Live Long and Prosper Nutraceutically

As Ive said many times, the best way to get rich is simply to live longer and let the mathematics of exponential portfolio growth do its work. This month, I have a company that has a synthesized form of a natural alkaloid I believe will allow you to do just that. I also believe that equity in this company will yield truly transformational returns. However and I admit this is a big however this technology is in the very early stages. This company is so disruptive, I wouldnt be surprised if some of the industries it will disrupt will try to discredit or stop the product. Moreover, we dont yet have long-term double-blind human studies on the use of this substance. On the other hand, we dont yet have blinded human data for quite a few of our companies drug candidates. This isnt unique. There is, however, something about this product that inspired in me a particular degree of skepticism and caution. I assume, therefore, that it may provoke the same skepticism in you. Specifically, this companys product is a nutraceutical. Nutraceuticals Vs. Drugs Nutraceuticals, as you know, are foods or food-derived products meant to provide health benefits. They may function exactly like substances considered drugs legally, but they are not categorized as drugs. For example, you may take or sell the extract of willow bark for use as an anti-inflammatory, anti-clotting agent or painkiller without getting government permission. You cant make medical claims about willow bark extract, or the active ingredient, salicylic acid, however. Current government policy in the U.S. and some other countries reserves that right for products that have passed extremely lengthy and expensive procedures. If you synthesize a very similar compound, acetylsalicylic acid or aspirin, you have a drug. With regulatory approval, you can, therefore, make certain kinds of claims regarding its efficacy in the prevention of heart attacks or strokes. There is very little difference in the actual function of the two products, though. One other difference is in the realm of patent law. Drugs can be patented, period. Nutraceuticals can be patented for specific uses only. Because nutraceuticals are not subject to testing requirements and regulations, they are much easier to bring to market. In some instances, impure and even dangerous nutraceuticals have been widely sold. The FDA can force a product off the market if it is found to be harmful, but the agency does not have legal authority to require clinical testing. As a result, there have been some major problems in this area. You undoubtedly recall when beta-carotene, derived from plants such as tomatoes, was widely heralded a panacea. Books were written claiming it would cure cancer and extend life spans. Despite the lack of blinded studies, untold millions were spent on beta-carotene supplements. Finally, when beta-carotene supplementation was tested clinically, the claims were discredited. Some clinical results showed that the nutraceutical actually increased cancer risk.

So supplement makers went back to the drawing board. We know there are clear benefits from eating lots of tomato products, particularly in the area of cancer prevention. Some reasoned that another nutrient, which is always found in conjunction with beta-carotene, was responsible for the solanaceous fruits health benefits. They settled on lycopene. In effect, they decided that beta-carotene is a marker for lycopene and they had mistaken the marker for the active ingredient. Thus far, theres little evidence that lycopene lowers cancer risks, either. Another nutraceutical that has proven disappointing is resveratrol, the anti-fungal phenol found in red grapes and other plants. You may have noticed that Ive never waved the resveratrol flag. There has never, in fact, been any real evidence that it conveys beneficial effects to mammals. At the height of the resveratrol craze, I tried the product for a while to see if I could detect benefits others swore they were experiencing. I noticed nothing and stopped. Recently, a concentrated drug form of resveratrol actually produced harmful effects in humans. Millions of words, though, have been written by people who claim incredible benefits from resveratrol supplementation. Lacking any real evidence, I have to conclude this may be a sort of group placebo effect. Supplement fads arrive and legions of seekers arise to praise some fresh nutraceuticals wondrous effects. Weve seen this cycle play out so many times. Fans of a product swear it is improving their health, but eventually stop taking it often just as another supplement fad arrives. The people who claim medical benefits are absolutely sincere, however. This makes it very difficult to judge anecdotal testimonials regarding nutraceuticals. On the other hand, there are incredibly important and effective nutraceuticals. Omega-3 fatty acids, in both the fish oil extract and the purified synthesized form, are linked by real data to improved health. The nutraceutical form of vitamin D is also an important supplement with clinically verified health benefits. If your circulating levels of 25-hydroxyvitamin D are below 45 ng/ml, I would strongly recommend that you speak with a doctor who keeps up with the scientific literature. Im telling you all this for a reason. Im recommending a company that has nutraceutical products, so I want you to go in with your eyes open. I also want you to know why I was so skeptical and why Ive gone to extra lengths to verify the story and the people involved. Im convinced that this is one of the most important breakthrough technologies of our time. I wont pretend, however, that were not in the Wild Wild West of investing when we venture into nutraceutical territory. That isnt necessarily a bad thing, though. The same dynamics that make this area volatile and unpredictable can also lead to enormous profits. (Incidentally, the Wild Wild West was never as dangerous as the urban east, past and present. My friends Dr. Terry Anderson and Dr. P.J. Hill of Montana State University demonstrate this in a wonderfully entertaining academic journal article that you can read at this link [2].) Given all these caveats, Im nevertheless convinced that the company were adding to the portfolio this month has a product that actually does what other supplements only wished they could do. As I said earlier, I believe that most people who take the anatabine citrate supplement made by Star Scientific Inc. (NASDAQ: CIGX) will see significantly improved quality and length of life.

