Mangosteen: A Friendly Skeptic Looks at Mangosteen By Dr. Ralph Moss from CancerDecisions.com Newsletter When I wrote Cancer Therapy in the early 1990s, I had the bright idea of putting my mailing address in the book in the hope that some readers would send me information on new treatments. Little did I imagine that such communication would become a torrent of proposals. Today, hardly a day goes by without my being made aware of some new "cure." Would that a fraction of these panned out as well as proponents claimed! One of the latest in this long line is an exotic fruit drink called mangosteen, or XanGo. Mangosteen should not be confused with mango, an entirely different plant. It is part of a group known as the Guttiferae, a family of mainly tropical trees and shrubs that secrete an acrid yellow resinous juice. Mangosteen's scientific designation is Garcinia mangostana (Campin 2004). It is reputedly named after a French explorer, Jacques Garcin (1673-1751). In Europe and North America, the most recognizable member of this family is the popular herb, St. John's wort. No one knows exactly where and when the mangosteen was first cultivated. One botanist, Julia F. Morton, believes it originated in the Moluccas and the Sunda Islands. Yet there are also wild mangosteen trees in the forests of Malaya. Some experts say the trees were first domesticated in Thailand or Burma. But in the 19th century, botanists brought seeds to Europe and America. Valiant attempts were made to cultivate the 18-foot high trees in Africa, the Caribbean and central America. But the plant is considered "ultra-tropical" and sensitive: nursery seedlings die at 45º F. In fact, there are few if any mangosteens growing in the continental US. A lone American tree in Florida was said to have yielded a single fruit...and then died. That was the beginning and end of the American mangosteen "industry." But attempts continued to bring mangosteen to Europe and America as a food. "Despite the oft-repeated Old World enthusiasm for this fruit," says Morton, "it is not always viewed as worth the trouble to produce. In Jamaica, it is regarded as nice but overrated; not comparable to a good field-ripe pineapple or a choice mango." The mangosteen fruit is the size of a small apple, purple colored, with a hard rind. Inside there are typically five to seven seeds surrounded by a sweet, juicy cover (or aril). The pulp, which is said to resemble a pineapple or peach in taste, is reputed to be a very delicious food - in Asia it is sometimes called the queen of fruits in honor both of its flavor and its economic importance. Uses in Traditional Medicine For many years dried mangosteen fruits have been shipped from Singapore to Calcutta and then on to China for medicinal use. As to its many uses in folk medicine, here is what botanist Julia Morton has written: "The sliced and dried rind is powdered and administered to overcome dysentery. Made into an ointment, it is applied on eczema and other skin disorders. The rind decoction is taken to relieve diarrhea and cystitis, gonorrhea and gleet [a watery discharge, ed.] and is applied externally as an astringent lotion. A portion of the rind is steeped in water overnight and the infusion given as a remedy for chronic diarrhea in adults and children. "Filipinos employ a decoction of the leaves and bark as a febrifuge and to treat thrush, diarrhea, dysentery and urinary disorders. In Malaya, an infusion of the leaves, combined with unripe banana and a little benzoin is applied to the wound of circumcision. A root decoction is taken to regulate menstruation. A bark extract called 'amibiasine', has been marketed for the treatment of amoebic dysentery." Morton also writes that "[t]he rind of partially ripe fruits yields a polyhydroxy-xanthone derivative termed mangostin, also beta-mangostin. That of fully ripe fruits contains the xanthones, gartanin, 8-desoxygartanin, and normangostin. A derivative of mangostin, mangostin-e, 6-di-O-glucoside, is a central nervous system depressant and causes a rise in blood pressure." A more complete listing of constituents is given at ethnobotanist Dr. James Duke's informative and useful Phytochemical and Ethnobotanical Databases (Duke 2004). We can conclude then that mangosteen has many uses in folk medicine, and as such, it can join a fairly long list of plants that can be considered as promising sources of new medicines. XanGo on the Go In this age of frenzied commercialism, entrepreneurs are always on the lookout for ways to make it big in the natural medicines market. Under such conditions, however, new medicines of botanical origin cannot be developed or tested in an orderly way. A common feature of the way in which natural medicines such as mangosteen are promoted is the use of network marketing. This involves the retailing of products through the use of independent distributors. These distributors are then encouraged to build and manage their own sales force by recruiting, motivating, supplying, and training others to sell products. Compensation in such arrangements includes the distributor's own sales as well as a percentage of the sales of his or her entire "downline" (i.e., all