by Duane Graveline, MD, MPH
Myth 1.) Most Doctors are Well Informed about the Adverse Reactions of Statin Drugs.
Doctors are far too busy to be kept properly informed about adverse reactions to drugs. This is particularly true with post-marketing drug reactions. For just one example, consider the side effect of transient global amnesia (TGA), a rare medical curiosity until 1999 when the first few cases were reported to Medwatch.
The United States Food and Drug Administration (FDA) elected to observe, rather than to warn clinicians about cognitive reactions to come. By 2003, a study team at Duke University reported 60 cases of Medwatch-derived statin-associated TGAs in the journal, Pharmacotherapy.1 By the end of 2006, 662 cases of TGA had been reported to Medwatch.
Still no warning was given to clinicians, despite the fact that amnesia episodes were but the tip of the iceberg of confusion, disorientation and forgetfulness associated with the use of statin drugs. Meanwhile, most of the cognitive reactions remained unreported because neither physicians nor patients were aware of a possible causative relationship. More recently, well over 1,000 TGA episodes have been reported just for the statin drug Lipitor, and all of the other statins cause this type of reaction as well.
Even today, more than thirteen years after statin associated cognitive impairment was first widely reported — and despite thousands of patients reporting the same adverse reactions since then — many physicians express surprise when first encountering this condition. You can be certain that their primary source of information, the drug reps, will never say a word about cognitive impairment to the doctors. Doctors should not have to read books and visit websites to learn the reality about statin side effects.
Myth 2.) If the FDA has Approved a Drug, it is Completely Safe to Use as Prescribed.
Statin drugs were marketed long before their effects on the human body were understood. Even now, thirty years after the first statin was marketed, we are still learning about the impact of statins on the human body.
One of the primary sources of adverse reactions, that of cognitive dysfunction, is due to the artificial lowering of one’s cholesterol. Cholesterol is so important to brain memory function that certain brain cells, known as glial cells, have been tasked with the job of synthesizing cholesterol for the brain upon demand. It is the effect of statins on glial cell cholesterol synthesis that is responsible for the cognitive impact of statin drugs.
This is also relevant to the inevitable consequence of mevalonate blockade. Cells in the body contain metabolic pathways which are essential chemical reactions. One of these is the mevalonate pathway. When statins block the mevalonate pathway to inhibit cholesterol, they must inevitably block other critical biochemicals such as dolichols and CoQ10 synthesized by the same mechanism. It is inhibition of these two biochemicals that has caused the great majority of adverse reactions.
Dolichols are critical to glycoprotein synthesis making them deeply involved in both neurohormone production as well as the glycohydrolase synthesis necessary for the identification and correction of the thousands of mitochondrial DNA errors daily.
CoQ10 is critical to adenosine triphosphate (ATP) production and prevention of mitochondrial DNA damage by free radicals. Nuclear factor kappa B inhibition, the reason for statins’ powerful anti-inflammatory and immunomodulatory action, is another consequence of mevalonate pathway blockade.
The FDA completely missed all of this during the approval process. I have learned that FDA approval is meaningless from the viewpoint of protection from adverse reactions because they failed to adequately identify the consequences of mevalonate blockade on the human body.
Myth 3.) Statins Drugs Work by Cholesterol Reduction.
This myth was wrong from the beginning. When statins were first marketed, doctors were delighted to get their first truly effective drug for lowering cholesterol. After decades of brainwashing about the evils of cholesterol, they finally had a drug that could significantly lower cholesterol, for most people, in a matter of weeks.
But then it was gradually noticed, in study after study, that statins worked their benefit in cardiovascular risk lowering independently of cholesterol reduction. Then Ora Shovman announced in 2003, “The Anti-inflammatory and immunomodulatory properties of the statin drugs.” 2
For the first time we learned about this independent effect of statin drugs, completely separate from the cholesterol reduction for which these drugs were intended. More recently, we have learned that the benefit of statins on cardiovascular (CV) risk reduction is the exclusive province of this novel anti-inflammatory and immunomodulatory activity of statins.
Cholesterol lowering appears to have nothing to do with atherosclerosis. We now know that inflammation underlies atherosclerosis, and in this new anti-inflammatory action of statins is hidden this beneficial effect, whether by platelet and thromboxane inhibition, monocyte adhesion, macrophage attraction, nitric oxide (NO) synthesis by endothelial cells, prostacyclin production or some element of smooth muscle migration, statins affect all of these elements to varying degrees.
Additionally, the JUPITER study was the final nail in the coffin for cholesterol causality, proving beyond any shadow of a doubt the irrelevance of cholesterol and introducing the first major advance in prevention and treatment of CV disease — the use of (hs)CRP as an accurate (inflammatory) marker of CV risk and the use of a low to moderate dose statin for treatment. Since cholesterol no longer appears to have a causative role in atherosclerosis, are we justified in using huge, cholesterol lowering doses of statins?
Duane Graveline MD MPH
Former USAF Flight Surgeon
Former NASA Astronaut
Retired Family Doctor