Consumer Confusion about Cholesterol and Statin Drugs

Statin drugs remain controversial because they are often overprescribed and present side effects such as fatigue and muscle pain.

Few physicians advise their patients that statins deplete CoQ10 from the body.

Restoring healthy levels of CoQ10 through supplementation has been shown to alleviate side effects as well as reduce the symptoms of heart failure.

If you or someone you know is on a statin, this article can help the patient and their physician make more educated decisions.

Statins and Heart Disease

Heart disease encompasses a range of cardiac disorders that include:

• Chronic heart failure
• Coronary artery disease
• Valvular disease (such as aortic stenosis)
• Sudden heart attack

Maintaining healthy levels of cholesterol is one way to help lower these risks.

There are people who question the evidence for the causal role of LDL cholesterol in atherosclerotic disease.

There is also disagreement about exactly which patient populations benefit most from cholesterol-lowering-type drugs called statins.

Concerns raised about statin drugs include:

• In people without known heart disease, there does not appear to be a mortality benefit with statin drugs, and the harms can outweigh the benefits,^1,2
• Clinical trials of statins are largely industry-sponsored, and the original data in those studies are mostly unavailable to researchers,^2,3 and
• Lifestyle factors including tobacco usage, unhealthy diet, and sedentary lifestyle are thought to account for as much as 80% of cardiovascular risk.^2,4

The sum of published research shows that:

• Simple ways exist to diminish the most common statin-drug side effect,
• In high-risk individuals, statins do reduce heart disease deaths and mortality from other causes, and
• Comprehensive evaluation and control of cholesterol and other risk factors achieve the greatest reduction in heart disease risk.

Aging often results in an increase in cholesterol. This age-related increase in cholesterol is primarily composed of small, dense LDL particles, especially those oxidized, which promote the formation of harmful plaque in the arteries.

As the decades add up, the damage inflicted by these cholesterol particles injures blood vessels, eventually obstructing blood flow to the heart muscle, brain, and other organs.

If an aging individual with poor and worsening cholesterol does not want to make radical lifestyle and dietary changes, then proper statin drug therapy (usually at a much lower dose than commonly prescribed) should be considered.

Reducing Statin Side Effects

Cholesterol is carried through the blood by transporters called lipoproteins, of which LDL (low-density lipoprotein) is one.

Statins lead to robust reductions in LDL (“bad”) cholesterol and decreases in C-reactive protein, a marker of inflammation, including C-reactive protein and interleukin-6.⁷

Statins have clearly defined benefits for high-risk individuals, but their use in prevention in low-risk individuals is not supported by that science.

Researchers and clinicians have pointed out that in individuals at low risk of cardiovascular events, side effects of statins outweigh benefits.^1,8

Life Extension^® was among the first to note that statin drugs were being overprescribed, often at unnecessarily high doses.

Statins deplete the body’s levels of coenzyme Q10, which causes many outward side effects, like muscle pain (myalgias) along with potential multi-organ damage.

Evidence also shows that statins interfere with the synthesis of vitamin K2.^9,10

The encouraging news is muscle pain caused by statins can be significantly reduced with the addition of coenzyme Q10.^11-14

The statin-induced decrease in coenzyme Q10 and vitamin K2 can be corrected by taking supplemental CoQ10 and vitamin K2.

CoQ10 Provides Support

A meta-analysis published in 2018 combined the results of 12 randomized, controlled trials that included a total of 575 patients.

This study concluded that coenzyme Q10 (CoQ10) supplementation ameliorated the muscle pain, cramps, weakness, and tiredness associated with statin drugs. It also showed that statins reduce CoQ10 levels by 16%-54%.¹⁴

In high-risk individuals (which includes a significant portion of the aging population), statin drugs help protect against cardiovascular disease, ¹⁵ including coronary artery occlusion and cerebral vascular insufficiency. In some observational studies, statin use showed potential in slowing aortic stenosis progression.¹⁶ Statins also reduce CoQ10 levels.¹¹

Low CoQ10 blood levels have been associated with higher mortality in heart failure patients.¹⁷

Continuing research shows that CoQ10 supplementation can effectively boost levels of this heart-essential nutrient, improving outcomes for heart failure patients.

