Do the Potential Benefits of Statins Outweigh the Risks of Side Effects?
Millions of people around the world have been prescribed statin drugs to try to reduce their high level LDL cholesterol levels in the expectation that this will help to reduce the risk of cardiovascular disease. It is likely that these numbers will continue to rise substantially as the recommended levels of LDL cholesterol continue to decrease.
Although the connection between high cholesterol levels and increased risk of heart disease is not a straightforward one of cause and effect (although, if you read information based on data released by the drug companies it may seem as if it is), patients who already have heart disease, or are perceived to be at risk of developing it, are advised to try to lower their cholesterol levels as much as possible.
However, it is worth noting that, far from being a miracle drug that prevents cardiovascular problems or slows their progression, there is a body of evidence about the effectiveness of statins which shows that, despite the fact that they undoubtedly lower cholesterol, they do not decrease the numbers of deaths in patients taking them.
In other words, although there may be a small decrease from the number of deaths from heart attack, the overall number of deaths and serious health events does not go down; patients simply die from different causes.
If your medical practitioner has recommended that you commence statin treatment, he/she may well have told you that these drugs are generally well tolerated, that for most people taking statins any side-effects will normally be mild and will go away if you stop taking the medication.
In fact statins have the potential to cause some extremely serious side effects (they have even caused deaths) and some of these may be irreversible. You need to be aware of these, in order to be able to make an informed judgment as to whether or not you wish to take these drugs.
Why the Side Effects of Statins Occur
Most medicines have multiple effects on the body. Those that we deem desirable we consider as evidence that the drug is working appropriately and the unwanted effects we label side effects and decide whether they are tolerable or not. In fact both desired and unwanted effects are all down to the way the drug affects our chemical balance and body processes.
Now not all people who take a particular drug will be affected in the same way – and this applies to both the desired outcomes and the side effects. When we take a medicine we expect that it will be effective and treat the problem it is being prescribed for. In fact this is far from the case; most drugs only work well in a percentage of the patients who take them.
It can actually be a pretty hit or miss affair as to whether or not a drug will help to improve a patient’s health. Similarly, it is by no means definite that an individual will experience unwanted effects from a drug, nor can it be predicted what problems they will experience if side effects do occur.
However since both desired and undesired effects are caused by changes to the body’s functioning, it is possible to look at the processes involved and see how they may bring about various side effects.
How Statins Effect Body Processes
In the case of statins, body processes are altered by inhibiting the production of an enzyme that is important in the production of cholesterol by the liver, resulting in a decrease in the amount of LDL cholesterol available to the body. However, it is not only the production of cholesterol that is interfered with but also other substances that have important functions to play.
Furthermore, cholesterol itself is essential to the functioning of the body and decreasing its availability has the potential to cause serious problems.
One of the substances affected by statins is called Ubiquinone, more commonly referred to as Coenzyme Q10 (CoQ10). The name ubiquinone gives a hint as to just how important CoQ10 is to the body as the word shares the same root as ubiquitous which means something that is (or seems to be) present everywhere. And indeed CoQ10 is found in every living cell of the body.
CoQ10 is an essential nutrient that is used to produce ATP (adenosine triphosphate) molecules which contain stored energy. Without ATP, cells could not function – damaged tissue could not be repaired, cells would not divide, or make or use, proteins, enzymes and hormones. CoQ10 is also a powerful antioxidant. Antioxidants help to protects us against cancer, aging, and disease.
The use of statins can decrease the body’s synthesis of CoQ10 substantially. If you lower cholesterol by 40% with statin drug therapy, you will lower CoQ10 levels by 40% too.
The production of other substances essential for bodily health, such as dilochol and squalene (which is the immediate precursor to cholesterol), are also reduced by statins.
Alcohol directs the proteins produced by the body to their proper targets, ensuring that cells work as they should. Interfering with the production of dilochol can therefore cause unpredictable problems at a cellular level.
Although squalene is a precursor (a building block) to cholesterol, it is much more than this. In fact, only 10% of squalene is used for cholesterol synthesis with the other 90% being stored or used as an antioxidant.
