Xanthones The Road to Health Albert Miller, M.D.

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TABLE OF CONTENTS The Mangosteen Fruit: An Introduction The History of Mangosteen Xanthones: Mangosteen's Key Ingredients The Science behind Xanthones What Causes Disease and Aging? Oxidation Inflammation Immune Dysfunction Cancer Other Considerations Clinical Experiences Case Reports America's Health Care is Inferior Conclusion References

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The Mangosteen Fruit: An Introduction FROM THE SLOW-GROWING, tropical Garcinia mangostana tree grows its leathery, thick-skinned fruit -commonly called the "mangosteen." The purple, tangerine-sized fruit, often called the "queen of fruits,"' grows mainly in Southeast Asia, where the climate, soil and other growing requirements are best for this amazing botanical. The creamy, white fruit segments inside the thick rind (pericarp) are quite delicious in taste, while the nutrient-rich pericarp is very astringent and contains most of the biologically active xanthones. Until recently, this nutritional treasure has been essentially unavailable to the Western world due to the sensitivity of the plant to cold temperatures and the illegality of its importation. However, the fruit is now available in the form of dietary supplement beverage products. The fruit is harvested, pureed in its entirety, flash frozen, and then shipped to the United States, where it is further processed and bottled for consumption. The plant is difficult to cultivate as it has specific requirements in regard to climate and soil conditions. A very fragile root system makes transplanting difficult, and propagation by conventional means, like grafting, usually fails. In some cases the tree bears fruit as early as eight years after planting; however, in most cases this occurs between ten and twenty years. The mangosteen tree was most likely first domesticated in Thailand, where the majority of mangosteen is currently grown and harvested. Kampuchea, southern Vietnam, Burma, Malaya, and Singapore have also successfully cultivated the mangosteen. On a smaller scale, the fruit is also available in India, the Philippines, Queensland, tropical Africa, Trinidad, Honduras, Guatemala, Ecuador, and Columbia. Recently, Hawaiian and Puerto Rican growers have succeeded in cultivating mangosteen and are pursuing the possibilities of making the fresh fruit available in the continental United States, perhaps as early as the summer of 2007.

The History of Mangosteen Long before anyone in the Western world had even heard about the remarkable mangosteen fruit, traditional healers in Southeast Asia and India were using mangosteen to treat a wide number of health problems. The knowledge of the plant's medicinal qualities was passed from generation to generation, and the native people were aware of the fruit's benefits for hundreds of years before the first scientific paper concerning the healing power of mangosteen was ever written. The medicine men and healers in various cultures and countries found that the mangosteen pericarp was effective for treating the diseases that manifested themselves from bacteria and parasites, such as dysentery and diarrhea. Skin disorders and other diseases were treated both topically and internally from different preparations – including teas and poultices – made from the fruit. The antiinflammatory properties of this botanical provided an analgesic (anti-pain) remedy for countless people suffering in tropical countries for centuries. Centuries after these ancient healers discovered it, mangosteen finally attracted the attention of modern scientists, who have studied it in laboratories and have proven it to be all the medicine men knew it was and much more. The large volume of people treated with mangosteen over hundreds of years is a far greater testimonial to the efficacy and safety of this fruit than the scientific studies done in the last thirty years with laboratory animals and apparatus.

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Xanthones: Mangosteen's Key Ingredients When a scientist extracted a yellow compound from the mangosteen's pericarp, he named the compound a "xanthone," which is the Greek word for yellow. Xanthones are in the class of chemicals known as polyphenols, and the basic structure is a three-carbon ring with six double bonds. This is a very stable molecule that tolerates temperature changes from extreme heat to extreme cold without structural change. In addition to xanthones' basic structure, at least eight carbon atoms serve as sites for a number of different side chains. These varying side chains create different biological activities, acting as anti-inflammatory, antimicrobial, anticancer and antioxidant agents. Approximately two hundred xanthones have been found in nature and over forty have been identified in this fruit, the majority of which are found in the pericarp. Since xanthones are not found in the mangosteen flesh, but are found in the pericarp, it is essential to use the whole fruit to obtain the full array of benefits available to you.

The Science Behind Xanthones The mangosteen fruit has been used for centuries for medicinal purposes in the native countries where it grows, but it has remained relatively unknown to Western societies. The first scientists to study the mangosteen came from the Far East near where the fruit grows. Recently, the scientific interest and studies has extended worldwide, now including the Western world. When I was initially asked to research the mangosteen fruit for a friend of mine in 2004, I found well over a thousand articles on xanthones, and in over twenty of these, the mangosteen fruit was the source of the xanthones studied. There are a number of nutritionals found in the mangosteen including xanthones, catechins, stilbenes, polysaccharides, and flavonoids. The xanthones appear to be the most abundant and most biologically active group of nutraceuticals found in this plant. Of the forty or so xanthones found in this fruit, only eight have been studied fairly extensively. The following studies on these eight xanthones were all done in scientific labs – that is in test tubes, petri-dishes, or other lab culture devices. These studies have shown that the xanthones have many health benefits. For one, they are potent antioxidants. Other studies have shown anti-inflammatory actions, including COX-2 inhibition. There are a number of studies showing anti-cancer activity in several different tissue types, including breast, colon, lymphoid, and hepatocellular (liver). Not only have the studies shown inhibition in cancer growth, but they have also been shown to induce apoptosis (tumor shrinking, or cancer cell death). Some other studies have shown prostaglandin E inhibition (which helps control inflammation) and antihistamine activity, both of which are helpful in combating allergy symptoms. Also noted was a study showing serotonin reuptake inhibition. Substances with similar activity have been shown to be effective in treating depression and mood disorders. The strong scientific findings, coupled with the folk medicine use and clinical experiences all have been impressive enough to prompt several pharmaceutical companies to research this further for the xanthones' potential to start a new category of drugs.

