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From the Townsend Letter
June 2009

Clearing Up the Cholesterol Confusion
by Stephen Sinatra, MD, FACC, FACN

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Every time I hold one of my subscriber seminars around the country, the subject of cholesterol comes up – again and again. Obviously, it's a source of great interest as well as confusion for many of you. The confusion part is this: you get one message from me, another from your doctor.

One subscriber told me privately that he showed a recent newsletter article I wrote about cholesterol to his cardiologist. After reading it the doctor said I was nuts and didn't know what I was talking about, and that the research has overwhelmingly determined that high cholesterol is a major risk factor for cardiovascular disease.

For years I've been writing about how I no longer buy into the cholesterol-lowering frenzy that has turned the medical profession into one big vending machine for statin manufacturers. Statins, as you know, are the blockbuster drugs that lower cholesterol, and most doctors today will recommend to you, and even nag you, to take them if your cholesterol numbers are "high," whether you have evidence of arterial disease or not, whether you are a man or woman, and at most any age. In their minds, you prevent heart disease by lowering cholesterol.

I used to believe that, too. It made sense, based on the research and information that was promoted to doctors. In fact, I even lectured on behalf of drug makers like Merck and Pfizer. High cholesterol was the big, bad villain of heart disease. Beat it down with a drug and you cut your risks.

But my thinking changed years ago when I began seeing conflicting evidence among my own patients and then in the medical research. I saw, for instance, many patients with low total cholesterol develop heart disease – as low, in fact, as 130! In those days we pushed patients to undergo angiograms (invasive arterial catheterization imaging) if they had sufficient symptoms of chest pain, borderline exercise tests, and especially if their cholesterol was greater than 280. We did this because our profession believed that all people with high cholesterol were in danger. We did the imaging to see how bad their arteries were. Indeed, many times we found diseased arteries. But often they were healthy. These patients were telling me something different than the establishment message – that it wasn't a simple cholesterol story.

Faced with these discrepancies, I began questioning and investigating. I found other doctors here and there who had made similar discoveries on their own, and heard how study findings were being manipulated. Biochemist George Mann of Vanderbilt University – who actually participated in the development of the world famous Framingham Heart Study that helped spawn the cholesterol danger hypothesis – later described it as "the greatest scam ever perpetrated on the American public." These, and other dissenting voices, were drowned out by the pro-cholesterol chorus. To this day, practically all of what has been published – and receives media attention – supports the cholesterol paradigm and appears to have the backing of the pharmaceutical and low-fat industries, along with leading regulatory agencies and medical organizations. However, I stopped being a choirboy for cholesterol. I stopped believing.

I found population studies that shredded my earlier belief. For instance, studies showing that the French had the highest average cholesterol levels – about 250 – in Europe but also the lowest incidence of heart disease. On the Greek island of Crete, a ten-year-study failed to register a single heart attack despite an average cholesterol well over 200 – a level, by the way, that would prompt most US doctors to prescribe a statin drug.
I also learned that half of all heart attacks occur in people with "normal" total cholesterol. This was reported in an eye-opening 1996 article by the then-director of the Framingham Study research group, William Castelli.

For the last five years or so, cardiology has turned away from a blinkered cholesterol perspective and toward the understanding that it is the inflammation of arterial tissue that leads to heart disease and most strokes. In the biochemical scenario that creates damage in the arterial walls, and then plaque, occlusions, and clots that follow, cholesterol plays a role, but in no way a leading role. You find cholesterol at the scene of arterial destruction. It is a participant in the crime, so to speak. But it is not the perpetrator.

Yet the word cholesterol remains for most people synonymous with death and disease. In this country we have created a nonexistent disease called hypercholesteremia – high cholesterol. I see the anxiety on patients' faces when they come to my office and the first words out of their mouth are: "My cholesterol is high and I'm really scared." People are indeed worried if they have a total cholesterol score of 200 or 250, and the first thing I have to do is reassure them and defuse their angst.

Thanks to medical science – and the merciful emergence of sophisticated lipid testing – doctors can finally show patients like these what their numbers really mean.

New Age Testing
The standard lipid tests that most doctors order for you really belong to the age of the dinosaurs. They tell you the level of your total cholesterol, LDL and HDL. In July of last year I wrote about the first of a new generation of tests called the VAP (vertical auto profile) test that breaks cholesterol down into fractions, appearances, and patterns, giving a much more accurate picture of what may or may not be a problem.

Now a second test has emerged that appears to be a notch better, the Lipoprotein Particle Profile (LPP) test offered by SpectraCell Laboratories in Houston. For more information on these tests, which are covered by Medicare and most health insurance plans, go to the following websites:,

Recently, I taught a continuing education course on anti-aging cardiology to 150 conventional doctors, including cardiologists. Most of them didn't know that these new tests exist and were extremely excited about them.