Squalene accumulates at the greatest concentrations in the skin, where it appears to play a vital role in mopping up free radicals and helping to prevent damage from ultraviolet light. Squalene is also known to play an important role in the functioning of the retina.
There is evidence that indicates that supplemental doses of squalene can prevent the development of some kinds of cancers, and helps the regression of some kinds of pre-existing tumors.
Cholesterol itself actually has an important role to play in the body. It is present in the walls of every cell in our body as it is what makes them waterproof. If cholesterol levels are inadequate cells become leaky and the body responds by taking cholesterol from other parts of the body to deal with the areas which do not have enough. Cholesterol is also an important part of the bodies healing mechanism – scar tissue (including that in the arteries) contains large amounts of cholesterol.
Cholesterol is also a precursor to the body’s manufacture of Vitamin D which is important for many bodily processes including mineral metabolism. Bile salts, which are necessary for the digestion of fat, are made from cholesterol. Cholesterol is also an antioxidant.
Side Effects Caused by Statins Inhibiting the Synthesis of Substances Essential to the Body
So now we have considered the ways in which statin drugs can interfere with some of the body’s processes, let’s look in more detail at the unwanted consequences (side-effects) that may be experienced.
Muscle problems are the most commonly reported side effects from statin use.
According to figures produced by the pharmaceutical industry, 23% of patients experience muscle aches and cramps, but research suggests that the numbers of people affected may actually be much higher. In one study it was found that 98% of the study subjects taking Lipitor and about a third of patients taking Mevachor (a lower dose statin) suffered from muscle problems.1
Muscle problems may emerge at any stage of treatment with statins. Some people experience an almost immediate onset of symptoms (within 30 days) whilst others find that their symptoms develop after a few years of statin use. However statins are generally considered to be a lifelong treatment, so it seems probable that the longer a patient takes statins, the greater the likelihood they will develop muscle problems or other side effect symptoms.
Muscle problems can be categorised under a number of different headings:
Myopathy, which literally means muscle disease, results mainly in weakness, particularly in the muscles of the shoulders, upper arms, thighs, and pelvis. Although in some cases, the muscles of the hands and feet may also be involved. Other symptoms of myopathy include aching, cramping, and pain, stiffness, tenderness and tightness.
It can cause people to feel fatigued, even when doing a very light physical activity and walk climbing stairs and rise from a chair may all become difficult. Muscle wasting may occur if the disease progresses.
Myositis means an inflammation of a muscle which can cause pain, tenderness, and sometimes spasm in the affected area.
Myalgia is a pain in the muscles; particularly a generalized, diffuse pain.
Rhabdomyolysis results from extreme muscle cell inflammation with rupture of the cell wall and spillage of cellular contents into the bloodstream, which leads to disturbances in electrolytes, causing nausea, vomiting, confusion, coma and cardiac arrhythmias (abnormal heart rate and rhythm).
The kidneys may also be damaged causing the passing of urine that is dark red or cola colored and which may also be foamy and this may lead to acute kidney failure. In rare cases, rhabdomyolysis can cause death.
Other symptoms of rhabdomyolysis include muscle pain and weakness, swelling, tenderness and unexplained pain and tiredness.
Some scientists think that this process is related to the depletion of coenzyme Q10 causing problems with cell wall integrity. Others research findings suggest that insufficient cholesterol within the muscle cells, causing altered cell signaling, may be the dominant factor.
Whatever the mechanism that is the causes this condition, FDA figures show that of the total number of rhabdomyolysis cases reported in their database, 42.7% were found to be statin associated cases – thus it seems a substantial proportion of all rhabdomyolysis cases may be associated with the use of statins.
Rhabdomyolysis is tested for by measuring patients for elevated levels of the chemical creatine kinase (CK). However, even when CK levels are considered to be within the normal range, many people on statins experience muscle pain, weakness, and fatigue.
Rippling muscle disease is a disorder involving skeletal muscle contractions which produce a visible rippling effect. Although the disease is commonly an inherited condition it can also be caused by an autoimmune reaction.
The disease can cause problems with exercise including difficulty walking.
Mitochondrial disorders: Mitochondria are tiny organelles found in almost every cell in the body. These organelles are responsible for creating 90% of ATP a source of cellular energy necessary to maintain life and support growth. Mitochondria are involved in a range of other processes, such as signaling, cellular differentiation, cell death, as well as the control of the cell cycle and cell growth.
