There are several reasons why arguments like this get mired in serious
confusion.  The first is a failure to distinguish between *serum*
cholesterol and *dietary* cholesterol.  It is true that in most people,
there's little correlation between the two.  It's quite correct that the
vast majority of the cholesterol in your blood was manufactured by your
body rather than directly consumed in your diet.  But it's an illogical
leap to then conclude that diet has no effect on blood cholesterol.  It
does, but the mechanism doesn't involve the cholesterol content of food to
any great extent (I'm sure *you're* aware of this, but many people aren't).

It's "common sense" that if your blood cholesterol is too high, it's
because you're eating too much cholesterol.  It's also "common sense" that
someone who had appendictis once is more likely to have it in the future
than someone who never had it.  It's also "common sense" that a heavier
object falls faster than a lighter one.  "Common sense" and "truth" have a
rather tenuous relationship.

Another is the cognitive distortion and logical fallacy of dichotomous
thinking.  It's certainly true that cholesterol levels are not the *sole*
risk factor for CAD.  There are certainly many people who have "perfect"
cholesterol levels and develop CAD and even die from it.  But it't
completely illogical to demand that any risk factor account for either all
of the risk or none of it.  CAD is multifactorial.  Nobody's ever seriously
proposed that it's unifactorial, and arguing against the latter is an
example of yet another logical fallacy, the straw man.

Another form of false dichotomy is the assumption that either "more is
better" or "less is better."  The fact that cholesterol levels can actually
be too low and that the body needs cholesterol for many metabolic purposes
in no way implies that cholesterol levels can never be too high.  The big
problem here is that people apply essentially religious modes of reasoning
to scientific matters.  Many religions divide foods into "good" and "bad"
categories (kosher/treyf, halal/haram, etc.).  But science talks about "how
much," not about "any at all."  That just isn't compatible with simplistic
religious reasoning (more sophisticated religious reasoning usually finds
virtue in moderation, which is a bit more compatible with science).

Never said it wasn't involved! it's just not causal.
Thought the analogy would be clear, my fault...

I think that the high total mortality/low cholesterol levels could also
be a marker of a deficient diet. Unsupplemented vegan diet would fit to
that picture. On average vegans have low cholesterol levels (mean 167
mg/dl) and still they've got an increased risk of stroke and some other
diseases. I am not quite convinced that very low cholesterol levels are
totally caused by diseases.

Jan

Mortality causes low cholesterol levels?!  Wow, that's not a step one
wants to take to lower cholesterol.   I've read a lot of dumb
statements in this thread but this one takes the cake.

Right, as long as you don't really heat up high cholesterol foods
while cooking exposed to air or cook it in polyunsaturated fats, the
cholesterol, which I'm assuming is from fresh food, shouldn't oxidize
too much.  When it's in your body, whether it's exogenous or
endogenous, it can be oxidized if you've got a lot of oxidative stress
going on.

Here are some interesting recent abstracts:

J Intern Med. 2004 Nov;256(5):413-20.   
Oxidized low-density lipoprotein in plasma is a prognostic marker of
subclinical atherosclerosis development in clinically healthy men.

Wallenfeldt K, Fagerberg B, Wikstrand J, Hulthe J.

Institute of Internal Medicine, Sahlgrenska University Hospital,
Goteborg University, Gothenburg, Sweden.

Abstract. Wallenfeldt K, Fagerberg B, Wikstrand J, Hulthe J (Institute
of Internal Medicine and Sahlgrenska University Hospital, Goteborg
University, Gothenburg; and Medical Advisors at AstraZeneca, Molndal,
Sweden). Oxidized low-density lipoprotein in plasma is a prognostic
marker of subclinical atherosclerosis development in clinically
healthy men. J Intern Med 2004; 256: 413-420.Objective. To investigate
the association between plasma oxidized low-density lipoprotein
(OxLDL) and the progress of clinically silent atherosclerosis, as
measured by ultrasound in the carotid arteries. Design. Prospective,
observational study with more than 3 years of follow-up. Setting.
One-centre study at university hospital. Material and methods. The
subjects (n = 326) were obtained by stratified sampling from a
population sample of men who were 58 years old at baseline. Carotid
artery intima-media thickness (IMT) was measured bilaterally by
high-resolution B-mode ultrasound at baseline and after follow-up.
Plasma OxLDL cholesterol concentrations and conventional
cardiovascular risk factors were measured at study entry. Automated
measurements of IMT were performed. Plaque occurrence and size were
assessed (plaque status). Plasma OxLDL at entry was measured by a
specific monoclonal antibody, mAb-4E6. Results. OxLDL at entry, but
not LDL cholesterol, was associated with the number and size of
plaques at follow-up (P = 0.008), also after adjustment for plaque
status at entry (P = 0.033). The plasma OxLDL concentration at entry
was associated with change in carotid artery IMT (r = 0.17; P = 0.002)
and in a stepwise multiple regression analysis this association
remained after adjustment for other cardiovascular risk factors (P =
0.005). Conclusions. These results provide new information, supporting
the concept that circulating OxLDL was associated with the silent
phase of atherosclerosis progression in clinically healthy men
independently of conventional risk factors.

