Sunday, July 06, 2008

AGE, RAGE and ALE: The AGE of LDL

A glucose molecule can assume various shapes. If presented as a linear rather than a ring structure, one of the two end carbons will contain an aldehyde grouping. The C=O structure of the aldehyde can react chemically with an amino group on another organic molecule to give a Schiff base. This is a horribly complex structure where the carbon of the sugar is double bonded to the nitrogen of the amino group, which stays attached by its third bond to whatever structure it's part of. Classically this is a "free" amino group of lysine or arginine. Needless to say this structure is unstable and falls apart in various ways. The sugar can remain attached or break off taking the amino group with it. Either way there is damage to the protein and the potential for cross linkages to form. Lysine and arginine are, as I mentioned, the most susceptible amino acids. Glucose is one of the least problematic sugars, fructose is one of the worst.

The end result of this sugar driven reaction is the generation of Advanced Glycation Endproducts (AGEs). They're probably bad.

There is a section of the apolipoprotein B100 molecule (That's that sole protein on the surface of the LDL cholesterol particle) which is very prone to AGE formation. These people have looked at the process in detail. They have located, within the apoB100 protein, a distinct continuous sequence of 67 amino acids which are exquisitely prone to AGE formation. This section of apoB100 is probably not part of the binding domain for the LDL receptor, but formation of AGEs here does strongly influence the binding domain and effectively stops it working. So AGE formation in this area inhibits LDL particle attachment to its receptor, so reduces clearance from the plasma.

This is highly reminiscent of the situation in familial hypercholesterolaemia.

Why is apoB100 designed this way? Stuff doesn't just happen "accidentally" like this. Evolution has selected the sequence of apoB100 protein to provide a 67 animo acid section in which AGE formation inhibits uptake of the LDL particle in to cells which might want it.

Let's look at the logic.

During glycation conditions the LDL cholesterol particle stops sticking to its normal receptor. Why? My answer is that under these conditions it is more advantageous for the body to have the LDL cholesterol particle in the blood stream than it is to have it endocytosed by an endothelial cell.

Glycation is related to sugar concentration. Glucose is the sugar least prone to glycate anything to an AGE. Couple that with the tendency for humans, over an evolutionary time scale, to eat diets that rarely budge the blood glucose outside of a relatively narrow range, and I'm not sure hyperglycaemia is what the "switch" on LDL is evolved to look at.

No, my guess is that fructose was the original lever to develop a glycation based switch on the apoB100 molecule. Just about the only time a human ought to get a big enough load of sugar to risk any damage to themselves is during late summer or autumn in temperate regions, the source would be fruit. Possibly large amounts during a short period. If this happens in autumn it's a good source of calories to convert to fat and not to be wasted. But fructose is ten or seventeen times as good as glucose at AGE formation, depending on which AGE you look at and which model you use.

Fructose appears to be bad news, especially if any gets in to the systemic circulation. I can see some logic in taking the LDL particle away from arterial endothelial cells, which can make their own cholesterol anyway, and having it handy in the circulation for other purposes, like patching up fructose induced damage. Bear in mind that, while fructose is only present in the systemic circulation in trace amounts (which are probably bad for you) it will be present in copious amounts in the portal vein from gut to liver after each fruit meal. Lipoproteins are present throughout the circulation. Fructose will meet LDL particles with head on impact in the portal vein. AGEs on apoB100 suggest AGEs elsewhere, which mean repair is going to be needed. The LDL particle is diverted away from the endocytosis receptor. This is probably physiological.

But raising blood glucose from below 6mmol/l to above 30mmol/l would allow glucose to become the primary glycating agent. For a diabetic on the ADA diet the glycosylation of apoB100 is probably a fact of life. This is not our normal autumn carb loading pre winter. It's more of a pathological process.