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What Causes Disease and Aging? Disease is generally an insult on a specific tissue or organ system. The face of disease has many origins, which include the genes we inherit, the environment we live in, and the substances we ingest, inhale, or otherwise expose ourselves to. While aging is not a disease, it is the gradual decay of our body that occurs slowly over time. This is a result of gradual oxidative or inflammatory damage, as well as the wear-and-tear component that we incur in our daily lives. This can be accelerated or delayed depending on how we take care of our bodies. Providing our bodies with proper supplementation limits the naturally occurring oxidative and inflammatory damage, promotes a healthy immune system, and is the best way to delay the aging process. I do not want to imply that you or I have the ability to live forever, but I do want to clearly state that we can control the functional state of our lives. To better understand the complexity of our bodies, we will explore its smaller components. Your body is a complex piece of machinery that consists of atoms, which combine to form molecules, which then combine to form substrates and organelles, which in turn combine to form cells. The cell is the basic building block of your body. Cells combine to form tissues and these tissues make up organs. The organ systems combine and function in unison to form the healthy human body. A state of health or wellness exists when each organ, tissue, and cell are working normally and in harmony. However, every day, intentionally or unintentionally, you expose your body to toxins and other insults. These attacks include free radicals, which cause cell and tissue damage by oxidation and inflammation, which destroy tissues and organs. Further adverse effects from these insults may cause damage to the immune system and gene function. Despite all this intentional or unintentional damage the body endures, it has the ability to heal itself from these effects, provided the right resources are available. The body uses vitamins, minerals, and nutritional supplements to optimize function and prevent damage that occurs from these daily insults. In some cases these nutritionals are used to repair the damages that have already occurred. I firmly believe that all diseases originate from oxidative damage, uncontrolled inflammation, immune system dysfunction, or in most cases a combination of the three. Oxidative damage can alter genes, which in turn alters the ability to perform their intended function. Even worse, uncontrolled inflammation will destroy tissue and damage organs. When the immune system, the body's main defense from exterior insults, fails to function properly, it will allow disease and illness to take their course.

Oxidation When an atom or a molecule is robbed of an electron, which molecules need to keep the positive and negative charges stable, a free radical is created. The creation of free radicals is a process called oxidation and it occurs naturally in the Krebs cycle. This cycle includes a sequence of reactions that allows living cells to create energy molecules called ATP (adenosine triphosphate). Even though the Krebs cycle includes oxidation, it provides an essential molecule (ATP) for the body. ATP is the source of energy for every movement you make from breathing and blinking your eyes, to the energy you require to metabolize the food you eat. Even so, the free radicals produced during the Krebs cycle are potentially dangerous to your body's normal function. Antioxidants are used to reduce these free radicals before they can cause damage to neighboring molecules or cells. In the absence of appropriate antioxidants, these free radicals will produce damage to neighboring molecules, cells, and tissue. 5|Page For information on purchasing mangosteen, please email Barbara Hahn - [email protected]

Other sources of free radicals occur in the body on a minute-to-minute basis. These come from the air we breathe, the food and other substances we ingest, and the substances we contact and absorb through our skin. Thus, aside from the Krebs cycle's natural oxidation, our body is constantly being attacked by external sources, and the need to include antioxidants in our diet becomes even more critical.

Inflammation Have you ever accidentally cut your finger or another body part? Did you notice, as this cut healed, that the skin around the cut was red and had mild swelling (edema)? This continued until the cut was healed and you had a scar that, in the ideal process, retracted or got slightly smaller over the next six months. This process is actually your white blood cells engaging in a "clean-up mission" that involves clearing fragments of tissue, debris, and bacteria that have entered the area. The fibroblasts create "collagen cross-bridges" and fibrous tissue that form the scar. This tissue then retracts and the scar decreases in size. This exemplifies how inflammation heals an injury in the normal fashion. Now let's take the same scenario, only this time the inflammation continues unabated. Eventually, the redness resolves but the scar is raised, thick, and protruding, forming what is called a keloid. This describes inflammation that has gone out of control and has caused a new problem in the process of repairing an injury: destruction of the surrounding tissue. You sustain many unseen and unfelt injuries within your body. When everything is working normally, these injuries are repaired and without you ever being aware of them. However, when inflammation goes out of control, it will result in tissue destruction. In most cases you are still unaware of a problem until it is severe enough to cause pain or other symptoms that draw your attention. In the case of arthritis, you first notice this when cartilage destruction and periostial (bone) involvement triggers pain. In the case of kidney disease this may happen in silence until nearly two thirds of your kidney function is lost and your blood chemistry changes to the point where you feel fatigued or ill. In the case of coronary artery disease, this process consists of plaque build-up, which goes on unnoticed until the plaque or a clot occludes the artery. At that time you experience a heart attack, which frequently results in death.