those people signed up by an individual, who in turn go on to become salespeople). The term network marketing is virtually synonymous with the older but now somewhat disreputable term 'multi-level marketing' (MLM). Network marketing turns mere consumers into determined marketers who aggressively sell their product, often to their own friends, relatives and neighbors. The more people they can recruit into the growing network the more money they themselves make. A sophisticated marketing blitz, including books and pamphlets, seemingly objective newsletters, press releases and chattering websites, inflate the importance of a product, creating a buzz that only dies away when the huge supply of potential customers and salespeople is finally exhausted. Or when, as it has on occasion, the government finally steps in. But the essential requirement for a successful MLM operation of this sort is a kernel of promising-sounding scientific evidence, coupled with a credible and compelling story, a compliant doctor willing to underwrite the concept, and finally some patients (who may themselves be distributors) willing to testify that the product led to astounding cures. Aloe vera, colloidal minerals, gingko biloba and ginseng were all popularized in this way. But perhaps the most memorable example of a network marketing stampede is noni juice, a once totally obscure Polynesian fruit that became the basis of a huge industry. Tahitian Noni International, formerly called Morinda, last year claimed to have passed the two billion dollar sales mark! This is the sort of performance that makes get-rich-quick artists drool. The techniques of network marketing, honed through decades of trial and error, are now being used by a Utah-based company to position mangosteen as the latest "miracle cure" craze. The price of their XanGo mangosteen juice is currently $37 per bottle (or four for $100). You have to ask yourself: who on earth would pay that much for a bottle of fruit juice, no matter how delicious it might be? The reason the marketers can succeed in selling juice at this price is obvious: when people are suffering from medical conditions for which there does not appear to be much hope, or for which the orthodox medical recommendations are too toxic or expensive, they will actively seek alternatives. And then someone, oftentimes someone they trust, such as a friend or neighbor, convinces them to give some new product a try. Products such as mangosteen exploit humanity's understandable desire to discover simple and painless solutions to intractable problems. Now that the commercial ball is rolling an increasing number of mangosteen brands are reaching the market. But for the time being the market leader is XanGo (www.myxango.com). A visit to their website triggers an audio webcast from a very pleasant sounding young lady, who assures us that "by integrating the Internet, teamwork, and personal mentoring, MyXanGo.com provides you a vehicle to improve the areas of your life that are most important to you, and we do it for FREE." I listened in amazement to her polished spiel and the brazen intrusiveness of this message. I was particularly amused when she said, "You should know that this message is not about selling." Right. "It's not about false claims and outlandish statements." Sure. "It's about sharing facts to help you decide if now is the right time in your life to consider XanGo." Really. The rhetoric gets even more effusive. A March 2004 press release from one seller proclaims: "Mangosteen is now on an unstoppable march to conquer the world" (Goss 2004). Put this way it sounds rather ominous…almost like a cross between Osama bin Laden and the Attack of the Killer Tomatoes. Xanthones As stated, one requirement for a successful network promotion is that there be at least a kernel of scientific truth around which exaggerated claims can be assembled. As with noni juice, mangosteen is not entirely without scientific documentation. The problem, as usual, is that the claims for mangosteen are inflated till they far outpace what has been established through careful experimentation. Some mangosteen promoters have mined James Duke's famous ethnobotanical database for confirmation of their product's value. And, indeed, Dr. Duke confirms that the plant contains several interesting components. But so do thousands of other plants in his voluminous database. For most of the chemicals contained in this fruit (such as beta-mangostin, catechins, cis-hex-3-enyl-acetate, gamma-mangostin, gartanin, garcinones) the database lists NO particular biochemical activities. Only the compound called "mangostin" seems to have some scientific backing for its antibacterial, antiseptic and fungicidal properties (Recio 1989). Yet scores of mangosteen websites now cite Duke's database as scientific justification for this product. In reality, Dr. Duke has absolutely nothing to do with any mangosteen distributor and is not particularly enthusiastic about the product. Much is made of the xanthone connection. According to the MyXanGo.com website: "There are over 200 xanthones in nature. Each xanthone can have specific effects on the body. What's remarkable about the