Wednesday, February 6, 2008

Oops, I Patented Your Natural Product

What are good ways to lower your cholesterol? You could eat less cholesterol. That helps, but the human liver is great at making cholesterol. In fact, it tends to do so pretty much constantly--but entertainingly enough, the liver works the hardest at producing LDL cholesterol (the "bad" cholesterol) while you're sleeping. No, you shouldn't give up sleep. But what's worth recognizing is that diet isn't the only source of cholesterol, and in fact, the liver probably contributes more bad cholesterol than diet. In fact, removing part of the liver reduced circulating LDL concentrations in animal studies. You could also exercise, drink less alcohol, and give up smoking. All of these things work. But what if they aren't enough?

Statins are a popular target for proponents of "alternative medicine." You don't need statins, they say, you can just take vitamins and eat healthy. Sometimes they promote other unproven supplements or "treatments." Statins are dangerous. Statins are worthless. The lipid hypothesis is false; scientists are lying to you and cholesterol has nothing to do with cardiovascular disease. Here, drink this Kool-aid.

Pigs fed high-cholesterol diets are more likely to develop cardiovascular disease (CVD). And Watanabe rabbits lack a specific gene that prevents them from manufacturing receptors for LDL cholesterol in the liver. Normally, the liver's LDL receptors sense circulating cholesterol levels as a regulatory mechanism; if there's a lot of cholesterol floating around, the liver will react by making less cholesterol. Since the rabbits' livers are unable to compensate for high levels of LDL, they develop arterial plaques with astounding frequency. If fed a high-cholesterol diet, the rate and probability of plaque formation increases. And if animal studies aren't good enough, check out the Framingham heart study, which involves an entire town in Massachusetts that's been followed for three generations to learn more about CVD risk factors. Scientists didn't just pull the lipid hypothesis of atherosclerosis out of thin air. There's a lot of very thorough research and credible data that's been taken into consideration.

All the attempts to "debunk" the lipid hypothesis and the value of statins are crackpottery. Are they miracle drugs or cure-alls? Of course not; no one says they are.

Anyway. "Natural" methods for treating illness are popular with a lot of patients. There's something wholesome-sounding about the word, like your mother would want you to take natural products. Nevermind that natural does not mean safe; botulinum toxin is one of the most dangerous substances in the world, and it's made by bacteria. All-natural! Maybe that's why people are willing to inject it into their faces to get rid of wrinkles.

Here's a secret. Statins are natural.

Have you heard of red yeast rice? It's an interesting product. Monascus purpureus, a fungus that grows on rice, produces a wide variety of chemical compounds, including a group called mevinic acids. Naturally fermented red rice yeast is about 0.4% mevinic acids by weight. Red yeast rice supplements are not always what they claim to be on the label, but there's presumably some statin-equivalent content in there.

How about mevastatin? Mevastatin was isolated from Penicillium citrinum mold. Man, mold is great stuff. We play with mold long enough and we have this interesting tendency to serendipitiously find antibiotics and anti-cancer compounds.

Like penicillin, statins were originally isolated as naturally-occuring substances. The major mevinic acid compound in red yeast rice was named lovastatin. And guess what? It got patented. It's called Mevacor. Huh. I thought the natural medicine folks were always saying that the reason Big Pharma isn't willing to seriously investigate "natural remedies" is because they can't be patented?

That claim, of course, is a load of Penicillium fungus. Sure, you can't patent vitamin C, but you can patent unique compounds that you discover, no matter where they come from. Statins are some of the top money-makers for Pharma today (for better or for worse), and they got their start in yeast and mold colonies. Pharma would have to be incredibly to stupid to ignore nature as a potential source for useful drug compounds. It's true that most of the statins prescribed are synthetic compounds like simvastatin (Zocor). But simvastatin was made by modifying lovastatin to increase its effectiveness. Inspired by nature, proven by science. Saying Zocor is unnatural is like saying cutting trees into two-by-fours to build houses instead of just using felled logs is unnatural. By altering a naturally-occuring substance, we can make it a better drug than it would be otherwise.

If something proves to be useful, medicine will use it, whether it's "natural" or not--a false dichotomy to begin with. And if it isn't, medicine will discard it. Scientific analysis is the only way to tell the difference. And anyone who tries to tell you differently needs to go read about penicillin.

2 comments:

Abel Pharmboy said...

Very nice post! Most folks don't realize how much natural medicine we use in medicine.

For more neat history on the discoverer of the first statin source, you should read the WSJ article cited in my post on the old blog from Peter Landers. Don't know if it's freely available but e-mail me if it isn't I'll send you a subscriber invitation link.

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