Re: Statins and LDL oxidation

[Guest guest]

--- In , " Masterjohn "

<chrismasterjohn@...>

wrote:

>

> http://www.ncbi.nlm.nih.gov/pubmed/18021066?

ordinalpos=12 & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVD

ocSum

>

> Studies on kinetics of free radical oxidation of rat liver membrane

> phospholipids have shown that ubiquinol Q(10) is the most active

> lipid-soluble natural antioxidant, and suppression of ubiquinol Q(10)

> biosynthesis by beta-hydroxy-beta-methylglutaryl coenzyme A reductase

> inhibitors (statins) is accompanied by intensification of lipid

> peroxidation in rat liver biomembranes and in LDL of human blood

> plasma. Injection of ubiquinone Q(10) protects the human blood plasma

> LDL against oxidation and prevents oxidative stress-induced damages to

> rat myocardium. A unified molecular mechanism of atherogenic action of

> carbonyl-modified LDL in disorders of lipid and carbohydrate

> metabolism is discussed.

>

So statins increase ox-LDL via HMG CoA inhibition, but injection of CoQ10

protects LDL

against oxidation and prevents OD to the myocardium.

No wonder the drug companies are trying to get supplements regulated. Lots of

money to

be made in a CoQ10 drug that you'll have to take concurrently with your statin

drug.

Maybe Law & Wald should just put it in the Polypill? Or how 'bout just don't

take statins.

Things get pretty complex with statins, and that's probably why the trials are

all over the

map. They increase ox-LDL and decrease CoQ10, but on the other hand they

inhibit Rho

activation and increase NO synthesis. Kind of like driving with your foot on

the accelerator

and brake at the same time.

Thanks for posting this Chris.

[Guest guest]

Forgot to mention that I'm somewhat surprised by this study as I've seen several

others which

indicate that statins reduce ox-LDL levels.

[Guest guest]

> Things get pretty complex with statins, and that's probably why the trials

> are all over the

> map. They increase ox-LDL and decrease CoQ10, but on the other hand they

> inhibit Rho

> activation and increase NO synthesis. Kind of like driving with your foot

> on the accelerator

> and brake at the same time.

This provides a good possible explanation for your previous conundrum.

I had pointed out that they lower CoQ10, which is protective against

heart disease, but I had forgotten about CoQ10 protecting LDL from

oxidation and I had not realized how important it is. The full-text

of this article cites a PNAS article from 1991 showing that CoQ10 is

FAR more important to LDL oxidation than vitamin E:

http://www.pnas.org/cgi/reprint/88/5/1646

This explains not only why statins might increase LDL-oxidation in

some scenarios (even though there are reasons for them to lower

LDL-oxidation in others), but also explains why vitamin E may have not

been successful -- because it is not very protective against LDL

oxidation, and CoQ10 is the main antioxidant in LDL.

Chris

> Thanks for posting this Chris.

De nada, mi amigo.

Chris

[Guest guest]

On 2/22/08, chriskjezp <chriskresser@...> wrote:

> Forgot to mention that I'm somewhat surprised by this study as I've seen

> several others which

> indicate that statins reduce ox-LDL levels.

Well first of all are they reducing total ox-LDL, or are they reducing

the proportion of LDL that is oxidized to a certain threshold, or the

proportion of oxidized components of LDL? They are lowering LDL, so

if they have no effect on oxidation at all they will lower ox-LDL.

Moreover, the fact that they lower LDL should lower the proportion of

LDL that is oxidized because they are lowering the oxidative liability

and, all things being equal, allowing a greater density of antioxidant

distribution in LDL. Moreover, by boosting nitric oxide synthase from

Rho inhibition, they boost the protective effect of nitric oxide

against LDL oxidation.

On the other hand, they powerfully inhibit synthesis of CoQ10, the

primary antioxidant in LDL.

So there are directly competing mechanisms and it is reasonable that

they may have opposing effects in different studies depending on the

precise context and how it influences the competition of these factors

in ways we might not completely understand.

Chris

[Guest guest]

Okay, trying to read this makes my brain hurt...Can someone translate into

layman's terms?

Thanks!

[Guest guest]

Hi ,

> Okay, trying to read this makes my brain hurt...Can someone translate into

> layman's terms?

Coenzyme Q10 is involved in energy production in the mitochondria, the

so-called " power house " of the cell, but also acts as an important

antioxidant. It is secreted into LDL and protects LDL from oxidation.

LDL that is not oxidized does not contribute to atherosclerosis, but

LDL that becomes oxidized does. Statins, which are meant to lower

LDL, also greatly reduce CoQ10 levels, and thereby could contribute to

increases in LDL oxidation under some circumstances.

Chris

[Guest guest]

Thank you Chris!

[Guest guest]

lol,... I would translate it as one of the numerous statin drug side effects.

Best Always, Jim

Masterjohn <chrismasterjohn@...> wrote:

Hi ,

> Okay, trying to read this makes my brain hurt...Can someone translate into

> layman's terms?

Coenzyme Q10 is involved in energy production in the mitochondria, the

so-called " power house " of the cell, but also acts as an important

antioxidant. It is secreted into LDL and protects LDL from oxidation.

LDL that is not oxidized does not contribute to atherosclerosis, but

LDL that becomes oxidized does. Statins, which are meant to lower

LDL, also greatly reduce CoQ10 levels, and thereby could contribute to

increases in LDL oxidation under some circumstances.

Chris

Well done is better than well said..., Jim Igo

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