Cholesterol 101

Overview:

Cholesterol is one of the human body’s most misunderstood, vilified, and yet essential molecules. The following article will introduce the molecule and why it is vital and clear up the confusion and fear surrounding it.

Key benefits and importance of cholesterol:

  • It is necessary for synthesizing and producing key hormones, including progesterone, testosterone, estrogen, and cortisol, as well as vitamin D.
  • It is the essential building block of every cell of your body, and it is critical for stabilizing every cell membrane.
  • It maintains the integrity of the cell membrane which encloses and protects the cells themselves.
  • The more cholesterol you have, the more your immune system benefits.
  • Cholesterol is the most important component and structural unit of cell membranes. (1) 
  • It ensures proper brain function as well as better cognitive function.(2) 
  • Cholesterol is a vital constituent for a normal functioning nervous system. It also plays an essential role in its development.(3) 
  • Cholesterol also acts as a natural anti-inflammatory agent.
  • Higher levels of cholesterol are associated with better immune systems.

 

Risks of Cholesterol:

  • Excessive cholesterol in the liver can lead to liver disease.
  • As a critical building block, when there are certain infections in the vessel walls, one defense against these infections or oxidated damage is using cholesterol to cover and protect the area. It’s important to note that it is not the cholesterol that causes the issue but the infection or oxidation damage.

You can now understand why cholesterol is essential for human health and life. It is so vital that all of our cells biosynthesize it. About 80% of total daily cholesterol production occurs in the liver and the intestines, with the brain, the adrenal glands, and the reproductive organs following.

A person weighing 150lb normally creates about 1,000mg of cholesterol per day. Most ingested cholesterol, however, is esterified (i.e., modified in the stomach by acid.), resulting in poor absorption in the gut.

The amount of cholesterol the body makes is regulated through homeostatic mechanisms that we are still trying to understand. Nonetheless, we know that dietary cholesterol affects, at most, a 10% variation in the amount of cholesterol in the system. Thus, eggs and other natural high cholesterol foods do not cause disease but improve your health and lower your risk of disease and mortality. (11)

The body has a recycling system for cholesterol. The liver excretes cholesterol into binary fluids, which are then stored in the gallbladder until it is later excreted in a non-esterified form (via bile) in the digestive tract. Typically ~50% of the cholesterol is reabsorbed by the small intestine back into the bloodstream.

One of the interesting aspects of cholesterol is that it is only minimally soluble in water. In other words, it dissolves in blood at exceedingly small concentrations. That is why the body wraps cholesterol in lipoproteins that allow them to be transported throughout the body. The lipoproteins are what we hear referred to when people talk about cholesterol. However, cholesterol is always the same molecule regardless of the lipoprotein. Some are carried in their native “free” alcohol form (the cholesterol-OH group facing the water surrounding the particles), while others as fatty acyl esters, also known as cholesterol esters, within the particles.

Very-low-density lipoprotein (VLDL)
Intermediate-density lipoprotein (IDL)
Low-density lipoprotein (LDL), and
High-density lipoprotein (HDL)

Interestingly, cholesterol is comprised of 11 oxygen molecules. In effect, cholesterol is a “sink” for excess oxygen, especially when oxidative stress starts rising. Cholesterol’s evolution alongside oxygen’s appearance on this planet was no accident. Cholesterol always rises in the presence of increased oxidative stress (especially when it involves increased hydrogen peroxide or H2O2), which rises as copper becomes bio-unavailable and iron becomes unbound, dominant, and more reactive in our metabolism.

Cholesterol is susceptible to oxidation. The liver oxidizes cholesterol into a variety of bile acids. These, in turn, are conjugated with glycine, taurine, glucuronic acid, or sulfate. A mixture of conjugated and nonconjugated bile acids and cholesterol is excreted from the liver into the bile. Approximately 95% of the bile acids are reabsorbed from the intestines, and the remainder is lost in the feces. This process of excretion and reabsorption forms the basis of the enterohepatic circulation, which is essential for the digestion and absorption of dietary fats.(4) 

Now, look at the history, myths, and the truth about cholesterol. Before we dive in, let’s revisit this idea of correlation vs. causation. If there is a correlation with something like cholesterol present, it may be a factor, but it isn’t the cause. Causation means it directly causes the aspect in consideration.

A great example is no direct evidence exists that elevated cholesterol causes heart disease. In fact, over half the people that die from heart attacks have normal cholesterol. Just because cholesterol is elevated in some people with coronary artery disease doesn’t mean it is the cause. (5)

For almost a century, medical research has shown that cholesterol is not the cause of plaque in coronary artery disease. In 1936, Landé and Sperry’s research found no correlation between serum cholesterol levels and the amount of plaque in the coronary arteries.(6) Since then, their observation has been confirmed in at least a dozen studies.

