Most people today think they know what cholesterol is, where it comes from, and what it does.  If you follow the popular media or most diet books, cholesterol is a deadly poison that comes from food which clogs arteries and causes heart attacks.  Like most things having to do with the human body, however, the role of cholesterol is much more complicated than this simple picture suggests.  In fact, all these assumptions are so oversimplified that they are flat-out wrong.

Myth #1: Cholesterol has no beneficial effects

The most basic misconception is that cholesterol is some sort of toxic substance that has only negative effects on the body.  Nothing could be further from the truth.  In fact, most of the cholesterol circulating in your blood is actually produced by the body instead of being derived from your food.  It is a necessary component of cell membranes and a precursor for many hormones.  It also plays a role in digestion in the synthesis of bile acids.

Cholesterol is synthesized in the liver and intestines from a substance called Acetyl-Coenzyme A (or Acetyl-CoA).  Acetyl-CoA is vital to aerobic respiration, helping extract energy from food.  All cell membranes contain cholesterol, where it regulates their flexibility and viscosity.  Cholesterol also helps regulate the passage of material across the membrane.  On the one hand, it reduces cell membrane permeability to various charged ions, while on the other it is part of the active transport mechanism that incorporates certain large molecules into cells.

Many hormones use cholesterol as a precursor.  The body uses cholesterol as the raw material for all steroid hormones.  Steroid hormones are involved in an enormous variety of signaling pathways in the body.  Hormones like aldosterone and cortisol regulate blood pressure, blood volume and stress responses.  The primary female sex hormones, estrogens and progesterone are also derived form cholesterol, as are the male sex hormones, testosterone and dihydrotestosterone.  It can also be converted by enzymes into vitamin D.

In addition to all these effects, the liver converts cholesterol to bile, which is necessary for digestion.  Bile makes fats in food soluble and aids in the absorption of fat by the intestines.  Bile is also necessary for the absorption of the fat-soluble vitamins, including vitamins A, D, E and K.

Myth #2: People with high cholesterol have short lives

The idea that high cholesterol can shorten lives is based on the erroneous assumption that people with elevated cholesterol inevitably develop cardiovascular diseases and therefore die earlier than others.  The reality is that high cholesterol has effects that vary by person and this assumption has not been demonstrated.

One meta-analysis of many different studies showed that studies which did not support a link between high cholesterol and high mortality have been systematically under-reported and ignored[1].  In some studies, groups that had cholesterol-lowering intervention had higher mortality than control groups.  This may be either due to possible beneficial effects of cholesterol[2] or it may be due to the side effects of the medications used to control cholesterol[3].  The side effects of statins, the drugs most often used to control cholesterol levels can be serious, and need to be balanced with the potential benefit of lowering cholesterol.  Some of these side effects include serious problems like muscular damage, liver damage, and kidney failure, especially when a statin is used with certain other medications[4].

Myth #3: High cholesterol causes heart disease

Cholesterol and heart disease are commonly linked, and have been ever since the discovery of the disease atherosclerosis.  “Athero-”refers to a soft gruel-like deposit and “sclerosis” means the process of becoming hardened, so the term indicates soft deposits are first laid down in a place they shouldn’t be (like the artery walls) and then become hardened over time.  The term “arteriosclerosis,” which literally means “hardened arteries,” is often used interchangeably.

Cholesterol crystals are often found at the center of the plaques that form in atherosclerosis.  This has been taken to indicate that high blood cholesterol causes these plaques, in turn causing narrowing of the arteries and eventually leading to complete blockage and heart disease.

The difficulty is that studies are not demonstrating that these changes are due to high cholesterol levels.  The concentration of cholesterol in the blood is not associated directly with heart disease in people with family histories of high cholesterol[5].  In one study, in fact, those with the highest cholesterol levels had the lowest risk of heart disease[6].

Emerging evidence implicates chronic inflammation in the etiology of cardiovascular disease.  According to the American Heart Association, “high-sensitivity C-reactive protein (hs-CRP) levels are an independent marker of cardiovascular disease risk.”[7] And, elevated homocysteine levels were associated with increased risk for mortality in patients with coronary artery disease.[8]

Myth #4: Cholesterol levels are an accurate measure of heart disease

Talking about your cholesterol count is now almost as common as discussing your golf score.  In both, the convention is that the lower the number, the better you are.  This assumption is again not demonstrated by the science.  Data from the landmark Framingham Heart Study revealed that the distribution of cholesterol levels among individuals that had a heart attack and those that did not essentially mirrored each other.  While cholesterol is involved to some degree in the development of arterial plaque, it alone is not the problem.

