Friday, September 4, 2009

Eating Meat or Going Vegan? Comparing AGE Levels in Vegetarians and Omnivores

Vegetarians have higher levels of AGEs than meat-eaters.
Vegetarians have higher levels of AGEs than meat-eaters. (Photo by Sandy Austin)

As a continuation of my previous post on the AGE content of foods, I'm currently going through a ton of papers on AGEs and desperately trying to organize them into blog posts in some sensible way.

In general, it seems that there is a lot of information on AGEs in vitro, but much less in vivo data. Specifically, only a few studies have looked at how various diets affect the accumulation of advanced glycation endproducts in humans – which is what we're really interested in, after all.

One of these studies compared serum levels of AGEs in omnivores and vegetarians (link). While this is from a few years back and has already been discussed on other blogs, I think it deserves another look. The full paper has some interesting details not mentioned in the abstract.

Since almost any variation of a vegetarian diet is lower in exogenous AGEs (that is, AGEs formed outside the body) than meat-based diets, the authors expected vegetarians to have higher levels of plasma AGEs. The surprising result of the study was that the vegetarians had higher levels of AGEs – despite consuming much lower amounts of AGEs in their diet. This means that endogenous AGEs (those formed inside the body) played a bigger role than previously thought.

The vegetarian and omnivore diets

So what did the diets look like in practice? Instead of one "vegetarian diet", there were in fact three different vegetarian diets: a vegan diet (V: plant foods only), a lacto-ovo-vegetarian diet (VLO: plant foods, milk, eggs, dairy products), and a semi-vegetarian diet (VS: the same as VLO but with fish). And then there was the omnivore diet (O), which was a traditional Western mixed diet without any food limitations. Here's a breakdown of the diets:

The composition of omnivore and vegetarian diets
Looking at the table, we can see a few important differences between the diets. First, protein consumption was lower in all the vegetarian diets compared to the omnivore diet. Second, perhaps surprisingly, carbohydrate consumption did not differ significantly between groups – if anything, the omnivores ate more carbs. Total calorie intake is not reported, but since the BMI was lower among vegetarians (especially vegans), they probably consumed less calories in general.

The third and most important difference is the amount of fructose in the diet. All vegetarians ate more high-fructose vegetables and fruits than the omnivores. The vegans ate more than twice the amount of high-fructose fruits than the omnivores. The difference in citrus fruit consumption between omnivores and vegetarians is very big. Vegetarians also consumed more honey. Interestingly, the omnivores drank more fruit juices than the VS and VLO groups, while vegans drank the most.

In addition, the vegetarians consumed less milk, yogurt, cream and cheese but more legumes than omnivores. Total grain product consumption was similar in all groups, but the intake of unheated processed grain products (such as muesli and oat flakes) and whole grain products was 3 to 6 times higher in vegetarians. On the other hand, cooked and baked grain product intake was higher among omnivores. So basically, the omnivores were eating their share of white bread, while the vegetarians favoured things like whole grain pasta.

Vegetarians, omnivores and AGEs

Two plasma measures of AGEs were used in the study: fluorescent AGEs and CML. Both are common markers of circulating AGEs. The amount of fluorescent AGEs in plasma was lowest in omnivores and highest in lacto-ovo-vegetarians. Among vegetarians, vegans had the lowest fluorescent AGE levels. The differences became more clear when AGEs were adjusted for the amount of protein in plasma. Therefore, if the vegetarians had consumed as much protein as the omnivores, their AGE levels would probably have been even higher. Still, even with this adjustment, vegans still had lower levels than other vegetarians.

The amount of CML in plasma followed a similar trend. Again, omnivores had the lowest levels, but this time semi-vegans had the lowest levels among vegetarians. Lacto-ovo-vegetarians had the highest levels, and vegans had somewhere in between.

So what could explain these findings? The authors rule out the possibility of age being a factor here, since plasma levels of CML and fluorescent AGE are not significantly different in the age bracket of 30-60 years. Both values are useful mostly as short-term markers of endogenous and exogenous AGEs. Indeed, neither measure tells us much about the tissue accumulation of AGEs, except that high serum levels of AGEs most likely cause high tissue levels of AGEs in the long run.

