Is Cholesterol Theory Completely Wrong?

[01dragonslayer]

High Cholesterol Might Make You Live Longer​

A couple of unheralded research papers claim that it’s actually low LDL cholesterol that’s bad and that statins should be discontinued.

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Cholesterol Science: Something is Off​

I want to tell you a story that offers up a little perspective on the topic of cholesterol. It involves my mother.

She was wasting away from a catastrophic trio of lung cancer, chemo, and radiation, and I tried to get her to eat some high-calorie foods, eat anything really, so she could keep from wasting away. She demurred and continued to only peck at her food. Why? Because she was worried about her cholesterol.

The poor woman had been given two years to live, tops, and she was more concerned about the possible effects high cholesterol would have on her heart than she was of the cancer in her lungs.

That’s how much the medical community has made us fear cholesterol. What makes my mother’s death possibly even more tragic is that there’s apparently some evidence that having low total cholesterol actually makes one more susceptible to cancer and other diseases.

But forget that for now. I’m personally at a crossroads here. I inherited high cholesterol from my mother and father, and, despite all my efforts, despite all I know about health, I haven’t been able to solve it.

Granted, my total cholesterol isn’t that bad compared to some. It usually hovers around 220 with an LDL of between 130 and 140, but my doc doesn’t like it. Neither does the American Heart Association. The doc wants me to take a statin, especially since I’ve got that familial hypercholesterolemia (FH) thing going on.

But the more I investigate it, the more questions I have. I’ve suspected something’s wrong with cholesterol science for a long time and even touched on this topic 26 a few years ago, but a couple of relatively unnoticed reviews of the current research makes a hugely compelling case that we know very little about the effects cholesterol – specifically low-density lipoprotein cholesterol (LDL-C) – has on cardiovascular health.

They believe the current cholesterol hypothesis might be based on misleading statistics, lots of ignored contradictory evidence, and the passing over of unsuccessful trials. Worse, these contrarians believe what we think we know is virtually the opposite of what’s true.

The first paper, published in a relatively obscure (more on that later) journal named “Expert Review of Clinical Pharmacology,” presents their argument on the alleged dangers of high LDL-C largely in an easily accessible question-and-answer format, which I’ve mimicked below.




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Does High Total Cholesterol Cause Atherosclerosis (the build-up of fats, cholesterol, and other substances on artery walls)​

The authors begin their answer by stating the obvious: If high total cholesterol (TC) causes atherosclerosis, people with high TC should have more atherosclerosis than people with low TC. However, in 1936, researchers Lande and Sperry found that, after correcting for age, people with low TC were just as atherosclerotic as people with high TC. While it’s easy to dismiss research from 1936 as possibly flawed, their observation has been confirmed by at least a dozen studies.

Granted, say the authors, a few studies have found a weak association between atherosclerosis and TC, but the authors of those studies only looked at patients who had been admitted to hospitals and, therefore, probably included patients with FH, which might have inadvertently introduced a bias.

Does High TC Cause Cardiovascular Disease (CVD)?​

The authors make the point that if TC was a major cause of CVD, people with high TC should be dropping dead of CVD at a higher rate. To argue this, they bring up the Framingham Heart Study, which began in the 1960s and followed the health of members of the Framingham community in England for 30 years.

What the 30-year follow-up revealed freaked me out. It allegedly concluded that for each 1 mg/dl drop in TC per year (e.g., TC dropping from 135 to 134), there was an 11% increase in coronary and total mortality. Holy crap!

Three years later, the American Heart Association and the U.S. National Heart, Lung and Blood Institute published a joint summary that included findings from the Framingham report, concluding that “a one percent reduction in an individual’s TC results in an approximate two percent reduction in CHD risk.”

Huh? How could such a disconnect have happened? Did the AHA and Heart, Lung and Blood Institute misinterpret the findings, or maybe cherry-pick them so as not to upset the cardiovascular apple cart?

It was too weird, so I dug up the Framingham study. I didn’t have to go past the abstract to find the following damning statement:

“There is a direct association between falling cholesterol levels over the first 14 years and mortality over the following 18 years (11% overall and 14% CVD death rate increase per 1 mg/dL per year drop in cholesterol levels).”

Granted, this statement was, according to the study, only true for people over 50, but since most people over 50 are routinely prescribed statins, even for mild hypercholesterolemia, it raises a whole bunch of questions about cholesterol science in general.

How Strong is the Association Between TC and CVD?​

The authors of the contrarian report assert that numerous studies have found that high TC isn’t associated with future CD, of which the strongest evidence of this lack of correlation is found in old people. They point, specifically, to a 2004 Austrian study that followed the health of 67,413 men and 82,237 women for several years.

They found that TC was weakly associated with CD mortality in men, except for those between 50 and 64 – the age group for whom it’s supposedly the biggest concern. For women, it was weakly associated with CD mortality in women under 50, but not at all for women past that age.

