Tuesday, March 14, 2006


It seems they're headline news again.

And indeed they are a wonderful drug in lowering cholesterol levels, but only if suffering from a condition that elevates LDL cholesterol levels, for example familial hypercholesterolaemia. A word of caution though, in my opinion I don't think these drugs are the best way of lowering LDL cholesterol for the general public, and it annoys me that they are available over the counter and this is why:

apologies for the technical nature of this, but it's important.

How statins work:

Statins are chemicals that bind to the enzyme HMG-CoA reductase, and in so doing inhibits the conversion of HMG-CoA into mevalonate. This is the rate limiting step in the chemical pathway that the body uses to produce cholesterol. Yes that's right, we actually produce our own cholesterol, because it is a very important molecule, and the production of this molecule is highly regulated. The liver is the main production plant for cholesterol, and it is here that it can become packaged with other fats and proteins in the low density lipoprotein, the body's transport vesicle for lipids. Incredibly a single liver cell can somehow measure the amount of cholesterol present (i'll spare the details) and if it is too low, the cell will begin to produce more of the HMG-CoA reductase enzyme. If there is sufficient cholesterol, then no more of the enzyme is required. Sometimes this pathway doesn't work properly and the cells continue to make the enzyme, and thus more cholesterol, which becomes packaged in LDL and can be dangerous.

Taking statins is really useful in these cases, as it inhibits the cholesterol produced by the body (de novo synthesis), thus the only cholesterol the body is utilising is that recieved from the diet.

All well and good, but in my investigations into the controlling mechanism that links the levels of cholesterol to gene expression, I carried out a few experiments using a cholesterol reduced model - ie a hamster fed diet supplemented with statins. Comparing the activity of the HMG-CoA reductase enzyme in livers from such treated animals to those fed a normal diet, I was initially amazed to find that it was around 10 times more active in the statin treated individuals. It was obvious when we thought about it, the statins had been washed away from my sample, during preparation of the assay, and the results suggested that in the statin treated animals there was far more of the HMG-CoA reductase enzyme present. Of course, because without the enzyme the level of cholesterol in the cell can't be regulated, and the cell thinks there isn't enough cholesterol present, so makes more of the cholesterol synthesising enzyme (which can't work in the presence of statins in vivo. So a positive feedback loop is produced, making more and more of the HMG-CoA reductase enzyme.

So you see, if anyone starts a course of statins, it's extremely dangerous to come off them, as the huge amount of emzyme produced would immediatley synthesise a whole load of cholesterol. So once started, you're on them for life. Very good for the pharmaceutical companies that sell them!

Cholesterol is also incredibly important in the developing embyo (exactly how is a mystery and something i'd love to investigate) and so these drugs are also very dangerous if you are pregnant.

My advise is this, if you don't have a genetic condition or illness that is raising your LDL cholesterol, then I suggest altering your diet, reducing foods high in saturated fat and cholesterol, a much better way to solve the problem.

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