Are statins really the wonder drug they are claimed to be? They do lower cholesterol, but at what cost? It’s important to weigh up the benefits and the adverse effects. This article takes a comprehensive look at the evidence.
WHAT ARE STATINS?
Statins are a group of drugs developed to lower cholesterol levels by inhibiting the production of an enzyme (HMG-CoA reductase), which results in a decrease in cholesterol synthesis in the liver. Although initially thought to be a wonder drug, they have become the subject of much debate regarding their relevance in lowering death rates from cardiovascular disease.
What they can do, and what they can’t
When statins were launched in the 1980s, their ability to reduce total cholesterol and LDL (low-density lipoprotein, also called ‘bad cholesterol’) was widely publicised, but it was subsequently discovered that they are not particularly effective in raising the levels of HDL (high-density lipoprotein, also called ‘good cholesterol’). Until the last few years, this was not cause for much concern, because the primary focus was on LDL as a cardiovascular risk factor. Recent research, however, has suggested that aggressively raising our levels of HDL (which acts as a vehicle for removing excess cholesterol from the circulation) may be much more valuable in reducing our risk than was previously thought, because low HDL has emerged as an important independent risk factor for cardiovascular disease.
Statins may have benefits other than just lowering ‘bad’ cholesterol. One promising benefit of statins appears to be their anti- inflammatory properties, which help stabilise the lining of blood vessels. This has potentially far-reaching effects, from the brain and heart to blood vessels and organs throughout the body, and is postulated to be a far more important benefit than its cholesterol- lowering effect. In the heart, stabilising the blood vessel linings would make plaques less likely to rupture, thereby reducing the chance of a heart attack. The level of inflammation in the blood vessels can be measured with the ultra-sensitive or high-sensitive CRP (hsCRP) level in the blood.
Statins also help relax blood vessels, thereby lowering blood pressure. In addition, statins could reduce the risk of blood clots. For these reasons, doctors are now beginning to prescribe statins before and after coronary artery bypass surgery or angioplasty, and following certain types of strokes.
Statins could also have benefits that help prevent diseases that aren't related to heart health, although more research is necessary. Other benefits of statins could include a reduced risk of:
- Arthritis and bone fractures
- Some forms of cancer
- Dementia and Alzheimer's disease
- Kidney disease.
Statins may also be helpful in controlling the body's immune system response after an organ transplant.
UNWANTED EFFECTS OF STATINS
The first problem with statins as a whole group is their prevalence of unwanted side-effects.
Muscle and joint aches, cognitive problems, peripheral neuropathy, or pain or numbness in the fingers and toes, are widely reported. A spectrum of other problems, ranging from blood glucose elevations, nausea, diarrhoea and constipation to tendon problems, can also occur as side-effects of statins.
A review paper by Prof Beatrice Golomb and Dr Marcella Evans published in 2008 cites 900 studies on the adverse effects of statins.1 The paper provides clear evidence that higher statin doses or more powerful statins – those with a stronger ability to lower cholesterol – as well as certain genetic conditions, are linked to greater risk of developing side-effects.
‘Physician awareness of such side-effects is reportedly low,’ Golomb said. ‘Being vigilant for adverse effects in their patients is necessary in order for doctors to provide informed treatment decisions and improved patient care.’ Other research shows patients who had definite or probable side-effects tended to be dismissed by their doctors, who denied any specific statin-linked side-effects and failed to appreciate the effect on their life.2
A Dutch survey of 4 738 statin users asked the users about side-effects. Just over a quarter (27%) said they suffered from them. Around 40% of these sufferers experienced muscle pain and almost a third (31%) had joint pain. It was also reported that 16% had digestion problems and 13% had memory loss.2
THE CAUSE OF SIDE-EFFECTS
There is powerful evidence that statins cause injury to the functioning of the mitochondria (body’s energy-producing structures within cells), and this underlies many of the adverse effects that occur to patients taking statin drugs.1
Mitochondria produce most of the oxygen free radicals in the body, which are harmful compounds that antioxidants seek to protect against. When mitochondrial function is impaired, the body produces less energy and more free radicals are produced. Coenzyme Q10 (CoQ10) is a compound central to the process of making energy within mitochondria and quenching free radicals. However, statins lower CoQ10 levels because they work by blocking the pathway involved in cholesterol production – the same pathway by which CoQ10 is produced. Statins also reduce the blood cholesterol that transports CoQ10 and other fat-soluble antioxidants.
