Saturday, March 26, 2011

2. Cholesterol and Statins

I would like to start by reexamining the claim that statins cut heart attack incidence by a third. What exactly does this mean? A meta study reviewing seven drug trials, involving in total 42,848 patients, ranging over a three to five year period, showed a 29% decreased risk of a major cardiac event (Thavendiranathan et al., 2006). But because heart attacks were rare among this group, what this translates to in absolute terms is that 60 patients would need to be treated for an average of 4.3 years to protect one of them from a single heart attack. However, essentially all of them will experience increased frailty and mental decline, a subject to which I will return in depth later on in this essay.

The impact of the damage due to the statin anti-cholesterol mythology extends far beyond those who actually consume the statin pills. Cholesterol has been demonized by the statin industry, and as a consequence Americans have become conditioned to avoid all foods containing cholesterol. This is a grave mistake, as it places a much bigger burden on the body to synthesize sufficient cholesterol to support the body's needs, and it deprives us of several essential nutrients. I am pained to watch someone crack open an egg and toss out the yolk because it contains "too much" cholesterol. Eggs are a very healthy food, but the yolk contains all the important nutrients. After all, the yolk is what allows the chick embryo to mature into a chicken. Americans are currently experiencing widespread deficiencies in several crucial nutrients that are abundant in foods that contain cholesterol, such as choline, zinc, niacin, vitamin A and vitamin D.

Cholesterol is a remarkable substance, without which all of us would die. There are three distinguishing factors which give animals an advantage over plants: a nervous system, mobility, and cholesterol. Cholesterol, absent from plants, is the key molecule that allows animals to have mobility and a nervous system. Cholesterol has unique chemical properties that are exploited in the lipid bilayers that surround all animal cells: as cholesterol concentrations are increased, membrane fluidity is decreased, up to a certain critical concentration, after which cholesterol starts to increase fluidity (Haines, 2001). Animal cells exploit this property to great advantage in orchestrating ion transport, which is essential for both mobility and nerve signal transport. Animal cell membranes are populated with a large number of specialized island regions appropriately called lipid rafts. Cholesterol gathers in high concentrations in lipid rafts, allowing ions to flow freely through these confined regions. Cholesterol serves a crucial role in the non-lipid raft regions as well, by preventing small charged ions, predominantly sodium (Na+) and potassium (K+), from leaking across cell membranes. In the absence of cholesterol, cells would have to expend a great deal more energy pulling these leaked ions back across the membrane against a concentration gradient.

In addition to this essential role in ion transport, cholesterol is the precursor to vitamin D3, the sex hormones, estrogen, progesterone, and testosterone, and the steroid hormones such as cortisone. Cholesterol is absolutely essential to the cell membranes of all of our cells, where it protects the cell not only from ion leaks but also from oxidation damage to membrane fats. While the brain contains only 2% of the body's weight, it houses 25% of the body's cholesterol. Cholesterol is vital to the brain for nerve signal transport at synapses and through the long axons that communicate from one side of the brain to the other. Cholesterol sulfate plays an important role in the metabolism of fats via bile acids, as well as in immune defenses against invasion by pathogenic organisms.

Statin drugs inhibit the action of an enzyme, HMG coenzyme A reductase, that catalyses an early step in the 25-step process that produces cholesterol. This step is also an early step in the synthesis of a number of other powerful biological substances that are involved in cellular regulation processes and antioxidant effects. One of these is coenzyme Q10, present in the greatest concentration in the heart, which plays an important role in mitochondrial energy production and acts as a potent antioxidant (Gottlieb et al., 2000). Statins also interfere with cell-signaling mechanisms mediated by so-called G-proteins, which orchestrate complex metabolic responses to stressed conditions. Another crucial substance whose synthesis is blocked is dolichol, which plays a crucial role in the endoplasmic reticulum. We can't begin to imagine what diverse effects all of this disruption, due to interference with HMG coenzyme A reductase, might have on the cell's ability to function.


Dave said...

I am worried about the effects of statins on my body. I'm also worried about having a second heart attack.

Do you have any statistics about the absolute reduction of risk for those who have heart disease and/or have had a heart attack, like me?

I've had muscle pain (after doubling my Simvastain dose to 80 mg; my cardiologist switched me to Lipitor), and a little over a year ago, after a 130 mi. bike ride, with 15000 feet of climbing up and down the mountains, I experienced rabdomyolosis - luckily, not to severe. And that was on 40 mg of Simvastatin. I suspected the statin had something to do with causing my rabdo.

Although I had no side effects from Lipitor the past few months, stopped taking it.

I'd still like to know if you have statistics for the absolute risk reduction in major cardiovascular events for someone like me.

Thanks and keep up the good work.

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