NMR Lipoprofile—the Most Important Test to Determine Heart Disease Risk

By Dr. Mercola

The incorrect idea that high cholesterol causes heart disease has led to the demonization of entire categories of extremely healthful foods (like eggs and saturated fats), and cholesterol has been falsely blamed for just about every case of heart disease in the last 20 years.

Fat and cholesterol are commonly believed to be the worst foods you can consume. Please understand that these myths are actually harming your health.

Not only is cholesterol most likely not going to destroy your health (as you have been led to believe), but it is also not the cause of heart disease.

Chris Kresser, L.Ac., an acupuncturist and a licensed integrative medicine clinician, has investigated risk factors for heart disease and promotes the use of a relatively novel way of assessing your heart disease risk based on your LDL particle number.

He's currently writing a book about this topic for the Paleo ancestral health community. His interest grew from losing his grandfather to heart disease several years ago. His grandfather's case was badly mismanaged, which spurred Kresser to learn more about what really causes heart disease.

A few years later, while in graduate school studying integrative medicine, he did a semester-long research project on the relationship between cholesterol and heart disease.

Since then, he's read about 750 peer-reviewed studies, consulted with numerous experts in the field, and has challenged everything he thought he knew about the role of cholesterol in heart disease.

Over the last several years, he's been sharing that information on his blog, in his podcast, and in educational seminars and programs.

The Problem with the Conventional Approach, in a Nutshell

For the past 50 years, you've been told that eating saturated fat and high-cholesterol foods will raise cholesterol serum levels. However, research published over the past 10 or 15 years suggests that neither of those statements are true.

Furthermore, the typical cholesterol tests your doctor prescribes, which are supposed to measure your risk for heart disease, don't actually do a very good job of predicting your risk.

You can have low or normal LDL or total cholesterol and still be at high risk from heart disease. Alternatively, you can have high or normal total or LDL cholesterol yet be at low risk. Subsequently, many are not getting enough treatment, and others are getting too much.

"We've learned a lot about what causes heart disease over the past 10 years," Kresser says. "But unfortunately, that knowledge hasn't really trickled down into the mainstream yet. So, your average general care physician, primary care nurse, or even science writer that's writing for the mainstream media is still operating on information from the old paradigm.

The other issue is that the current dietary guidelines that are offered for how to reduce your risk for heart disease are based on this information that's still 30 to 50 years old. And they're clearly not working. Cardiovascular disease is still the number one killer. One out of every three deaths is due to this cardiovascular disease, and it affects about 65 million people in the U.S. alone."

The INTERHEART study, which looked at heart disease risk factors in over 50 countries around the world, found that 90 percent of heart disease cases are completely preventable by modifying diet and lifestyle factors. As Kresser points out, we clearly need a new approach that's based on more current evidence.

"The problem, of course, that we face is that the old paradigm is so entrenched. The idea that cholesterol and saturated fat are bad for us is so deeply engrained in our society that a lot of us don't even question that anymore.

One of the main problems there is the massive conflicts of interest in the medical profession. We have a situation where two-thirds of medical research is sponsored by pharmaceutical companies. Eight out of nine of the doctors who are on the National Cholesterol Education program that write the guidelines for cholesterol receive money from pharmaceutical companies," he says.

Conventional Tests Are Not Accurate Predictors of Heart Disease

If you've had your cholesterol levels checked, your doctor most likely tested your total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides. But we now know those are not accurate predictors for cardiovascular disease risk. According to Kresser, a much more accurate predictor is testing your LDL particle number. He explains:

"To use an analogy: if you imagine your bloodstream's like a river, the LDL particles are like the boats that carry the cholesterol and fats around your body. The cholesterol and fats are like cargo in the boats. Right now doctors are usually measuring the amount of cargo or cholesterol in the LDL particles. But what we should be measuring is the number of LDL particles, or the number of boats in the river, so to speak, because that's a much more accurate risk factor for heart disease."

