1 in 4 Americans over the age of 40 are taking a statin drug such as atorvastatin, rosuvastatin, simvastatin, and pravastatin. That equates to over 40 million people in the US alone!
We know that statins lower cholesterol levels which reduces the risk of heart disease, myocardial infarction, and stroke.
But is it really that simple? What does the data really show? Should so many of us be taking these medications?
In this article I will discuss this class of drugs and why they are recommended. I will also discuss the many potential side effects that statins can cause, most of which you may not have even heard about.
I will also give my recommendations on who should consider taking statins and who should not.
Let's get started...
Before we get into treatments for high cholesterol, we need to discuss cholesterol and what it does in the body.
Cholesterol is a lipid molecule that is produced by all animal cells. It is an essential structural component of all animal cell membranes. In fact, about 30% of cell membranes are cholesterol. The vast majority of cholesterol is made by the liver.
Within the cell membrane, cholesterol also functions in intracellular transport, cell signaling and nerve conduction.
Cholesterol is also a precursor to the production of hormones, bile acids, and vitamin D.
Cholesterol is transported inside lipoprotein particles throughout the body. These lipoproteins come in 2 primary forms - LDL and HDL (there are also VLDL and IDL particles, which I will not discuss in this article).
It is believed that low density lipoproteins (LDL) particles (as well as IDL and VLDL) promote the development of atheromas in artery walls while high density lipoproteins (HDL) particles promote the removal of those atheromas from the artery walls.
As a result, most people call LDL the "bad" cholesterol while HDL is the "good" cholesterol. Again, more recent research has shown a much more complicated picture than that, but we will stick to this narrative for the sake of this article.
The belief is if you can reduce the amount of LDL in the body, it will reduce the incidence of atherosclerosis (the laying down of plaque in the arteries).
Statins are a class of drugs that lower the level of cholesterol in the blood by reducing the production of cholesterol by the liver.
Statins block the enzyme in the liver that is responsible for making cholesterol. This enzyme is called hydroxy-methylglutaryl-coenzyme A reductase (HMG-CoA reductase). Scientifically, statins are referred to as HMG-CoA reductase inhibitors.
Examples of these drugs include atorvastatin (Lipitor®), simvastatin (Zocor®), rosuvastatin (Crestor®), and pravastatin (Pravachol®).
Over 40 million people in the US are currently taking a statin. That equates to about 1 out of every 4 US adults over the age of 40 taking this class of drug!
If 2013 guidelines released by the American College of Cardiology and American Heart Association are followed, it is estimated that the number of people taking a statin could rise to 1 out of every 2 adults!
Even more shocking, statins are now being used for children as young as 8 years old with elevated LDL levels.
So the obvious next questions should be:
1. Do statins work?
2. Are statins safe?
Let's try to get some answers.
There are multiple studies that show that reducing LDL cholesterol results in a reduction in cardiovascular disease and events.
Studies have also shown that statins can reduce atheroma progression.
Various other studies have shown a reduction in cardiovascular death in patients taking statins by as much as 25-40%. Here is one of those studies for reference.
It is considered standard of care to place a patient that has suffered an MI on a statin, regardless of their cholesterol level. This is called secondary prevention (preventing an MI from occurring in someone who has already had an MI).
Because of some of these studies, experts now recommend statins for primary prevention, meaning giving them to patients that have multiple risk factors for developing an MI in the future.
However, there are becoming more critics regarding statins and their beneficial effects.
Much of this controversy stems around the fact that almost all of the large studies regarding statins were sponsored by pharmaceutical companies that were making the statin being tested.
Another controversy is in regard to how the numbers accumulated in the study were calculated.
Let's spend a moment to explain this further.
I don't want to bore you with a statistics lecture, but please bear with me. This concept is critical to your understanding of the true benefit vs. harm caused by statin drugs or any other study you are reading.
When a study states that a drug reduced the incidence of something by a certain percentage, it is important to note whether the reduction was an absolute risk reduction (ARR) or a relative risk reduction (RRR). There is a huge difference between the meanings of those 2 statistical terms.
The absolute risk reduction is the change in the risk of an outcome of a given treatment or activity in relation to a comparison treatment or activity. I know, that sounds confusing.
The relative risk reduction is a measure calculated by dividing the absolute risk reduction by the control event rate.
To better understand this concept, let's imagine a study that was designed to determine if a new drug reduced the incidence of heart attacks. One group was given a placebo while the other group was given the new drug. There were 5000 people in each group.
So suppose the placebo group in the study had 100 people suffer an MI during the study. This equated to 2% of that group. Let's say the drug group only had 50 people suffer an MI. That means 1% of people taking the drug suffered an MI.
The relative risk reduction in this study would be 50%. That sounds incredible!
However, the absolute risk reduction was only 1%. Instead of 2% of the people suffering an MI, only 1% did that were taking the drug. 100 people would have to take the drug in order to prevent 1 person from having an MI. That term is called the number needed to treat (NNT).
