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New Chapter Health Report
Beyond Aspirin:

The COX-2 Medical Revolution

Our most recent book, Beyond Aspirin, focuses on the medical revolution of COX-2 inhibition. Hailed by the Wall Street Journal in October 1999 as the next major milestone in preventative medicine, COX-2 inhibition was recently acknowledged by the Science section of the New York Times as a method of preventing cancers of the colon, skin, esophagus, and bladder. And that's just the beginning of the story, as COX-2 inhibition is also associated with reducing arthritic pain, inflammation, and damage, and arresting the development of Alzheimer's Disease. So it is no surprise that we chose to write a book examining the connection between traditional medicine, herbs, and COX-2 inhibition.

The book Beyond Aspirin began its life as a contemplated article on prostate cancer. The authors are somewhat addicted to an on-line medical database called "Medline," which is the on-line version of the National Library of Medicine. Paul, the most seriously addicted of the two authors, is often on Medline hours at a time, researching every nook and cranny of medical and herbal issues and late one night Paul called Tom to breathlessly report a late-breaking medical news item. For dramatic purposes, the conversation is reconstructed as follows:

      Paul: "Tom, go on Medline immediately and check out the latest article from the Proceedings of the National Academy of Sciences."
     Tom: (who is used to such late-night emergency calls from Paul on obscure medical topics): "And why should I do that?"
      Paul: "Because the National Academy has published an amazing article from the University of Virginia Cancer Center on a novel method of defeating prostate cancer, and you have to see it."
      Tom: "But Paul, how does research from a mainstream cancer center relate to our work on herbal medicine?"
      Paul: "The University of Virginia study demonstrates that prostate cancer cells only eat one kind of food. They are like children who will only eat peanut butter and jelly sandwiches, and simply will not eat anything else at all. The University of Virginia research determined that the prostate cancer cells will only eat a chemical called 5-HETE."
       Tom: "How does that relate to herbal research?" he asked with growing exasperation.
       Paul: "Well, the cancer center determined that 5-HETE was created from the body's 'combustion' of an Omega-6 fatty acid called arachidonic acid. There is an enzyme called 5-lipoxygenase (or 5-LO for short), and when 5-LO burns or oxidizes the fatty acid, out plops 5-HETE."
       Tom: "Well, this is all very interesting, but where does it lead and why should I be interested?"
       Paul: "Tom, the researchers concluded that prostrate cancer cells eat ONLY this food, and that if the 5-LO enzyme is inhibited, and the food is not around, then the prostrate cancer cells experience massive and rapid 'apoptosis,' or cellular suicide, within 1 to 2 hours."
       Tom: "Paul, I admit that is astounding, and probably the most important knowledge obtained to date on prostate cancer prevention and treatment, but Paul, it's late at night, and how does this all pertain to herbal medicine?"
        Paul: "Tom, you've forgotten my research in my earlier book Ginger: Common Spice and Wonder Drug. If you had studied the book as I have often asked [Paul often took this chiding tone with his friend!], you'd recall that ginger is a powerful inhibitor of the 5-LO enzyme."
        Tom: "Now I'm starting to see the importance of this call. How effective is ginger in inhibiting this 5-LO enzyme?"
        Paul: "I just jumped over to the USDA Phytonutrient Database [created by the world's leading ehtnobotanist Dr. James Duke], and his database and my research demonstrates that ginger is the world's most comprehensive herbal inhibitor of 5-LO, with at least 22 proven phytonutrient inhibitors of that enzyme. What is more, Oriental cultures that regularly consume ginger as spice, or which take it therapeutically, experience a fraction of the cancer mortalities compared to the United States. In other words, men don't die from prostrate cancer cells (which most of us get by the time we're in our thirties)- we die from the growth and proliferation of the cancer. Once we know that ginger inhibits the process that leads to the creation of the ONLY food the cancer cells will eat, it gives us confidence that an herbal approach to 5-LO inhibition is an indispensable part of prostate health. Tom, the cancer cells only eat 5-HETE, their 'peanut butter and jelly,' and without it they begin to massively and rapidly die within 1 to 2 hours."
       Tom: "Paul, we need to do a research paper on this. I realize that the University of Virginia Cancer Center is focusing on pharmaceutical 5-LO inhibitors, but the experience of herbal intervention is compelling. I see from the USDA Database that a particular fraction or fatty acid from saw palmetto also inhibits 5-LO, which probably accounts for some of that herb's efficacy in promoting prostate health. Let's pull together the research and see where it leads us"
        And that's how the article on prostate cancer began, and it led us in an unanticipated direction. Almost every time we found an interesting article on 5-LO inhibition, the research mentioned a "brother" enzyme called cyclooxygenase-2, or COX-2 for short. This research project began some time ago, and neither of us had ever heard of this enzyme. After all, there are thousands of enzymes in the human body, and one major school of pharmacognosy, the University of Illinois, tracks over 700 enzymes for herbal interactions or activity. So, we didn't feel totally stupid, but this COX-2 enzyme was starting to get quite a bit of international medical press, and it also worked by metabolizing or oxidizing Omega 6 arachidonic acid. We decided to follow the COX-2 thread for a bit and see where it took us, and to our amazement it was literally the mother lode. Three decades of research on inhibiting this enzyme led to one inescapable conclusion: inhibiting this enzyme would likely prevent or impede cancers of the colon, esophagus, skin, bladder, and pancreas, would reduce inflammation associated with several forms of arthritis, and would also disrupt the progress of Alzheimer's Disease.
       We reached these rather startling conclusions because the research would permit no other inference. There are over twenty reputable scientific studies on the clear relationship between reducing COX-2 inflammation and the reduction of the frequency of colon cancer, and there is a similar weight of authority on the Alzheimer's front. Here was the common denominator of several seemingly strong disparate disease processes which can all be understood as inflammation gone haywire and attacking not an invader, but our own bodies. Here is how science has pieced together the COX-2 inflammatory puzzle:

