The Collison Newsletter August 2009

  

                     STATINS – ADVERSE EFFECTS* 

Introduction 

‘Statins’ are a class of drugs widely used to treat high cholesterol levels in the blood.

 

HMG-CoA reductase inhibitors are called ‘statins’. In Australia they include:

·       atorvastatin

·       fluvastatin

·       pravastatin

·       simvastatin

·       rosuvastatin.

These are the generic (chemical) names. They are marketed under a variety of trade names such as, for example, Crestor, Lipex, Lipitor and Pravachol.

 

Statins act by blocking the enzyme responsible for the conversion of 3-hydroxy-3-methylglutarate to mevalonate which is the early rate limiting step of cholesterol synthesis. This also leads to an upregulation in LDL cholesterol (low density lipoprotein cholesterol, the ‘bad’ cholesterol) receptors and hence a greater clearance of LDL cholesterol from the blood stream. Statins are said to lower cholesterol and LDL cholesterol by 30-35% and this is associated with a smaller fall in plasma triglycerides (10-30%) and a 5-15% rise HDH cholesterol (high density lipoprotein cholesterol, the ‘good’ type).

 

There is an epidemic in Western countries of overweight/obesity. In Australia, some 60% of the population is now overweight and 25% are obese. This is, in part, the result of excessive calorie/kilojoule intake from diets high in ‘junk’ food and high in animal products containing cholesterol. This results in raised levels of cholesterol in many people, for whom statin drugs are now widely prescribed. They are indeed among the most commonly prescribed drugs in the world.

 

In my July 2006, February 2007, January 2008 and January 2009 newsletters Drugs - The Top 10 (for the relevant years), it was shown that two statins drugs (atorvastatin and simvastatin) were the top two (numbers 1 and 2) of the Top 10 drugs by:

·       Defined daily dose per 1000 population per day

·       Prescription counts

·       Cost to the Australian Government.

The statin drug pravastatin is also included in the Top10. The cost to the Government for these three drugs was in excess of A$900,000,000 each year.

 

There are clear guidelines for the prescribing of these drugs. These are spelled out in detail by the manufacturers, as well as in publications such as MIMS Australia (published by CMPMedica Australia Pty Ltd, see website mims.com.au).

Contraindications 

Contraindications (ie, when the statin drug should not be taken) include: “Active liver disease or elevation in liver enzymes. Pregnancy, childbearing potential and lactation. Known hypersensitivities to statins. Risk of myopathy is increased with concomitant use of fibrates, cyclosporin, erythromycin and niacin.” (MIMS).

ADVERSE REACTIONS 

One of the concerns of these statin drugs is the side effects or adverse reactions. These are listed as: “Adverse reactions … include gastrointestinal side effects (nausea, flatulence, dyspepsia, constipation, diarrhoea and abdominal pain), myopathy with raised plasma creatine phosphokinase and aches and pains. Non specific adverse reactions include headache and fatigue.” (MIMS).

A New and Detailed Review of the Adverse Effects of Statins 

The article Statin adverse effects: a review of the literature and evidence for a mitochondrial mechanism, by Drs B.A.Golomb and M.A.Evans, was published in the American Journal of Cardiovascular Drugs in 2008. Dr Beatrice Golomb is associate professor of medicine at the University of California, and director of the UC San Diego’s Statin Study group. This is the first comprehensive paper on statins’ adverse effects.

 

This publication cites nearly 900 studies on the adverse effects of HMG-CoA reductase inhibitors, or statins. This review provides the most complete picture to-date of reported side effects of statins, showing the state of evidence for each. The paper also helps explain why certain individuals have an increased risk for such adverse effects.

 

What are the Common Adverse Side-Effects of Statins as Reported in this Article?

·       Muscle problems 

These are the best known of statin drugs’ adverse side effects. In the paper by Drs Golomb & Evans, these come under the heading of myopathy with raised levels of plasma creatine phosphokinase. Aches and pains are very common. In addition to the muscle pain is weakness. There is also a condition called rhabdomyolysis, where there is a rapid breakdown (lysis) of muscle tissue (rhabdomyo).

·       Cognitive problems 

These, too, are widely reported. They include difficulties in concentration, memory impairment and general reduction of cognition. Of real concern is the fact that some cognitive dysfunction can continue when the statin drug is no longer taken.

·       Peripheral neuropathy

Pain and numbness in the extremities like the fingers and toes are also very common.

·       Other problems

A spectrum of other problems including gastrointestinal side effects, headaches, fatigue (often chronic),elevated blood glucose and tendon problems are linked to statin drug usage. 

Also listed as adverse effects are pancreatic and hepatic dysfunction and sexual problems, as well as immune system suppression.