Finding high levels of LDL cholesterol is one of the more logical aspects of the hyperglycaemia of type 2 diabetes. Putting these patients on to LC diets usually drops their calculated LDL cholesterol levels along with their blood glucose levels. It probably markedly reduces AGE formation throughout their physiology. LDL can then get back to supplying normal lipid to normal cells through the LDL receptor.

Peter

36 comments:

Misty said...

Again thanks for such an extensive and detail explanation of how our body is not ment to process fructose (is hard sometimes to convince yourself of it since --at least here in New York-- that is all people it, you find a fruit vendor in literally every corner).
Peter when you have your fermented cream how much of the 85 % chocolate bar do you it? (because I have a tendency to it all the Lindt 85% big cocoa bar, but I do it with pasteurized non fermented cream) (I know you explain the reasoning on the fermentation process you put the cream to go through but could you please explain in short why do you fermented adding the milk and bacteria).
Thanks and I must say you have helped me a lot (along with JK book....but of course it comes back to you since I learned about it through this blog)

Bruce K said...

It seems that raw sugars would be a lot less likely to glycate than the cooked and processed sugars. Claims about glycation potential are based on refined sugar (pure glucose is a refined sugar). I don't think it is fair of scientists to assume that a fresh raw food (like comb honey) is the same as table sugar or purified glucose/fructose. Cooking starch is known to create acrylamides, unless you cook in water. Exposure to open air generates acrylamides. A baked potato might be safe, if you leave the skin on, but things like french fries and potato chips are clearly toxic. On a related note, PUFAs can cause glycation-like damage roughly 23 times faster than glucose. This is still faster than fructose. So, the worst possible diet is one high in refined sugar, PUFAs, and starch products cooked in open air.

http://raypeat.com/articles/articles/fats-degeneration.shtml
http://www.ncbi.nlm.nih.gov/pubmed/8626637

Misty said...

Bruce K,
I thought acrylamide is produced largely by the reaction of PUFA with proteins I read it in an article by Ray Peat). And if you are cooking the potato chip in butter or beef fat would be ok?
I am correct?

Peter said...

Flick down and click on Figure 2 in this paper.

Normal people have about 50 units/ml of AGEs in their blood on the SAD. Diabetics without renal problems have 60-70 U/ml.

Now take 55g of egg white protein and heat it to just below boiling (90 deg C) with 100 grams of fructose. Simmer it there for one to three HOURS, then eat it. Try not to vomit. You can get your plasma AGEs up to 80U/ml, just above the value for a "normal" diabetic. The normal diabetic got these values from simple hyperglycaemia using glucose and maybe a little fructose on top of the SAD.

I'd suggest no one tries the sweet egg whites thing. But it puts dietary AGEs in perspective.

It's nice to think that raw fruit doesn't glycate proteins. Personally I'm not up for taking the chance beyond my few grams per day in season. Some AGEs from cooking are inevitable and excreted through the kidneys. Those from fruit or hyperglycaemia are unnecessary. Why take the chance?

BTW my family doesn't fancy raw meat! We're not stopping cooking soon. I thought baked potatoes were an excellent source of acrylamide?

Peter

Bruce K said...

I saw no mention of fresh fruits in the 3 studies cited. Studies mostly look at processed fructose and then extrapolate to natural foods, which reminds me of T. Colin Campbell and his argument that animal protein is carcinogenic, because casein powder is. There may be some truth in such an extrapolation, but where are the studies testing raw fruit and honey that confirm it? Where are raw milk studies confirming Campbell's view?

So much of what goes by the name of science is not really scientific at all. Like saying that casein powder = raw milk = pasteurized milk = all animal protein. I think each of the steps in this extrapolation must be proven with impeccable science. The same goes for claims like processed sugars = raw unprocessed sugars. It seems likely that the results would be different if these were compared directly in a long-term experiment.

Frank said...