The use of relative risk reduction can be deceiving and is a way of manipulating statistics to make the outcome look better than it really is.
If the absolute risk reduction is small like in the above example, then the potential side effects and consequences of taking the drug should be considered. If the side effects are minimal, then giving it to people in order for a small percentage of them to get benefit might be worth it.
However, if the side effects are substantial, then it would not make sense to give it to a large number of people that will receive more harm than good from it.
There have recently been 2 independent meta-analyses of studies that have questioned the use of statins, especially for primary prevention. This meta-analyses did not find any benefit in statin use for primary prevention. This one didn't either, and even went so far as to scold the pharmaceutical companies for adversely influencing study results.
So what are the most common side effects of statins?
You will be aware of some of these listed below, but several may surprise you.
I have been in medical practice for over 21 years, and I was not aware of some of these prior to looking at the research in depth during my preparation for this article. You can bet that your doctor is not aware of all of them either.
Muscle pain is the most common and well-known of the side effects caused by statins.
In my personal experience, up to a third of my patients have been unable to tolerate them primarily because of muscle aches and pains.
Some patients develop almost flu-like symptoms. Others state that many of their muscles just feel "sore." Still others can develop tendonitis and other musculoskeletal disorders. Rarely, more serious conditions such as rhabdomyolysis or autoimmune muscle diseases can develop.
This study confirmed a substantial increase in these conditions in people taking a statin drug.
Fortunately, the majority of these issues will resolve once the medication has stopped.
Statins commonly cause an increase in liver function tests (LFTs) found on routine labs.
The most common of these tests are the AST and ALT.
This is such a well-known side effect of statins that it is considered acceptable as long as these tests do not rise more than 2-3x their normal ranges.
Fortunately, serious liver damage is relatively rare with statin use.
My primary concern with this side effect is it has the potential to mask liver function test elevations that could be caused by other potentially dangerous conditions.
For example, if a patient is on a statin and has mildly elevated LFTs, it could cause their medical provider to ignore it because they assume that the elevation is due to the statin drug.
Also, even a mild impairment of liver function has the potential to affect detoxification and other essential functions that the liver provides.
Statins have been shown to increase the risk of development of type 2 diabetes. This particular study showed a 9% increased risk. For every 255 people that were put on a statin, one person developed diabetes as a result of taking the drug.
In this study, statin use was associated with an increase in blood plasma glucose in people with or without diabetes. This rise was independent of other factors including age, aspirin use, beta blocker use, or ACE inhibitor use. In non-diabetics, statin use increased their glucose level by 7 points, while in diabetics the glucose level increased 39 points!
The increase in glucose appears to be dose-dependent. The higher the dose of statin drug, the higher the glucose level.
Statins interfere with the production of mevalonic acid, which is a precursor in the production of CoQ10. Statin users routinely have low CoQ10 levels when it is tested.
CoQ10 is used for energy production in the cells. It is a critical component of cellular respiration and production of ATP, the primary fuel used in cell function.
A deficiency of CoQ10 is generally considered to be one of the primary reasons why statins cause muscle pain.
The heart is the most energy-demanding organ in the body, so it makes sense that a CoQ10 deficiency can increase the risk of acute heart failure.
CoQ10 deficiency can also cause symptoms such as fatigue and brain fog and has been implicated in things such as dementia and other neurodegenerative disorders.
The risks of vitamin K2 deficiency have only come to light in the past few years. Most medical providers are not aware of its importance.
Vitamin K2 helps move calcium into the proper areas of your body, including your bones and teeth. It also helps remove calcium from places where it shouldn't be, such as in our arteries and soft tissues.
A deficiency of vitamin K2 has been shown to result in an increase in arterial calcification. It also increases the risk for osteoporosis.
Statin drugs inhibit the synthesis of vitamin K2 which increases the risk of atherosclerosis, or calcification of arteries.
These risks appear to decrease with proper vitamin K2 supplementation. Since the vast majority of people are also deficient in vitamin D (your level should be at least 50), I typically recommend a supplement with both vitamins K2 and D3 such as this one.
Statins also block the production of selenium containing proteins. The most important of these appears to be glutathione peroxidase.
These proteins play a vital role in protecting the cells of the body from oxidative damage that comes from hydrogen and lipid peroxides.
When you are low in glutathione peroxidase, you develop a high level of free radicals and inflammation that results in damaged tissue. This is felt to result in an increased risk for heart failure and atherosclerosis as well as myalgia and other muscle/tendon issues.
This is another risk that is not well known.
Studies have shown an increased risk of ductal and lobular breast cancer in patients that have taken a statin drug for 10 or more years.
In this study from Taiwan, statin use was also associated with an increased risk for prostate cancer.
In this letter to the editor in the Journal of Clinical Oncology, the authors discuss the fact that several cholesterol-lowering drugs, including statins, have been shown to increase cancer risk in rodents.
