Thursday, October 20, 2011

What is Cholesterol?

Cholesterol has been a favourite theme on the airwaves fpr the past 30 years, and mostly it seems to get a pretty harsh press.

The main risk associated with high cholesterol is coronary heart disease (CHD). This is caused by blood vessels becoming narrowed with fatty deposits called plaques, which cholesterol contributes to. The narrowed blood vessels reduce blood flow to the heart. This can result in angina [chest pain) or, if the vessel is blocked completely, a heart attack.

Based on information such as this, most people naturally think of cholesterol as something damaging, something to be avoided. But I think it is important to make it clear that cholesterol is absolutely essential for life. It is not some alien chemical that we can remove from our diets, or our bodies.

On this topic, I was amused to read an article in the Independent newspaper about the Buncefield Depot fire (when much of Britain's fuel stores went up in smoke, if you remember). This article highlighted the dangers in the fire-fighting foam that was used, which contains perfluorooctane sulfonate (PFOS). Among the serial terrors of PFOS  was the fact that ... 'The chemical is believed to interrupt the body's ability to produce cholesterol, a necessary building block of nearly every system in the body.' Quite.

I sometimes remark to those who think my ideas on heart disease are entirely batty, 'Why do you think that an egg yolk is full of cholesterol?' Answer: because it takes one hell of a lot of cholesterol to build a healthy chicken. It also takes a hell of a lot of cholesterol to build, and maintain, a healthy human being. In fact, cholesterol is so vital that all cells, apart from neurones, can manufacture cholesterol, and one of the key functions of the liver is to synthesize cholesterol. We also have an entire transportation system dedicated to moving cholesterol around the body.

Effects of Smlth-Lemli-opitz Syndrome (SLOS) Spontaneous abortion of fetuses with SLOS is not unusual. Stillbirths have also been reported. Death from multl-organ system failure during the first weeks of life is typical In Individuals with SLOS type II. Congenital heart disease Is not uncommon in SLOS and can cause cyanosis and congestive heart failure. Vomiting, feeding difficulties, constipation, toxic megacolon, electrolyte disturbances and failure to thrive are common and, in some cases, related to gastrointestinal anomalies. Visual loss may occur because of cataracts, optic-nerve abnormalities, or other ophthalmologic problems. Hearing loss Is fairly common. Cause of death can Include pneumonia, lethal congenital heart defect, or hepatic failure. Survival is unlikely if the plasma cholesterol level is less than approximately 20mg/dL.

To highlight what happens when cholesterol levels are very low, it is enlightening to look at a rare genetic  condition called Smith-LemliOpitz Syndrome (SLOS). In this syndrome there is a defect in cholesterol synthesis, resulting in very low blood cholesterol levels. Listed opposite are some of the effects.

From this cheery little list of deadly abnormalities, at least one thing becomes clear. The only good cholesterol molecule is not a dead cholesterol molecule. A very, very low cholesterol level is not something we should strive too hard to achieve.

Moving on, here are some of the things that we need cholesterol for in the body:

• Brain synapses. Synapses, the vital connections between nerve cells in the brain, and elsewhere, are made almost entirely of cholesterol.
• Vitamin D. This is a highly important vitamin, not only needed to create healthy bones, but now also known to be protective against a number of cancers. Vitamin D is synthesized from cholesterol by the action of sunlight on our skin.
• Cell membranes. All cells in our body need cholesterol in their cell membranes. Without it they would disintegrate, as cholesterol provides structural integrity.
• Sex hormones. Cholesterol is a building block for most sex hormones.
• Bile. Cholesterol is a key component of bile, which is released from the gall bladder to help with food digestion. Indeed, many gallstones are made entirely from crystallised cholesterol.

It should be' pointed out that all of this requires a great deal cholesterol. So much so that it is nigh on impossible to eat enough cholesterol to meet your daily cholesterol needs. In order to meet this gap, the liver has to produce four or five times as much cholesterol as you ingest. In fact, you would need to eat about six to eight egg yolks each and every day to meet your daily requirement. As most of us never do this, the liver fills the gap.