As mentioned, it's possible to have normal total or LDL cholesterol yet have a high number of LDL particles. This is completely missed using the conventional testing. On the other hand, you may end up being prescribed a statin drug to lower your cholesterol when in fact your LDL particle number is normal, placing you in the low risk category for heart disease. (As a general rule, regardless of your LDL particle number, chances are you do NOT need a statin drug to address high cholesterol. The only people who may truly benefit from a statin drug are those with the genetic defect called familial hypercholesterolemia.)

How to Test Your LDL Particle Number

Some groups, such as the National Lipid Association, are now starting to shift the focus toward LDL particle number instead of total and LDL cholesterol, but it still has not hit mainstream. Fortunately, if you know about it, you can take control of your health and either ask your doctor for this test, or order it yourself.

There are several ways to test for your LDL particle number. Kresser recommends using the NMR LipoProfile, offered by a lab called Liposcience. The test uses FDA approved technology for testing LDL particle number, and it's the test used in most of the scientific studies on LDL particles.

"All the different lipoproteins have a unique magnetic signature, and this test uses a nuclear magnetic resonance technique to pick up on that signature. It can correctly identify the number of particles in each case," he explains.

It's easy to get and all major labs offer it, including LabCorp and Quest. Most insurance policies cover the test as well. Best of all, even if your doctor were to refuse to order it, you can order it yourself via third-party intermediaries like Direct Labs, or you can order the test online, and get blood drawn locally.

In Europe and other parts of the world, LDL particle number is more commonly measured using an indirect marker, apolipoprotein B (apoB). ApoB is a protein required for the formation of the LDL particle. About 90-95% of apoB particles are LDL particles, which makes apoB a fairly accurate measure of LDL particle number. If you live in a country where the NMR profile is not available, you can use the ApoB test to roughly determine your LDL particle number, and then use triglycerides, HDL, fasting blood sugar, blood pressure and waist-to-hip ratio to determine if you have insulin resistance.

The Devil Is in the Details... How Medicine Got the Wrong Idea about Fats

Saturated fat has long been demonized as a heart attack waiting to happen, and many doctors still cling to this outdated view. Ironically, saturated fat is not only healthful fat, it's one of the most important dietary factors to support health! There's simply no way to calculate the harm inflicted by the low-fat craze. We now know that if you avoid saturated fats, you're asking for trouble. Not only is saturated fat the optimal fuel for your brain, it also:

Provides building blocks for cell membranes, hormones, and hormone-like substances	Acts as carriers for important fat-soluble vitamins A, D, E and K	Is required for the conversion of carotene to vitamin A, and for mineral absorption
Acts as antiviral agents (caprylic acid)	Helps lower cholesterol levels (palmitic and stearic acids)	Modulates genetic regulation and helps prevent cancer (butyric acid)

 

The US Department of Agriculture's dietary guidelines¹ advises you to consume less than 10 percent of calories from saturated fats. I and other nutritional experts have warned that most people actually need upwards of 50-70 percent healthful fats, including saturated fat, in their diet for optimal health. How did medicine get this so wrong?

A combination of factors is likely to blame. There were early studies showing that saturated fat raised cholesterol levels in the blood, but they were almost always short-term studies. Since then, much larger observational studies, conducted for extended periods of time have been done, completely refuting earlier short-term results. Later studies have shown absolutely NO relationship between saturated fat intake and blood cholesterol levels.

"We're talking about some really big, well-known studies that cover tens of thousands of people," Kresser says. "In fact, there was research published in the American Journal of Clinical Nutrition that covered about 350,000 people in a follow-up period of five to 23 years. And there was no relationship at all between saturated fat intake and heart disease. And then a large Japanese study of about 58,000 people actually found an inverse association between saturated fat intake and strokes. So, in other words, the people who were eating the most saturated fat actually had the lowest levels of stroke."

