Cholesterol and Statins: Who’s the Hero? Who’s the Villain?

Read the full article HERE. This is only an exerpt.
=================================================================

Cancer

It is not easily shown that statins increase risk to cancer, because it takes considerable time for cholesterol to become depleted in the tissues as the supply line to replenish worn out cholesterol is reduced, and then more time for this depletion to lead to cancer due to genetic mutations. However, low cholesterol is a risk marker for cancer [15], and, despite the fact that statin trials are usually too short to reveal the trend towards increased cancer risk, several statin trials have resulted in observable differences between treatment and control groups, with treatment groups faring worse. In the first two trials on simvastatin, non-melanoma skin cancer was more prevalent in the treatment group, a result that becomes statistically significant if the data from the two trials are combined. In the CARE trial, which involved exclusively women, 12 women in the treatment group developed breast cancer, as against only one in the control group, a result that was highly significant (p = 0.002). Two other trials, both PROSPER and SEAS, also showed statistically significant increases in cancer incidence in the treatment group compared to the control group.

The story, in my view, for how statins increase your risk to cancer, involves a number of players and some complexity regarding mechanism. But it’s a very logical step-by-step progression, taking place steadily over an extended period of time. To understand the story, you first have to know something about vitamin B12 (cobalamin), a key player in the story. Vitamin B12 catalyzes a great number of reactions that require methionine, an essential sulfur-containing amino acid, as substrate, extracting the methyl group from methionine and adding it to some other molecule. One of the key molecules that benefits from such reactions is DNA. Methylation of DNA protects it from damage due to exposure to carcinogens or oxidation or radiation.

Methionine can also be degraded via a different pathway, and it’s an either-or situation here. This alternative fate results in the production of homocysteine, which later becomes substrate for the synthesis of sulfate. So, logically, if sulfate is in short supply, then methionine would get side-tracked down the homocysteine pathway, and less of the DNA would get methylated. Eventually, this would manifest as an increased risk to cancer.

Why might sulfate supply be deficient? This is something I have already discussed in previous blog posts, and one way it could happen is if the cells in the epidermis didn’t have enough cholesterol. This is because they need cholesterol in order to produce cholesterol sulfate, upon exposure to sunlight. The cholesterol sulfate is then shipped out via the blood stream to all the tissues, which eagerly take it up to resupply themselves with both cholesterol and sulfate.

The cells in the skin can synthesize their own cholesterol, but statin therapy would interfere with this process. As a result, they would not be able to spare cholesterol to ship out. What happens first is that, due to cholesterol deficiency in their membranes, they start leaking potassium at an excess rate, and an energy burn they can’t afford ensues, to pump the potassium back in. This becomes untenable, so calcium is brought in to replace some of the potassium as a positively charged electrolyte. Being a much bigger molecule, calcium doesn’t leak out nearly so easily. Its presence has a dramatic effect, however, on the eNOS molecules that had been responsible for synthesizing sulfate. They detach from the cell membrane and start making nitric oxide (−→ nitrate) instead. Unfortunately, this also results in some nasty side products like peroxynitrite and superoxide, which are potent oxidizing agents.

One of the first molecules that gets oxidized is cobalamin [1]. This drives the cobalt atom in cobalamin to a +3 charge, which inactivates the molecule, meaning that it will no longer support the methylation of the vulnerable DNA, thus increasing the risk to cancer. This is interesting from a biological standpoint, because it means that the methionine will naturally shift towards producing sulfate, a good idea since the skin is no longer going to be able to keep up with the supply.

One of the other molecules whose synthesis is catalyzed by cobalalmin is coenzyme Q10, probably the most important antioxidant in the mitochondria. The mitochondria are the chambers where sugars and fats are oxidized to produce ATP, the energy currency of the cell. Mitochondria are the organelles in the cell that suffer the greatest exposure to oxidizing agents, because oxidative metabolism takes place there. They contain their own separate mitochondrial DNA, now highly vunerable to attack.

To add insult onto injury, statins also interfere with the synthesis of coenzyme Q10, so this potent antioxidant is now in very short supply in the mitochondria of any cell in the skin that has been hit hard by a statin drug. The cells in the skin are now poised to develop cancer: they’ve got an extra burden of oxidizing agents, an increased vulnerability in their DNA to susceptibility to damage due to the demethylation process, and a decrease in the agents that would mop up extra free radicals. It’s not at all surprising that skin cancer is where the increased risk to cancer with statin therapy was first noted.