In a recent study, researchers selected 142 patients who developed heart failure while on statins.¹²

Of these patients, 94% had diastolic heart failure (inability of their left ventricle to relax normally and properly fill) and 6% had systolic heart failure (lack of their left ventricle contracting normally and pumping blood out into circulation).

The patients were taken off statins and put on an average dose of 300 mg/day of CoQ10. The study primarily used the ubiquinol form of CoQ10, which is more readily absorbed into the bloodstream than ubiquinone.

By the end of follow-up (mean 2.8 years) the number of patients who had no limitations of physical activity increased from 8% to an astounding 79%.

For the patients with diastolic heart failure who received CoQ10, at final follow-up:

• Approximately 34% had complete normalization of diastolic function,
• 60% had sustained improvement in diastolic function, and
• 25% showed improvement but not normalization of diastolic function.

For the patients who had systolic heart failure, ejection fraction increased by a mean of 12%.

Ejection fraction is the percentage of blood pumped out of the heart’s left ventricle with each beat. Measuring this percentage is essential to the proper evaluation and management of those with systolic heart failure.¹⁸

Why Early Statin Trials Were Short Term

Some critics of statins contend the research does not consistently show they reduce cardiovascular or all-cause mortality.

However, real-world obstacles stand in the way of long-term, placebo-controlled human trials designed to test the effects of statins or other interventions on mortality, which is the proof we need to establish a life-extending benefit.

A study evaluating human mortality would require many decades to produce meaningful results. Humans live longer than lab animals, which makes us more difficult to study, and makes such research prohibitively costly.

Other factors add to the complexity. People often change their diet, exercise, and lifestyle habits. Compliance with any nutritional or pharmaceutical intervention tends to be inconsistent. Additional confounding factors that are difficult to control are stress levels, environment, and individual genetics.

For these reasons, long-term, randomized, placebo-controlled trials of potentially life-extending interventions—such as statins—present an enormous challenge to the scientific community.

Newer Trials Show Reduced Mortality

But statin critics may be overlooking newer studies that are showing meaningful mortality benefits.

One large-scale meta-analysis published in 2016 showed that statins were significantly more effective for patients in reducing the odds of dying from coronary heart disease and from any cause, compared to control groups.²¹

Specifically, statin users had 31% lower odds of dying from coronary heart disease and 16% lower odds of dying from any cause, compared to controls.

20-Year Study Yields Robust Mortality Benefit

A study published in 2017 was one of the first to truly examine the impact of statin use over the long term.

This study analyzed evidence after the termination of a randomized, placebo-controlled statin trial. One arm of this study evaluated the effects of statins in men with LDL of 190 mg/dL or higher and without preexisting vascular disease.

This analysis divided a total of 5,529 men into two groups, those with LDL levels under 190 mg/dL and those with LDL levels at 190 mg/dL or higher.

The randomized, controlled phase of this trial was about five years and used a statin drug called pravastatin.

What makes this study significant is that the observational follow-up on patients was an additional 15 years, meaning the whole study population was followed for 20 years.²²

At the end of the 20-year follow-up, an analysis was done comparing the placebo group to men with LDL ≥ 190 mg/dL and originally assigned to the pravastatin group in the initial trial. Here are the findings over this 20-year period:

• The risk of coronary heart disease mortality was reduced by 28% in pravastatin drug users,
• Cardiovascular death was reduced by 25% and all-cause mortality by 18% respectively, in people remaining on pravastatin over this 20-year period.

In the participants whose LDL was lower than 190 mg/dL, pravastatin reduced the risk of coronary heart disease and major adverse cardiovascular events. The participants with LDL ≥190 mg/dL had greater reductions in cardiovascular and all-cause mortality from pravastatin treatment compared to placebo.

The average LDL cholesterol level dropped by 23.3% from its baseline value in the treatment group of those with LDL ≥190 mg/dL.

