By Duane Graveline, M.D., M.P.H.
Not only can statin drugs cause myopathy ( muscle disease ) of varying degrees but this myopathy is greatly exacerbated by exercise. ( Ref 1 ). The effect of exercise is such that most experienced athletes will not use statins for fear of predisposition to muscle side effects of all kinds.
The severity of the muscle side effects from statins vary widely from relatively benign CPK elevation without symptoms, to muscle tenderness, aching, soreness and pain, and rarely, even to death from rhabdomyolysis.
The existing literature is lacking as to definite identification of mechanisms but a number of potential mechanisms include:
1. Induction of skeletal muscle fiber apoptosis ( cellular death, the usual result of accumulation of sufficient mitochondrial DNA mutations so the cell is taken out of service, so to speak ).
2. Alterations in ubiquitin-proteasome pathway activity ( a cellular system that identifies and degrades proteins ) leading to mitochondrial dysfunction ( the ultimate effect of CoQ10 inhibition secondary to mevalonate blockade ).
3. Terpenoid depletion ( consequence of dolichol inhibition and aberration in glycoprotein synthesis ).
These three pathways are also considered to be the primary channels by which we age - mitochondrial damage, CoQ10 depletion and dolichol inhibition. Additionally, I suspect that these three pathways that explain statin drug effects on muscle cells are the same for damage to other cell types as well.
Ten years ago an internet search would have come up with little to nothing on the subject of statin associated myopathy pathways but now the general pathophysiology has been defined by the many studies now in progress.
A major problem at present is that although these pathways are now well known to the research community, the clinical community of doctors is mostly lacking in the knowledge of even the basics of this statin effect and the very idea that statin damage uses the same pathways as aging is particularly difficult for clinicians to conceive.
The very idea that deficiency of this quaint supplement, CoQ10, is now considered by researchers to be a major foundation of statin damage and that many alternative medicine physicians are now far ahead of "regular doctors" in both their understanding and treatment of statin damage is particularly galling.
Dysfunction of the so called ubiquitin-proteasome pathway is a fancy way of saying CoQ10 inhibition, clearly defined in my first book, Lipitor®, Thief of Memory, years ago. What this refers to is the two-pronged statin attack on our mitochondria: first blocking the vital anti-oxidant role of CoQ10 and next blocking uptake of CoQ10 into the structure of complexes 1 and 2, major elements of electron transfer and ATP production. This occurs in every cell of our bodies.
It is difficult to understand how the developers of statins failed to recognize this potential, inevitable effect of compactin ( Mevastatin ) and lovastatin ( Mevacor ) the first statin drugs. The effect is there for all to see. What researchers are saying today had to have been clear to the original makers of statins.
Next on this list of statin damage mechanisms currently reported by the research community is the consequence of terpenoid depletion. This is a fancy way of saying dolichol inhibition, additional collateral damage from mevalonate blockade. Remember, statin drugs are reductase inhibitors. To achieve reduction of cholesterol synthesis they have blocked the mevalonate pathway, inevitably blocking CoQ10 and dolichols ( and many other vital biochemicals as well ).
If the full range of CoQ10 deficiency on cellular function is difficult to accept, that of dolichols is nearly impossible for most clinicians since they have barely been introduced. Dolichols orchestrate the entire process of glycoprotein synthesis, the linkage of peptide fragments and certain sugars so the resulting strand not only determines our very emotionality but also cellular identity, communication and immunodefense. Without at least some basic understanding of dolichol biochemistry the possible effects of statins become unimaginable.
Not only do these processes of apoptosis, CoQ10 mediated mitochondrial damage and dolichol mediated glycoprotein dysfunction help to explain the full range of effects seen with statin myopathy but this same group of factors is involved in all other types of statin damage.
What we have found to be true as the underlying mechanism of statin injury to muscle cells is true for every other cell in our bodies as well. As to the aggravation of statin muscle damage from exercise, the ubiquitin-proteasome pathway in particular addresses this CoQ10 mandated process. When one's CoQ10 is at a minimal level, the slightest exercise is bound to aggravate.
Duane Graveline MD MPH
Former USAF Flight Surgeon
Former NASA Astronaut
Retired Family Doctor