For sure, these analyses help doctors and patients make sense out of the cholesterol confusion. They break down the major cholesterol components and take you light-years beyond generalizations like "LDL cholesterol is the bad cholesterol and HDL cholesterol is the good cholesterol." The reality is much more complex. It is not just about how high the LDL is, but what kind it is and how much of it you have. The same with HDL. Keep in mind that the liver – where a good chunk of your cholesterol is produced – dispatches cholesterol throughout the circulatory system in the form of protein-wrapped fatty bundles called LDL. As LDL travels through the system, the cholesterol is accessed and used by cells as needed. Similarly, spent and oxidized cholesterol is picked up by HDL particles for return to the liver and subsequent excretion.

The SpectraCell test, originally developed at Texas A & M University, homes in on research that has introduced the medical community to subgroups of lipoprotein particles and how their different sizes and numbers can play a role in the inflammatory destruction of arteries.

LDL particles, for instance, can be large or small. It is the small, dense LDL particles that can readily enter into compromised arterial walls and stoke the inflammatory process. Higher numbers of these LDL particles represent a higher risk. Genetics play a major role here, and not diet, as most people have been erroneously led to believe. If you have significant numbers of these factors present, in the presence of cigarette smoke, mercury, lead, trans-fatty acids, insulin, homocysteine, or radiation, the potential for arterial damage increases. This is where I, as a cardiologist, become concerned, and particularly when there is a significant presence of Lp(a) – the most dangerous of these lipids and truly what we can refer to as "ugly cholesterol." This small, dense LDL entity is a major thrombotic factor. It inflames the blood and makes it sticky. Another small, dense particle that has emerged with an inflammatory reputation is called RLP (remnant lipoprotein). It plays a role in the formation of plaque.

You want to have fewer of these subtypes and instead have more of what are called large, buoyant LDL. That kind of result suggests less of a risk. With this kind of advanced testing, two people with the same total measurement of LDL cholesterol may be at opposite ends of risk. One, with a predominance of small, dense LDL particles, may have three times the risk of someone with mostly large, buoyant LDL.

Similarly, there are significant differences among subgroups of HDL that relate to how well or not they carry out their removal of excess lipids. You want to be high in the most functional HDL subgroup, labeled 2b. Not all HDL is created equal.

The worse scenario, with this kind of testing, would be to have a predominance of small, dense LDL particles and low HDL 2b.

What about your total cholesterol? you may be asking. Well, it doesn't mean much unless you have a level over 320 or so, which increases the risk of stroke; and then it certainly behooves you to bring it down. And you can readily do that with lifestyle modification, weight reduction, and eating a lot of good fiber. I wouldn't recommend a statin drug unless you had evidence of arterial disease and were a male. I have been very disappointed with the lack of results among women.

What about your total LDL level, according to standard tests? If your doctor thinks it is too high, suggest having the advanced testing done. In any case I would be extremely reluctant to bring down an LDL level to below 80, which some doctors are pushing. It's dangerous, in my opinion. Too-low cholesterol has been associated with cancer, aggression, cerebral hemorrhages, and amnesia, and could affect your ability to combat infections (see sidebar on cholesterol facts).

Here's what you have to remember if your standard cholesterol numbers are "high" and your doctor tells you to take a statin:

  • Don't do it. Ask your doctor to follow up with a VAP or LPP test that determines your individual cholesterol fractions.
  • If you are a male between the ages of 50 and 75 and have coronary artery disease, and the advanced test shows you have a predominance of small, dense LDL, go for the statin drug. It's a good idea. Statin drugs are also anti-inflammatory, and that's the powerful effect you are looking for, not the cholesterol-lowering activity. I say thumbs down on statins over the age of 75.
  • If you are a woman, and do not have unhealthy levels of inflammatory types of cholesterol and inflammatory substances such as homocysteine, fibrinogen, and C-reactive protein, I would pass on statins. I've been disappointed with the results. However, if you are a woman with arterial disease and have a profile of high inflammatory cholesterol and other substances, a statin may provide you benefit as an anti-inflammatory agent.
  • Male or female, do not take a statin on the basis of high Lp(a). Statins do not lower Lp(a). Your best bet to neutralize the inflammatory activity of Lp(a) is the B-complex vitamin niacin (500 mg–2 g daily) of the type that causes a flushing sensation, along with 2–3 g of fish oil and 100 mg of nattokinase. That's my most potent cocktail for neutralizing Lp(a).


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