Immune Dysfunction The immune system is a complex mechanism our body uses to protect us from any invasion or intrusions into our body that may threaten its healthy state. It consists of the thymus, the spleen, the bone marrow, white blood cells, and a complex array of lymph nodes and the lymphatic system. The components of this system release numerous chemical messengers that send signals to enable the components to work together to fight off foreign invaders and protect your body. Many different invaders (including viruses, bacteria, yeast, toxins, foreign proteins, and inorganic matter) can enter the body from four potential entry sites: the gastrointestinal tract, the respiratory tract, the skin, and the genitourinary tract. The gastrointestinal tract is the largest, the most vulnerable, and the location where the body's most dense lymph node and lymphatic tissues reside. So, if you receive an insect bite, the toxin is injected into your skin and chemical signals are released. Right away, the immune system goes to work with an array of white blood cells, each with a specific task, in an attempt to neutralize this toxin. Another good example is getting a splinter. If you remove the splinter, the immune system's task is simplified and there are now only a few toxins and foreign materials to clean up before repairing the opening in the skin. If the splinter is not removed, you will see a very aggressive reaction as the white cells try to phagocytize (to ingest) and remove the 6|Page For information on purchasing mangosteen, please email Barbara Hahn - [email protected]

splinter. If this task is too overwhelming, the immune system resorts to forming a wall around the object to keep it from invading the body. This is called a foreign body granuloma. When bacteria are walled off in the body's attempt to control them, abscesses can form. However, bacteria growth continues without blood supply, and the abscess expands and eventually breaks the walls the body has created in its own defense. We have described the immune system functioning normally. As you might imagine, a complex system like this will have multiple potential malfunction sites. Often, when this occurs, an autoimmune disease emerges. Autoimmune diseases are numerous, and the more common conditions include asthma, some skin disorders, rheumatoid arthritis, lupus, psoriasis, scleroderma, and multiple sclerosis. In each of these diseases the immune system, for some reason, misinterprets a normal tissue, usually a protein, and views it as foreign. Immediately, the immune system begins to mount a destructive attack against it. This destructive process results in tissue damage of the involved tissue, or organ malfunction. A wide variety of vitamins and supplements can help make the immune system more efficient. Mangosteen is such a supplement, and in my experience it has proven to be the best single supplement to help in enhancing the function of the immune system. The effects on the immune system from mangosteen are more of a modulation, in that the mangosteen makes the immune system smarter. In cases where mangosteen was used to help autoimmune diseases, we saw improved disease markers similar to what is seen with immune suppressant medication, and yet the immune system was not suppressed but functioned more effectively.

Cancer Everyone has heard of cancer, yet few people really know more than it is a tumorous growth that often kills the affected person. Cancer begins at a cellular level. All of our cells "turn over;" that is, they die and the body makes new cells to replace the old ones as the need arises. Cancer occurs when cell reproduction goes unchecked and exceeds that of cell death. A cancerous growth is a group of cells of a particular tissue that has altered its genetic code and is reproducing in an uncontrolled fashion. These cells initially form a tumor that expands and encroaches, crowding the surrounding tissue. All of these new cells have the same altered genetic code telling them to continue to reproduce. When the tumor grows larger, some cells break away, invading the blood or lymphatic system or moving to different parts of the body. They may then start a new colony of cells that we call a metastasis or metastatic tumor. Normal treatments for cancer include anti-cancer medications that are usually toxic drugs whose goal is to kill cells. Cells that are rapidly reproducing are more vulnerable, therefore most of the damage is done to the cancerous cells; however, the side effects are massive as many normal cells are also attacked because most cancer drugs kill all vulnerable cells indiscriminately.

Other Considerations Although this booklet is written to elaborate on the benefits of mangosteen, there are other factors aside from adding mangosteen to your diet that are necessary to achieve optimal health. First, it is best to eat healthy foods and avoid all unnecessary food additives. Eat organic foods whenever possible. Second, exercise on a regular basis. This can be one of the most important lifestyle changes you can make. Third, add vitamins and supplements to your diet. This is far more important today than ever before, because the food we eat has fewer vitamins and minerals than it did fifty years 7|Page For information on purchasing mangosteen, please email Barbara Hahn - [email protected]

ago. This modern loss is due to mass production, fertilizers used in modern farming, and the need to pick fruits and vegetables before they are ripe. As a result of the massive amount of pesticides and herbicides in use, we are exposed to more toxins. Thus, making these changes can protect your body from the onslaught of toxins it comes in contact with daily. To neutralize this exposure to toxins, we have a greater need for antioxidants and other supplements. The best approach to neutralize the toxins is, in my opinion, to use a good multivitamin and mineral as your base and add supplements based on your needs and health risks. Mangosteen also makes for a good base supplement. Because of its antioxidant and antiinflammatory actions, antimicrobial effect and immune system modulation capabilities, it has the potential to positively affect every cell in the body. For this reason, I believe mangosteen to be the best nutritional supplement available today.

