The Lipitor lawsuits

[Biologist]

Brooks,

Here is pretty much the answer that I have been after. Note the use of the terms "endogenous" and "exogenous" in the following text. It appears the pathway is found and used not just in the liver but in all cells of the body (all of which are apparently subject to individual on-site statin inhibition of the pathway). The liver may even be a "net importer" at times based on the following due to its high demand, like the brain. I'm thinking even single-celled organisms make their own and that this is basically where we got our pathways for it -- that is what's meant by a process being "highly conserved" in evolution.

We do see -- but once again -- that supplementation can work from this experiment, and there is no doubt that CoQ10 natually circulates in the blood -- and probably not just from ingestion. My guess is that the liver may be one of the blood stream's prime "CoQ10 pumps" like it is for cholesterol, but I ain't guaranteeing right it at this point. Regardless your discovery makes it more likely that we are now doing supplementation right.

"The main objective of this study was to
resolve the issue of whether the amounts
of Coenzyme Q (CoQ), which is endogenously
synthesized in cells, can be elevated in
tissues and mitochondria of young mice by
dietary supplementation with CoQ10. The
prevalent view is that the uptake of exogenous
CoQ by tissues other than plasma and liver
either does not occur or is quite minimal."

*http://jn.nutrition.org/cgi/content/abstract/133/10/3175

Vitamin E is also discussed. You might like the full version by clicking the link on the top right-hand side of the page.

Biologist

[cjbrooksjc]

Biologist: I don't see any proof in these findings that UBQ is generated endogenically by individual body cells. I didn't read it all through though. Where did you see that? I do see that exogenic (dietary) availability is utilized and increases the levels in heart, liver, and skeletal muscles. See below:

DISCUSSION:
The finding that amounts of CoQ, especially in mitochondria from skeletal muscle, heart and brain, can be elevated in young mice by dietary supplementation of CoQ argues against the classical view that uptake of exogenous CoQ by tissues other than plasma and liver is very low or absent (12–14). In contrast, the present results clearly indicate that CoQ levels were not only elevated in heart and skeletal muscle mitochondria in response to dietary supplementation, but such increases were greater than those occurring in the liver.

I'm missing something I think. I can't find any reference to the natural, internal origination of UBQ at all; even the mevolonate pathway. This reads to me solely like a report on the uptake of orally supplemented UBQ by the cellular mitochondria. It's late though, and maybe I'm missing the point. I may, in fact, be missing the question; THAT is a REAL possibility! And, as I said, I didn't read everything in the report findings. Anyway, off to bed. Straighten me out tomorrow, will you?

Thanks,

Brooks

[Biologist]

OK, try this then:

*http://www.pubmedcentral.nih.gov/botrender.fcgi?blobtype=html&pubmedid=17094036

"Coenzyme Q10 (CoQ10) is the predominant
human form of endogenous ubiquinone.
Synthesized in the mitochondrial inner
membrane..."

Hey, you're up way too late. I am about to pop one of Brian's suggested L-Tryptophans right now myself...

Biologist

[Brian C.]

As ubiquinone is essential for electron transport from complex II to complex III in the mitochondrial respiratory chain so also is another product of the melavonate - farnesyl pathway, heme a in cytochrome c, essential for transport between complex III and complex IV. It is the denial of oxygen in this step that makes cyanide and carbon monoxide so deleterious to life.

The constant weakness I felt whilst taking the Lipitor used to make me think we may have had a problem with our gas boiler causing low level CO poisoning, so I had it replaced. Now I know what I was feeling was EXACTLY the same as I would have felt if that boiler was leaking because the effect is identical!

I haven't yet discovered quite how farnesyl is involved in the production of heme.
Biologist, you got any idea? Anything in your textbooks?

Brian.

[cjbrooksjc]

Biologist, Brian: This is WAY more than I ever wanted to know about biochemistry, but here is something to consider:

Below is the url link to the following paragraph.
*http://www.pubmedcentral.nih.gov/botrender.fcgi?blobtype=html&pubmedid=17094036

"CoQ10 biosynthetic pathway has eight known biosynthetic enzymes denoted as COQ1 thru 8. CoQ10 is composed of a benzoquinone and a decaprenyl side chain. While the quinone ring is derived from amino acids tyrosine or phenylalanine, the isoprenoid side chain is produced by addition of isopentenyl pyrophosphate molecules to geranylgeranyl pyrophosphate (DERIVED FROM THE MEVALONATE PATHWAY) by decaprenyl diphosphate synthase. After para-hydroxybenzoate and decaprenyl pyrophosphate are produced, at least seven enzymes (encoded by COQ2 thru 8 ) catalyze condensation, methylation, decarboxylation, and hydroxylation reactions to synthesize CoQ10."


