Cholesterol – what does the blood cholesterol test actually measure?
This post is dedicated to Mat Cooke who asked a great question!
Cholesterol targets for USA, Australia and UK
The world is obsessed with cholesterol levels. The UK and Australia work in mmol/l and the USA works in mg/dl. Americans are told to have a total cholesterol level below 200 mg/dl and LDL below 100 mg/dl. These guidelines, issued by the National Cholesterol Education Programme, actually call LDL ‘cholesterol’, which is ignorant as we will see shortly. Appendix 1 has the drug industry conflicts of interest of the committee members setting these USA targets, just in case you thought that they had been set independently, with your health interests at heart, rather than in conflict, with drug industry profits in mind.
Australians are told total blood cholesterol levels above 5.5 mmol/l “are an indication of a greatly increased risk of developing coronary heart disease“.
Did you know that the National Institute for Clinical Excellence (NICE) has not issued cholesterol targets for the UK? NICE is the evidence based body for the UK and this summary states: “A target for total cholesterol or low-density lipoprotein (LDL) cholesterol is not recommended for primary prevention of cardiovascular disease.” The basis for recommendation is summarised as follows: “The National Institute for Health and Clinical Excellence (NICE) does not recommend the use of target levels of cholesterol for people taking statins for primary prevention of cardiovascular disease. This is because it found no clinical trials in primary prevention that have evaluated the relative and absolute benefits of achieving different cholesterol targets in relation to clinical events.”
This doesn’t stop the General Practice Notebook – a UK Medical Reference placing the British Hypertension Society and Joint British Societies (never heard of either of these) guidelines above the absence of NICE guidelines. The GP Notebook says that “The BHS and JBS2 guidelines stated that the ideal cholesterol targets are: to lower total cholesterol by 25% or LDL cholesterol by 30% or to reach < 4.0 mmol/l or < 2.0 mmol/l respectively, whichever is the greater – however a total cholesterol concentration < 5.0 mmol/l or LDL cholesterol < 3.0 mmol/l or reductions of 25% or 30%, respectively (whichever is the greater), provides a minimal acceptable “audit” standard.”
So the USA advise total cholesterol below 200 mg/dl and LDL below 100 mg/dl. To convert mmol/l (UK) to mg/dl (USA) we multiply by 38.66. To convert mg/dl (USA) to mmol/l (UK) we divide by 38.66. Hence 200 mg/dl equates to 5.17 mmol/l and 100 mg/dl equates to 2.58 mmol/l.
Australia favours total cholesterol below 5.5 mmol/l (213 mg/dl).
UK doctors are astonishingly aiming for total cholesterol of 4 mmol/l (155 mg/dl) or LDL of 2 mmol/l (77 mg/dl) although they consider total cholesterol of 5 mmol/l (193 mg/dl) or LDL of 3 mmol/l (116 mg/dl) as a “minimal acceptable audit“. I say “astonishingly” knowing the vital role that cholesterol plays in every cell in the human body.
But what are all these measurements? What exactly does a total cholesterol level mean?
The conversion factors & a good question
Mat Cooke spotted that, for triglyceride, the conversion is: To convert mmol/l to mg/dl for triglyceride you multiply by 88.6.
This is because of molar mass. The chemical formula for cholesterol is C27H460 with a molar mass of 386 g/mol. The chemical formula for triglyceride is C55H98O6 with a molar weight of 856 g/mol.
This led Mat to ask a clever question… “When they measure cholesterol levels.. They are presumably measuring the total molar mass of all of the lipoproteins in the blood. Who’s to say what proportion of that is actually cholesterol and what proportion is other lipids and proteins?”
The blood cholesterol level
We need to start by saying that the blood cholesterol level is about as reliable as the England football team in penalty shootouts. The time of day, the time of year, whether or not you fasted beforehand, how much sun you’ve had recently, current stress levels, even running late for the blood test appointment – all can impact blood cholesterol levels. When people talk about their test results as if they are accurate they should be made aware of all of this.
The formula for blood cholesterol levels is: Total cholesterol = LDL + HDL + triglycerides/5
Few people know that we can only measure total cholesterol and HDL with the standard blood test. Yes – 1 equation, 4 unknowns, 2 measurable = not very scientific.