Clinical Experiences The science reviewed earlier in this publication leads us to recommend the use of mangosteen in your diet because of the beneficial health results found. And, due to the results found, we are also led to suggest possible health benefits you could have by taking mangosteen. Following are some clinical experiences, or documented patients' results from a health care practitioner, that involved the use of mangosteen. The information given here is some of what I have personally observed in my practice, though the cases presented represent only a few of the patients I have followed or have seen in consultation. First, I will give you an overview. The more I use mangosteen (as it has only been available commercially for three and one-half years, it is still young, and my personal experience with mangosteen is limited to about two years) the more I am surprised at its diverse beneficial effects on the human body. Patients usually comment first on an improvement of general health and wellbeing. That is, they have more energy, sleep better, and feel emotionally happier and better. Many people refer to this as their "happy juice." The next benefit patients see is pain relief, which for some people occurs within one to two days, but more commonly starts in two to four weeks and continues to improve (i.e. show more and more pain reduction) for up to three to six months. Other such benefits have included an improvement in skin conditions like eczema and psoriasis, the reduced or discontinued use of depression medication, and an improvement in diabetes, which also leads to reduced or discontinued medication use. Hypertension (high blood pressure) is another condition in which we see improvement, although I do want to state that some people see no results while others see dramatic results. This I feel is best explained by the fact that hypertension is a disease with multiple causes, and while some patients respond to mangosteen, others do not. CRP (Creactive protein, which is the most reliable heart disease risk factor) and cholesterol are both lowered, resulting in a reduced risk of the number one cause of death-heart disease. Kidney failure is also usually improved. As in all conditions, the earlier the intervention, the more impressive the results. If treatment is delayed until end-stage kidney failure when the patient is on dialysis, kidney function is far less likely to return as the kidney tissue has become scarred. Perhaps the most impressive disease modification I have seen mangosteen produce is in autoimmune diseases. As explained earlier, in this group of diseases, the body misinterprets normal tissue as a foreign substance and attacks it. Rheumatoid arthritis is perhaps the best-known autoimmune disease, and with mangosteen added to the patient's medical regiment, we saw reduction in pain and swelling as the initial improvement. This was followed with improved results in the lab tests we used to follow the severity of this disease, such as erythrocyte sedimentation rate (ESR, which measures the degree of inflammation), and anti-nuclear antibodies (ANA, which 8|Page For information on purchasing mangosteen, please email Barbara Hahn - [email protected]

measures the severity of the disease). Another disease that shows improvement with the use of mangosteen is multiple sclerosis. Multiple sclerosis, with mangosteen used as an additional treatment, has shown an improvement in the current state of disease, and I expect it will show a slower rate of progression, although the length of use to date is too short for us to make a definite conclusion. Other autoimmune diseases including lupus, scleroderma, psoriasis, and others show similar beneficial results. Another disease where we expect positive benefits will prove themselves is with cancer. Cancer is undoubtedly the disease most dreaded by the majority of people. As mentioned previously, the lab data suggests that we should see positive results with cancer when mangosteen is taken. Personally, I would not face this disease without mangosteen as part of my treatment plan. I frequently get questions about the use of supplements, and especially antioxidants with chemotherapy and radiation. Although, I am aware that many oncologists (cancer specialists) are opposed to using antioxidants with certain cancer treatments, I see no reason for that position. There are numerous studies supporting the use of antioxidants with chemotherapy and radiation. I would encourage you to verify this by doing your own Medline search. This can be done by logging on to www.pubmed.gov When you do your search, first type in "chemotherapy, antioxidants," and then click on "search." You will find well over one thousand articles that will help you draw your own conclusions. My personal belief is that the oncologist's response reveals an attitude of, "If I don't know about it, it can't be good." Unfortunately, most traditionally trained allopathic physicians know very little about nutritional supplements and cannot give you educated recommendations. Medical knowledge is rapidly expanding and to think that one physician can be well-informed in all areas is unreasonable. Most physicians, as I do, receive three or four journals each month and glance through each, reading only the articles that are of interest to us. You, as the consumer and an involved individual, need to be in charge of your own health. I suggest that you do some research on your own, get several medical specialists' opinions, and then find a well-rounded primary care medical specialist to help you review and analyze your options. Despite the inability of doctors, including myself, to know everything, as you research mangosteen, I think you will find numerous positive sources of information. No matter what disease or condition you are suffering from, or even if your health is good, mangosteen is likely to add a positive benefit to whatever other treatments your physician has recommended.

Case Reports Although individual results do vary, the following are a few clinical summaries that help illustrate the findings mentioned previously. Chronic renal (kidney) failure Diabetes mellitus Hypertension (high blood pressure) Congestive heart failure Anemia J.B. is an 83-year-old female with a long history of diabetes mellitus, hypertension, congestive heart failure, and advanced renal failure with a creatinine clearance of 24ml/min (normal for females is 60ml/min or more). She was being prepared for dialysis when she started taking mangosteen juice for pain control due to compression fractures in her back. Dialysis is typically started at about the time the creatinine clearance drops to 20ml/min. After about two weeks into her mangosteen use of 9|Page For information on purchasing mangosteen, please email Barbara Hahn - [email protected]

