AGEs / ALEs

[JeffC]

Would love to see a study done in humans in this context. As far as I know, rats are not evolved on fruits, and may react very differently on fructose.

You'd have to identify a particular significant reason that rats would react differently. Rats are used for tests because they're mammals that are biologically similar to humans. Rats absorb fructose in the small intestine and metabolize it in the liver, just like humans.

Here are a few other rat fructose studies, for fun:
"Dietary fructose causes tubulointerstitial injury in the normal rat kidney." Nakayama
"Rats Fed Fructose-Enriched Diets Have Characteristics of Nonalcoholic Hepatic Steatosis" Kawasaki
"Deficiency of dietary n-3 increases vulnerability to impaired cognitive functions, and intake of a high fructose diet exacerbates this condition" Agrawal

Where are the Sources or Citations?
Did they specify what units (g,°C) is considered as: "no", "low", "medium", or "high" ?

The table is from the Uribarri study. They measured CML. I wrote the high/low descriptions in order to spotlight that temperature was not the only factor in CML content, and fructose was not being picked on by researchers. A raw food with no fructose had much higher CML than some heated foods.

The basic Wai diet theory seems to go like so:
Raw food (0-35°C) = very low temp = very low exogenous AGEs = healthy
Dehydrated food (35-70°C) = low temp = low exogenous AGEs = healthy
Moist-heated food (100°C) = too high temp = too high exogenous AGEs = unhealthy
Dry-heated food (120+°C) = very high temp = very high exogenous AGEs = very unhealthy

My view is that this theory oversimplifies things, does not look at the entire picture, and is improperly used to justify high fruit intake. Each food needs to be individually assessed. Temperature can be one factor in healthiness, but there are others. Toxicity is the only thing other than temperature mentioned in the Wai 'optimal diet' PDF. The thing that is most overlooked is endogenous AGEs. Fructose is especially a concern here. The Wai diet seems to ignore or downplay what fructose does to the body.

You are on very slippery ice now... Are you claiming that there is no overwhelming evidence that fruit and vegetable consumption is statistically associated with better health?

Again, you can also say alcohol is associated with better health. As long as you focus only on the few benefits while ignoring all of the problems.

[Kasper]

You'd have to identify a particular significant reason that rats would react differently. Rats are used for tests because they're mammals that are biologically similar to humans. Rats absorb fructose in the small intestine and metabolize it in the liver, just like humans.

You are contradicting yourself, as before you said you agreed with the following article: http://chriskresser.com/ask-chris-is-fr ... y-that-bad

Dr. Lustig argues that, when compared to glucose, fructose is uniquely fattening. He claims that fructose is the most efficient substrate for de novo lipogenesis (DNL), which is the process by which the liver converts carbohydrates to fat.

However, Dr. Lustig relies on animal evidence that doesn’t apply to humans. There’s a big difference between mouse carbohydrate metabolism and human carbohydrate metabolism. When mice are on a high-carbohydrate diet that doesn’t provide excess calories, it’s common to see DNL rates of 50 percent and up. In other words, they are efficient at converting carbohydrates into fat, even when they’re not overeating. (1)

But in humans on an isocaloric diet (without excess calories), de novo lipogenesis falls into the range of 10 to 20 percent. The conversion of carbohydrate is less efficient in humans than it is in mice.

The research in this area is robust and uncontroversial. Nearly 50 controlled feeding studies have been performed on various aspects of cardiometabolic control. Most investigators working in this field believe that DNL in humans is negligible in response to fructose, and doesn’t comprise a significant source of dietary calories.

There’s another problem with extrapolating the animal evidence to humans in this case. The mice in the studies Lustig cites are eating huge amounts of fructose: up to 60 percent of total calories. You’d have to drink more than four 44 ounce Super Big Gulps a day to get that much fructose. Ain’t gonna happen.

According to researcher Dr. Sievenpiper in an interview with science writer David Despain at Evolving Health, the 50th percentile intake for people in the U.S. is 49 grams per day, which works out to 10 percent of total calories. Even the 95th percentile intake of 87 grams per day doesn’t exceed 20 percent of calories. That’s a lot of fructose, but it’s nowhere near the 60 percent of calories fed to mice.

60% of calories being fructose is crazy. Everybody can tell you that. Even if you eat 400 gram of sugar in a 3000 cal diet, you only have 25% of your calories from fructose.

