Peter on cholesterol….pt 2

Following on from last week…. and trying to summarise Peter Attia’s cholesterol talk at AHS12 to illustrate why the cholesterol reading you get from Medlab doesn’t give you a good indication of your risk of atherosclerosis and subsequent heart disease. Cholesterol. The internal regulatory process responsible for cholesterol involves both the production of cholesterol and absorption of it. There are a few reasons why some people have higher cholesterol levels, and broadly speaking there are people who are good at producing cholesterol, and people who are good at absorbing it. The absorption of cholesterol is governed by a receptor in the gut which is responsible for allowing the movement of sterols in and out of the gut. There is also a receptor in the gut that is responsible for getting rid of all unwanted sterols (and excess cholesterol) from the gut to be excreted (called ABCG5 and ABCG8). It’s only ‘free’ sterols that are able to get in – esterified cholesterol (i.e. that which is delivered through food) is not able to enter the gut. For this reason there is very little, if any, relationship between cholesterol in food choices and our total blood cholesterol level. Health professionals have been aware of this for a few years now, however the general public is still confused and I can’t tell you how often I get asked the question of whether there is a limit on eggs. However some may have a defect with the receptor in the gut letting too many of the sterols in, or a problem with the ABCG5/G8 getting rid of the unwanted sterols. The effect this has on overall cholesterol homeostasis is not clear at this stage.

 I can't get enough of eggs, even the grumpy ones. (image from

I can’t get enough of eggs. (image from

While we hear a lot about LDL-cholesterol, the lipoproteins responsible for carrying HDL and LDL also carry triglycerides and phospholipids. These are produced by the liver and are known as Apo-A (HDL cholesterol) and Apo-B (LDL cholesterol). Apo-B lipoproteins contain more triglycerides than Apo-A lipoproteins, and include very low density lipoprotein (VLDL), which (when it sheds its triglycerides and phospholipids) converts to IDL (intermediate density lipoprotein) and LDL. VLDL contains more triglycerides than cholesterol (5:1 ratio) compared to LDL which is more in the vicinity of 4:1. When the VLDL are transported from the liver they release triglycerides and phospholipids and triglycerides to be used for energy by the muscles or stored in the adipose tissue. In people that are metabolically healthy, the triglycerides are delivered to the muscles by VLDL to be used for energy – however in those that have metabolic health problems, the triglycerides are more likely to be stored as fat. In addition, as they contain a lot of triglycerides, when we have high levels of processed carbohydrate we are going to have a lot more VLDL in our bloodstream as these excess carbohydrates are converted to triglycerides and packed up in the VLDL. Research has shown that the number of VLDL particles increases risk of athleroschlerosis. In addition, there is a lipoprotein Apo-E which is found in Apolipoprotein E (ApoE) is a class of apolipoprotein found in the chylomicrons (carriers of dietary fat after we eat) and Intermediate-density lipoprotein (IDLs) that is essential for the normal breakdown  of triglyceride-rich lipoprotein constituents such as VLDL, and there exists three main forms – E2, E3 and E4. These differ in the position of certain amino acids in the structure, but alters the function of the Apo-E lipoprotein significantly. Those people with the E2/E2 and E4/E4 expression have been found to be at greater risk of atherosclerosis.

The whole cholesterol issue is confusing. I spent about 3 hours writing that last paragraph and its very rough and actually probably didn’t mention 18 other ‘must knows’ in order to understand it properly. However, I think that, really, the most important thing to understand is that JUST knowing your LDL number (or total cholesterol number) is not going to provide you with a good idea of your risk of atheroschlerosis. Firstly – in NZ we aren’t able to quantify LDL – instead it is a calculated number based on the direct measurement of total cholesterol and HDL cholesterol. That’s an issue. However, moreso, there are certain conditions which can increase risk associated with cholesterol. The Apo-B lipoproteins can get into the sub endothelial space in the artery wall and can spark an immune response, causing inflammation. This inflammation can then increase the number of particles being delivered to the site (as LDL is released in response to inflammation) thus further particles get into the artery wall. The Apo-A lipoproteins, responsible for delivering HDL don’t.

Of course, inflammation is not just caused by one factor – and I bang on about this a lot in pretty much every health related post I write here and on my facebook page. The oxidation and glycation (binding of a glucose molecule to a protein) of the particles can change the functionality of the lipoproteins which causes them to damage the endothelial cells I mentioned above. These processes are caused by an overload of stress in the system: dietary, activity, toxins and the like. Result? Increased likelihood of atherosclerosis. Oxidised LDL can’t be measured in New Zealand but people can send their results to a laboratory in Australia to get this measured.

Another important factor is the size and the number of LDL particles in our system. There are two different patterns – and those with fluffy LDL particles (bigger) are less likely to get stuck in the artery all compared to the smaller (pattern B) particles, which are more atherogenic. It’s not just size that matters, though – it’s overall particle number. And when the size of the LDL particles have been controlled for, it suggests that overall the number of particles is more important. The greater the number of particles, the less able they are to move efficiently around the bloodstream, the more likelihood of being oxidised and subsequent inflammation.

Also important to consider that LDL cholesterol is used as a patch to help with inflammation in the body – if you have high LDL then that could very well be indicative of an underlying issue that needs to be addressed. Interestingly, while we’ve understood that a high HDL is a good thing and the higher the better, in fact a high HDL is not a get out of jail free card either. Indeed, trials that increase HDL levels through therapeutic means have been stopped before their planned end dates due to the lack of clinical benefit in people who have established cardiovascular disease. If HDL is high, then there may well be a reason outside of just eating a good quality diet. There are different forms of HDL and, its primary role is a carrier to remove excess cholesterol away from the blood vessel wall to be excreted, if it is not functioning correctly then that in itself can increase risk of heart disease (depending on other risk factors). If we use the car analogy (as people tend to do when it comes to cholesterol, quite useful), then if the car breaks down, then the cholesterol is not going anywhere – this is double-whammy bad actually, as it is unable to break down the plaque at the artery wall and in itself can cause inflammation.

Yeah. Cholesterol. So how useful are your own cholesterol readings? First – there are a couple of good ‘proxy’ measures that can be gleaned from your results to give you an idea of risk. Triglyceride/HDL can give you an indication of particle size. The smaller the ratio, the larger the particle size, the less risk. You need to calculate this as it’s not given to you. However, this may not be as important as total cholesterol/HDL, which can give you an indication of particle number. The smaller the ratio better and this is likely to be a better indicator of overall risk. Finally, and most importantly, is the context. As I said last week, our cholesterol readings are nowhere near as important as we once thought with regards to atherosclerosis and heart disease – and can’t be looked at in isolation of other risk factors. The context matters, so evaluate them in light of your current lifestyle to get a better understanding of their usefulness.

6 thoughts on “Peter on cholesterol….pt 2

  1. Wow Mikki. I am in awe. I look forward to your posts with a certain amount of trepidation. I try and understand them with the same intensity as what it must take to write them. Whew. There goes my Sunday.

    Keep it up

  2. Well written. A most complex subject.
    I have written a piece for my local newspaper that I would appreciate an informed opinion on before it’s published. I have been Banting for 9 months and have some fairly good results in mass, girth and chemistry. Being a physio it’s important for me to do this article in an accurate non partisan way, lest I look to be stepping outside of my HPCA obligations.
    I think you came across well on Nigels doco. Good work!
    Greg Bell

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