Iatrogenesis: Sick from your Cholesterol Medications

NOVEMBER 2014

When Your Cholesterol Medications are Making You Sick

Written By: Millie Lytle, ND, MPH, CNS

Prescription medications are studied for their efficacy, timing, dosage and risks. It could be said that approved prescription medications have “direct effects”. But they also have side-effects or undesired effects. Some of these undesired effects are due to nutrient depletions that may often cause disease. For example, think of scurvy as Vitamin C deficiency and anemia as Iron and/or B12 deficiency. In our developed nation where most people have access to doctors, an abundant food supply, and a public health system that fortifies food with under-consumed nutrients, we are not accustomed to worrying about nutrient deficiencies. However, the world is changing. Billions of people around the world are affected by micronutrient deficiencies that may cause birth defects, learning disabilities, mental retardation, reduced immunity, blindness, poor work capacity, or premature death¹. This is more common in developing nations.

The Center for Disease Control, however, also states that “dietary deficiencies …have been associated with risks of adverse health effects including cardiovascular disease, stroke, impaired cognitive function, cancer, eye diseases, poor bone health, and other conditions”¹ common in the developed world. Dietary supplements may come in to play as the result of a low nutrient diet, environmental exposures, other nutrient toxicities, illness, recreational drug and alcohol use, as well as a result of prescription and over-the-counter medications.

Therefore, prescription medications cause disease. This is known as iatrogenesis, when a patient gets sick at the hand of his or her physician’s treatment or advice. Iatrogenic disease can occur for various reasons, from known side effects to unintended results to error, and even negligence to malice.

Causes of iatrogenesis include, but are not limited to

• Side effects of a treatment

• Over-recommendation of a drug, such as antibiotic resistance
• Complications from surgery, such as infection or nerve damage
• Drug interactions and drug-nutrient interactions
• Chance, or unexpected effects of a medication or treatment

• Medical error, such as a wrong prescription/misunderstood handwriting
• Negligence or incompetence, such as misdiagnosis or misunderstanding of patient complaint
• Patient experiencing anxiety or annoyance in the physician or treatment provider in relation to medical procedures or treatments
• Poor bedside manner that upsets the patient
• Unnecessary treatment for profit

The Mayo Clinic reports that almost 70% of Americans are taking at least one prescription medication.² For health-minded people, over-medicalization is a concern for more than one reason, in no small part because of risk of harms, such as known or expected side-effects and even unknown nutrient deficiencies. While many drugs have never been studied to evaluate which important nutrients they deplete, we do know the risks of taking many commonly prescribed medications.

Here is a list of drug-nutrient depletions/interactions as published pharmacist Jerry Hickey. ³

We know that drugs cause nutrient depletions, however their safety profile does not need to include research into unknown drug-nutrient depletions. Nor do medical doctors make a habit of recommending supplementation when patients are taking certain medications.

Heart Health and Statin Medications

Statin medications are among the most commonly prescribed and their prescription is becoming more routine, even for younger and healthy patients⁴. The New Heart Disease and Stroke Prevention Guidelines for Doctors’ were released in November 2013 by the American Heart Association and the American College of Cardiology. From the title, these guidelines sound helpful, as they are basically recommendations for healthcare providers across the nation created through years of scientific research.  Some could say the research they focused on was extremely biased, promoting statin medications for children and healthy adults, who could be managed through diet and safer nutrient alternatives. The guidelines quote⁴: Cholesterol-lowering HMG-COA reductase Inhibitors, commonly known as statin drugs, could be prescribed to an estimated 33 million Americans without cardiovascular disease who have a 7.5 percent or higher risk for a heart attack or stroke within the next 10 years, including younger, overweight people who are otherwise still healthy. They are also recommended for people 1) with a history of heart attack, stroke or blood vessel condition such as chronic artery disease, 2) 21 and older who have a very high level of bad cholesterol (190 mg/dL or higher) and 3) Type 1 or Type 2 diabetes who are 40 to 75 years old. Whether or not statin medications are effective in these groups or not still puts the population at risk for suffering side effects from the medications themselves. Side effects also need to be treated. Here are the common side effects⁵ associated with Statin medication⁶ and some correlating nutrient deficiencies.

