4 Things the Big Pharma Companies Don’t Want You to Know about Statins
In the autumn of 1986, Merck sent a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) and lovastatin was given FDA approval to become the first commercial statin in 1987. In the years that followed, 6 additional statin medications, including 2 semi-synthetic statins (pravastatin and simvastatin) and 4 synthetic statins (atorvastatin, fluvastatin, pitavastatin, and rosuvastatin) have been approved.
Today, half of men ages 65 to 74 and 39% of women ages 75 and older take statin. What’s more, if you combine the 45+ age groups and look at both genders, more than one in four Americans are taking a statin drug. We also know statin use among adults 40 years or older have increased from 17.9% between 2002-2003 to more than 28% today. Big pharma stands to profit from this uptick in usage; in fact, it is almost a $18 billion dollar industry today. Could this have something to do with the increase in usage despite evidence that points to its devastating side effects?
The Great Statin Paradox
You have likely heard of statin from TV commercials or because a family member takes it. But, what exactly is a statin drug?
Statins are a class of drugs used to lower cholesterol in the blood by inhibiting a liver enzyme, HMG CoA reductase, responsible for producing around 70% of the body’s cholesterol. This can be problematic for several reasons. The biggest issue, though, is that this blocked pathway can lead to mitochondrial dysfunction, which is at the root of numerous devastating diseases, including diabetes, epilepsy, strokes, and neuropathy. Mitochondrial dysfunction also plays a significant role in mitochondrial myopathy, or muscle damage.
How does this happen, exactly? Well, HMG CoA reductase is an enzyme early in the pathway leading to cholesterol synthesis, so it is prone to therefore reduce other end products in this pathway, which includes ubiquinone, also known as CoQ10.
CoQ10 is an imperative component on the electron transport chain (ETC) during mitochondrial respiration. In plain english, this means it is absolutely necessary for proper functioning of cellular energy (ATP). Unfortunately, statin usage has been linked to reduced blood levels of CoQ10 in the amount of 16 to 54 percent (Qu, 2018) depending on which statin drug is being used. This then can lead to mitochondrial devastation.
When Big Pharma company Merck first received approval from the FDA to commercially sell lovastatin, it was widely known that the drug was highly effective at lowering cholesterol. But, before going into detail about the studies used, it is first important to understand cholesterol and what it does inside the body.
Cholesterol circulates in our blood bound to special proteins called lipoproteins; these lipoproteins are categorized according to their density. So, HDL cholesterol is high density cholesterol (“H” can be remembered as “healthy”) and LDL cholesterol is low density cholesterol (“L” can be remembered as “lethal” or bad cholesterol). There is also VLDL cholesterol (“very lethal”), which is primarily made of triglycerides, and is of very low density that increases the risk of cardiovascular disease. Cholesterol, particular HDL, is essential for life and crucial for normal functioning of muscles, nerves, and the brain. It also helps our body manufacture many hormones, such as estrogen and testosterone.
Statins are approved to treat high levels of LDL cholesterol and are prescribed for people who have plaque in their arteries or are at risk for cardiovascular disease. However, those prescribed statins still had high residual risk for a heart attack or stroke even when their LDL cholesterol had been brought to low (or very low) levels.
Even more interestingly, the absolute risk of having a cardiac event in someone who takes a statin to lower their cholesterol is only a few percentage points different than someone who never takes the medication at all. This is because LDL is generally not the only factor impacting heart disease or cardiac events.
Other issues contributing to heart attacks other than cholesterol include a person’s abdominal obesity; elevated triglycerides; low HDL (healthy cholesterol) levels; higher blood pressure; or having a fasting glucose over 100. Rather ironically, many individuals who have atherosclerosis do not have high levels of LDL on average, and the high doses of statins usually lower their HDL, or healthy, cholesterol, which is not the intended effect of the medication or gets at the root of maintaining health while living with heart disease.