Peter I feel much the same about raw meat – I did try Anthony Bourdain’s steak tartare but while the flavours were good, I couldn’t cope with the texture, so it was gratifying to discover that carnosine and taurine in the meat suppresses AGE formation. It is ironic that research is currently focussed on drugs to inhibit AGE formation in diabetes while advising a high fructose diet, and drinks like diet colas (very high in preformed AGEs due to the caramel).
Incidentally, vegetarians have higher serum AGE products than omnivores despite gentler cooking methods and similar “saccharide” (both high) intake due to high “natural” fructose load. http://tinyurl.com/6yddkd
And yet the low fat vegan diet with taurine supplementation has been proposed to reduce AGEs in diabetics! http://tinyurl.com/6mf76a

Gyan said...

Wont it be more relevant to focus on Tropics as the enviroment humans evolved in?.
How much fruit do the modern tribals that live in Tropics consume?.

I find that I can not meet RDA for vitamin A unless I eat some fruit.

Dr. B G said...

Peter,

This is powerful. And explains so much!

Fruit must have had a special role in our ancient diet and it explains why fructose escapes normal carb metabolism (ie, delayed insulin surges -- despite high vitamin D blood levels during summer sun). It may explain why our ancient immune system gets out of kilter as well with this ONE CARB SOURCE...

Speculatively speaking (meaning there is no 'impeccable science' behind it), fructose may also cause huge autoimmune dysregulation... (not antibody related -- the OTHER immunity system, the innate one) that is why fructose is even worse than gluten/wheat. Innate is systemic which is way more widespread. Like diabetes -- a systemic disease.

I never thought of blueberries as 'junk food' until you had a picture of your amazing creme fraiche/blueberry/chocolate-ganache dessert that made my mouth-start watering!! (even now!!)

Guess what our increases CRP and parts of the innate immunity (via IL1 IL6 and TNFa)?

Mannose-containing or fructose-containing bacteria!!

Mannose-binding lectin (MBL) from our innate/nonspecific/broad-spectrum immunity will bind fructose-containing cell surfaces of invading viruses, bacteria, fungi, protozoa and trigger complement (or act directly on the foreigner).

No wonder fructose can be so BAD BAD BAD. Perhaps its triggering high CRP and inflammatory responses to our liver via the portal vein (prior to conversion from fructose to glucose or to sorbitol) which leads to 'fatty liver' NAFLD/NASH? It starts at the liver then it affects the endothelium... and the brain.

FRANKIE -- (do you really have an untitled book? AWESOME!!) you know I've learned so much from you! You are truly a gift. You confirmed that Taurine is great stuff... Had no idea people with diabetes were full of SORBITOL.

Did you know that fructose is converted to sorbitol!!?

Are we all a bit on the autism spectrum if our astrocyte glial cells start getting auto-phagocytosed by our immune system by consuming excessive fruit/HFCS? Perhaps that explains the dementia and 'brain fog' of people with diabetes? (Was I stunning my puny brain with each daily cup of cranberry juice/HFCS? Because I thought it was HEALTHY??)

http://members.jorsm.com/~binstock/astro.htm

-G

Sven said...

Gyan: Fruit doesn´t contain any vitmin A. Only a minimal percentage of beta carotene is converted into vitamin A.

Sue said...

Have some cod liver oil and you'll meet the RDA for vitamin A.

Misty said...

Liver=Vitamin A

marco said...

Hey Peter.

What do you think about these guys?
They eat fruit and raw fish (sashimi)...
Don't seem so worried about fructose (in the absence of cooking).

(http://www.waisays.com/index.html)


Marco

Cristian Stremiz said...

Spices to the rescue!

J Med Food. 2008 Jun;11(2):275-281.

Inhibition of Protein Glycation by Extracts of Culinary Herbs and Spices.

Dearlove RP, Greenspan P, Hartle DK, Swanson RB, Hargrove JL.

Department of Foods and Nutrition, Department of Pharmaceutical and Biomedical
Sciences, University of Georgia, Athens, Georgia.

