Updated: Feb 25
I commonly hear from patients that are struggling with brain health issues, such as depression and memory loss, that they never had any of these issues before starting a statin drug. They often report that when they ask their doctors about if the statin could be causing these side effects they have been laughed at and ridiculed for considering such a link. This is just baffling to me, as statin drugs have a clear side effect profile and track record of damaging brain health! This article will explore the research and biochemistry of statins so that you or your loved ones that are on them may understand what they are doing, how to counteract the side effects, and what other options are available.
How Statins Function
The common statin drugs include: Lipitor (atorvastatin), Zocor (simvastatin), Mevacor (lovastatin) and Pravachol (pravastatin).
The main mechanism of action involves inhibition of an enzyme call HMG-CoA reductase (3-hydroxy-3-methyl-glutaryl-coenzyme A reductase), the rate-controlling enzyme of the mevalonate pathway (the metabolic pathway that produces cholesterol and other isoprenoids). As such, they slow the production of cholesterol in the body. Many doctors have touted statins as a type of miracle drug for heart disease prevention. This is especially believed by those who believe the lipid hypothesis of heart disease (increased fat and cholesterol in the blood clogs the arteries) popularized by Ancel Keys in the mid-twentieth century. Keys findings have been widely accepted by the medical community, but also receive significant criticism from many doctors. The question is still out there, does increased cholesterol cause heart disease?
Back to statins. Besides blocking cholesterol production, blocking HMG-CoA also inhibits Ubiquinone (Co-Q10) and dolichol. Ubiquinone is essential for energy production within the electron transport chain of mitochondria. Mitochondria are the little organelles inside every cell of your body responsible for energy production. It is no surprise that people would develop fatigue and depression when this enzyme is blocked. Other side effects of low Co-Q10 include: muscle wasting leading to weakness, severe back pain, and heart failure (ironic no?), numbness and tingling of the extremities, and inflammation of the tendons and ligaments that can lead to ruptures. Dolichol is responsible for directing proteins encoded by DNA to their sites of action in order for a cell to function properly. A deficiency here leads to deranged cellular function.
The likely real reason statins have been shown in some studies to reduce heart disease is due to the inhibition of mevalonate. Reduced mevalonate makes smooth muscle cells less active (which decreases arterial wall thickening) and platelets less able to produce thromboxane (which is used to make clots). (14)
Doubts of the Lipid Hypothesis
Today there is solid evidence that increased cholesterol in the walls of arteries is the result of a deeper disease process, rather than the cause of blood vessel problems. Cholesterol is a building block, a fatty molecule that is used to repair damaged tissues. Research since the mid-twentieth century has indicated that things like hypertension (high blood pressure), stress, smoking, toxin exposures, refined sugars, and oxidized vegetable oils will cause damage to blood vessels. As a result, the body will use LDL (low density lipoprotein, a vilified form of cholesterol) to deliver important phospholipids and vitamins to repair the damaged vessels. The cholesterol accumulation is a result of prior damage, not the cause of it! Much of the modern science on saturated fat and cholesterol is in direct contradiction to these older ideas (1) (2) (3) (7) (8) (9) Furthermore, history elucidates more truth. Prior to 1920 very few people developed or died from heart disease. People before this time ate high fat diets without issue. It wasn't until the industrialization of our food supply and the resulting increase in vegetable oils, margarines, sugar, and processed foods that heart disease started to show up. During most of the 20th centure, fat consumption in Americans actually went down while heart disease continued to rise! (4)
Effects of Low Fat Diets and Lowering Cholesterol With Drugs
Unfortunately, low fat diets are unsustainable for many people as they lead to low energy, difficulty in concentration, depression, weight gain, mineral deficiencies, and fat soluble vitamin deficiencies (A,D,E,K). (5) Studies looking at cholesterol lowering drugs have been shown to increase rates of cancer, stroke, violence, and suicide. (6) Statins are associated with cognitive decline and dementia.(15) (16) (17) In fact, a large analysis of the large controlled trials from before 2000 found that long-term use of statins for the primary prevention of heart disease actually produced a 1% greater risk of death over 10 years compared to a placebo. (18) It would seem that promoting a low fat, low cholesterol lifestyle is not a great choice.
Other Necessary Uses for Cholesterol
Cholesterol is an essential building block for sex hormones (testosterone, estrogens, progesterones, etc.), protective stress hormones, and for repairing brain tissues (the brain is mostly fat and water after all). It is a precursor to vitamin D needed for healthy bones, growth, insulin production, immune system function, and brain health. Bile salts are made from cholesterol, which are essential for absorbing your fat soluble vitamins A, D, E, and K which play critical roles in health. Bile is also an essential way we rid the body of toxins and is essential for good liver health. Cholesterol acts as an antioxidant, protecting our tissues (10), is needed for your brain to respond to serotonin (which promotes happy mood and relaxation) (11), and maintains the health of your gut lining (essential to reducing body inflammation, pain, and food sensitivities) (12).