Yes, I realize how radical that statement really is. If I heard this from someone else, I would almost certainly dismiss the claim as ignorant or dishonest. In fact, I did. For that reason, Ive wrestled with the best way to present the science behind this product. Having spent more than a month researching this biochemical technology, Ive come to the conclusion that there is no way to completely convey the scientific and financial story behind this company in one issue. It took me weeks to overcome my initial skepticism regarding this technology. Ive spoken at length to extremely important respected scientists and have hours of taped interviews. Ive read tens of thousands of words on the science behind this breakthrough. Ive visited one of the worlds top biotech research laboratories and have met researchers whom Ive known about for over a decade, but never expected to meet. Ive never wanted you, my readers, to blindly take my opinion about anything. Im paid to give you disruptive technology companies but obviously, they cannot all be equal. This is why I lay out the evidence and science with source materials included. I do this so you can come to your conclusions and make decisions based on your own situation. Given my own initial rejection of this biotechnology, I have to believe that intelligent readers will be as skeptical as I was when it first came to me. You should be, in fact. I doubted even though I was already familiar with much of the science and many of the researchers whom Ive encountered in the past month. Nevertheless, it was difficult for me to accept the importance and magnitude of this discovery. For many of you who do not follow medical research obsessively, as I do, this story will sound more like science fiction than science. Therefore, this issue is going to serve only as an introduction to this nutraceutical biotechnology. A single comprehensive article on the core science would be too long and technical for almost anybody but doctors and scientists. Therefore, this will have to serve as an initial overview. More detail will be provided in forthcoming issues. That said, I warn you that it is also one of my longest. I beseech you, though, to read this issue entirely. This technology is going to have a far bigger impact on a wider variety of companies than you might initially think. Moreover, telling the story in even more depth would require that I get the approval of numerous scientists Ive interviewed. I never quote any of my sources without approval, and usually only after they have seen the quotation in writing. Because this month has been so unusual, I didnt have time to do that. I will, though, have verified quotations regarding this biotechnology in future updates. More data, including real human clinical data, will be available within the next few months. Ill keep you up-to-date as evidence appears. I believe that Star Scientifics anatabine supplement will not only make you healthier and wealthier, it will have an impact on the U.S. and world economies. I dont know how soon the biggest impacts will arrive, but its going to happen unless something completely unexpected prevents it. There is no one among all my readers, by the way, who has not already taken anatabine in some form. It is, after all, basically, food. You were not, however, taking it at the currently achievable level of purity or in optimal quantities. It is, in fact, found in members of the Solanaceae family of plants. These include tomatoes, red peppers and, most important from the perspective of this story, tobacco. The Star Scientific Story You may know that I have been extremely fortunate to have had a number of articles about biotechnologies published by John Mauldin. With his 1.5 million readers, including many extremely influential thinkers, Mauldins network is formidable.

