A Closer Look At HDLc: The “Happy Cholesterol”

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Focusing solely on the results of your HDLc blood test isn’t the best way to wellness. Learn the reason in this post.

RELATED: Cholesterol, High Blood Pressure, Diseased Arteries: Making the Connection

In this article:

  1. The Growing Demand for a Cholesterol Test
  2. HDL: The Good Cholesterol?
  3. All HDL Is Not Created Equal
  4. Understanding HDLc Associated Protein, PON1
  5. PON1 and Toxic Oxidants
  6. What’s New?
  7. At the Heart of Your Health
  8. Is It Still Necessary to Undergo an HDLc Blood Test?
  9. Beyond HDLC Test: How to Lower Your Cholesterol Naturally

HDLc Blood Test and Other Lipid Profile Exams Don’t Provide the Complete Answer

The Growing Demand for a Cholesterol Test

More people are asking for an HDLc blood test, and here’s why. How many of you remember four decades ago when the media first bombarded us with dire warnings about the dangers of consuming cholesterol-rich foods, such as eggs and red meat, on a regular basis?

It turns out, the cholesterol connection with heart disease is complex.

The advice was scary. It made the connection between high levels of cholesterol in our blood and the clogging of arteries and heart disease.

Obviously, this was bad news for poultry and cattle farmers who argued there was no compelling evidence showing an association between eating eggs or meat and increased incidence of heart disease.

Could it be that the farmers were, for the most part, correct? It turns out, the cholesterol connection with heart disease is complex.

Juvenon Health Journal explores recent findings that may help you determine the best ways to maintain a healthy cardiovascular system.

HDL: The Good Cholesterol?

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Cholesterol is carried in the bloodstream and present in the tissues of the body. It is normally combined with different molecular species, predominantly proteins.

This molecular association imparts different properties to the cholesterol particle. The most conspicuous property is its density.

Two of the most common forms of cholesterol-carrying particles are termed LDLc (low-density lipoprotein) and HDLc (high-density lipoprotein).

LDLc carries cholesterol from the liver, where it is manufactured, to outlying tissues to be utilized for the synthesis of important cellular molecules. These molecules include steroids such as progesterone and testosterone.

However, LDLc is susceptible to oxidation. This results in its conversion to LDLox, a toxic-inflammatory molecule.

LDLox contributes to heart disease and can be measured as a marker for heart disease.

HDLc, on the other hand, is known as the good or “happy” cholesterol. It carries cholesterol away from the tissues back to the liver to be excreted in bile.

HDLc helps endothelial cells activate an enzyme, eNOS, to produce nitric oxide (NO).

What are endothelial cells? These are cells that comprise the lining of blood and
lymphatic vessels.

Recently, HDLc has been shown to have additional positive effects on vascular health, in particular, the stimulation of an enzyme endothelial nitric oxide synthase (eNOS). It is involved in the production of nitric oxide.

This gaseous molecule relaxes blood vessels, reduces blood pressure, and protects endothelial cells lining our arteries.

The latest research may clarify conflicting reports on the effects of certain therapeutics demonstrated to raise HDLc. Basically, it appears that some HDLc-raising therapeutics improve cardiovascular health.

Others may have no effect or may even be detrimental. These varied effects of HDL-raising therapeutics on cardiovascular health have led many in the field to conclude there are different forms of HDLc, and some may not be healthy.

All HDL Is Not Created Equal

Investigators have discovered, after extensive analysis, different forms of HDLc with different associated molecules bound to the core HDL particle. A study shows that HDLc in patients with coronary artery disease (CAD) is not equivalent in composition to HDLc in healthy patients of similar age.

Past studies have demonstrated the protective effects HDLc has on the endothelial cells, important cells that line the arteries in a single layer.

These delicate yet hardworking cells are largely responsible for keeping our arteries healthy and disease-free. HDLc helps endothelial cells activate an enzyme, eNOS, to produce nitric oxide (NO).

The released NO diffuses into the smooth muscle cells within the artery wall. This action, in turn, signals the muscle to relax, lowering blood pressure and improving circulation.

Importantly, nitric oxide prevents inflammation that can lead to atherosclerosis and heart disease. This is the normal healthy effect of HDLc on the endothelial cells from normal, healthy patients.

Still, scientists were curious about how the endothelial cells of patients with heart disease react to HDLc. The experimental results astonished the investigators.

They discovered that the HDLc taken from CAD patients and placed in a culture dish containing endothelial cells did not stimulate the beneficial eNOS release that occurs with HDLc isolated from normal healthy patients.

What’s more, scientists found that the HDLc isolated from CAD patients may actually activate disease-promoting biochemical pathways typical of diseased arteries. Why?

Understanding HDLc Associated Protein, PON1

Armed with these surprising results, the investigators wanted to find out why the HDLc from CAD patients was toxic to arteries. They first examined the HDLc particles purified from serum from both normal and CAD patients.

At first, they found little difference in composition. However, upon further examination, the investigators found a dramatic decrease in the activity of an antioxidant enzyme, paraoxonase 1 (PON1), in the CAD HDLc compared to that of a normal subject’s HDLc.