ABSTRACT We tested whether polyphenolic substances in extracts of commercial
culinary herbs and spices would inhibit fructose-mediated protein glycation.
Extracts of 24 herbs and spices from a local supermarket were tested for the
ability to inhibit glycation of albumin. Dry samples were ground and extracted
with 10 volumes of 50% ethanol, and total phenolic content and ferric reducing
antioxidant potential (FRAP) were measured. Aliquots were incubated in triplicate
at pH 7.4 with 0.25 M fructose and 10 mg/mL fatty acid-free bovine albumin.
Fluorescence at 370 nm/440 nm was used as an index of albumin glycation. In
general, spice extracts inhibited glycation more than herb extracts, but
inhibition was correlated with total phenolic content (R(2) = 0.89). The most
potent inhibitors included extracts of cloves, ground Jamaican allspice, and
cinnamon. Potent herbs tested included sage, marjoram, tarragon, and rosemary.
Total phenolics were highly correlated with FRAP values (R(2) = 0.93). The
concentration of phenolics that inhibited glycation by 50% was typically 4-12
mug/mL. Relative to total phenolic concentration, extracts of powdered ginger and
bay leaf were less effective than expected, and black pepper was more effective.
Prevention of protein glycation is an example of the antidiabetic potential for
bioactive compounds in culinary herbs and spices.

IWFC0dN7oN.NyycUvuSp2UfBTUwR_Fo- said...

Good stuff peter as always.

I have two topics of interest: 1) chocolate, and 2) sex

For the less interesting topic, does anyone have a good cheap source for bulk 70 or 85% chocolate? Also, I recently tried Green & Blacks chocolates (they're all organic I believe). The 70% had quite a different taste from the Lindt 70%.

On to the second topic. Any of you smart/forward thinkers know of research into ideal sexual release frequency? I hope this isn't inappropriate to ask and everyone isn't too bashful to discuss :)

Cheers as usual

Frank said...

Dr B G you’ll give me cranial oedema syndrome! The book is still in the scribblings all over the hard drive stage and will be for a while. But I shall say the thrombogenic theory of heart disease is another doozy based on what drugs can be sold to an unsuspecting public and little to do with hard science (like so many other medical theories).
The immunity and CRP angle are very interesting – all those trying to eat a “healthy diet” with lots of fruit also seem to be the ones falling prey to colds and other beasties. One person I know eats 15 pieces of fruit per day (!!!) and wears sunblock to walk 2 metres to her car even in winter – she and her kids are constantly sick!
A few years ago a Nutrition Foundation clinical director came to give a talk to the endocrinology/diabetes journal club and described 10-year-olds in the US needing liver transplants due to NAFLD caused by HFCS-laden food and drinks. We don’t allow children to drink alcohol but it seems the USDA, ADA, and other useless alphabetti organisations think feeding toxic fructose is perfectly okay. You also have to wonder if the cirrhosis has as much a fructose component as alcohol itself.
High mM glucose increases both fructose and sorbitol in immortalised mouse Schwann cells due to spill over into the aldose reductase pathway.
I think sorbitol can also be converted back to fructose – these polyol sugars are touted as natural because they are found in the body in smallish amounts. I’d like to see if they are found in people not eating fructose. The rise in the use of the other polyol sugars may be problematic too because little is known about their metabolism, and their high osmolarity could be especially dangerous for diabetics. That said, other sugars like maltose have very little study as to metabolism, which annoys me because I enjoy the odd beer in hot weather. The only fructose going into my pie-hole is in small quantities of vegetables.

Peter this is a complete coincidence but I came across LDL apo B yesterday while researching an entirely different subject (thalassaemias).
“The dissimilar behavior of the liposomes and LDL indicated that LDL protein apo B rather than phospholipids is the actual LDL surface component which interacts with the hemoglobin variants. This agrees with the finding that apo B protein underwent oxidative crosslinking by the hemoglobin variants among which alpha-chains were most active.” [1]
Can we invent a new phrase – “liposylated haemoglobin”?