Through Mauldin, I have gained access to biotech scientists whom I might not have encountered until they achieved a much higher level of visibility. Word of Breakthrough Technology Alert, because of his generous help, has penetrated much further into the world of emerging biotechnologies. These days, Im regularly approached by people who believe they have important technologies. This is an enviable position to be in. Some of these companies dont measure up. Usually, it is because theyre unaware of progress in related fields that will make their platforms prematurely obsolete. Generally, however, people dont approach me unless they believe their science is solid and their potential is transformational. One such person is now a reader of this newsletter. He sent me, though Mauldin, information about a company that claims to have a nutraceutical that significantly reduces chronic low-level inflammation. This is such a big claim. I assumed I was seeing the same old beta-carotene resveratrol health food fad cycle playing out once again. Such a compound would be a world-changing breakthrough, even if it were a regulated drug. A safe nutraceutical that controls chronic low-level inflammation, outside the bureaucrats regulatory reach, is just too good to be true. I didnt believe it for a second. I didnt even consider it. Let me explain why. The Inflammaging Story The name of the neural circuit that regulates the immune response to injury and invasion is the inflammatory reflex. Inflammation is an extremely complex mechanism that involves the destruction through apoptosis of damaged cells, the healing of salvageable cells and the growth of entirely new cells. In the last decade or so, it has become increasingly clear that inflammation plays a major complicating role in almost all diseases. When we are young, the primary role of this important biological response is to heal injury or infection. In the last century or so, the inflammatory reflex has begun to play a role that it almost never did in the past. For the vast majority of human history, life was hard and life spans were short. For Greeks during the Classical period of the 5th and 4th centuries B.C., the average person lived only about 28 years. It was nearly the same for ancient Romans. Life spans rose to about 30 years in medieval Britain and reached, in the developed world, about 45 in the early 20th century. I think people tend to underestimate just how rough life was until very recently. Before it was possible to mass-produce penicillin, during the Second World War, a broken bone that protruded through the skin resulted in death at least 50% of the time. Being thrown from a horse, kicked by a cow or bitten by any kind of animal was a serious, potentially life-ending matter. Early automobile accidents were far more dangerous because of the risk of secondary infection. Lacking safer modern technologies, industrial and household accidents were more common and far more lethal. In the olden days, the only way to survive a nearly inevitable sequence of injuries was a strong inflammatory immune response. If individuals didnt have the ability to mount a powerful inflammatory response, they were unlikely to live long enough to pass on their DNA. Today, however, life expectancies are pushing 80 years in North America. Despite the inane delusions of green fantasists, modern life is altogether safer and better. Medical technologies allow us to survive injuries and infections that would have quickly killed our grandparents. Herein lies the rub, however. We still have an inflammatory reflex that was tuned in ancient Greece and medieval Europe.

It is now understood that inflammation plays a role in virtually all diseases. In fact, inflammation increases the rate of aging itself and leads to various pathologies. This is why your dentist lectures you about flossing. Inflammation from unhealthy gums increases the odds of getting heart disease and even Alzheimers. Even with perfect gums, however, chronic inflammation increases as you age. Eventually, it creates a problem serious enough to trigger a cascade effect. Uncontrolled inflammation causes the simultaneous healing and destruction of cells. This can lead to cancers, heart attacks, lupus, IBS, macular degeneration, stroke, obesity, ED, allergies, psoriasis, Crohns disease, endometriosis, rheumatoid arthritis, hair loss, diseases of the organs such as the thyroid and liver as well as well, you name it. The general public learned about this for the first time in a 2004 Time magazine cover story titled The Fire Within [3]. Today, scientists have advanced the science much further. Many are now using the term inflammaging, [4] coined by Claudio Franceschi, professor of immunology at the University of Bologna. It appears, in fact, that our immune systems react to the normal effects of aging as if they were injuries. This initiates inflammation, an immune response. This inflammation causes cellular stress, which increases the degree of chronic inflammation which causes even more damage. It is, by definition, an autoimmune disorder. Some scientists call it auto[innate]immunity [5] subclinical syndrome. It is a vicious circle, a chronic cycle that spins faster and faster until the organism itself eventually fails. Aging, we now know, is not linear. Like so many other things, it is an exponential process that accelerates over time. If there were a way to stop chronic low-level inflammation, however, we could put the brakes on the autoimmune inflammation cycle. If we could stop chronic low-level inflammation, our bodies could heal naturally, just as they did before inflammaging kicked in. We would even see cells damaged by past inflammation-related diseases heal normally. Were not talking about regenerative medicine, of course. Our cells eventually reach their Hayflick limit [6] even if we halt the inflammaging cycle. We will eventually run out of the telomeres used every time a cell replaces itself through chromosome replication. Cells that are running out of telomeres stop functioning properly and eventually fail. Regenerative medicine promises to replace aged cells and tissue with young telomere-restored cells and tissue. An alternative route is the activation of the telomerase gene, which we know can restore telomeres to youthful lengths. In the meantime, however, we need to slow the process of telomere loss. For some time, scientists have known that inflammation is the primary accelerator of telomere loss. This is why so few of us reach our theoretical maximum life spans, which could be 120 years or more. We would be much, much more likely to reach that theoretical upper limit if we aged as we did when we were young. Its often said that time speeds up as get older. Now we know there is a great deal of truth to that adage, though not in the sense it is usually intended. A drug that actually controlled inflammaging would restore the aging process to a more linear progression, as it was when we were young. For this reason, many scientists are looking for the means to reduce or stop inflammaging. Not infrequently, this hypothetical drug has been referred to as the holy grail of drug discovery.

