Monday, November 28, 2011

Triglycerides, VLDL, and industrial carbohydrate-rich foods

Below are the coefficients of association calculated by HealthCorrelator for Excel (HCE) for user John Doe. The coefficients of association are calculated as linear correlations in HCE (). The focus here is on the associations between fasting triglycerides and various other variables. Take a look at the coefficient of association at the top, with VLDL cholesterol, indicated with a red arrow. It is a very high 0.999.

Whoa! What is this – 0.999! Is John Doe a unique case? No, this strong association between fasting triglycerides and VLDL cholesterol is a very common pattern among HCE users. The reason is simple. VLDL cholesterol is not normally measured directly, but typically calculated based on fasting triglycerides, by dividing the fasting triglycerides measurement by 5. And there is an underlying reason for that - fasting triglycerides and VLDL cholesterol are actually very highly correlated, based on direct measurements of these two variables.

But if VLDL cholesterol is calculated based on fasting triglycerides (VLDL cholesterol  = fasting triglycerides / 5), how come the correlation is 0.999, and not a perfect 1? The reason is the rounding error in the measurements. Whenever you see a correlation this high (i.e., 0.999), it is reasonable to suspect that the source is an underlying linear relationship disturbed by rounding error.

Fasting triglycerides are probably the most useful measures on standard lipid panels. For example, fasting triglycerides below 70 mg/dl suggest a pattern of LDL particles that is predominantly of large and buoyant particles. This pattern is associated with a low incidence of cardiovascular disease (). Also, chronically high fasting triglycerides are a well known marker of the metabolic syndrome, and a harbinger of type 2 diabetes.

Where do large and buoyant LDL particles come from? They frequently start as "big" (relatively speaking) blobs of fat, which are actually VLDL particles. The photo is from the excellent book by Elliott & Elliott (); it shows, on the same scale: (a) VLDL particles, (b) chylomicrons, (c) LDL particles, and (d) HDL particles. The dark bar at the bottom of each shot is 1000 A in length, or 100 nm (A = angstrom; nm = nanometer; 1 nm = 10 A).

If you consume an excessive amount of carbohydrates, my theory is that your liver will produce an abnormally large number of small VLDL particles (also shown on the photo above), a proportion of which will end up as small and dense LDL particles. The liver will do that relatively quickly, probably as a short-term compensatory mechanism to avoid glucose toxicity. It will essentially turn excess glucose, from excess carbohydrates, into fat. The VLDL particles carrying that fat in the form of triglycerides will be small because the liver will be in a hurry to clear the excess glucose in circulation, and will have no time to produce large particles, which take longer to produce individually.

This will end up leading to excess triglycerides hanging around in circulation, long after they should have been used as sources of energy. High fasting triglycerides will be a reflection of that. The graphs below, also generated by HCE for John Doe, show how fasting triglycerides and VLDL cholesterol vary in relation to refined carbohydrate consumption. Again, the graphs are not identical in shape because of rounding error; the shapes are almost identical.

Small and dense LDL particles, in the presence of other factors such as systemic inflammation, will contribute to the formation of atherosclerotic plaques. Again, the main source of these particles would be an excessive amount of carbohydrates. What is an excessive amount of carbohydrates? Generally speaking, it is an amount beyond your liver’s capacity to convert the resulting digestion byproducts, fructose and glucose, into liver glycogen. This may come from spaced consumption throughout the day, or acute consumption in an unnatural form (a can of regular coke), or both.

Liver glycogen is sugar stored in the liver. This is the main source of sugar for your brain. If your blood sugar levels become too low, your brain will get angry. Eventually it will go from angry to dead, and you will finally find out what awaits you in the afterlife.

Should you be a healthy athlete who severely depletes liver glycogen stores on a regular basis, you will probably have an above average liver glycogen storage and production capacity. That will be a result of long-term compensatory adaptation to glycogen depleting exercise (). As such, you may be able to consume large amounts of carbohydrates, and you will still not have high fasting triglycerides. You will not carry a lot of body fat either, because the carbohydrates will not be converted to fat and sent into circulation in VLDL particles. They will be used to make liver glycogen.

In fact, if you are a healthy athlete who severely depletes liver glycogen stores on a regular basis, excess calories will be just about the only thing that will contribute to body fat gain. Your threshold for “excess” carbohydrates will be so high that you will feel like the whole low carbohydrate community is not only misguided but also part of a conspiracy against people like you. If you are also an aggressive blog writer, you may feel compelled to tell the world something like this: “Here, I can eat 300 g of carbohydrates per day and maintain single-digit body fat levels! Take that you low carbohydrate idiots!”

Let us say you do not consume an excessive amount of carbohydrates; again, what is excessive or not varies, probably dramatically, from individual to individual. In this case your liver will produce a relatively small number of fat VLDL particles, which will end up as large and buoyant LDL particles. The fat in these large VLDL particles will likely not come primarily from conversion of glucose and/or fructose into fat (i.e., de novo lipogenesis), but from dietary sources of fat.

How do you avoid consuming excess carbohydrates? A good way of achieving that is to avoid man-made carbohydrate-rich foods. Another is adopting a low carbohydrate diet. Yet another is to become a healthy athlete who severely depletes liver glycogen stores on a regular basis; then you can eat a lot of bread, pasta, doughnuts and so on, and keep your fingers crossed for the future.

Either way, fasting triglycerides will be strongly correlated with VLDL cholesterol, because VLDL particles contain both triglycerides (“encapsulated” fat, not to be confused with “free” fatty acids) and cholesterol. If a large number of VLDL particles are produced by one’s liver, the person’s fasting triglycerides reading will be high. If a small number of VLDL particles are produced, even if they are fat particles, the fasting triglycerides reading will be relatively low. Neither VLDL cholesterol nor fasting triglycerides will be zero though.

Now, you may be wondering, how come a small number of fat VLDL particles will eventually lead to low fasting triglycerides? After all, they are fat particles, even though they occur in fewer numbers. My hypothesis is that having a large number of small-dense VLDL particles in circulation is an abnormal, unnatural state, and that our body is not well designed to deal with that state. Use of lipoprotein-bound fat as a source of energy in this state becomes somewhat less efficient, leading to high triglycerides in circulation; and also to hunger, as our mitochondria like fat.

This hypothesis, and the theory outlined above, fit well with the numbers I have been seeing for quite some time from HCE users. Note that it is a bit different from the more popular theory, particularly among low carbohydrate writers, that fat is force-stored in adipocytes (fat cells) by insulin and not released for use as energy, also leading to hunger. What I am saying here, which is compatible with this more popular theory, is that lipoproteins, like adipocytes, also end up holding more fat than they should if you consume excess carbohydrates, and for longer.

Want to improve your health? Consider replacing things like bread and cereal with butter and eggs in your diet (). And also go see you doctor (); if he disagrees with this recommendation, ask him to read this post and explain why he disagrees.