. You'll love to read his blog. In fact, he's done many tests on flaxseed oil-- you should look through his blog if you have the time.

Anonymous October 10, 2009 at 4:07 AM  

PUFAs having a 2yr half-life confuses things.

I swear I have a reaction to too much n3s. To slopped together a theory, maybe it's a reaction involving the loads of n6s strapped to my body.

In a recent post, Dr. Davis doesn't have great blood levels of n3s though he's been supplementing for long.

Aaron October 10, 2009 at 9:23 AM  

Jack, I've noticed that my blood sugar seems to get really low on occasion when i consume a lot of omega 3s-- especially when i consume a lot of chia or flax oil.
The reaction also occurs when I eat something with a ton a sugar--

I can't tell if this is a good thing to be so sensitive to sugar that I get hypo symptoms from omega 3 intake. One things for sure-- my joints always feel so good on flax oil-- without question! While i always seem to get cranky joints after eating potatoes or beans (which i don't eat much) -- flax oil is the complete opposite, making my joints feel like a well oiled machine. Also, I notice an increase in leg fidgetiness, not sure if I can classify that as being good.

I just don't think we can dismiss the benefits to parent omega 3 intake (ALA). Your body then controls how much fully formed omega 3 to make (which is better than consuming fish oil which go rancid fast).

stern November 8, 2009 at 11:06 PM  

ages in meat ? for a while they got also ages in crust carbs now they found crust is full with antioxidant that counteract any age effect

stern November 8, 2009 at 11:07 PM  

ages in meat still ages in carbs crust ?now they found crust is full of antioxidans that counteract any ages

gwarm July 30, 2011 at 8:36 PM  

Looks like DrGreger's latest video is out - 2011:​1autoplays

What do you make of this? Arachidonic acid and mood: (@4m48s neuroinflammation)

Old videos:​plete​10pdfs

JLL August 2, 2011 at 11:42 AM  


Thanks for the links, I'll look into them. I'm now watching DrGreger's latest video on antioxidants. The paper he refers to is interesting, but I'm no longer very impressed by antioxidants (especially when we're talking about ORAC scores). Where is the evidence that more antioxidants is better in vivo?

For example, he says liver has less than antioxidants than a Snickers bar -- yet does anyone really think eating Snickers bars is healthier for humans than eating liver? I don't.

Hormesis, which I believe is the key to any health benefits from antioxidants, follows an inverted J- or U-curve, it's not a straight line. Taking a thousand blueberry extract pills is not necessarily a good idea.


Anonymous October 29, 2011 at 12:18 PM  

Hi, I stumbled upon your blog and I've been reading through the articles non stop for the past 2 hours.... I LOVE it.. So addictive!

I find this post really fascinating. I switched to a mostly raw food diet because of AGE's and other toxins generated during the cooking process. But maybe you're right, maybe the AGE's generated inside our bodies matter more! It makes sense.

What do you think about monounsaturated fats for cooking and salads? For some reason, I'm still scared of saturated fats, most mainstream nutritionists make it out to be the big dietary villian. I use olive oil for salads and Avocado oil for occasional cooking (has almost the same fatty acid profile as olive oil except a much higher smoke point). Olive oil is made up of oleic acid and the graph shows that oleic acid is much more stable than arachidonic and linolenic acid inside the body.. so why not use these instead of saturated fat for frying? Sorry if thats a dumb question, would be really interested to hear your opinion though..

Have a great day- I can't wait to try out some of the experiments on your blog for myself! :)
- Laura

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