The loss of CoQ10 leads to loss of cell energy and increased free radicals which, in turn, can further damage mitochondrial DNA (genetic material in cells). Because statins may cause more mitochondrial problems over time – these energy powerhouses tend to weaken with age — new adverse effects can also develop the longer a patient takes statin drugs. This also helps explain why the benefit of statins have not been found to exceed their risks in those over 70 years old, even those with heart disease. High blood pressure and diabetes are linked to higher rates of mitochondrial problems, so these conditions are also clearly linked to a higher risk of statin complications. As these conditions commonly occur together in the same patient, the chances of problems are increased in these individuals.
MORE SERIOUS SIDE-EFFECTS
Liver damage
Occasionally, statin use causes an increase in liver enzymes. If the increase is only mild, one can continue to take the drug. Rarely, if the increase is severe, one may need to stop taking the statin drug. Certain other cholesterol-lowering drugs, such as gemfibrozil and niacin, increase the risk of liver problems even more in people who take statins.
The lower levels of CoQ10 also tend to put undue stress on the liver and the heart.
Although liver problems are rare, the doctor should order a liver function test before or shortly after one begins to take a statin. One shouldn't need any additional liver enzyme tests unless signs or symptoms of liver stress develop. The doctor should be contacted immediately if unusual fatigue or weakness, loss of appetite, pain in the upper abdomen, dark-coloured urine, or yellowing of skin or eyes develops.
Muscle problems
As stated above, statins may cause muscle pain and tenderness (called statin myopathy). The higher the dose of statin one takes, the more likely one is to have muscle pains. In severe cases, muscle cells can break down (rhabdomyolysis) and release a protein called myoglobin into the bloodstream, which can damage the kidneys. Certain drugs, when taken with statins, can increase the risk of rhabdomyolysis. These include gemfibrozil, erythromycin, antifungal medications, nefazodone, cyclosporin as well as the vitamin supplement niacin in high doses.
Increased blood sugar or type 2 diabetes
It's possible that one’s blood sugar level may increase when one takes a statin, which may lead to developing type 2 diabetes mellitus. The risk is small, but important enough that the Food and Drug Administration (FDA) requires a warning on statin labels regarding blood glucose levels and diabetes. Despite this possible connection between increased blood sugar and statin use, it's still safe for most people with high cholesterol, including diabetics, to take statins.
Neurological side-effects
Some researchers have studied whether statins could be linked to memory loss or amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease. While there's little evidence that statins can cause ALS, the FDA says some people who take statins have developed memory loss or confusion while taking statins. These side-effects reverse once the medication is stopped.
TO EASE SIDE-EFFECTS OF STATINS
As many of the side-effects are due to the depletion of CoQ10 in the cells, it is beneficial to supplement daily with CoQ10. This can be effective in minimising the muscle and joint pains and in boosting energy levels. Ubiquinol is a form of CoQ10 which is shown to be eight times more bio-available, and therefore more effective than ordinary CoQ10, also known as ubiquinone. An effective dosage is between 50 and 100 mg daily.
OTHER PROBLEMS CAUSED BY STATINS
Apart from the frequency of side-effects, there are other problems caused by the statins in aggressively lowering cholesterol levels. Cholesterol is essential for:
- Formation and maintenance of cell membranes, which help the cells resist changes in temperature.
- Protection and insulation of nerve fibres.
- Formation of sex hormones such as progesterone, testosterone, oestradiol and cortisol.
- Production of bile salts, which help to digest food.
- Vitamin D conversion in the skin, when exposed to sunlight.
The formation of cholesterol involves a series of complicated biochemical reactions. Cholesterol is made primarily in the liver (about 1 000 milligrams a day), but it is also created by cells lining the small intestine and by individual cells in the body.
