From the viewpoint of side effect causation, there are two primary effects of statins. The first is what this class of drugs was designed for – inhibition of cholesterol synthesis through inhibition of the mevalonate pathway.
The second has to do with the other consequences of mevalonate blockade – cellular dysfunction brought on primarily by reduction of CoQ10 and dolichols. There are many, many other consequences of mevalonate blockade, but these two effects are those having the most important and disastrous clinical consequences.
My focus here is that other main group of side effects, those due to the other consequences of mevalonate pathway inhibition – CoQ10 and dolichols. These effects strike at the very heart of cellular function, our mitochondria that create the energy for the cells in our bodies.
A report by a research group in France – F. Galtier and others – titled Effects of high dose statins on muscular mitochondrial metabolism (Toxicology and Applied Pharmacology. 28 June 2012) highlighted the effects of statins on mitochndria.
A decade ago I postulated a mitochondrial DNA origin to statin damage. This French study appeals because it is so clear-cut. Twenty-four healthy male subjects were used. Half received simvastatin (Zocor) 80 mg daily for 8 weeks. The remaining half took a placebo. Blood, urine and a stress test were done at baseline and at follow-up 8 weeks later and studies of mitochondrial oxidative function were done on muscle biopsies taken 4 days before the second stress test.
The results were analyzed and compared, documenting that the statin induced muscle toxicity was directly related to mitochondrial oxida-tion. The reduction of CoQ10 and dolichols by the use of the statin had led to excess mitochondrial oxidation.
Most of us have no awareness of just how critical CoQ10 is to our function. After the age of 50 we become increasingly unable to synthesize it and must depend almost entirely on what we take in by mouth. Since dietary CoQ10 is usually completely inadequate, supplements become the mainstay of CoQ10 function as we age (the richest dietary sources are foods not widely eaten like hearts from cows, lambs, pigs and chickens).
Even on our best days, mitochondrial mutations occur by the tens of thousands. They are an inevitable consequence of normal metabolic activity. The “reactive oxygen species” (ROS) such as peroxidases and hydroxyl radicals, are produced as a byproduct of metabolism and desperately seek electrons to balance their electrical state.
It is this “stealing” of electrons from adjacent tissue, including DNA strands, that causes the damage. We have evolved a very efficient anti-oxidative system for the purpose of minimizing this electron theft. Included in this system are such enzymes as superoxide dis-mutase and glutathione, and such non-enzymatic substances as coen-zyme Q10 and vitamins C and E.
Although CoQ10 has plenty of help in its anti-oxidant role, I stress CoQ10’s special importance because of its location within the mitochondria as a vital component of both complex one and complex two of the mitochondria’s electron transfer sequence. What better location for the job at hand than being physically there, where the action is occurring.
CoQ10 is not only a vital component in this process of energy formation, it is also superbly placed for its powerful anti-oxidant function. In concert with the other members of this protective system, CoQ10 suffices to keep oxidative damage to a minimum.
The DNA lesions that finally occur after the neutralizing effects of our legions of anti-oxidant warriors are then identified and corrected by another protective system of amazing efficiency. Tens of thousands of DNA lesions occur daily despite all our anti-oxidant system can do. This is a sobering reality of the constant skirmish for change, seeking the best solution for meeting environmental differences.
Fortunately most of these errors never make it beyond the next cell division, at which point they are replaced naturally by normal configurations. But the gradual buildup of these DNA errors can result in progressive loss of functional DNA, the usual cause of chronic disease and aging.
Most of the serious damage is to our bases, those four amino acids: adenine, cytosine, thymine and guanine, comprising our DNA strands. Some of the oxidative damage can be reversed simply by direct chemical means.
Far more important to us is the base excision repair process, in which faulty bases must be excised and replaced by correct ones. This is one of the major repair requirements, occurring tens of thousands of times daily and each one requiring a specific glycohydrolase.
Since glycohydrolase is one of our ubiquitous glycoproteins, requiring dolichols for synthesis, one must consider the possibility of altered glycohydrolase availability with statin use because of the well-known tendency of statins to inhibit dolichols along with CoQ10.
Please understand that the effect I am writing about is not some rare, remotely possible event. Mevalonate blockade of varying degrees is inevitable when statins are used. Although every cell in our bodies is affected by reductase inhibition, those cells having greater need of energy such as muscle and heart cells, kidney and liver will be affected more.
The only escape from the consequences of this inhibition is the presence of pathway alternatives to the usual mevalonate one for synthesis of CoQ10, dolichols or even cholesterol. Serum cholesterol occasionally does not respond to statin use, suggesting the presence of alternative pathways for synthesis. If this is true for cholesterol, it is true for all other biochemicals equally dependent upon the mevalonate pathway.
Other than for these considerations, mevalonate blockade is inevitable with statin use and is the cause of the overwhelming majority of adverse reactions. The consequence of CoQ10 and dolichol inhibition is mitochondrial damage. It is inescapable and every doctor using or recommending these drugs needs to understand this.
Duane Graveline MD MPH
Former USAF Flight Surgeon
Former NASA Astronaut
Retired Family Doctor
Updated August 2016
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