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LDL Cholesterol: Genetics, personalized solutions

Key takeaways:
~ Heart disease is the leading cause of death in the US and around the world, and high LDL-cholesterol levels have been linked in many studies to increased heart disease.
~ Cholesterol is essential and needed in your cells, in the right amounts.
~ Genetic variants can cause high cholesterol, and specific natural supplements or diet changes may work well, depending on your genes.

Members will see their genotype report below, plus additional solutions in the Lifehacks section. Join today 

Cholesterol: Necessary in the right amounts

When you read about cholesterol and heart disease, it is easy to believe that cholesterol is something terrible that you don’t want in your body. But that is far from the whole picture! Cholesterol is essential for your health and well-being.

Cholesterol is a type of lipid (fat) created only by animals. It is an essential part of every cell and important for digesting foods and creating hormones.

A membrane composed mainly of phospholipids surrounds every cell in your body. Cholesterol molecules make up part of that cell membrane, stabilizing the membrane to help maintain its integrity. Cholesterol keeps the membrane firm enough to keep some very small water-soluble molecules out, yet not too rigid.

 

Cell membrane showing cholesterol molecules within the phospholipid bilayer. Wikimedia Commons.

In addition to being part of the structure of cells, cholesterol is also the precursor for bile acids, vitamin D, and steroid hormones.

  • Bile acids are essential for digesting fats in the diet
  • Vitamin D plays a significant role in calcium metabolism and bone health.
  • The steroid hormones include testosterone, estrogen, progesterone, cortisol, and aldosterone.

What is the right level of cholesterol?

Like most things in the body, optimal health is a matter of having neither too much nor too little cholesterol. The right amount is personal, and it depends on our genes, diet, age, and lifestyle.

Below is a chart showing that mortality is lowest in people with an LDL that is a little over 100. The chart shows a sharp increase in mortality with low cholesterol levels and with really high cholesterol levels. One reason for the high mortality rates with low cholesterol is that cholesterol helps protect against infectious diseases.[ref] Somewhat higher cholesterol is also associated with a lower risk of diabetes.

Chart from a study of over 500,000 adults in S. Korea,  comparing LDL levels to mortality rates. PMC6832139

A large 10-year study out of Norway found the lowest mortality rates occurred in people with cholesterol levels between ~190 to 270 mg/dl (5 and 7 mmol/l).[ref]

The CDC and many other health organizations, though, have a narrower range of what they consider healthy.

The CDC range for healthy cholesterol is:[ref]

  • Total cholesterol: Under 200 mg/dL is normal
  • LDL cholesterol: Under 100 mg/dL is normal
  • HDL cholesterol: Best to have more than 40 mg/dL
  • Triglycerides: Normal is below 150 mg/dL

These ranges vary in other countries, and the ‘normal’ level changes periodically. For example, according to a JAMA article, normal cholesterol ranged from 240 mg/dL in 1986 and up to 260 mg/dL in 1983.[ref]

Where does cholesterol come from?

There are two sources of cholesterol:

  • Cholesterol in foods
  • Cholesterol that your body makes

In addition to the cholesterol that your body makes, cholesterol from food (animal products) is absorbed in the intestines. Eating foods that contain cholesterol causes a temporary increase in serum cholesterol levels, with levels dropping to baseline in about seven hours.[ref]

Generally, eating cholesterol causes the body to produce less of it, and decreasing your cholesterol intake will trigger the body to make more of it. This doesn’t hold true for everyone, but this is the way that it usually works.

Most cholesterol in the body is synthesized in the liver, intestines, adrenals, and reproductive organs. It is a multi-step, complex process to make it.

The regulation of cholesterol synthesis occurs through several processes, with one of the main regulators being the SREBP protein, coded for by the SREBF1 and 2 genes. Other genes involved in your cholesterol levels include cholesterol transport and receptor genes.

How is cholesterol stored?

