When I first sat down to write about cholesterol a few weeks ago, I had been drinking the cholesterol cool-aide like everyone else.  My dive into the research, however, was  a frustrating experience of Alice-In-Wonderland-Logic.  Here’s a typical example of clear results and a puzzling conclusion:


Forty studies (17 cohorts in 19 publications with 361,923 subjects and 19 trials in 21 publications with 632 subjects) published between 1979 and 2013 were eligible for review. Dietary cholesterol was not statistically significantly associated with any coronary artery disease (4 cohorts; no summary RR), ischemic stroke (4 cohorts; summary RR: 1.13; 95% CI: 0.99, 1.28), or hemorrhagic stroke (3 cohorts; summary RR: 1.09; 95% CI: 0.79, 1.50).


Reviewed studies were heterogeneous and lacked the methodologic rigor to draw any conclusions regarding the effects of dietary cholesterol on CVD risk. Carefully adjusted and well-conducted cohort studies would be useful to identify the relative effects of dietary cholesterol on CVD risk.  – The American Journal of Clinical Nutrition 2015

That’s right the researchers found NO statistically significant association between cholesterol and ANY form of cardiovascular disease and yet they conclude that no conclusion can be drawn from the results.  Really?! No conclusion can be drawn?

I would love to tell you that this is an isolated example, but pretty much every study for decades that finds evidence that conflicts with the establishment dogma on cholesterol goes weak in the knees and adds a conclusion the varies from apologizing to scratching of the head, to acknowledging the results but stating that it is somehow an error because “we all KNOW that cholesterol is the cause of heart attacks.”  How do we know this?  Everyone says it is so.

This reminds me of the Asch conformity experiments from the 1950’s.  When 7 study participants in a row gave the wrong answer out loud (on purpose) the 8th participant (not in on the deception) was much more likely to also give the wrong answer.  When interviewed afterwards, the 8th participant often explained that they just went along even though they were pretty certain the answer was wrong.  Imagine how much more pressure there is on the “8th participant” if their career, research funding, or big pharma support could be at risk by making a fact-supported conclusion that cholesterol and heart disease are not related.

Well dear reader I guess this is where I come in.  I have nothing riding on the results and would have been fine with studies that clearly showed the connection between cholesterol and heart disease, but the evidence just isn’t there.  Because I have nothing at stake (and I generally don’t give a damn for public opinion) I will make conclusions based on the facts even if those conclusions fly in the face of the strongly held establishment position.  N.B. – If I’m found floating face down in a river in 2019 please alert the authorities to the possibility of foul play. Thank you kindly.

The Cholesterol Hypothesis

For the past 50 years or more we have been told repeatedly that elevated levels of cholesterol (as measured by lipoproteins in blood) result in the accumulation of cholesterol along the walls of the arteries.  This accumulation forms a plaque.  Plaques eventually close off arteries and are responsible for cardiovascular disease (CVD) which is mainly heart attack and stroke, but includes variations such as heart failure (heart can’t pump hard enough) and Arrhythmia (abnormal heart rhythm).  Some forms of the hypothesis also include high blood pressure and blood clotting, but the number one culprit is always cholesterol because cholesterol is found in all plaque.

Throughout this article I will refer to cholesterol and various lipoproteins such as LDL and HDL without much explanation – fortunately I explained these terms in the previous article “Cholesterol or Lipoprotein?”

You Know Your Hypothesis Is In Trouble When….

The cholesterol hypothesis is what I call a straight line cause and effect.  The more cholesterol you have the faster you clog up and die.  Except that it is not true.  “Nearly 75 percent of patients hospitalized for a heart attack had cholesterol levels that would indicate they were not at high risk for a cardiovascular event.”  That’s from a UCLA study in 2009.  The other dirty little secret is that many of us with high cholesterol never have a heart attack.

Using the generally accepted levels in the U.S. (less than 200 milligrams per deciliter or mg/dL which equates to 5.172 mmol/L or millimole per liter) and Europe (below 5 mmol/L which equates to 193 mg/dL) we find that 50% of people with low cholesterol have heart attacks and 50% of people with high cholesterol do NOT.   Wait, what?!  Next you’re gonna tell me that raised cholesterol levels don’t result in more strokes!  Um, well cholesterol does not/not increase your stroke risk (unless it’s too low).