IWFC – LOL I’m not sure anyone has defined that yet

1. Altamentova, S.M., E. Marva, and N. Shaklai, Oxidative interaction of unpaired hemoglobin chains with lipids and proteins: a key for modified serum lipoproteins in thalassemia. Arch Biochem Biophys, 1997. 345(1): p. 39-46.

Peter said...

Marco,

I just loved that link! The section on the health benefits of the clitoral orgasm was amazing. Blokes loose out again! But their concept of running muscles on glucose and the conversion of fructose to glucose don't fit my view of how metabolism works. You could always hope fruit based fructose doesn't trigger NAFLD the way colas do. Maybe. I also thought their ideas of carbs and serotonin was a the flipside of how I look at it. Carbs at 5pm means sleep from 6pm to 10pm and insomnia there after. Those folks see carb sleep as good. No way!

IWFC, decent chocolate always costs too much, it's a big chunk of my calories as I'm back to working full time. I buy what's on offer, if any, of the 85% stuff. The organic does have an odd flavour but Sainsburys have improved the flavour of their organic 85% and had it at 1/2 price to get people trying it. Got through about 10 bars before the offer ended.

Re sex, dunno, Being young is probably the biggest determinant of frequency. Actually, being in love is even more relevant, as might be avoiding sleep deprivation!

Christian,

This is interesting. Obviously anything other than normoglycaemia for a diabetic should be considered wholely unacceptable and fruit has no role in normoglycaemia for said diabetic. But if fructose really does collide with LDL primarily in the portal vein then the anti AGE chemicals in plants might actually do some good. That is before the liver dumps them asap, the way it does fructose. But in the portal vein both mix on a similar timescale.... No orgasms in the paper though, so not quite so err, umm, err eye catching as Marco's link!

Frank and g,

Liposylated Hb is glycosylated Hb! The chemistry is interesting and I'll post it in this series if it turns out to be how I think it is. Haven't picked through the paper yet. The role of the LDL particle in immunity, like that of the Lp(a) particle, is fascinating. Both clearly matter. Got some reading to do about mannose binding lectins I can see.

Peter

Peter said...

Hi Gyan,

I'm not sure that fruit would be available continuously year round in the equatorial regions. There was a comment from a poster on Dr B's forum who pointed out that anyone who thought you could wander through the Amazonian rain forest picking fruit off of trees was likely to be disappointed and hungry if they ever actually tried it. The use of protective mechanisms against glycation damage may not have been so intermittent/seasonal there but it would still be needed. The Kitavans lived on fish, coconuts, yams and sweet potatoes. Some fructose in the latter only. I guess fruit would be an occasional treat even if you live on a tropical island just north of the equator.

Peter

Aaron said...

Great Article. Tweaking within proteins, fats and carbs are where all the juicy research could be done- We still don't know the optimal types or amounts of protein (ie it seems to be that methionine reduced diets are great for longevity, etc). Lower amounts of PUFAs seem to be good- but we need to tweak amounts. Even tweaking carbs- (like less fructose) is beneficial. I'm sure your on to something peter with you idea that there may be anti-AGE compunds that work well in the plants to help protect us (at least for veggies). As for what types of foods humans have eaten (in tropical places) in really seems to be that we ate lots of tubers (low in fructose!) . Now all that is left is determining how much of the macronutrients is optimal for longevity (some carbs may be good to stave off too much of a stress reaction in the body!)

Dr. B G said...

Frankie,

Well... unpublished scribblings or comments adding to Peter's brilliant blog... they are all GENIUS.

I've seen the same thing. When people stop fruit their glucoses drop 200-400 mg/dl points!! 'fruit is so healthy!' they always argue... Well, not the Costco (American warehouse)-sized bananas 3x/day...