* Some trauma, injury, or hostile microorganism confronts the body, and the cells somehow experience this threat. Intelligence is present everywhere in the body-not just in the brain (our central intelligence agency) but also in the scouts and spies located everywhere in the body. Our cells feel or sense the threat, and send this impulse to our DNA within the cell.

* The DNA orders the creation of the enzyme COX-2, which is a little like calling 911. COX-2 knows it has a job to do-create inflammation. It goes to the cell wall, the phospholipid membrane, and seeks out something to burn. To send up a "smoke signal" summonsing the troops. The full name of COX-2 tells the story: "cyclooxygenase-2." The enzyme is able to "oxidize" fatty acids, and those acids are housed in the cell membrane.

* COX-2 thus oxidizes (the very opposite of "anti-oxidants") certain fatty acids it finds in the cell wall. If it finds Omega 6 arachidonic acid, it creates the PRO-inflammatory hormone PGE2, which is one of the body's prostaglandins. If COX-2 encounters Omega 3 fatty acid, like those present in ocean salmon or other deep and coldwater fish, then it creates an ANTI-inflammatory hormone called PGE3.

* In a state of ideal dietary balance, our Omega 6 to Omega 3 ratio would be 1:1, certainly no worse than 2:1. Unfortunately, because of our modern dietary indiscretions and the general unavailability of wholesome food, most Americans have an Omega 6 to Omega 3 ratio of 40:1 to 50:1! Simply put, when COX-2 does its job and creates the prostaglandins that control inflammation, we are giving the enzyme the raw materials to create fire, but not the raw materials to put out the fire. It's not that COX-2 is a "bad" enzyme. To the contrary, we need it for life. It's just that our diets and the stresses we live in today create way too much inflammation, and we don't have the resources to put out the fires.

