Right, now, forget everything you have just read. (What do you mean you already have? Damn cheek.) The fact is that, after all that I have written about cholesterol and related subjects … you do not actually have a cholesterol level in your bloodstream at all.
You can read that statement again if you want to.
This fact, I believe, underpins the confusion highlighted in the letter below.
I am 52 and recently had my first cholesterol test. When I rang the surgery for my results, the receptionist said that they were ‘3.3, well below the 5.5 safe maximum – and 5.5, well below the safe maximum of 7.4.’ I am confused as to why I was given two numbers, and the receptionist couldn’t explain. What do they mean?
Letter in Health Section of the Independent, 27 September 2005
Curiouser and curiouser. Well, what could this possibly mean? Is it really possible to have two levels of the same substance in your bloodstream? Actually, nowadays, you can have at least four different cholesterol levels:
The ‘good’ cholesterol level
The ‘bad’ cholesterol level
The ratio of ‘good’ to ‘bad’ cholesterol
And just to warn you, several more types of cholesterol level are on the way.
Ah yes, good cholesterol and bad cholesterol. A concept so mind-boggling in its stupidity that it should really have won first prize in the ‘Alice in Wonderland Comes to Life in the Real World’ contest. Below is a diagram of cholesterol.
Fig. 12 Cholesterol
This is the only form that cholesterol comes in. It does not have right-handed ‘good’ cholesterol with a sinister twin called ‘bad’ cholesterol. So, what is all this terminology about? What does it all mean? And why can’t you have a cholesterol level?
Back to basics
Cholesterol does not dissolve in water; thus, it does not dissolve in blood. This means that it has to be transported around the body inside a small transportation molecule, known as a lipoprotein (Fig.13).
Fig. 13 Lipoprotein
Another substance that cannot dissolve in blood is fat. So fats also travel about as part of lipoproteins. A-ha! A connection between fat and cholesterol. Yes, you’re right. Fats/triglycerides and cholesterol are copassengers inside lipoproteins. Hold that thought … then bin it – it doesn’t actually go anywhere.
There are several different types of lipoprotein. The biggest is called a chylomicron, not a lipoprotein. As with almost everything in the wacky world of heart disease, the nomenclature appears to have been designed to make things difficult to follow. A chylomicron is one form of lipoprotein, but of course it isn’t called a lipoprotein. That would be far too easy.
Anyway, this particular lipoprotein is manufactured in the guts. After a meal it fills up with triglyceride (fat), alongside a relatively small amount of cholesterol. The chylomicron then travels straight to fat cells in the body without passing through the liver. When the chylomicron reaches fat cells, the triglyceride is sucked out, and the chylomicron shrivels up into a little wizened remnant that is then, probably, hoovered up by the liver.
One level down in size from a chylomicron is a lipoprotein known as a very low density lipoprotein (VLDL). VLDLs are manufactured in both the guts and the liver. Just to add even greater confusion to this area, VLDLs are usually referred to as ‘triglycerides’. Some of you may even have been informed as to your triglyceride level (this is a relatively new thing to worry people with).
A further level down in size is the intermediate density lipoprotein (IDL). This is formed when a VLDL loses triglyceride to fat cells, and shrinks. So far the world seems to have been spared worrying about IDL levels. However, I await the paper any day now that heralds IDL as the new, greatest danger to health.
Moving on. When the IDL shrinks to a level even further down in size it becomes the low density lipoprotein (LDL). The … (speak each word slowly in an awestruck voice) Low … Density … Lipoprotein. Isn’t this the killer? Yes, gentle reader, we have reached the lair of the dark lord himself. This is the substance guilty of wiping out millions of people each and every year.
For LDL is also known ‘bad’ cholesterol. Even though, of course, it isn’t cholesterol at all. So stop calling it cholesterol … you idiots! Sorry, that doesn’t mean you. I am ranting here at scientists, doctors and the healthcare profession in general. No wonder everyone is confused, when the terminology used is completely bonkers:
• A chylomicron is a lipoprotein, but it’s never called that.
