Re: Re: The Oxidized Lipid Hypothesis

[Guest guest]

,

> what *exactly* were these rabbits fed? Is it possible to

> refine the true chemical cholesterol without any lipids and feed that

> to the rabbits? I find discussions of " cholesterol " very confusing

> because more often than not, what is being discussed is lipoproteins

> that have a little bit of cholesterol in them and NOT pure

> cholesterol. It's kind of like calling a car a seat. Yes a car has a

> seat in it, but is it appropriate to call the whole vehicle a seat?

Did you read the article?

Chris

[Guest guest]

Hi ,

> I thought I did because I read the link you sent earlier, but

> now I see this is a different link, which I haven't read. My response

> was really to the discussions of cholesterol and rabbits in your

> review of The Cholesterol Myths.

Well the short answer to your question is that all the research is in

German and I'm having a heck of a time trying to get ahold of the

original German references, so I'm left to English reviews.

All I know is the following are true for the rabbits:

-- Cholesterol dissolved in sunflower oil causes atherosclerosis, but

sunflower oil does not.

-- Milk causes atherosclerosis, but solid cholesterol stuffed in bread does not.

-- Solid cholesterol and whole oats causes atherosclerosis, but unlike

the other models the degree of atherosclerosis does not correlate to

the degree of hypercholesterolemia.

-- Anitschkov in his 1933 review cited three studies that did not show

cholesterol to produce athersclerosis in rabbits but something like a

dozen that did, and suggested the difference was in the type of

vegetable oil used as a solvent, but did not expand on this or name

the solvents used.

-- Cholesterol injected does not produce atherosclerosis but

cholesterol fed does.

On the whole, the evidence indicates to me that the cholesterol is

functioning to remove PUFA from the liver and transfer them to the

blood where they are more easily oxidized, and then they contribute to

inflammation and injury of the arterial wall and atherosclerotic

plaque.

The rabbit no doubt makes its own PUFA, but in the absence of dietary

PUFA, the amount of PUFA and the degree of unsaturation of those PUFA

is greatly reduced. Moreover, it may be that circulating lipoproteins

are coated primarily in dietary fatty acids when dietary fat is

supplied, but in endogenous fatty acids when dietary fat is not

supplied. Since sunflower oil would provide a far higher proportion

of PUFA than the proportion of PUFA present in endogenous fatty acids

stores, the lack of dietary fat might result in lipoproteins with a

far lower concentration of PUFA in the membrane.

Feeding cholesterol produces lipoprotein particles coated in

PUFA-containing phospholipids in amounts that greatly exceed the

capacity of LDL receptor to absorb them into cells, so they hang out

in the cellular environment and go rancid. Injecting

cholesterol/sunflower probably results in rapid absorption of free

cholesterol directly into cells, which does not require LDL receptor,

and absorption of triglycerides into the lymph.

That is my working hypothesis right now.

Chris

[Guest guest]

,

> now I've read the article as well as the book review and both

> are excellent as usual, although I did find a few typos

Thanks. I put the article up at 2AM last night so I probably need to

go through it a bit.

> I still have the general complaint that often the word " cholesterol "

> is used in place of " lipoprotein " and sometimes it is not and that

> makes it difficult to tell which is which at times.

I don't think I do that.

> The highway is full of seats ... or is that cars? Or trucks? Or

> buses? Or bicycles? Or all of the above?

>

> For instance, where you say:

> " The lesion possessed a fatty core rich in crystalized and calcified

> cholesterol deposits and was covered with a fibrous cap. "

> Are these deposits some form of lipoproteins or pure chemical

> cholesterol with calcium?

It is cholesterol, probably esterified to fatty acids. The foam cells

metabolize the lipoproteins, and they accumulate the cholesterol

esters. Eventually I think they basically blow up and leave a pile of

cholesterol esters in their place. So usually at the core you have

cholesterol esters and maybe some other fatty material and that is

surrounded by foam cells that haven't blown up yet.

> Likewise:

> " The rabbits developed cholesterol deposits all throughout their

> bodies, in their eyes and internal organs. "

> Again, are these deposits some form of lipoproteins or pure chemical

> cholesterol?

I think the pattern of deposition is very similar to the above.

Usually accumulates in cells, so the lipoproteins become less relevant

since they are metabolized by the cell.

> I'm guessing that since the rabbits injected with pure cholesterol did

> not develop atherosclerosis, that the deposits are lipoproteins of

> some sort that include cholesterol. It's interesting that they

> produced " disease by feeding pure cholesterol dissolved in sunflower

> oil " . Apparently the cholesterol was converted into LDL in the

> rabbits, which then induced the atherosclerosis in the rabbits when it

> could not be properly metabolized. Sunflower oil is high in PUFA, so

> I'm guessing that the LDL would also be high in PUFA.

