Straight Dope on Medicine: There is Something about Cholesterol

Author

Scott Ganser
January 05, 2024

Cholesterol is the boogeyman of the medical realm. It strikes fear deep into the hearts of the populace. It really, really is up to no good and is doing terrible, dreadful things.

Like what?

One form of it, LDL, or low-density lipoprotein builds up plaque in arteries and eventually restricts blood flow or blocks it. When blood flow to the heart is blocked, it can cause angina (chest pain) or a heart attack.[i]

Good Cholesterol

Not everyone may be aware of this, because cholesterol gets such bad press. HDL, or high-density lipoprotein wears a white hat. It is actually beneficial. HDL carries cholesterol back to the liver. The liver then flushes it from the body. High levels of HDL cholesterol can lower your risk for heart disease and stroke.  

HDL is like a marble. It is compact, tight and tends not to stick. LDL is like cotton candy. It is diffuse and sticky. It gets over everything and stays.

What is the prevalence?

“Although the prevalence of severely elevated LDL-C (bad cholesterol) has declined, 1 in 17 U.S. adults still have LDL-C levels of 160 to 189 mg/dL [high cholesterol] and 1 in 48 adults have LDL-C levels of 190 mg/dL or greater [extremely high],” write the study authors.[ii]

The authors are Salim Virani, MD, and colleagues. The article is in JAMA Cardiology.

This a new scientific analysis finds that over 40 percent of people with high cholesterol don’t realize they have it — and are not getting treatment to improve it.

The silver lining is that high LDL levels among Americans has been dropping for two decades. Scientists calculated that high cholesterol declined from about 12 percent of adults (representing 21.5 million Americans) to about 6 percent (14 million) over roughly two decades.

The prevalence of extremely high cholesterol also fell, dropping from about 4 percent (6.6 million adults) to 2 percent (4.8 million adults) over that time period.

Too much of a good thing

How much of this good cholesterol do you need then? Health experts say that men should aim for an HDL level of 40 to 60 milligrams (mg) per deciliter (dL), and women should aim for 50 to 60 mg/dL to protect against heart disease and stroke.[iii]

Can HDL cholesterol be too high? It looks that way.

An elevated, or abnormally high, HDL level is anything above 80 mg/dL. One thing that can make your HDL cholesterol high is a genetic mutation. Some mutations to your genes can cause your body to produce too much HDL cholesterol or have trouble getting rid of it.[iv] For example, a mutation to the CETP gene can cause your HDL to be higher than 150 mg/dL.

Other causes of abnormally high HDL can include:

· Certain medications.

In one study, people who had HDL cholesterol levels above 60 mg/dL were nearly 50% more likely to have a heart attack or die from heart disease than people whose HDL levels were between 41 and 60 mg/dL.

Very high HDL levels could slow the process of clearing LDL cholesterol from your arteries.

Now they are also saying that very high HDL levels could be linked to dementia.

With more than 18,000 participants ages 65 years and older, the study was one of the largest yet to analyze the potential relationship between HDL cholesterol and dementia. Results of the study were published Thursday in The Lancet Regional Health – Western Pacific.[v]

People with levels higher than 80 mg/dL had a 27% increased risk of developing dementia during an average follow-up period of 6.3 years, compared to people in the optimal range. People age 75 years or older who had very high levels had an increased risk of dementia of 42%.

Aging really doesn’t help anything.

Cholesterol Positives

It isn’t completely one-sided. Cholesterol is important for maintaining cell membranes, the immune system, making hormones like estrogen, testosterone and adrenal hormones, and vitamin D synthesis.

Cholesterol Protocol

Steps to help lower unhealthy cholesterol include following a healthy diet (particularly limiting the amount of saturated fat you eat), getting regular exercise, and taking a cholesterol-lowering medication such as a statin.

“Statins are largely responsible for the decreased risk of heart attack and stroke that we've seen over the last few decades in the United States,” says Dr. Knowles, who was not involved in the research. “We’re in a golden age of medications that can be used to treat LDL very effectively and very safely.”

People should be exercising and not just be sitting behind a desk or playing X-box.

The right kinds of workouts, done regularly, can raise heart-protecting HDL (“good”) cholesterol levels and drop dangerous triglyceride levels, says Robert H. Eckel, MD, an emeritus professor at the University of Colorado School of Medicine in Aurora. “By losing fat and building muscle, your numbers can really improve.” [vi]

A review of studies on the relationship between cholesterol levels and exercise found a strong correlation between healthy cholesterol levels and exercise, partly due to weight loss. One study in the review found that for each kilogram (about 2.2 pounds) a person lost, their LDL (“bad”) cholesterol level went down by about 0.8 milligrams per deciliter.