Again, you can also say alcohol is associated with better health. As long as you focus only on the few benefits while ignoring all of the problems.

Alcohol is U-shaped assiociated with better health, there is no linear correlation.

[RRM]

You are on very slippery ice now... Are you claiming that there is no overwhelming evidence that fruit and vegetable consumption is statistically associated with better health?

Again, you can also say alcohol is associated with better health.

No, you cannot.
Studies overwhelmingly show that veggies and fruits are statistically associated with better health.
This is not true for alcohol.

[JeffC]

animal evidence that doesn’t apply to humans.

Dietary fructose induces endotoxemia and hepatic injury in calorically controlled primates
"Even in the absence of weight gain, fructose rapidly causes liver damage that we suggest is secondary to endotoxemia and microbial translocation. Hepatic steatosis relates to the duration of fructose consumption and total calories consumed. These data support fructose inducing both MT and ectopic fat deposition in primates."

No, you cannot.
Studies overwhelmingly show that veggies and fruits are statistically associated with better health.
This is not true for alcohol.

Here is an example of someone who says alcohol is better for health by arguing only the benefits while ignoring the problems.
Benefits of Moderate Drinking Result from Alcohol Itself
"It’s clear that the moderate consumption of alcohol improves health and increases longevity."

You do not seem to understand the point of what I'm saying. I will give an extreme example.
Imagine that you have a headache, and so you drill a hole through your skull into your brain. The headache goes away.
RRM's way of thinking: "It has been shown that skull-drilling cures a headache."
JeffC's way of thinking: "Yes, there is the benefit of curing the headache. You can have benefits and problems at the same time. You are ignoring all of the problems with skull-drilling, such as major bleeding, skull damage, and brain damage."

[Kasper]

Ah, that is an interesting study, thanks for sharing it. I wonder what RRM has to say about it.
http://ajcn.nutrition.org/content/early ... l.pdf+html

Not completely sure about the study design. There seems to be a lot more differences than only frcutose in the two groups. But assuming that is done for a good reason, I don't think this really shows that fruit is unhealthy. This study basicly shows that adding a very high amount of pure fructose to a diet causes problems in primates. I'm not that suprised about that. But do you really think if they instead of pure fructose, they had enriched the diets with fruits, or honey, they would have got the same results ?

For example, if instead of fructose they had put bananas in there. Do you think primates eating bananas, all get liver damage ? But those primates eating wheat flour, or whatever they are giving them, will be much better off ?

[JeffC]

But do you really think if they instead of pure fructose, they had enriched the diets with fruits, or honey, they would have got the same results ?

The study says that the HFr monkeys got 24% of energy from fructose. This number is interesting to me, because at my Waipocalypse peak, I was getting about the same amount. It wasn't all refined sugar. I was drinking a lot of orange juice. Fruits may slow down the damage compared to fructose alone, but I still think it happens over time.

[JeffC]

Recap of discussion

Question: Are boiled potatoes a healthier choice than raw fruits?

Disagree (Wai):

1. Higher temperature foods always have more exogenous AGEs than lower temperature foods. (Source: RRM)
--Counter: Boiled potatoes have only 17 kU CML, raw fruit level. (Source: Uribarri)
----Reply: CML is only one AGE and it is fructose specific. Potatoes have more total AGEs. (Source: RRM)
------Counter: CML is not fructose specific and is used by researchers as a general indicator of AGEs. (Source: Min-Xin Fu, Semba, etc)

2. Potatoes contain toxins.
--Counter: Glycoalkaloids/solanine are avoided by removing skin. Acrylamide does not form at 30 minutes of 100°C. [RRM deleted all posts related to acrylamide.]

3. Fruits are high in antioxidants.
--Counter: Potatoes are also high in antioxidants. (Source: Prior)

Agree (JeffC):

1. Potatoes lack the amount of highly damaging fructose that fruits have. (Source: Levi, Kudlácková, Lustig, etc)
--Counter: A lot of things can form endogenous AGEs, not just fructose.
----Reply: But fructose forms more. (Source: Suarez, Hinton, etc)
--Counter: Higher levels of fluorescent AGEs actually indicate better health(!!). (Source: Kudlácková)
----Reply 1: That was not Kudlácková's conclusion. ("The risks of [the high-fruit diet] may be reduced by better choice of foodstuffs.")
----Reply 2: AGE fluorescence is significantly higher in chronic alcoholics than in healthy subjects. Kalousová
--Counter: There are health benefits to fruits.
----Reply: Yes, but having some benefits does not entail the absence of problems (as in alcohol).
--Counter: Rat fructose studies don't apply to humans. (Source: Kresser)
----Reply: There is a primate study as well. (Source: Kavanagh)

[Kasper]

Nice recap JeffC.

