You Need To Know The Cholesterol-Lowering Medication’s Side Effects
If you and your physician have made a joint educated decision to initiate statin use, you should be cognizant of their potential side-effects. The pharmaceutical giant Merck has already submitted three applications to the Food and Drug Administration to obtain permission to sell lovaststatin over the counter without a prescription. This may be a dangerous proposition taking into consideration the outlined side effects. I strongly believe that statins should be prescribed and not found over-the-counter.
Liver:
If your physician decides to start you on a statin drug, the main side effect s/he should discuss with you is liver dysfunction and advises periodic monitoring of your liver enzymes. Liver function is adversely affected in direct proportion to the dose of statin used. The degree, to which cholesterol is lowered, however, has not been shown to correlate with liver dysfunction. Statin dose therefore is the primary determinant of liver toxicity, not degree of cholesterol lowering. (Alawi A, Alsheikh-Ali, et al. Effect of the Magnitude of Lipid Lowerinf in Risk of Elevated Liver Enzymes, Rhabdomyolysis, and Cancer Insights from Large Randomized Statin Trials. J Am Coll Cardiology. 2007; 50(5):409-418.) Your doctor may tell you that as long as liver enzymes are three times the level of normal, that is, a three hundred percent elevation; it is alright to continue stain use. Most patients find this to be a rather scary approach to a medication. Is a slight decrease in the risk of heart disease worth a 300 percent increase in liver enzyme production, marking a considerable decline in liver function?
There are ways to protect the liver if you actually are on statins. First, you must discuss with your doctor the appropriate schedule to check the liver so that you are cognizant of what those numbers are. Ask for copies of all your blood work and make a chart for yourself monitoring their ups and downs. Second, one important piece of information to keep in mind is that your muscles may release the exact same enzyme that is elevated in the setting of liver dysfunction. It is referred to as AST. Being that statins can adversely affect our muscle tissue, these two side effects must be differentiated. So, if you are told that you have a liver dysfunction due to statin use, be certain to ask whether or not the elevated enzymes are those released by muscle injury, rather than the liver. In order to differentiate between the two, your doctor should check a creatine phosphokinase level, or CPK, which would be elevated in muscle injury.
In addition to monitoring your blood for liver enzyme elevation, you must monitor yourself for physical signs of liver dysfunction. They include a yellowish hue to your skin and to the whites of your eyes, pain in the upper right part of the abdomen, yellowish or tan colored stool, tea-colored urine, profound fatigue, and generalized itching.
Lastly, you should take supplements that can protect the liver from being adversely affected by statin use. The ones I recommend routinely with great success are N-acetyl-cysteine (600 mg twice a day) and alpha-lipoic acid (200 mg twice a day), among many others. I find that these work well in both protecting and helping to reverse a damaged liver secondary to medication. I would also maintain adequate hydration. I would stay away form a commonly used herb for liver dysfunction called milk thistle. It changes the rate at which medications are metabolized by the liver.
Now you are officially in charge of your liver! Let’s turn to another body part.
Myopathy:
I regularly see patients complaining of aches and pains that are rather nonspecific. Many times there aches are associated directly with statin use. Statins can cause a fall in coenzyme q 10 levels, which may be one of the key mechanisms of action of statin induced muscle aches, or myalgias. Coenzyme Q 10 plays a critical role in the production of energy in the mitochondria of muscle cells. In order to prevent the side effects of myopathy, CoQ10 supplementation has show to be of benefit as evidenced only in small studies. It makes logical sense to give coQ10, an antioxidant, when treating someone with a statin even is there is a small chance that muscle injury may be prevented. In addition to coenzyme Q 10, it is important to figure out whether or not it is appropriate to discontinue statin use or at least to lower the dose as much as possible and still maintain the same benefit. If you have been told you have fibromyalgia after having suffered this particular statin side effect; that is wrong. It is especially wrong if you have been given a form of pain killer for this side effect.
One fascinating fact is that Merck, a manufacturer of a statin drug, actually patented the use of CoQ10 to be combined with statin drugs knowing that the statin drug would indeed deplete the patient of CoQ10. This patent, however, was never exercised. This is unfortunate. To this day, pharmaceutical companies are not engaged in a massive effort to educate the medical community about statin’s effects of CoQ10 depletion.
We can never tell for sure who will be the one suffering from myopathy. There are quite a few patient populations that will have this side effect more frequently. Those at greatest risk include: patients with underlying kidney dysfunction, a sluggish thyroid, are on drugs that inhibit CYP3A4 or a detoxification pathway in the liver (cyclosporine, gemfibrizole, macrolide antibiotics such as erythromycin, HIV protease inhiboitors, fibrates, niacin, as well as many others others), or with a genetic predisposition to not tolerate the myopathic effects of statins. Pharmacogenetics will get more advanced in the upcoming years and patients will have the opportunity to know which drugs they will not do well with prior to starting the drug. The technology is not quite there yet.