• A VLDL is a lipoprotein but it is usually called a triglyceride.
• A LDL is a lipoprotein but it is called ‘bad’ cholesterol.
• A high density lipoprotein (HDL), the smallest lipoprotein, is called ‘good’ cholesterol.
I’m a little teapot short and stout; lift me up and pour me out.
Actually, just to make things even more confusing – if that were possible – there is another form of LDL. Yes, I’m afraid so. It is exactly the same as LDL, apart from one thing. It has two types of protein attached to the outside. (All lipoproteins have proteins attached to their outer surface. This is how receptors on cells throughout the body recognise them.) This form of lipoprotein, however, is called lipoprotein(a). Good heavens, a lipoprotein that is called a lipoprotein – it must be some sort of a record. Anyway, this lipoprotein is usually pronounced as ‘el pee little A’ and written as Lp(a). Almost no one, including 99 per cent of doctors, knows that Lp(a) is actually LDL. Even though this fact is of fundamental importance to understanding heart disease. (More on this later.)
Why isn’t Lp(a) called LDL(a), or something of the sort? Because then everyone would know what it was, and that would never do. (By the way, no one ever tells you what your Lp(a) level is. Which is typical, as it is the only one that may actually be important.)
I have just realised that I have been remiss in not mentioning high density lipoproteins, or HDL, or ‘good’ cholesterol. This lipoprotein, it is thought, is mainly manufactured in the liver. (‘What do you mean ‘thought,’ surely all this stuff is known?’ Sorry, no it’s not.) Anyway, it is believed that HDL ‘removes’ cholesterol from plaques in arteries and transports it back to the liver for reprocessing. So HDL protects you from heart disease and is therefore ‘good’. Even if it is not cholesterol, and, pound for pound, contains more cholesterol than any other sort of lipoprotein in the body.
Frankly, the idea that an inanimate molecule can suck cholesterol out of a plaque is so laughable that I can’t begin to explain here how preposterous an idea it is. And moreover, I would challenge any scientist anywhere to explain exactly how it happens. A molecule that travels both ways through a concentration gradient? ‘Of course it does, now run away and play with your friends and leave the adults alone.’
The million-dollar question
As I hope I have now made abundantly clear, you do not – indeed, cannot – have a cholesterol level in your blood. So, what happened to the cholesterol hypothesis? Where’d it go? Well, although it has changed almost completely from its first incarnation, somehow or other it has also managed to remain the same.
The cholesterol hypothesis started out as something pure and simple: ‘If you eat too much cholesterol, the level of cholesterol in the blood rises. Cholesterol is then deposited on artery walls causing them to thicken and narrow.’ But it sure as hell hasn’t stayed that way:
Problem number one:
Cholesterol in the diet does not raise blood cholesterol levels. Ancel Keys proved this.
Adaptation:
Let’s say that is it is both saturated fat and cholesterol that raises cholesterol levels. Then keep shifting between the two when challenged.
Problem number two:
You don’t have a cholesterol level, you have lipoprotein levels.
Adaptation:
We will call certain lipoproteins ‘cholesterol’ and carry on as if nothing had really happened.
‘Four legs good, two legs bad’ has become ‘Four legs good, two legs better.’ And, as George Orwell predicted, no one noticed.
Up to this point I have actually highlighted only the first two major adaptations to the cholesterol hypothesis. But over the years there has been adaptation after adaptation after adaptation. One of the more convoluted adaptations (following some horribly contradictory evidence against saturated fat causing heart disease) was that it is not saturated fat in the diet that matters, it is the ratio of polyunsaturated to saturated fat that is really important. Then it changed again, and a lack of monounsaturated fats seemed to be the critical factor. Then … well, who knows. It’s tough keeping track.
Indeed, the closer you look, the more you find that the cholesterol hypothesis is a truly amazing beast. It is in a process of constant adaptation in order to encompass all contradictory data without keeling over and expiring. I sometimes think of it like a monster from a 1950s horror movie – The Thing, or The Blob. Every time you think you have killed it, it just gets back up and carries on. ‘My God Chuck, attacking it with electricity has just made it stronger!’