Mitochondrial disease arises when mitochondria in the cells fail to produce enough energy to sustain cell life. When enough cells cease to function properly organs, motor functions, and the neurological system can become impaired.
There are multiple symptoms associated with the mitochondrial disorder and these include numerous muscle related problems such as myopathy and rippling muscle disease and the many other side effects associated with statin use.
A wide range of drugs has been shown to cause mitochondrial damage including statins, bile acid sequestrants and fibrates all of which are used to treat cholesterol levels.
Mitochondrial disorders caused by CoQ10 depletion may, therefore, be the root cause of many (or all) statin side effects.
A study published in 2004 in the American Journal of Cardiology documented evidence of early heart muscle weakness in 70% of patients taking statin drug therapy for a period of six months. This early heart muscle weakness reversed back to normal by adding supplemental CoQ10 at 100mg three times daily (total of 300mg/day).Other studies have shown a reversal of skeletal muscle pain and weakness by adding supplemental CoQ10 to statin drug therapy.
Neuropathy is a disorder of the nerves. Peripheral neuropathy is damage to the nerves of the peripheral system (i.e. the whole body excluding the brain and the spinal cord which comprise the central nervous system) which connect the limbs and organs to the central nervous system.
Symptoms of peripheral neuropathy include weakness, numbness, and pains in the hands and feet. Neuropathy can also cause problems with walking and may even be associated with increased numbers of accidents as a consequence of a loss of sensation.
A Danish study found that people taking statins were between 4 and 14 times more likely to develop peripheral neuropathy than people who were not taking statins. Taking statins for longer periods of time and taking higher doses of them increased the risk of developing neuropathy.
Nerve problems are one of the three most commonly reported side effects of statins (the others were cognitive problems and the most commonly reported side effect: muscle problems).
People who have taken high doses of statins for a prolonged period may find that nerve problems persist even after they have stopped taking the drugs – statins can cause irreversible nerve damage.
Cognitive and Mood Problems
A respected doctor studying the side effects of statins has found that around 15% of patients taking statins will develop cognitive side effects. A study that looked at cognitive ability found that patients treated with statins for six months did much worse than the control group (who had been taking a placebo) when solving complex mazes, psychomotor skills and memory tests.
Memory loss and abnormal thinking have also been shown to occur during trials of statins. While the number of people suffering these problems was only around 0.5% of the study group, cognitive problems were not the specific subject of the study and it is quite possible that the true rate of problems was higher but not reported as patients may not have put the symptoms down to factors such as aging.
And we’re not just talking about brief periods of absent mindedness or what is sometimes referred to as “senior moments”. Statins can cause almost complete memory loss for either brief or extended periods. These episodes may occur totally unexpectedly and leave the sufferer unable to do some simple tasks they normally manage. Not only is this frustrating and distressing for the sufferer, it may put the wider population at risk if, for example, the individual is operating machinery (perhaps driving a car).
Half of the memory problems reported to the FDA occurred within 60 days of a patient starting on statins, although problems were also reported after taking the drugs for just 5 days. Most people did return to normal after stopping the drugs, with the recovery time corresponding with the amount of time it took the symptoms to appear (the longer it took for symptoms to appear, the longer it took for the patient to recover). Some people, however, continue to suffer long after they stop taking statins.
Other cognitive symptoms include reduced ability to concentrate, Alzheimer-like symptoms and memory loss severe enough to be described as amnesia. Mood swings and behavioral changes are also associated with taking statins.
Depression has been linked to low cholesterol levels in a number of studies. Women with low cholesterol are twice as likely to suffer from depression and anxiety, while men who lower their cholesterol levels with drugs have increased rates of suicide and violent death. Perhaps this is not that surprising when you know that cholesterol levels directly affect the activity of serotonin (which affects mood, sense of wellbeing, etc).
Heart failure occurs when the heart is unable to provide sufficient blood flow to meet the body’s needs and the heart becomes enlarged. It is not the same as heart attack, although the heart attack can cause heart failure. One of the major causes of heart failure is cardiovascular disease, which is associated with high cholesterol levels, with the formation of plaques and thrombosis often being blamed on high LDL cholesterol levels.