Most heart attacks occur in people who have “normal” cholesterol.  Using cholesterol as the predictor of a future heart attack is not even as good as flipping a coin.  In a very large study looking at the lipid numbers of more than 136,000 people admitted to hospitals with coronary artery disease, more than 70% of those individuals had LDL cholesterol numbers in the “normal” range, and 50% had numbers considered in an “optimal” range.[9]

Much more important than total cholesterol, HDL and LDL cholesterol are the various sub-particles.  Cholesterol is carried in the blood in a variety of different proteins.  Each of these particles contains cholesterol, triglycerides and lipoproteins.  HDL cholesterol (“good”) has different lipoproteins than LDL cholesterol (“bad”).  Within each class, the particles differ in size and density.  Simply measuring LDL tells nothing about the particle size or number.  The ability of cholesterol to penetrate the arterial lining is dependent on the amount of inflammation present, type of lipoprotein carrying it, the particle size and number rather than on the level of cholesterol in the blood.  Two of the most important sub-particles are: Apolipoprotein (apo) B, a component of LDL and apo A-1, a component of HDL.  Several international studies have concluded “the apo B/A-1 ratio was the most important risk factor” and its “predictive power is superior to…any other lipid parameter or ratio”.[10]

The best assessment of your risk for future heart attack is to measure the actual disease process, not just a surrogate marker.  In the past, this would have meant an invasive procedure like a coronary catheterization that carries a not inconsequential risk.  More recently calcium scoring by high speed CT scan has been promoted but there are concerns about the amount of radiation exposure.  What is one to do?  There is another option:  carotid intima-media thickness measurement using carotid ultrasound.  The value of this technology has been recognized by the American Heart Association, the American College of Cardiology and the American Society of Echocardiographers for the early detection of heart disease is asymptomatic individuals.  A study out of the Mayo clinics found CIMT superior to calcium scoring, concluding that “subclinical vascular disease can be detected by CIMT in young to middle-aged patients with a low Framingham Risk Score and a Coronary Artery Calcium Score of zero”[11]

Myth #5: Everyone should be on prescriptions to control cholesterol

This scenario would certainly provide considerable benefit to the financial balance sheets of pharmaceutical companies that make statin drugs, but the public health benefits are somewhat more dubious.  Statin drugs deplete coenzyme-Q10, which is central to cellular energy production and heart health.  They can also cause muscle pains and weakness, flu-like symptoms, liver dysfunction, peripheral neuropathy, cognitive impairments, total global amnesia and interfere with neuro-synaptic transmissions in the brain.

Although some statin drugs, most notably Lipitor, have been shown to lower heart attack risk and lower cholesterol, it is now believed that they are two independent effects.  The latest scientific information suggests that statins reduce heart attack risk by reducing silent inflammation; the same risk reduction mechanism attributed to fish oil, stress reduction and healthy lifestyles.  All of the latter do not carry the potential risk of statin side effects and are quite a bit less costly to implement.  Several studies comparing omega-3 fish oils to statins demonstrate significant reduction in all cause mortality in heart failure patients taking fish oil, but statins did not affect all cause mortality or cardiovascular admissions.

One drug, Zetia, is not absorbed and lowers cholesterol in the gut.  It has no effect on blood vessels or systemic inflammation and has failed to demonstrate any effect on the progression of atherosclerosis.  Recent studies have shown participants taking Ezitimibe (active ingredient in Zetia and Vytorin) may actually have an increased risk for cardiovascular events by increasing carotid intima-media thickness.[12]

A recent pharmaceutical industry sponsored study concluded that giving Crestor to people with normal cholesterol reduced the risk of cardiovascular events by 50%.[13] This reduction was attributed largely to the reduction of inflammation as measured by C-reactive protein.  This sounds impressive until one scrutinizes the raw data.  It turns out that the 50% percent risk reduction occurred in less than 3% of the study population.  In other words, there was no effect in more than 97% of participants.  Things that make you say: “Hmmm…”

Myth #6: “Zero-cholesterol, low-fat” foods are “heart healthy”

This is a myth that is heavily promoted by packaged food companies.  As mentioned, dietary cholesterol is not the source of most blood cholesterol.  By saying “low-fat” or “zero cholesterol” on the package, however, they hope to convince the consumer their product is good for your health and will protect your heart.

Unfortunately, this can be a very poor assumption.  Typically low fat means increased carbohydrates; and frequently highly refined carbohydrates and simple sugars.  The heart disease epidemic in the US mirrors our obesity epidemic.  These modern phenomena coincide with the dramatic increase in the consumption of sugar and other highly refined carbohydrates.  This excessive carbohydrate diet leads to excess insulin production and insulin resistance, predisposes to type-2 diabetes and metabolic syndrome, reduces the size of LDL and HDL particles and results in increased inflammatory cytokines.  Reading the standardized “Nutrition Facts” label is always a more-accurate source of nutritional information than claims made on the package.