This 23.3% reduction is still a considerable distance from what is generally accepted as a healthy LDL range, which is below 100 mg/dL for primary prevention of cardiovascular disease in people with low risk.²³

For people with high risk, such as individuals who have already suffered a cardiovascular event, some experts recommended that they achieve LDL levels below 70 mg/dL.²⁴

If LDL cholesterol had been brought down even further in the patients in the 20-year study using pravastatin, the risk of cardiovascular events and all-cause mortality would likely have fallen with it.

It is important to note that these relatively recent studies were published after many decades of criticism were lodged against statin drugs.

No one questions the side effects statins can inflict. Much has to do with excess dosing and prescribing statins to patients who did not need them, and not advising patients to supplement with CoQ10 and vitamin K2.

Multiple Risk Factors for Cardiovascular Disease

There are some patients with high LDL cholesterol who do not have cardiovascular disease, while some with lower cholesterol do have it. These paradoxical findings have led some to downplay the risks posed by elevated LDL cholesterol. However, this does not mean that cholesterol plays no role in cardiovascular disease.

People sometimes forget that there are multiple risk factors contributing to the threat of every illness, and cardiovascular disease is no exception.

Scientific data accumulated over decades demonstrate that excess LDL cholesterol is one of the primary culprits.⁶

Impact of Apolipoprotein B

Apolipoprotein B is found on all non-HDL-cholesterol-carrying lipoprotein particles, such as LDL and VLDL.²⁵

High apolipoprotein B is a recognized marker for damage to arterial walls and risk of atherosclerosis. This is important because the basic laboratory tests for lipids, including LDL, HDL, and total cholesterol and triglycerides, often don’t give the full picture of cardiovascular disease risk.

Research on certain populations shows a correlation between maintaining lifetime low levels of apolipoprotein B and a roughly 90% decreased risk of coronary artery disease.²⁶

Elevated apolipoprotein B is a more reliable marker for cardiovascular disease than LDL,HDL, and total cholesterol.^6,27-29

Despite intensive educational efforts, apolipo-protein B blood tests are not routinely incorporated into primary care medicine. The tragic result is a failure to prevent heart attacks, strokes, and other occlusive arterial diseases.

For Life Extension^® readers, this problem was resolved when apolipoprotein B was added to the comprehensive Male and Female Panel blood tests they undergo each year.

Summary

Published data define the importance of maintaining optimal LDL and HDL cholesterol levels to lower heart disease risk.

Statins can help keep cholesterol levels in optimal ranges in those for whom diet and lifestyle measures aren’t enough.

To achieve the most significant heart disease risk reduction, one must monitor and address every risk factor related to heart diseases. That includes testing for apolipoprotein B and other atherogenic risk factors.

Controlling the vascular damage created by elevated LDL cholesterol levels is challenging. Altering one’s diet to reduce excess saturated fat intake might enable a lower statin drug dose to achieve optimal cholesterol levels.^4,36-38

Anyone using a statin must ensure their coenzyme Q10 levels are not compromised.

This can be achieved by taking 100-200 mg a day of CoQ10, preferably the ubiquinol form. CoQ10 should be taken with the heaviest meal of the day that contains some fat, to facilitate its absorption.

Those with heart failure usually need to take around 400 mg of ubiquinol a day to achieve optimal CoQ10 blood levels.

Recent data also point to the value of vitamin K2 use with statin drugs. For those interested in supplementing with vitamin K who are taking Coumadin^® or Jantoven^® (warfarin), please discuss with your doctor first. The box on the next page describes what some warfarin users are doing to supplement with low-dose vitamin K2 under physician supervision.

These steps can lessen the side effects of statins and help to lower the risk of cardiovascular disease.

If you have any questions on the scientific content of this article, please call a Life Extension^® Wellness Specialist at 1-866-864-3027.

