[Ed. Note: Dr. KSS writes about medical topics and biotech stocks for the Irregulars. He has agreed to our trading restrictions, and his thoughts and words are his own. Enjoy!]
Any discussion of cholesterol immediately turns Brobdingnagian, such are the extremes in question.
Statins, which lower LDL cholesterol, are bombastically the best-selling drugs of all time. They’ve left a Paul Bunyan-size footprint in medicine. But they are hardly ancient and hoary. The prototype statin was discovered by Akira Endo, PhD, in 1970 while he worked for Japanese chemical giant Sankyo. Despite the Saganesque billions and billions of dollars, euros and yen his discoveries fetch every year, Endo has never seen even a nickel of the profits. Endo has been mildly honored, while those acting on principles he first introduced to the world, such as Brown and Goldstein, have gone on to Nobel notoriety.
Endo began with a hunch: cholesterol is an elemental life-cycle molecule for many organisms, and so maybe other organisms had stumbled onto ways to knock the cholesterol underpinnings out from potential invading pathogens as a safety measure. The fungi, for example, are famous sources of antibiotics that snuff bacteria. Maybe fungi had also devised a way to attack cholesterol production as a defense? Fungi have ergosterol rather than cholesterol in their cell membranes, and so could poison cholesterol-making machinery at no harm to themselves.
I’ve lived in Asia, and so have often searched for analogies to help Westerners understand how sharply Asian cultures differ from each other. One archetype is a thought exercise in which a representative of an Asian nation is given an uncut loaf of bread and asked to slice it in a way that reflects his/her culture. A Thai person, for example, would slice it ornately, lovingly, and so beautifully you’d be reluctant to eat it. A Vietnamese person would have it all sliced for you by the time you are finished explaining what you want. A Japanese person would devise a way to make bread slices that are but a few molecules thick. No culture has the fixity of purpose and ruthless attention to microscopic painstaking detail that the Japanese have. Endo went after this issue like a good Japanese scientist, and personally screened 6,000 individual compounds that had been purified from various fungi for one that could inhibit cholesterol synthesis. He didn’t have a high-throughput nanosensor-based microchip array to do it for him. He rolled up sleeves, told his wife not to wait up, and did it the old fashioned way.
Endo’s work led to identification of monacolin K, later dubbed lovastatin, the first such agent used as a drug, in certain oyster mushrooms and other species of fungi. To this day, many statins used as drugs are purified from fermenting yeast rather than synthesized. Although the fungus-derived statins are natural products, somehow patent protection on them was finagled (now lapsed). Meanwhile, in its most legendary abuse of power, the FDA in 1998 tried to ban red yeast rice because it naturally contains lovastatin, made by the yeast. All statins are inhibitors of a liver enzyme called hydroxymethylglutaryl CoA reductase. 85-90 per cent of the body’s total cholesterol burden is made in liver, which is why the weak anti-cholesterol agent ezetimibe, which only blocks absorption of dietary cholesterol, has little effect and really does not warrant clinical use as it is not cost-effective.
The Brobdingnagian thing, again: no topic incites more vigorous discussion, more one-off hyperbole, than statins. Character X emerges from stage left to say he knows someone who lived to be 100, ate bacon and fried eggs for breakfast every morning, and never took any pills. Mrs. Y flies out of stage right to say that one dose was all it took…..a statin nearly killed her husband and she can prove it. A chorus begins a strophe: “We’ll all get muscle aches anon!,” though perhaps only a fourth of statin users get meaningful muscle pain. Offstage a mournful basso begins a lacrimae about how his best friend took statins every day just like the doctor ordered and they didn’t save him from The Big One. I’ve posted commentaries on them, as has Michael Jorrin, and invariably the threads that follow become tempestuous. Many readers are angered by their doctors’ glib default recommendations that all should be on them and others assert their exceptional wellness in the absence of, or because of the absence of, a statin prescription. Statins are blockbuster drugs, and are so avidly believed in by both the medical and pharma establishments (which rarely are so aligned) that some only half-jokingly think statins should be in the water supply.
Even so, statins have their vigorous detractors, many of whom are quite learned. The International Network of Cholesterol Skeptics makes interesting if insufficient arguments. Every major medical credo always has passionate critics; Peter Duesberg, PhD, of UC-Berkeley has actively, savagely denied for 30 years that HIV causes AIDS. Duesberg is a member of the National Academy of Sciences. Statins are roundly bashed by abominations like Dr. Joseph Mercola at his appalling website, and commonly if people do quite the opposite of what Mercola asserts they should, they will be far better off and healthier. Mercola’s interests are not, of course, in health; they’re—-you guessed it!—-pecuniary! He tells you that health comes only from what he sells you, from his special nostrums that the establishment denies exist.
Where cooler heads prevail about vascular disease, the following large tenets usually emerge, on the basis of large numbers of studies of large numbers of people for large numbers of years:
(1) there is great merit to linking cholesterol with vascular disease. It is not the only factor, as insulin resistance, blood pressure and inflammation play roles too, but it is a major factor.
(2) statins are poorly tolerated in some patients, but by no means all. Most can muddle through, especially if they dose their statins at night and sleep through the muscle-ache interval.
(3) statins may not provide be-all-end-all vascular disease prevention because they address only the cholesterol aspect, but they do play a vital role, as the overpowering evidence is that cholesterol contributes to vascular disease and is easily modified.
(4) statins are definitively, overwhelmingly helpful in secondary prevention: preventing a second MI or CVA after a patient has had a first one. For primary prevention, helping a patient never have an initial event, their merit is debated still. The bulk of data shows them helpful in primary prevention, but that data is not as stark as for secondary prevention.
(5) statins do have other effects: they may worsen insulin resistance in some patients, intensify dementia in others (cholesterol is the most abundant substance in br