Myth #7: Eggs are bad for you

On the contrary, a special edition published in the American Journal of Clinical Nutrition contained nine separate articles demonstrating the importance of high quality protein in the diet to maintain a healthy body composition.  A major finding was that inadequate protein in the diet contributes to increased risks for obesity, muscle wasting (sarcopenia) and chronic diseases.   Eggs are a source of all natural and very high quality protein that keeps you satisfied longer.  More than half of the eggs protein is found in the yolk.

Another recent study reported in the European Journal of Nutrition followed a group of overweight but otherwise healthy adults given 2 eggs daily for 12 weeks while on a calorie restricted diet.  A control group followed the same diet but avoided eggs altogether.  Both groups lost the same amount of weight and had drops in their blood cholesterol levels.   Lead researcher, Dr. Bruce Griffen, stated, “There is no convincing evidence to link an increased intake of dietary cholesterol or eggs with coronary heart disease through raised cholesterol.  Indeed, eggs make a nutritional contribution to a healthy, calorie restricted diet.  We have shown that when two eggs a day are eaten by people who are actively losing weight on a calorie restricted diet, blood cholesterol can still be reduced”[14]

Does all this mean that cholesterol is a scam, or that it is perfectly OK to eat all the saturated fat one wishes?  No.  The bottom line is this: cholesterol is necessary for normal function by the body.  Blindly reducing cholesterol levels without actually assessing the risk is not a wise course of action.  Villifying cholesterol in general obscures the wide variety of biological responses for which it is essential.  While some patients with established or advance coronary artery disease can indeed benefit from reducing cholesterol, others may not, and pharmaceutical interventions are not without risk.  Having a doctor that can accurately determine the cardiac risk through measurements like carotid intima-media thickness (CIMT), sub-particle lipid profiles such as the VAP panel or LPP test, and inflammatory markers gives the best chance of having guided, targeted intervention with optimal results.  The Institute of Medicine estimates that more than 90% of all cardiovascular disease is preventable through appropriate lifestyle modifications.

[1] Ravnskov U. Cholesterol lowering trials in coronary artery disease: frequency of citation and outcome. BMJ. 1992;305(6844):15-19.

[2] Ravnskov U. High cholesterol may protect against infections and atherosclerosis. QJM. 2003 Dec;96(12):927-34.

[3] Langsjoen PH, Langsjoen JO, Langsjoen AM, Lucas LA. Treatment of statin adverse effects with supplemental Coenzyme Q10 and statin drug discontinuation. Biofactors. 2005;25(1-4):147-52.

[4] United States Food and Drug Administration. Information on Simvastatin/Amiodarone. Accessed 2010, Jan 4

[5] Miettinen TA, Gylling H. Mortality and cholesterol metabolism in familial hypercholesterolemia. Long-term follow-up of 96 patients. Arteriosclerosis. 1988 Mar-Apr;8(2):163-7.

[6] Hopkins PN, Stephenson S, Wu LL, et al. Evaluation of coronary risk factors in patients with heterozygous familial hypercholesterolemia. Am J Cardiol. 2001 Mar 1;87(5):547-53.

[7] Americna Heart Association Scientific Sessions, 2008

[8] Mager A, Orvid K, et al. Impact of Homocysteine-Lowering Vitamin Therapy on Long-Term Outcome of Patients With Coronary Artery Disease. Am J Card. Vol 104, (6), Pages 745-749 (15 September 2009)

[9] Sachdeva A, Cannon C, et al. Lipid levels in patients hospitalized with coronary artery disease: An analysis of 136,905 hospitalizations in Get With The Guidelines. Am Heart J, Jan 2009 111-117

[10] Yusuf S, Hawken S, Ounpuu S, on behalf of the INTERHEART Study Investigators. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet. 2004;364:937-952.

[11] Carotid Intima-Media Thickness and Coronary Artery Calcium Score as Indications of Subclinical Atherosclerosis.  Mayo Clin Proc. March 2009 ; 84(3):229-233

[12] Tatlor A, Villines C, et al. Extended-release Niacin or Ezitimibe and Carotid Intima-Media Thickness. NEJM Nov 26, 2009 (22) Volume 361:2113-2122

[13] Ridker P, Danielson C, et al. Rosuvostatin to prevent vascular events in men and Women with Elevated CRP. NEJM Nov 20, 2008. (217) Volume 359:2195-2207

[14] Nicola L. Harman, Anthony R. Leeds and Bruce A. Griffin. Increased dietary cholesterol does not increase plasma low density lipoprotein when accompanied by an energy-restricted diet and weight loss. European Journal of Nutrition. Volume 47, Number 6, September, 2008.