Cholesterol: Good Guy or Bad Guy?

January 11, 2024

Diet time is upon us and with diet always comes the question, what is my cholesterol level?  We have been taught cholesterol is the bad guy, but is it a bad guy or a good guy?  Like everything else in the body, we need a balance, not too high and not too low.

Cholesterol is Essential for Health and Life.

We need cholesterol in order to function normally.  The body naturally produces more cholesterol than most people consume daily from diet.  Cholesterol has 4 major functions in the body:

  • Regulating cell membranes
  • Serving as a precursor for the synthesis of our hormones
  • Necessary for synthesizing vitamin D
  • Serving as a precursor for bile acids which are essential for proper digestion and absorption of fats

Cholesterol insulates nerves and aids in the repair of injured tissues.  It is so essential, it makes up a significant percentage of human breast milk.

A far less known function of cholesterol in the body is it serves as an antioxidant.  As the name implies, antioxidant means something that works against oxidation which in turn results in decreased inflammation.  HDL cholesterol protects LDL cholesterol from oxidative damage.  LDL contains antioxidants such as ubiquinol-10, a-tocopherol (isomer of Vitamin E) and b-carotene to protect itself from oxidative damage and free radicals.  Could the presence of high cholesterol then be a powerful innate protective mechanism of the body?

Since more than half of those who suffer a heart attack have “normal” cholesterol levels, is the problem really cholesterol itself?

For over a century, cholesterol has been implicated in the pathogenesis of atherosclerosis and cardiovascular disease (CVD).  Therapy with statins has been widely used and promoted to prevent CVD, though statin therapy is now highly debated and comes with risks.  In a recent study, LDL-C does not cause cardiovascular disease: a comprehensive review of the current literature, three large reviews published by statin advocates have been reviewed in order to assess the current dogma and cholesterol CVD hypothesis.  What is the truth about cholesterol?  What is the truth about the cholesterol CVD hypothesis?

Cholesterol Hypothesis and Statin Treatment as A Safe Way to Lower CVD Risk Found Invalid

The authors of the study followed philosopher Karl Popper’s principle showing a theory can be shown to be untrue if falsified and applied that principle to the cholesterol hypothesis.  The following summarizes the key findings:

  • There is no association between the degree of atherosclerosis and total cholesterol (TC) levels
  • Cholesterol-lowering drug trials showed no exposure-response or benefit with lowered cholesterol levels
  • High total cholesterol (TC) levels do not cause CVD
    • The high TC causing CVD hypothesis came about in the 1960s by the publication of the Framingham Heart Study though at a 30-year study follow-up, they found…
      • “For each 1 mg/dl drop in TC per year, there was an 11% increase in coronary and total mortality.”
    • Total cholesterol and CVD association is absent, weak or inverse in many studies
    • There is a lack of association between high LDL-C levels and atherosclerosis
    • Elderly people with high LDL-C levels live the longest
    • Cholesterol-lowering drugs such as statins have not shown to lower the risk of CVD in trials
    • Statin treatment benefits have been exaggerated
    • There are significant side effects from statin therapy that have been minimized
    • A small percentage of familial hypercholesterolemia die prematurely and there was no difference between LDL-C levels between FH people with and without CVD

The conclusion of this study is:

“The idea that high cholesterol levels in the blood are the main cause of CVD is impossible because people with low levels become just as atherosclerotic as people with high levels and their risk of suffering from CVD is the same or higher. The cholesterol hypothesis has been kept alive for decades by reviewers who have used misleading statistics, excluded the results from unsuccessful trials and ignored numerous contradictory observations.”

It is estimated more than 200 million people in the world are on statin therapy though statins have shown serious side effects and unproven benefits.  Given this review, the authors suggest clinicians should abandon the use of statins and instead identify the underlying cause of CVD and target it for treatment.

Is LDL Really “Bad” Cholesterol?

LDL has become viewed as bad cholesterol though it has demonstrated protective benefits.

  • LDL carries antioxidants with a predominance of CoQ10 and vitamin E
  • A large study including nearly 140,000 patients with acute myocardial infarction (heart attack) showed at the time of hospital admission, those patients had LDL-C levels lower than normal
  • Lowering patients LDL levels further at 3-year follow-up showed a total mortality twice as high than those with higher LDL levels
  • What may explain this is infections and microorganisms could cause CVD and LDL inactivates them and serves as a protective mechanism. Supporting this is a study showing healthy people with low LDL had a significantly increased risk of cancer and infectious diseases
  • If high LDL levels were a significant cause of CVD, those with higher levels should have shorter lives though this was shown to be false in a systematic review of more than 68,000 people over the age of 60. The opposite was shown to be true as those with higher levels were shown to live the longest.

