Re: (Oxydized) LDL not Mr. Bad Guy?

x-no-archive: yes

Just Cocky said:

Enrico C said:

A new 8-year-long research says:
"there was no relation between level of antibodies to oxidized LDL and
the development of CHD or CVD."

Based on my readings of recent literature, isn't chronic inflammation
the real culprit? Shouldn't people be paying attention to their
C-reactive protein and fibrinogen levels, instead?

Not *instead.* People should be paying attention to their TGLs, TGL/HDL
ratios, blood glucose, too.

Susan

Susan wrote:
: x-no-archive: yes
: Just Cocky wrote:
:: On Wed, 22 Feb 2006 15:20:18 +0100, Enrico C
:: <[email hidden]> wrote:
::
::: A new 8-year-long research says:
::: "there was no relation between level of antibodies to oxidized LDL
::: and the development of CHD or CVD."
:::
:: Based on my readings of recent literature, isn't chronic inflammation
:: the real culprit? Shouldn't people be paying attention to their
:: C-reactive protein and fibrinogen levels, instead?
:
: Not *instead.* People should be paying attention to their TGLs,
: TGL/HDL ratios, blood glucose, too.

The predictive value of certain markers depends on the metabolic type of the
person. For those people who have insuline resistance/abdominal fat/ type 2
diabetes TGLs, TGL/HDL ratios and blood glucose have good predictive value,
for others, less.

In general the total cholesterol: HDL ratio has still the best predictive
value. ApoB/ApoA1 ratio is an equally important ratio which is especially
useful for diabetics as a test because no fasting is required.

--
Juhana

x-no-archive: yes

Juhana Harju said:

The predictive value of certain markers depends on the metabolic type of the
person. For those people who have insuline resistance/abdominal fat/ type 2
diabetes TGLs, TGL/HDL ratios and blood glucose have good predictive value,
for others, less.

I was slim when I was severely IR as are many other folks, and still had
the dyslipidemia to show for it. I would guess that the vast majority
of those with elevated risk are at risk due to being IR.

Susan

Susan said:

Juhana Harju said:

The predictive value of certain markers depends on the metabolic type of the
person. For those people who have insuline resistance/abdominal fat/ type 2
diabetes TGLs, TGL/HDL ratios and blood glucose have good predictive value,
for others, less.

I was slim when I was severely IR as are many other folks, and still had
the dyslipidemia to show for it. I would guess that the vast majority
of those with elevated risk are at risk due to being IR.

Susan

Nobody gives a rats ass, to quote TC.

I agree with Just Cocky. Among "Asian Pacific" peoples, you will find
big differences. For example, that guy who is always posting anti-iron
studies here posted a study (I think it was less than a year ago) that
said that Asians with high iron levels did not have the "diseases" that
Western medicine "experts" would have predicted. I'd like to see
oxidized LDL studied this way in a country like the USA. Also, they
looked for antibodies for oxLDL, which again may not be the best idea,
especially for this population, and they only let it go for 8 years.
Also, was the difference between those with low oxLDL and high oxLDL
similar to what it would be in the USA? And did these populations have
the incidence of CHD that is common in Western nations? Thus, as
usual, there is a need for better studies, and in the absence of them,
there are foods you can eat that are not problematic in any of these
contexts, so you can just avoid the ones that are most likely the
"culprits," like refined oils with high unsaturated fatty acid
contents, and cooking meat while exposed to air.

To get a little technical about my "agreement" about the inflammation
comment: Asians with no AA in their cells will not have the same
"inflammatory" response as a "typcial" American, for example. oxLDL is
still "bad" in such Asian peoples, but it would take a lot more than 8
years to see the "badness" in the form of CHD. The high omega 6 PUFA
diet makes the body "hyper-responsive," and therefore speeds up the
processes involved here in CHD. You want to get AA out of your cells,
and let your body make the Mead acid PUFA as it sees fit. Then there
should be little oxLDL problem, unless you are inhaling powerful toxins
at work or something like that. Here are just a couple of studies that
make the point:

Oxidized LDL contains inflammatory PAF-like phospholipids.
Trends Cardiovasc Med 2001 Apr-May;11(3-4):139-42
Marathe GK, Prescott SM, Zimmerman GA, McIntyre TM.