So how can it possibly make sense to claim that eating, say, one-third of our daily cholesterol requirement (which would only happen if you nearly doubled your intake) - instead of the normal one-fifth, or one-sixth, that most people manage - will overwhelm our metabolic control systems, causing cholesterol. levels to spiral out of control? If we did managed to eat four eggs a day, the liver would simply produce less cholesterol to keep the levels steady.
This form of physiological 'downregulation: also known as a 'negative feedback system: is something found in all other biological systems, in all other organisms discovered to date. But not, it would appear, with cholesterol, according to the 'cholesterol is bad' theory.

However much cholesterol you eat, the liver just keeps churning away, manufacturing as much as ever. Hmmmm, let me think. This would be like ... Actually it would be just like nothing else at all ever discovered in nature, ever. (I'll return to this subject later.)
Now it is time to move on to fats, with a special focus on our friendly neighbourhood saturated fat - aka the mass murderer. Saturated fats, so we are repeatedly informed, raise our cholesterol levels, thus killing us all from heart disease. 'Super-size me, baby, one more time .. .' In addition to this, they have also been implicated
in causing cancer and diabetes, and other nasty conditions too numerous to mention.

So I think it is time to reveal this monster of the deep.

Eeeeeeeehhhhhh! Run for the hills, hide your children, cover your eyes! Here, in all its terrifying glory, is a saturated fat. The greatest killer in the western world.

OK, I know what you're thinking. Is that it? Yup, that's it. Saturated fats are among the simplest of all molecules in the body. They contain carbon, oxygen and hydrogen, and they all have a COOH group at one end. They can be rather longer than the one in the diagram - i.e. they can have a longer chain of carbon atoms, each with two hydrogen atoms attached. Or they can be shorter. But that's about as exciting as saturated fats get.

So what is it about this substance that is so deadly? Frankly, I'm the wrong person to ask, because I don't happen to think that saturated fats are in any way damaging or dangerous. If they were, they wouldn't taste so damn delicious. Nature tends to warn us off dangerous foods by making them taste bitter and icky. Or giving them a bright-red colour. But hey, I know the counter argument in all its Darwinian glory: nature doesn't care about us after we are too old to procreate, so things that kill us after the age of 50 don't matter. I refuse to enter this debate because it is neither winnable, nor loseable. You either accept it, or reject it, according to your preexisting philosophical prejudices.

Anyway, now you know what a saturated fat is, perhaps I should introduce you to an unsaturated fat, those tree-hugging, Gaia-loving, spiritual healers of all mankind - sorry, humankind.
Can you spot the difference between a saturated and unsaturated fat? Jhe difference is that a section of the unsaturated fat is missing two hydrogen atoms. With two hydrogen atoms missing, a double bond has formed between two carbon atoms in the chain. Because this fat has a double bond in the middle of it, it is deemed to be not fully 'saturated' with hydrogen atoms. Thus, it is 'unsaturated:

There is something else about this particular unsaturated fat that I should point out. It is an Omega 3 fatty acid. Which is officially the healthiest molecule in the world. Indeed, you are looking at the substance that cures just about every ailment of mankind. A veritable Beecham's Powder of the early 21st century.

Perhaps I should explain exactly what makes this fat an Omega 3 fatty acid. Firstly, it is called a fatty acid because it has a COOH at one end (the acid group). In fact, all fats have this. Ergo, all fats are fatty acids, and all fatty acids are fats. But fatty acid does sound so much more scientific and clever than 'fat: Try saying 'Omega 3 fat: It just does not have the same ring to it. How can a fat possibly be healthy? But an 'Omega 3 fatty acid' ... Now you're talking!
The 'Omega 3' refers to the position of the double bond. In. the diagram above, you will notice the double bond is three carbon atoms along from the right-hand end. This end of a fat is known as the Omega end. The other end is known as the Alpha end. It's a Greek language thing: from alpha to omega, or A to Z.

I think it would be useful if I explained four more things about fats. Namely:
• What, exactly, a polyunsaturated fat is.
• How to turn a liquid fat into a solid fat (e.g. a 'cholesterol-reducing' spread).
• How fats are transported and stored in the body.
• The lack of connection between fats and cholesterol.