The Market Potential for a Safe Anti-Inflammaging Compound The market for such a compound would be so big it is nearly incomprehensible. It is instructive, though, to consider one relatively weak anti-inflammation drug. Lipitor, technically atorvastatin, does lower indicators of inflammation. The most well-known, because doctors can test for it easily, is C-reactive protein (CRP). CRP levels rise with inflammation and their reduction demonstrates lowered inflammation. As a result, Lipitor is known to reduce the danger of cardiovascular and other diseases for many people. Measured by sales, Lipitor is the most successful drug in history. Last year, Pfizer sold over $5 billion of Lipitor. This is despite a broad range of adverse effects and competing anti-inflammatory statins. At its peak in 2006, Pfizer was earning almost $13 billion annually from Lipitor. The patents expire this year [7], by the way, and Lipitor represents about 15% of Pfizers total revenues. The reason I didnt take Star Scientific seriously was that the company was saying, essentially, that it had found a compound that is far more effective than Lipitor or the other statins while being safer and cheaper. That, my friends, is the holy grail of modern medicine so many scientists are seeking. More unbelievable still, theyre saying it isnt even a drug in the legal sense. The holy grail is an extremely safe nutraceutical a food that all of us consume in small quantities regularly. This, I believed, was simply way too good to be true. I never read past the first few paragraphs of their materials. I didnt like the name of the company, Star Scientific. I didnt like its ticker, CIGX. Nothing more would have come of it if I had not accepted an invitation from John Mauldin to a dinner in Palm Beach. My associate Ray Blanco and I drove across the state and found ourselves in a bar with John. Shortly thereafter, the Breakthrough Technology Alert reader who had originally sent me the information about Star Scientific joined us. With him was the CEO of Star Scientific, Jonnie Williams. The Jonnie Williams Story I didnt initially recognize the name, but as soon as he began talking about himself, it all came together. I remember when Jonnie Williams invented the tobacco curing technology that dramatically reduces carcinogenic toxins. He financed that research, by the way, with a small part of the fortune he had made as a major investor or co-founder in several successful biotechs, including VISX. Williams improved tobacco technology is universally used today. This technology has extended millions of lives around the world. I remember also when Williams entered into Americas largest patent lawsuit, by size of damages requested, with R.J. Reynolds Tobacco Co. An associate of Williams, a world-renowned scientist, has since described him to me as a force of nature. Its a good description. Without his drive and particular combination of curiosity, optimism, skills and character, this discovery might never have been made. Williams has absolutely no doubt about the nutraceutical he has discovered. If youre accustomed to speaking with extremely careful scientists, as I am, hes nothing like that. Nothing. That evening in Palm Beach, he repeated to me the basic claims his friend had sent me. He said, though not in these words, that he had discovered a safe nutraceutical that controls the vicious cycle of inflammaging. At that point, I was smiling politely and listening. I still didnt believe him, but he convinced me he was sincere. He wasnt lying, I figured. He was just wrong.