OK -- if that is liposylated Hgb (which I think ur right!) -- you know those statinators are gonna jump all over that! LDL-hemoglobin!! Let's add Crestor to kid's cafeteria food! *heh*

-G

Stephan said...

Indians in the Pacific Northwest here harvested a lily bulb known as 'camas' in large quantities. Its storage carbohydrate is primarily inulin, which they broke down into fructose by prolonged cooking. These things become 1/3 fructose by weight. They then made cakes out of them that were traded and eaten.

I wish they were still around so we could study them! Some of them still do eat camas, but it would be too hard to disentangle the effects of it from the effects of the Amercian diet at this point.

Dr. B G said...

Frankie... Cirrhosis of underaged kids' liver with adulterated beverages and foods (ie, fructose)... You've hit on something... AGAIN...!! My Goodness!! let's say...Sorbitol could be broken down (to 3 x EtOH's)... my biochem SUCKS... could be liver ketohexokinase or a fru-aldolase... that's a lot alcohol-damage(with a fructose -'BUZZ')... Wow! G

Peter said...

I really really really hate to say this, but statins are inhibitors of glycation.

Hee hee, and I though angiotensin receptor blockers lowered blood pressure... Who knows what Big Pharma does by accident! Some of it's beneficial!!!!!

Peter

team smith said...

>>What do you think about these guys?
They eat fruit and raw fish (sashimi)...
Don't seem so worried about fructose (in the absence of cooking).

(http://www.waisays.com/index.html)<<

Re: the above quote and link, has anyone read about what that site suggests we should be eating? i am not sure whether i should take anything they say seriously or give that website any more of my time, but my curiosity is piqued.

they suggest 4.4 pounds of raw fruits/day for the glucose as "brainfood". pregnant women should consume mostly fruits, raw fish and raw egg yolks. they shouldn't eat any dairy or wheat or cooked proteins.

is there any reason i should believe that about dairy products interfering with lactation after birth? or child development in utero, for that matter?

is the person who wrote that website just a wacko?

amanda

Bruce K said...

"I thought baked potatoes were an excellent source of acrylamide?"

Well, one part of that study used "dried mashed potato, corn meal, wheat flour, rice flour, glutinous rice flour, dried sesame and dried almond..." They don't say how they prepared other foods for baking. I think that leaving the skin on the potato would create less AGEs than peeling or mashing it, because the inside of it isn't exposed to air. But cooking in water is the safest method and doesn't create AGEs.

Here's an interesting study. Some highlights of the abstract:
"Foods of the fat group showed the highest amount of AGE content with a mean of 100+/-19 kU/g. High values were also observed for the meat and meat-substitute group, 43+/-7 kU/g. The carbohydrate group contained the lowest values of AGEs, 3.4+/-1.8 kU/g. The amount of AGEs present in all food categories was related to cooking temperature, length of cooking time, and presence of moisture. Broiling (225 degrees C) and frying (177 degrees C) resulted in the highest levels of AGEs, followed by roasting (177 degrees C) and boiling (100 degrees C)."

"http://www.ncbi.nlm.nih.gov/pubmed/15281050

Bruce K said...

"It's nice to think that raw fruit doesn't glycate proteins."

The problem seems to be greatest in sugars cooked in presence of PUFAs, and proteins. I believe raw sugars, proteins, and fats would be greatly immune to AGE formation. Can anyone point out a study that used natural raw foods, instead of cooked foods, refined foods, and processed foods? The best cooking method seems to be IN water (submerged) rather than in open air. Water should be consumed. The cooking material also has to be considered. Aluminum and teflon are best avoided. Cast iron, stainless, and enamel are probably best.

"Personally I'm not up for taking the chance beyond my few grams per day in season."

I don't recommend fruit, unless you know it is picked at peak ripeness. Frozen fruits, sun-dried fruits, or canned fruits are more likely to be picked ripe than stuff like citrus, tomatoes, peaches, etc. Bananas are the only exception that might be OK to pick unripe, provided you eat it with plenty spots or totally black. Unheated honey (or comb honey) is a good source of carbs IMO and IME. I never get blood sugar highs or lows from unprocessed honey.