Another problem is that early studies did not differentiate between critically important omega-3 and less health-promoting omega-6 fats.

"There's a study... that went back and looked at some data. Some of the early data suggested that replacing saturated fat with industrial seed oil or polyunsaturated fat would lower cholesterol and lower the risk of heart disease. But what they didn't realize back in the '60s when they were doing those studies [was the difference between omega-3 and omega-6]; they thought all polyunsaturated fats were the same, so they would lump them together in the studies.

Now we understand that omega-6 has very different effects from omega-3. When you study them separately, you see that omega-6 actually doesn't reduce the risk of heart disease and may increase the risk of heart disease when it's studied independently of omega-3s."

Today we have yet another complicating factor when it comes to omega-6 fats and that's the fact that many of them now come from genetically engineered corn and soy. When you add that into the mix, the health hazards may be worse than we currently imagine.

Which Fats Are Healthy?

Sources of healthful fats (and in some cases cholesterol) include:

Olives and Olive oil	Coconuts and coconut oil	Butter made from raw grass-fed organic milk
Raw nuts, such as almonds or pecans	Organic pastured egg yolks	Avocados
Grass-fed meats	Unheated organic nut oil

 

Another healthful fat you want to be mindful of is animal-based omega-3. Deficiency in this essential fat can cause or contribute to very serious health problems, both mental and physical, and may be a significant underlying factor of up to 96,000 premature deaths each year. For more information about omega-3s and the best sources of this fat, please review this previous article.

High Cholesterol Is NOT the Cause of Heart Disease

There are two parts to this persistent myths relating to cholesterol and heart disease:

1. The idea that eating cholesterol and saturated fat raises cholesterol levels in your blood, and
2. That high cholesterol in your blood is what drives the risk for heart disease

Some of the healthful fat sources listed above are also sources of dietary cholesterol, such as eggs. Contrary to early studies, which suggested eating cholesterol-rich egg yolks raises your cholesterol levels, we now know that's actually NOT true.

"That's been pretty thoroughly disproven in the scientific literature," Kresser says. "You have between 1,100 to 1,700 milligrams of cholesterol in your body at any given time. But only 25 percent of that actually comes from your diet, and 75 percent is internally produced primarily through your liver. Why would that be? Because cholesterol is so important to the proper function of your body that your body tightly regulates its production. If you don't eat enough cholesterol, your body will make more. It needs more cholesterol, not less.

The other thing that most people don't know is that only free or unesterified cholesterol can be absorbed from the diet through the intestines. Most foods have esterified cholesterol that can't actually be absorbed."

The first thing to understand is you don't have a cholesterol level in your blood, actually. Cholesterol is fat-soluble, and blood is mostly water. For it to be transported around the blood, cholesterol needs to be carried by a protein, specifically by a lipoprotein. These lipoproteins are classified by density. So, you have very low-density lipoprotein or VLDL, low-density lipoprotein or LDL, and high-density lipoprotein or HDL, which are the main ones.

I mentioned before the analogy that our bloodstream is like a river. Remember that the lipoproteins are like boats that carry the cholesterol and fats around the body. The cholesterol and fats are like cargo in the boats.

So, here's the really crucial point: up until about 10 or 15 years ago, we thought that it was the concentration of cholesterol in the lipoprotein (or the amount of cargo in the boat) that was driving the risk of heart disease. But recent research indicates that it's the number of boats or the number of LDL particles that's really the driving factor."

So, it's not the amount of cholesterol that is the main risk factor for heart disease, rather it's the number of cholesterol-carrying LDL particles. Oxidized LDL can also be a greater risk factor for heart disease. When oxidative stress is high due to poor diet, insufficient exercise and sleep, and chronic stress, or when your antioxidant capacity is low (again usually because of a poor diet), then oxidative damage can occur. Oxidized LDL is more harmful than normal non-oxidized LDL because it's smaller and denser. This allows it to penetrate the lining of your arteries, where it will stimulate plaque formation associated with heart disease.