Another cancer which I suspect is increasing in incidence directly due to statin therapy is prostate cancer, which is the most common cancer by far in men. A very interesting recently noted observation is that prostate cancer tumors actually are producers of cholesterol sulfate! [3]. It has been suggested that this feature might be useful as a more reliable indicator of prostate cancer than the PSA test. I suspect in fact that this is a positive role they play, to try to correct a severe deficiency in this vital molecule, as cholesterol sulfate plays an essential role in fertilization [6]. Unlike women, men normally remain fertile throughout life, but not if cholesterol sulfate is insufficient. I would predict that surgery to remove a prostate tumor, beyond rendering a man infertile, will lead to an increase in various medical problems related to cholesterol sulfate deficiency.

From:  http://cindy-on-health.blogspot.com/2011/12/cholesterol-and-statins-whos-hero-whos.html

See also: http://stephanie-on-health.blogspot.com/

The author Stephanie is a research scientist at MIT.

"Ezetimibe and Cancer — An Uncertain Association"

The New England Journal of Medicine (NEJM) editorial article published September 2, 2008 bears the title "Ezetimibe and Cancer — An Uncertain Association". You might ask 'what the heck is Ezetimibe?' It is another one of those drugs used to lower serum cholesterol levels frequently in conjunction or parallel with a statin drug. Of late it has actually been combined into the same pill with Simvastatin also known as Zocor and the combination called Vytorin.

Also in the above mentioned issue of NEJM they published the results of the SEAS trial (Simvastatin and Ezetimibe in Aortic Stenosis). "In the trial, a combination of simvastatin and ezetimibe (Vytorin) was compared with placebo with respect to the incidence of cardiovascular events in older people with aortic-valve stenosis. The treatment had no impact on the progression of aortic stenosis or on cardiovascular clinical events in general, ..."

Now note the following from the NEJM editorial....

"There was, however, an unexpected finding in the trial. An excess of incident cancers was observed in the simvastatin–ezetimibe group, with 105 in that group as compared with 70 in the placebo group (P=0.01). There was an increase in the incidence of a variety of cancers, including prostate, gastrointestinal, and skin cancers. Also, deaths from cancer were more frequent in the active-treatment group (39 deaths, vs. 23 in the placebo group), ..."

WOW!

Finally the editorial says ...

"Ezetimibe interferes with the gastrointestinal absorption not only of cholesterol, but also of other molecular entities that could conceivably affect the growth of cancer cells. The fact that the combined data from all three trials showed an increase in cancer mortality with ezetimibe should not be assumed to be a chance finding until further data are in. It is appropriate that SHARP and IMPROVE-IT continue. Careful follow-up of the patients in these trials will be essential, and other existing data sets on ezetimibe-treated patients should be analyzed for cancer end points. The Food and Drug Administration has already announced that during the next few months it will conduct its own analysis of the potential cancer hazard of ezetimibe."

Note: In the above quotes from the NEJM editorial the 'bolded' text was emphasis added my me and did not occur in the original article which you can read in its entirety here. You can also read results of the (SEAS) trial here.

See also this Natural News article on the same subject.

Now a bit of personal history as related to the above information and also cited in this blog over one year ago ( see it here).

• I was on cholesterol lowering statins for roughly 20 years beginning in the mid 1980s.
• In 1994 (with low cholesterol) I had a heart attack resulting in open heart surgery.
• P.S. Four subsequent heart attacks (most recent June 2006), three requiring stents - all while having well below 'their recommended' serum cholesterol readings. (added this item Oct 8, 2007)
• In 2003 I had a fist sized gastrointestinal cancerous tumor removed along with about 9 inches of my small intestine.
• I've had one basal cell carcinoma (skin cancer) surgically removed about 3 years ago.
• I personally have no data to tie these events in my life together. (I might change this statement as this connection is further explored)
• I feel good now - like none of the above had happened. It almost seems surreal. But I've had four subsequent heart attacks - three with stents and there is some possibility that the cancer could reappear.

And a piece of info not included in the above is that for a significant length of time while taking statin drugs to lower my cholesterol and thus presumable reduce chances of heart attack, I was also taking Ezetimbe. All that before the gastrointestional cancer and basal cell carcinoma (skin cancer) were discovered and treated seemingly successfully.