That should be enough for the medical profession to walk away from this terrible model of prediction and search for something better.  Instead doctors rush into the breach and attempt to shore up the defenses of the cholesterol hypothesis.

It’s Not TOTAL Cholesterol, it’s LDL?

Low Density Cholesterol (LDL) must be the culprit because it packs a lot of cholesterol (found in arterial plaques) and hauls them to cells that need them.  Except that LDL falls just as flat as total cholesterol as a predictor of CVD.

Not LDL, it’s….

Ha now I’ve got it, it’s really oxidized-LDL!

Increased oxLDL concentrations were associated with an increased risk for incident CHD. Nevertheless, because this effect became nonsignificant after adjustment for covariates (emphasis mine), particularly the ratio of total cholesterol to HDL cholesterol, it may be mediated primarily by lipid parameters. Further studies are warranted to clarify this issue” (i.e. we don’t have anything here we can hang our hat on so maybe someone else can find a relationship between ox LDL and CVD????).

By the way, the vast majority of oxidized LDL is removed by the liver leaving very little in the circulating blood.  Theories that try to advance oxLDL hinge on the bizarre notion that the endothelial cells of the artery grabs stray oxLDL and transports it to the artery wall in order to…hell if I know.  Not only does no one have a good reason for the endothelium to do this, they also cannot explain the mechanism by which it supposedly occurs.  Other versions have the LDL clinging to the endothelium and THEN becoming oxidized, but it really doesn’t make any more sense than the other version.

LDL/HDL Ratio?

Maybe it’s the ratio of HDL to LDL that matters (I’ve heard this before but I could not find a study that supported the idea).  It has to be SOMETHING with cholesterol – just look at those plaques!  And yet….

High LDL In The Elderly Is GOOD

High LDL-C is inversely associated with mortality in most people over 60 years. This finding is inconsistent with the cholesterol hypothesis (ie, that cholesterol, particularly LDL-C, is inherently atherogenic). Since elderly people with high LDL-C live as long or longer than those with low LDL-C, our analysis provides reason to question the validity of the cholesterol hypothesis.” 2015

At this point I hope you are at least starting to question the cholesterol hypothesis, regardless, the beat down continues.

OK, So It’s Not Too Much LDL…It’s Too Little HDL?

High Density Lipoprotein (HDL) is not able to penetrate plaque, yet it is purported to somehow remove LDL from plaque.  Ignoring that leap in logic one must conclude that elevated levels of HDL are protective.  If so, the higher the level of HDL the better, except that’s not what the data show.

High HDL Also Causes Heart Disease

Participants with HDL cholesterol levels greater than 60 mg/dl (1.5 mmol/L) had a nearly 50% increased risk of dying from a cardiovascular cause or having a heart attack compared to those with HDL cholesterol levels 41-60 mg/dl (1.1-1.5 mmol/L).”

One study that did find a relationship between Trigyceride/HDL ratios and CVD used a pool of high risk subjects who not only had high cholesterol markers, but were diabetic smokers with high blood pressure.  It’s hard to imagine a study with more confounding variables (i.e. it is impossible to say that cholesterol is a cause rather than a lagging indicator).   

The data is pretty overwhelmingly stacked against the cholesterol hypothesis given that high cholesterol is not linked to increased risk of heart disease, but let’s give the hypothesis another chance.  If low levels of cholesterol lead to improved health this will be a big boost for the cholesterol hypothesis.  Specifically, lowering cholesterol should reduce or eliminate cardiovascular disease.  That’s exactly what the statin industry says and they argue that the incidence of heart attack in people with normal cholesterol levels simply tells us that “normal” is too high.

So what happens when cholesterol levels are lowered either by disease or statin use?

Low Cholesterol Increases Your Risk of Stroke And More

Dang it.  My investments in big pharma are losing value by the paragraph.

This study confirms an increased risk of primary ICH (intracerebral hemorrhage – this is when when a diseased blood vessel within the brain bursts) associated with low cholesterol both in men and women, especially in older individuals.

“…pronounced low LDL-C levels and disease states such as cancer, depression, infectious disease and others can generally be explained as secondary phenomena. Drug-related side effects including an increased propensity for development of type 2 diabetes occur during statin treatment….