I was curious enough, however, to take Williams up on his offer to meet with scientists working with his technology in Sarasota, Fla., where hes based. I had asked him questions that he didnt have answers to, so he encouraged me to come up and see the lab and talk to the scientists. Road Trip to Sarasota Ray Blanco and I programmed the GPS locator and drove to Sarasota with the windows open. Florida is beautiful this time of year, and we have similar tastes in music. I was prepared to waste a day. We arrived at Williams office at the airstrip where he keeps his plane. On the way to the lab, he gave us the backstory to the discovery of anatabine. Im going to give you a very abbreviated version, because the whole saga could and ought to fill a book. Its a truly fascinating scientific and entrepreneurial detective story. Williams Virginia family had been associated with the tobacco industry for generations and he had seen cigarettes prematurely kill many friends and family. Wealthy from his biotech investments, he retired. Nearly by accident, however, he found himself the owner of a tobacco processing plant. With the raw materials at hand and an insatiable curiosity, he started wondering if he might be able to make tobacco less dangerous. This was based on the fact that the tobacco plant itself contains no carcinogens. Only when its cured do the toxins form. Eventually, he invented a superior processing technology using microwaves to speed the drying process, reducing carcinogenic toxin creation significantly. It wasnt enough for him, though. He then set out to find a way to help people quit smoking entirely. The standard smoking-cessation aid at the time, and today, is nicotine chewing gum. Unfortunately, the success rate for nicotine gum is barely higher than for normal chewing gum. You would probably be better off using a xylitol [8] gum, a clinically validated nutraceutical. Williams reasoned that there must be something in tobacco other than nicotine that draws people back to the whole tobacco plant product. He was not the only person to reach this conclusion, though he was the first person to methodically and earnestly look for the answer. The Crow Connection On a personal note, Ive been fascinated with the medical properties of tobacco my whole life. Because my great-grandfather was honored by the Crow, or Apsalooke, tribe for some technology-related things he did for them following the Battle of the Little Big Horn, Ive always had family among the Crow. As a child, I lived in Crow Agency, Montana, and saw traditional Crow rituals and dances. Many dealt with the medicinal properties of tobacco. The tobacco medicine pipe is common to many tribes in North America. For the Crow [9], however, the sacred tobacco bundle is the central religious icon. The legend of the creation of the Crow tribe begins, in fact, with the gift of tobacco to the Apsalooke patriarch by his star-faring father. The medicine pipe is on the tribes modern emblem and the sacred tobacco bundle is at its center. The Mesolithic Crow, however, were not chain-smoking cigarettes. Tobacco cultivation was rigidly ritualized and forbidden to all but a few. The medicine pipes use was limited to certain important occasions and locations, such as the sweat lodge. Used with that sort of moderation, tobacco seems to have very few ill effects. Beyond its pleasant antidepressant monoamine oxidase (MAO) [10] inhibiting effect, there are well-documented medical benefits.

For example, its long been known that smokers are much less likely to get Parkinsons disease [11]. This applies even to very moderate smokers, such as people who only occasionally sneak a cigarette. I suspect that the Mesolithic Crow smoked about as much tobacco as was needed to get the benefits of tobacco without most of the ill effects. (Personally, when I smoked, I was never able to achieve that level of moderation. It would require, I think, a strict social and religious structure such as the Crow had.) Secondhand Smoke Signals Ironically, there are even some benefits from secondhand smoke. I remember when the flight attendants organization funded a study to determine just how bad cabin smoke is on thyroid health. The study was performed by prominent Johns Hopkins endocrinologist Dr. Paul Ladenson and others. When the study was completed, the data actually showed a reduction in Hashimotos thyroiditis, commonly called thyroid disease, among those exposed to secondhand smoke and smokers. Subsequently, other studies have verified those results [12]. Today, incidentally, Dr. Ladenson advises Star Scientific. He is the John Eager Howard Professor of Endocrinology and Metabolism at Johns Hopkins as well as the director of the Division of Endocrinology and Metabolism Medicine. I was given access to him for purposes of clarifying and verifying my conclusions. Ill have more on that when I get the time for him to approve quotes. We can see other benefits of tobacco by looking at population studies of smokeless tobacco (ST) users. Decades of data have been collected on the Scandinavian form of ST, called snus [13]. No evidence has been found of any increase in cancer rates, including mouth and stomach. ST users exhibit a number of health benefits, including an approximate 10-year delay in the onset of Alzheimers disease. This benefit is not found in smokers. Apparently, inhaling large quantities of smoke is so damaging to the brain, it counteracts tobaccos AD-delaying benefits. No health benefits accrue to users of nicotine gum, however. So theres plenty of evidence to conclude that people are drawn to something else in tobacco than nicotine, apparently as a form of self-medication. If the active ingredients that satisfied those urges could be included in a chewing gum, Williams believed that he would have a smoking-cessation aid that could put big tobacco out of business. The company started with hard dissolvable ST lozenges made from Virginia tobaccos. Star Scientific believes it has the lowest level of the tobacco-specific nitrosamines (TSNAs) of any tobacco product in the world. TSNAs are the source of cured tobaccos toxicity. The Anatabine Discovery Jonnie Williams also gave top scientists the resources they needed to find out whats in tobacco that people actually crave. Eventually, he discovered the active ingredient he was seeking. It is an alkaloid called anatabine found in many other solanaceous plants, including tomatoes. He then had to learn to synthesize this food-derived nutraceutical so that it was safe for human consumption. A nonfood form of anatabine, available through chemical suppliers, is highly toxic. When he had accomplished this, the nutraceutical was subjected to extensive toxicity tests by a team of world-class scientists. Williams has attracted truly extraordinary people to his cause, including Dr. Curtis Wright, his current medical director and senior vice president of the wholly owned subsidiary that