* Think of this analogy: A burglar breaks into our home, and we call 911. (That's COX-2) COX-2 sends in the SWAT team of killer white blood cells, which have wonderful names like "macrophages (big eaters)." In other words, these killer cells are called in to kill and then eat the invaders or damaged tissue. When their job is done, we expect the "Big Eaters" to stop their work and go home. They've shot and killed and eaten the invaders, and it's time to let life return to normal. That is normal, natural, balanced inflammation. But what happens if the SWAT team doesn't go home? If the killer cells go on a rampage, stay for 15 or 20 years, and start to fire oxidative blasts of free radicals at healthy tissue? Imagine if the police killed the burglars, and then turned their guns on the parakeets, the dogs, the walls, the lights, and then on us! That, sadly, is the madness of "chronic" inflammation.

* We need the SWAT team to do its job, so we need COX-2 and some arachidonic acid. We then need them to go away, so we need the COX-2 enzyme to stop calling for reinforcements and we need to create anti-inflammatory hormones such as PGE3 made from Omega 3 fatty acid, which is the "go home" food needed to put the killer forces to rest.

* If the process of inflammation becomes chronic, the "collateral damage" to healthy tissue can result in a number of diseases. If the beta amyloid plaque in the brain becomes unduly inflamed, the brains literally fester in a fire of chronic inflammation. As Uncle Remus once said, you can hide the fire, but what can you do with the smoke. The fire, the inflammation, born of festering plaque may be localized, but the smoke damage from that fire is akin to a cloud of neurotoxins sweeping through the brain, deadening mental faculties. Chronic brain inflammation leads to Alzheimer's Disease. Similarly, chronic inflammation in the colon, perhaps from polyps that become severely irritated, can lead to colon cancer. You don't find a normal colon cell suddenly degrade to a cancer cell. There is a continuum: normal cell, inflamed cell, precancerous cell, dysplastic cell, and cancer cell. Too much COX-2 inflammation, over time, creates the ground state for cancer in the colon, as well as other organ systems. For example, a cancerous pancreas has 60 times the COX-2 enzyme as a normal pancreas. Rheumatoid arthritis, menstrual migraines, periodontal gum disease, juvenile onset diabetes-these are just some of the many diseases or medical conditions that correspond in some way to an overexpression of the COX-2 enzyme.
As a consequence of this emerging picture of the body on fire-the body in a state of perpetual "road rage"-drug companies are looking for ways to pharmaceutically inhibit the COX-2 enzyme. Let's examine the history of this process:

Before Aspirin
Imagine life in ancient Greece: The philosophical societies, the discourses on politics and geometry, the Platonic academies. It was all so civilized and informed, and medicine was no exception. The father of Western medicines, Hippocrates, was sometimes called upon to treat fevers and inflammation, and he would tell his patients to chew on the bark of the white willow tree. And it worked. That was "Before Aspirin."

Aspirin
In the 1890s, scientists at Bayer felt that Hippocrates' remedy was too primitive for modern life. Who wanted to chew on white willow bark, after all? So these scientists set out to locate the one chemical within the white willow they believed responsible for its anti-inflammatory effects. It was, they believed, a salicin derivative, to which they added vinegar (acetic acid). Voila! Acetylsalicylic acid, or aspirin. It may well have been the first standardized and synthetic herbal preparation, and it really worked great. It cut fevers, reduced inflammation, was a fabulous analgesic, and over time was discovered to reduce the incidence of certain cancers and even Alzheimer's Disease. To top it off, this wonder drug reduced platelet stickiness, thus helping to ward off strokes and heart attacks. These successes led people to consume over one trillion aspirins over the next 100 years, and we can call the 20th Century the Aspirin Century. The good news we can also call "Dr. Jeckyl." Now meet Mr. Hyde. Last year, more people died from the hemorrhaging, bleeding, and renal failures associated with aspirin consumption then from the AIDS virus. And hundreds of thousands more were hospitalized from aspirin-related side effects. The cruelest irony is that the very people who benefit most from aspirin, namely the elderly, are the ones who tolerate it the worst. When we are 18 and sprain our ankles or have a cut, our bodies heal quickly. But at 60 or 70 or 80, the healing is slower and less complete. So an 18 year old can slough off the tiny ulcers and bleeding caused by aspirin consumption, but those same side effects may be lethal for someone older. We all needed something better. We all needed a "safer" aspirin.