Cholesterol can be stored in fat droplets packaged with triglycerides and lipoprotein. Chylomicrons are created from dietary fats and contain apolipoproteins, triglycerides, and cholesterol. The backbone of chylomicrons is ApoB. Chylomicrons are taken up by the lymphatic system and then transferred to blood circulation. Once in circulation, chylomicrons incorporate into adipose (fat) or muscle tissue.[ref]

Chylomicron packing up triglycerides, cholesterol

 

Additionally, cholesterol can be made in the liver and packaged into LDL particles of different densities and sizes, such as VLDL (very low-density lipoprotein) particles. These circulating LDL particles can then bind to cells with an LDL receptor to be utilized by the cell.

How is cholesterol used?

Cholesterol levels are tightly regulated by cells.

LDL receptors control the uptake, and the cell then controls how many LDL-Rs are available via a couple of proteins, including PCSK9.

When excess cholesterol is available, excretion through the liver into the feces occurs. This process is called reverse cholesterol transport. The ABCA1 protein is responsible for moving cholesterol back out of the cells.

See the genotype report section for more on how these gene impact your cholesterol levels.

Cholesterol and Heart Disease: Controversial?

According to the CDC, LDL, or ‘bad’ cholesterol, increases heart disease and stroke risk. They recommend eating “foods with plenty of fiber, such as oatmeal and beans, and healthy unsaturated fats, such as avocados, olive oil, and nuts.”[ref]

One reason that LDL is linked to heart attacks is because cholesterol is a component of plaques that can build up in the arteries. When the cells lining the blood vessels (endothelial cells) become inflamed, LDL particles are included in the layers of the arteries. When the LDL cholesterol becomes oxidized by reactive oxygen species, it increases inflammation in the vessel.[ref]

ldl cholesterol
CC image showing plaque buildup in artery

It’s simplistic to say that LDL-c is “bad cholesterol” since it is necessary and essential at the right levels. Let’s dig into the research here because the truth isn’t always as black and white as health websites claim.

A 2010 meta-analysis of twenty-six large clinical trials using statins to reduce cholesterol found the following.[ref]

For every 39 mg/dL reduction in LDL cholesterol level:

  • all-cause mortality is 10% lower
  • mainly due to reduced heart attack deaths
  • no effect on strokes or cancer

Studies using genetic risk scores (looking at multiple genetic variants related to cholesterol) find that a lifetime of lower cholesterol levels is associated with lower overall mortality risk.[ref]

“Results of the current study indicate that a genetic predisposition to high LDL-C levels contributes to mortality throughout life, including in the oldest old, and a beneficial LDL genetic risk profile is associated with familial longevity.”

On the other hand, some researchers argue that there is no causality between high cholesterol and heart disease.[ref] Naturally, many of the research studies on statins, cholesterol levels, and heart disease are funded by pharmaceutical companies. And the endpoints and definitions of ‘high’ cholesterol make it hard to compare between studies. It makes it easy to create doubt about the link between really high cholesterol and heart disease.

Familial Hypercholesterolemia (FH): Really high cholesterol genes

Genetic mutations can cause what is known as familial hypercholesterolemia or FH, which is lifelong high cholesterol. Estimates show that 1 in 200 people have FH mutations, which increases the risk of heart disease by 20-fold. In adults, LDL-C levels are often over 190 mg/dL in people with FH mutations.[ref][ref]

While this is still an area of active research, so far, mutations have been identified in the PCSK9, APOB, LDLR, and LDLRAP1 genes.

Statins and Cholesterol-Lowering Medications

Statins, one type of cholesterol-lowering medicine, are among the most prescribed medications in the US and UK. In 2014 about 28% of Americans over age 40 were taking a statin.

A Cochrane study on atorvastatin found that LDL cholesterol decreased by 37 – 51%.[ref] However, this doesn’t answer the question of whether that is beneficial to health or prevents death.

