1. What is cholesterol?

 

Cholesterol is a lipid molecule essential to all animal life on Earth including humans. If you get some on your hands, it feels like a waxy substance. That’s partly why it has the latin word sterol in it, meaning ‘solid’. Cholesterol makes up about 30% of the lipids in animal cell membranes [1] and is found in much lower amounts in plants [2].

The sterol of cholesterol also refers to the fact that it’s a modified steroid hormone and as such it is a precursor for bile salts (crucial for absorbing nutrients and for the immune function), vitamin D (all-round important vitamin) and 5 major classes of steroid hormones pictured below [3].

 

 

Although we’d die without it in our bodies, we don’t need to get cholesterol from food as it’s technically a non-essential nutrient. We can make our own through cholesterol synthesis. But cholesterol is in foods containing other nutrients that are essential for us to obtain through our diet – like animal sourced foods – so you can’t really avoid cholesterol in any healthy diet and you shouldn’t try to!

 

 

 

 

 

 

 

 

Blood cholesterol is one of five biological measure doctors check on to see whether or not you have Metabolic Syndrome, a physiological state you want to avoid because it’s linked to common conditions like diabetes and obesity. Clearly it can be helpful to know if your cholesterol levels and patterns are outside of the normal range but if they are, you should not automatically assume they’re unhealthy.

 

The structure of cholesterol

 

One of biology’s mantra is ‘structure = function’. There are three parts to the structure of cholesterol: the hydroxyl group labelled with an OH visible on the top of the molecule (green arrow), the hydrocarbon tail at the bottom of the molecule (blue arrow) and the central region made of four hydrocarbon rings (red arrows).

 

 

 

 

 

 

The OH part is ‘water loving’ (water soluble) and its hydrocarbon tail ‘water hating’ (hydrophobic), a combination which makes the overall structure of cholesterol versatile in a manner called ‘amphipathic’. It still ‘hates’ water too much to circulate in your bloodstream on its own though, so it does so by being on the inside of globular proteins (lipoprotein).

You might be surprised to know that the OH part technically means cholesterol contains alcohol but don’t worry, eating cholesterol isn’t anything like drinking vodka!

To understand why cholesterol is a precursor enabling the appropriate production of hormones, compare the ringed structure of cholesterol with the ringed region of the hormone aldosterone (red arrows) for example.

 

 

Both cholesterol and aldosterone have this very similar ringed structure as do many other hormones. These shared structures are part of why having enough cholesterol is crucial for the good production of hormones.

 

Cholesterol structure : what’s so special about it?

 

Again, ‘structure = function’ in biology. The cholesterol structure is such that the molecular complexes it’s part of can change shape quickly. Its structure is a big part of why animals and by extension their cells can be more dynamic, especially compared to plants. The image below illustrates its adaptability as a function of being able to pack together more or less tightly (condensing versus being more fluid).

 

 

Cell membranes with more cholesterol will usually be more rigid and cell membranes with less cholesterol will usually be more fluid. Another important aspect of cholesterol structure is that it makes it possible for animal cells to use ‘lipid rafts’, allowing them to do way more complex and advanced cellular tasks.

One hypothesis is that because cholesterol’s structure contains both high-melting point and low-melting point lipids, the high-melting lipids can form lipid rafts floating in a ‘sea’ of low-melting lipids [4] – an interesting mechanism many researchers have linked to disease processes [5, 6].

Once more it’s clear that understanding cholesterol structure is key to understanding its functions.

  

2. What cholesterol does

 

How does cholesterol function in your body ?

 

Cholesterol function has already been touched on above because it’s inseparable from its structure. However, its principle functions includes

  • maintaining the integrity of cell membranes (e.g. having healthy skin)
  • as well as serving as a precursor for vitamin D (e.g. having strong bones)
  • steroid hormones (e.g. a healthy libido)
  • bile salts (e.g. good digestion)

 

A lesser appreciated cholesterol function is to travel in particles through the bloodstream to reach tissues in need of repair, while triglyceride passengers also in the particle are being dropped off to fuel the cells. Cholesterol function is thus inextricably linked to the complex network of energy distribution that we rely on to keep fit and healthy – so you can stay warm and feel energetic.

 

3. Many doctors say too much cholesterol is bad

 

Many doctors still believe that ‘fat = high blood cholesterol = heart attack’ but this theory wrong.

Dietary cholesterol is not a bad thing, in fact it’s found in many healthy but much maligned  foods likes eggs, liver and shellfish. People make three to four times more cholesterol than they typically eat so remember that the cholesterol in your diet has a negligible impact on your blood cholesterol.