Bruce K said...

(http://www.waisays.com/index.html)

Amanda and Marco, I think there are some good articles on the site, but most of it is drivel. The diet they promote is fruit, raw egg yolk, raw sashimi, raw brazil nuts shelled by hand, and extra virgin olive oil. I like her article on the toxicity of veggies, beans, and grains.

We don't need to eat plants.
http://www.youngerthanyourage.com/13/plants.htm

Here are some other articles with a detailed view of the diet. Her diet is low-protein, mostly simple sugar with fat, and largely raw.

http://www.youngerthanyourage.com/13/brainfood.htm
http://www.youngerthanyourage.com/13/zombie.htm
http://www.youngerthanyourage.com/13/index.html
http://www.waisays.com/AcneSampleDiet.htm

Peter said...

Hi Bruce,

"Can anyone point out a study that used natural raw foods, instead of cooked foods, refined foods, and processed foods?"

Probably not, though I've not particularly looked. But if there are no studies on real food it's equally impossible to claim they are safe, so I'd continue to avoid those with short term markers of problems, particularly grains, fruits, vegetables and fiber. Dairy I have some reservations about but not so many. Again re state of ripeness of fruits etc, it doesn't matter if you leave them on the supermarket shelf...

BTW you are obviously aware of William Brown's attempt to induce EFA deficiency in himself in George Burr's lab: Semi synthetic diet?

"Each day, he consumed three quarts of defatted milk, a quart of cottage cheese made from it, sucrose, potato starch, orange juice, and some vitamin and mineral supplements. The decrease in his blood levels of arachidonate and linoleate was similar to that seen in cases of infant eczema associated with EFA deficiency, but rather than experiencing adverse effects, he experienced a marked absence of fatigue, a normalization of his high blood pressure, and the complete disappearance of the migraines he had suffered from since childhood."

I have to say I find this experiment fascinating.

Peter

Bruce K said...

"But if there are no studies on real food it's equally impossible to claim they are safe..."

True. You can't prove a hypothesis, you can only disprove it. I believe nothing should be extrapolated from studies. A study only shows what it shows. Colin Campbell's studies may show that casein's bad, but only in the context of corn oil, sugar, and corn starch. His studies don't show that animal protein is bad, or even that casein is bad. They only prove that it's bad in the context of the diet he tested (based on corn oil, refined sugar, and refined starch). Another study would have to be done to tease out which of those factors was to blame and it would be costly to do, because you would need lots of experimental groups. Lacking any better evidence, I can only say the study proves what it proves, that a diet of corn oil, sucrose, refined starch, and casein is bad.

"BTW you are obviously aware of William Brown's attempt to induce EFA deficiency in himself in George Burr's lab: Semi synthetic diet?"

I've read many reported benefits of "EFA" deficiency, from Ray Peat and others. I think it would be all but impossible to induce EFA deficiency with natural foods like potatoes or milk or orange juice or red meat or tropical oils. It is a question how low you want to go and should go to get the most benefits. Ray Peat has been aiming at 1% PUFAs by calories and 2% by total fat. He eats mostly beef and lamb (boiled), coconut oil refined with clay, cheeses, butter, eggs, shellfish, white fish, orange juice, potatoes, honey, fruits, and root vegetables.

westie said...

Peter you wrote: "Just about the only time a human ought to get a big enough load of sugar to risk any damage to themselves is during late summer or autumn in temperate regions, the source would be fruit. ...If this happens in autumn it's a good source of calories to convert to fat and not to be wasted."