Arch Immunol Ther Exp (Warsz). 2004 Jul-Aug;52(4):225-39.       

Rethinking oxidized low-density lipoprotein, its role in atherogenesis
and the immune responses associated with it.

Shaw PX.

University of California, San Diego, La Jolla, CA 92093, USA.
pshow@ucsd.edu

Atherosclerosis is a chronic inflammatory disease, resulting from
hyperlipidemia and a complex interplay of many environmental,
metabolic, and genetic risk factors. The unregulated macrophage uptake
of cholesterol and lipids through modified forms of low-density
lipoprotein (LDL), such as "OxLDL", transforms macrophages into "foam
cells" to form the initial morphological lesion (the fatty streak).
The modification of LDL not only enhances its uptake by macrophages,
but also changes the natural structures of these otherwise ubiquitous
molecules to generate a variety of modified lipids and proteins that
represent highly immunogenic neo-determinants. For example, in ApoE-/-
mice, autoantibody titers to epitopes on OxLDL are correlated with the
extent of atherosclerosis. Similarly, oxidative stress on cellular
membranes could also give rise to "oxidation-specific" epitopes and
common autoantibodies. However, OxLDL is not uniform, but rather
contains complex structures, ranging from a small conformational
change in surface lipids to the breakdown of the peptide chain.
Therefore, the immune responses to the variety of OxLDL and their
association to atherosclerosis progression are very different. For
example, phosphorylcholine (PC) is a natural component of
phospholipids and exists in LDL and plasma membranes. "Natural"
antibodies against PC can distinctively react to PC on bacteria, OxLDL
and apoptotic cells, but not to those on unoxidized phospholipids,
native LDL and viable cells, which suggests the broader role of such
autoantibodies in maintaining the homeostasis of the host. While
malondialdehyde-modified structures resemble more the exogenous
changes and associate with advanced stage of lesion, they are more
likely to associate with adaptive immunity.

Sichuan Da Xue Xue Bao Yi Xue Ban. 2004 Sep;35(5):690-2.       

[Study on serum oxidized low density lipoprotein and anti-oxidized
competence in patient with coronary heart disease]

[Article in Chinese]

Li GX, Li P.

Laboratory department, West China Hospital, Sichuan university,
Chengdu 610041, China.

OBJECTIVE: To analyze the serum oxidized low density lipoprotein
(OX-LDL) and anti-oxidized competence in patients with coronary heart
disease, and to explore the correlation between OX-LDL and
atherosclerosis (AS). METHODS: The samples of fasting blood-serum were
collected from 50 patients with coronary heart disease (CHD) and 50
normal controls with no cardiovascular disease, diabetes mellitus and
nephrosis. The levels of triglyceride (TG), cholesterol (Chol), high
density lipoprotein cholesterol (HDL-C), low density
lipoprotein-cholesterol (LDL-C), apoproteinA1 (Apo A1), apoproteinB100
(Apo B100), lipoprotein a (Lpa), OX-LDL, lipid oxidation (LPO) and
anti-oxidized competence (AOC) were detected. RESULTS: The levels of
TG, Chol, HDL-C, LDL-C, Apo B100 and NO were no difference between the
patient with CHD and the normal controls (P>0.05). Lpa, OX-LDL and LPO
were significantly higher than those of controls (P<0.05). ApoA1 and
AOC were significantly lower than those of controls (P<0.01).
CONCLUSION: There were no differences in respect to TG, Chol, HDL,
LDL, Apo B100 between the CHD patients and normals, but OX-LDL was
significantly higher than that of controls (P<0.05) and AOC was
significantly lower than that of controls. These data suggest that
OX-LDL and AOC promise to find applications as more sensitive and
valid markers for evaluating CHD.

