Articles on oxidized (bad) cholesterol

[Wintran]

Besides the obvious Scandalous Lies About Cholesterol I've been gathering some other articles and scientific experiments that support the claim that cholesterol is only dangerous in its oxidized form (referred to as oxysterol or oxycholesterol).

Feel free to expand the list with additional articles or science.

Articles:
* The role of eggs, margarines and fish oils in the nutritional management of coronary artery disease and strokes
* The Cholesterol Scam by Eric Armstrong
* Cholesterol - A predictor of heart disease? by Norman Scherer
* Oxycholesterol versus cholesterol, Gabe Mirkin, M.D.

Scientific experiments (PubMed and such):
* Oxidized cholesterol in the diet accelerates the development of aortic atherosclerosis in cholesterol-fed rabbits
* Oxidized lipids in the diet accelerate the development of fatty streaks in cholesterol-fed rabbits
* Dietary oxysterols are incorporated in plasma triglyceride-rich lipoproteins, increase their susceptibility to oxidation and increase aortic cholesterol concentration of rabbits
* The role of dietary oxidized cholesterol and oxidized fatty acids in the development of atherosclerosis

[RRM]

Thank you Hannes, thats a great help!!
What I found to be weird is that the connection between heat and oxysterols is made, but not between cooking food and oxysterols, whereas it has clearly been shown that cholesterol already spontanously oxidizes at 100 degrees C (boiling point)

[Wintran]

The most powerful method of oxidizing cholesterol is by heat. Heated egg yolk and milk can produce atheromas in hamsters, an animal known to be resistant to atherosclerosis. Today’s egg industry puts out eggs free of oxidation products. In rabbit feeding, fried or hard-boiled eggs produced the highest serum cholesterol (10 to 14 times the experimental level). Scrambled eggs increase cholesterol six to seven times above the preexperimental level, and soft boiled eggs increase it by only three to four times. Other high cholesterol foods such as milk fat become oxidized during the pasteurization process. Powdered milk is exceptionally high in oxidization products. Cheeses exposed to air for long periods during processing and stored at room temperature are likely to contain significant toxic cholesterol oxidation products.[/quote]
Check out the full article (free downloadable PDF).

[Marty]

Udo Erasmus, Ph.D.'s writings on fats emphasize coldpressed plant oils but comment less on raw cholesterol and fat:

http://www.hdlighthouse.org/see/diet/tr ... musrec.htm

His advice is not that raw cholesterol should be consumed, but rather that cured meats and cooked eggs, meat and milk-- which undoubtedly contain harmful oxysterols-- should be avoided.

But while he notes that curing implies oxidation of fats, his advice on cooking is split: fats are trimmed off meat but the meat is cooked; eggs are to be soft-boiled in their shells but not scrambled outside the shell.

The recommendations this site makes re: sashimi and raw yolks reconciles some of the contradictions I found while interpreting the above. And of course once one has found a taste for sashimi and raw yolks, cooking treatments of any type do not seem attractive.

[Gerard]

I've noticed that many do not distinguish between oxidized and unoxidized cholesterol. Udo Erasmus, as above, does, but not in a consistent way; Uffe Ravnskov ("The Cholesterol Myths") also does not.

Here is a citation where the difference is central to a study's findings:

http://freeradicalfederation.com/archiv ... terol.aspx


Interestingly, most ghee (even if produced at a 'safe' temperature that leaves most of its cholesterol unoxidized) is used to cook foods at high temperatures that would perhaps destroy this advantage.

But it seems that the scientific health literature on ghee is the clearest on distinguishing between the advantages of unoxidized cholesterol and the disadvantages of oxysterols.

I eat a good quality ghee occasionally (made by a local raw dairy from raw butter) with sugar mixed in; it is very good.
it strikes me-- on sites that talk about using or preparing ghee-- that there is a lot of discussion on being careful with it: not heating it too high; not burning the spices (if one cooks with it in Indian cuisine and uses it to heat spices initially in a dish). In making it, you cannot melt the (presumably raw) butter at too high a temperature, as the milk solids and sugars will burn in the pot.

The brand I sometimes eat as munch food in the U.S. is Purity Farms ghee (purityfarms.com), and it says specifically on the label "ZERO PERCENT OXIDIZED CHOLESTEROL" or something like that.