"The more LDL particles you have, the more likely you are to have some oxidized LDL, and they can be more atherogenic. However, oxidized LDL loses their predictive value when it's adjusted for LDL particle number. That suggests that LDL particle number may be an even more important risk factor and may need a high number of LDL particles before oxidation becomes a big problem," Kresser explains.

What Raises Your LDL Particle Number?

If the primary cause of heart disease is not high cholesterol, then what is? Part of the reason why statins are ineffective for heart disease prevention (besides the fact that the drug causes heart disease as a side effect) is that drugs cannot address the real cause of heart disease, which is insulin and leptin resistance, which in turn increase LDL particle number via a couple of different mechanisms. While some genetic predisposition can play a role, insulin and leptin resistance is primarily caused by a combination of factors that are epidemic in our modern lifestyle:

• A diet high in processed and refined carbohydrates, sugars/fructose, refined flours, and industrial seed oils
• Insufficient everyday physical activity. Leading a sedentary lifestyle causes biochemical changes that predispose you to insulin and leptin resistance
• Chronic sleep deprivation. Studies have shown that even one night of disturbed sleep can decrease your insulin sensitivity the next day and cause cravings and overeating
• Environmental toxins. Exposure to BPA, for example, can disrupt your brain's regulation of weight
• Poor gut health. Studies indicate that imbalances in your gut flora (the bacteria that live in our gut) can predispose you to obesity and insulin and leptin resistance. According to Kresser, gut inflammation can even affect your cholesterol more directly.

"There are some studies that show that lipopolysaccharide, which is an endotoxin that can be found in some types of bacteria in the gut… If the intestinal barrier is permeable, which shouldn't be, of course, some of that lipopolysaccharide can get into your bloodstream. LDL particles actually have an antimicrobial effect. So, LDL particles will increase if there is some endotoxin going into the bloodstream... causing a direct increase of LDL particles."

The culmination of the synergistic effect of these factors will put pressure on your liver to increase production of lipoproteins, more specifically: low-density lipoproteins (LDL), (i.e. more "boats in the river"), which increases your heart disease risk.

Another way leptin resistance contributes to increased LDL particle number, and hence increased heart disease risk, is as follows: when a cell signals that more cholesterol is needed for the cell to perform its function, LDL receptor activity increases. The LDL receptor sits on the outside of cells, and its job is to act as a docking station for the LDL particles floating around in your blood. Once "docked" into the LDL receptor, the LDL particle can deliver the nutrients it carries into the cell.

However, if you're leptin resistant, the LDL receptor doesn't get the message. It's not sensitive enough to hear the signal. And without LDL receptor activity, the LDL particles floating around are never encouraged to "dock" into the receptor, and this too directly increases LDL particle numbers.

Besides insulin and leptin resistance, another common cause of elevated LDL particle number is poor thyroid function. T3 hormone (which is the most active form of thyroid hormone) is required to activate the LDL receptor, which is what takes LDL out of the circulation. If you have poor thyroid function or low T3 levels, then your LDL receptor activity will be poor, and you'll have a higher number of LDL particles. The good news is, if this is the cause for your elevated LDL particle number, then addressing your thyroid problem will reduce it.

How Intermittent Fasting Can Help You Address High Cholesterol

I'm particularly fond of coconut oil because I believe it's a useful therapeutic agent to help you implement intermittent fasting, which is perhaps one of the most valuable stealth strategies to get healthy—largely because it can radically improve your insulin and leptin resistance. In that respect, intermittent fasting is also a powerful way to address cholesterol and LDL particle number. Kresser explains:

"Insulin resistance and leptin resistance are widespread problems... and that's one of the main driving forces in elevated LDL particle number. The reason for that is that LDL particles carry not only cholesterol, but also triglycerides, fat-soluble vitamins, and antioxidants... If you have high triglycerides, which you often will when you have insulin or leptin resistance, then that means a given LDL particle can carry less cholesterol, because it's stuffed full of triglycerides. Your liver will then have to make more LDL particles to carry that same given amount of cholesterol around the tissues and cells in your body.