The cholesterol in your cells is not a bad thing either, in fact it’s pretty crucial as Dr.Uffe Ravnskov explains [7].

“The fact that cells are waterproof is especially critical for the normal functioning of nerves and nerve cells. Thus, the highest concentration of cholesterol in the body is found in the brain and other parts of the nervous system”

The cholesterol in your blood is also not a bad thing. Blood cholesterol levels can fluctuate over a day and can be manipulated with the energy and fat content of your diet. However, blood cholesterol levels are tightly coupled to your energy needs, so the range within which your diet affects your blood cholesterol remains limited. But how do dietary manipulations make your blood cholesterol go up and down? The first thing to know is that cholesterol ride-shares with triglycerides in particles shuttling to and from cells in order to meet long-term and moment-to-moment energy needs.

So knowing how much cholesterol is being transported and in which kind of particles is valuable  information. It can give you a lot of clues about your health or your disease.

The differents kinds of particles are called chylomicron, chylomicron remnant, VLDL, LDL, IDL and HDL and they’re all of different sizes and densities, transporting different ratios of cholesterol, triglycerides and nutrients amongst other cargo in order to fulfill their various roles. The acronyms stand for very low-, low-, intermediate- and high-density lipoprotein.

Total blood cholesterol levels drop up to 33% in people who die of sepsis (a severe infection) and bump up 28% in those who survive it [8]. The more  cholesterol particles you have in your blood the more lipopolysaccharides (LPS) it can bind and thus fight the infection. Cholesterol helps spur even more of a robust general immune system responses. For example, people with less than 70 mg/dL (< 1.8 mmol/L) of LDL cholesterol were observed to be 530% more likely to die of hematological cancer, fever and sepsis than people with more than 70 mg/dL of LDL cholesterol [9].

Total cholesterol and cholesterol subtypes can be lowered by a few percent over the long-term by eating a lot of unhealthy refined seed oils, like soybean or sunflower oil. This increases your risk of death and specifically of a heart attack [10]. You’re better off avoiding seed oils entirely and eating foods like avocados, salmon and steak containing the right kind of fats in the right amounts, even though your LDL and total cholesterol may increase when doing so. Not to worry though, eating that sort of food instead of refined flours and added sugar lowers inflammation and oxidative stress markers [11].

“High cholesterol” does not give you heart disease. Most people who are admitted for a heart attack have normal to low cholesterol levels [12]. LDL cholesterol-lowering drugs do, in fact, lower cholesterol levels but remain quite ineffective in reducing overall risk of death or of preventing another cardiac event [13]. They also come with serious and common side-effects, like diabetes and muscle associated problems symptomatic of larger metabolic disturbances [14, 15, 16, 17]. Elderly people with high total cholesterol levels in the blood generally tend to live longer and are less likely to die from an infection or cancer [18]. At the very least, we can be confident that “high cholesterol” is not a universally bad thing.

 

4. Different kinds of cholesterol measures and how much is too much

 

It is often said that there are different kinds of cholesterol but that’s not quite right; the cholesterol in LDL particles is the same as in HDL particles. When you get blood drawn for a cholesterol check the numbers you get back are actually about how much cholesterol you have in one kind of particle versus how much you have in another. You can also request tests measuring your particle numbers, how much you have of one kind versus another.

 

Average cholesterol levels

A large Japanese study found that a total cholesterol level of 160 – 199 mg/dL (4.14 – 5.16 mmol/L)) in men and ≥ 240 mg/dL (≥ 6.21 mmol/L) in women was associated with the lowest risk of death [19]. This data runs counter to mainstream medical thinking. Comprehensive life insurance data from 2009 reveals that females under 60 years of average have a total cholesterol value of 193 mg/dL (5 mmol/L) that increases to 228 mg/dL (5.9 mmol/L) when over 60. In males it’s 205 mg/dL (5.3 mmol/L) when under 60 and 211 mg/dL (5.5 mmol/L) when over 60 [20]. These averages are higher than averages obtained in other studies preferably used by mainstream medicine

What about LDL cholesterol levels? In a study from 2009 of more than 200 men and 200 women aged 75 and above, the median LDL cholesterol was 147 mg/dL (3.8 mmol/L) for males and 159 mg/dL (4.1 mmol/L) for females [21]. Another study in younger children found that 12 year old boys had an average cholesterol of 153 mg/dL (4 mmol/L) and girls of 160 mg/dL (4.1 mmol/L) [22]. One again, these average LDL cholesterol figures may alarm some doctors but in fact they apparently aren’t unhealthy.