While this doesn’t perfectly support the argument of the contrarians, it’s an example of how current cholesterol science is horribly imprecise at best.

Does High LDL-C Cause Atherosclerosis?​

If LDL-C cholesterol causes “hardening of the arteries,” then it stands to reason that people with high LDL-C have more atherosclerosis than people with low LDL-C. To counter this, the contrarian authors point to four studies that show a complete lack of association between high LDL-C and atherosclerosis.

To be fair, though, they did find a study of 1779 healthy people that found that LDL-C was significantly higher among people with (subclinical) atherosclerosis. They argue, however, that “association does not prove causation,” pointing out that simple mental stress, for one, can affect LDL-C readings mightily, as much as 10 to 50% in just a half hour. (This fact alone makes virtually all clinical measurements of TC suspect.)

Mental stress may also cause atherosclerosis by other mechanisms, e.g., through high blood pressure or platelet aggregation.

Does High LDL-C Cause CVD?​

A large American study found that the LDL-C of 140,000 patients with acute myocardial infarction was actually lower than normal upon admittance to the hospital. The authors of another study who discovered the same thing decided to take it one step further: They intervened and lowered the patients’ LDL-C even further. Unfortunately, after three years, the mortality rate of the patients with lower LDL-C was twice as high as those with a higher LDL-C, even after they corrected for confounding variables.

Do Old People with High LDL-C Die Younger?​

The authors point to a recent review of 19 cohort studies (ones that follow people for several years) that found that the people over 60 who had the highest LDL-C levels lived longer than those on statins.

What About People with FH? Do They Die Earlier?​

Apparently not, at least according to what the cholesterol contrarians unearthed. They point to the Simon Broome registry, which lays out diagnostic criteria for the determination of genetically influenced hypercholesteremia based on clinical, genetic, and familial history.

This registry allegedly found that only a small percentage of FH people die at an early age, and the mortality among old patients with high LDL-C doesn’t differ from those of the general population.

If The Contrarians are Right, Why Would High LDL-C Prolong Life?​

If what the cholesterol theory contrarians are saying is true – that there’s an inverse relationship between LDL-C and mortality, what’s the possible explanation?

They propose that it may also have to do with the largely unheralded role LDL-C plays in the functionality of the immune system. LDL-C adheres to and inactivates many types of microorganisms and their toxic byproducts. Consistent with that theory is that many patients with low LDL-C have a significantly increased risk of infectious diseases and cancer.

Infections, they say, may be a factor in the development of heart disease instead of high LDL-C.

Most of the Preceding Applies to Older People. What About Young People and LDL-C?​

It must be said that several studies of young and middle-aged people have found a link between high-HDL and CVD.

However, it could be, as the contrarians suggest, a failure of researchers to consider many CVD-promoting factors like inflammation, mental stress, coagulation factors, infections, and endothelial sensitivity, all of which are closely related to abnormalities in LDL receptors.

As pointed out earlier, mental stress can raise TC within minutes, possibly because cholesterol is needed to produce cortisol and other stress hormones, i.e., high TC fuels the production of epinephrine and norepinephrine, which are key players in hypertension and hypercoagulation (clotting that can lead to heart attack or stroke).

This is why, according to the contrarians, high TC is indeed a risk factor for young and middle-aged people because mental stress is usually more of a problem in the working young than it is in retired folk.

To synopsize this:

• High TC and stress might lead to CVD in younger people.
• High TC and no stress mean they aren’t at great risk for CVD.

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How Well Do Statins Work?​

As you might have guessed, the anti-cholesterol theory authors aren’t too keen on the use of statins to treat high LDL-C. For one thing, they think they’re mitotoxic. In other words, they believe statins damage mitochondria (in the cells of the heart and throughout the body).

In turn, this damage to mitochondria leads to decreased oxidative phosphorylation, which, it stands to reason, isn’t good for the heart or any other part of the human body, for that matter.

Then there’s the myopathy issue associated with the use of statins. The contrarians refer to a study that found that muscle myopathy was only associated with 0.01% of treated individuals (Collins, et al, 2016). Unfortunately, it seems, myopathy is only recorded in most statin studies if creatine kinase (a marker of muscle breakdown) is more than 10 times normal. Yikes.

They also cite a study of 22 statin-treated professional athletes, 17 of which terminated the treatment because of adverse muscular symptoms.

Statins, they write, are also linked to cataracts, hearing loss, suicidal ideation, peripheral neuropathy, depression, Parkinson’s, interstitial cystitis, herpes, and diabetes. Cholesterol is a vital substance for the renewal of all cells, so they feel it’s inevitable that they lead to a slew of unfortunate side effects like the ones just listed.

They even tie the use of statins to heart attacks they’re supposed to prevent. The drugs block the production of several important molecules, an example of which is coenzyme Q10, which is essential for energy production in the muscles and in the heart. As such, they suspect the extensive use of statins might have led to epidemics of heart failure in countries where they’re widely prescribed.