...Intermittent fasting is one of many ways to improve insulin sensitivity and leptin sensitivity, because there are certain processes in the body that engage after you haven't eaten for a period of time. They're all evolutionary mechanisms that are designed to help us survive in periods of food scarcity. You have an upregulation in metabolism basically, and... your insulin and leptin sensitivity improves.

It's a really good way for people to lose weight, which again will improve insulin and leptin sensitivity, because obesity is both a cause and an effect of leptin resistance. I think it's a really great strategy for most people; I do use it in my practice a lot.

The only kind of caution might be in people who have pretty severe fatigue, or are suffering from some kind of chronic illness, and need to eat more often. But for most people, I think it's great."

Coconut oil is most beneficial during the transition period from burning sugar to burning fat, as it will not upset insulin and leptin resistance. It's neutral, yet it is rapidly metabolized and provides a good source of energy. Fatigue can be a real challenge, so if you want to try intermittent fasting but worry about flagging energy levels, coconut oil can be a useful tool. You can even have some coconut oil during your fasting period as it will not interrupt the beneficial processes that are happening while you're fasting. It's mainly protein and carbohydrate that will interrupt those processes. So having a little coconut oil in the morning might help you make it through until you break your fast for your first meal. Kresser recommends putting it in a smoothie, or even adding it to your tea or black coffee, if the idea of eating the coconut oil by itself is too unappealing.

Tying It All Together

Remember, the most important test you can get to determine your heart disease risk is the NMR lipoprofile, which measures your LDL particle number. This test also has other markers that can help determine if you insulin resistance, making it doubly useful. If you have insulin or leptin resistance, you'll have an increase in LDL particle number and specifically the number of small LDL particles. The NMR lipoprofile measures that too, and gives you an objective score called the lipoprotein insulin resistance score or LP–IR. If your LP–IR is above the recommended reference range, chances are that you have leptin and insulin resistance.

Insurance usually covers the test, but if you order it yourself from Direct Labs or Access Labs, it costs about $100. If your LDL particle number is high, Kresser recommends searching for the cause. Again, two of the major ones are insulin and leptin resistance, which the NMR test will alert you to. The third common cause is poor thyroid function. Chronic infections could also be a factor.

Once you've determined the cause, you need to address those. Remember, statin drugs CANNOT address insulin or leptin resistance, and they do NOT affect particle size or particle number. They ONLY suppress cholesterol production in your liver, which can make your situation worse. Kresser advises paying careful attention to the following seven factors when addressing insulin and leptin resistance:

1. Diet: shifting toward the nutrient-dense-food-based diet with higher fat and lower carbohydrate intake
2. Intermittent fasting may be useful
3. Make sure you're getting enough sleep
4. Exercise regularly, and make sure to incorporate high intensity interval exercises, as they are particularly effective for improving insulin and leptin sensitivity
5. Avoid sitting too much, as that can have a direct adverse effect on insulin and leptin sensitivity
6. Minimize your exposure to environmental toxins as much as possible
7. Optimize your gut health by eating fermented foods, soluble fiber that enriches the beneficial gut flora, and avoiding food toxins and things that harm your gut flora

As you can see, the things you need to do to treat your high LDL particle number are identical to what you would do to promote optimal health in general.

"To me, that just makes sense. The things that keep us healthy in one department or one area are more likely to make us healthy in another. And this is no different from that," Kresser says.

For more information, see Kresser's website: ChrisKresser.com. He also has an Internet radio show called "Revolution Health Radio", available on his site and on iTunes, where he discusses these topics on a regular basis. His web site also offers educational programs, including a nine-week long self-guided multimedia course called "The High Cholesterol Action Plan", which goes into a whole lot more detail on the subject.