How Did LDL Cholesterol Come to Be the Bad Guy?

Oxidation in the body means oxygen is metabolized.  When this happens, it creates unstable molecules called free radicals.  These free radicals can then steal electrons from other circulating molecules in the body leading to the damage of cell membranes, DNA, proteins and lipids.  Oxidation in the body causes inflammation, accelerates atherogenesis, CVD and other chronic disease.

As previously mentioned, cholesterol serves as an antioxidant.  LDL contains antioxidants and HDL also protects LDL from oxidation.  LDL is particularly susceptible to oxidation and oxidized cholesterol correlates with CVD.  Oxidized LDL is a sensitive biomarker for atherosclerosis and a blood test called oxLDL can be helpful in assessing CVD risk.  High levels of oxLDL are associated with not only CVD progression but also impaired glucose homeostasis, insulin resistance, metabolic syndrome and untreated overt hypothyroidism.

If over half of people suffering a heart attack have “normal” cholesterol levels, what is the problem?

It is likely due to oxidized cholesterol LDL leading to inflammation.  Patients sustaining a heart attack have been found to have twice as high oxLDL levels compared with patients experiencing angina but no heart attack and four times as high as healthy controls.  Among patients with high cholesterol levels, the majority is almost entirely comprised by oxidized LDL.

A stronger predictor of CVD than LDL is high sensitivity C-reactive protein (hs-CRP), indicating systemic inflammation.  “A person with high levels of LDL-cholesterol but low levels of hs-CRP has a lower risk of a heart attack than a person with low levels of LDL-cholesterol but high levels of hs-CRP.”

How Do We Prevent and Eliminate Oxidized Cholesterol?

The underlying cause of CVD should always be sought and treated.  The following can lead to CVD via oxidation and inflammation.  It is important to know these are modifiable risk factors:

  • Poor diet
  • Tobacco use
  • Excessive alcohol
  • Excessive weight
  • Chronic illness
  • Dental infection
  • Stress
  • Sedentary lifestyle
  • High blood pressure
  • Environmental toxins
  • Vitamin deficiencies

Oxidation can occur in the body due to various causes.  Diet and cooking methods are a major source of this process.  Identifiable causes and the solutions for these causes are summarized in the following table from The Vilification of Cholesterol (for Profit?):

 

How Do We Predict Your Personal Cardiovascular Disease Risk?

At RMC, an advanced blood test panel called Cardio IQ is ordered on patients to help identify early cardiovascular risks to prevent high blood pressure, heart attacks, and strokes.  Addressing inflammation is key to defining and treating cardiovascular risk which is why this panel includes extensive direct and indirect markers of inflammation.  Vitamin deficiencies and evidence of chronic diseases are also evaluated at RMC.  With this information, specific abnormalities can be addressed, and cardiovascular risk can be decreased.

An extensive in-depth summary of the biomarkers included on the Cardio IQ panel and what can be done for elevated levels can be read here:

Assessing your cardiovascular risk before adverse events occur is critical to prevention.  In addition to the biomarkers on the Cardio IQ, the Coronary Calcium Scan (CCS) is a non-invasive CT scan utilized to predict your 5-year risk of having a cardiovascular event by identifying calcium within the coronary arteries of the heart.  The CCS is summarized in-depth here:

The Cleerly Scan is another non-invasive scan using coronary CT angiogram (CCTA) that works to identify early heart disease by generating an AI 3D model of the patient’s coronary arteries, vessel walls which clearly identifies and categorizes 4 different kinds of plaque.  This scan is more comprehensive than the CCS as it can stage and differentiate low-risk versus high-risk plaque.  Today, CCTA is considered the gold standard for the assessment of coronary artery disease.  At the time of this publication, the Cleerly Scan is not available in Pittsburgh but is in other major cities.

The differences between the two diagnostic tests are:

  • CCS measures how much calcium is present in the arteries of the heart using cardiac CT, showing calcified plaque.
  • Cleerly uses CCTA and AI software to identify not only total plaque volume but also different types of plaque in the arteries of the heart, not just calcified plaque.

Have an awesome day!   Dr. D and Drew Chernisky, PA-C

Posted in Cholesterol