mangosteen is that there are over 40 xanthones identified in the pericarp, or rind, making it the single most xanthone-rich source in the world….Only six of the xanthones have been studied in depth. While we don't know fully why the mangosteen works on such a wide variety of physical conditions, we know it has to do with being the world's most potent source of xanthones. Each xanthone has its own effect, and when combined, they take on a synergistic quality that supports the health of the entire body." But all of this is speculative. It is undoubtedly true that there are many xanthones (a kind of antioxidant) in mangosteen. In fact, according to the Merck Index (11th Ed., p. 5613) the first scientifically defined substance to be derived from mangosteen was the xanthone mangostin. This was isolated by a German scientist named Schmid in 1855. In 1979, mangostin was found to have significant anti-inflammatory and anti-ulcer effects in rats (Shankaranarayan 1979). Yet although mangosteen's xanthones have been known for almost 150 years, there are still only 19 PubMed articles on these xanthones and none of these articles concerns the use of xanthones in the actual clinical treatment of human disease. So I would say the jury is still out on their effectiveness in treating anything. The main XanGo website also claims that the antioxidant ORAC (oxygen radical absorbance capacity) value of mangosteen is the highest of all edible plants. "It is so potent that literally I know of nothing else in the supplement market that can possibly come even close to it," says J. Frederic Templeman, MD, a Georgia family practitioner who is interviewed at the MyXanGo website. Many other XanGo-promoting websites repeat the claim that while the previous champion, prunes, have an ORAC value of 7,000 per ounce, mangosteen has an ORAC value of 17,000 to 24,000. Yet XanGo sites claim that "a new champion" has been born in the worldwide contest for ORAC supremacy. But where in the scientific literature is the ORAC value of XanGo published? The source of these numbers is hard to track down. For instance, the Sunsweet prune website states that 100 grams (3.5 ounces) of prunes have an ORAC value of 5,770. While the ORAC values for most fruits and vegetables have been determined by standard laboratories and published in scientific journals, this is not so for mangosteen. I have not seen independent confirmation of these confidently promulgated claims. However, even if we assume for the sake of argument that the figures cited are indeed accurate, it must be pointed out that merely having an astronomically high ORAC value does not in and of itself confer any particular advantage. Not all antioxidants that are confirmed as present in the laboratory can be absorbed by human beings. And there is a limit to how much we can benefit from an increased intake of antioxidants. According to Dr. Ronald Prior of the US Department of Agriculture Research Service at Tufts University, Boston, Massachusetts, "a significant increase in antioxidants of 15 to 20 percent is possible by increasing consumption of fruits and vegetables, particularly those high in ORAC value." However, in order to have a significant impact on plasma and tissue antioxidant capacity one can only meaningfully increase one's daily intake by 3,000 to 5,000 ORAC units. Any greater amount is probably redundant. That is because the antioxidant capacity of the blood is tightly regulated, says Dr. Prior. Thus there is an upper limit to the benefit that can be derived from antioxidants. Taking in 25,000 ORAC units at one time (as reputedly occurs with mangosteen) would be no more beneficial than taking in a fifth of that amount: the excess is simply excreted by the kidneys. Marketers of the drink have widely claimed that XanGo has exceptional health-giving properties based on its very high ORAC score. (ORAC stands for oxygen radical absorbance capacity - a measure of the antioxidant value of a substance.) But having a high ORAC value does not necessarily confer any health advantage. According to Dr. J. Frederic Templeman, a Georgia family practitioner who has written a small book on mangosteen, and who is widely quoted by XanGo marketers, if you take these antioxidants "you aren't going to probably have a heart attack as fast as someone who doesn't take them" and consuming them could therefore constitute "literally the difference between life and death." Although I myself have written a book on the subject of the benefit of antioxidants (Antioxidants Against Cancer), I would say it is a tremendous stretch to claim that antioxidants are predictably going to save anyone's life. Good health is achieved through a combination of many factors, hereditary as well as environmental. Effects on Cancer At the XanGo website, a company spokesperson interviews Dr Templeman on the subject of mangosteen's beneficial effect on cancer. They both agree that a single test tube experiment is proof of the anticancer value of the juice: Dr. Templeman: "That's striking." XanGo spokesperson: "It's incredible." At various other websites devoted to XanGo (and there are now over 21,000 of them!) we read in glowing terms