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Natural Alternatives to PCSK9 Inhibitors

According to conventional medicine, lowering cholesterol is the primary way to avoid having a heart attack. But is this intense fixation on cholesterol as the enemy the right approach? One look at heart disease numbers today and the answer is a resounding no. 

Approximately one in four American adults over 40 take cholesterol-lowering medication to reduce their risk of strokes, heart attacks, and other cardiovascular diseases. Statins have been the first-line drug of choice for both primary and secondary prevention. However, there’s a relatively new medication gaining popularity when it comes to treating high cholesterol. 

In 2015, the Food and Drug Administration (FDA) approved using PCSK9 inhibitors to help lower cholesterol, specifically low-density lipoprotein (LDL). But, while being hailed by some as a miracle drug, are these injectable cholesterol-lowering medications safe and effective? 

Understanding cholesterol and lipoproteins

Cholesterol is a waxy type of lipid, a fatty compound. The liver makes all the cholesterol the body needs to function, although we also obtain some through our diets. Sadly, cholesterol has often been vilified. However, the body needs cholesterol to build healthy cells, produce hormones, and help make substances that aid digestion. 

Have you ever heard the phrase oil and water don’t mix? The same is true for fatty cholesterol and blood. Cholesterol can’t travel through blood alone. Instead, it’s packaged into round particles called lipoproteins. Lipoproteins are the vehicles that carry cholesterol and triglycerides through the body. Think of cholesterol as the passengers and lipoproteins as the car that delivers them to their destination.

There are a few different kinds of lipoproteins. Although characterized as the “bad” type of cholesterol, low-density lipoproteins (LDL) carry fundamentally important chemicals to all body cells. According to conventional medicine, too much circulating LDL leads to plaque build-up in the blood vessels, causing them to become narrow and increasing the risk of a heart attack. 

The liver has LDL receptors that pick up LDL, thus lowering the amount circulating in the blood. The lower the number of receptors on the liver, the higher the LDL plasma levels. 

What are PCSK9 inhibitors?

In the early 2000s, scientists discovered a genetic mutation that caused certain individuals to develop cardiovascular disease at a young age. In addition, the subjects had higher than normal LDL levels in their blood. This discovery opened the door for understanding proprotein convertase subtilisin/kexin type 9, or PCSK9.

Everyone is born with the PCSK9 gene, which instructs the liver to make PCSK9 protein. PCSK9 binds to and destroys LDL receptors in our liver. Therefore, the more PCSK9 protein in the body, the fewer LDL receptors and the higher the circulating LDL in the blood. 

Individuals with mutations in this gene – referred to as familial hypercholesterolemia- often have higher levels of PCSK9. As such, they have lower LDL receptors, resulting in higher levels of circulating LDL in the bloodstream. 

PCSK9-inhibiting drugs are monoclonal antibodies, which means they are lab-made antibodies. These drugs are typically prescribed to individuals under the following conditions:

  • High-risk cardiovascular patients whose cholesterol is not controlled with statins
  • Those with familial hyperlipidemia 

What do PCSK9 inhibitors do to cholesterol? 

PCSK9 inhibitors attach themselves to PCSK9 proteins, blocking them from acting on LDL receptors. As a result, LDL receptors increase, pulling more LDL from the blood. So, theoretically, PCSK9 inhibitors allow the body to remove cholesterol more efficiently.

There are currently two FDA-approved monoclonal antibodies that inhibit the action of PCSK9: 

  • alirocumab (Praluent)
  • evolocumab (Repatha) 

What is the difference between PCSK9 drugs and statins?

PCSK9 inhibitors work differently than statin medications. Statins block a compound called HMG-CoA reductase. Because the liver needs HMG-CoA reductase to make cholesterol, statins reduce the amount of cholesterol made by the liver. Additionally, statins also remove excess cholesterol from the blood. 

StatinsPCSK9 inhibitors
How they are made?Small molecule drugs made from chemicalsBiologics – meaning they are produced from living sources
How are they given?Oral medications given by mouthInjectable medications given subcutaneously under the skin
How often do you take them?Daily1-2 times per month
How much do they cost?Approximately $600 a year for generic drug Approximately $6000 a year 

Do PCSK9 inhibitors work?

PCSK9 inhibitors are effective at lowering LDL cholesterol. In fact, this class of pharmaceuticals lowers LDL cholesterol by over 50 percent. 

In a 2017 NEJM randomized, double-blinded study of over 27,000 people, LDL cholesterol levels dropped from 92 mg/dL to 30 mg/dL after 48 weeks of taking the PCSK9 inhibitor, evolocumab.

