This article first appeared in the St. Louis Beacon, Dec. 16, 2009 - Last week I discussed the dangers of a high-fat diet. This has been of some interest to me, as by a cruel twist of fate I was born loving steak, a 1 1/2 inch Porterhouse my idea of culinary perfection. I love French fries, too, and more than anything else, Big Macs.
What is cruel about my love affair with Big Macs is that a dozen years ago my doctors informed me I have high levels of cholesterol in my blood, well over the upper recommended level of 200. Because all this cholesterol in my blood tends to deposit itself along the insides of arteries, this puts me at high risk of heart attack if I don't do something about it.
Thus began my decade-long battle with cholesterol. My old friends the Big Mac and French fries pretty much became history, and steak a much more casual acquaintance. My wife and three daughters, knowing my weakness of character when it comes to things bovine, started to do more of the grocery shopping, buying lots of chicken.
Didn't do any damn good. After two years of Big Mac-less days and steakless nights, my cholesterol levels rose higher than before. When measured 10 years ago in October of 1999, my total cholesterol was 274, the highest it had ever been. When you consider that every 1 percent increase in level over 200 increases my risk of heart disease 2 percent, this report was frightening.
I called my brothers to report the bad news, only to find that they too wage the same battle. The problem, it appears, is that I and my brothers inherited a defective steak-hating gene. We suffer from hypercholesterolemia. This mouthful of a word simply means inherited high cholesterol. People inheriting a copy of the defective gene from one of their parents have elevated levels of cholesterol in their blood serum that dietary restriction (taking away my steaks) cannot reduce.
My frustrating on-going battle with cholesterol is not unique. More than half a million Americans suffer from hypercholesterolemia, the most frequent of all gene disorders. None of my hundreds of thousands of brothers and sisters in this war, fellow victims of this genetic quirk, are able to reduce cholesterol levels by diet and exercise alone. They, and I, must rely on modern medicine to defeat our Mendelian enemy.
Even a quick look at the biology of cholesterol suggests a likely line of attack. Cholesterol is a special kind of fat that your body uses to control the flexibility of its cell membranes and to insulate nerves. Your liver makes about 80 percent of the cholesterol in your body, up to 800 mg. a day. You take in the rest when you eat steak and other fatty foods
You can see why my attempting to lower total cholesterol by reducing dietary input of fat (steaks, peanut butter, fried food, chocolate, ice cream -- all the good stuff) didn't get the job done. Dietary cholesterol is only 20 percent of my body's total. Most is manufactured by my liver, and because of hypercholesterolemia, my liver is churning out cholesterol twice as fast as a normal liver does. To solve the problem, I need to put the breaks on my liver's cholesterol-making frenzy.
In the 1980s, researchers determined that the rate-limiting step in the liver's manufacture of cholesterol occurs early in the process, when a 6-carbon molecule called mevalonate is converted to something called hydroxy methyl glutaryl CoA (HMG-CoA, for short). This reaction is carried out by an enzyme called HMG-CoA reductase. If we want to slow cholesterol production, that's our target.
In the past 20 years, a series of drugs called statins have been developed that reduce levels of cholesterol by inhibiting HMG-CoA reductase. Among them are fluvastatin (Lescol), lovastatin (Mevacor), simvastatin (Zocor), and pravastatin (Pravachol).
The newest member of the pack available to me then, introduced a dozen years ago, is atorvastatin (Lipitor). Lipitor is a particularly potent inhibitor of HMG-CoA reductase with fewer side effects than other statins. Developed by Warner-Lambert and marketed by Pfizer, Lipitor is a blockbuster drug. It generated $4.4 billion in sales its first year, and became the top-selling global drug by 2005, with sales in excess of $10 billion.
It is upon Lipitor that I have banked my future. I started taking it 10 years ago this week, a little white pill every morning before breakfast. It is likely I shall be taking it the rest of my life.
How well did it work? Very well indeed. Within three months of starting daily Lipitor tablets, my cholesterol level has fallen to below 200. In the 10 years since then, it has never risen above 200. Not once. When last measured a month ago, my cholesterol level was 158.
In "The Naming of Cats," -- the poem on which the broadway musical "Cats" was based -- T.S. Eliot says "a cat must have three different names." I think of my anticholesterol drug as being like T.S. Eliot's cat. Like his cat, my drug has a "sensible everyday name," Lipitor; a name which anyone can use. Then Eliot says a cat needs a second name, "a name that's particular," "a name that never belonged to more than one cat." Pravastatin is such a name, one that drug manufacturers and scientists use.
According to T.S. Eliot, every cat also needs a third very private name, a "deep and inscrutable singular name." For lipitor, this name, its chemical soul, is [R-(R*,R*)]-2-(4-fluorophenyl)-B,d-dihydroxy-5- (1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl] -1H-pyrrole-1-heptanoic acid.
To someone looking at a cholesterol level 116 points below 274, that's beautiful.
George B. Johnson's "On Science" column looks at scientific issues and explains them in an accessible manner.
Johnson, Ph.D., professor emeritus of Biology at Washington University, has taught biology and genetics to undergraduates for more than 30 years. Also professor of genetics at Washington University’s School of Medicine, Johnson is a student of population genetics and evolution, renowned for his pioneering studies of genetic variability. He has authored more than 50 scientific publications and seven texts.
As the founding director of The Living World, the education center at the St Louis Zoo, from 1987 to 1990, he was responsible for developing innovative high-tech exhibits and new educational programs.
Copyright George Johnson