Statins Stimulate Atherosclerosis and Heart Failure:
Pharmacological Mechanisms
Expert Review of Clinical Pharmacology
March 2015; Vol. 8; No. 2; pp. 189–199
Harumi Okuyama, Peter H Langsjoen, Tomohito Hamazaki, Yoichi Ogushi, Rokuro
Hama, Tetsuyuki Kobayashi, Hajime Uchino
BACKGROUND FROM DAN MURPHY:
The “cholesterol hypothesis” essentially holds that the:
• Higher the levels of total cholesterol the higher the risk of heart disease
• Higher the level of LDL cholesterol the higher the risk of heart disease
• Lower the levels of HDL cholesterol, the higher the risk of heart disease
In 2007, the lead author of this article wrote a book titled:
Prevention of Coronary Heart Disease:
From the Cholesterol Hypothesis to Omega-6/Omega-3 Balance
This book concludes that:
• “High blood cholesterol level is not a major causative factor for
atherosclerosis”
• “High cholesterol is a predictor of low mortality rates from cancer and all
causes.”
• High dietary omega-6/omega-3 ratios “is the major risk factor for coronary
heart disease.”
Congestive Heart Failure occurs when heart cells cannot make adequate levels of
ATP. ATP production is dependent upon levels of CoQ10. Statin Drugs impair the
synthesis of CoQ10, and therefore reduce production of ATP and therefore increase
the risk of Congestive Heart Failure.
Vitamin K1 is abundant in non-hydrogenated vegetable oil and in vegetables.
Vitamin K2 prevents the depositing of calcium into arteries, joints, and kidneys.
Without adequate levels of vitamin K2 atherosclerosis increases. Statin Drugs
inhibit the conversion of Vitamin K1 into vitamin K2, and thereby increase the
incidence of atherosclerosis.
KEY POINTS FROM THIS ARTICLE:
1) “In contrast to the current belief that cholesterol reduction with statins
decreases atherosclerosis, we present a perspective that statins may be causative
in coronary artery calcification and can function as mitochondrial toxins that impair
muscle function in the heart and blood vessels through the depletion of coenzyme
Q10 and ‘heme A’, and thereby ATP generation.”
2) Vitamin K2 protects arteries from calcification. Statins inhibit the synthesis of
vitamin K2.
3) Mitochondrial DNA is more susceptible than nuclear DNA to oxidative stress
injury and free radicle damage. The most important protector of mitochondrial DNA
from oxidative stress is glutathione peroxidase. Glutathione peroxidase is a protein
that requires the mineral selenium for function. Glutathione peroxidase is known as
a “selenoprotein.” Statins inhibit the biosynthesis of the selenoprotein glutathione
peroxidase. “An impairment of selenoprotein biosynthesis may be a factor in
congestive heart failure.”
4) “The epidemic of heart failure and atherosclerosis that plagues the modern
world may paradoxically be aggravated by the pervasive use of statin drugs.”
5) “We propose that current statin treatment guidelines be critically
reevaluated.” “Current statin therapy should be critically and urgently reevaluated.”
6) The “good and bad cholesterol hypothesis” is based on the simplified and
flawed interpretations that LDL carries triglycerides and cholesterol to peripheral
tissues, whereas HDL reverse-transports cholesterol to the liver to excrete excess
cholesterol to feces, mostly as bile acids. The flaw is now understood to exist
because HDL also transports cholesterol to LDL.
7) Statins drugs are effective in lowering LDL cholesterol “but were essentially
ineffective in preventing coronary heart disease.”
8) Statins were introduced to clinical medicine in 1987. Initial studies (1990s)
showed that statins were effective in lowering LDL cholesterol and also in
preventing coronary heart disease. “However, unfair and unethical problems were
associated with clinical trials reported by industry-supported scientists, and new
penal regulations on clinical trials came into effect in 2004.”
9) After 2004–2005, all clinical trials, performed by scientists relatively free of
conflict of interest with pharmaceutical industries, reported that statins were
effective in lowering LDL cholesterol but no significant beneficial effects were
observed for the prevention of coronary heart disease. Consequently, scientists and
physicians who continue to claim that statins are effective in preventing coronary
heart disease are mistaken.
10) These authors “support the pharmacological interpretations that statins
stimulate the development of atherosclerosis and heart failure.”
11) The mitochondria subcellular organelles produce stored energy ATP with the
essential enzyme coenzyme Q10 (CoQ10). “Statins inhibit CoQ10 biosynthesis and
thereby ATP generation.” “Statins are mitochondrion toxic.”
12) ATP is essential for normal heart muscle function and other activities in cell
life. “Statins are mitochondrial toxins making all cells ATP depleted.” “Statins are
general cell toxins.”
13) “Cholesterol is a major component of cell membranes, functioning to maintain
their integrity, which is likely to be affected by statins.”