one ounce three times per day, she started to notice an increase in her kidney function, which she noted as an increased urine output and loss of edema or swelling in her legs and elsewhere in her body. When her creatinine clearance was rechecked one month later it had increased to 49ml/min. This has kept her from having to go on dialysis and experiencing the many adverse effects of it- not to mention all the restrictions it would have imposed on her daily life. In addition to the above life-changing benefits, J.B. no longer needed erythropoetin injections, which she previously received every two weeks to correct her anemia, a common finding in the advanced stages of renal failure. "I want to thank you for suggesting to me to try mangosteen juice. I have been taking mangosteen juice for over a year now and I love the taste. I was scheduled to start pre-dialysis procedures but due to mangosteen juice I am no longer having the problems I had with my kidneys and no longer need dialysis. I am now able to do things I couldn't have done should I have not started the juice. I have traveled to Alaska [July 2006], I do my own housework, prepare my meals, do laundry, etc., and I am still able to drive and visit with friends whenever I want. My life has improved so much. Thank you." J.B. Rheumatoid arthritis Gastroesophageal reflux disease (GERD) Migraine headaches G.W. is a 55-year-old female with a fifteen year history of rheumatoid arthritis who had been experiencing a gradual worsening of her disease (as would be expected during that time frame). With the increase of symptoms, there was a corresponding increase in medications in an effort to control her symptoms and in effort to maintain her normal daily activities. In spite of her everincreasing medications, G.W. continued to have a gradual progression of her worsening disease state. She decided to try mangosteen juice in an attempt to regain better control of her symptoms. At the time of starting mangosteen juice, she was on Enbrel injections twice weekly, methotrexate weekly, Bextra daily, and intermittent prednisone use based on her symptoms. The above medications were managed by a rheumatologist (a physician specializing in autoimmune diseases). As G.W. began using mangosteen juice at one ounce three times a day, she continued the use of the above medications. As her symptoms started to improve, i.e. the pain and the swelling in her joints decreased, she was able to gradually decrease her medication. She made regular visits to her rheumatologist who gradually decreased her medications with the improvement of her symptoms as well as her rheumatoid disease markers (ANA, ESR, rheumatoid factor), which are used to monitor the severity of the disease. After taking mangosteen juice for six months, she, with the guidance of her doctor, had successfully tapered herself off of all of the above medications. In addition to the above, G.W. also was able to discontinue her Prevacid, which she needed for chronic heartburn symptoms possibly caused by the medications. Migraine headaches have also subsided and Zomig is another drug that G. W. no longer needs. Along with the decreased pain, G.W. has experienced increased energy and an overall sense of well-being. "I'II Drink Mangosteen Juice Every Day!" "I feel wonderful! Mangosteen juice has literally changed my life! I have so much energy now, and can do things that I could not do for many years. Simple things,like shaking hands to greet someone and wearing high heels. I will drink mangosteen juice every day for the rest of my life, with absolutely no regrets or hesitation!" G.W 10 | P a g e For information on purchasing mangosteen, please email Barbara Hahn - [email protected]

Polymyalgia rheumatica Allergies S.R. is a 71-year-old male who suddenly developed multiple joint, muscle pain, and swelling. The painful, stiff, and weak muscles interfered with the active lifestyle he had been accustomed to. Many tests were done and several medication trials started with little relief. He was then referred to a rheumatologist who diagnosed him with polymyalgia rheumatica (PMR). He was started on prednisone and was told he would need to take it daily for at least one year. When diagnosed with PMR, he was on one ounce of mangosteen juice twice daily. Given the prolonged course of prednisone along with the known side effects, we decided to increase his mangosteen juice to two ounces three times daily. This resulted in a dramatic reduction in his symptoms, and on the fourth week he was able to discontinue the prednisone completely. Over a year later his symptoms remain controlled and have not required any further prednisone use. In addition, S.R.'s sinus and allergy symptoms, which he has had for all his adult life, are nearly completely resolved. He has also had recurring problems with hemorrhoids that have surprisingly resolved. "No More Prednisone!" "I started taking mangosteen juice for joint pain, allergies and pain in my right side. I was later diagnosed with PMR and was prescribed the drug, prednisone, and was told l would have to take this drug for one to one and one-half years.By taking mangosteen juice three times daily,I was able to decrease my prednisone from 15mg/day down to 5 mg/day over the course of three weeks. On the fourth week I took only the juice three times a day - no more prednisone. "Prior to taking mangosteen juice I had hemorrhoids for over thirty years. After six weeks on the juice the hemorrhoids were gone. "I also had sinus allergies for sixty years and the juice has taken care of approximately 80 percent of the problem. 1 also no longer have severe pain in the right side." S. R. Fibromyalgia Cluster headaches P.M. is a 54-year-old female with a long history of fibromyalgia. Suffering from daily pain, she was used to relying on ibuprofen, naproxen, and/or Excedrin on a daily basis, usually at higher than the maximum recommended daily doses. She found this a necessary routine in order to control the pain which interrupted her work schedule and life's daily routine. Since all of these products were available over-the-counter, she mostly self-medicated until an episode of vomiting blood resulted in a diagnosis of bleeding ulcers. This resulted as a side effect of these medications and she realized the need to refrain from the chronic use of these dangerous drugs. Looking for safer alternatives resulted in using a mild narcotic, Darvocet, on a regular basis. This did control her symptoms somewhat, but she was now dealing with a potential habit-forming drug. Luckily, she never did develop any addiction to this medication. She agreed to try the mangosteen juice at my recommendation, but really was not expecting positive results. She started at two ounces three times daily and did get some relief; in fact, enough relief that she decided to go to three ounces three times daily, which is her current dose. She reports