My view is that any hypothesis that has to keep changing all the time to survive the relentless assault of contradictory facts is, in reality, a dead hypothesis. To quote James Black from a 200-year-old lecture:
A nice adaptation of conditions will make almost any hypothesis agree with the phenomena. This will please the imagination, but does not advance our knowledge.
J Black, Lectures of the Elements of Chemistry, 1803
Clever chap, James Black.
However, having an endlessly adaptable hypothesis does provide a major challenge to me. If I attack it, I will be informed that I have just attacked something that doesn’t exist: ‘Why are you bothered about fat intake? You should know that the real problem is a lack of Omega 3 fatty acids, and/or plant stanols, and/or antioxidants, and/or monounsaturated fats … Of course saturated fats are important, but you must consider the other important factors in conjunction. Heart disease, you see, is very much a multifactorial disease.’
If anyone ever tells me that heart disease is multifactorial again, I shall scream. It is the ultimate cop-out statement. It allows anyone to say anything, without bothering with the tiresome problem of thinking first: ‘All diseases are multifactorial in some way, so let’s give up trying to look for causes.’ I think not.
So, at the considerable risk of zeroing in on a moving target, I will state that, as of today, the most widely accepted version of the new, improved (yet – somehow – still the original) cholesterol hypothesis is as follows:
Eating excess saturated fat in the diet raises LDL levels. The LDL, otherwise know as ‘bad’ cholesterol, then causes thickening and narrowing in the arteries.
Which is not really a cholesterol hypothesis, but it is still a ‘diet-heart hypothesis’ I guess, and perhaps it could even be true. If it is true, though, how does it actually work? How does saturated fat raise LDL levels? A primary requirement of any half-decent hypothesis in medicine is that it is biological plausible – i.e. there should be some understandable, and seemingly reasonable, underlying mechanism of action.
It must be admitted that the original idea, which was that cholesterol in the diet increased cholesterol levels, at least had the advantage of superficial plausibility. Even if, when you get down to studying it in any detail, it is revealed as total baloney. But where is the link between eating saturated fat and raising LDL levels?
As I have already explained, most of the fat in the diet – saturated or otherwise – is transported directly to fat cells, travelling inside chylomicrons. No impact on LDL there. Fat that does manage to reach the liver has zero impact on cholesterol production too. So, I will ask again: how does saturated fat (or any other type of fat, come to that) raise LDL levels?
Well, moving a step back, surely we must look at where LDL comes from? After all, LDL is what remains of a VLDL after it has shrunk in size by losing fats. VLDLs are made in the liver and are used to transport both fat and cholesterol out of the liver, and deliver both substances to cells around the body*. So, if we want to know what raises LDL levels, we surely have to ask what raises VLDL levels in the first place, as this is the one and only source of LDL. A-ha! I can almost hear you thinking: saturated fat consumption must raise the VLDL levels. Yes?
No. The thing that raises VLDL levels is eating carbohydrates … On the other hand, a high-fat diet lowers VLDL levels. Here is one more guilty little secret of heart-disease researchers exposed.
You don’t believe me? Then perhaps you’ll believe the American Journal of Medicine. Spurred on by a desire to prove that the Atkins diet (high fat, low carb) was dangerous, researchers fed a group of obese people an Atkins-type diet. Here are the highlights:
PURPOSE: To compare the effects of a low-carbohydrate diet and a conventional (fat- and calorie-restricted) diet on lipoprotein subfractions and inflammation in severely obese subjects.
RESULTS: Subjects on a low-carbohydrate [i.e., high-fat] diet experienced a greater decrease [my emphasis] in large very low-density lipoprotein [VLDL] levels.4
And subsequently, a bigger study presented at the American Heart Association demonstrated the following:
In the most recent study, presented at the annual scientific meeting of the American Heart Association in Chicago, Duke University researchers randomly assigned 120 overweight volunteers to the Atkins diet or to the American Heart Association’s low-fat ‘Step I’ diet. People on the Atkins diet restricted their carbohydrate intake to less than 20 grams a day, with 60 percent of their calories coming from fat.