The study says that the HFr monkeys got 24% of energy from fructose. This number is interesting to me, because at my Waipocalypse peak, I was getting about the same amount. It wasn't all refined sugar. I was drinking a lot of orange juice. Fruits may slow down the damage compared to fructose alone, but I still think it happens over time.

How are you sure that you don't just have fructose malabsorption ? Or, maybe you just have specific problems with orange juice ? You have done a dextose experiment, what about a sucrose experiment ? Or a honey experiment ?

Personally, I have had times that I wouldn't react good on orange juice at all, and I still sometimes have problems with orange juice. But for example, pure sucrose, doesn't seem to give me problems, at least not anymore. I can drink 1 L of coke daily without problems, but 1L of orange juice daily sometimes give me problems.

My personal opinion is that potatoes after fruit are the best source of carb, and the ideal carb source if you don't react good on fruits (or fructose). And the best practical solution, if you don't react good on oranges or bananas in the Wai Diet.

Not just because they may contain very little AGE, but also important, because the vitamin/mineral content of a potato is very comparable with fruit. And I think that the resistant starch in potatoes may be very beneficial.

[RRM]

ha, ha , yes, nice recap.

Studies overwhelmingly show that veggies and fruits are statistically associated with better health.
This is not true for alcohol.

Here is an example of someone who says alcohol is better for health

Lots of people SAY lots of contradicting stuff.
Im not talking about opinions here.
The point is: what do very large long term population studies show us statistically.
They show us that veggies and fruits are correlated with better health.

CML is not fructose specific and is used by researchers as a general indicator of AGEs.

Of course CML is not fructose specific.
Thats is not the issue.
The issue is that CML is not representative for AGEs.
Sure, you may use it as a marker for specific AGEs.
You can use any AGE as a marker for similar AGEs.

Which group of AGEs may CML represent?
That group of AGEs that may already form at 37°C.
The ones that are the least harmful.
Which AGEs can CML etc. NOT represent?
The AGEs/ALEs that only form at higher temperatures, which includes all the worst AGEs/ALEs,
including the most cancerous HCAs and acrylamide.

Suppose that CML could represent all AGEs.
Suppose CML was a good marker for all AGEs.
That would mean that the consumption of fruits and veggies would result in the highest levels of all AGEs/ALEs.
More than other foods, including grilled meat, fried chicken, hamburgers etc.
Why?
Because the consumption of fruits and veggies results in higher levels of CML = all AGEs/ALEs, including the worst ones.
In that case, fruit and veggie consumption would be statistically related with poorer health.
Since the opposite is true, it is impossible that CML may be a good marker for AGEs/ALEs in general.
CML may only be a good marker for similar AGEs/ALEs that already may form at 37°C.

Question for you:
Would you think that CML might be a good marker for acrylamide?
PhIP?

[Aytundra]

Recap of Discussion Distractors
The idea of:
- CML as an indicator of AGEs is a red herring (distraction) in this discussion.
- Fructose equals alcohol is also a distraction in this discussion.
- book references, tunnels, tall men, money and brain surgery... are also absurd distractions in this discussion.

Current summary of main ideas:
- AGEs formed at higher and higher temperatures means more and more types of bad AGEs. (Source: RRM)
- Fructose is bad as shown in some animal studies with fructose consumed. (Source: JeffC)

[Aytundra]

Question: Are boiled potatoes a healthier choice than raw fruits?

Aytundra is still not sure which is healthier.

1. Higher temperature foods always have more exogenous AGEs than lower temperature foods. (Source: RRM)

But some trivial (uninteresting) example that support this statement is to compare boiled sugar water with any raw meat. This cooked "food" contains no AGE, so the point that JeffC was trying to make holds.

Aytundra agrees but only if stated like this:
1. Higher temperature (whole) foods always have more exogenous AGEs than lower temperature foods (of the same type of food items).

because as Kasper pointed out hot water with sugar is very unlikely to have AGEs.

3. Fruits are high in antioxidants.
--Counter: Potatoes are also high in antioxidants. (Source: Prior)

But heat may reduce a lot of heat-sensitive antioxidants like some heat-sensitive vitamins.

