By Duane Graveline, MD, MPH
In the past decade of statin use, a number of epidemics have emerged associated with mevalonate pathway blockade and nuclear factor - kappa B (NF-kB) inhibition, two biochemical mechanisms of critical importance to cellular function.
Originally designed to block just the reductase step to cholesterol synthesis, the final truth about statins is that they block the entire mevalonate pathway, including the synthesis of CoQ10 and dolichols and several other biochemicals of critical importance to cellular function.
In addition, only in the past five years have we been informed that statins also block the transcriptase, NF-kB, present in the cytoplasm of each of our nucleated cells with both anti-inflammatory and immunomodulatory properties. I now believe that it is the anti-inflammatory properties of NF-kB that reduces heart disease risk.
The first epidemic that has emerged has to do with the subject of cognitive dysfunction as reflected in the numbers of documented cases of transient global amnesia (TGA) reported to Medwatch.
When NASA cardiologists put me on Lipitor 10mg in 1999 for modest hypercholesterolemia, all went well for 3 months when I experienced my first episode of transient global amnesia (TGA) lasting for 6 hours.
The E.R. doctors and my neurologist all said statins do not do that. Having 33 years of family practice behind me, I stopped on my own. The following year at my repeat NASA physical they insisted on re-challenge. I concurred at 5 mg.
Again, several months later I had my next, much worse episode of TGA when I became a 13-year old high school student for an incredible 12 hours.
TGA is the abrupt (in seconds) loss of ability to formulate new memory usually associated with retrograde memory loss for weeks, months, years and even decades into the past. Along with this goes any special training you might have received. For me it was medical school, flight training – everything!
The mechanism here is excessive lowering of cholesterol secondary to mevalonate blockade. This was the original purpose of statins. The first case was reported by me to Medwatch in 1999 when NASA prescribed me Lipitor for my mild hypercholesterolemia. Since I reported my first case in 1999 nearly 10,000 cases of TGA or severe memory loss have been reported to Medwatch - nearly 3,000 just from use of the single statin, Lipitor®. In the pre-statin era it took 50 years for the first 1,000 cases of TGA to accumulate from when the first case was reported in the early 1950's. But in the statin era since 1999, we already have close to 10,000 cases.
Another epidemic has to do with that of excessive numbers of congestive heart failure cases now being reported. The mechanism here is inhibition of CoQ10 synthesis. In mid-life our ability to synthesize CoQ10 already has plummeted when cardiovascular disease usually becomes manifest in mid-life.
Placing heart disease cases on statins is almost automatic but this predictably inhibits CoQ10 synthesis even more, reducing energy to heart cells and provoking congestive heart failure in thousands of patients. It is amazing to me that clinicians are not more aware of the vital importance of CoQ10.
Yet another epidemic is occurring with rhabdomyolysis. Back in 2004, the media response to 60 Baycol® deaths caused Bayer to remove this statin from the marketplace. Yet during the period 2007-2012 some 811 statin associated rhabdomyolysis deaths have been reported to Medwatch.
The mechanism here is CoQ10 and dolichol inhibition secondary to mevalonate blockade. When statins first were marketed we were told to expect myopathy in some 2 percent of statin users. That incidence figure, I believe, is now much closer to 20 percent and athletes are now often advised never to use statins because the muscle damage incidence is far higher in more active people.
Think of rhabdomyolysis as a more severe form of myopathy where the muscle cell walls break down releasing cell contents into the circulation thereby blocking kidney tubules contributing to kidney failure, the usual cause of death.
Non-melanoma skin cancer is now at epidemic levels. Since 1999 when the use of statins was estimated at 8 percent of the screened population, the use of statins has more than doubled.Statin drugs inhibit nuclear factor - kappa B giving the anti-inflammation effect so important for reduction of heart disease risk but at the same time interfering with our immune system and in so doing has opened up a Pandora's Box of adverse effects.
Kidney graft patients on statins report a 90-fold increase of non-melanoma skin cancers and the figures are much worse for heart graft patients placed on statins, whose age as a group is higher.
Peripheral neuropathy is now at an all-time high among statin users and it is almost always permanent. Dr. Beatrice Golomb of the statin research group at San Diego college of medicine reports that of the 20 percent of statin users who get myopathy, it will prove to be permanent in 68 percent of the cases.
And last but not least, statin associated diabetes is now said to have an incidence of up to 15 percent. These last three are all sort of epidemics by my standards.
I want you to question your doctor about his reasons for placing you on statins. If you are a high risk male or female, meaning you already have had a heart attack or it is prevalent in your immediate family, of course use statins but think about the dose. Why use a cholesterol lowering dose when we now know that cholesterol is not the cause? Think about lower doses. Growing evidence supports this view.