After six months, participants on the Atkins diet had lost 31 pounds, had an 11 percent increase in HDL [i.e., ‘good’cholesterol] and a 49 percent [my emphasis] drop in their triglyceride [VLDL] levels.’
Here you have it, then. VLDL is the only source of LDL, but when you eat more fat the VLDL level drops. In one study it dropped by very nearly 50 per cent. This should mean that eating fat will, in turn, lower LDL levels, shouldn’t it? Well, actually it doesn’t. A high-fat diet neither raises nor lowers LDL levels.
How can this be? If VLDL is the only source of LDL then if you have more VLDL to start with, you must end up with more LDL in the bloodstream in the end, surely? Help, what on earth is going on?
It’s time for the final twist in this particular saga: there is absolutely no connection whatsoever between the VLDL level and the LDL level. It has been known for a long time that over a period of days – even weeks, months and usually years – the LDL level remains fixed – no matter what you eat. And no matter what happens to the VLDL level. LDL levels can rise and fall, true, but in the majority of people this only happens gradually, and certainly not within a 24-hour period. In short, the VLDL level can shoot up and down while the LDL level remains locked.
And what does this tell us, exactly? It tells us that LDL can be removed at whatever rate is needed to keep LDL levels constant, no matter how much VLDL shrinks down to become LDL. Also, that the system controlling LDL levels is unaffected by what you eat, or the amount of VLDL manufactured by the liver. All of this, by the way, is known by researchers who specialise in lipids. And now you know it too.
However, it rather begs the question: if they know all this, what is their explanation as to how saturated fat raises LDL levels? I would ask you to have a guess, but there is no way on earth you would be able to come up with the current, preposterous, conjecture. For it is this:
If you eat saturated fat, this will reduce the number of LDL receptors – the things that lock on to LDL and pull it out of the bloodstream – thus causing the LDL level to rise.
Why would eating saturated fat do this? There is no connection between saturated-fat consumption and the needs of cells around the body to absorb LDL – none. You might as well suggest that eating protein causes your hair to grow faster. It makes as much sense.
Perhaps you think that this is all theoretical, and doesn’t matter at all. ‘Surely it must have been proven by now that saturated fat does cause LDL levels to rise, so forget the clever arguments, Dr Kendrick.’ In fact this has never been proven. Or, to be more accurate, some studies have shown a rise, some a fall. Others have shown nothing at all. I will mention some of these later.5
For now, I will stick to one quote from the Framingham Study which is the most influential, longest-running, and most oft-quoted study in heart-disease research. It began in 1948, and it is still running today, which also makes it the longest study that has ever be done.
In Framingham, Massachusetts, the more saturated fat one ate, the more cholesterol one ate, the more calories one ate, the lower people’s serum cholesterol [by which he means LDL – my note].
Dr William Castelli, Director of the Framingham Study, 1992
When I show this quote to other doctors it makes them choke on their tea. But it shouldn’t. How can eating saturated fat raise LDL levels? It is not merely biologically implausible, it is biologically impossible. It always was, and it always will be. (Boy, does that statement mak me a hostage to fortune!)
AND FINALLY…
Before moving on from this area, I thought I should give you a quick rundown on the different cholesterol levels that you hear about nowadays, and what they are thought to represent.
Total cholesterol
This is still, probably, the most common figure given out to patients. The total cholesterol level is reached by adding together levels of the ‘evil’ LDL, plus the ‘saintly’ HDL, plus a few other wayward lipoproteins – IDL and suchlike – that get mixed up in the analysis. (You think that cholesterol level is a super-accurate measurement? Ho, ho.)