 

Clear evidence, cited in this paper, shows 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. Statin drugs have been shown to have adverse effects on:

·       Mitochondria

·       CoEnzyme Q10

 

Mitochondria

 

Mitochondria are the energy source within all cells. They also produce most of the free radicals in the body, harmful compounds that cause damage to the cells and other structures of the body. When mitochondrial function is impaired, the body produces less energy and, at the same time, more free radicals are produced.

 

This paper by Drs Golomb & Evans summarises powerful evidence that statin-induced injury to the function of the energy-producing components of the cells, called mitochondria, underlies many of the adverse effects that occur in patients taking statins.

 

CoEnzyme Q10

 

CoEnzyme Q10 (‘Q10’) is a compound central to the process of making energy in the mitochondria and destroying or inactivating free radicals.

 

Statins lower Q10 levels. Statins work by blocking the pathway involved in cholesterol production - the same pathway by which Q10 is produced. Statins also reduce the blood cholesterol that transports Q10 and other fat-soluble antioxidants.

 

“The loss of Q10 leads to loss of cell energy and increased free radicals which, in turn can further damage mitochondrial DNA.” said Dr Golomb. In the paper, Dr Golomb explains that the loss of Q10 may lead to a greater likelihood of symptoms arising from statins in patients with existing mitochondrial damage. Because statins may cause more mitochondrial problems over time, and as these energy powerhouses tend to weaken with age, new adverse effects can also develop the longer the patient takes statin drugs. This is why the risk of adverse effects increases with age. “This also helps explain why statins’ benefits have not been found to exceed their risks in those over 70 or 75 years old, even those with heart disease” (Dr Golomb).

 

Conditions at Higher Risk of Statin Adverse Effects

 

High blood pressure and type 2 diabetes are linked to higher rates of mitochondrial problems, so these conditions are also clearly linked to a higher risk of statin complications. Mitochondrial or metabolic vulnerability are present in the metabolic syndrome and thyroid disease and so these conditions are also at higher risk.

Delayed Side-Effects of Statins 

Statin drugs often do not have any immediate side effects, and they are quite effective in lowering cholesterol levels. This makes it appear that they are beneficial to health. As a result, health problems that occur later on are frequently not interpreted as a side-effect of the drug, but rather as a brand new and separate health problem. The potentially serious adverse effects or side-effects begin to manifest several months after the commencement of therapy.

Do we Need Statin Drugs? 

In my January 2008 newsletter Drugs - The Top 10 for 2006-2007, there is a section entitled Lifestyle Change Versus Drugs, with an illustrative case history showing that it is possible to control cholesterol levels without resorting to statin drugs. Drugs are the ‘quick fix’. Lifestyle change requires discipline and time for the positive changes to come about. A diet that is mainly plant-based and low in fat is essential. Weight loss to the desirable weight, in the region of a body mass index (BMI) of 21, is also a key to cholesterol control, as is regular aerobic-type exercise. A positive mental attitude and some form of regular relaxation activities also help.

 

Short-term, when the total cholesterol level is very high, statin medication could be indicated, while lifestyle changes are put in place. It should not be continued beyond six months without close supervision. Lifestyle changes should be started when the statin drug is commenced. With the improved diet (see my September 2005 newsletter Acid/Alkaline Balance - The Ideal Diet), weight loss and exercise, the need for cholesterol lowering drugs will most likely no longer be required.

Finally 

There is a lot of confusion with regard to the importance of cholesterol as a risk factor in heart disease. Some authors have gone as far as saying that cholesterol is not the cause of heart disease.

 

Dr Joseph Mercola has a Special Report on Cholesterol’ on his website mercola.com.

There are also several books devoted to this topic.

One example is the book The Cholesterol Myths – exposing the fallacy that saturated fat and cholesterol cause heart disease, by Dr Uffe Ravnskov, MD, PhD. Dr Ravnskov is an independent researcher. His website is ravnskov.nu.

Another example is the book Health Myths Exposed by Shane Ellison M.Sc, in which he sets out three myths regarding cholesterol:  Myth #8 ‘High Cholesterol is a Major Risk Factor for Heart Disease’, Myth #9 ‘Cholesterol is Bad for You’ and Myth #10 ‘Cholesterol-lowering Drugs are Safe and Effective’. This book is published by Health Myths Exposed and is available via www.amazon.com.

These are recommended reading.

  

*Copyright 2009: The Huntly Centre.

Disclaimer: All material in the Huntlycentre.com.au website is provided for informational or educational purposes only. Consult a health professional regarding the applicability of any opinions or recommendations expressed herein, with respect to your symptoms or medical condition.

 

    

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