Interestingly, in earlier studies, this enzyme was also reported to be present at low levels in the serum of CAD patients compared to that of normal healthy subjects. However, the study discussed here was the first to show an important connection between the activity of PON1 and heart disease in humans.

PON1 and its possible relationship with heart disease has long flown under the radar. Today few medical professionals even know this enzyme exists.

PON1 and Toxic Oxidants

The results of the above studies indicate that the HDL-bound enzyme PON1 is an important component of HDLc in preventing heart disease.

The speculation is this enzyme protects the endothelial cell by preventing the production of toxic oxidants, such as LDLox, which is produced by inflammatory cells and found in the atherosclerotic plaques of diseased arteries.

Niacin remains one of the best therapeutics for maintaining a healthy cardiovascular system.

These studies help explain why a CAD patient’s HDLc, which has low levels of PON1 activity, is ineffective in protecting our arteries. It’s simply no match for the disease-producing toxins!

Additionally, this may explain why some therapeutic drugs that are effective in raising HDLc in CAD patients may offer little benefit to the patient’s health. Sure, the drug increases HDLc.

Unfortunately, it’s the HDLc with ineffective PON1! However, one HDL-raising therapeutic with positive effects on PON1 activity is niacin.

It is often prescribed for patients with unhealthy lipid profiles. Not only does niacin increase HDLc, but it also increases the antioxidant bound to the HDL, PON1.

Interestingly, niacin was the first therapeutic to be prescribed to patients with abnormal blood-lipid levels (high LDLc and triglycerides) more than five decades ago. Niacin remains one of the best therapeutics for maintaining a healthy cardiovascular system.

What’s New?

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Promising new research indicates that the nutrients in pomegranates have a stimulatory effect on the activity of the antioxidant enzyme, PON1. Berberine is another potential natural substance shown to help neutralize toxic oxidants (such as, LDLox) involved in inflammatory reactions in arteries.

In a different article, I’ll examine berberine, as well as a fermented yeast product that may help maintain a healthy level of the cholesterol-carrying molecule, LDLc.

RELATED: 7 Steps to Managing Cholesterol

At the Heart of Your Health

Fortunately, there are many simple ways to improve our cardiovascular health that don’t require a prescription or even a supplement. Topping your cardiovascular must-do list should be regular exercise, followed by a healthy diet rich in fruits and vegetables and stress management.

Is It Still Necessary to Undergo an HDLc Blood Test?

Based on the information above, does this mean you no longer have to take an HDLc blood test? The answer is no, but there’s a caveat.

Before we explain it fully, it’s best to have some idea what these exams are about. Many labs offer cholesterol blood tests or lipid profile testing.

These may be exams that measure two different types of lipids or fats: blood cholesterol (HDL cholesterol and LDL cholesterol levels) and triglyceride levels. Triglycerides are the types of fat that store the unused calories.

Some labs, meanwhile, can provide more specific exams. For example, they may provide only an HDLc blood test or LDL screening test.

The type of test the doctor may recommend depends on your risk factors. You may need to do more comprehensive blood cholesterol or lipid profile test if you:

  • Have metabolic disorders such as type 2 diabetes, cardiovascular disease, and lipid disorders or are at risk of these conditions
  • Are older (the average age is 45 for men and 55 for women)
  • Are living a sedentary or inactive lifestyle or obese
  • Have elevated levels of LDL or low high-density lipoprotein numbers during the previous exam

The Reliability of These Blood Tests

In hindsight, the likes of HDLc tests and other exams that monitor LDL cholesterol levels are essential to give you a picture of these biomarkers. Much of the contention, however, revolves around the reliability of the results.

Can you trust the HDL cholesterol number you see?

As discussed earlier, not everyone who takes medications to increase their HDL good cholesterol or bring down “bad cholesterol” can benefit from them.

Particular compounds such as niacin and PON1 have significant impact on the ability of HDL cholesterol to decrease cardiovascular risk.

Not all doctors also agree that the standard tests for assessing LDL cholesterol levels or HDL good cholesterol are necessary or even accurate. Instead, some suggest doing an ApoB test instead.

What is an ApoB test? It is a blood test that measures a lipoprotein called apolipoprotein B, which is a kind of low-density lipoprotein or LDL.

These lipoproteins combine with fats such as cholesterol and triglycerides to form LDL or VLDL (very low-density lipoprotein). All these are bad news when their numbers are high since they can lead to issues with the coronary artery and other blood vessels such as clogging.

For this reason, ApoB sounds to be a better indicator for cardiovascular risk than the routine HDLc blood test or lipid profile test.

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The other doctors and scientists, however, counter this by saying ApoB tests don’t provide any more critical information than the present ones.

It’s also possible for an HDLc blood test or other exams to provide false negatives or false positives. For example, LDL levels actually decrease after a person suffers from either a cardiac event like a heart attack or stroke.

Whether you need to fast or not can also affect the results of your HDL or LDL levels. Recent guidelines suggest you may no longer have to skip meals before you can undergo a blood screening test.