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feeling better and having less pain from the fibromyalgia now than when she was on any of her previous medication regimens. P.M. also reports sleeping better and having more energy. She also suffered from frequent headaches and she is pleased that these have also subsided. "It is so much easier to start the day with mangosteen juice! I no longer feel the need to take pain medication, either prescription or over-the-counter, unless I'm having a flare-up or the barometric pressure drops. At these times an extra ounce or two of juice and two ibuprofen always get me through. I'm so fortunate to have been introduced to mangosteen juice and the safe, worry-free relief it offers!" PM Depression Migraine headaches E.M. is a 21-year-old female who has been on several different antidepressant medications, most recently Effexor, with the dose varying from 150 to 300 mg daily for about seven years. In addition she had been seeing a psychologist for counseling to help manage her symptoms, which included self-destructive behavior. She had set a goal to get off of her medication. Repeated attempts all failed, due to the return of her symptoms or the resulting medication withdrawal side effects, or a combination of the two. Now, more than a year has passed and E.M. is off all medication, and is free of symptoms of depression, and is no longer seeing a counselor. E.M. also suffered from somewhat frequent migraines, and has not experienced any since introducing mangosteen. "ThankYou for FreeingMe!" "Current research shows that young developing women on antidepressants are adversely affecting their bone density. Therefore I felt it was extremely important to get off my medication, though many previous attempts failed. After learning about how mangosteen juice contains natural serotonin and hearing how it could help with the withdrawal symptoms, I was excited. The mangosteen juice made the withdrawal side effects manageable and after a month of slowly reducing my dose of Effexor, I was finally drug free. I truly believe that my continued daily dosage of mangosteen juice has kept me from having to return to the ball and chain of antidepressant medication. Thank you for freeing me!" E.M. Dementia Diabetes mellitus Hypertension (high blood pressure) Hyperlipidemia (high cholesterol) A.J. is an 81-year-old female who has a long history of diabetes mellitus type II, hypertension, hyperlipidemia, chronic anemia, and depression, and had developed a gradual increase in dementia over approximately the past five years. Along with this she became withdrawn and developed insomnia. Her loving husband always accompanied her to the office and she grew more and more dependent on him. Over approximately the last two years, she looked to him to answer any questions she was asked regarding her health. Her husband, who had assumed most of the household chores and meal preparation, reported that she no longer initiated conversation and needed to be reminded of nearly everything.

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AJ. was started on mangosteen juice at one ounce three times daily, and the gradual improvement in her symptoms and lab tests over the next six months enabled her to reduce medications, which improved her quality of life. First, and most important, now when asked questions about her health, she answers them. She initiates conversation again, and she smiles more and seems happier. Some of her lab changes include the following: HgbAlC (a marker of the average blood sugar for past 3 month) went from 6.8 to 6.1; total cholesterol went from 163 to 154, HDL (good) cholesterol from 23 to 32, LDL (bad) cholesterol from 75 to 68, triglycerides from 325 to 271; hemoglobin from 11.4 to 13.4. All of this occurred while we reduced her medication as follows: Avandia (for diabetes) from 8 mg daily to none; Lipitor (for cholesterol) from 40 mg daily to 10 mg daily; hydrochlorothiazide (water pill for blood pressure) from 50 mg daily to none; potassium (for the side effects from the water pill) from 20 mg daily to none; Doxepin (for depression) from 50 mg twice daily to 25 mg once daily. A.J.'s husband says, "I wish to give my thanks to mangosteen juice for returning my wife to a sociable, friendly, outgoing person. She feels so much better and she and I have many good times together." (D.J.) Congestive Heart Failure Diabetes mellitus Coronary artery disease Chronic renal (kidney) failure Anemia Obesity F.H. is a 72-year-old male with history of congestive heart failure, coronary artery disease, diabetes mellitus, chronic renal failure, chronic anemia, and obesity. Needless to say, he needs to take multiple medications to manage his diseases. He started on mangosteen juice with a goal to increase his energy and feel better and maybe reduce his medication. Prior to starting mangosteen juice, his medication list included Lasix (water pill) 80 mg twice daily, hydralazine (blood pressure) 12.5 mg twice daily, spironolactone (water pill) 25 mg daily, zaroxlin (water pill) 2.5 mg daily, potassium (counters effect of water pill) 16 mg twice daily, Coreg (blood pressure or heart) 25 mg twice daily, isosorbide (heart) 30 mg twice daily, simvostatin (cholesterol) 40 mg daily, and testosterone 100 mg weekly. One year later, his medication list includes, Lasix 40 mg twice daily, hydralazine discontinued, spironolactone 25 mg daily, zaroxlin discontinued, potassium 16 mg twice daily, Coreg 12.5 mg twice daily, isosorbide 30 mg twice daily, simvostatin 20 mg daily, and testosterone discontinued. Prior to starting mangosteen juice, F.H's weight was at 306 pounds. His lab data included a creatinine clearance of 58 (normal is above 90), HgbAlC was 6.0 (normal is less than 6.0), total cholesterol 113 (normal 120-200), HDL (good) cholesterol 32 (normal greater than 35), LDL (bad) 69 (normal less than 130), and hemoglobin 12.5 (normal 13.6 to 17.4) One year later his weight has dropped to 275 pounds. His lab data has changed to creatinine clearance 95, HgbAlC is 5.3, total cholesterol 124, HDL (good) cholesterol 48, LDL (bad) 66, and hemoglobin 14.9. F.H. achieved his goal of increased energy, and feels better than he has in many years. As you can see from above, he has been able to decrease or eliminate a number of medications, while still showing a significant improvement in his lab results.

