What is Cholesterol?

We can think of cholesterol as one of the building blocks of our body; It is a fat-like, waxy substance that strengthens our cell walls, plays a role in the production of vitamin D and some hormones (e.g. stress and sex hormones), and is even used in the production of bile acids that aid digestion. Every cell in our body needs it to function healthily.

Interesting information: Most of the cholesterol in our body does not come from the food we eat. Most of our cells, especially our liver, can produce the cholesterol they need in their own little factory. In other words, most of the cholesterol in our blood is actually “domestic production”.

How Does Cholesterol Travel in the Blood?

Since cholesterol has a fat structure, it cannot circulate freely on its own in the aqueous environment of our blood. Just like water and olive oil do not mix. So our body has come up with a clever solution: It loads cholesterol and other fats (like triglycerides) into special carrier packages. We call these packages lipoproteins. We can think of these as trucks carrying cholesterol:

LDL Trucks (Low-Density Lipoprotein): These trucks transport cholesterol from the liver to other tissues in the body. Cells need cholesterol, but too much of these trucks can cause problems. That’s why it is popularly known as “bad cholesterol”.

HDL Trucks (High-Density Lipoprotein): These trucks do the opposite; It collects excess cholesterol in the tissues and carries it back to the liver, that is, the recycling center. Because of this cleaning task, it is called “good cholesterol”. In fact, the cholesterol in both LDL and HDL is exactly the same. Good and bad are lipoproteins, the packages in which they are carried.

VLDL Trucks (Very Low-Density Lipoprotein): These, too, are produced in the liver and carry mostly triglycerides (another type of blood fat), but they can convert to LDL in the circulation over time.

If Cholesterol is So Important, Why Are We Trying to Lower It?

This is where the confusion begins: “If cholesterol is so vital for our cells, why do we doctors say ‘lower your cholesterol’?”

It’s a very valid question. To understand this, we need to clarify: Our goal is not to eliminate all the cholesterol in our body, it is already impossible to do this and it would be incredibly harmful if we could. Our main goal is to reduce the amount of fat in the bloodstream, especially the “bad” ones (like LDL). To reduce them, we need to reduce cholesterol, especially the cholesterol produced in the liver. At least this is one of the most important methods. Because it is not the cholesterol inside the cells that causes the problem, but the cholesterol packages that accumulate in the blood and stick to the vessel wall.

Imagine that there are trucks carrying many goods in the city. There are also items inside the houses, and these items are very necessary for people to live. Our goal is not to completely destroy these items, but to reduce the number of trucks in traffic. Because if there are too many trucks in traffic, especially those carrying dangerous loads, the risk of accidents and congestion increases. That’s what we’re doing: Trying to reduce the excess LDL trucks and the load they carry, which cause “traffic jams” and “accidents” (i.e. plaque buildup) in the arteries. So, what we are actually trying to reduce is the number and density of lipoprotein particles (especially those containing ApoB) circulating in the blood and having the potential to leak into the vessel wall, rather than directly the total amount of cholesterol in the body.

Traffic Jam and Plaques

If there are too many LDL trucks circulating in the blood, over time they start to “bump” and stick to the inner walls of our arteries. As our body tries to repair this situation, things can get even more complicated and structures we call “plaque” form here. These plaques grow and harden over time, narrowing the vessels and obstructing blood flow. We call this condition atherosclerosis (hardening of the arteries) and it is the main cause of serious problems such as heart attack and stroke.

Is the Real Issue Load or Number of Trucks? Why is ApoB Important?

When talking about cholesterol for years, we always focused on the amount of cholesterol carried by LDL (LDL-C). However, in recent years, scientific studies have shown us another important point: Perhaps what is more important is the number of trucks on the road and their size, rather than the load inside the trucks [3, 4].

Each “bad” or potentially “bad” truck (such as LDL, VLDL, IDL) carries only one protein molecule called Apolipoprotein B (ApoB). So measuring the level of ApoB in your blood is actually like directly counting the total number of trucks circulating in your veins that have the potential to form plaque [3, 5].

