Causes of Statin Adverse Effects

"After years of studying this subject I now have research documentation for the hundreds of case reports of unusual behavioral manifestations associated with statin use. There are now compelling explanations for the many reports of aggressiveness, hostility, sensitivity, paranoia, homicidal ideation, road rage like reactions, profound depression, suicidal ideation and even suicides associated with the use of statin drugs. And there is no doubt in my mind that many more statin associated problems may be involved with this dolichol function as we gain more knowledge."

Duane Graveline MD MPH
Former USAF Flight Surgeon
Former NASA Astronaut
Retired Family Doctor

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Statins are one of the most widely prescribed class of drugs for the reduction of cholesterol.  I have written several articles about the adverse effects of these drugs.  I consider them to be dangerous and best not taken. There are safe and effective alternatives.

Here is an article that explains the disturbing litany of adverse effects of statins.  This was sent to me some time ago by M J Hope Cawdrey, a respected and widely published researcher (I am not quite sure how to describe him other than as a "Bioclimatologist").  His additions and comments are in blue.

Thanks, Mike, for allowing me to reproduce your contribution to this most important health issue.

Gary

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Causes of Statin Adverse Effects  Article by Duane Graveline MD MPH


Here is Dr Graveline's website - a must read! (Gary)

The reasons for statin drug side effects are better appreciated by using this figure of the Mevalonate Pathway ( also known as the HMG-CoA reductase pathway ) adapted from any medical school biochemistry book.

All statins are reductase inhibitors and therefore exert their effect at the very beginning of the mevalonate pathway, the location of this key reductase step. When statin drug manufacturers make the claim of reduction of cholesterol synthesis, it is based upon inhibition of the mevalonate pathway, shared by the other major elements such as CoQ10 and dolichols.

Statins act by inhibiting HMG-CoA reductase as indicated in this figure. All metabolic functions further down the pathway are consequently affected.
Acetyl and Mevalonate Pathway

1.) Cholesterol Inhibition
Not only is glial cell cholesterol synthesis in our brains vital for memory function and cognition, cholesterol also is the substrate for our most important homones: aldosterone, cortisone, estrogen, progesterone and testosterone as well as the quasi-hormone, vitamin D (calcitrol). Cholesterol's vital role in membrane structure and function and lipid raft formation, makes it of critical importance in cell identification, cell communication and immunodefense.

Glial Cell Inhibition Potential Side Effects:
Amnesia
Forgetfulness
Confusion
Disorientation
Increased Senility

Hormone Lack Potential Side Effects:
Loss of Libido ( sexual desire )
Erectile Dysfunction ( ED)
Osteoporosis
Hair Loss

2.) CoQ10 ( Ubiquinone ) Inhibition
Coenzyme Q10 (CoQ10) is important for structural integrity of cells, anti-oxidation and, as part of the mitochondria, the production of Adenosine Triphosphate ( ATP ) energy. Part of its extreme importance in anti-oxidation is because of its location within the mitochondria, protecting the delicate components of the mitochondria from excess oxidative change and mutation.

Lack of Energy Potential Side Effects:
Chronic Fatigue Syndrome
Congestive Heart Failure
Fluid Retention
Shortness of breath

Loss of Cell Wall Integrity Potential Side Effects:
Hepatitis
Pancreatitis
Myopathy ( muscle pain and weakness, cramps )
Peripheral Neuropathy ( numbness, tingling or burning sensations particularly in hands and feet )
Rhabdomyolysis ( rapid breakdown of skeletal muscle tissue )

Excessive Oxidation Potential Side Effects:
Mitochondrial Damage
Permanent Neuropathy
Permanent Myopathy
Neurodegeneration


3.) Dolichol Inhibition
Dolichols are vital to the process of glycoprotein formation in the endoplasmic reticula of cells. In this capacity it is critical to the formation of the glycoproteins involved in neuropeptides, cell identification, cell messaging and immunodefense. Reduced bioavailability of dolichols can affect every cellular process in the body.

Neuropeptide Dysfunction Potential Side Effects:
Aggressiveness
Hostility
Irritability
Road Rage
Homicidal Behavior
Depression
Suicide

Altered Glycoprotein Synthesis Potential Side Effects:
Impairment of DNA error correction
Dysfunction of almost any cellular process
Altered cell identification
Altered cell messaging
Altered immunodefense

4.) Tau Protein Synthesis
When normal phosphorylation is interfered with by mevalonate blockade, our cells increase the production of Tau protein. Tau is the protein substance of the neurofibrilatory tangles common to Alzheimers and other neurodegenerative diseases. 