Right.

> Why didn't they feed pure cholesterol with normal rabbit food? Does

> this not cause atherosclerosis? I'm guessing it wouldn't because I

> don't think rabbits normally eat much in the way of fats to produce

> excess LDL with pure dietary cholesterol.

The cholesterol will probably get made into VLDL either way, which

then turns into LDL in the blood, but I think it would be much lower

in PUFA without the sunflower oil.

I do think dietary PUFA is involved, as I indicated in my last post,

which I don't think you've read yet. But I need to get the original

studies and translate them somehow to know for sure.

> I'm surprised that they were able to get rabbits to eat meat, eggs,

> and milk in the initial tests. That would be like trying to feed

> rabbit food to cats. I guess if they're hungry enough....

Part of the reason they used rabbits, I think, is because they are so

placid and easy to get along with.

However, some of the feedings were forced. There was some discussion

of whether the feeding tube could have an effect, with the conclusion

being that the evidence pointed away from that.

> It was also interesting that they could induce the atherosclerosis in

> rabbits by feeding them milk. Was that an all milk diet? And what

> happens in other adult mammals when fed milk? Would it matter if the

> milk was raw versus pasteurized?

I think the point is that the milk contains cholesterol, and the

rabbit is not equipped to consume dietary cholesterol so does not

adjust its own synthesis, thus secretes more lipoproteins into the

blood in response.

> As you can tell, I have more questions than answers

I think there are many remaining questions, but a substantial handful

of answers.

Chris

[Guest guest]

,

> thanks for clarifying. I would guess there's a lot more fatty

> acids than cholesterol in atheromas and that they would be better

> characterized as " lipid " deposits than " cholesterol " deposits.

>

> Part of the confusion is my own. I looked up cholesterol in wikipedia

> and it says cholesterol is BOTH a lipid AND a sterol:

> http://en.wikipedia.org/wiki/Cholesterol

>

> I thought it was just a sterol. Furthermore, I thought " lipids " and

> " fats " were interchangeable, but I see now they are not - fats are a

> subset of lipids, which also include sterols, waxes, and even the

> fat-soluble vitamins:

> http://en.wikipedia.org/wiki/Lipid

True, but I don't see why you think they have more fatty acids than

cholesterol. I'd have to look it up, but they should probably have

roughly equal amounts if the main source of each is cholesterol

esters.

> So, I guess some mammals, like humans can adjust their cholesterol

> production to keep a steady supply of LDL and cholesterol related

> hormones regardless of the amount of cholesterol that's in the diet.

> Whereas, rabbits apparently continue producing the same amount of

> cholesterol even when large amounts are incoming from the diet and

> thus end up with a large excess that can't be metabolized readily.

I think that is basically it. By the way, I corrected an error in the

article to this effect: the liver secretes VLDL, not LDL. VLDL

converts to LDL after delivering some nutrients to cells.

> What do you know about human adult consumption of milk in regards to

> atherosclerosis? I would assume that raw milk from grass-fed cows

> would be protective, although I'm not sure that would apply to

> pasteurized milk.

I would guess so, because of the protective effect of butter fat and

because of the nutrients, but I don't know. The milk was probably raw

in the rabbit experiments, since it was early 1900s Europe (Russia,

maybe Germany, I think). I don't know for sure when pasteurization

started there.

> Speaking of milk, I've noticed that milk is relatively low in some

> nutrients we are supposed to need in much more abundance. How can

> that be, if young mammals thrive entirely on milk? Milk is fairly low

> in potassium, sodium, niacin, and vitamins C, E, and K1, relative to

> dietary " standards " . Perhaps another reason to suspect that some of

> these standards are too high. Is there any reason adults would need

> much more potassium than young children, for instance?

The vitamin E standard is WAY too high. Its basis is a total joke.

The potassium requirement is probably exaggerated by sodium intakes.

The ratio of the two in milk is similar to the ratio of the RDA.

There should be differences between young and adult requirements and

requirements of different species, and differences between standard

milk and ideal milk.

> Children are growing fairly rapidly in size, but adults are also

> growing in the sense that the body is constantly re-building itself.

> Why wouldn't milk be the perfect food for adults as well? What

> happens with exclusive raw milk diets for other adult mammals and does

> it matter whether the milk is species specific?

Children grow much more than adults. They need to do the repairing

and the actual growth.

> Since dairy was one of the three key foods that Weston Price found to

> provide good health, I'm curious what form of dairy is best - whether

> to go with more kefir and cheese and less milk, or if it's beneficial

> for adults to drink a cup or two of raw milk a day.