I am ALSO confused now (thank you Biologist) as to exactly where and how CoQ10 is manufactured and, in fact, whether there is a single site one might point to at all. If the Mitochondria can manufacture CoQ10, why is the Statin effect so damning? Is it because the end step in manufacture (mitochondrial synthesis) relies on the single component contributed by the liver and detailed above? I haven't been this confused since I dropped my gum on the hen house floor; so, I will leave it to those better suited. I'm off to mow the lawn.

Regards,

Brooks

[Brian C.]

From Wikipedia :

*http://en.wikipedia.org/wiki/HMG-CoA_reductase_pathway

"The mevalonate pathway or HMG-CoA reductase pathway or mevalonate-dependent (MAD) route, is an important cellular metabolic pathway present in all higher eukaryotes and many bacteria."

Eukaryotes are cells containing organelles, e.g.mitochondria, performing vital processes for the cell's well-being. Mitochondria are a type of bacteria long assimilated that allowed cells to function in an oxygen atmosphere.

Thus the mevalonate pathway is in each of our cells AND in each of our cells mitochondria. If the quantity and/or rate of assimilation of statins is gradually increased we would reach the point of no return (cell apoptosis/death in critical organs) and die.

The drug companies are smart enough to discourage overdosing by enthusiastic quacks so we are only dosed to incapacity, not death.
We are also told to lay off the grapefruit, which enhances assimilation of the incapacitating agent.

Brian.

PS I learned about eukaryotes and mitochondria from the fascinating book by Nick Lane - "Power, Sex, Suicide: Mitochondria and the Meaning of Life"

[Biologist]

Thanks, Brian.

Wish I had thought of that.

Could have saved me half a day... :cry:

Hey, Brooks, it appears your idea of high Vit. E was a reasonable idea. I am glad I did not find and read my last hyperlink earlier as I would have been dosing even higher levels of E. And regardless, you may have been doing much good over your dosing period, and now are ready for the next step in the treatment -- more CoQ10. Note the following:

"Oxidative damage and mitochondrial dysfunction have also been implicated in neurodegenerative diseases such Parkinson disease (PD), Alzheimer disease (AD), and Friedreich’s ataxia (FRDA) [39–41]. Preclinical studies have indicated that CoQ10 can protect the nigrostriatal dopaminergic system and high doses (1200 mg daily) of CoQ10 for 16 months appeared to slow progression PD [40, 42]. In 10 FRDA patients treated for 47 months high doses of CoQ10 (400 mg daily) with vitamin E (2100 IU daily), improved bioenergetics in heart and skeletal muscle, improved cardiac function by echocardiography, and, possibly less clinical decline compared to historical controls [43]. Larger studies are necessary to better define the short- and long-term effects of CoQ10 as primary or adjunctive therapy in neurodegenerative diseases."

Biologist

[Biologist]

Sorry, Brooks, I completely missed your last post when posting my last post. I went directly to Brain's from the main menu but noticed it just now. I see where the confusion lies and will post for you on it before long. No big deal.

xrn,

the reason I came back just now -- and I AN a little busy now -- was specifically to mention that your site is looking real good. It has been on my list for sometime to go through more fully and now it is higher on the list. Keep up the good work!

Biologist

[Biologist]

Without being on the front line of research ourselves, there is really not much need for us to get into the serious Organic Chemistry (Ooouch!) from the first paragraph you cited. That is some serious physics there. (Yes, I actually meant to say "physics" over "chemistry" as it is a more encompassing term that includes chemistry just as one aspect of it all.) I consider molecular biology to be physics. I am not alone there, I believe.

"I am ALSO confused now (thank you Biologist)
as to exactly where and how CoQ10 is manufact-
ured and, in fact, whether there is a single site
one might point to at all."
--Brooks

It is manufactured in the mitochondria of the cells (and possibly partly or also in the cytoplasm of the cells?).. All cells have 100s or more mitochondria (small organelles floating around independently in the cell) depending on the cell type and the energy requirements for the cell. Consider the M. Pathway as being a series of sequential chemical reactions. A substrate is "operated on" with the help of an enzyme to become changed in one manner or another and then another reaction takes it the next step towards an end product; however, the next step may not occur right away or even at the same location (while it might) -- the molecule my be transported to another location before the next step is completed. It is just that they (the reactions) have to occur in order, the timing to completion is not as important. This pathway can occur anywhere the conditions are right including in a test tube.

If the Mitochondria can manufacture CoQ10,
why is the Statin effect so damning?
--Brooks

The statin is apparently getting into the mitochondria, as best I can surmise -- which is not so surprising really. There it throws a monkey wrench in the works. The mitochondria needs ATP to power itself to make CoQ10 in order to make ATP, which it needs to make CoQ10, and on and on. Look at it as jump-starting the process. Also, the machinery may become ruined by the lack of Q and may always need supplementation? That is where the research is trying to get things figured out, but what we seem to know at this point is that the mitochondria and the cells start working better with supplementation. The exact mechanism of it all is still a question as far as I know. The Q also makes the cell more sound by improving the integrity of the outer cell wall. Otherwise, it may not adequately bring in and keep in the substrates that the mitochondria need to do their job of making Q to improve the cell wall, and around and around we go...