References

1. Available at: http://www.thennt.com/nnt/statins-for-heart-disease-prevention-without-prior-heart-disease/. Accessed July 8, 2020.
2. Hobbs FD, Banach M, Mikhailidis DP, et al. Is statin-modified reduction in lipids the most important preventive therapy for cardiovascular disease? A pro/con debate. BMC Med. 2016 Jan 14;14:4.
3. Available at: https://www.pharmaceutical-journal.com/news-and-analysis/opinion/insight/cholesterol-lowering-statin-therapy-for-healthy-people-is-not-as-simple-as-yes-or-no/20202407.article. Accessed July 8, 2020.
4. Sacks FM, Lichtenstein AH, Wu JHY, et al. Dietary Fats and Cardiovascular Disease: A Presidential Advisory From the American Heart Association. Circulation. 2017 Jul 18;136(3):e1-e23.
5. Uranga RM, Keller JN. Diet and age interactions with regards to cholesterol regulation and brain pathogenesis. Curr Gerontol Geriatr Res. 2010;2010:219683.
6. Ference BA, Kastelein JJP, Ginsberg HN, et al. Association of Genetic Variants Related to CETP Inhibitors and Statins With Lipoprotein Levels and Cardiovascular Risk. JAMA. 2017 Sep 12;318(10):947-56.
7. Milajerdi A, Sadeghi A, Mousavi SM, et al. Influence of Statins on Circulating Inflammatory Cytokines in Patients With Abnormal Glucose Homeostasis: A Meta-analysis of Data From Randomized Controlled Trials. Clin Ther. 2020 Feb;42(2):e13-e31.
8. Available at: http://utswmed.org/medblog/statins-debate/. Accessed July 8, 2020.
9. Okuyama H, Langsjoen PH, Hamazaki T, et al. Statins stimulate atherosclerosis and heart failure: pharmacological mechanisms. Expert Rev Clin Pharmacol. 2015 Mar;8(2):189-99.
10. Parker BA, Thompson PD. Effect of statins on skeletal muscle: exercise, myopathy, and muscle outcomes. Exerc Sport Sci Rev. 2012 Oct;40(4):188-94.
11. Derosa G, D’Angelo A, Maffioli P. Coenzyme q10 liquid supplementation in dyslipidemic subjects with statin-related clinical symptoms: a double-blind, randomized, placebo-controlled study. Drug Des Devel Ther. 2019;13:3647-55.
12. Langsjoen PH, Langsjoen JO, Langsjoen AM, et al. Statin-Associated Cardiomyopathy Responds to Statin Withdrawal and Administration of Coenzyme Q10. Perm J. 2019;23:18-257.
13. Littlefield N, Beckstrand RL, Luthy KE. Statins’ effect on plasma levels of Coenzyme Q10 and improvement in myopathy with supplementation. J Am Assoc Nurse Pract. 2014 Feb;26(2):85-90.
14. Qu H, Guo M, Chai H, et al. Effects of Coenzyme Q10 on Statin-Induced Myopathy: An Updated Meta-Analysis of Randomized Controlled Trials. J Am Heart Assoc. 2018 Oct 2;7(19):e009835.
15. Available at: https://www.uptodate.com/contents/management-of-low-density-lipoprotein-cholesterol-ldl-c-in-the-secondary-prevention-of-cardiovascular-disease. Accessed July 29, 2020.
16. Griffin BP. Statins in aortic stenosis: new data from a prospective clinical trial. J Am Coll Cardiol. 2007 Feb 6;49(5):562-4.
17. Available at: https://www.uptodate.com/contents/statin-therapy-in-patients-with-heart-failure. Accessed July 8, 2020.
18. Available at: https://www.uptodate.com/contents/tests-to-evaluate-left-ventricular-systolic-function. Accessed July 8, 2020.
19. Available at: https://patents.google.com/patent/US4933165A/en. Accessed July 8, 2020.
20. Available at: https://www.nutraceuticalsworld.com/contents/view_online-exclusives/2016-04-07/more-education-needed-to-bolster-coq10-market/. Accessed June 29, 2020.
21. Lu Y, Cheng Z, Zhao Y, et al. Efficacy and safety of long-term treatment with statins for coronary heart disease: A Bayesian network meta-analysis. Atherosclerosis. 2016 Nov;254:215-27.