In US adults aged 20 and up the average LDL cholesterol levels decreased from 126 mg/dL to 111 (3.3 mmol/L to 2.9) during the 14 years between 1999/2000 to 2013/2014 [23].

#1 Why is LDL calculated and not measured?

Nearly all lab results have LDL calculated, not measured. The LDL calculation is known as the Friedewald equation.

TC – (HDL + triglyceride / 5)

The Friedewald LDL calculation is not a good estimate when triglycerides are less than 100 mg/dL or (1.1 mmol/L) [24] and it’s not uncommon to have triglycerides under 100 mg/dL.

So if you get a LDL cholesterol result after having dropped your triglycerides below 100 mg/dL by strongly restricting your calories or going on a low-carb or ketogenic diet, that LDL cholesterol result is probably inflated around (around 12.2 mg/dL or 0.3 mmol/L). This is further reason for you and your doctor not to panic over a ‘high cholesterol’ result.

In any case, there is a better LDL calculation for people with triglycerides under 100 mg/dL called the Iranian equation.

In mg/dL it’s

LDL = TC / 1.19 + TG / 1.9 – HDL / 1.1 – 38

In mmol/L it’s

LDL = TC / 1.19 + TG / 0.81 – HDL / 1.1 – 0.98

#2 Should you want a low LDL cholesterol level?

Not particularly. Low LDL and total cholesterol is associated with increased risks of cancer, liver disease and all-cause mortality, although it’s unclear if this association is causal [24, 25]. What is low and high cholesterol is always being redefined but low LDL are usually given as being < 100 mg/dL (2.6 mmol/L) or < 70 mg/dL (1.8 mmol/L).

 

#3 What is non-HDL cholesterol?

Non-HDL cholesterol is all the cholesterol left over after subtracting the cholesterol in HDL particles from the cholesterol in all other types of lipoprotein particles (chylomicron, chylomicron remnant, IDL, LDL and VLDL).

Non-HDL cholesterol has been considered the better risk marker for all-cause mortality on a cholesterol panel when compared to LDL or total cholesterol, but this is contradicted by larger datasets. One such study found quite convincingly that non-HDL, LDL and total cholesterol are essentially equally poor risk markers – the total cholesterol to HDL cholesterol ratio is the better cholesterol-only risk marker, but it remains only moderately useful (at best) [26].

Remnant cholesterol, a measure of the cholesterol leftover in all the non-HDL particles: chylomicron remnant, VLDL and IDL. It’s currently a much better risk marker than all other cholesterol markers go [27, 28] for assessing your risk of cardiovascular disease or all-cause mortality. Plug in you cholesterol values into Dave Feldman’s Cholesterol Remnant calculator to figure out your atherogenic risk!

 

What is cholesterol synthesis?

 

Technically, cholesterol synthesis is actually cholesterol biosynthesis since it’s made in a living organism – you! Pedantic points aside, the point is that humans can make their own cholesterol and regulate it appropriately. There are many steps in making your own but they can be broken down into five main stages, starting with a very simply molecule called acetyl-CoA and ending with the conversion of squalene into cholesterol.

Since cholesterol has been vilified for so long it’s not surprising many will reflexively consider anything that stops its production – stops cholesterol synthesis – as good. The point of knowing about cholesterol synthesis is that it’s necessary and healthful. You should not worry about dietary cholesterol or the naturally occurring fats in foods like nuts, fish, meat and shellfish “negatively” impacting your cholesterol levels.

When your ATP (energy) levels are low, cholesterol synthesis is downregulated. If your ATP isn’t low but you still need cholesterol downregulated, a protein called SREBP senses your intracellular levels of cholesterol and changes how much is made accordingly.

This example serves to make the point that your body didn’t produce a molecule so that you would be harmed prematurely. Rather, we should wonder why cholesterol is found in atherosclerotic arteries, at the crime scene so to speak, rather than assume it committed the crime. 

Takeaways

#1 Cholesterol is essential for a healthy brain and for many other crucial body functions

#2 Your body makes the vast majority of cholesterol circulating in your blood and is perfectly capable of making more or less depending on how much is coming in through your diet. There’s no need to avoid dietary cholesterol and especially not foods high in it.

#3 ‘Lower is better’ does not apply to total blood cholesterol or LDL cholesterol levels. In fact, efforts are often better spent ensuring that the amount of cholesterol transported in certain lipoprotein particles, like HDL, are kept well above the uncontroversial pathological range which starts below 40 mg/dL (1 mmol/L).

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