1. Potatoes lack the amount of highly damaging fructose that fruits have. (Source: Levi, Kudlácková, Lustig, etc)

No.
Aytundra thinks: Potatoes have very little amounts of fructose compared to most fruits, potatoes still have fructose in it.

----Reply: But fructose forms more. (Source: Suarez, Hinton, etc)

"more" means something is relative to something.
but why does it form more?
more because of fructose floating around freely exogenously because of high heat?
OR
more because of fructose floating around freely endogenously because not enough cells to process excess fructose all at the same time?

--Counter: Rat fructose studies don't apply to humans. (Source: Kresser)
----Reply: There is a primate study as well. (Source: Kavanagh)

are there more studies?

[RRM]

CML as an indicator of AGEs is a red herring (distraction) in this discussion.

Actually, imo its the core of this discussion.
AGEs/ALEs are by far the largest group of various types of reactive molecules, associated with ageing and diease.
That is what we agree on.
Some of them can (also) be formed endogenously, at body temperature.
But most of these AGEs can only be formed at much higher (than body) temperatures.
The former group of AGEs (CML etc) is relatively harmless, compared to those that may only be formed at higher temperatures (eg acrylamide, PhIP etc).

JeffC thinks the boiled potatoes are more healthy than fruits, because they (in comparision with fruit consumption) result in lower levels of endogenously formed AGEs/ALEs.
He thinks that these endogenously formed AGEs/ALEs may fairly represent AGEs/ALEs that are only formed at high temperatures.
That CML levels may represent acrylamide and PhIP levels.
He bases this notion on an article that lets CML represent AGEs, but only mentions AGEs that may form endogenously.
This article never mentiones those AGEs/ALEs that may only form at higher temperatures.

So, the essential question here is:
Can CML and similar AGEs that may (also) be formed endogenously, fairly represent all AGES/ALEs?

If the answer would be "yes", this would mean that veggies and fruits are most unhealthy,
because levels of AGEs that may form endogenously is higher in people consuming more fruits and veggies.
Large, long term population studies however, show the opposite: that the consumption of veggies and fruits is positively associated with better health.

Conclusion:
Endogenously formed AGEs/ALEs represent only a fraction of all AGEs/ALEs, and only the least harmfull group.
Consumption of fruits and veggies results in lower levels of AGEs/ALEs that may only be formed at higher temperatures.
As potatoes contain reducing sugars, boiling potatoes will result in the formation of AGEs/ALEs only formed at higher (than body) temperatures,

[Kasper]

... levels of AGEs that may form endogenously is higher in people consuming more fruits and veggies

Large, long term population studies however, show the opposite: that the consumption of veggies and fruits is positively associated with better health.

Could you link to the studies supporting those claims ?

[RRM]

Could you link to the studies supporting those claims ?

1) Intake of vegetables and fruit with predominance of fructose is significantly higher in vegetarians. leading to significantly higher CML and fluorescent AGE values.Krajcovicová-Kudlácková M et al

2) Fruit / vegetable intake is associated with better health; meta-analyses:

all cause mortaility: http://www.ncbi.nlm.nih.gov/pubmed/25073782
diabetes: http://www.ncbi.nlm.nih.gov/pubmed/25377009
stroke: http://www.ncbi.nlm.nih.gov/pubmed/24811336
cancer: http://www.ncbi.nlm.nih.gov/pubmed/20843486
gastric cancer: http://www.ncbi.nlm.nih.gov/pubmed/24613128
lung cancer: http://www.ncbi.nlm.nih.gov/pubmed/21422002
bladder cancer: http://www.ncbi.nlm.nih.gov/pubmed/25248495
glioma: http://www.ncbi.nlm.nih.gov/pubmed/25194962
nasopharyngeal cancer: http://www.ncbi.nlm.nih.gov/pubmed/25008797
esophageal adenocarcinoma: http://www.ncbi.nlm.nih.gov/pubmed/24448974
colectoral cancer: http://www.ncbi.nlm.nih.gov/pubmed/23563998
breast cancer: http://www.ncbi.nlm.nih.gov/pubmed/24606455
asthma: http://www.ncbi.nlm.nih.gov/pubmed/24947126
pancreatic disease: http://www.ncbi.nlm.nih.gov/pubmed/24509242
non-Hodgkin's lymphoma: http://www.ncbi.nlm.nih.gov/pubmed/23238796

[Kasper]

Thanks !