What’s the Best Step?

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Blood exams such as HDLc blood test are still impactful. They remain one of the most effective ways to assess your health and well-being.

These are often not enough, however. For a more complete picture, consider getting exams for blood glucose levels and kidneys.

People with cardiovascular risk or disease are also more likely to have or be predisposed to diabetes or kidney disease (or both).

You can also undergo a nutritional deficiency test to assess if you have a poor uptake of B vitamins. Note, though, that for niacin, urine, rather than blood test, is a better indicator for a problem.

Beyond HDLC Test: How to Lower Your Cholesterol Naturally

Dr. Treadwell* answers your questions.

Question: I’ve never had a heart attack, but recently, my physician prescribed a statin drug to lower my cholesterol.

However, I stopped taking the drug as it made my muscles ache. Do you have any suggestions as to how I can lower my cholesterol?

Thank you,

Dave, – Fort Meyers Beach, FL

Answer: I assume it is your LDL cholesterol that tested at a high level, and this is the reason your doctor prescribed a cholesterol-lowering drug.

There are a number of lifestyle changes proven to help reduce LDLc levels, and raise the good cholesterol, HDLc. These changes include:

  • Regular aerobic exercise
  • Diet low in sugar and refined grain products such as white bread, pastry, and high-glycemic junk foods

Additionally, your diet should be rich in fruits, berries, vegetables, and fish. Exercise and a healthy diet may help reduce the LDLc, but it might not be enough to get your LDLc to what is considered a healthy level (<200 mg/dl).

Red yeast rice is a natural substitute for the commonly prescribed statin class of cholesterol drugs. Available in vitamin stores, it has been demonstrated to be effective in lowering LDLc.

However, small amount of statins may be present in the red yeast rice, so it is recommended to have regular check-ups to be sure your liver enzymes are in the normal range. It is also important to consult with your health professional to be on the safe side.

*Dr. Benjamin V. Treadwell is a former Harvard Medical School professor and member of Juvenon’s Scientific Advisory Board.

A group of investigators from several institutions in Europe and the United States recently pooled their intellectual and technical resources.

The team devised an experimental protocol to determine the mechanism(s) involved in the negative effects on the health of arterial endothelial cells from HDLc isolated from patients with coronary artery disease.

They were aware of published results that had shocked the cardiology world. These surprising results showed the therapeutic used for raising HDLc in patients with coronary artery disease (CAD), actually produced an unexpected negative effect on their health.

In the experiment reported here, scientists took blood samples from normal, healthy patients and patients with CAD. The HDLc in the blood samples was isolated and purified.

The investigators were aware of results from previous studies demonstrating the capacity of HDLc to bind to endothelial cells and to stimulate those cells to produce the vaso-relaxant, nitric oxide. Nitric oxide has a positive impact on the arteries.

It acts to relax blood vessels, lower blood pressure, and consequently, the stress on arteries, as well as the health of the endothelial cells. The investigators confirmed these early results by repeating this experiment where they added HDLc isolated from the normal patients to human endothelial cells.

The obvious next step was to see if a similar effect occurred with the HDLc taken from patients with CAD. The result showed an astonishing lack of effect on nitric oxide production. Additionally, the endothelial cells appeared damaged.

Further analysis of the HDLc isolated from CAD patients revealed a dramatic decrease in the activity of an enzyme normally associated with HDLc, paraoxonase 1 (PON1), as compared to HDLc isolated from normal patients’ serum.

PON1 is believed to act as a potent antioxidant. The investigators speculate that in CAD patients’ HDLc, the enzyme (PON1) is inactive.

It, and may be at least partially responsible for the negative effects their particular HDLc has on endothelial cell health.

Additional experiments designed to examine the metabolic pathways associated with the activation of the enzyme, endothelial nitric oxide synthase (eNOS), demonstrated the susceptibility of eNOS to inhibition by cellular oxidants such as malondialdehyde, as well as oxidized LDL.

PON1 is crucial because it prevents the formation of these oxidants. The exact mechanism(s) involved in the inactivation of PON1, in CAD patients, is currently under further investigation.

Read the abstract here.

Disclaimer: This Research Update column highlights articles related to recent scientific inquiry into the process of human aging. It is not intended to promote any specific ingredient, regimen, or use and should not be construed as evidence of the safety, effectiveness, or intended uses of the Juvenon product.

The Juvenon label should be consulted for intended uses and appropriate directions for use of the product.

In the end, good and bad cholesterol isn’t as simple as you think. There are other factors that can affect their levels and, in turn, results of HDLc blood test or lipid profile test.

The more it becomes necessary to work with a doctor who advocates your overall health. This is especially true when you’re feeling unwell despite the positive or normal results.

It means your condition demands further investigation or perhaps better support besides a personalized diet and more physical activity. It may include specialized supplements like Essential Multi Vitamin or Q-Veratrol Antioxidant.

What do you think of the findings about “good cholesterol”? Is an HDLc blood test still reliable? Let us know your thoughts in the comments section below.

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Editor’s Note: This post was originally published on July 5, 2012, and has been updated for quality and relevancy.