While this study is often cited as proof of why PCSK9 inhibitors are effective, there are some weaknesses. For example, the study subjects were very homogenous. While the average age was 63, 85 percent of the participants were white, and 75 percent were male. Moreover, the study subjects were extremely high risk as follows: 

  • 81 percent had prior heart attacks
  • 20 percent had a previous stroke
  • 80 percent had high blood pressure
  • 37 percent had diabetes 
  • 28 percent were current smokers
  • 100 had used statins
  • 93 percent had used aspirin or other antiplatelet therapy

The study showed a modest 1.5 percent reduction in heart attacks, stroke, unstable angina, and cardiovascular death for those taking the PCSK9 inhibitors. However, it’s worth noting that more people died in this group, with 444 deaths compared to 426 deaths in the placebo group. In addition, the study did not examine the long-term risks associated with this novel therapy. 

A recent study reanalyzed the findings from the 2017 study and concluded that some deaths might have been misclassified. This new paper concludes that the risk of cardiovascular death is higher with evolocumab than initially reported in the trial. The researchers found eleven more heart attack deaths in the PCSK9-treated patients and three fewer deaths from heart attacks in the placebo group than initially reported in the NEJM study. 

While PCSK9 inhibitors work to lower cholesterol significantly, they are barely effective in reducing the rate of serious cardiovascular incidents and death. Why take a risky medication with substantial side effects to lower cholesterol if it does not enhance survival? The cost – both monetarily and physically – outweighs the potential benefits by far. 

Size matters! 

Doctors get caught up in cholesterol numbers, and while the numbers matter to a degree, it’s much more important to look at cholesterol particle size. This is because health risk has more to do with particles’ quantity and size than with overall cholesterol numbers. 

Small, dense particles are much more likely to cause a build-up of plaque in the arteries, leading to a potential heart attack or stroke. On the other hand, large, fluffy cholesterol particles are less problematic. 

Many patients have seemingly normal cholesterol numbers by conventional medical standards. For example, someone might have an LDL cholesterol of 90, but if the LDL particles are small, they are very dangerous. Measuring particle size is a simple blood test, but most doctors don’t order it. 

5 Natural alternatives to PCSK9 inhibitors

Unfortunately, there are enough unanswered questions about PCSK9 inhibitors to deem them safe and effective. But the good news is there is a better way to lower lipids naturally.

  1. Eat like our ancestors 

Consuming a healthy diet free of pesticides, GMOs, and other processed chemicals are the absolute best way to improve your lipid profile. Studies show that diet can trump genetics even if high cholesterol runs in your family. 

Increase your intake of antioxidant-rich foods and omega-3s. An ideal diet consists of organic produce, grass-fed meat, pasture-raised poultry, and wild seafood. It also includes plenty of nuts and seeds. 

  1. Move your body 

Exercise is an integral part of improving lipid levels in the body. Exercise helps to move LDL from the blood to the liver. Moreover, studies show that regular movement increases the size of LDL protein particles, making them more fluffy and buoyant. 

While all exercise matters, evidence suggests that high-intensity interval training (HIIT) lowers dense LDL. Animal studies have also concluded that HIIT is more effective than moderate-intensity continuous training at restoring cholesterol ratios to a healthy level. 

  1. Prioritize sleep 

Sleep is often overlooked when it comes to lifestyle habits that impact cholesterol. However, poor sleep is a crucial contributing factor to high cholesterol. 

Studies show that finding the right balance of sleep matters. For example, men who slept less than six hours increased their LDL by 9 mg/dL. However, other studies have found that sleeping too much negatively impacts lipid levels. Therefore, aim for 8-9 hours of undisturbed, quality sleep each night. 

  1. Spend time in the sun

Believe it or not, spending time in the sunshine is a natural way to lower cholesterol. When sunlight hits the skin, cholesterol is used to make vitamin D. The more vitamin D the body produces, the lower the cholesterol levels in the body. Therefore, expose as much of your naked skin to the sun each day as safely possible. 

  1. Use evidence-based supplements

While most conventional doctors are running to their prescription pads, those in the know about true health are running to natural supplements. 

One of the most effective natural supplements to treat high cholesterol is berberine. Berberine is a chemical compound found in plants such as goldenseal, goldthread, tree turmeric, and European barberry. 

Scientific studies show that berberine is nearly as effective as PCSK9 inhibitors in lowering LDL cholesterol and improving lipid levels without all the worrisome side effects. 

Next steps 

Conventional medicine tends to over-prescribe pharmaceuticals while underemphasizing the importance of dietary and lifestyle changes for cholesterol levels. 

If you are on a statin or a PCSK9 inhibitor, you should know that there are safer and more effective options. Our specially formulated Optilipid, created by cardiologist Jack Wolfson, is an excellent alternative to pharmaceutical drugs. Made with berberine, resveratrol, ginger, silymarin, ginger, and green tea, Optilipid is an effective statin alternative for healthy cholesterol levels. 

Medical Review: Dr. Jack Wolfson, 2023

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