Cholesterol is surrounded by a lot of myths and controversies. While most doctors will tell you it is an important predictor of heart disease, some medical experts believe your risk of heart disease has nothing to do with elevated cholesterol levels.

Well, not many people understand that cholesterol plays some very important functions. You need healthy levels of this waxy substance for healthy brain function, to maintain the structure and integrity of cell membranes, and to make important hormones, vitamin D and bile. Another very important and almost unknown function of cholesterol is to help repair damaged cells and tissues.

Mainstream health practitioners advocate that elevated cholesterol leads to the formation of plaque that clogs your arteries – increasing your risk of heart attack and stroke. And to reduce this risk, your doctor is likely to get you on statin therapy. Statins are a class of drugs routinely prescribed to reduce raised cholesterol levels, which in turn reduce your risk of developing cardiovascular disease such as angina, coronary heart disease, heart attacks and stroke. So far so good.

Do statins really help? It is true that these drugs lower your cholesterol levels. But the science is not yet clear on whether statins reduce your risk of heart disease or help you live longer. In fact, studies show that high cholesterol levels may not be associated with an increased risk of heart disease at all.

In addition, there have been studies that prove that statins are:

  • Not useful in primary prevention of cardiovascular disease, which means statins are ineffective in people who have no history of heart disease or in people with a high-risk scenario such as diabetes and smoking but who have not yet developed any clinical signs of heart disease.
  • Not useful for women irrespective of their history of heart disease
  • Not useful for men over 65 years with no existing heart problem or diabetes
  • May work for middle-age men with a previous history of heart attack or those who have undergone angioplasty.
If anything, use of statins may increase the risk of cardiovascular disease in young people, in women and in people with type 2 diabetes. [1]

While this seems to be an on-going debate, the focus of this article is to look into the side effects of statins; most importantly how it may increase your risk of developing type 2 diabetes and what can you do about it.

A quick rundown on how statins work


Your liver is responsible for making cholesterol through an enzymatic pathway called mevalonate pathway, which comprises of a series of chemical reactions.

Mevalonate pathway, at the very beginning, involves an enzyme called HMG-CoA reductase. This enzyme facilitates various reactions – that eventually lead to the production of various important molecules including cholesterol, CoQ10, vitamin D, steroid hormones, dolichols, selenoproteins, heme, vitamin k2 and heme.

Now, what statins do is that they block HMG-CoA reductase. This sounds like a perfect strategy if you are looking to reduce the production of cholesterol in the body. However, if you have noticed, this enzyme, sitting at the base of mevalonate pathway, is giving rise to a number of chemical reactions and not just one branch that is making cholesterol.

So, what happens when statins block HMG-CoA reductase enzyme? This action not only blocks the production of cholesterol but also impacts other reaction pathways that are busy making important molecules and compounds critical for your overall health.

The net result is that long-term statin therapy damages your overall health with side effects such as muscle pain and weakness, joint pain, memory loss, confusion, elevated liver enzymes, nausea, upset stomach, headaches, and increased risk of diabetes. In very rare cases, statins are also known to cause kidney failure.

Statins and diabetes


A lot of studies claim that people on high doses of statins have a higher risk of developing high blood sugar levels, insulin resistance and diabetes. It appears that the risk of diabetes increases with the dosage: higher the dose, higher is the risk of elevated blood sugar levels. And it is a well-known fact that diabetes is one of the major risk factors in development of heart disease. 

In addition, some studies also report that postmenopausal women and people with kidney transplants (renal allograft recipients) are at a particularly higher risk of developing diabetes when they are on statins.

A 2018 systematic review suggests that treatment with atorvastatin may increase the risk of new onset diabetes. Most importantly, it showed that using high doses of atorvastatin negatively influences the glycaemic control in diabetic patients. [2]

The review highlights various mechanisms through which statins may increase this kind of risk. For example, statins interfere with the production of isoprenoids and dolichols, which has an effect of glycaemic control.

Statins cause insulin resistance and also decrease insulin secretion by interfering in the production of CoQ10. Since C0Q10 is an integral substance in the production of energy in every cell, this leads to reduced production of energy in pancreatic ß-cells, which are responsible for secreting insulin.

Another 2018 review compared the link between individual statins and their impact on glycaemic control in patients with type 2 diabetes mellitus. It concluded that,” Statins were associated with an increase in HbA1c compared with placebo. In patients with T2DM, moderate-intensity pitavastatin improved the glycaemic control whereas high-intensity atorvastatin worsened it. Appropriate statins should be administered for patients with diabetes mellitus.”  [3]

A 2015 study concluded that “Statin treatment increased the risk of type 2 diabetes by 46%, attributable to decreases in insulin sensitivity and insulin secretion.” [4]

In all, it appears statins do appear to increase the risk of insulin resistance and diabetes. While some statins at medium dose may not exert these adverse effects, high doses of statins - especially atorvastatin - appear to worsen the glycaemic control.