Carbohydrate consumption is also unable to explain the difference in AGE levels between omnivores and vegetarians.
Since there were no significant differences in fasting blood glucose levels between the groups, and the omnivores ate more carbohydrates, elevated blood glucose levels are probably not reason for increased glycation in vegetarians. Also, the omnivores ate less whole-grain products, so clearly, the explanation for higher AGE levels in vegetarians can't be that they should have chosen "healthier" grain products instead.

Inflammation and oxidative stress are also out of the question, because inflammation markers were within the normal range in all participants, and plasma antioxidant levels were actually higher in vegetarians. Furthermore, lipid peroxidation was lower among vegetarians.

Does meat protect from the effects of fructose?

Two possible explanations come to mind: either the higher fructose consumption among vegetarians resulted in higher levels of endogenous AGEs, or there is something in animal protein sources that protects from AGEs.

Fructose is indeed much more prone to glycation than glucose (link), which would explain why the same carbohydrate intake can result in different AGE levels depending on the ratio of fructose to glucose. On the other hand, if this were the only explanation, then one would expect to see the highest levels of AGEs in vegans, who presumably ate the most fructose. Yet, it was the lacto-ovo-vegetarians who had the highest levels. The VLO group ate less high-fructose vegetables and fruits, less honey, and less fruit juices than vegans.

What about the animal protein explanation? Vegans obviously consumed no animal protein at all, while the VLO group consumed less than the semi-vegans and much less than omnivores. They consumed less protein in general, despite eating the most legumes. It seems unlikely that animal protein from dairy products had a significant protective effect, because semi-vegans and lacto-ovo-vegetarians ate dairy products while vegans didn't.

It has been hypothesized that a deficiency in taurine is the reason vegetarians have higher AGE levels and that taurine supplementation might bring AGE levels down (link). Since taurine is found mostly in meat and seafood, strict vegan diets have very little taurine. Carnosine is another molecule found mostly in animal sources. Both carnosine and taurine prevent glycation in vitro. Unfortunately, taurine and carnosine intakes between the groups were not measured in this study, and there are no human studies on glycation in vegans supplementing with taurine and/or carnosine.

Neither of these explanations is entirely sufficient. If fructose is the main cause of serum AGEs, and carnosine and taurine protect from glycation, then one would expect to see the highest levels of AGes in those who eat the most fructose and the least carnosine and taurine – vegans. But this is not the case. The amount of AGEs in food is obviously also not the only explanation, because omnivores must have consumed the most AGEs and vegans the least.

It's quite possible that a combination of all these factors is the reason behind the differences in AGE levels. Meat is very high AGEs, and yet eating meat does not result in huge levels of AGEs in the serum. On the other hand, eating very little AGEs with food does not guarantee low serum levels of AGEs. Perhaps eating foods somewhat high in AGEs and fructose while not eating meat is the worst combination of all, as the high levels of AGEs in lacto-ovo-vegetarians seems to indicate.

I will continue with the AGE theme in upcoming posts, once I finish reading the papers and making more sense out of all this.

For more information on diets and glycation, see these posts:

Yerba Mate Inhibits AGE Formation
The 7 Types of Aging Damage That End up Killing You
Green Tea Reduces the Formation of AGEs
A High-Protein Diet Is Better than a High-Carbohydrate Diet for Weight Loss

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25 kommenttia:

Aaron September 6, 2009 at 8:05 AM  

JLL, any mention of the fat content of the different diets-- that would tell me if Fat was partially to blame for the high AGEs reported in the people.

I'm a little worried about butter these days-- it is so loaded with AGEs

JLL September 6, 2009 at 12:28 PM  


There's no mention of fat intakes, strangely. Given that the omnivores used cream and cheese quite liberally, I would imagine they ate some butter as well.

Aaron September 6, 2009 at 5:56 PM  

This study would have been the god of all studies if it showed fat intake.

The reason why I worry so much-- even if you are low carb and burn fat like crazy-- the fat you eat becomes you before you burn it-- I don't want high AGE foods to become me.

Think of the difference in using cold-pressed olive oil vs butter in terms of AGE content-- BIG DIFFERNCE.

I'm also starting to think that it might just be better to let your body create fats out of carbs because then you KNOW there won't be AGEs.