will develop a drug form of anatabine using the isomer they have isolated, Rock Creek Pharmaceuticals. Formerly the acting director of the FDAs division that covered analgesics, anesthetics and addictive substances, Wright is a leading expert on toxicity and regulatory issues. Even at massive doses, anatabine proved remarkably safe in multiple animal tests. So Star Scientific then created CiGRX, pronounced cig-ar-ex. CiGRX contains anatabine and yerba mate, another nutraceutical MAO inhibitor. It is widely available in supplement sections of stores today as a natural smoking-cessation aid. People began to use the product, which looks and tastes like mint tic tacs. Soon, users began reporting more-than-successful efforts to quit smoking. People began talking about unexpected improvements in a range of inflammation-related conditions. Though anecdotal, evidence began to mount. A different sort of turning point took place when Williams wife developed severe thyroid disease. Famously devoted to her, Williams arranged for his wife to be treated by one of the top thyroid specialists in the world, Dr. Patrizio Caturegli. Caturegli studied with internationally known Italian endocrinologist professor Aldo Pinchera of the University of Pisa. Today, Caturegli is associate professor of pathology, endocrinology and immunology at Johns Hopkins. Williams wife had already developed thyroid nodules. At that point, surgery was necessary and scheduled 30 days out. Williams told Caturegli about the anatabine supplement. Caturegli suggested that there would be no harm in her trying the product. She did. The fibrosis reversed and the surgery was canceled. Her condition has continued to improve, and Williams reports that she is completely free of the symptoms of thyroid disease. Dr. Caturegli told me he is currently arranging human clinic trials of anatabine for thyroid disease with professor Pinchera and the University of Pisa. Italys regulations are less onerous than Americas, so FDA-compliant results will be produced rapidly. Roskamp Institute When Williams suggested that I see the lab, I had no idea. In fact, we went to the Roskamp Institute, founded by philanthropist Robert Roskamp. Roskamps life itself is inspiring, as is the work of his institute. When Robert Roskamps emotionally troubled brothers life ended prematurely, he quit his teaching post and set out to design and provide better facilities for emotionally disabled adults. His efforts were extremely successful, resulting in many facilities across America. In the process, he became very familiar with the tragedy of Alzheimers disease. Upon retiring, he sold his holdings and found himself very wealthy. He and his wife founded the Roskamp Foundation [14]. In 2003, they opened the Roskamp Institute to tackle the problems of Alzheimers and other disorders of the brain. Based in Sarasota, this world-class research facility has laboratories equipped for biochemistry, genomics, proteomics, mass spectrometry, in silico simulations with their own supercomputer and more. Running the Institute with a staff of more than 50 researchers are two of the worlds leading Alzheimers scientists, Dr. Michael Mullan and Dr. Fiona Crawford. They are renowned for discovering an amyloid link to AD as well as the so-called Swedish mutation. That breakthrough led to the creation of genetically engineered mice that are critical to the entire field of Alzheimers research [15]. I personally find the synchronicity involved in the Williams/Roskamp alliance startling. I assumed that Williams had located in Sarasota because of the Roskamp Institute. In fact, hes there because his son and daughter are at the