It is ironic, therefore, that there is evidence that statins can cause heart failure. While the number of heart attacks has decreased slightly since the introduction of statins, the incidence of heart failure has increased at a greater rate.
The most likely explanation of why statins can cause heart disease relates to their incidental suppression of CoQ10. As previously explained, CoQ10 is critical in the production of ATP which is used to power our cells. Muscles use a lot of energy and therefore require lots of ATP (which means there needs to be enough CoQ10 for its production).
The heart is, of course, a muscle and one that uses huge amounts of energy to pump blood around the body. If CoQ10 is depleted by statin use, then the heart will not have enough energy to pump enough blood to meet the body’s needs.
Symptoms of heart failure include shortness of breath, coughing, ankle swelling, exercise intolerance.
In a small study of patients with normal heart function who were given a low dose of statins for 6 months, two thirds of the patients had developed abnormalities of their heart’s filling phase by the end of the trial period.
Eight out of nine trials investigating CoQ10 depletion in humans caused by statin use showed that the significant CoQ10 depletion resulted in a decline in the left ventricular function of the heart.
There is no evidence from studies to prove that statins offer benefits to people suffering from heart failure, as these individuals have been excluded from clinical trials. There is, however, evidence that patients who had diastolic heart failure (nearly half the cases of heart failure are diastolic, the rest are systolic) and who were taking statins had worse outcomes than those patients with diastolic failure who did not take statins. Those patients taking statins experienced more problems with their lungs had weaker muscles and poorer exercise tolerance.
At least one study has indicated that patients with chronic heart failure do better if they have high cholesterol levels rather than low.
Despite this, statin treatment will be recommended to almost all heart failure patients, whether or not they have high cholesterol levels.
The extent to which statins increase the incidence of cancer is, as yet, not established since cancers can develop slowly and the trial periods for drugs testing are normally only 2 or 3 years.
Despite this, the evidence does exist strongly suggest that statins can cause cancers. In a trial referred to as the CARE trial, the breast cancer rate among patients taking statins was 1,400% higher than the rate of the control group (incidence of breast cancer was 0.3% in control group and 4.5% in the statin treated group – a 1,400% increase in relative risk or a 4.2% increase in absolute risk).2 In a study called the Heart Protection Study (HPS) a nonmelanoma skin cancer appeared in 243 patients treated with a specific statin compared with 202 cases that occurred in the control group. A significant difference.
If you look at the trials of statins with rodents, then every one of these has indicated that statins cause cancer.
Statins are known to depress the immune system and decrease antioxidant levels and these factors are likely to increase the risk of both cancers and infectious diseases.
Increased Risk of Diabetes
In a trial of a statin drug (Crestor), it became apparent that there was a link between it and an increased risk of diabetes. The people who took Crestor in the trial had a 25% increased risk of developing diabetes compared to the control group.
Ironically, diabetes is itself an extremely strong risk factor for heart disease.
Other Side Effects of Statins
The side effects mentioned above are perhaps some of the most widely documented, but other significant side effects include:
- Increased incidence of lung disease (and increased risk of pneumonia serious enough to require hospitalization),
- Pancreatitis (inflammation of the pancreas, with symptoms of severe upper abdominal pain radiating through to the back, nausea, and vomiting).
- Increased risk of kidney failure
- Increased risk of cataracts
- Dizziness (possibly due to the blood pressure lowering effect of statins)
It seems quite likely that the longer that you take statin drugs, the greater the chance that you will experience side effects and also the more serious and long-lasting those side effects may be.
This is because it may take some time for the reduction in the availability of substances such as CoQ10 to impact on your health. Eventually, however, continuing statin treatment will result in further depletion of levels of essential alcohol, squalene, CoQ10, etc, and this will impact on the body’s ability to maintain itself in good health.
It has been suggested that people who do take statins should also consider CoQ10 supplementation, although there is (as yet) little clinical evidence to indicate that this is beneficial.
However, given the nature of the possible side effects of statins and the evidence that exists to indicate that statin treatment is actually not effective in reducing deaths, then you may want to think twice before you get your prescription for statins filled.