To improve your cholesterol numbers, lower your blood pressure, and reduce your overall risk for heart attack and stroke, the American Heart Association (AHA) recommends getting at least 150 minutes (2.5 hours) of moderate exercise or 75 minutes (1.25 hours) of vigorous exercise per week. This works out to be about 20 minutes of exercise every day, or 30 minutes of exercise five days a week.

The optimal TC (total cholesterol) range for survival was 210–249 mg/dL for each age-sex group, except for men at 18–34 years (180–219 mg/dL) and for women at 18–34 years (160–199 mg/dL) and at 35–44 years (180–219 mg/dL).[vii]

Diet Matters

1. Legumes

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Legumes, also known as pulses, are a group of plant foods that include beans, peas, and lentils.

A 2021 study compared the effects of eating beans or white rice on LDL levels. After 29 days, the researchers found that the group who consumed 1 cup of beans each day had significantly lower LDL levels than on day 1.

Similarly, a 2019 review found that eating legumes helped lower LDL levels.

Legumes may also decrease your risk of certain health conditions, such as:

Try swapping legumes for refined grains and processed meats in dishes like chili, salads, and pasta.

2. Avocados

Avocados are a rich source of monounsaturated fats and fiber, two nutrients that help lower LDL and raise HDL cholesterol.

A 2015 study in 45 adults with obesity measured the effects of avocados on LDL cholesterol. The researchers found that participants who ate one avocado daily lowered their LDL levels more than those who didn’t eat avocados.

Similarly, a 2016 review of 10 studies determined that substituting avocados for other fats was linked to lower total cholesterol, LDL, and triglycerides.

There are many ways to eat avocados, such as in salads, guacamole, and on toast.

3. Nuts

The authors of a 2023 review found that nuts helped lower levels of LDL cholesterol, triglycerides, and total cholesterol. In particular, the following nuts had many benefits:

According to a 2016 review, one study found that eating a daily serving of nuts is linked to a 30% lower risk of cardiovascular disease.

The authors note that walnuts are also a rich source of omega-3 fatty acids. These are a type of polyunsaturated fats that have been associated improved heart health, lower LDL cholesterol levels, and reduced inflammation.

Similarly, almonds in particular are a natural source of phytosterols, which may help lower your LDL cholesterol.[viii]

Follow the Money

Statins are big business and have been for a long, long time. They rake in billions. So much so that Lipitor is the best-selling drug of all-time. It is the GOAT of pharmaceuticals.

Statins have been around for 40 years.

Lipitor is the main drug from a family of medicines called statins, which are used to lower blood cholesterol levels. Other drugs in this class include: fluvastatin, pravastatin, rosuvastatin and simvastatin. Generic versions of the drug are available and are sold under the name atorvastatin.[ix]

Lipitor was first approved in 1997. While under patent protection it was the highest-selling drug of all time, with worldwide sales at one stage of more than US$12 billion a year.

How it works

The human body requires a constant supply of a fat called cholesterol, which it uses to make hormones, bile and vitamin D.

Lipitor acts in the liver to stop the production of cholesterol, which has the flow-on effect of lowering the amount of LDL in the bloodstream. A daily dose of 40mg can be enough to reduce LDL levels by almost 50%.

Lipitor is supplied in packs of 30 as round, white tablets with the letters ATV stamped on one side and the dose (10mg to 80mg) stamped on the other side.

Statins taken as oral tablets or capsule can:

  • block HMG-CoA reductase, an enzyme that your liver uses to make cholesterol.

  • help your body reabsorb built-up cholesterol deposits from your arteries.

What do Statins do to HDL?

The first thought is that it probably lowers HDL because it shuts down cholesterol production in general. But, that is not the case. This is why we conduct studies. Our first thought might be wrong.

Statins cause modest increases in HDL-C and apo A-I probably mediated by reductions in CETP (cholesteryl ester transfer protein) activity. It is plausible that such changes independently contribute to the cardiovascular benefits of the statin class but more studies are needed to further explore this possibility.[x]

These elevations are maintained in the long-term. In hypercholesterolemia, HDL-C is raised by approximately 4% to 10%.

Side effects

Like all medicines, patients can experience side effects from the use of Lipitor. Common side effects include headache, sleep disturbance, dizziness and muscle pain. Rare side effects can include memory loss, allergic reaction, liver failure and nerve damage.

