By Duane Graveline MD, MPH
Statins and Mitochondrial Damage Part 1 of 11
Tens of thousands of statin users have complained to their doctors of weakness, instability, easy fatigue, muscle aches and pains, burning of their extremities, depression, personality change and faulty memory, to which their doctors generally have responded, "You have to expect this now. You are over fifty."
Although these experienced doctors all have pointed to a reasonable presumptive diagnosis, few have been entirely comfortable with this explanation because of a curious recurring pattern in their presentation.
All of these patients have been on statins of one brand or another and the transition from midlife vigor to the multiple infirmities of the elderly has been much too swift in most. In the few months since the previous office visit, an aura of senescence has evolved in these patients. Doctors deal with the passage of time on a daily basis and are acutely sensitive to its telltale first traces. All of us are vulnerable in time.
Somehow the word time seems to suggest a more appropriate meaning and the mind finally jumps to the correct interpretation - premature. The complaints their patients are reporting may be common, even routine, in the elderly yet these people are for the most part in their sixties and seventies, and sometimes even much younger!
If anything out of the ordinary can be attached to these complaints of faulty memory, weakness and various aches and pains, it is their prematurity - premature aging.
Conditions are being complained about that ordinarily would not be seen until much later in life. Are these statin users being robbed of their "golden years"? Is it possible that their passage to senescence has been expedited? If so, what could be the mechanism?
This series will take you on a journey where many really do not want to go - not after decades of use of reductase inhibitor (statin) class of drugs. What doctor wants to admit that he or she has been wrong about the side effects of statin drugs that now appears to be much more important than originally thought?
I have been there, and I have done that, and it has not been easy. The very idea that my practice philosophy was wrong for many years is a bitter pill for me to accept, and to think, I was following the dictates of national leadership, marching in lockstep with everyone else to the misguided fallacy of cholesterol causation of arterial damage.
Many of us have doubted the hypothesis of cholesterol causation from the very beginning, placing it at about 1988 when statin marketing first began. I had begun to use it in my office at that time. As I recall, Lovastatin was the first. But I was soon to retire and at best had only a few patients on it when I finally gave up after 23 years of practicing medicine and began my retirement.
Those were the days when we were delighted to have statins. After almost 40 years of beating on cholesterol with ineffective medicines we finally had a drug that really worked. Cholesterol dropping 40 points in just a few weeks was a whole new world for us. And hardly a word about side effects. We were advised to look out for the liver by doing a blood test after a few weeks and told to expect a few muscle problems in under 2% of our patients for which we needed only to drop the dose a bit.
Not a word about transient global amnesia, permanent myopathy, diabetes, peripheral neuropathy, rhabdomyolysis, ALS and serious neuro-degenerative conditions. Strangely, in almost half of the new heart attacks the cholesterol levels were normal. Gradually, very serious reports of adverse reactions started to come in along with surprising reports of studies showing benefit of statin use even when the cholesterol remained unchanged.
Evidence of another effect of statins, independent of cholesterol, began to accumulate. The one that made the difference was a study called JUPITER. This study selected men and women with cholesterol levels all less than 130 and no significant CV risk but whose inflammatory marker, (hs)CRP, was elevated. Half of these took a statin, the other half took a placebo. The ethics committee forced the stopping of the study after 19 months because of excess heart attacks and stroke in the placebo group. Knowing what they did, it was deemed unethical to proceed.
Naturally there was a furor of controversy about these findings but we learned two very important things from this study: cholesterol level had no relationship to cardiovascular disease risk and statins did work to lower this risk level. Doctors have been reluctant to accept this because they have bought into cholesterol causality for over a decade. Drug companies had only to shift gears a bit to overcome this new reality.
So now we have a statin drug designed to be a reductase inhibitor that suddenly turns out also to have anti-inflammatory and immuno-modulatory properties and it is this aspect of the drug that gives the benefit. The reductase inhibitor function blocks the the reductase step in the mevalonate pathway which synthesizes cholesterol along with CoQ10 and dolichols. The other new function is based upon the blocking of a cell transcriptase known as nuclear factor kappa B.
So where are we? Statins now block cholesterol, perhaps the most important biochemical in the body, especially for the cognitive function of the brain, along with blocking CoQ10 and dolichols, critical to mitochondrial function and responsible for almost all of the side effects. Additionally, statins block NF-kB giving a modest anti-inflammatory benefit to high risk heart patients but decreasing the immune status, increasing cancer risk.
I want you to read this last paragraph again slowly. This is what statins do and how they do it and to think that NF-kB inhibition was discovered only within the past few years. I have said before that statins were marketed long before they were fully understood and this just proves my point.
Duane Graveline MD MPH
Former USAF Flight Surgeon
Former NASA Astronaut
Retired Family Doctor