13 | P a g e For information on purchasing mangosteen, please email Barbara Hahn - [email protected]

"Mangosteen has enabled me to reduce my medication, and has given me more energy. I feel better, I get more done, and I feel like I did ten years ago." F.H. Cancer My usual recommendation for the use of mangosteen juice in the treatment of cancer is as an adjunct to traditional therapies such as surgery, radiation, and chemotherapy. Based on my clinical observations, mangosteen's anticancer activity adds to the traditional treatments and typically shows enhanced response. In addition, mangosteen decreases the intensity of the adverse effects of these therapies in most cases. The two cases below were chosen for their illustrative purposes, as they are cases where mangosteen was the only treatment used. J.G. is a 58-year-old male with a history of squamous cell cancer of his left ear, and when he developed a lesion on his right ear that looked similar, he knew that it was another cancer. His suspicions were confirmed after a visit to his dermatologist. The prior cancer was treated three years earlier, was removed surgically and required a skin graft. While waiting for the surgery for his right ear, he took two ounces of mangosteen juice twice daily and applied it topically twice daily. Within the first month he saw significant improvement and decided to cancel the surgery, and after two months the lesion was no longer visible. It is now one year later and there is no evidence of any skin cancer. "No Pain. No Surgery and I Feel Great!" "What price can you put on results such as I have seen? No surgery, no pain, and I feel great! Now I am committed to this wonderful juice the rest of my life! In addition to my daily doses, I use it topically on my face twice daily to hopefully prevent any more skin cancers." J.G. L.T. is a 60-year-old male with a prior history of colon cancer that was treated with surgery and followed with radiation and chemotherapy. Unfortunately, L.T. developed chronic radiation colitis, which left him with disabilities affecting his daily living activities. Approximately four years later he developed an isolated lesion in his lung. L.T. refused biopsies, as he is not open to any form of treatment due to his earlier adverse experience with cancer treatment. Since this is, and has remained an isolated lesion for two and a half years, it is presumed to be a primary lung cancer. (A metastatic lesion from the colon would be expected to result in multiple lesions.) Due to the fact that he has refused traditional medical treatments, the only treatment he has received is mangosteen juice. Unfortunately, L.T. continues his long history of smoking in spite of recommendations to quit. The lesion, followed regularly by x-rays approximately every six months, has shown a much slower rate of growth than would be expected by any form of lung cancer or metastatic colon cancer. Although it is unlikely that L.T.'s cancer will be "cured" by mangosteen, it has slowed the growth rate with no side effects. "After my first encounter with cancer and the devastating side effects of traditional cancer treatment, I knew I would never allow myself to go through that torture again. My second diagnosis of lung cancer left me with no real option for treatment that I could accept – until I was offered the option of mangosteen juice. Though I can't feel what it is doing to slow the growth of my tumor, I do know that I feel great – actually better than I have felt in years!" L.T.

14 | P a g e For information on purchasing mangosteen, please email Barbara Hahn - [email protected]

America's Health Care is Inferior As Americans, we have grown to believe that we have the best healthcare system in the world. This is, however, questionable when one looks at the statistics available through the Center for Disease Control (CDC) and The World Health Organization (WHO). The varied ways of expressing statistics does result in slightly varied results; however, if we look at life expectancy, the United States is not in the top ten. In fact, it is below the twentieth in rank. Furthermore, when we look at morbidity or end of life disabilities, the average American can expect to live nine to ten years with some form of morbidity. This is also worse than any other developed country. All of the above is in spite of the fact that we spend far more for health care per capita than any other country. It is clear that we must be spending our dollars in the wrong area. My opinion is that we should start by directing more dollars to prevention. Diseases start at the cellular level and it makes sense that optimal prevention needs to be directed at the cellular level as well. This starts with providing each cell with ample vitamins, minerals, and other supplements. When mangosteen is added to your vitamins and minerals, you dramatically enhance your free radical protection, control your inflammation, and enhance your immune system. Healthy cells result in healthy tissue, which yield healthy organs, and that combination results in a healthy body.

Conclusion What we have covered is indeed impressive. This powerful potential found in one fruit is rare. There is no such thing as a magic bullet or one supplement that heals all conditions. Whether for prevention or disease management, the mangosteen is, in my opinion, a supplement for everyone. We have discussed many proven health benefits and examples of conditions that have been improved in people using this product. Before one experiences symptoms of a heart attack, the disease that constricts arteries has been at work for decades. Before one is diagnosed with diabetes, the disease process has been at work for years or decades. The same can be said for nearly all other diseases including arthritis, strokes, and so on. The xanthones all serve as antioxidants and in this fashion help protect every cell against the daily free radical exposure by maximizing cellular health and preventing disease. Proven COX-2 inhibition along with other presumed anti-inflammatory effects help heal your body, control pain, and protect your body's tissues and organs from illness and disease. The autoimmune modulation helps your immune system perform optimally, fight off disease, and prevent illnesses, as well as assisting in the healing process of illness already present. The anti-cancer effects shown in the laboratory science imply a beneficial action in prevention, as well as in treatment. Now, for a moment imagine a product with the potential in disease modification for a person with no known health challenges. Do you think this product may just go to work and delay the onset of the disease each individual has going on silently? This is what I perceive to be the greatest power of this little purple fruit, mangosteen : prevention. You may still have one unanswered question: What will mangosteen juice do for me? As I tell my patients, the only way you can really know what this product will do for you is to use it. My recommendation for you, the reader, is to drink mangosteen juice at the recommended dosage for your particular state of health and see what it does for you.