(One adverse effect of statins that the contrarians didn’t bring up was the fact that they inhibit the synthesis of vitamin K, which is vital for the prevention of vascular calcification. That means that if statin users don’t supplement with vitamin K, they could, ironically, be hastening the development of the very disease they’re trying to prevent.)

All of this has forced the contrarians to conclude that clinicians should discontinue the use of statins (along with another anti-statin family of drugs, PCSK-9 inhibitors) “and instead identify and target the actual causes of CVD.”

Possible Problems with the Contrarian Cholesterol Position Paper​

The paper was written by researchers from the University of South Florida, the Japan Institute of Pharmacovigilance, and other instates in Japan, Sweden, the United Kingdom, the US, and Italy.

It needs to be pointed out that four of the authors have written books that are critical of the cholesterol hypothesis and that nine of the authors, at least, are members of THINCS – The International Network of Cholesterol Skeptics, an organization that opposes the theory that animal fat and cholesterol play a role in heart disease.

That, however, isn’t necessarily damning. It might be proof of pre-existing bias, but on the other hand, it tells us they’ve spent a lot of time studying and thinking about the topic. I mean, we didn’t automatically dismiss Einstein’s papers and lectures on relativity because he had previously written a book about it.

Another legitimate criticism, as pointed out by a physician friend of mine, is that the paper was published in a somewhat obscure pharmacology journal, which he suggests they didn’t meet the publication standards of the more well-known journals, “who would love a good article that challenges current theory.”

That’s true, but another group, consisting of mostly the same authors, wrote a similar paper that was accepted and published in the British Medical Journal (BMJ), which is widely known and respected.

As far as his point about journals liking articles that challenge current theory, that’s probably true, at least in most cases. Now, I’m hardly a conspiracy theorist, but I wonder if there’s just too much money and too much influence directly involved in statins. There are plenty of physicians who joke that statins be added to drinking water, but they might as well be, given the number of statin users in the world.

Lastly, cholesterol and statin beliefs might be so firmly entrenched in the medical community that arguing against them is futile. The cholesterol believers might be exhibiting the “Semmelweis reflex,” which is a reflexive attitude to any information that contradicts established norms.

I need to point out, though, that other studies have found a clear link between TC and heart disease, most notably one published in The Lancet (Lewington, et al, 2008) that involved nearly a million people. However, despite its supposedly inarguable results regarding TC and heart disease, it found no association between TC and stroke mortality, which only adds to the confusion.




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What Are We to Make of All This?​

The oddest thing about these two papers and their damning evidence is that virtually no one has, or is, paying any attention to them. I only stumbled on them because someone in T Nation’s forum 16 posted a link to one of them.

It’s difficult to know what to believe. It’s maddening, frankly. Are the contrarians who authored these papers the only ones with their eyes open, or are they, too, hopelessly trapped by their own confirmation bias and unable to honestly tease apart legitimate research?

Or are they right, that tens of thousands of researchers and medical personnel have simply ignored all the allegedly contradictory evidence and simply continued to blame cholesterol for CVD and in doing so, ironically damaged the health of millions of patients?

Hell if I know. Clearly, we need more research conducted without bias or preconceived notions.

FOR WHAT IT’S WORTH, HERE’S WHAT I BELIEVE​

Inflammation may be the true villain in heart disease, and if statins do prolong life, as some studies seem to indicate, they probably do so because they’re powerful anti-inflammatories.

One of the things that causes inflammation is an excess of saturated fat intake, along with a dietary imbalance between omega-3 fatty acids and omega-6 fatty acids. Maintaining optimal blood pressure is also paramount to heart health, and the keys to that are exercise, of course, and stress reduction, whether that comes from meditation, walking in nature, or playing stupid video games.

I’ve also chosen to compromise on the statin issue. Most of the side effects, if they’re true, probably come from the use of higher dosages (up to 80 mg. a day). With that in mind, I’ve opted to take one relatively tiny 5 mg. rosuvastatin (Crestor) pill twice a week. While the dosage is minuscule, there’s research to support such a protocol (if it can be believed).

Lastly, I don’t worry about cholesterol in food 9, as there is very little evidence that it affects levels of blood cholesterol. Instead, as mentioned, I watch my intake of saturated fat. Quite contrary to popular thinking, an egg 3 (or two or three) is heart-healthy because, while being relatively high in cholesterol, is low in saturated fat.

But I could easily be wrong on one or more counts. So could the contrarians. What should be clear at this point is that regardless of whether you believe current cholesterol theory or not, it sure looks like there might be better ways to treat CVD than is currently being practiced.

Whatever you do, don’t stop taking statins based on anything you read in this article. The contrarians might be wrong, dead wrong. Stopping medication should be a decision made with your doctor. I offer this article only to ask some needed questions.