Elderly people are already at a high risk of developing diabetes. Lifestyle changes such as exercise, healthy diet and nutrition may be helpful in mitigating some of this risk. 

Can CoQ10 help people with insulin resistance and diabetes?


Studies show that CoQ10 can be helpful in the management of type 2 diabetes. It improves glycaemic control, vascular function and insulin sensitivity in people with diabetes. [5] [6] [7] CoQ10 supplementation also protects beta cells of the pancreas from oxidative damage and improve their function, which is to release insulin. Insulin is a hormone that helps your cells to take up glucose from the bloodstream. 

Increased levels of sugar in the blood will damage blood vessels, resulting in vascular complications. Damage and inflammation in large blood vessels cause endothelial dysfunction, heart disease and ischemic stroke. There are also small blood vessels that supply blood to nerves, kidneys and eyes. Oxidative damage, caused by excess sugar in the blood, can damage these small blood vessels – leading to vision loss (diabetic retinopathy), damage to kidneys (diabetic nephropathy) and damage to peripheral nerves (neuropathy). CoQ10 may help improve vascular function, mitigating some of the risk to blood vessels.

CoQ10 could be the best thing when you are taking statins


Statins can cause several side effects, where CoQ10 can be useful.

Some other prominent side effects of statins include:

  1. Muscle fatigue
  2. Increased risk of heart disease
  3. Impaired immunity
  4. Low sex drive
  5. Memory loss and poor brain function
  6. Increased risk of cataracts

CoQ10 in heart disease


Statins block the production of CoQ10 – a coenzyme that helps in energy production and works as an antioxidant. While CoQ10 is present in every cell, tissues that require more energy to function such as the heart, liver and skeletal muscles have higher levels of CoQ10. CoQ10 is one of the most important - and irreplaceable - components in the production of energy (ATP).

Your heart needs a lot of energy to do its job and CoQ10 deficiency can spell serious trouble. An energy starved muscle can cause heart failure and associated symptoms like shortness of breath, fatigue, weakness and swelling in the feet.

Why CoQ10 supplements are good for your heart?

  • Reduces oxidative damage and inflammation
  • Prevents oxidation of LDL cholesterol, a critical step in atherosclerosis, inflammation and heart disease
  • Reduces the risk of heart failure, improves symptoms of heart failure and improve quality of life in patients
  • Improves endothelial functions and vascular health
  • Improves energy production in the heart muscle
  • Helps recycle other important antioxidants such as vitamin C and vitamin E
  • Required for making selenoproteins, which reduces oxidative stress
There are other ways statins may adversely affect your heart health.

One: these drugs interfere with the synthesis of selenoproteins – selenium containing proteins that are great in preventing oxidative stress that can damage endothelial health and function. 

Two: statins also block the production of vitamin K2 – a vitamin that is mostly known for its role in blood clotting process. But vitamin K2 is also important for healthy bones and heart. For example, vitamin K2 activates osteocalcin, a protein that binds calcium from the blood to the bones. It also activates another protein called Matrix Gla-protein (MGP), that prevents calcium build-up in the arteries. Studies show that low levels of vitamin K2 are associated with poor heart health. Inadequate activation of MGP, as with vitamin K2 deficiency, can increase your risk of calcification in arteries and vascular stiffness.

In people with diabetes, high levels of inactivated MGP means increased odds of heart disease, [8] artery stiffening [9] and calcification of peripheral arteries. [10] Calcification in small and large blood vessels can give rise to complications commonly associated with diabetes – such as retinopathy (damage to retina), neuropathy (damage to peripheral nerves) and nephropathy (kidney damage).

A 2017 review reported that vitamin K2 improves insulin sensitivity through various mechanisms. [11] Insulin resistance increases the risk of metabolic syndrome, obesity, type 2 diabetes and cardiovascular disease.  

A 2015 research reported that statins deplete CoQ10 and heme A, which results in reduced energy in muscle cells of the heart and blood vessels, concluding that statins may even cause in coronary artery calcification. [12]

CoQ10 in muscle fatigue


Muscle weakness and muscle pain are the most common side effects experienced by people on statins. Again, it is because of impaired production of CoQ10, which your muscles need for making energy. Low levels of CoQ10 can cause muscle pain and fatigue.

A 2013 study reported that statin users are likely to suffer from musculoskeletal conditions, pain and soft tissue injuries such as dislocation, sprain, and strain. And these side effects of statins could be due to “inhibitory effect on coenzyme Q10 synthesis, selenoprotein synthesis and the mitochondrial respiratory chain.” [13]

In fact, statin use can even increase the risk of falls in the elderly. [14] Muscle fatigue and sprains also interfere with exercise, one of the most recommended lifestyle strategies to reduce one’s risk of heart disease, stroke and risk factors such as obesity, diabetes and high blood pressure. 