[Gerard]

The vegetarian vegetable ghees are the worst; I think they are hydrogenated plant oils and of course researchers know hands-down that this is worse than (non-oxidized) animal source ghee, for the heart.

I eat it because I like it once in awhile and the goat butter available to me is processed so that it has oxidized cholesterol. So I eat raw cow's-milk butter or-- better yet-- cow's milk ghee is small quantities.

Tastes good with egg yolk.....And when I can't travel with egg yolk, it is a good source of cholesterol.

This is interesting too-

http://www.thincs.org/discuss.JanFeb03.htm

[dime]

Recent research confirming that cholesterol itself is not bad, but oxidized cholesterol is: http://www.sciencedaily.com/releases/20 ... 151254.htm
(article summary)
Also fascinating that it's done by a 98 years old scientist!

[RRM]

In atherosclerosis not just oxidized lipids, oxysterols and calcium (attracted by oxysterols induced sphyngomyelin) precipitate,
but also LDL modified by AGEs (advanced glycation end products, as in the Maillard reaction). Jinnouchi Y et al
So that clogged arteries are the result of all kinds of compounds in cooked foods.
Cholesterol is relatively susceptible to oxidation,
so that high cholesterol is logically associated with atherosclerosis.
But without all these pro-oxidative compounds, high serum (unoxidized) cholesterol seems safe to me.

[RRM]

Recent research confirming that cholesterol itself is not bad, but oxidized cholesterol is: http://www.sciencedaily.com/releases/20 ... 151254.htm

From this article it says:

"Other studies had demonstrated a link between increases in sphingomyelin and the deposit of calcium in the coronary arteries. The mechanism by which this occurred was unclear, however. Kummerow's team searched the literature and found a 1967 study that showed that in the presence of certain salts (in the blood, for example), lipids like sphingomyelin develop a negative charge. This explains the attraction of the positively charged calcium to the arterial wall when high amounts of sphingomyelin are present, Kummerow said."

I thought it to be a bit simplistic, and its also based on just one (1967) observation.
But i think his hypothesis in general might be correct here:

"Oxysterols promote atherosclerosis through sphingomyelin-mediated arterial calcification" Kummerow

because, yes:

"the plasma from cardiac catheterized patients suffering from chest pains contained higher levels of oxysterols".Kummerow FA et al
"Oxysterols replace cholesterol in the cell membrane, increasing calcium influx.Zhou Q et al
"the plasma of patients with cardiovascular disease contains excess concentration of oxysterols, resulting in more calcium in endothelial cells".Zhou Q et al
"oxycholesterol decreases phosphatidylethanolamine and AA, and increases sphingomyelin, LA and calcium.Kummerow FA et al
*The arteries from patients who had had coronary artery bypass operations, contained elevated concentrations of oxysterols and sphingomyelin, increasing calcium influx into endothelial cells. The phospholipd sphingomyelin fraction in replaced arteries was 48.2%, compared to 24% in healthy arteries, and to 10% in arterial tissue from umbilical cords". Kummerow FA et al

and yes...

"Oxidized LDL induces an immediate and oscillatory increase in intracellular calcium.Chen JH et al
*Oxidized LDL-induced apoptosis of endothelial cells is calcium-dependent.Escargueil-Blanc I et al
"aging is the single most important risk factor for cardiovascular diseases, and increased vessel rigidity appears to be a major hallmark of cardiovascular aging".Smith AR et al
and "Sphingomyelin in arterial tissue increases with age".Eisenberg S et al

But the exact mechanism by which elevated sphingomyelin causes calcification appears to be a bit more complex:

"Oxidized LDL (oxLDL) induces neutral sphingomyelinase activity, evoking sphingomyelin turnover to ceramide".Augé N et al Full Free Text "oxLDL also increased the activities of both acidic and alkaline ceramidases as well as sphingosine kinase (evoking turnover of ceramides to S1P), elevating the level of sphingosine-1-phosphate (S1P)". Augé N et al Full Free Text

"Sphingosine-1-phosphate (S1P) is a major (and potent) Full Free Text polar sphingolipid metabolite (from ceramides, derived from sphingomyelin) released from activated platelets that (also) acts as an intracellular lipid messenger, regulating calcium mobilisation".Toman RE et al

"S1P can act through both receptors and a novel intracellular pathway to activate store-operated calcium entry (SOCE) in vascular smooth muscle cells".Hopson KP et al Full Free Text