22. Vallejo-Vaz AJ, Robertson M, Catapano AL, et al. Low-Density Lipoprotein Cholesterol Lowering for the Primary Prevention of Cardiovascular Disease Among Men With Primary Elevations of Low-Density Lipoprotein Cholesterol Levels of 190 mg/dL or Above: Analyses From the WOSCOPS (West of Scotland Coronary Prevention Study) 5-Year Randomized Trial and 20-Year Observational Follow-Up. Circulation. 2017 Nov 14;136(20):1878-91.
23. Available at: https://medlineplus.gov/cholesterollevelswhatyouneedtoknow.html. Accessed July 8, 2020.
24. Nayor M, Vasan RS. Recent Update to the US Cholesterol Treatment Guidelines: A Comparison With International Guidelines. Circulation. 2016 May 3;133(18):1795-806.
25. Shapiro MD, Fazio S. Apolipoprotein B-containing lipoproteins and atherosclerotic cardiovascular disease. F1000Res. 2017;6:134.
26. Tabas I, Williams KJ, Boren J. Subendothelial lipoprotein retention as the initiating process in atherosclerosis: update and therapeutic implications. Circulation. 2007 Oct 16;116(16):1832-44.
27. Levinson SS. Comparison of apolipoprotein B and non-high-density lipoprotein cholesterol for identifying coronary artery disease risk based on receiver operating curve analysis. Am J Clin Pathol. 2007 Mar;127(3):449-55.
28. Contois JH, McConnell JP, Sethi AA, et al. Apolipoprotein B and cardiovascular disease risk: position statement from the AACC Lipoproteins and Vascular Diseases Division Working Group on Best Practices. Clin Chem.2009 Mar;55(3):407-19.
29. Trompet S, Packard CJ, Jukema JW. Plasma apolipoprotein-B is an important risk factor for cardiovascular disease, and its assessment should be routine clinical practice. Curr Opin Lipidol. 2018 Feb;29(1):51-2.
30. Diffenderfer MR, Schaefer EJ. The composition and metabolism of large and small LDL. Curr Opin Lipidol. 2014 Jun;25(3):221-6.
31. Lorenzatti AJ, Toth PP. New Perspectives on Atherogenic Dyslipidaemia and Cardiovascular Disease. Eur Cardiol. 2020 Feb;15:1-9.
32. Chouinard JA, Grenier G, Khalil A, et al. Oxidized-LDL induce morphological changes and increase stiffness of endothelial cells. Exp Cell Res. 2008 Oct 1;314(16):3007-16.
33. Bergheanu SC, Bodde MC, Jukema JW. Pathophysiology and treatment of atherosclerosis : Current view and future perspective on lipoprotein modification treatment. Neth Heart J. 2017 Apr;25(4):231-42.
34. Available at: https://www.merckmanuals.com/professional/cardiovascular-disorders/arteriosclerosis/atherosclerosis. Accessed February 26, 2020.
35. Available at: https://www.sciencedirect.com/topics/medicine-and-dentistry/foam-cell. Accessed February 26, 2020.
36. Chiu S, Williams PT, Krauss RM. Effects of a very high saturated fat diet on LDL particles in adults with atherogenic dyslipidemia: A randomized controlled trial. PLoS One. 2017;12(2):e0170664.
37. Ulven SM, Leder L, Elind E, et al. Exchanging a few commercial, regularly consumed food items with improved fat quality reduces total cholesterol and LDL-cholesterol: a double-blind, randomised controlled trial. Br J Nutr. 2016 Oct;116(8):1383-93.
38. Jafari M, Ebrahimi R, Ahmadi-Kashani M, et al. Efficacy of alternate-day dosing versus daily dosing of atorvastatin. J Cardiovasc Pharmacol Ther. 2003 Jun;8(2):123-6.
39. Orkaby AR, Driver JA, Ho YL, et al. Association of Statin Use With All-Cause and Cardiovascular Mortality in US Veterans 75 Years and Older. JAMA. 2020 Jul 7;324(1):68-78.