14) The reduced form of CoQ10 (ubiquinol) is a clinically relevant antioxidant,
especially in the mitochondria where it “protects mitochondrial DNA from damage.”
15) “It is well known that mitochondrial DNA is much more vulnerable to oxidative
damage than nuclear DNA.”
16) “In the case of statins, ATP generation is impaired by their inhibition of CoQ10
biosynthesis. “Limited supply of ATP could be a major cause for heart muscle and
coronary artery damage.”
17) As compared to non-users, statin users exhibit:
HIGHER
• Systolic blood pressure
• Elevated glycated hemoglobin (HbA1c) level
• Glucose levels
LOWER
• CoQ10
• Glutathione peroxidase
• Complex IV electron transport protein [key in low-level laser therapy]
18) “Statin administration & selenium deficiency cause heart failure through a
common mechanism.”
19) Selenium is an essential trace element and is incorporated into
selenoproteins. Selenoproteins include glutathione peroxidase. “When glutathione
peroxidase synthesis is inhibited by statins, peroxidative stress is elevated, which is
generally accepted as causative for atherogenesis, carcinogenesis and aging.”
[Very Important]
20) Statins also lower the levels of antiperoxidative enzymes superoxide
dismutase and catalase.
21) Glutathione peroxidase activity is inversely associated with coronary heart
disease.
22) Selenoproteins are also “involved in several steps of glucose metabolism and
insulin actions, providing a potential etiologic basis for statin-induced diabetes
mellitus.” “We presented an urgent proposal that statins are contraindicated in
patients with diabetes mellitus.”
23) “Statins inhibit vitamin K2 synthesis and accelerate artery calcification.”
• Vitamin K1 is rich in non-hydrogenated vegetable oils and vegetables.
• The enzymes synthesizing vitamin K2 from vitamin K1 are present in many
tissues, including the brain, and statins inhibit the conversion of VK1 to VK2.
• “Statins inhibit vitamin K2 formation, and thereby accelerate coronary artery
calcification, an important marker of the progress of atherosclerosis.”
24) The authors cite a study indicating “high-frequency statin users were shown
to exhibit accelerated coronary artery calcification compared with low-frequency
statin users.”
25) In a study involving 6,673 subjects, “statin use was associated with a
significant increase in the prevalence and extent of coronary plaques containing
calcium.”
26) Statins can stimulate atherogenesis and heart failure.
27) The authors cite a 2013 study questioning why the goals of cholesterol levels
are set so low?, noting:
• The risk of death for all causes was lowest at total cholesterol levels at 240
mg/dl.
• When total cholesterol levels went below 180 mg/dl, all causes of death rose
significantly and essentially linearly as total cholesterol levels dropped to less than
160 mg/dl. [the lower the total cholesterol, the higher the risk of death from all
causes]
• The death rate for cancer was also lowest at 240 mg/dl, and increased as
total cholesterol levels went lower.
• Strangely, there was very little change in risk of death from stroke and/or
cardiovascular disease when total cholesterol was between 160 mg/dl to 260 mg/dl.
• These authors question the value of lowering total cholesterol to below 240
mg/dl.
28) These authors cite studies that support that the incidence of diabetes mellitus
is greater in the statin user group and it appears that statins increase diabetes
mellitus.
29) Coronary heart disease mortality in the statin-user group was higher and
increases with the length of statin use when compared with the statin nonuser
group. These authors interpret the results that statins increased coronary heart
disease mortality.
30) These authors note that the statin clinical trials performed in the 1990s that
show a relative risk reduction of approximately 30% in coronary heart disease are
erroneous.
31) Statin adverse effects on skeletal muscle (damage) are the most commonly
reported statin side effects, and include skeletal muscle weakness, muscle pain and
skeletal muscle cell death with elevated creatinine kinase levels.
[Statin drug induced muscle damage may be the symptoms that bring such
patients to the chiropractic office]
32) Statins decrease the concentration of mitochondria in muscle. “In view of
this obvious skeletal muscle toxicity, it would be naive to assume that statins would
not likewise negatively impact the much harder working heart muscle cells, which
have exceedingly high ATP requirements.” In animals, statins increase
cardiomyopathic mortality.
33) There is evidence for a causative role for statins in human heart failure:
• The first reported cases of statin-related heart failure was in 1990.
• Statin users can experience dramatic deterioration in myocardial function and
clinical status shortly after beginning statins.
• 200 mg/day supplementation with CoQ10 can stabilize these patients.
• Patients with statin induced diastolic dysfunction (an early finding in
congestive heart failure), could reverse their pathology to normal after 3 months of
supplemental CoQ10 at 300 mg/day.
• “Patients who have been on statin treatment for an average of 6 years
presented with overt and often permanent congestive heart failure.”