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References 1. Morton J. Fruits or warm climates. Miami: 1987. 2. Krap, David. Forbidden? Not the Mangosteen. New York Times. August 9, 2006 3. Weissman G. Prostaglandins as modulators rather than mediators of inflammation. J Lipid Mediat. 1993; 6:275-286. 4. Smith WL DD, and Garavito RM. COX-2 and PGE2 biosynthesis by IL-l is mediated by PKC and Mitogenactivated Cyclooxygenase: structural, cellular and molecular biology. Annu Rev Biochem. 2000:69: 145-182. 5. Shankaranarayan D KL, Nazimudeen. Effect of Mangostin, a Xanthone from Garcinia mangostana Linn. In Immunopathological & Inflammatory Reactions. Indian J Exp BioI. 1980; 12:843-846. 6. Nakatani K, Nakahata N, Arakawa T, Yasuda H, Ohizumi Y. Inhibition of cyclooxygenase and prostaglandin E2 synthesis by gamma-mangostin, a xanthone derivative in mangosteen, in C6 rat glioma cells. Biochem Pharmacol. Jan 1,2002.63(1):73-79. 7. Nakatani K, Yamakuni T, Kondo N, et al. gamma-Mangostin inhibits inhibitor-kappaB kinase activity and decreases lipopolysaccharide-induced cyclooxygenase-2 gene expression in C6 rat glioma cells. Mol Pharmacol. Sep 2004;66(3):667-674. 8. Nakatani K, Yamakuni T, Kondo N, et al. gamma-Magnostin Inhibits IkappaB Kinase Activity and Decreases Lipopolysaccharide Cyclooxygenase-2 Gene Expression in C6 Rat Glioma Cells. Mol Pharmacol. Jun 24 2004. 9. Fan C SJ. Antioxidative mechanism of isolated components from methanol extract of fruit hulls of Garcinia mangostana L. Journal of the Chinese Agricultural chemical Society. 1997; 35:540-551. 10. Williams P, Ongsakul M, Proudfoot J, Croft K, Beilin L, Mangostin inhibits the oxidative modification of human low density lipoprotein. Free Radic Res. Aug 1995; 23(2):175-184. 11. Chen S WM, Loh B. Active constituents against HIV-l protease from Garcinia mangostana. Planta Med. 1996; 62:381-382. 12. Sundaram BM, Gopalakrishnan C, Subramanian S, Shankaranarayanan D, Kameswaran L. Antimicrobial activities of Garcinia mangostana. Planta Med. 1983; 48(1 ):59-60. 13. Chanarat P, Chanarat N, Fujihara M, Nagumo T. Immunopharmacological activity of polysaccharide from the pericarb of mangosteen garcinia: phagocytic intracellular killing activities. J Med Assoc Thai. Sep 1997; 80 Suppll: S149-154. 14. Suksamrarn S, Suwannapoch N, Phakhodee W, et al. Antimycobacterial activity of prenylated xanthones from the fruits of Garcinia mangostana. Chem Parm Bull (Tokyo) Ju12003; 51(7):857-859. 15. Suksamrarn S, et al. Cytotoxic prenylated xanthones from the young fruit Garcinia Mangostana. Chem Pharm Bull 2006:54(3): 301-5.

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16. Ho CK, Huang YL, Chen CC. Garcinone E, a xanthone derivative, has potent cytotoxic effect against hepatocellular carcinoma cell lines. Planta Med. Nov 2002; 68( 11 ):975-979. 17. Matsumoto K, Akao Y, Kobayashi E, et al. Induction of apoptosis by xanthones from mangosteen in human leukemia cell lines. J Nat Prod.Aug 2003:66(8):1124-1127. 18. Matsumoto K, et al. Preferential target is mitochondria in alpha-mangostin-induced apoptosis in human leukemia HLA60 cells. Bioorg Med Chem 2004; 12(22):5799-5806. 19. Moongkarndi P, Kosem N, Luanratana O, Jongsomboonkusols S, Pongpan N. Antiproliferative activity of Thai medicinal plant extracts on human breast adenocarcinoma cell line. Fitoterapia. Jun 2004; 75(3-4):375-377. 20 Moongkardi P, Kosem N, Launratana 0, Pongpan N, Neungton N, Antiproliferation, antioxidation and induction of apoptosis by Garcinia mangostana (mangosteen) on SKBR3 human breast cancer cell line. J Ethnopharmacol. Jan 2004; 90(1):161-166. 21. Chairungsrilerd N, Furukawa K, Ohta T, Nozoe S, Ohizumi Y. Histaminergic and serotonergic receptor blocking substances from the medical plant Garcinia mangostana. Planta Med. Oct 1996; 62(5):471-472. 22. Nakatani K, Atysumi M, Arakawa T, et al. Inhibitions of histamine release and prostaglandin E2 synthesis by mangosteen, a Thai medicinal plant. Biol Pharm Bull. Sep 2002;25(9):1137-1141. 23. Chomnawang MT, Surassmo S, Nukoolkarn VS, Gritsanapan W. Antimicrobial effects of Thai medicinal plants against acne-inducing bacteria. Journal Ethnopharmacology, 2005, July 8 24. Gopalakrishnan G, Banumathi B, Suresh G. Evaluation of the antifungal activity of natural xanthones from Garcinia mangostana and their synthetic derivatives. J Nat Prod 1997; 60(5):519524. 25. Nabandith V, Suzi M, Morioka T, Kaneshiro T, Matsumoto K, et al. Inhibitory effects of crude alpha-mangostin, a xanthone derivative on two different categories of colon preneoplastic lesions induced by 1,2-dimethylhydrazine in the rat. Asian Pac J Cancer Prev. 2004 Oct-Dec; 5 (4): 433-8. 26. Jung HA, et al. Antioxidant xanthones from the pericarp of Garcinia mangostana (mangosteen). J agric Food Chem 2006; 5 (6): 2077-82.

17 | P a g e For information on purchasing mangosteen, please email Barbara Hahn - [email protected]