What is a polyunsaturated fat?
A polyunsaturated fat is a fat .with more than one double bond in it. Such fats tend to come from vegetable sources, e.g. olive oil. At this point I should probably mention that a 'monounsaturated fat' is an unsaturated fat with only one double bond.
And, to be frank, that's quite enough about unsaturated fats.

How to turn a liquid fat into a solid fat?
A significant problem with liquid fats (oils) is that it is kind of difficult to spread them on bread. Speaking as a butter fan, this is not something that has ever bothered me. However, many years ago, a clever chemist worked out that if you fired hydrogen atoms at great speed at an unsaturated fat, you could saturate it with a few more hydrogen atoms. The alternative chemical name for this process is hydrogenation - which literally means adding more hydrogen atoms. Whatever you call it, this chemical adaptation prevents fats from going rancid (i.e., picking up random oxygen atoms), and it also turns liquid fats into solid fats.

In this way, olive oil can be turned into olive fat - 'Zo 'ealthee as part of a Mediterranean diet: (Cue Italian music on an accordion, with 120- year-old men dancing the tango while charming their equally ancient wives.) Just what the world always needed. Solid olive oil.

Something else that I should mention at this point is that when you fire hydrogen at unsaturated fat, you create a strange type of molecule - one that is not really found in nature at all. It is a molecule with a hydrogen atom either side of the double carbon bond. This is known as a 'trans' bond, and is a bit difficult to explain in words. So, here is a diagram:

Fig.1 Comparison of a trans bond and a cis bond

Nature tends to make all double bonds with hydrogen on the same side, which is known as a 'cis' bond. But mankind, with a big machine, extremely high pressure and a few heavy-metal catalysts, can manufacture 'trans' bonds. And fats containing trans bonds are known as 'trans-fatty acids: There are those - and I rank myself among them - who believe that trans-fatty acids are both, literally, 'unnatural' and potentially damaging to our health.

How so? Because our enzyme systems are designed to deal with cis bonds, not trans bonds. And while the difference may seem trifling, consider the humble prion. A prion is a misfolded protein. If you eat prions from an infected source, you may develop BSE (bovine spongiform encephalopathy) and your brain will turn to mush. Ergo, unnatural differences in molecular structures can be extraordinarily damaging to biological systems - e.g, human beings.

If you want to know more about the potential damage caused by trans fats, just type 'Mary Enig' and 'trans fats' into any search engine, and be prepared to be scared. You may never eat margarine again. Despite the fact that such unnatural spreads' ... are clinically proven to lower cholesterol as part of a healthy diet' - A Celebrity. ('Can I have my cheque now, please?') Ah yes, anyone of the well known brands of substitute butter spreads are as natural as high-pressure, platinum-catalyst-based, hydrocarbon-cracking chemistry itself.

How fats are transported and stored around the body I will attempt to explain fat transportation in the next chapter, as it is key to the entire batty 'high cholesterol causes heart disease hypothesis: Here, however, I want to point out that fats do not wander through the body all alone or randomly. They are almost exclusively grouped together as three fats, attached to a backbone. Thus, they are knows as triglycerides (tri: three; glyceride: from 'glycerol' - the backbone molecule that holds the fats together).

Triglyceride
I am not entirely sure why fats do this, possibly the body finds it easier to pack three fats configured like this into smaller spaces. Also, they are less likely to react with surrounding chemicals. Whatever the main reason, this is the primary structure of fats in the body (see Fig.2.).
  Fig.2 Triglyceride

At this point I am going to mention a little more about glycerol, the backbone molecule in a triglyceride. Glycerol is actually half of a glucose or sugar molecule and when triglycerides are broken down into their component parts, glycerol travels to the liver, which combines two molecules to form glucose. The fats go to muscles to be burned up. (In short, stored fats are part sugar, providing energy.)

You probably do not think this matters at all. However, later on, when I attempt to explain the true cause of heart disease, this information will become rather more important.

The lack of connection between fats and cholesterol 
At this point, you may have noticed that I have talked about fats'and cholesterol without there seeming to be the slightest connection between them. The reason for this is because there is no connection. between them. Yet the way they are discussed today, the impression seems to be given that the two things are virtually the same. Fats, cholesterol; cholesterol, fats. Low-fat diet lowers cholesterol; high-fat diet raises cholesterol ... rhubarb, rhubarb.