The authors felt that statins themselves may not be carcinogenic, but their increase in cancer risk may result from their ability to lower blood lipids. It is documented that lipoproteins, particularly LDL (your "bad" cholesterol), work in the immune system by binding and inactivating all kinds of microorganisms and their toxic products. Many of those microorganisms have been implicated in the development of many cancers.
Maybe LDL isn't so "bad" after-all!
As I explained earlier, cholesterol is essential for normal brain function.
Statins obviously reduce cholesterol levels. They also secondarily reduce ketone levels in the brain.
Ketones are an essential energy source for the brain. They have also been shown to be protective against brain diseases such as Parkinson's Disease.
This study from Penn State showed an increase risk of Parkinson's Disease in patients taking statin drugs. Conversely, an elevated cholesterol level was associated with a lower risk for Parkinson's.
This study from JAMA showed an increased risk for cataracts in statin-users compared with non-users.
This was also shown in a review of PubMed, EMBASE, and Cochrane review databases that found that for every 10,000 people taking a statin, there were 307 extra patients with cataracts.
Up to 25% of the cholesterol in our body is in the brain.
Cholesterol is essential for normal brain function. It is a vital component of the connections between brain cells (neurons) called synapses.
It only makes sense that if you deplete the cholesterol levels in the body, it has the potential to affect brain functions such as memory and thinking. Statins also reduce CoQ10 and Vitamin K2 as I discussed earlier, both of which are vital for normal brain function.
Several studies have suggested that statin use can increase the risk for development of Alzheimer's and other types of dementia.
This study showed a significant increase in acute memory loss within 30 days of taking a statin.
However, subsequent studies like this one have actually suggested that prolonged statin use is associated with a decrease in dementia.
The jury is still out on this issue, but you need to be aware of the possible link.
Most people will agree that statins are extremely effective at lowering cholesterol levels in the body. That fact is not in question.
The question I have attempted to answer in this article is: Are statins effective at reducing heart disease and death due to cardiovascular disease?
The short answer is yes.
However, the even bigger questions should be:
When including potential side effects, do the benefits of taking a statin outweigh the risks?
Who should be taking a statin medication?
After my personal review of the research and listening to many authorities on the subject, I personally would recommend statin therapy to the following groups:
With just about everyone else, I believe the data shows that dietary and lifestyle changes should be front and center in the treatment of someone with high cholesterol. Changing a diet is massively more effective than a statin at reducing cholesterol levels.
In my opinion, there is not enough data to support the use of statins in primary prevention. In other words, if you have never had a heart attack but you have high cholesterol and several other risk factors for heart disease (family history, overweight, high blood pressure, smoking, diabetes, etc.), taking a statin medication may not be necessary.
What about women?
The data supporting the use of statins in women is very weak. They just don't seem to work well.
If a woman has progressive heart disease, then they should definitely consider statin therapy. Otherwise, they really need to focus on their diet and lifestyle first!
Of note, it can be argued that the reduction is death in patients taking statins may have nothing to do with cholesterol-lowering at all!
Some experts instead argue that the reduction in risk by statins may be due to their anti-inflammatory and anticoagulant effects instead of their cholesterol-lowering abilities.
If you and your doctor decide you should take a statin drug, PLEASE consider taking a CoQ10 supplement.
As I have shown above, statins dramatically reduce CoQ10 levels in the body which can result in several serious conditions, including acute heart failure, muscle pain, fatigue, and brain fog.
The effectiveness of CoQ10 supplementation has been mixed in several studies, although using the ubiquinol form of CoQ10 appears to offer the most benefit.
Researching this topic has caused me to make a change in my personal practice. For patients taking statins, I believe that ALL of them should be taking a ubiquinol/CoQ10 supplement. Click here for my brand of choice.
Statins are the 3rd most commonly written medication in the US, accounting for billions of dollars per year.
While there are multiple studies showing the benefit of statins in reducing plaque progression in arteries and reduction of death in patients that have had a previous MI, the recent guidelines recommending statins for primary prevention have been called into question.
Statins are not benign drugs. They can cause many side effects, some mild and some very serious. These include, muscle pain, liver irritation, cancer, cataracts, nutrient depletions such as CoQ10 and glutathione, and others.
Anyone considering taking a statin should be aware of these potential side effects so that a truly informed consent can be made.
Patients with familial hyperlipidemia and men who have had a previous MI should strongly consider taking a statin medication.
The data supporting the use of statins in women is weak, unless you have familial hyperlipidemia.
If you are taking a statin, I strongly recommend taking a ubiquinol supplement, vitamin K2 (if you aren't on a blood thinner), and monitoring your glucose level periodically.
Now it's your turn....
Are you taking a statin drug?
Have you had any of the side effects that I discussed?
Leave any questions or comments below.
Dr. Whelchel is a family physician who specializes in functional medicine, especially hormone optimization. He has over 20 years experience in private practice managing patients with various medical issues. His passion is helping patients reach their full potential of wellness and quality of life. He grew up in the Texas Panhandle where he currently lives. He is married and has 3 awesome children.