One way to monitor for myalgia is to check blood CPK levels, the enzyme released when muscle tissue is destroyed. This number may or may not be high in the setting of myopathy. Many times patients will suffer the ill-effects of statin therapy without ever once having an elevated CPK level. In the setting is significant muscle necrosis, or death, where the constituents of the muscle are released into the circulation, CPK elevation usually does occur. This may affect kidney function, change the color of the urine to reddish-brown, and change electrolyte balance to dangerous proportions. This is referred to as rhabdomyolysis, a potentially dangerous situation. It is not enough to simply monitor CPK levels. Your physician must routinely ask you about symptoms of myalgia.
Even though the above is common knowledge for most physicians, simple and benign actions such as coQ10 supplementation are often not upheld. Instead, the side effects are blanketed by muscle relaxants or non-steroidal anti-inflammatories, prescribed to counteract the negative myopathic effects of statin drugs. These drugs of course have their own side effects. Here the domino effect continues.
A study reported in the Lancet in March 2004 brought to light that the myopathy associated with statin use is similar to that of selenium deficiency. It is established that selenium plays a significant role in skeletal and cardiac muscle metabolism. Statins inhibit a pathway that is necessary for the production of selenoprotein, which could potentially contribute to myopathy. (Moosmann B, Behl C. Selenoprotein synthesis and side-effects of statins. Lancet 2004; 363:892-894.)
Cancer:
An alarming association between the degree of lipid lowering and new onset cancer has been made (Alawi A, Alsheikh-Ali, et al. Effect of the Magnitude of Lipid Lowerinf in Risk of Elevated Liver Enzymes, Rhabdomyolysis, and Cancer Insights from Large Randomized Statin Trials. J Am Coll Cardiology. 2007; 50(5):409-418.) This association is not definitive enough to reach the popular press, but should be discussed when delving into statin’s potential side effects. The PROSPER study, discussed above, showed that new cancers were more likely to be diagnosed in those on pravastatin as compared to those on placebo. Less attention was given to this conclusion of the PROSPER trial than other conclusions in that trial.
The Heart Protection study, however, which is the largest randomized statin trial with more that 10,000 patients taking simvastatin, showed that there was no significant difference in the rate of cancer for those on a statin vs. those not.
An unexpected finding from the manufacturer-sponsored SEAS study has also raised questions about the safety of statins in terms of cancer risk. The SEAS study set out to find out whether aggressive lowering of LDL levels, using a combination of simvastatin (40 mg) and ezetimide (10 mg), would slow or halt disease progression in patients with mild-to-moderate aortic stenosis. After 52 months, LDL levels dropped dramatically by 53.8% with no difference noted in aortic stenosis, although there was a significant decrease in events attributable to atherosclerosis. This, however, was not the surprising part. The rate of cancer was found to be significantly higher in the combined-therapy group than in the placebo group 11.1% vs. 7.5%. In addition there was a 67% increase seen in the rate of cancer deaths. These significant findings of this recent study need to be addressed with patients started on this regimen. (Rossebø AB et al. for the SEAS Investigators. Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis. N Engl J Med 2008 Sep 2). There is a counter theory; however, stating that the cancer itself can lower cholesterol about a decade or so before the cancer is diagnosed.
The PROSPER, SEAS and the HPS study, however, do not address whether or not a very low cholesterol itself is associated with an increase in the rate of new cancer. The studies quantitate cancer occurrence and its relationship to statin use in general. Past epidemiologic studies have associated low cholesterol levels with elevated cancer risk (D Jacobs, H Blackburn, M Higgins. Report of the Conference on low Blood Cholesterol: Mortality Associations. Circulation; 86:1992, 1046-1060.) Thus, it may actually be that low cholesterol levels themselves, not necessarily stain use, are associated with cancer. Does cancer cause a drop in cholesterol levels or does too low a cholesterol level make someone more prone to a cancer. These are questions that still need to be addressed.
Brain Food:
Greater than half of our brain’s chemistry is made up of fats. If that fat supply is diminished, theoretically, cognitive function may suffer. Cholesterol helps insulate the nervous system by supporting what is referred to as the myelin sheath which lines the nerve cells. A healthy myelin sheath allows for neurologic impulses to be carried efficiently from one part of the body to another. Cholesterol is also required for the formation of synapses, which are spaces between nerve cells through which information is conducted. The bottom line is that your brain needs cholesterol in order to be able to pass information from cell to cell and thus function effectively.
If the myelin sheath is disrupted, there can be a decrease in the nerve conduction velocity, or the time it takes for a thought or other neurologic impulse to travel from one part of the body to another. Memory becomes an issue if cholesterol reaches a nadir. Some studies point to a deterioration of memory when cholesterols levels plummet post statin use. Whether or not there is a correlation between actual statin use and cognition irrespective of cholesterol levels still needs to be determined. This is further evidence that elderly patients need to take a more conservative approach to statin dosing.
Other side effects may include malaise, abdominal discomfort, numbness and tingling, rash, diarrhea, constipation, joint aches, and thinking ability. There have been some controversial associations between statin use and congestive heart failure possible via the mechanism of action of coenzyme Q 10 depletion.