• Muscle aches, tenderness, weakness (myalgia) or inflammation (myositis) - Depletes CoQ10, Vitamin D, Magnesium
• Drowsiness - Depletes CoQ10
• Dizziness - Depletes CoQ10
• Forgetfulness - Depletes CoQ10, L-Carnitine
• Abdominal cramping or pain - Depletes CoQ10, Magnesium

CoEnzyme Q10 Deficiencies

CoEnzyme Q10 (CoQ10) deficiency can also lead to heart failure, hypertension, arrhythmias, cardiomyopathy, and atherosclerosis, hyperthyroidism and male infertility6. A deficiency in CoQ10 leads to fatigue, mental confusion, tired, heavy and stiff muscles, shortness of breath and forgetfulness⁶.

While these side effects are well known, what is not known by patients and physicians alike, is these side effects are the result of drug-induced nutrient depletions. Even more important is that combination prescribing, a drug and a nutrient could potentially alleviate side effects from medications, reducing the burden on both patient and doctor. For instance, statin or cholesterol medication depletes an innate energy nutrient called CoQ10⁷. While the literature has been clear on this since at least 2005, it has never been deemed “strong enough” to warrant the recommendation of CoQ10 for all or even a portion of cholesterol or heart patients⁸. Medical Science Monitor published just this month, a Randomized Clinical Trial showing that CoQ10 supplementation (50 mg twice daily) effectively reduced mild to moderate statin-induced muscular symptoms in 75% of the test subjects, effectively helping people complete their daily activities without pain⁹.

In patients who have coronary artery disease and using statin therapy, CoQ10, at 300mg per day has been shown to reduce the levels of inflammatory markers Tumor Necrosis Factor-αlpha and increase antioxidant status (Vitamin E, superoxide dismutase, catalase, and glutathione peroxidase as compared to the placebo group at week 12 and week 429. Therefore CoQ10 supplementation at 300 mg/d significantly enhances antioxidant enzymes activities and lowers inflammation in patients who have CAD during statins therapy, which is protective for people with this deadly disease.

L-Carnitine Deficiency

One hundred and two patients meeting the American College of Rheumatology criteria for FMS were randomized into the study. The treatment consisted of 2 capsules/day of 500 mg L-Carnitine or placebo plus one intramuscular (i.m.) injection of either 500 mg L-Carnitine or placebo for 2 weeks. During the following 8 weeks the patients took 3 capsules daily containing either 500 mg L-Carnitine or placebo. The "total myalgic (muscle pain) score" and the number of positive tender points declined significantly and equally in both groups until the 6th week of treatment. After the 10th week, a statistically significant improvement in depression and musculo-skeletal pain resulted in the L-Carnitine group. Significantly larger improvements in quality of life were observed in L-Carnitine group than in placebo group for most parameters. Therefore L-Carnitine improved pain, mood and quality of life in fibromyalgia patients¹⁰.

Vitamin D3 Deficiency

One study found Vitamin D3 deficiency was most common among Arab and Indo-Pakistani, veiled and non-veiled, as compared to Caucasian pain and fibromyalgia patients. Once the pain patients were supplement with Vitamin D, this treatment resulted in clinical improvement in 90% of patients¹¹. In 2009 study published in the Journal of Clinical Rheumatology found that 74% of fibromyalgia/muscle pain patients were deficient in Vitamin D3. Treatment resulted in clinical improvement in 90% of patients¹².

Some research studies will mislead the physician by celebrating short term increases of plasma Vitamin D in conjunction with the onset of statin use. This is likely because the medicine drives the available form from of Vitamin D the liver before it depletes it. Longer term, and therefore more important relevant studies show that for instance, low serum 25 (OH) vitamin D levels (under 32 ng/mL) are also involved with painful inflammation of the muscles with statin use¹³. This was shown to be reversible with the increase of Vitamin D status through supplementation¹³. Of the 82 vitamin-D-deficient, myalgic patients taking statins, 38 were given vitamin D (50,000 I.U. /week. After 12 weeks, serum vitamin D went from 20 to 48 (normal range 30-100) and a decrease of muscle pain in 92% of the subject¹⁴. Researchers concluded that muscle pain in statin-treated patients with concurrent vitamin D deficiency correct the drug-nutrient interaction’s painful side effect between vitamin D deficiency and taking statin medications for high cholesterol.