Becoming fat on a higher carb diet is only a problem if you overconsume.

Overall, I'm starting to assume a Kitavan type diet is best for all: its low in anti-nutrients,low in fructose, low in protein, low in fats (but then low in AGEs as well)

Remember, we can't infer much from the omni diet-- they consumed tons of carbs-- its possible that if they lowered carbs and up'd fat intake-- the AGEs might have gone up or down (but I think up because fat contains so much of them).

Honestly, I look at people who consume a lower fat diet and they almost always look younger if they don't eat processed crap (look at asian peoples).

Eating a low protein, low fructose, low fats in AGEs, and eating carbs that are low in anti-nutrients seems the perfect way to go.

Otherwise, you'll have to find a fat that is low in AGEs which is hard to find. I can't help but think most of the positive benefits to low carb studies has to do with the fact that calorie intake drops significantly.

We need to think about this--

Daniel September 6, 2009 at 11:44 PM  

I've been coming to a similar conclusion lately. For some time, I was trying to figure out how to thread the needle between (i) limited and balanced polyunsaturated fat intake, (ii) low sugar, especially fructose and lactose, (iii) proper nutrition, (iv)low AGEs, and (V) low-carb.

There's basically no way to do it. Raw eggs and coconut oil as major sources of calories get you all except proper nutrition -- you will have way too much biotin, riboflavin, and panthothetic acid for instance.

However, giving up the constraint that seems least necessary (i.e., low carb) allows one to solve the problem by eating a high starch diet. Potatoes and rice as major sources of calories get the job done.

That said, an extremely low-carb diet may offer some AGE benefits if you are in ketosis - by inducing chaperone-mediated autophagy:

JLL September 7, 2009 at 12:02 AM  

@Aaron & Daniel,

As long as you consume carbs, there will be endogenous glycation. If the carbs raise blood sugar substantially, glycation goes up as well.

I'm also not sure all fats are high in AGEs -- butter probably has AGEs because of the way it's processed, but saturated fats not susceptible to oxidation might be low in AGEs.

We don't know what the serum levels of AGEs are in Kitavans. I wouldn't be surprised if they were high. Maybe they do well despite high levels of endogenous AGEs.

With ketosis, there's the issue with methylglyoxal. Dr. Eades doesn't think it's a big deal, but I'm not sure. Periodic ketosis is probably good, at the very least.

Aaron September 7, 2009 at 4:35 AM  

JLL-- do you believe glycation goes up even if we have room to store glycogen in our liver and muscles? Isn't that what our IF feed schedule is for-- to give ourselves room to eat foods that will optimize our activity and recovery.

We know fructose and high protein is destructive( at least in terms of methionine). We obviously have a tolerance for other fat/carb ratios-- but it would be nice to know the ratio that leads to the greatest longevity. We can lower protein intake to the lowest possible intake by consuming enough carbs so that out body doesn't have to make much from glycogenesis.

What about this study:

I'll also grant that ALEs in food might not go that much damage (vindicating butter)

As a side note-- i saw that you had slower wound healing since your change in diet. 10 days ago I separated my shoulder (type 3) I up'd my carb intake under the premise that it might speed my healing- I had a HUGE black and blue mark all over my shoulder and pec-- after about 7-8 days after the injury-- it was subsiding and starting to turn yellow-- I have noticed faster wounder healing in my bruises now on a higher tuber diet than when I was at 40-50 carbs a day-- now i'm at 100-200 a day.

I also grant that after topping off liver glycogen stores-- excess carbs might cause you to AGE faster-- but i worry more about having too much junk spit out from mitochondria-- high fat diets increase the number of mito in the body-- how can this be a good thing if they generate byproducts that damage our genes?

JLL September 7, 2009 at 9:37 AM  


I don't see why intracellular glycation wouldn't happen even when blood sugar isn't constantly high. IF is most likely better than constantly eating, but nothing can completely prevent AGEs from forming.

Yes, it would be nice to know which fat/carb/protein ratio leads to the greatest longevity. Why do you think low protein is the way to go? To avoid methionine? Methionine restriction can't be done by eating a low protein (human) diet. The methionine restriction diets on rodents have been engineered specifically for the task. To see results, methionine has to be extremely low, which is impossible if one is eating real foods. And just cutting back on methionine, say 10-20%, hasn't been shown to do anything. Vice versa, is there any evidence showing more methionine is bad? I have not seen any.