Doctor Malcolm Kendrick in his book “The Great Cholesterol Con” does the heavy lifting of converting UK measurements to US and further crunching the numbers from the famous and much vaunted Framingham Heart Study which started in 1948 and is on-going.  The Framingham researchers publish from time to time with updates and insights and here’s the largely ignored shocker from April 24, 1987 – for every 20% drop in total cholesterol your risk of dying (all-cause death) increases by more than 400%.  Ok, so we’re trading lower heart disease for increased cancer incidence, right?  Nope – your risk of dying of CVD increases even more to 546%!

Dr. Kendrick also alerts us to this study you’ve never heard of “Why Eve Is Not Adam: Prospective Follow-Up in 149,650 Women and Men of Cholesterol and Other Risk Factors

Related to Cardiovascular and All-Cause Mortality.”  The results? – for men of all ages and women (from the age of 50 onward)  “low cholesterol was significantly associated with all-cause mortality, showing significant associations with death through cancer, liver diseases, and mental diseases.”  This is not good news for the statin industry.

If you still think the Cholesterol Hypothesis holds any water then I encourage you to read Dr. Kendrick’s book.  He knocks the stuffing out of each and every cholesterol and statin argument (many of which are not included in this article) and made me laugh out loud more than a few times.

Lest you think that Dr. Kendrick and I are alone in the cholesterol-is-ok-wilderness, here are two more brave souls (I should probably google to find out if they have been fired or not):

Nearly twenty years ago two landmark randomized clinical trials appeared in The Lancet which forever changed the course of medicine for patients with coronary heart disease (CHD). The 4S study employed a cholesterol-lowering statin drug and reported a 30% mortality reduction[]. The Lyon Diet Heart Study utilized the Mediterranean diet and reported a 70% mortality reduction[]. Subsequent studies of the Mediterranean diet have confirmed these findings and also shown a reduced risk of cancer, diabetes, and Alzheimer’s disease[]. Subsequent statin studies have led the United States Food and Drug Administration to issue warnings regarding the increased risk of diabetes and decreased cognition with statin drugs. Paradoxically, statins have gone on to become a multi-billion dollar industry and the foundation of many cardiovascular disease prevention guidelines while the Mediterranean diet has often been ignored. We believe this statin-centric cholesterol-lowering approach to preventing CHD may be misguided.  –  World Journal of Cardiology 2015

A word on the mortality reduction of statins as it involves a bit of statistical trickery as detailed by Dr. David Diamond:

We have described the deceptive approach statin advocates have deployed to create the appearance that cholesterol reduction results in an impressive reduction in cardiovascular disease outcomes through their use of a statistical tool called relative risk reduction (RRR), a method which amplifies the trivial beneficial effects of statins. We have also described how the directors of the clinical trials have succeeded in minimizing the significance of the numerous adverse effects of statin treatment. – Expert Review of Clinical Pharmacology 2015

In layman’s terms and paraphrasing Dr. Kendrick, if you purchase 3 lottery tickets instead of just 2 you will increase your offs of winning by 50%.  That sounds impressive, as does a 30% reduction in (cvd) mortality from statins, but your beginning odds are so laughably small to begin with that the reality is, as Dr. Diamond says, trivial.

In real terms the most positive statin related studies have come up with life extension numbers that seem pretty good until you consider this example from Dr. Kendrick ” if 10 million people (at very high risk of heart disease) took a statin for a year they would all live – on average – two days longer.”  Put another way, to increase average life expectancy by 1 year using statins that same group of high risk individuals would need to take them every day for over 182 years.

What ARE The Relative Risk Factors for CVD?

I hope you now know that cholesterol levels (no matter how you add, subtract, or divide the various lipoproteins) are terrible predictors of future heart attacks and strokes.  Let’s take a look at the risk factors identified by the American Heart Association (AHA), the World Health Organization (WHO), and the National Institutes Of Health (NIH), and the Centers For Disease Control and Prevention (CDC):

  1. Blood Cholesterol Levels
  2. Tobacco Use
  3. High Blood Pressure
  4. Type 2 Diabetes
  5. Obesity
  6. Physical Inactivity

We know that the first risk factor is false so please ignore.  The remaining five risk factors are valid, but what’s the underlying connection?  All will be revealed in the next article “The Real Cause Of Heart Disease.”

Update December 20, 2018 – I just found this gem regarding unpublished data from the Framingham Heart Study and had to share it.