Statins drugs deplete vital nutrient CoQ10, but they are also being researched for their long term depletions of several essentials fatty nutrients such as Omega 3 fatty acids, Vitamin D, Lutein and Vitamin E. Due to these statin’s are being studied for their risks of developing immune issues and Myositis-myalgia (Vitamin D deficiency and Omega 3 fatty acids), macular degeneration (Lutein deficiency and omega 3 fatty acids), accelerated aging (Vitamin E and Omega 3 fatty acids) and other inflammatory diseases of the heart, brain, pancreas, liver and arteries (likely nutrient combinations). If we knew more about which drugs deplete which nutrients, such as the effects of statins on L-Carnitine, we would all be able to make a better science of dietary supplementation. As it is, only the experts have access to this random slew of evidence, and depending on which expert you reach out to, they may not have the entire picture.

1. http://www.cdc.gov/nutritionreport/pdf/exesummary_web_032612.pdf
2. http://newsnetwork.mayoclinic.org/discussion/nearly-7-in-10-americans-take-prescription-drugs-mayo-clinic-olmsted-medical-center-find/
3. http://www.invitehealth.com/Drug-Induced-Nutrient-Depletion.html
4. http://www.heart.org/HEARTORG/Conditions/Understanding-the-New-Prevention-Guidelines_UCM_458155_Article.jsp
5. http://www.webmd.com/cholesterol-management/side-effects-of-statin-drugs
6. http://www.mayoclinic.org/drugs-supplements/coenzyme-q10/evidence/hrb-20059019
7. Skarlovnik A, Janić M, Lunder M, Turk M, Sabovič M. Coenzyme Q10 Supplementation Decreases Statin-Related Mild-to-Moderate Muscle Symptoms: A Randomized Clinical Study. Med Sci Monit. 2014 Nov 6;20:2183-8.
8. Nawarskas JJ.HMG-CoA reductase inhibitors and coenzyme Q10. Cardiol Rev. 2005 Mar-Apr;13(2):76-9.
9. Lee BJ, Tseng YF, Yen CH, Lin PT. Effects of coenzyme Q10 supplementation (300 mg/day) on antioxidation and anti-inflammation in coronary artery disease patients during statins therapy: a randomized, placebo-controlled trial. Nutr J. 2013 Nov 6;12(1):142.
10. Rossini M, Di Munno O, Valentini G, Bianchi G, Biasi G, Cacace E, Malesci D, La Montagna G, Viapiana O, Adami S. Double-blind, multicenter trial comparing acetyl l-carnitine with placebo in the treatment of fibromyalgia patients. Clin Exp Rheumatol. 2007 Mar-Apr;25(2):182-8.
11. Badsha H, Daher M, Ooi Kong K. Myalgias or non-specific muscle pain in Arab or Indo-Pakistani patients may indicate vitamin D deficiency. Clin Rheumatol. 2009 Aug;28(8):971-3. doi: 10.1007/s10067-009-1146-7. Epub 2009 Mar 10.
12. Ahmed W, Khan N, Glueck CJ, Pandey S, Wang P, Goldenberg N, Uppal M, Khanal S. Low serum 25 (OH) vitamin D levels (<32 ng/mL) are associated with reversible myositis-myalgia in statin-treated patients. Arch Intern Med. 2008 Jun 9;168(11):1228-9.
13. Glueck CJ, Abuchaibe C, Wang P. Symptomatic myositis-myalgia in hypercholesterolemic statin-treated patients with concurrent vitamin D deficiency leading to statin intolerance may reflect a reversible interaction between vitamin D deficiency and statins on skeletal muscle. Med Hypotheses. 2011 Oct;77(4):658-61. doi: 10.1016/j.mehy.2011.07.007. Epub 2011 Jul 29.
14. Mergenhagen K, Ott M, Heckman K, Rubin LM, Kellick K. Low vitamin D as a risk factor for the development of myalgia in patients taking high-dose simvastatin: a retrospective review. Clin Ther. 2014 May;36(5):770-7. doi: 10.1016/j.clinthera.2014.02.023. Epub 2014 Apr 16.

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