Studies have shown that ApoB may be more sensitive than standard LDL-C measurement in predicting heart disease risk, especially in some cases (for example, high triglycerides, metabolic syndrome, or very low LDL levels). Sometimes even if LDL-C appears normal, ApoB may be high (i.e. trucks may be small but very numerous – a “small dense LDL” situation), which may mean a hidden risk[4, 6].

Cholesterol Drugs and the Brain: Should We Worry?

Now that we know all this, let’s answer another frequently asked question that starts with “if cholesterol is so important”: Do cholesterol-lowering drugs (especially statins) harm the brain? To understand this issue, we first need to understand the production of cholesterol in the brain:

Our brain has a self-contained cholesterol system that operates largely independently of the rest of our body. Brain cells produce almost all the cholesterol they need and do not release this cholesterol into the bloodstream [7, 8]. There is a very tight firewall between the blood and the brain called the “blood-brain barrier”. This wall prevents the passage of lipoproteins (such as LDL) in the blood to the brain [8, 9]. The brain uses unique proteins such as ApoE and specialized transport systems for cholesterol transport [10, 11].

So how do statins affect this condition? Most statins (water-soluble) have little or no ability to cross the blood-brain barrier. Although some fat-soluble statins may have some effect, they do not produce a significant lowering effect on cholesterol production or levels in the brain [12]. Studies show that lowering blood cholesterol does not “starve” cholesterol, which is necessary for brain functions [8]. In short, concerns that the cholesterol treatment your doctor recommends will harm your brain are unfounded. If you are still very concerned about statins that may leach some, you can use one of those that do not (water soluble – hydrophilic).

So How Does What We Eat Affect Truck Traffic?

Our diet can affect our cholesterol levels, but the effect varies from person to person.

Saturated Fats: A diet rich in saturated fats such as butter, fatty red meat, and processed meat products can increase the number of LDL trucks [13]. This increase is limited unless excessive (up to 20%).

Unsaturated Fats and Fiber: Healthy oils such as olive oil, avocado, walnuts and almonds; Fiber foods such as oats, legumes, vegetables and fruits can help lower LDL. Many studies have shown that dietary patterns such as the Mediterranean diet are beneficial to heart health[14].

Special Diets: Special diets such as the “Portfolio diet” (which includes plenty of fibre, plant protein, nuts and plant sterols) have been shown to lower LDL by around 17%.

Cholesterol in Food: The effect of cholesterol-containing foods, such as eggs, on blood cholesterol is not as great as thought in most people, because the body can reduce its own production when external intake increases. But some people may be “hyper-responsive” and be more affected. Therefore, as long as you don’t overdo it, you won’t increase your cholesterol levels much by eating a normal number of eggs.

Cholesterol Management: How Do We Relieve Traffic?

If your cholesterol levels are high or you are at increased risk of heart disease, your doctor may recommend various treatments:

Lifestyle Changes: This is always the first step! Healthy eating, regular exercise, weight control, quitting smoking, etc.

Medicines:

Statins: They are the most commonly used drugs. They reduce the liver’s production of cholesterol and accelerate the clearance of LDL trucks in the blood.

Ezetimibe: It reduces cholesterol absorption from the intestines.

PCSK9 Inhibitors: They are newer, stronger drugs and are administered as injections. They prolong the life of the receptors that allow LDL trucks to be cleared from the blood.

Bempedoic Acid: It is an option especially for people who cannot use statins, as it blocks cholesterol production in the liver through a different pathway [15].

All of these drugs essentially aim to reduce the number of ApoB-containing (i.e., potentially harmful) lipoprotein particles in the blood.

What is the situation in Türkiye?

Unfortunately, cardiovascular diseases are still the leading cause of death in our country[16]. Research shows that average LDL cholesterol levels in adults in Türkiye are above the target and cholesterol imbalance (dyslipidemia) is very common. This situation also puts a great burden on our healthcare system [17].

In summary: 

– Cholesterol is necessary for our body, but too much of it causes plaque accumulation in our veins.

– Cholesterol is carried in the blood in packages (trucks) called lipoproteins; LDL is known as “bad” and HDL is known as “good”.

– In determining the risk of atherosclerosis, not only the amount of cholesterol carried by LDL (LDL-C), but also the total number of “bad” trucks (ApoB) is very important.