Bollettieri tennis school in Bradenton, near Sarasota. Williams wife heard about Roskamp Institute through a local magazine article and suggested to him that he talk to the scientists there about anatabine. Today, anatabine is a major research focus at Roskamp. Given what I told you earlier about smokeless tobaccos ability to delay onset of AD, you shouldnt be surprised to learn that animal studies are extremely promising. Moreover, Mullan and Crawford have learned a great deal about anatabines mechanism of action. I always feel somewhat guilty for taking time from scientists as important as Crawford and Mullan, but they have been extremely generous in helping me understand what theyve learned about anatabine. So finally, were getting to the really good part. Fasten, as they say, your safety belt. NF-B (Nuclear Factor Kappa-Light-Chain-Enhancer of Activated B Cells) In recent months, Ive written to you often about gene transcription factors. As you know, transcription factors are the biological command codes that activate the incredibly complex genetic program that is our DNA. Transcription is the process by which DNA is read. This reading of DNA sequences happens faster than the rotation speed of a jet engine and results in a kind of mirror image protein called RNA. RNA is the language that DNA uses to communicate with the rest of the body. This animation [16] of transcription is helpful. At the molecular level, transcription is so complex that nothing else compares. The sophistication of our genome is simply indescribable; the most advanced electronics are laughably primitive in comparison. Transcription factors trigger additional transcription factors. Sequences of DNA are turned on or off, depending on the sequence of the program, leading to precise changes in the cell. The result can be as simple as a response to a change in temperature or one cell changing into an entirely different type of cell. One transcription factor has particularly interested scientists. It is NF-B. Pronounced N F kappa B, it is shorthand for nuclear factor kappa-light-chain-enhancer of activated B cells. You dont have to know that. What you should know, however, is that NF-B is a sort of primary master transcription factor for the immune response system. Unlike exists always it can most gene transcription factors, it doesnt have to be synthesized. NF-B in almost all human and animal cell types. It acts as a first responder, on call and ready to mount an immune response if needed. Unfortunately, also mount that response when its not needed.

Remember, almost none of those who contributed to your genetic makeup, your ancestors, lived past the age of 30. Survival past that age was not selected for genetically. Its possible to live a lot longer now, but this new longevity has existed for only the last few hundred years or so. Thats a blip on the clock of human existence. Being old is an aberration, historically and biologically. As a result, were not very good at it. Its now clear that inflammaging is an autoimmune disorder caused when the immune regulatory system interprets the effects of aging as injury. Therefore, the very condition of being old provokes NF-B activation, initiating an immune response to injury. Injuries and disease require immediate response, and thats what NF-B facilitates. If you dont have an actual injury or disease, however, the NF-B creates all manner of havoc on the cellular level. For more on this, you might read the Finnish study titled Activation of Innate Immunity System During Aging: NF-B Signaling Is the Molecular Culprit of Inflamm-Aging. The abstract and outline are here [17]. So when inflammaging occurs due to wrongly deployed NF-B, we see important

