Tuesday, 13 April 2010

Whatever happened to...Torcetrapib?

Peter of Hyperlipid mentioned this stuff back in July 2007 but it didn't get much attention back then, so I am resurrecting it. It's another "Great Idea" that turned out to be absolute crock.

Inhibiting the enzyme that converts A into B results in less of B but more of A. This also applies to something called Cholesterol Ester Transport Protein (CETP) that transports esterified cholesterol (acid + alcohol = ester + water & cholesterol is technically an alcohol) from the tiny HDL discs to the much larger LDL & relatively huge VLDL particles. To see what HDL, LDL, VLDL & chylomicrons look like, see Large LDL and small HDL particles: The best combination.

Inhibiting CETP with Torcetrapib reduces LDL and increases HDL which sounds absolutely wonderful. Unfortunately, what has actually happened is that the cholesterol reverse transport pathway has been buggered-about with. Not surprisingly, this results in increased mortality. To see how cholesterol transport pathways work, see Figure 3 in Effect of Torcetrapib on the Progression of Coronary Atherosclerosis. See also Effect of Torcetrapib on Carotid Atherosclerosis in Familial Hypercholesterolemia.

If you want to raise your HDL, be more active and eat more monounsaturated fats, also fish oils and/or take high-dose extended-release niacin. Don't bugger-about with your cholesterol reverse transport pathway!

3 comments:

ET said...

The longer I look into the connection between heart disease and lipoproteins, the more I start to wonder if actual levels are that much of a factor. Three good examples are ezetimibe, statins, and niacin.

Ezetimibe lowers LDL but not the progression of atherosclerosis. Statins also lower LDL but it has never been proven that that is how they possibly slow the progression of atherosclerosis. Their anti-inflammatory effects might be the way they exert "beneficial" effects. Sames for niacin, except that it does a much better job at raising HDL. Niacin also has anti-inflammatory effects, as well as PPAR-gamma activity.

That being said, until I know differently for sure, I'm sticking with my high-fat diet and niacin.

Nigel Kinbrum said...

Hi ET.
I had to look up Ezetimibe to find out what it does. So, lowering serum cholesterol and changing nothing else doesn't reduce atherosclerosis? Hmmm...

Statins do loads of other things as well as lower cholesterol, which is why there is a slight benefit as well as loads of side-effects.

I was on Niaspan years ago (for hypertriglyceridaemia) but achieved much lower fasting serum TGs by drastically reducing my intake of sugary & starchy carbohydrates. The delayed reaction flush on Niaspan was interesting, though!
Nige.

dextery said...

I can take 2,000 mg of Slo-Niacin but I have to take it 1,000mg at a time over a 2 hour period. Lots of pinprick tinglies and blotchy red skin if I forget to space. It is made by Upsher-Smith Labratories, Minneapolis, Mn
www.slo-niacin.com

Raised my HDL from 42 to 86 in 3 months. One must exercise weekly in order for homocystine levels not to rise when taking any brand niacin...according to Life Extention Foundation.