This study and numerous studies disprove the “Cholesterol Hypothesis.” The hypothesis postulates that high total cholesterol causes cardiovascular disease. It was introduced in the 1960s by the authors of the Framingham Heart Study. However, in their 30-year follow-up study published in 1987, the authors reported that ‘For each 1 mg/dl drop in TC (total cholesterol) per year, there was an eleven percent increase in coronary and total mortality. During the years following the report of the Framingham Heart Study, numerous studies revealed that high total cholesterol is not associated with future cardiovascular disease. (7) 

A systematic review of studies shows that high LDL-C actually lowers the rate of mortality in people over 60. This finding is inconsistent with the cholesterol hypothesis. (8) 

Rather than lowering mortality, the data shows that higher cholesterol results in substantially improved immune response throughout the body. As a result, not only does it protect against infections, but it also protects against atherosclerosis. (9) 

So it is not the mainstream narrative that serum cholesterol and lipoproteins influence the endothelium (a thin membrane that lines the inside of the heart and blood vessels) and lead to diseases. Instead, atherosclerosis and cardiovascular diseases are caused by the following issues:(10) (11) 

  • Infections
  • Oxidative stress & metabolic dysfunction
  • Nutritional deficiencies (namely mineral deficiencies)
  • Toxins
  • Heavy metals
  • Pharmaceutical drugs
  • Hypothyroidism and low testosterone
  • Hormonal imbalance in women – estrogen dominance makes women hypothyroid, leading to increased inflammation.
 

References:

  1. The Role of Cholesterol in Membrane Fusion
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4972649/
  2. Long-Term Increase in Cholesterol Is Associated With Better Cognitive Function: Evidence From a Longitudinal Study https://www.frontiersin.org/articles/10.3389/fnagi.2021.691423/full
  3. Cholesterol: Its Regulation and Role in Central Nervous System Disorders https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3483652/#:~:text=Cholesterol%20is%20a%20major%20constituent,essential%20for%20normal%20brain%20development
  4. https://en.wikipedia.org/wiki/Cholesterol
  5. LDL-C does not cause cardiovascular disease: a comprehensive review of the current literature https://www.tandfonline.com/doi/full/10.1080/17512433.2018.1519391
  6. Human atherosclerosis in relation to the cholesterol content of the blood serum. https://www.cabdirect.org/cabdirect/abstract/19361403668
  7. Cholesterol and mortality. 30 years of follow-up from the Framingham study https://pubmed.ncbi.nlm.nih.gov/3560398/
  8. Lack of an association or an inverse association between low-density-lipoprotein cholesterol and mortality in the elderly: a systematic review https://bmjopen.bmj.com/content/6/6/e010401
  9. High cholesterol may protect against infections and atherosclerosis https://academic.oup.com/qjmed/article/96/12/927/1533176
  10. DISPELLING THE CHOLESTEROL-HEART DISEASE MYTH https://www.hotzehwc.com/blog/cholesterol/dispelling-the-cholesterol-heart-disease-myth/
  11. Inflammation, not Cholesterol, Is a Cause of Chronic Disease https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5986484/
  12. Dietary cholesterol and the risk of cardiovascular disease in patients: a review of the Harvard Egg Study and other data https://pubmed.ncbi.nlm.nih.gov/19751443/

    Dietary cholesterol and cardiovascular disease: a systematic review and meta-analysis
    https://pubmed.ncbi.nlm.nih.gov/26109578/

    Associations of egg and cholesterol intakes with carotid intima-media thickness and risk of incident coronary artery disease according to apolipoprotein E phenotype in men: the Kuopio Ischaemic Heart Disease Risk Factor Study https://pubmed.ncbi.nlm.nih.gov/26864369/

    Dietary cholesterol provided by eggs and plasma lipoproteins in healthy populations https://pubmed.ncbi.nlm.nih.gov/16340654/

    Egg consumption and risk of coronary heart disease and stroke: dose-response meta-analysis of prospective cohort studies https://www.bmj.com/content/346/bmj.e8539

    A Prospective Study of Egg Consumption and Risk of Cardiovascular Disease in Men and Women https://jamanetwork.com/journals/jama/fullarticle/189529

    Egg consumption in relation to risk of cardiovascular disease and diabetes: a systematic review and meta-analysis https://pubmed.ncbi.nlm.nih.gov/23676423/

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