I have an idea how our body has developed a method to maximise this fat accumulation before dark and cold winter (at least here in the North)

As we know fructose uses same portal vein route as glucose from gut straight to liver. If amounts of fructose are very low there are no problems to handle it but with higher doses of fructose (and especially with starch?!) I think something like this might happen:

In the liver fructose needs to be converted quikly to neutral fatty acids because otherwise it will form glycation products which are harmful; of course some of it still manage to glycate with hepatic proteins. Glycation might also disturbe the transport of the fatty acids from liver by the VLDL's.

So with higher doses of fructose you will end up with growing amount of fatty acids and glycation in the liver. This will lead to steadily growing hepatic insulinresistance and that will make insulin to stay up longer times which will help body to maxise to storage of the fat and minimize its use as a energy source. This has been a really beneficial thing for past generations.

What do You think about these thoughts?

Bruce K said...

Peter, are there any articles about William Brown's experiments online? You are right, it is fascinating. I suspect he was using raw milk, back then. Many doctors used raw milk to cure disease and 2 of them said raw skim milk was as good or whole milk or better. Bernarr Macfadden and Dr. Charles Sanford Porter used the raw milk cure. Here are two quotes from their books found online.

"The fat in cream has little or nothing to do with the cure of disease. Many of my best cases were cured on skim milk, even separator skim milk." (p 9)

http://www.rebuild-from-depression.com/resources/Porter.pdf

"Average milk, with four per cent of butter fat, yields about 675 calories per quart, at 314 calories to the pound. Skim milk, while equally good as a tissue builder, quite as rich as is whole milk in vital mineral salts, and equally satisfactory as a healing diet, contains much less of calory value..."
"However, it must be remembered that the calory is, after all, only a unit of measurement - nothing that contributes to the nutritive value of the food it measures."

http://www.milk-diet.com/classics/macfadden/chapter1/chapter1.html

team smith said...

i like that Ray Peat guy---he says coffee/caffeine is really great for our health! and especially for women--it's supposed to help hypoglycemia, which is not what i have ever heard! i think i'll go make myself a cup right now--with lots of cream, of course!

http://raypeat.com/articles/articles/caffeine.shtml

Bruce K said...

Caffeine causes an insulin release, according to Owsley "Bear" Stanley. I'm not sure if that's true, but it has probably been tested and one of the bright readers here will have a study that shows this. I think Bear also said that caffeine wasn't what caused the insulin release, because it happened with decaf too.

LeonRover said...

Re: AGEd egg whites etc.

For how long do you cook your meringues? Or perhaps you don't cook 'em.

BTW I recommend "Poor Cook" by Susan Campbell & Caroline Conran, published 1971 by Macmillan. It has so many offal, egg, cheese, brawns, stews and all that old-fashiond country cooking. Of course it may only be found in "previously read" bookshops. It was £2.50 new.

LeonRover

Peter said...

Leon,

Ice cream is where it's at for me. I pour the whites down the sink and keep the fructose as low as practical in an ice cream maker. Mmmmmmm

Poor Cook is currently unavailable, a bit like many of the ingredients!

Peter

Christine Kalmbach said...

I was referred to your site by Kelly the Kitchen Kop! I am very interested in what all are saying, but I am not a scientist! I am not a left brain and so while I get some of what you're saying on this post, can someone break this down in laymen's terms for me? Or is there another place on the blog to find this broken down already? Please advise. Thank you, Christine

Peter said...

Christine,

This is all fairly old stuff nowadays and I'm really much more interested in what is happening at the very basic molecular level of energy generation... The bottom line is that, at any given level of metabolic ageing, anything which causes elevated blood glucose is bad. Oddly enough there is a variant of fructose processing (Essential Fructosuria) which leads to marked elevations of fructose in the bloodstream without glycation problems and without elevated CVD risk. Bearing in mind that the condition is very rare.

So a lot of the data on glycation has to taken read carefully. Metabolism of fructose is much more problematic in that it leads to high glucose when it leads to insulin resistance and then the glycation really starts.

Sorry not to be more help but that's just how my brain works...

Peter