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:
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