After measuring (albeit inaccurately and inconsistently) total cholesterol and HDL, triglycerides and LDL together are assumed to account for the difference. The estimation is refined with the Friedewald equation, using the two assumptions that i) virtually all triglyceride is carried by VLDL and ii) that the triglyceride: cholesterol ratio of VLDL is constant at approximately 5:1 (Friedewald et al 1972) (neither assumption being strictly true) to establish the final equation:
Total cholesterol = LDL + HDL + Triglyceride/5
There are five lipoproteins – in order of size (largest to smallest) they are chylomicrons, Very Low Density Lipoprotein (VLDL), Intermediate Density Lipoprotein (IDL), Low Density Lipoprotein (LDL) and High Density Lipoprotein (HDL). (Ideally chylomicrons would be called Exceptionally Low Density Lipoproteins (ELDL’s) and then the density concept would be more consistent. However…). Confusingly, VLDL is also referred to as triglyceride. People will tell you their triglyceride levels after their blood test and are pleased when these are low. They don’t know that VLDL isn’t even measured, let alone triglyceride.
The National Cholesterol ‘Education’ Programme have no right to educate anyone about cholesterol if they don’t know that LDL is not even cholesterol. LDL is Low Density Lipoprotein. LDL contains cholesterol; it is not cholesterol.
All five lipoproteins contain four substances – cholesterol, triglyceride, phospholipids and protein. The proportions of each substance vary.
The Garrett & Grisham, book “Biochemistry” estimates:
– VLDL is approximately 50% triglyceride, 22% cholesterol, 18% phospholipids and 10% protein.
– LDL is approximately 8% triglyceride, 45% cholesterol, 22% phospholipids and 25% protein.
– HDL is approximately 4% triglyceride, 30% cholesterol, 29% phospholipids and 33% protein.
So, Total cholesterol = LDL (all approximate – 8% triglyceride, 45% cholesterol, 22% phospholipids and 25% protein) + HDL (all approximate – 4% triglyceride, 30% cholesterol, 29% phospholipids and 33% protein) + VLDL/5? (all approximate – 50% triglyceride, 22% cholesterol, 18% phospholipids and 10% protein) or just the triglyceride part of VLDL/5?
So what is the blood cholesterol measurement? Is it the cholesterol in each lipoprotein? Is it the whole lipoprotein? If the latter – then we’re back to the relevance of Mat’s original observation – if cholesterol is converted at a factor of 38 and triglyceride at a factor of 86 – how is this being allowed for?
Mat and I know that cholesterol is utterly life vital. We know that our body makes it – it is so utterly life vital that the body cannot leave it to chance that we could get it from food. We know that “There’s no connection whatsoever between cholesterol in food and cholesterol in blood. And we’ve known that all along” to quote Ancel Keys – the man who arguably started the whole war on cholesterol.
We think that people who try to lower the blood cholesterol levels of their fellow humans are guilty of what will go down in history as one of the greatest crimes against humankind. The fact that one statin alone, Lipitor, has been worth $125 billion to Pfizer since 1997, should surely raise alarm bells. Lipitor is the most lucrative drug in the world. It is by no means the only statin.
Our request is this – please can someone tell us what the blood cholesterol test actually measures? Notwithstanding that we know it only ‘measures’ two from four unknowns, is it claiming to measure cholesterol? lipoproteins? triglyceride? a mixture? If anything other than cholesterol alone, how is the molar mass allowed for in conversion? It’s bad enough to have drug industry influenced targets to lower a life vital substance. It compounds the crime if you’re making up the numbers as well as the targets.
The 2004 NCEP financial disclosure report reveals that all members of the 2004 guideline participants had received payments and/or grant funds from the following organisations:
Dr Scott Grundy: Abbott, Astra Zeneca, Bayer, Bristol-Myers Squibb, Glaxo SmithKline, Kos, Merck, Pfizer, Sankyo.
Dr Bairey: Astra Zeneca, Bayer, Bristol-Myers Squibb, Kos, Merck, Novartis, Pfizer, Procter & Gamble, Wyeth.
Dr Brewer: Astra Zeneca, Esperion, Fournier, Lipid Sciences, Merck, Novartis, Pfizer, Sankyo, Tularik.
Dr Clark: Abbot, Astra Zeneca, Bristol-Myers Squibb, Merck, Pfizer.
Dr Hunninghake: Astra Zeneca, Bristol-Myers Squibb, Kos, Merck, Novartis, Pfizer.
Dr Pasternak: Astra Zeneca, BMS-Sanofi, Pfizer, Johnson & Johnson, Kos, Merck, Novartis, Takeda.
Dr Smith: Merck.
Dr Stone: Abbot, Astra Zeneca, Bristol-Myers Squibb, Kos, Merck, Novartis, Pfizer, Reliant, Sankyo.