As for the study you posted, well, I'm not worried. First, it was done on mice, not humans. Second, the mice got diabetes from eating a high-fat diet. Humans don't. Usually these "high-fat diets" are just ordinary diets with extra fat, which is different from a low-carb, high-fat diet.

I'm currently at about 100 grams of carbs per day.

Your point about increased mitochondria = increased damage is interesting, but ketogenic diets increase mitochondrial function as well:

All in all, I assume it's a net positive.


Daniel September 8, 2009 at 9:20 PM  

So in healthy non-diabetic people, is the idea that a high starch meal raises postprandial glucose more than a high fat meal and that such increase results in more endogenous AGEs?

I think it's clear that if a the cumulative effect of high starch meals over a life-time produces insulin resistance and chronically elevated blood sugar, then lots of endogenous AGEs result.

However, I didn't know that in healthy people a high starch meal raised blood sugar comparatively more than a high fat meal, resulting in a similar, albeit temporary, detriment.

I know there are studies that show that vegetarians and raw food adherents have higher AGEs, despite consuming diets lower in them. I thought that their extra fructose consumption was the likely problem. And, I thought the mechanism was that fructose would fructate protein (i) in the stomach and (ii) in the blood on its way to the liver through the portal vein. It sounds like you're suggesting that the problem was higher average (time average) blood sugar levels.

That's not what I thought but maybe that's right...

Is that what you were thinking?

Aaron September 9, 2009 at 8:18 AM  

Well, whats interesting Daniel is that over time, most people on super high fat diets have higher readings of blood glucose (like around 100) but it never really goes anywhere because barely any carbs are consumed (think peter at hyperlipid)- this is different then people (who eat some moderate carbs) who have a reading of around 80 (during fasting) but the value jumps whenever they have carbs in a meal.

JLL -- I'll admit, in theory I used to think a higher carb diet might have been better than a higher fat one because of increased SHBG on a higher carb diet-- and reduced hormone levels-- but if you keep fat high, carbs low, and protein low/moderate -- your levels of growth producing hormones also drop (one of the main reasons why bodybuilders use carbs-- for anabolic action) -- not to mention all of the glycation from a higher carb diet--

As of right now-- I'm not going to worry about carbs (as long as i only eat around 100-150 g a day, but I want the ALE and AGE question of the equation soloved so I don't have to worry about foods like butter--

Reamz September 9, 2009 at 2:22 PM  

i just found this blog and am just reading through all the archives - really interesting stuff!
but I have a few questons (forgive me if they're stupid, its difficult to get my head round all the science!)
first of all, about the statement above - higher blood glucose levels in people with high fat/VLC diets - is this a bad thing?
Also, as regards ketosis, if one is eating practically no carbs are they always in ketosis (i've heard the eskimos who eat practically zero plant foods are not in ketosis) - what does this mean?

And finally, do you think some of the AGE content in foods that have been analysed are partly due to the animals not fed their natural diet? ie the butter/meat etc comes from grain-fed cattle rather than grassfed so theyactually have more AGEs? (when looking through the tables of AGE content in foods i noticed some raw foods like raw salmon or raw chicken had some AGEs in them)
If regular pasteurised butter had AGEs would raw cream/butter have AGEs too?

Daniel September 9, 2009 at 7:58 PM  

I didn't know that people eating very low carb can have such high blood sugar = do you have a reference you can point me to/
Thanks, Dan

Aaron September 27, 2009 at 6:19 AM  

I keep coming back to this article-- first off, having the fat content absent is unfortunate- interesting that the vegans had the lowest AGE formation of the group-- especially considering they probably had the highest fructose intake!

I'm starting to think saturated fat-- coupled with a lower polyunsaturated fat intake, is what make the AGEs lower in the meat eaters-- I bet that polyunsaturated consumption was highest in the group with the highest AGEs-- believe it or not, I'm starting to view fructose in a little better light!

I don't always agree with Ray Peat-- but the link below is what made me think of these things-- he is on to something here- his article also explains possibly my body feels so stressed when going low carb (50 or less carbs per day, of course I don't think you should go 200+). And it also explains the stresses of eating tubers in comparison to fruits-- its a gem.