A few things to remember:

  1. Statins are not magic bullets, and studies suggest that these cholesterol busting drugs may not even be helpful in primary prevention. That is, in people who have no previous history of cardiovascular disease they may very well be useless and even harmful.
  2. Statins are associated with a wide range of side-effects including muscle pain, joint pain, nausea, heart disease, increased blood sugar levels and a possible risk of new onset diabetes.
  3. High intensity statin therapy carries the maximum risk when it comes to the risk of developing side effects including type 2 diabetes. Women and elderly are at high risk.
  4. One should not underestimate the role of lifestyle and dietary modifications in not only lowering your risk of diabetes, but also of cardiovascular disease. 
  5. If you have been prescribed statins, it is important to monitor your fasting glucose level and HbA1c.
  6. Doctors must screen their patients for vitamin D levels, as deficiency in sunshine vitamin has been linked with insulin resistance. 
  7. If you are already taking a statin, be sure to ask your doctor to put you on a high quality CoQ10 supplement.

What can you do to lower your cholesterol levels naturally?


So much focus on fats and cholesterol has distracted us from the real challenge: sugar and refined carbohydrates. This is the real reason why obesity, heart disease and other chronic ailments are rampant in spite of cutting down on saturated fats.

A study published in Lancet concluded: “High carbohydrate intake was associated with higher risk of total mortality, whereas total fat and individual types of fat were related to lower total mortality. Total fat and types of fat were not associated with cardiovascular disease, myocardial infarction, or cardiovascular disease mortality, whereas saturated fat had an inverse association with stroke. Global dietary guidelines should be reconsidered in light of these findings.” [15]

We are loading our diet with highly processed carbohydrates, vegetable oils and sugar. And factors like sleep deprivation, stress, sedentary lifestyle and continuous exposure to chemicals, toxins and pollution are not helping either. The idea is to control inflammation caused by all these factors.

  1. Eat a well-balanced diet –and include lots of fruits of vegetables, variety of nuts, seeds, fatty fish, and omega 3 fatty acids your diet.
  2. Cut down on sugar and avoid highly refined, processed carbohydrates
  3. Exercise regularly
  4. Get a good amount of sleep and maintain a regular sleep routine
  5. Reduce stress
  6. Quit smoking and alcohol misuse
It is advisable to consult your healthcare practitioner before taking any supplement as they may interfere with any existing health condition, or any medication you are currently taking. But always weigh up the advantages, and pros and cons for yourself. Do your own research and never rely solely on what others tell you. Even your doctor does not know everything.

References:

  1. Sherif Sultan, Niamh Hynes. The Ugly Side of Statins. Systemic Appraisal of the Contemporary Un-Known Unknowns. Scientific Research. OJEMD> Vol.3 No.3, July 2013.
  2. Angelidi et al. Is Atorvastatin Associated with New Onset Diabetes or Deterioration of Glycemic Control? Systematic Review Using Data from 1.9 Million Patients. International Journal of Endocrinology. 2018.
  3. Cui JY et al. Statin therapy on glycemic control in type 2 diabetic patients: A network meta-analysis. J Clin Pharm Ther. 2018
  4. Cederberg et al.  Increased risk of diabetes with statin treatment is associated with impaired insulin sensitivity and insulin secretion: a 6 year follow-up study of the METSIM cohort. Diabetologia. 2015
  5. Hodgson et al. Coenzyme Q10 improves blood pressure and glycaemic control: a controlled trial in subjects with type 2 diabetes. EJCN Europeon Journal of Clinical Nutrition.
  6. Mohammadi et al. The effect of coenzyme Q10 supplementation on metabolic status of type 2 diabetic patients. Minerva Gastroenterol Dietol. 2013
  7. David Mantle. Coenzyme Q10 supplementation for diabetes and its complications: an overview.  The British Journal of Diabetes. 2017.  
  8. Dalmeijer et al. Matrix Gla protein species and risk of cardiovascular events in type 2 diabetic patients. Diabetes Care. 2013
  9. Sardana et al. Inactive Matrix Gla-Protein and Arterial Stiffness in Type 2 Diabetes Mellitus. Am J Hypertens. 2017
  10. Liabeuf et al. High dp-ucMGP levels were independently associated with below-knee arterial calcification score in patients with type 2 diabetes and normal or slightly altered kidney function. Cardiovascular Diabetology. 2014
  11. Li Y et al. Effect of vitamin K2 on type 2 diabetes mellitus: A review. Diabetes Res Clin Pract. 2017
  12. Okuyama et al.  Statins stimulate atherosclerosis and heart failure: pharmacological mechanisms. Expert Rev Clin Pharmacol. 2015.
  13. Ishak Mansi, Christopher R. Frei, Mary Jo Pugh, et al. Statins and Musculoskeletal Conditions, Arthropathies, and Injuries. JAMA Internal Medicine. 2013.
  14. James Wright, Tom Perry. Therapeutics Initiative highlights potential harms from statins. The University of British Columbia. May 28, 2014.
  15. Dehghan et al. Associations of fats and carbohydrate intake with cardiovascular disease and mortality in 18 countries from five continents (PURE): a prospective cohort study. The Lancet. 2017.