J Nutr Biochem. 2004 Sep;15(9):540-7.       
 
Decreased aortic early atherosclerosis and associated risk factors in
hypercholesterolemic hamsters fed a high- or mid-oleic acid oil
compared to a high-linoleic acid oil.

Nicolosi RJ, Woolfrey B, Wilson TA, Scollin P, Handelman G, Fisher R.

Department of Health and Clinical Sciences, Center for Health and
Disease Research, University of Massachusetts Lowell, 3 Solomont Way,
Suite 4, Lowell, MA 01854, USA. Robert_Nicolosi@uml.edu

Currently, diets higher in polyunsaturated fat are believed to lower
blood cholesterol concentrations, and thus reduce atherosclerosis,
greater than diets containing high amounts of saturated or possibly
even monounsaturated fat. The present study was designed to
investigate the effect of diets containing mid- or high-linoleic oil
versus the typical high-linoleic sunflower oil on LDL oxidation and
the development of early atherosclerosis in a hypercholesterolemic
hamster model. Animals were fed a hypercholesterolemic diet containing
10% mid-oleic sunflower oil, high-oleic olive oil, or high-linoleic
sunflower oil (wt/wt) plus 0.4% cholesterol (wt/wt) for 10 weeks.
After 10 weeks of dietary treatment, only the animals fed the
mid-oleic sunflower oil had significant reductions in plasma LDL-C
levels (-17%) compared to the high-linoleic sunflower oil group. The
high-oleic olive oil-fed hamsters had significantly higher plasma
triglyceride levels (+41%) compared to the high-linoleic sunflower
oil-fed hamsters. The tocopherol levels in plasma LDL were
significantly higher in hamsters fed the mid-oleic sunflower oil
(+77%) compared to hamsters fed either the high-linoleic sunflower or
high-oleic olive oil. Measurements of LDL oxidation parameters,
indicated that hamsters fed the mid-oleic sunflower oil and high-oleic
olive oil diets had significantly longer lag phase (+66% and +145%,
respectively) and significantly lower propagation rates (-26% and
-44%, respectively) and conjugated dienes formed (-17% and -25%,
respectively) compared to the hamsters fed the high-linoleic sunflower
oil. Relative to the high-linoleic sunflower oil, aortic cholesterol
ester was reduced by -14% and -34% in the mid-oleic sunflower oil and
high-oleic olive oil groups, respectively, with the latter reaching
statistical significance. Although there were no significant
associations between plasma lipids and lipoprotein cholesterol with
aortic total cholesterol and cholesterol esters for any of the groups,
the lag phase of conjugated diene formation was inversely associated
with both aortic total and esterified cholesterol in the high-oleic
olive oil-fed hamsters (r = -0.69, P < 0.05). The present study
suggests that mid-oleic sunflower oil reduces risk factors such as
lipoprotein cholesterol and oxidative stress associated with early
atherosclerosis greater than the typical high-linoleic sunflower oil
in hypercholesterolemic hamsters. The high-oleic olive oil not only
significantly reduced oxidative stress but also reduced aortic
cholesterol ester, a hallmark of early aortic atherosclerosis greater
than the typical high-linoleic sunflower oil.

That's true. Its all about stages. LDL causes the problems because
it's a) smaller than the other lipoproteins and b) hangs around far
longer in the blood. Both of these mean it is far more likely to end
up lodged in an artery wall. Whether it then leads to fatty streak
formation depends on whether the protein in the lipoprotein gets
oxidised or not. The lipid part of the lipoprotein is irrelevant,
beyond providing the free radicals that oxidise the protein, since
it's damaged protein that macrophages react to.

LDL contains about as much cholesterol as VLDL and IDL, but it
contains less of the other types of fat, so is proportionally enriched
in cholesterol. This is where the more cholesterol = heart disease
idea springs from: LDL lodges in arteries, LDL is richer in
cholesterol, therefore cholesterol is to blame. It's correlation
rather than causation.

MattLB