The "Safer" Aspirin
The legitimate desire to have aspirin's good news without the unwelcome side effects-to have Dr. Jeckyl without Mr. Hyde-led scientists to search for the hidden mechanisms by which aspirin worked. The funny thing about aspirin is that even though Americans take 100 million aspirin or other non-steroidal anti-inflammatories a day, no one knows precisely how they work. Sir John Vane received a Nobel Prize in the 1970's for discovering that aspirin inhibited the creation of inflammatory prostaglandins, but how? It was thought that aspirin inhibited the creation of "cyclooxygenase," but scientists believed that it was this one thing called cyclooxygenase that both protected the stomach and kidneys and created inflammation. Wrong. Scientists later discovered, in the early and mid-1990's, that there were two cyclooxygenases. There was COX-1, responsible for certain "housekeeping functions" like maintaining the kidneys and the stomach, and COX-2, responsible for, among other things, inflammation. Scientists later synthesized a number of designer molecules that would inhibit the COX-2 enzyme while basically leaving the COX-1 enzyme to do its important work. Enter the "safer" aspirin such as Celebrex® and Vioxx®. They were supposedly "safer" because they didn't disrupt quite as much of the activity of COX-1. But there was a catch. They also didn't inhibit platelet stickiness or aggregation, so they didn't offer aspirin's stroke or heart attack prevention features. What is more, the University of Pennsylvania determined in 1999 that at least as far as Celebrex® was concerned, there was the possibility that the drug could actually increase platelet stickiness, so the university researchers suggested that if people took Celebrex® to avoid the side effects of aspirin, then those people should take aspirin to avoid the side effects of Celebrex®! Maybe there was another path, a path to reducing inflammation without the risks associated with the synthetic pharmaceutical approach. Perhaps we could go "Beyond Aspirin" altogether, and through the window of modern science revive the wisdom of the first doctor, Hippocrates.

Beyond Aspirin
The first doctor of the Western World, Hippocrates, prescribed white willow bark. The first doctors of the Eastern World, in Traditional Chinese Medicine and Ayurvedic Medicine of India, prescribed such anti-inflammatories as ginger, turmeric, hu zhang, scutellaria, baicalensis, and holy basil. All of those herbs, and a number of others revered in traditional medical systems, have now been scientifically proven to inhibit the COX-2 enzyme, safely reduce inflammation, and all without the side effects associated with the synthetic approach. With new methods of plant analysis and extraction, such as supercritical CO2 extraction, the "folklore" of herbalism has now become the "science" of herbal medicine. It is now possible, for example, to identify the various herbs like ginger that are biologically most active from an anti-oxidant and proteolytic perspective, and to extract and powerfully concentrate the healing resins of the herb without the use of damaging chemical solvents.

Our book, Beyond Aspirin, identifies all the leading COX-2 inhibiting herbs, the types of extracts, most notably supercritical extracts, best suited for reducing inflammation, and a practical guide for leading a life where inflammation is our weapon and friend, and not our deadly enemy. We invite you to go "Beyond Aspirin," and return to the balanced and time-tested methods of traditional herbal medicine.

-Thomas M. Newmark and Paul Schulick
Authors of Beyond Aspirin

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(If you would like the entire New Chapter Health Report on Beyond Aspirin: The COX-2 Medical Revolution, see www.babyboomers-seniors.com and go to Boomer Times & Senior Life Index for the September "Book of

The Month" or send $1.50 for a hard copy to Boomer Times & Senior Life, 1515 N. Federal Highway, #300, Boca Raton, FL 33432 (561-736-8925 or email srlife@gate.net).
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