Department of Pathology, University of Utah, Salt Lake City, Utah, USA.

Atherosclerosis has an underlying inflammatory component. Oxidation of
low-density lipoprotein (LDL) particles to modified forms promotes
atherogenesis by supplying cholesterol and through the oxidative
generation of agents that activate macrophages, smooth muscle and
endothelial cells. A primary target of oxidizing compounds, derived
from cigarette smoke, dietary sources, exuberant inflammatory cell
responses and normal cellular metabolism among other sources, are the
esterified polyunsaturated fatty acids in the phospholipid shell that
surrounds the insoluble lipids of the lipoprotein core. One type of
phospholipid oxidation product mimics the structure of the potent
inflammatory mediator platelet-activating factor (PAF), and these
oxidation products activate the PAF receptor found on platelets,
monocytes and leukocytes. Production of such PAF mimetics is, in
contrast to the physiologic generation of PAF, uncontrolled. PAF
mimetics and other phospholipid oxidation products are found in
atherosclerotic lesions or even in blood after exposure to cigarette
smoke. Here we summarize our data describing the structure, activity
and metabolism of the PAF-like lipids found in atherogenic LDL
particles.

Publication Types:
· Review
· Review, Tutorial

PMID: 11686003 [PubMed - indexed for MEDLINE]

Ital Heart J 2001 Dec;2(12):867-72
Low-density lipoprotein oxidation.

Iuliano L, Micheletta F, Violi F.

Istituto di I Clinica Medica Universita degli Studi La Sapienza
Policlinico Umberto I Viale del Policlinico, 155 00161 Roma.

Free radical mediated oxidation of low-density lipoproteins (LDL),
which has been extensively studied in the last two decades, plays a
central role in the development of the atherosclerotic plaque.
Oxidation involves the lipid moiety of LDL in a chain reaction
mechanism. In the initial phase, free radicals preferentially attack
highly oxidizable polyunsaturated fatty acids. Subsequent recruitment
of other molecules includes cholesterol and phospholipids. The process
of oxidation is counteracted by antioxidants present in LDL.
By-products formed during oxidation of LDL lipids, which may have
biological activity, react with amino acid residues of the LDL protein
backbone with the consequent modification of chemical and immunological
properties responsible for cellular receptor shift. Oxidation-altered
apolipoprotein B of oxidized LDL is, in fact, recognized by the
macrophage scavenger receptor responsible for foam cell formation. The
mechanism of LDL oxidation and the impact on atherogenesis are
discussed.

montygram said:

You want to get AA out of your cells,
and let your body make the Mead acid PUFA as it sees fit. Then there
should be little oxLDL problem,

You don't understand the mechanism of plaque formation, then.

Quoted message said:

unless you are inhaling powerful toxins
at work or something like that. Here are just a couple of studies that
make the point:

The second one doesn't make the point it contradicts it.

Quoted message said:

Free radical mediated oxidation of low-density lipoproteins (LDL),
which has been extensively studied in the last two decades, plays a
central role in the development of the atherosclerotic plaque.
Oxidation involves the lipid moiety of LDL in a chain reaction
mechanism. In the initial phase, free radicals preferentially attack
highly oxidizable polyunsaturated fatty acids.

This includes any Mead acid, ergo Mead acid is no protection in LDL.

Quoted message said:

Subsequent recruitment
of other molecules includes cholesterol and phospholipids. The process
of oxidation is counteracted by antioxidants present in LDL.
By-products formed during oxidation of LDL lipids, which may have
biological activity, react with amino acid residues of the LDL protein
backbone with the consequent modification of chemical and immunological
properties responsible for cellular receptor shift. Oxidation-altered
apolipoprotein B of oxidized LDL is, in fact, recognized by the
macrophage scavenger receptor responsible for foam cell formation.