– The brain produces its own cholesterol, and drugs that lower blood cholesterol generally do not adversely affect brain health.

– A healthy lifestyle (nutrition, exercise, smoke-free life) is the basis of cholesterol management, and medications are lifesaving when necessary.

What to Do?

If you have risk factors for heart disease (such as a family history of heart disease at an early age, diabetes, high blood pressure, smoking, obesity), consult your doctor to find out your cholesterol status. Your doctor may recommend that you evaluate not only standard cholesterol measurements, but perhaps also more detailed tests such as ApoB to better understand your risk. After this, as I wrote before, a risk assessment can be made and, if necessary, even further tests may be requested.

Remember, health decisions are personal. Determine the most suitable road map for you by talking to your doctor, not by looking for advice on the internet or from friends. Unconscious “check-up” tests or misinterpretations can cause more confusion and unnecessary anxiety than benefit!

References:

1. Li Y, Chen Y, Li S, et al. Regulation of cholesterol homeostasis in health and disease. Signal Transduction & Targeted Therapy 2022;7:265. 
2. Guo J, Chen S, Zhang Y, et al. Cholesterol metabolism: physiological regulation      and diseases. MedComm 2024;5(2):e476. 
3. Awwad O, Sniderman A, Hammond G, et al. Physiological bases for the superiority of apolipoprotein B over LDL-cholesterol. J Am Heart Assoc 2022;11:e025858.
4. Sniderman A, Lamarche B, Lawler PR, et al. Interplay of atherogenic particle number      and particle size and the residual risk of atherogenic dyslipidemia. Clinical Chemistry 2023;69(1):48-55. 
5. European Society of Cardiology & European Atherosclerosis Society. 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to      reduce cardiovascular risk. Eur Heart J 2020;41(1):111-188.
6. Sniderman A D, Hegele R A, Lukens J N, et al. Standardization of apolipoprotein B, LDL-cholesterol and non-HDL-cholesterol. J Am Heart Assoc 2023;12:e030405.
7. Keep RF, Jones H C, Hamilton M G, Drewes L R. A year in review: brain barriers      and brain fluids research 2022. Fluids & Barriers of the CNS 2023;20:30. 
8. Savulescu-Fiedler I, Kühl S J, Schmidt P, et al. The cross-talk between peripheral and brain      cholesterol metabolisms: implications for neurodegenerative diseases. Current Issues in Molecular Biology 2025;47(2):115.
9. Chaves J C S, Dando S J, White A R, Oikari L E. Blood-brain barrier transporters:      an overview of function, dysfunction in Alzheimer’s disease and strategies      for treatment. Biochim Biophys Acta Mol Basis Dis 2024;1870(2):166967.
10. Rawat V, Kim P K. The cell biology of APOE in the brain. Trends Cell Biol      2023;33(12):1012-1030.
11. Yin J, Spillman E, Cheng E S, et al. Brain-specific lipoprotein receptors interact with astrocyte-derived apolipoprotein and mediate neuron-glia lipid shuttling. Nat Commun 2021;12:2408.
12. Thelen K M, Rentsch K M, Lütjohann D, et al. Brain cholesterol synthesis in humans is affected by statins. Arch Neurol 2006;63(1):104-107.
13. Law H G, Khan M A, Zhang W, et al. Reducing saturated fat intake lowers LDL-C but increases Lp(a) levels in African Americans: the GET-READI feeding      trial. J Lipid Res 2023;64(9):100420.
14. Karam G, Nu Y, Rehman N, et al. Comparison of dietary programmes for prevention and treatment of cardiovascular disease: systematic review and network      meta-analysis. BMJ 2023;380:e072003.
15. Nissen S E, Lincoff A M, Brennan D, et al. Bempedoic acid and cardiovascular outcomes in statin-intolerant patients. N Engl J Med 2023;388:1353-1364.
16. Bayram F, Kocer D, Gundogan K, et al. Prevalence of dyslipidemia and associated risk factors in Turkish adults. J Clin Lipidol 2014;8(2):206-216.
17. Balbay Y, Gagnon-Arpin I, Malhan S, et al. Modeling the burden of cardiovascular disease in Turkey: a microsimulation model. Anatol J Cardiol      2018;20(4):235-240.