Read the full article HERE. This is only an exerpt.
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 , 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
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.
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 . 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
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! . 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 . 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
See also: http://stephanie-on-health.blogspot.com/
The author Stephanie is a research scientist at MIT.