"The endothelium can evoke relaxations (dilatations) of the underlying vascular smooth muscle, by releasing vasodilator substances, particularly nitric oxide (NO), synthesized by nitric oxide synthase (eNOS). The release of NO is down-regulated by oxidative stress and oxidized LDL".Michel T et al "S1P inhibits IL-1beta induction of NO production and iNOS expression in rat vascular smooth muscle cells through multiple mechanisms, playing an important role in the progression of atherosclerosis".Machida T et al

[overkees]

Feeding a diet rich in oxidized-lipid resulted in a 100% increase in fatty streak lesions in the aorta. Additionally, rabbits that were fed the oxidized-lipid++ diet had a >100% increase in total cholesterol in the pulmonary artery that was primarily due to an increase in cholesteryl ester.Staprãns et al

cholesterol itself is antiinflammatory Zagryagskaya AN et al

Rabbits were fed either standard chow, chow supplemented with 1.0% oxidized cholesterol (containing 6% oxysterols), or 1.0% purified cholesterol (control)...
The presence of 7-ketocholesterol in LDL was exclusive to animals fed the oxidized cholesterol diet. In addition, oxidation of triglyceride-rich lipoproteins was significantly greater in rabbits fed oxidized cholesterol compared to the pure cholesterol-fed animals. The oxidized cholesterol-fed animals also had a 64% increase in total aortic cholesterol, despite lower plasma cholesterol levels compared to the pure cholesterol control animals. Vine DF et al

[RRM]

the trans fats and cigarette smoke interfere with the production of a compound, prostacyclin, which normally keeps the blood fluid

but what they actually found was that "trans fatty acids inhibit prostacyclin release in the presence of high level of linoleic acid". Kummerow FA et al.
In another study they attributed the inhibition of prostacyclin by trans fats to the reduction in arachidonic acid. Loi C et al
and in 2 other studies they found no difference between the effects of stearic acid (saturated fat) and trans fat on prostacyclin levels Turpeinen AM et al Full Free Text, and no effects of dietary trans fats on prostacyclin.Kuhnt K et al

[dime]

This is not specifically an article on oxidized cholesterol, but on how LDL may be messing things up.

Cholesterol Increases Risk of Alzheimer's and Heart Disease

Using insights gained from studying two much rarer disorders, Down Syndrome and Niemann Pick-C disease, researchers at the Linda Crnic Institute for Down Syndrome and the Department of Neurology of the University of Colorado School of Medicine found that cholesterol wreaks havoc on the orderly process of cell division, leading to defective daughter cells throughout the body.
...
cholesterol, particularly in the LDL form, called 'bad cholesterol', causes cells in both humans and mice to divide incorrectly and distribute their already-duplicated chromosomes unequally to the next generation. The result is an accumulation of defective daughter cells with the wrong number of chromosomes and therefore the wrong number of genes. Instead of the correct two copies of each chromosome, and thus two copies of each gene, some cells acquired three copies and some only one.

[Oscar]

...cholesterol, particularly in the LDL form...

Cholesterol only has one form. LDL is not cholesterol, it's a lipoprotein. Interestingly enough it seems that more and more HDL and LDL are really considered to be forms of cholesterol instead of transporters.

[dime]

Yeah the article is just breaking it down for consumption to the general public, I'm sure the original paper makes it all clear.

Anyway, I'm really baffled as to why would cholesterol mess up cell division, it just doesn't make sense. I will read the original article eventually, here it is full free: http://www.plosone.org/article/info%3Ad ... ne.0060718

[RRM]

This is the goal of the study:
"We sought to determine whether there is a common pathogenic pathway by which cholesterol/LDL promotes the development of both atherosclerosis and Alzheimer’s disease."
Of course you will find cell cycle defects in both (and most other) chronic conditions, and of course there will be a dysregulation of cholesterol homeostasis (as in most chronic diseases).
There is actually a huge number of overlapping 'abnormalities' in these 2 conditions, including the degeneration of large numbers of cells, the subsequent formation of reactive species (through lipoxidation) and their effects on cell cycles.
The way they try to make a case for cholesterol being the linking factor (through aneuploidy), is extremely far-fetched, though.
Aneuploidy (extra / missing chromosome) may cause birth defects and is present in virtually any type of cancer (and in developing brain).
Inside cells, most carcinogenics (from diet, car exhausts, cigarette smoke etc) may evoke aneuploidy, but also non-mutagenic chemicals.