Neuro-Degenerative Diseases Include:
Parkinson's Disease
Alzheimer's Disease
Amyotrophic Lateral Sclerosis ( ALS )
Primary Lateral Sclerosis ( PLS )
Multiple Sclerosis ( MS )
Multiple System Atrophy ( MSA )
Frontal Lobe Dementia

5.) Selenoprotein
Only recently discovered were selenoproteins and the effect of statin blockade of the mevalonate pathway on their role in human physiology. Deficiency of selenoproteins has been proven to result in various types of myopathies formerly seen only in areas known to be deficient in this trace element. Additionally cognitive dysfunction is known to be associated with selenium lack.

My addition to the selenium paragraph -MJHC

    General:

    Selenoproteins (30+ at the last count) are important constituents of a number of enzymes with a range of functions including antioxidant function, thyroid hormone metabolism, male fertility and immune mechanisms and particularly in relation to cancer and cardiovascular disease.

    These selenoproteins include:
        Four glutathione peroxidase (GP) enzymes, a major class of functionally important selenoproteins and the first to be characterised:
        Classical GPx1 
        Gastrointestinal GPx2 
        Plasma GPx3 
        Phospholipid hydroperoxide GPx4 
        Thioredoxin reductase (TR), a seleno-cysteine containing enzyme important in regulating metabolic activity. 
        Selenoprotein P (60% of plasma selenium is held in this form) may have a role in the transport of selenium but also may have other functions. 
        Several iodothyronine deiodinase enzymes. These are responsible for conversion of the prohormone thyroxine to the active thyroid hormones (triiodothyronine or T3). 
        Sperm capsule selenoprotein which may be responsible for maintaining integrity of the sperm flagella (and hence motility of sperm). 
        Selenoprotein W. This is involved in muscle metabolism.

    In general selenium is thought to be important in a number of varied aspects of health (for a healthy immune system, for a protective effect against some forms of cancer, to maintain and enhance male fertility, for a reduction in cardiovascular mortality and to regulate inflammatory markers in asthma).
        Depletion of Antioxidant function - but oxidants are supposed to be a major cause of CHD
        Thyroid hormone metabolism.
        The selenoproteins are also involved in insulin/insulin resistance. (Would this account for the JUPITER finding of increased diabetes and other similar observations?)
        Keshan disease or Keshan-Beck disease - a cardiomyopathy - (a known adverse effect of statins)
        Counteracting the development of virulence and inhibiting HIV progression to AIDS. (And general effects on immunity)
        Enhancing sperm motility. 
        A possible role in preventing pre-eclampsia, although the Cochrane review suggests more trials are necessary. 
        A possible relationship between mood disturbance and selenium deficiency (a known adverse effect of statins)
        A possible association between elevated selenium intake and reduced cancer risk (a known adverse effect of statins).

        Overall, this destabilisation of much of the human metabolism by depleting the selenoproteins (apart from the effects on your other five points) must have serious consequences that seem to be overlooked in the use of statins in the interest of “THE BOTTOM LINE” and status (and in the UK of professorships, knighthoods and peerage apart from the money).

6.) Nuclear Factor - kappa B (NF-kB)
The benefit of statin drugs in cardiovascular disease control is in their ability to inhibit this vital transcriptase. The entire anti-inflammatory and immunomodulatory effect of statins is mediated by statin inhibition of nuclear factor-kappa B. Improvement in atherosclerosis results from the inhibition of the key inflammatory elements: smooth muscle migration. lymphocyte adhesion, macrophage attraction and platelet activation associated with inhibition of NF-kB. The immunodefense system is also keyed to NF-kB, explaining the changing patterns of certain infections and cancers. The rise in cancers of all kinds secondary to statin use is of major concern.                 

Article by Duane Graveline MD MPH
Former USAF Flight Surgeon
Former NASA Astronaut
Retired Family Doctor  http://www.spacedoc.net

          You will realise that statins do an immense amount of potential harm that statins can do. The elderly, prime targets for statins, frequently have low levels of CoQ10, selenium, antioxidants ( the selenoproteins), Vit D, steroids and hormones; their immunity is often reduced. Thus statins may well be causing more long term damage than they are solving, particular with the myth that the "euphimistic side effects" are usually trivialised by doctors.  The MHRA database gives another picture (see DAP on simvastatin  - all 54 pages)

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