Oxidised LDL is taken up by scavenger macrophages which is the start of
the plaque. whether it's Mead acid or arachidonic acid in the LDL makes
no difference. OxLDL alone is enough to start a fatty streak in the
artery through local effects.

MattLB

Just Cocky said:

Based on my readings of recent literature, isn't chronic inflammation
the real culprit? Shouldn't people be paying attention to their
C-reactive protein and fibrinogen levels, instead?

And active, accidently released myeloperoxidase and eosinophil
peroxidase producing still HOCl in such inflammation areas.
(C-reactive protein is most probably a marker of amount of PMN's and
monocytes that has died an too quickly death by necrosis (or
apoptosis) because HOCl has damaged far too much of the cell itself
instead of the infectious agent.

One report conclude that more than 85% material damaged by HOCl is the
immune cells macromolecules, mostly inside the phagolysosomes where
synthesis of HOCl mainly occure, except in eosinophils who release the
enzyme into serum in order to kill bigger invaders, like Candida and
other yeast cells etc.

Juhana Harju said:

In general the total cholesterol: HDL ratio has still the best predictive
value. ApoB/ApoA1 ratio is an equally important ratio which is especially
useful for diabetics as a test because no fasting is required.

Predictive value for what??

On 22 Feb 2006 19:21:01 -0800, "montygram" <[email hidden]>

Quoted message said:

I agree with Just Cocky. Among "Asian Pacific" peoples, you will find
big differences. For example, that guy who is always posting anti-iron
studies here posted a study (I think it was less than a year ago) that
said that Asians with high iron levels did not have the "diseases" that
Western medicine "experts" would have predicted. I'd like to see

One difference is that people living in Asia and using either lot of
fish in diet or using ertain berries like Chines Wolf Berry, has an
enormouse intake of taurine compared to Western hemisphere. (A quick
computation based on average food intakes in Norwegians a few years
ago, based on knowledge about how much taurine is present in those
nutrients, did show average intake would be around 30 mg taurine pr
day, while in Japan it exceed by far 500 mg, possibly more than 1 g
daily.

Taurine has a structure that combined with phosphate groups of DNA
form a mixed complex with iron completely locking it up from doing any
harm at all. This is most probably lacking in Western hemisphere.

Alf Christophersen wrote:
: On Wed, 22 Feb 2006 21:13:51 +0200, "Juhana Harju"
: <[email hidden]> wrote:
:
:: In general the total cholesterol: HDL ratio has still the best
:: predictive value. ApoB/ApoA1 ratio is an equally important ratio
:: which is especially useful for diabetics as a test because no
:: fasting is required.
:
: Predictive value for what??

For cardiovascular disease in general.

--
Juhana

Rather than do a large study measuring a few variables, why not do a
smaller study and measure all the plausible confounding variables?
This study would have been a lot more enlightening if they'd measured
C reactive protein
HbA1c
EPA and Arachidonic acid in the white blood cell membranes
Lp(a)
Those are my top 4. If they've got the inclination I'd also like to
see fibrinogen, homocysteine, some measure of serum antioxidant status
(ORAC, FRAP), white blood cell count, some measure of fitness.

They could have done these tests as a nested case control study. That
is, do an extra blood draw on everybody in the study, and freeze it.
At the end of the study, pull the blood on those participants who've
hit an endpoint (e.g. heart attack) and choose a matching set of
incident-free participants. Only do the extra testing on those blood
samples. Shouldn't run up the cost of an 8 year study very much. And
it would have told us so much more!

==========

Are there common lab tests for oxidized LDL, or is this just a test
that research labs run? Are these tests standardized enough, or does
one need a rich description of the "lab normal" outcomes in order to
interpret the result? Is there one widespread test, or are there a
bunch of different methods, with varying accuracies, to choose from?
Is getting a reading after overnight fasting enough, or does one need
multiple draws to get a meaningful measure? If I pressure my endo to
test my oxidized LDL, am I asking for a $20 test or a $600 test?

Anybody?