The average total cholesterol level in the UK is about 6.1 – expressed as mmol/l (millimoles per litre). Anything above 7mmol/l and your GP will send for the local priest to read out the last rites. At present, the figure that the healthcare profession aims to achieve, through statination, is about 5.0mmol/l. Oh we do like a nice round figure, it’s so neat and tidy and scientific – not.
‘Good’ cholesterol
This is the high density lipoprotein level (HDL), which normally sits at about 1.3mmol/l. Anything below 0.9mmol/l and your life-insurance company will cancel your subscription, then paint a little black spot in the middle of your palm for good luck. Above 2.0mmol/l, and you can get the Saga booklets out and look forward to a long and happy career in lawn-green bowling.
‘Bad’ cholesterol level
This is the low density lipoprotein (LDL) level. On average, this is about 3.5mmol/l. Anything above 4mmol/l and you will be statinated. Resistance is useless.
The ratio of good to bad cholesterol
Clearly, if HDL is good and LDL is bad, you could have a high total cholesterol level yet still be ‘healthy’. If, that is, your total cholesterol level is boosted by a high HDL. So some people think that what’s really important is the ratio of good to bad cholesterol. I shall remain silent on this point, because I was taught that if you can think of nothing nice to say, you should say nothing at all.
One rather critical point about cholesterol levels that I have not mentioned so far is that the level which is considered high has been falling relentlessly. Twenty years ago, GPs in the UK would only get excited if your total cholesterol level was above about 7.0mmol/l. Ten years ago, anything above 6.5mmol/l had moved into the ‘treatment’ zone. Today, if your level is above 5.0mmol/l you will be earmarked for ‘statination’. Tomorrow, if current trends continue, the level will be 4.0mmol/l. It already is for those who have suffered a heart attack. Some ‘experts’ believe that the true, healthy level of cholesterol is about 2.5mmol/l. Therefore, no matter what your level of cholesterol, according to the prevailing wisdom, you will benefit from having it lowered.
Here is a short section from an article by Law and Wald in the British Medical Journal (BMJ) from 2002. They argue that the levels of both cholesterol (and blood pressure) in all westernised societies are far higher than those of our ancestors and the remaining hunter-gatherer populations dotted around the world. In their opinion, therefore, limiting statin treatment to people with a total blood cholesterol of 4.0mmol/l, or even 3.0mmol/l, is actively dangerous.
… everyone needs blood pressure, and cholesterol is essential for life. These lower limits are, however, beyond Western values and not reached by current dietary or drug interventions. They should not be invoked as obstacles to offering effective preventive treatments.
Translation: everyone in the UK should take statins now, and for the rest their lives. You may have heard of Law and Wald before, via their Polypill concept. A concept that – were the Polypill to take off – would make Law and Wald rich beyond the dreams of Croesus. Yes, these were the authors of that piece.
Moving on, here is a section from the BBC’s website, reporting on a conference on the wider use of statins:
Dr John Reckless, chairman of Heart UK and a consultant endocrinologist at Bath University, put forward the case.
‘The whole point of the debate is to bring out the fact that we are under-treating and the fact that a lot more people could benefit.
‘The whole population should be following diet, lifestyle and weight loss measures. We shouldn’t have our high-fat meals and we shouldn’t lounge around, we should all be taking exercise and so on.
‘Of course we all need that. But on the other hand, rather more people do need statins than are currently getting them.
‘So maybe people should be able to have their statin, perhaps if not in their drinking water, with their drinking water.’
Statins in the drinking water?
*(Pedantic point) The VLDL that is made in the guts does not become LDL, so for the purposes of this discussion we can ignore it. The reason why it doesn’t become LDL is that VLDL made in the gut has a different type of protein attached to it, so although it does shrink in size, it is not recognised by LDL receptors. If you really want to know the detail, gut-derived VLDL has apolipoprotein B–48 attached to it. Liver-derived VLDL has apolipoprotein B-100 attached to it. It is the B-100 apolipoprotein that locks into an LDL receptor, at which point the entire LDL is pulled into the cell and broken down into its component parts.