34) Statin adverse effects include:
• Muscle pain and weakness
• Fatigue
• Dyspnea
• Peripheral neuropathy
• Memory loss
• Congestive heart failure
These symptoms can be dramatically improved with statin drug discontinuation and
supplementation with 240 mg of CoQ10 per day (but it may take 2 years).
35) “Statin cardiomyopathy can be defined as an impairment in heart muscle
function consequent to statin drug therapy and not explainable by any other
underlying pathophysiology.”
• “Physicians in general are not aware that statins can cause heart failure and
are clearly not recognizing it.”
• “The mechanism for the impairment in heart muscle function appears to be
related to impaired mitochondrial function, which in turn is related to statin
depletion of CoQ10 [41], selenoproteins and ‘heme A’, all required for normal
mitochondrial function.”
• “Statin-induced impairment in heart muscle function appears to be
permanent.” Yet, discontinuing statin drugs and supplementation with CoQ10 will
clinically benefit these patients.
36) “Prolonged decrease in mitochondrial CoQ10 would diminish the ability to
protect mitochondrial DNA from free radical damage. After a critical percentage of
mitochondrial DNA is mutated, offspring mitochondria will progressively lose their
efficiency to produce ATP and simultaneously can generate more free radicals and
result in a self-perpetuating vicious cycle. The negative consequences of statininduced
increase in coronary artery disease, coupled with a direct statin toxicity
upon the myocardium, can be expected to be additive with enormous clinical
implications.”
37) “With more than one million heart failure hospitalizations every year in the
USA, the rapidly increasing prevalence of congestive heart failure is now described
as an epidemic and it is likely that statin drug therapy is a major contributing
factor.”
38) “Statins seem to act as immune suppressive agents and may have beneficial
effects on those who have excessive and/or life threatening immune-inflammatory
reactions, such as in transplantations. However, immune suppression may be
harmful in those who have no immune/inflammatory disease.”
39) “Few cardiology specialists around the world have accepted that there is no
clinical evidence for ‘the lower, the better hypothesis’. The majority of clinicians still
appear to accept the results of meta-analysis of reports, including those published
before 2004 when new penal regulations on the clinical trials came into effect.”
40) Evidence since 2004 indicates that statins are ineffective in preventing
coronary heart disease. The severe and often irreversible adverse effects of statins
indicate that their use “should be severely restricted.”
41) “Clinicians should not rely on drug information provided by industry-funded
trials or should trust study abstracts of clinical publications, which frequently do not
provide the full picture and present many deceptions.”
42) CONCLUSIONS
• “Statins stimulate atherogenesis by suppressing vitamin K2 synthesis and
thereby enhancing artery calcification.”
• “Statins cause heart failure by depleting the myocardium of CoQ10, ‘heme A’
and selenoproteins, thereby impairing mitochondrial ATP production.”
• “Statins are not only ineffective in preventing coronary heart disease events
but instead are capable of increasing coronary heart disease and heart failure.”
• “Physicians who are involved in prescribing cholesterol lowering medications
cannot ignore the moral responsibility of ‘informed consent’,” including their ability
to cause:
•• Coronary disease and heart failure
•• Onset of diabetes mellitus
•• Carcinogenicity
•• Teratogenicity
•• Central and peripheral nervous disorders
•• Rhabdomyolysis
•• Hepatic injury
“Most of these adverse effects of statins become apparent after 6 or more years of
statin therapy.”
COMMENTS FROM DAN MURPHY
I believe that all patients on statin drugs should discuss this article with their
physician who put them on the statin drug. Apparently, a critical determinant is
whether they relied on studies that were published before or after 2004.
This is the 9th article we have reviewed pertaining to statin drugs:
Article Review 25-09:
The case for statins: has it really been made?
Journal of the Royal Society of Medicine; 2004
Article Review 26-09:
Do Cholesterol Drugs Do Any Good? Research suggests that, except among highrisk
heart patients, the benefits of statins such as Lipitor are overstated
BusinessWeek; 2008
Article Review 07-10:
Carcinogenicity of Lipid-lowering Drugs
Journal of the American Medical Association; 1996
Article Review 22-11:
Statins and All-Cause Mortality in High-Risk Primary Prevention
Archives of Internal Medicine; 2010
Article Review 29-11:
Cholesterol Lowering, Cardiovascular Diseases
Archives of Internal Medicine; 2010
Article Review 39-12:
Should we lower cholesterol as much as possible?
British Medical Journal; 2006
Article Review 31-13:
Statin Use and Risk of Diabetes Mellitus in Postmenopausal Women
Archives of Intern Medicine; 2012
Article Review 06-13:
Statin Use and Musculoskeletal Pain Among Adults With and Without Arthritis
The American Journal of Medicine; 2012
Article Review 30-13:
Effects of Statins on Energy and Fatigue With Exertion
Archives of Internal Medicine; 2012