Onto the Side Effects… What Big Pharma is Hiding from You
Muscle Damage and Pain
Myopathy (muscle inflammation, weakness, pain, or damage) has been well established as a result of statin use under certain circumstances. The most egregious event in statin history that is currently available for review is the story of cerivastatin (Baycol) produced by Bayer Pharmaceuticals in 2001. When cerivastatin came onto the market in 1997, it was issued at 0.4-milligram doses with the goal of lowering cholesterol. At the time, Lipitor, a competitor statin, was producing cholesterol lowering effects at 10-milligram doses. Scientists at Bayer urged company executives not to provide a dosage higher than 0.4-milligrams as the side effects increased drastically at higher dosages; nonetheless, Bayer issued the drug at a 0.8-milligram dose, knowing inherent risks associated with myopathy and rhabdomyolysis, a serious and sometimes fatal condition in which damaged muscle tissue releases its proteins and electrolytes into the bloodstream, damaging the heart and kidneys along the way.
In 2000, Bayer executives became increasingly aware that their cerivastatin drug was causing unfavorable health outcomes, including death. However, the company’s medical director “mentioned that [a leaflet in the drug packaging explaining the risks, particularly when used in conjunction with a fibrate medication used to lower triglycerides] should not be prepared before 12 July 2000, when a meeting [was] scheduled with the FDA to discuss labeling” for their drug…
A consultant had advised Bayer executives that the leaflet warning would lead to resistance for the higher dose being administered from 0.4-milligrams to double that at 0.8-milligrams being approved by the FDA. For reasons unknown, the Bayer executives desperately wanted to continue the 0.8-milligram dosage despite what it was doing to innocent people taking the drug simply looking for better health outcomes.
From September 2000 to February 2001, eighteen people died of rhabdomyolysis, and the final death toll was over 30 people.
As expected, the drug was only then pulled off the market. (As a side note, clinically important rhabdomyolysis with statins is rare as of this writing, but mild muscle pain and myopathy continue).
Beyond this chilling example, it is believed that statins lead to the inhibited synthesis of compounds arising from the synthetic pathway of cholesterol, disturbing cellular respiration used to make energy (ATP), which may lead to myopathy. A common complaint among statin users is non-specific muscle aches or joint pains. A rarer reported condition is severe myositis, characterized by muscle aches, soreness, or weakness associated with elevated kinase levels (Pasternak, 2002). Dr. Paul Thompson, Chief of Cardiology at the Hartford Hospital and Staff Cardiologist at the Massachusetts General Hospital, continues to study the effect of statins on muscle function. In one study including 7924 patients treated with high dose statins, 11% developed muscle muscles and 4% had muscle symptoms so severe that it interfered with activities of daily life (Thompson, 2012).
There are three main theories for why myopathy occurs in statin users. The first is due to the depletion of CoQ10, producing mitochondrial dysfunction and abnormal muscle energy metabolism; the second is that specific exercises done by the patient (at the gym or through activities of daily life) may alter muscle membrane integrity, protein folding, and catabolism, which may disrupt the balance of cell degradation and repair; lastly, statins may cause calcium leaking from mitochondria impairment. Research continues to search for the underlying cause of myopathy due to statin use as of this writing, and Dr. Paul Thompson is leading the way.
Nerves and Cognitive Damage
The nervous system is comprised of the brain and spinal cord, and the nerves on the spinal cord that reach out to all of your organs. It is the nervous system’s job to monitor our environment, interpret whether or not we are in danger, and organize appropriate behavioral and bodily responses. The nervous system is divided into the central nervous system (CNS), or the brain and spinal cord, and the peripheral nervous system (PNS), or the nerves outside of the central nervous system (this part is subconscious) and includes tasks like how quickly to beat your heart, the duration it takes for your nails and hair to grow, and how long it takes for wounds to heal.
Within the PNS, there are two additional subgroups: the somatic nervous system (that includes our skin, muscles, and joints) and the autonomic nervous system (that provides nerves to our organs, blood vessels, and glands in order to manufacture hormones).
Nerves are built from bundles of neurons, which have slender dendrites that pick up on electrochemical impulses and process the information, and axons, which carry the nerve signal away from the body. So, once the dendrites pick up on a signal, it travels along the axon and is transmitted to a neighboring cell across the synapse. Axons are protected in an insulation layer called myelin sheath, which plays a critical role in how electrical impulses transmit information quickly and efficiently along the nerves.
As you may imagine, many diseases can be caused by a loss of myelin. And what is myelin made of? Protein and fatty substances, such as cholesterol. And what does statin lower? Cholesterol.
Diseases that come from dysmyelination, or the lack of myelin, include Charcot-Marie-Tooth Disease (CMT), Guillain-Barre syndrome, and Multiple Sclerosis (MS), to name a few. In one study, Christopher Lock, MBBS, PhD, concluded “MS patients treated with atorvastatin seemed to get worse. [58.8% patients] who received either 40 mg or 80 mg of atorvastatin had either a relapse or a new lesion on MRI.”