Raw kefir's probably better, but I don't know for sure.

Chris

[Guest guest]

,

> but since both cholesterol and fatty acids are lipids, it would

> be more correct to characterize the deposits as " lipid " , which

> includes both. Calling the deposits " cholesterol " is a bit misleading

> since there are also fatty acids involved.

I primarily referred to them as " lipid deposits, " " fatty plaques, "

" lipid-loaded white blood cells, " etc, etc.

Usually, cholesterol esterified to fatty acids is referred to as

" cholesterol esters, " because fatty acids are generally the common

denominator in lipid esters. For example, the word " triglyceride "

emphasizes the glycerol, which is esterified to three fatty acids.

The word " phospholipid " emphasizes the phosphate head group, which is

esterified to two fatty acids, etc.

> Yes, I've been suspecting the conventional vitamin E daily requirement

> is too high for diets low in PUFA, since most foods high in vitamin E

> also are fairly high in PUFA.

The study used for the RDA was done with prisoners, and they spent a

very long time (years? I forget) trying to induce a sign of E

deficiency (lysis of extracted red blood cells with hydrogen peroxide)

on a regular diet (I think lard was used as the fat), but never could

induce deficiency. So the switched to rancid corn oil, and then took

the blood level and dietary intake of a single individual out of a

small group to be the minimum necessary to prevent deficiency, but

never stipulated that it was only relevant to someone consuming their

main fat as rancid corn oil. Most Americans have a sufficient blood

level but deficient intake according to this criteria, which just goes

to show that the RDA is not required to maintain the blood level that

it is based on, even on the standard American diet.

> Below is a list of the percent of the official " Dietary Reference

> Intake " (DRI) levels for males age 19-50 provided by 2.25 cups of milk

> - enough to provide about 100 percent of the DRI for vitamin B12,

> based on the USDA nutrient data base that is likely using factory farm

> pasteurized milk that has added vitamin D3.

>

> %DRI

> 109.8 Vitamin D

> 100.7 Vitamin B12 cobalamin

> 84.0 Iodine

> 77.3 Vitamin B2 riboflavin

> 71.4 Phosphorus

> 62.0 Calcium

> 60.0 Vitamin B7 biotin

> 39.7 Vitamin B5 pantothenic acid

> 36.9 Selenium

> 20.1 Vitamin B1 thiamin

> 20.0 Zinc

> 18.7 Vitamin A Equivalent

> 17.1 Vitamin A Retinol

> 16.7 Potassium

> 15.2 Vitamin B6 pyridoxine

> 14.6 Sodium

> 14.3 Choline

> 13.1 Magnesium

> 6.9 Vitamin B9 folate

> 6.7 Copper

> 3.7 Vitamin B3 niacin

> 2.2 Vitamin E alpha tocopherol

> 2.1 Iron

> 0.9 Vitamin K naphthoquinone

> 0.7 Manganese

> 0.0 Vitamin C ascorbic acid

> Notice that copper, iron, and manganese are way down the list. On the

> flip side, maybe B12 is under-rated in the DRI. And of course,

> vitamin K2 is not even listed in the DRI

There are a number of additional issues, such as pasteurization,

bioavailability, and production practices. For many nutrients, such

as folate, milk contains special proteins that dramatically enhances

its bioavailability, and pasteurization generally destroys these

proteins. Grass-feeding, soil quality, etc, make big differences in

some nutrients (for example gras-feeding produces a 4-6-fold

difference in vitamin E). Raw milk cures scurvy in infants, so it

must contain either some highly bioavailble vitamin C or something

else that effectively acts as vitamin C.

> I compared the USDA data to measurements reported for raw milk at:

> http://www.raw-milk-facts.com/what_is_in_raw_milk.html

> and the differences are not all that great for most vitamins and

> minerals. The largest differences were that raw milk had about a

> tenth of the vitamin D (since none was added), about 30% more vitamin

> A (that would push it up to 24% of the DRI), and 19 mg of vitamin C

> (21.1% of the DRI versus none from USDA).

That's a pretty hefty amount of vitamin C when you consider preventing

deficiency diseases such as scurvy. As per above, the simple nutrient

facts are not enough information because of differences in

bioavailability.

> I haven't seen detailed figures on how typical human milk varies from

> typical cow's milk, although I would not expect huge differences for

> most nutrients.

Those figures and comparisons float around on the internet. There are

many similarities and some differences.

> That's what I'm guessing too, since I make about half of my raw milk

> into kefir. I suspect diabetics should go with all kefir, yogurt, and

> or cheese and no milk.

Yep. Of course cheese would be the most effective way to reduce carbs.

Chris