Here is the report written by our wonderful Project Manager, Jamie Smith…
The twins’ cholesterol story
James Smith, 20 November 2012
Cholesterol is seen as the ultimate rival in the war against coronary artery and heart disease but it is often a poorly understood enemy, even by many physicians. If you take a closer look at the complex role that cholesterol plays in the body, you’ll see that it is not quite as simple as finding ways to lower your ‘bad’ cholesterol and raise your ‘good’ cholesterol. It should also become clear that measuring total cholesterol is virtually useless to assess ones risk for disease.
Cholesterol plays many crucial roles in the body. These include regulating what can pass into and out of cells and the production of hormones. In other words cholesterol is critical for life. The problem arises when cholesterol lands up in the wrong place, the most dangerous of these places being the cells that line the major artery walls.
So how does cholesterol land up in the wrong place? To understand this, one needs to know a little more about how cholesterol gets transported around the body. Cholesterol is hydrophobic which means that it cannot dissolve in water or more importantly, in blood. To be transported in the blood stream it therefore needs to be packaged in something that doesn’t mind floating around in water. For cholesterol, this comes in the form of a protein wrapped vehicle called a lipoprotein. You may have heard of LDL and HDL cholesterol. This refers to two different types of cholesterol containing lipoproteins. There are also others, for example IDL, VLDL, Lp(a) and chylomicrons, which are closely related to LDL particles, but lets ignore them for now and try to keep things relatively simple.
LDL has been dubbed the ‘bad’ cholesterol but in fact it plays a crucial role transporting triglycerides (fats) to muscles for energy and returning cholesterol to the liver so that it can be processed for other functions. The problem is that under certain conditions LDL-C (LDL-cholesterol) will penetrate and deliver its cholesterol to the cells in artery walls. This is bad news. The body will immediately mount an immune response and hopefully rid the cells of their unwanted guests. If these cells are continuously bombarded with LDL-C particles the immune response will battle to cope and inflammation will occur. This may lead to narrowing of the artery and the formation of a plaque, which can rupture and block the artery resulting in the tissues being starved of oxygen. If that tissue is the heart the consequences can be deadly. This is why considerable emphasis has been placed on measuring the amount of cholesterol found in LDL and in reducing this number. The real threat however is not the total amount of cholesterol packaged into the LDL particles but in the number of LDL particles present in the blood. It is a concentration game so the more particles present in the blood, the more particles will violate the barrier to the artery cells and the more cholesterol will be delivered to these cells and cause havoc. Measuring LDL particle number is key to determining true risk for atherosclerosis but this is only done commercially by a handful of companies worldwide. An alternative is to measure LDL particle size under the assumption that the smaller the particles the more there are likely to be. However, this test is not offered commercially in South Africa either. The standard LDL-C concentration test which is offered by most pathology labs, only estimates the amount of cholesterol carried by LDL particles. This is only useful if LDL-C correlates well with LDL particle number, however this is not reliably the case. In fact, in about a third of the population, LDL-C and LDL particle number do not predict the same thing. LDL-C is therefore not always particularly useful for estimating risk of cardiovascular disease.
HDL-C and has been dubbed the ‘good cholesterol’. It gained this reputation because it mops up excess cholesterol, for example from the cells in artery walls, and returns it to the liver or gut where it can be processed or excreted. It also delivers cholesterol to hormone producing tissues or fat cells where it is used or stored. Many studies have shown that people with high levels of HDL-C in their blood have a lower incidence of coronary artery disease. Hence it is seen as desirable to have high levels of HDL-C in the blood. However, drugs designed to raise HDL-C do not necessarily reduce cardiovascular events. The reason for this appears to be that it is actually the higher number of HDL particles and in particular the larger, more mature particles that are important to decrease the risk of cardiovascular disease and not simply HDL-C concentration.
Clinical trials have shown that a low carbohydrate diet tends to favorably increase blood HDL-C and reduce triglycerides whereas a low fat, high carbohydrate diet tends to do the opposite. Jax’s HDL-C seemed to drop ever so slightly on the high carb diet which was a bit worrying since it meant that she dipped below level of 1.2 mmol/L which places her at increased risk. Jeanne’s HDL-C was in the healthy range to start off with and didn’t really change much during her high fat diet. Neither Jax nor Jeanne’s triglycerides changed significantly over the 8 weeks and both were well within the healthy range.
Jax and Jeanne’s blood samples were also analysed for LDL particle size because small dense particles are more dangerous than the large fluffy ones. This was done by the lipid expert, Prof. Marais, at the University of Cape Town. He used a method that can place their LDL particle size into one of 5 categories (A, AI, I, IB, B). ‘A’ is the largest particle size category with ‘A’, ‘AI’ and ‘I’ being desirable, whereas ‘B’ is the smallest category and places the individual at a 3 fold greater risk for cardiovascular disease. ‘IB’ is also regarded as undesirable. Jeanne’s LDL particles were in the ‘AI’ category, which places her safely at the larger end of the spectrum. Her particle size did not change much during the 8 weeks. Jax’s LDL was in the ‘I’ category and was therefore less favorable than Jeanne’s but still considered ‘desirable’. Interestingly, Jax’s particle size decreased ever so slightly over the 8 weeks on the high carb diet but this change is probably not clinically significant as it was minor and did not shift to a smaller category. Another interesting finding from the particle size test is that Lp(a) was present in both Jax and Jeanne’s blood sample. Lp(a) is a lipoprotein in the same class as LDL but is absent in most people. Its presence at high levels in the blood increases ones risk for atherosclerosis (artery disease) but unfortunately the quantity of Lp(a) could not be determined by this test. Blood Lp(a) is genetic, hence the reason that both twins had it and according to Prof Marais, it is not influenced by external factors such as diet.
In clinical trials, blood LDL-C (ie cholesterol in LDL particles measured by the lab) seems to respond differently to a low carbohydrate diet depending on the person and on how much saturated fat is eaten. More often than not it goes up a little while in some cases it comes down. Either way LDL-C is not as important as it was once thought to be because LDL particle size tends to increase and the particle number decreases with a low carbohydrate diet (i.e. becoming less dangerous). Conversely, a diet high in carbohydrate and particularly poor quality carbohydrates such as sugars and refined starches results in a significant shift towards the more dangerous, small-dense-LDL particles. For these reasons a moderate increase in LDL-C is considered safe when other risk factors (e.g. HDL-C, triglycerides, LDL particle size etc.) are favorable.
Having said that both Jax and Jeanne had high LDL-C levels to start with, which in itself is not much cause for concern. However Jeanne’s LDL-C increased dramatically over the 8 weeks on a high fat diet. Since both twins have Lp(a) present in their blood, Jeanne’s sharp rise in LDL-C is worth keeping a close eye on. However, the fact that she has favorably high HDL-C, low triglycerides, low fasting glucose, low HbA1c and large LDL particles is reassuring. Their elevated LDL-C may indicate an underlying familial genetic predisposition to high LDL-cholesterol and is certainly worth investigating further. It may be a good idea for Jeanne to cut down on the saturated fat content of her diet until we fully understand the implications of a very high LDL-C level in her case.
If you would like to read more about cholesterol and other health issues related to diet, I would highly recommend Peter Atilla’s website (www.eatingacademy.com) for which I am grateful for much of the information present in this article.