While muscle pain and myopathy is the most common statin side effect reported, the next most common is cognitive impairment: when a person has trouble retaining information, learning new things, concentrating, or making important decisions that may impact his or her life.
Going back to CoQ10, we know this coenzyme is necessary for mitochondrial function and may be inhibited by statin use. This is important to note as mitochondrial density is high in brain tissue, and therefore decreased CoQ10 impacts cognition function or impairment.
Dr. Matthew Muldoon of the University of Pittsburgh is a cardiologist and hypertension specialist who has studied the usage of lovastatin on cognitive function. In his double-blind investigation, he looked at 209 generally healthy adults with LDL cholesterol of 160 mg/dL or higher. They were randomly assigned a 6-month treatment of lovastatin (20 mg) or a placebo. Assessments were made before and after the statin use of neuropsychological performance, depression, hostility, and quality of life.
Dr. Muldoon’s team found significant effects of lovastatin treatment on measures of psychomotor and attentional processes compared to the placebo group. Performance in mental flexibility, working memory, and memory recall also decreased compared to the placebo group. It is not currently understood what causes the neural impact, though it has been hypothesized that this may also have to do with the lower CoQ10 which impacts the synthesis of fatty acids that are integral to neuronal membranes and mitochondrial density in brain tissue.
Increase in Diabetes
Dr. Naveed Sattar, a Professor of Cardiovascular and Metabolic Health at the University of Glasgow and Honorary Consultant at the Glasgow Royal Infirmary, is currently involved in multiple lifestyle and drug trials in diabetes and CVD. In one study conducted by Dr. Naveed, statin therapy was associated with a slightly increased risk of development of diabetes. This is suggested to be because statin use may cause blood sugar to rise, and there is documented evidence to support increased levels of A1c, which measures the blood glucose average level over three months).
Further, in the JUPITER trial, patients who took 20-milligrams of rosuvastatin daily experienced a significant increase in A1c levels and a 25% greater risk of a diabetes diagnosis compared to those in the placebo group. Recent studies continue to suggest that all statin drugs are associated with a modest increase in the risk of type 2 diabetes. As of March 1, 2012, the FDA has issued a warning label in all statin packaging to raise this concern, which has been largely followed also be European drug authorities.
Tendonitis
Tendons connect our muscles to our bones. They not only allow us to move our limbs, but they also absorb impact to our muscles when we run, jump, or do other types of movement, preventing muscle injury. Tendonitis is deep pain experienced by those who have inflamed tendons. Both tendonitis and tendon rupture have been associated with statin use.
Statin use may impair cell membranes and cell functions associated with mitochondrial dysfunction. Statins impact the synthesis of the membrane glycoproteins (proteins that have carbohydrate groups) and manipulate certain activation channels in the muscle membrane, which leads to impaired function. This then leads to myocyte injury (injury of the smallest subunit of muscular tissues).
The myocyte impact is important because the attachment between muscles and the tendon is located in a specialized region where collagen fibrils are inserted into deep recesses formed by myocytes. As a result of this, one study notes atorvastatin users recovered suboptimally after surgical repairs of ruptured tendons due to the impact of impaired collagen construction, harmed myocytes, and inflammation (Esenkaya, 2012).
In Summary…
Statins have balanced dualism when considering their positive and negative effects. The positive aspects of statin include the ability to lower LDL cholesterol while combating inflammation and decreasing the likelihood of clots to form. However, there are often serious, and sometimes fatal, side effects of statin use that include mitochondrial dysfunction, myopathy, nerve damage, tendonitis, and an increase in diabetes.
The absolute risk reduction of a heart attack (lethal or non-lethal) only differs a few percentage points between control groups versus statin users in countless clinical trials, whereas diet and lifestyle changes can also provide similar outcomes. The question needing to be addressed is why does Big Pharma tend to hide these profound side effects associated with these drugs, and why are those at risk or suffering from heart disease not informed of dietary and lifestyle holistic options? Could it be that statins are over an $18 billion industry and profits are at stake?
Works Cited
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Disclaimer: This is for informational and educational purposes only. Heart conditions are serious and this article does not substitute professional medical advice with a healthcare professional.