Forget about the liver where CoQ10 is concerned. Cholesterol is manufactured and stored there. Q appears to be a different animal. But like Q, when it travels, it calls LDL Cab Co., Inc.

That's about the current state of my knowledge on the subject. 75% probability of being 65% accurate.

Biologist

[Brian C.]

Biologist - 75% probability of being 65% accurate.

So less than 50%
Fat lot of good you are then, better off tossing a coin

Of course it's physics. After all, everything is all-singing, all-dancing space-time, innit

Brian

[cjbrooksjc]

Biologist: I was confidently postulating and didn't even know what the real story was. I thought the mevalonate pathway was a liver function exclusively and that the Statin effect was focused there; the resultant global physical effects being caused by the lack of manufactured CoQ10 from the liver. I've been looking at the mevalonate world thru a tube; I'd no idea it was so all-encompassing.

It's like learning boolean logic - just when you think you understand it... BOOM! - you're back in kindergarten picking your nose in public!

Thanks for the insight.

Regards,

Brooks

[Biologist]

"Biologist - 75% probability of being
65% accurate....Fat lot of good..."
--Brian

Brian, my back of an envelope calculations at the time had indicated an approximate 48.75% chance of being right on all major issues discussed. Not to impressive perhaps.

But with BigPharma's approved statistical analysis accounting methods for research reporting -- which, as you can see, I used -- the probabilities are quite nicer to look at, wouldn't you agree?

Biologist

[Brian C.]

:lol: :lol: :lol:

[SusieO]

I was doing a bit of Lipitor lawsuit searching today and ran across this article. It appears attorney Mark Krum has many clients now that he is representing with statin damage from Lipitor. This may be my own speculation, but why is it that all these folks appear to be "someone special" other than a normal Dick or Jane type person????

Here is the website (remove the *) *http://www.krumlaw.com/press.html

I sent them another email asking about my situation since I suffer from Lipitor damage, but I am no one special i.e. a doctor or dentist or prominent politician or what have you...yet I am a special person to my family!!!

I also filled out a request form with this law firm (remove the *) *http://www.statindruglawyer.com/statin_drug_news_060806.html in hopes of someone helping us to have our voices heard and get this monster drug off the market!

[Dee]

Hi Susie,

That article about Mark Krum has no date, but I think it goes back to last fall. I wish there was a status update about the suits he has filed. I don't know why, though, just some kind of morbid curiosity on my part. It appears that most of us with statin damage are being ignored by the legal profession.

I wonder how many calls Krum took to sort out these special 17, and what his criteria was for selection.

I keep thinking that a lawyer somewhere has to see the dollar signs if nothing else...there HAS to be hundred of thousands of victims if not millions.

[Dee]

Susie,

Also, having talked to some folks that have sued for other medical errors, many of them would not bother to go through it again. The lawyers, insurance companies, and Uncle Sam ended up with most of the settlement, and the victims ended up with stress and aggravation.

Our government needs to step up to bat on this statin disaster because it was the FDA that is suppose to protect us from just this kind of massive drug farce and ruined lives. There should be a fast track program developed for those that involves NO lawyers, just settlements to make it right with the victims, to the extent that is possible. We all know there is not enough money to exchange for the quality of life decline we have experienced, but I would like to see them try!

[UK alien]

Hi Suzie,

as one of the "special" 17 of Mark Krums class action lawsuit I can only imagine he picked 16 fellow statinsufferers whom he knew to have a long, well documented history of Lipitor side effects. Believe me, for the last two years I have done very little else but complete forms for Pfizers lawyers who insist on having the last 20 years of medical, social, employment, recreational and family history. We are not yet even at the discovery stage!!

I get the impression (and I could be wrong) that the outcome of the class action lawsuit of this group of 17 will determine whether to open the floodgates of the thousands and thousands of other statinsufferers! My guess is that a precident needs to be set first and probably the best way of doing that is with a limited group with a long, proven history of side effects.

[Dee]

UK alien,

Thanks for the info on the Lipitor suit. Very interesting, though a little discouraging that things are taking so long.

I would think that those on lipitor, with the memory problems it creates in some, would have a hard time remembering details from 20 yrs ago to the present time.

Thanks again.

Dee

[UK alien]

Hi Dee

apparently the long and drawn out procedure is primarily due to Pfizers lawyers demands for detail, intricacy and accuracy! No doubt well proven delaying tactics are involved here.

Yes, its been a test on memory and indeed patience as some of the questions and requests are well beyond asinine in their relevance, logic or reasoning but that is the game they play in the hope people forget or become discouraged.

I am informed that Pfizer make a cool $1 million in NET profit for every hour of every day fom Lipitor alone so it would appear they have enough money to finance the escapades of their lawyers, both internal counsel and subcontracted. With that level of extortion they have all the time and money in the world to ensure this does NOT have a speedy conclusion.

I'll post any further and future developments as and when (and IF) they occur