indicators of inflammation. These includes CRPs, tumor necrosis factors and Interleukin-1 betas (IL-1). Now we know, thanks to Roskamp labs, that anatabine moderates these excess NF-Bs. This is nearly miraculous. This is as far upstream in the inflammation regulatory system as you can go. Scientists have been going after things downstream like CRPs, IL-1s and MAOs, but this is always hazardous. It creates unexpected problems and can throw the entire regulatory axis out of balance. Anatabine doesnt work like that. It simply calms NF-B activity so the inflammation doesnt lead to increased CRP, IL-1and other inflammatory actors. Look closely at the following chart published by Roskamp. It shows the impact of anatabine and Lipitor on mice given an inflammation-inducing substance, LPS-1. This is a lipopolysaccharide that is found in bacterial cell walls and provokes a strong inflammatory immune response in animals. The chart shows IL-1 levels, which are a more important indicator of inflammation than CRPs. This chart clearly shows that anatabine, labeled by its laboratory designation RCP, is far more effective than Lipitor. At the right dose, anatabine appears to shut down inflammation completely: [18] Because this is a nutraceutical, many people are already taking it. Both Ray Blanco and I are using it, as is everybody I know who has anything to do with Star Scientific. Anecdotal evidence is not double-blind science, but the sheer volume and consistency of personal reports is overwhelming. The fact that so much is coming from scientists is also significant. Im not going to give you specifics at this time, but I will say that I cannot imagine doing without this nutraceutical after having taken it for only six weeks. Moreover, I spoke with Dr. Dale Wilson of the McLaren Regional Medical Center, who is organizing a major blinded study to take place in Flint, Mich. CRP data from this study will be available in a few months. Roskamp is also in the process of organizing an Alzheimers test. Dr. Wilson also pointed out to me that NF-Bs are involved in apoptosis, programmed cell death. This means that, theoretically, anatabine may increase the life of healthy cells and prevent the cell immortality that occurs in cancer cells. One of the most exciting things about anatabine is its potential role as a telomere protector. Studies are under way right now, and Ill go back to Roskamp to view the results soon. I am struck, incidentally, by the timing of this technologys emergence only months after BioTimes launch of a subsidiary to provide truly rejuvenative therapy for the cardiovascular and immune systems. For many who might not live to acquire those upgrades, I believe this simple, inexpensive nutraceutical could buy you the time you need. I also believe stock in this company could provide the funds to pay for the procedure. Incidentally, the U.S. Patent Office has just confirmed Williams safer tobacco curing patents [19], now owned by Star Scientific. His application has been confirmed a year earlier than Reynolds. This clears the way for the company to go after billions in past royalties from the many tobacco companies that currently use Williams technology. I so wish I were allowed to buy the stocks I recommend. Williams legal victory in the patent arena highlights another important point about Star Scientific. Having taken on big tobacco, he may be the most lawyered up man in America. His legal team is as good as they get, and hes patented every conceivable nutraceutical use of anatabine. One of the most interesting is use in conjunction with spinal cord injuries. Its been known for some time that

suppressing NF-B activity after an injury promotes neural healing. Moreover, there are significant trade secrets and patents regarding the process of making the food grade that belong to Star Scientific. Its not yet clear to me how disruptive this technology will be to the existing pharmaceutical industry. Reducing inflammation will certainly delay onset of many serious illnesses. Its not obvious, though, that it will actually prevent those illnesses from re-emerging when were much, much older and closer to our Hayflick limits. This is one of the many questions Im going to try to answer in the months to come.

Article /2011/03/18/live-long-and-prosper-nutraceutically/ URLs in this post: [1] Click Here for PDF: http://breakthroughtechnologyalert.agorafinancial.com/files/2011/03/LiveLonger.p df [2] link: http://mises.org/journals/jls/3_1/3_1_2.pdf [3] The Fire Within: http://www.time.com/time/magazine/article/0,9171,993419,00.html [4] inflammaging,: http://www.ncbi.nlm.nih.gov/pubmed/17116321 [5] auto[innate]immunity: http://www.immunityageing.com/content/3/1/12 [6] Hayflick limit: http://en.wikipedia.org/wiki/Hayflick_limit [7] patents expire this year: http://www.dailyfinance.com/story/investing/top-selling-drugs-are-about-to-losepatent-protection-ready/19830027/ [8] xylitol: http://en.wikipedia.org/wiki/Xylitol [9] the Crow: http://www.crowtribe.com/emblem.htm [10] monoamine oxidase (MAO): http://www.biopsychiatry.com/maoi-smoke.htm [11] Parkinsons disease: http://www.sciencedaily.com/releases/2000/03/000329081250.htm [12] results: http://jcem.endojournals.org/cgi/content/full/jcem;89/12/6077 [13] snus: http://www.tobaccoprogram.org/pdf/TC12349.pdf [14] Roskamp Foundation: http://www.rfdn.org/index.html [15] Alzheimers research: http://www.ncbi.nlm.nih.gov/pubmed/1302033?dopt=Abstract [16] animation: http://www.youtube.com/watch?v=ztPkv7wc3yU [17] here: http://www.sciencedirect.com/science?_ob=ArticleURL_udi=B6X1H-4PPMXJW1_user=10_coverDate=04%2F30%2F2008_rdoc=1_fmt=high_orig=gateway_origin=gateway_s ort=d_docanchor==c_acct=C000050221_version=1_urlVersion=0_userid=10=df2264d08b72

a7b1d36e0501c216dc5a=a [18] Image: http://breakthroughtechnologyalert.agorafinancial.com/files/2011/03/IL1beta.png [19] safer tobacco curing patents: http://phx.corporate-ir.net/phoenix.zhtml?c=105863&p=irolnewsArticle&ID=1538610&highlight=