There has been substantial research since 1994, which links very low cholesterol levels (i.e. below 4.1 mmol/l) to an increased risk of depression, suicide, anxiety, impulsivity and aggression in men and women, adolescents and adults alike. Also noted was an increase in deaths from trauma (possibly due to increased impulsive and aggressive behaviour), some types of cancer, haemorrhagic stroke, and respiratory and infectious diseases. A study of Japanese men found that the suicide rate declined when cholesterol levels were allowed to rise.
Prof Majid Ali, head of the New York Hospital of Integrative Medicine, has stated that (based on scientific studies): ‘More people die from a low cholesterol than from a high cholesterol.’
Men with low total cholesterol plus symptoms of depression were seven times more likely to die prematurely from suicides, drug over-doses, and accidents and injuries than those without those markers. It is proposed that low cholesterol, being necessary for nerve function, may lower serotonin levels. The National Human Genome Research Institute (NHGRI), part of the National Institutes of Health (NIH), has found that pregnant women who have very low cholesterol levels have an increased chance of delivering a premature baby. Previous studies have shown that women with very high cholesterol levels also have an increased risk of premature birth.
Several studies in recent years have shown that although statins are effective at reducing bad cholesterol levels, there is little or no improvement in the death rate from all causes.3 Men who already have cardiovascular disease have been shown to have some benefit from statins; but for the majority of users who do not have cardiovascular disease, there appears to be little or no benefit.
To date, no large trial of female statin users who already have cardiovascular disease has successfully shown an increase in life expectancy. More importantly, the use of statins in women at lower risk has not increased life expectancy nor prevented heart attacks and stroke.
It raises the question whether women should be prescribed statins at all, since it appears that statins fail to provide any overall health benefit to women. The more recent heart protection study was hailed as a success for men and women, but despite the hype there was no effect on mortality in women.
JUPITER STUDY3
This massive study published in 2008 showed that high doses of an expensive statin (rosuvastatin) could lower cardiovascular events in men and women with normal LDL values and raised hsCRP. There is much controversy surrounding the results, with accusations of bias and inflated benefits gained by stopping the trial prematurely. It can be viewed as a flawed study, as the overall mortality rate did not appear to be significantly improved by taking the drug, and possible long-term unwanted effects were not taken into account.
TO BOOST THE BENEFITS OF STATINS
Niacin (vitamin B3) has shown to boost levels of HDL in the blood. It usually causes flushing, which can be uncomfortable, but this often eases after a while. No-flush forms of niacin are available. It can be combined with low-dose statins, but has been found to increase the likelihood of statin side-effects when combined with higher doses.
ALTERNATIVES TO STATINS
One of the most effective alternatives to statin drugs is a formula comprising citrus and palm fruit extracts that contains polymethoxylated flavones and tocotrienols. It has been shown in human trials to significantly reduce total cholesterol, LDL cholesterol, and triglycerides. Additionally, the powerful antioxidant and anti-inflammatory properties of the extracts in this natural formulation are known to contribute to managing additional cardiovascular disease risk factors. Tocotrienols (natural vitamin E compounds), flavonoids and policosanol are other useful natural substances that are effective in lowering cholesterol levels.
CONCLUSIONS
When one is prescribed a statin drug, there are several factors to consider. Although it will reduce the level of LDL in the blood, which will make one’s doctor happy, will it improve overall life expectancy? Will the potential risks outweigh the potential benefits? Should one take a CoQ10 supplement with the statin or even a natural alternative to the statin? How important is cholesterol as a factor in improving health and life expectancy, or should one rather be focusing on improving lifestyle and reducing many other cardiac risk factors?
See my response to a reader query: How to lower Cholesterol Naturally
Recommended reading
Kendrick M. The Great Cholesterol Con. John Blake, 2007.
References
- Golomb B, Evans MA. Statin adverse effects: a review of the literature and evidence for a mitochondrial mechanism. Am J Cardiovasc Drugs 2008;8(6)373-418.
- Kendrick M. The Great Cholesterol Con. John Blake, 2007.
- Ridker PM, Danielson E, Fonseca FA, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med 2008;359:2195-2207.
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