The use of statins, including Lipitor, is associated with an increased risk of new-onset diabetes. The drug is not recommended for children, or for women who are breastfeeding or planning on becoming pregnant.

Cost

The maximum price for the lowest dose (10mg) is A$18.91 for 30 tablets, while the price for 80mg tablets is A$24.79.

Statins No More

Some patients really, really don’t like statins. I have heard it over and over again. Typically these people experience muscle weakness.

And statins don’t work for everybody.

Fortunately for them we now have the PCSK9 inhibitors.

What is the difference between statins and PCSK9 inhibitors?

Statins work at the production level. They turn off the spigot. PCSK9 inhibitors work at the receptor level. The shut down/lower the body’s use of the cholesterol.

PCSK9 inhibitors are injected.

Evolocumab (Repatha)

One common PCSK9 inhibitor called evolocumab (Repatha) was approved by the Food and Drug Administration (FDA) in 2015.

The substance evolocumab used in Repatha is known as a monoclonal antibody protein. In this case, which means the evolocumab protein attaches to and blocks the PCSK9 gene from reducing LDL receptors.

This action allows more receptors to lower LDL cholesterol in the blood without the interference of the PCSK9 gene.

A2015 clinical trial found that people taking evolocumab for 1 year reduced their LDL cholesterol by about 60 percent compared to those who didn’t take it. In the following year, just under 1 percent of people taking evolocumab had a heart-related event as compared to over 2 percent of people who weren’t taking the medication.

Alirocumab (Praluent)

Alirocumab (Praluent) is another commonly used PCSK9 inhibitor that was approved by the FDA in July 21015.

Just like evolocumab in Repatha, the substance alirocumab used in Praluent is a monoclonal antibody protein that attaches to the PCSK9 gene. This blocks the gene from reducing LDL receptors that help lower LDL cholesterol in the body.

A 2015 clinical trial also showed success in lowering LDL cholesterol — only 1.7 percent of people studied experienced some type of heart-related event during the trial’s 78-week period.

A 2107 review in the World Journal of Cardiology suggested that using PCSK9 inhibitors could help lower LDL cholesterol levels in the blood by 50 percent or more above that achieved by statins alone.[xi]

Cholesterol Vaccine

Oh yes, we are going there.

In a recent study published in NPJ Vaccines, a team led by Bryce Chackerian, PhD, Regents’ Professor in the Department of Molecular Genetics & Microbiology, reported the vaccines lowered LDL cholesterol almost as effectively as an expensive class of drugs known as PCSK9 inhibitors.[xii] 

Nearly two in five U.S. adults have high cholesterol, according to the Centers for Disease Control and Prevention (CDC). Untreated, high cholesterol can lead to heart disease and stroke, which are two of the top causes of death in the U.S. Worldwide;, cardiovascular diseases claim nearly 18 million lives every year, according to the World Health Organization. 

 Study in a nutshell

  • UNM researchers developed a vaccine to block a protein that heightens cholesterol levels, by creating an antibody response against the particles.

  • The remedy was created with vaccine platform technology developed at The University of New Mexico.

  • The vaccine has been tested on mice and monkeys with promising results.

A new vaccine developed by researchers at The University of New Mexico School of Medicine could be a game-changer, providing an inexpensive method to lower “bad” LDL cholesterol, which creates dangerous plaques that can block blood vessels. 

 

LDL Evil Twin

Lp(a) or lipoprotein-A is a cardiovascular risk as well. Statins don’t lower this number, but the PCSK9 inhibitors will by about 25%.

You only need to get this checked once in a lifetime. It does not change.

At normal levels, Lp(a) may help promote tissue repair and accelerate wound healing.

At elevated levels of ≥50 mg/dL (≥125 nmol/L), Lp(a) can increase lifelong risk of cardiovascular disease, aortic valve stenosis, coronary artery disease, heart attack, and stroke via proatherogenic, proinflammatory, and prothrombotic mechanisms.[xiii]

The normal range is 5 to 30 mg/dL. It isn’t desirable to be near 30.

All that is available right now for potential treatment are PCSK9 inhibitors, niacin and lipid apharesis.


[vii] Yi, SW., Yi, JJ. & Ohrr, H. Total cholesterol and all-cause mortality by sex and age: a prospective cohort study among 12.8 million adults. Sci Rep 9, 1596 (2019). https://doi.org/10.1038/s41598-018-38461-y