It also semi-explains an idea I've had for some time in how carbs might be longevity preserving because if its effects on mitochondria (he explains it because of a carbon dioxide mechanism).

please comment if you can!

JLL September 28, 2009 at 2:02 PM  


I'm also beginning to think PUFAs are the main culprit. It is possible that the vegans ate more PUFAs, but of course we don't know that because the data isn't available.

Unlike Ray Peat, I would choose tubers over fruit. The body isn't used to handling large amounts of fructose, but it can cope quite well with glucose. The liver is going to have problems with high fructose loads, plus there's the ten-fold reactivity to form AGEs.

But, that's my opinion at the moment, if further evidence comes along, I'm willing to modify it.

Lacto Ovo Vegetarian October 1, 2009 at 11:12 PM  

We need to be careful of fat intake...that is the major driver of a lot of these diseases. btw check out this great site for helping men in becoming vegetarian.

Med Dog November 25, 2009 at 2:56 AM  

Wait a tick. "Healthy" grains? What about the high lectin and phytotoxin content of unprocessed grains? Isn't the whole point of fermenting bread to reduce the toxins in monocots (and help liberate calories)? If you want to look at something "bad" that vegetarians eat, how about those unprocessed grains? Then again, if the omnivores are getting plenty of gluten as well, maybe this isn't the issue. Just a thought.

Anonymous December 2, 2009 at 1:04 PM  

What about meat substitutes?

"The results indicate that diet can be significant environmetal source of AGEs, which may constitute a chronic risk factor for cardiovascular and kidney damage"
"High values obsevered for the meat and meat-substitute group"

llow-calorie-diets February 15, 2010 at 6:42 AM  

I also grant that after topping off liver glycogen stores-- excess carbs might cause you to AGE faster-- but i worry more about having too much junk spit out from mitochondria-- high fat diets increase the number of mito in the body-- how can this be a good thing if they generate byproducts that damage our genes?

JLL February 15, 2010 at 10:22 AM  


Are you saying that a lower number of mitochondria is better than a higher number? Even though the number of mitochondria decreases with age?

PhilipJTerry April 5, 2010 at 11:51 PM  

This study may give us a few clues although not conducted on humans... Why are we lacking in such valuable studies...??

What do you make of this?

Read the part: "Life Span of Female Drosophila Given Foods of Different Caloric Value"

PhilipJTerry April 21, 2010 at 3:48 PM  

Fantastic debate JLL...

It looks like fructose is bad news if mixed with protein.
"A 1997 study concluded that adding sugar to egg whites causes diabetics to be 200 times more AGE immunoreactive.["

They are mixing their foods together milk protein with fructose = greater ages higher reaction between them
On top of that milk protein contains methionine which I understand induces hyperglaecmia - high blood sugar

Vegans dont eat that much protein which does not react with the sugar.

fructose, or fruit sugar, seems more reactive than glucose...?

As for the fats it seems Mono's are favourite AND it helps HDL transport LDL out of the arteries:

I am eating more avocadoes and olive oil now... :) I think they are more protective than destructive as
per your table of AGES.

In this study we found that serum fructosamine in subjects
with no history of diabetes and with normal serum glucose
( 126 mg/100 mL) is directly associated with glycemic load.
Furthermore, fructosamine was directly associated with **polyunsaturated
fats and alcohol in the diet, and inversely with
***monounsaturated fat, and physical activity.

The most important findings of this study are the positive
association of glycemic load, ***saturated and ***polyunsaturated fat
(animal fats) and alcohol with fructosamine, and its inverse
relationship with monounsaturated fat (vegetable fat), and
physical activity

To conclude, the results of this study support the hypothesis
that not only the quantity but also the quality of carbohydrate
and fat are important for control of fructosamine, a measure of
glycated serum proteins, and a marker associated with both
cardiovascular disease and overall mortality.

My conclusion don't mix egg whites mixed with fructose (see wikipedia on advanced glycation)

Every problem in aging seems to stem from strict control of blood glucose and lowering insulin.
Then we depend on fat which is highly reactive as I understand around the mitochondria...

We should bring in something else to the equation - oxygen.