Be Careful About Damaging Healthy Cholesterol
While cholesterol can be a potent protective compound that will actually protect you from heart disease, damaged cholesterol can do the opposite. It turns out that the processing of foods (again) is what determines if it is healthy or not. Highly damaged cholesterol is found in powdered eggs, powdered milk (added to reduced-fat milks to give them more body) and in meats and fats that have been heated to high temperatures in frying and other high-temperature processes (don't eat your meats fried, burnt, or well done).
Should I Take Statin Drugs?
With all of this considered, are statins necessary or even a wise recommendation? Are they worth the side effects? I would argue not. Of course I am not your doctor and you should not take this as me recommending you stop your prescribed medications. I do encourage you to continue your research and decide if they are right for you (as you should with any medication). Choosing a healthy diet free of processed foods will do the most for protecting your arteries. There is no such thing as a magic pill that will prevent you from having a heart attack or stroke. The only good solution is to take control of your health through an appropriate diet, exercise, and stress reduction regimen.
Eliminate vegetable oils, hydrogenated fats, and refined carbohydrates (sugar and white flours).
Do not consume fried foods (chips, fries, deep fried meats, etc.)
Consume foods high in magnesium, iodine, selenium, vitamin C, and vitamin E (like vegetables and organ meats).
Eat animal products and fats from pasture raised animals only (the have high quality fat produced in their tissues that will protect your blood vessels).
Consume foods high in folate, vitamin B6, vitamin B12 and choline to reduce homocysteine to prevent vascular damage (again, found in animal products and vegetables).
Keep your blood pressure low through daily exercise and plenty of blood pressure lowering foods (like celery, beets, and garlic).
Detoxify your body of heavy metals and toxins that can damage your blood vessels (like lead that is famous for causing atherosclerosis).
Lower inflammation in the blood vessels by adopting an anti-inflammatory diet.
Quit smoking and minimize alcohol use.
If you want to be assessed more completely for your heart disease risk you can also schedule an appointment. If you have been on a statin drug for long term it is essential to work with someone who can assess the side effects and get you the right therapies to correct the deficiencies that have been created. At the very minimum, consider taking Co-Q10 (ubiquinol) in conjunction with taking a statin, as this will prevent fatigue. However, this still only addresses a small fraction of the side effects from these drugs.
Yours in health and wellness,
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(1) Ravnskov U. The Fallacies of the Lipid Hypothesis. Scand Cardiovasc J. 2008 Aug;42(4):236-9. doi: 10.1080/14017430801983082.
(2) Rosch PJ. Cholesterol Does Not Cause Coronary Heart Disease in Contrast to Stress. Scand Cardiovasc J. 2008 Aug;42(4):244-9. doi: 10.1080/14017430801993701.
(3) Ravnskov U. A Hypothesis Out-of-date. The Diet-heart Idea. J Clin Epidemiol. 2002 Nov;55(11):1057-63.
(4) Enig, Mary G, PhD, Trans Fatty Acids in the Food Supply: A Comprehensive Report Covering 60 Years of Research, 2nd Edition, Enig Associates, Inc, Silver Spring, MD, 1995, 4-8
(5) Gittleman, Ann Louise, MS, Beyond Pritikin, 1980, Bantam Books, New York, NY
(6) “The Lipid Research Clinics Coronary Primary Prevention Trial Results. I. Reduction in Incidence of Coronary Heart Disease,” JAMA, 1984, 251:359
(7) DeBakey, M, et al, JAMA, 1964, 189:655-659
(8) Lackland, D T, et al, J Nutr, Nov 1990, 120:11S:1433-1436
(9) Nutr Week, Mar 22, 1991, 21:12:2-3
(10) Cranton, E M, MD, and J P Frackelton, MD, Journal of Holistic Medicine, Spring/Summer 1984, 6-37
(11) Engelberg, Hyman, Lancet, Mar 21, 1992, 339:727-728; Wood, W G, et al, Lipids, Mar 1999, 34(3):225-234
(12) Alfin-Slater, R B, and L Aftergood, “Lipids,” Modern Nutrition in Health and Disease, 6th ed, R S Goodhart and M E Shils, eds, Lea and Febiger, Philadelphia 1980, 134
(15) Duane Graveline, MD. Lipitor: Thief of Memory, 2004
(16) Muldoon MF and others. Am J Med 2000 May;108(7):538-46.
(17) Colomb, B. Geriatric Times, May/June 2004, Vol V, Issue 3
(18) Jackson PR. Br J Clin Pharmacol 2001;52:439-46.