The Number Needed to Treat website has an extensive review of studies on statins, including the significantly increased risk of diabetes and muscle pain. It is an interesting, well-crafted assessment of the risks and benefits that concludes that statins’ risks outweigh the benefits for most people. Everyone is unique. Talk with your doctor about your specific risks and benefits.

Related article: Statins, genetics, and muscle pain

Recent Studies on Cholesterol

Studies on both high and low LDL cholesterol show a variety of different effects.

Low cholesterol links:

  • A March 2018 study found that lung cancer patients with low cholesterol were at a 61% higher risk of death.[ref]
  • Low LDL-C is associated with greater rates of sepsis in the elderly.[ref]
  • A study of over 100,000 people in Denmark found that having a lifeline lower LDL cholesterol level (1 mmol/L lower) reduced the risk of Alzheimer’s and dementia.[ref]

High cholesterol links:

  • A review in the JAMA found that each “additional 300 mg of dietary cholesterol consumed per day was significantly associated with a higher risk of incident” of cardiovascular disease.[ref]
  • A large review in the Lancet recently found that reducing LDL cholesterol reduces the risk of “major vascular events”.[ref]

A picture emerges that LDL levels that are neither lower than normal nor higher than normal are best for overall mortality rates.


Cholesterol Genotype Report:

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Lifehacks:

If you have high cholesterol and are trying to avoid going on a statin, here are some diet and supplement ideas to try. Of course, talk with your doctor if you have any medical questions.

Modifying Cholesterol with Diet

The old advice to give up eggs to lower your cholesterol is inaccurate[ref]. Similarly, choline from eggs or supplements does not raise cholesterol levels.[ref]

So what works to lower cholesterol? A whole-food diet and moderate exercise are usually beneficial for keeping cholesterol levels in check. Yep – standard advice to cut out fast food and hit the gym a few times per week. Cutting out processed food should decrease inflammation and lower cholesterol levels. Cleaning up the diet does work for most people and is an obvious route to try.[ref][ref]

A meta-analysis that combined the data from a bunch of studies found that fruit and vegetable intake of 3+ servings per day decreases triglyceride levels and improves total cholesterol. (Interestingly, the study found no extra benefit from consuming five or more servings of fruits and vegetables per day.)[ref]

How much does diet matter? Type 2 diabetics on a low-fat vegan diet (lots of fruits and vegetables) had a decrease in cholesterol levels of 13.5 mg/dL.[ref]

Ketogenic Diet and LDL:

A recent study of healthy, normal-weight women found that a low-carb, high-fat ketogenic diet for a month increases LDL cholesterol significantly (~70 mg/dL). The diet was high in saturated fats and low in fiber.[ref]

Keep in mind that individual results will likely vary – the range of increase was between 40 and 90 mg/dL for these study participants.

7 Natural supplements with solid research for lowering cholesterol

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Related Articles and Topics:

Triglyceride Levels
High triglycerides are linked with an increased risk of cardiovascular disease. Both genetics and diet combine to elevate triglyceride levels. Learn how your genes interact with what you eat to lower your triglycerides.

Lipoprotein (a)
High Lp(a) levels are a big risk factor for sudden heart attacks. Your genetic variants mainly control your Lp(a) levels. Check to see if you carry genetic variants that increase or decrease Lp(a).

Top 10 Genes to Check in Your Genetic Raw Data
Wondering what is actually important in your genetic data? These 10 genes have important variants with a big impact on health. Check your genes (free article).

Sudden Cardiac Death and Hypertrophic
Genetic mutations that cause hypertrophic cardiomyopathy can increase the risk of sudden cardiac death.

Originally published 2/2015

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About the Author:
Debbie Moon is the founder of Genetic Lifehacks. Fascinated by the connections between genes, diet, and health, her goal is to help you understand how to apply genetics to your diet and lifestyle decisions. Debbie has a BS in engineering from Colorado School of Mines and an MSc in biological sciences from Clemson University. Debbie combines an engineering mindset with a biological systems approach to help you understand how genetic differences impact your optimal health.