If we run low on oxygen our body turns to fat instead of glucose as an energy source. That gets more reactive around the mito's

So far my conclusion

. Mono's good
. moderate Omega 3 fish good (the omega 3 i think over compensates for the PUFA's and mercury, but please challenge me on this?!)
. predominant diet based on low fructose fibrous vegetables (kale, spinach, brocolli, asparagus, greens) that have a slow trickle release of just enough carbs
. occasional black beans, lentils low sugar slow release carbs seem to be the favourite carb source for me anocynanins

A low carb, moderate mono, high vegetable, moderate white protein (lowish methionine) diet is my favourite option so far...

And this ties in with all the blue zones - mediteranean, okinawa etc..

protein that triggers IGF'1 does not look good (red meat is positive in that area)

I guess it depends on what your goal is - to go for extending mean or maximum lifespan as these two goals
from some research seem to conflict each other a lot... (the PUFA/ saturated fat debate for example)

please argue against me on this for discussion.

Thanks for the great info JLL


JLL April 22, 2010 at 5:41 PM  


Fructose is indeed much more reactive than glucose; excessive fructose consumption in general seems to be very bad. It's good to keep in mind that PUFAs are even more reactive. Importantly, however, in vitro results don't always translate into in vivo results -- e.g. fish oil and high-fructose fruit such as apples may be a net positive despite how bad they look in vitro. At the moment, taking some fish oil to balance omega-3/omega-6 ratios looks okay, and the vitamin E probably counteracts much of the lipid peroxidation. I guess its usefulness depends on what your PUFA & omega-6 intakes are.

I'm still not sure whether MUFAs or SAs are better -- there is more evidence in favor of MUFAs, but most of the studies are not very well controlled. I'm steering clear of excess PUFA consumption in any case. The fructosamine study you linked to is interesting, I will look further into that.

How can you have a low-carb, high-vegetable diet? What kind of macronutrient balance are we talking about exactly?

By red meat being positive, do you mean that it increases IGF-1? Because I'm not sure it does:

"The major sources of animal protein, including milk, fish, and poultry, but not red meat, as well as total vegetable protein, were associated with an increase in IGF-I levels."

I find it kind of strange that poultry raises IGF-1 but red meat doesn't, given that total protein intake is, at least in some studies, associated with increased IGF-1.

"Serum IGF-I levels were positively related to protein intake (P(trend)<0.001), but not related to energy, fat or carbohydrate intake."

For now, I try to avoid too much casein, which pretty consistently raises IGF-1. I probably still get too much casein from drinking cafe lattes and eating cheese occasionally...


Sandy September 6, 2010 at 9:46 PM  

Philip wrote-
"A low carb, moderate mono, high vegetable, moderate white protein (lowish methionine) diet is my favourite option so far...

And this ties in with all the blue zones - mediteranean, okinawa etc.."

not sure if it's worth posting this given the age of the post, but thought I'd write this after a recent discovery-

The data for what blue zone folk eat may not be quite as the researches make it out to be, for example the research team claim the Sardinian blue-zoners eat a plant based diet whereas the bbc link below says 'meat is firmly on the menu' and they don't restrict calories either. Good news if it's true!

Anonymous March 4, 2014 at 6:10 PM  

Ask Dr. Wallach he would be happy to explain it all.

Anonymous August 28, 2014 at 9:04 AM  

JLL, I know this is an old article, and not sure if you still check the comments, but anyway...

If there is something in meat preventing AGEs, is it possible it has not been discovered yet, rather than carnosine or taurine being responsible?

I wonder if it's to do with the fact vegetarians take in more anti-nutrients from vegetables and grains, thus being deficient in minerals that play a role in reducing AGE formation? Or perhaps lectins or WGA from wheat inhibiting important enzymes?

Just thinking out loud here. Good post.

JLL August 28, 2014 at 6:12 PM  


Yes, I still read the comments (there's so much spam that I have to read them before I publishem each comment). And yes, it's possible we haven't found all the things that protect from (or cause) AGEs.

One thing I learned after writing this post was that perhaps consuming AGEs isn't as important as eating foods that cause AGEs inside the body -- that is, even though meat is high in AGEs, only a small percentage of them is absorbed.


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