It is true that foods containing cholesterol also tend to contain fats - specifically,'saturated fat. That's because foods containing cholesterol usually come from animal sources, and so do foods containing saturated fat. This is both the beginning and the end of any dietary connection. Yet for some reason it has become a canon of medical faith that eating saturated fat raises cholesterol levels,' and the two substances have become almost interchangeable in discussions on heart disease.

Here, for example, is a short passage plucked off the internet from a US governmental organisation:

Dietary cholesterol comes from animal sources such as egg yolks, meat (especially organ meats such as liver), poultry, fish, and higher fat milk products. Many of these foods are also high in saturated fats. Choosing foods with less cholesterol and saturated fat will help lower your blood cholesterol levels.

Within one quick paragraph, cholesterol and saturated fats have, somehow, become inextricably intertwined.

Moving ahead of myself just for a moment, I think it might be interesting to set the above quote beside one from Ancel Keys. The name probably means nothing to you, but Keys is 'Ie Grand Fromage' himself. The man who, almost single-handedly, set the world implacably against saturated fat. As part of his one-man crusade against saturated fat, Ancel Keys studied the impact of cholesterol consumption on cholesterol levels in humans, and the results of his research can' be neatly encapsulated in the following quote:

There's no connection whatsoever between cholesterol in food and cholesterol in blood. And we've known that all along. Cholesterol in the diet doesn't matter at all unless you happen to be a chicken or a rabbit.

Presumably, therefore, if cholesterol in the diet does not raise cholesterol levels - which it doesn't - it must be saturated fat? But what is the connection? Does saturated fat act as a building block for cholesterol? If you pump saturated fat into the liver, does it automatically churn out cholesterol- like inserting a pig in one end of an abatt~ir and watching sausages come out the other end?

I would like to say that there is absolutely no way that you can turn saturated fat (or any other sort of fat) into cholesterol. But human biochemistry is so complicated and interconnected that I can't really be so bold as to make that claim. The liver is the most fantastic chemical factory in the world. It can take almost any molecule and, through a series of mind-bogglingly complicated steps, turn it into another molecule (with certain important exceptions). So you can't say, for absolute certain, that fat doesn't become cholesterol, because some bits of fat probably do become incorporated into cholesterol, after the liver has mashed it about, and cleaved it, and added a few different atoms here and there. However, let me point out the following two facts, and leave you to draw your own conclusions.

Fact one
The fundamental building block for cholesterol is a substance called Acetyl CoA. You need know only two things about this substance:
Fig.3  Acetyl CoA

1: It contains phosphorous, sulphur and nitrogen (none of which isfound in fats, they are found in proteins).
2: It has several ring structures (none of which are found in fats).

Perhaps I should start a new competition. In Fig.3 of Acetyl CoA, can you 'Spot the fat'?

Fact two
Synthesis of cholesterol is horribly complicated. Again, the purpose of Fig. 4 is simply to illustrate this fact (and also to highlight the complete absence of saturated fat anywhere in this process).
Fig. 4 Cholesterol Synthesis

Cholesterol biosynthesis
Given these facts, I will reiterate the question: why would eating saturated fat have any impact on cholesterol production in the liver, or anywhere else in the body? If you can see how this happens, perhaps you could write to me and explain just exactly how it does so. Up to now, no biochemist has managed this clever trick.

I will finish this chapter by pointing out a fact that I find pertinent to the discussion. The liver is quite capable of turning one type of chemical into almost any other type of chemical. It can turn protein into sugar, sugar into fat, glycerol into glucose, etc. If you eat a great deal of carbohydrate (which is all converted into glucose), the liver will then convert excess glucose into fat. The body can only store about 2,000 calories of glucose in total, and once this limit is reached there is only thing to do with it: convert it to fat, then store it in adipose (Le. fatty) tissue.

And what sort of fat does the liver choose to make in this situation? Super-healthy unsaturated fats? Ah, that would be a no. When the liver makes fats, it makes saturated fats, and saturated fats alone. My God, do our own livers not know how unhealthy this is? Killed by our own treacherous physiology ... Or perhaps the liver knows that saturated fats are not actually unhealthy at all.
I will let you decide.

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