about both the supposed quantity and quality of scientific research on this previously obscure fruit. Reality Check So it is high time for a reality check. Has mangosteen really been thoroughly studied in terms of its effect on cancer and a host of other diseases? Or is this simply a wild extrapolation driven by strong commercial motives? Dr. Templeman refers to 44 scientific publications on this topic but there are just 29 articles on the topic of Garcinia mangostana in PubMed, the US National Library of Medicine database of 14+ million citations. A total of four of these studies relate to cancer. In one test tube experiment it was shown that a xanthone found in mangosteen kills cancer cells as effectively as many chemotherapeutic drugs. It also appears (on the basis of limited data) that compounds found abundantly in mangosteen can inhibit the harmful Cox 1 and Cox 2 enzymes, and can also induce programmed cell death (apoptosis) in aberrant cells (Ho 2002). Mangosteen thus joins a fairly long list of naturally derived compounds that might potentially have some anticancer activity. These 29 articles do not constitute a wealth of data. For example, by contrast, PubMed lists over 2,300 articles on the topic of vitamin C and cancer, 125 of which refer to clinical trials. There are a similar number of studies on vitamin E and cancer. There are 835 studies of melatonin and cancer, and a truly impressive 16,000 on polysaccharides and cancer, including 536 clinical trials and 277 randomized controlled trials (RCTs). Yet, we're to believe that four test-tube experiments constitute - to quote the aforementioned Dr. Templeman - "mountains of evidence" on the benefits of XanGo. According to the promotional website of one of XanGo's many "independent distributors" at http://bjsbytes.com/Xango/Questions.htm: "...much of the science behind xanthones is predominantly available to those in the medical community until recently. Many of the clinical studies on xanthones have been done in universities and testing facilities throughout Asia and have recently started to catch the attention of Western researchers." But is this true? Reputable researchers the world over, including those in Asia, publish in PubMed-listed journals. For example there are over 63,000 articles on cancer in PubMed in the Japanese language. Yet despite the website's misleading talk about "clinical studies," PubMed does not contain a single clinical trial of mangosteen in the treatment of cancer, or any other disease. Perhaps these promoters don't realize that a clinical study is not something done in a laboratory, but a study that by definition is carried out on living patients. Laboratory studies on cell lines or even animals do not qualify for the title 'clinical study'. Thus, despite what you may read at any one of those 21,000 promotional websites, very little scientific evidence exists concerning mangosteen's anticancer activity in humans. In my opinion, what we have here is simply an overpriced fruit drink. Fruit drinks are often healthful beverages. But the only reason I can see that the promoters of mangosteen can get away with charging $37 for this product is that they are playing on patients' hopes and fears in a cynical way. Without the health claims, open or implied, the product could only be sold for at most $5 or $6 (which, for example, is the cost of antioxidant-rich pomegranate juice). The mangosteen phenomenon is a reprise of the aloe vera, gingko biloba, and especially the noni juice story, complete with exaggerated claims for the health benefits of an exotic fruit. It should come as no surprise that both the President and the Chief Financial Officer of Xango once worked for Morinda (now called Tahitian Noni International). Compounds found in plants have long been of great interest to cancer researchers. We must never forget that about one-fifth of all chemotherapeutic agents (including Vincristine, Vinblastine, Etoposide, Teniposide, and Taxol) are ultimately derived from plant sources. Many of these took a long time to pass through the regulatory process, since serious research into botanical medicine often goes begging for financial and intellectual support. Starved of funds in this way, the riches of the natural world are often neglected by mainstream science, only to be plundered by less scrupulous organizations. The patient loses twice - by not having the fruits of serious research and by being deceived by slick operators posing as friends and benefactors. Some may even opt for unproven miracle juices in lieu of more certain therapies that might save their lives. When it comes to cancer, we truly live in a topsy-turvy world. Note from Chet: Be sure to sign up for Dr. Moss's excellent newsletter at his website. References: Campin, Jac. Guide to Plant Relationships (for food allergy and intolerance identification),Version 12 (14 April 2004. Retrieved April 27, 2004 from: http://www.purr.demon.co.uk/Food/RelatedPlantList.html Duke, James, ed. Dr. Duke's Phytochemical and Ethnobotanical Databases. United States Department of Agriculture, Agricultural Research Service, Accessed April 27, 2004 from: http://www.ars-grin.gov/cgi-bin/duke/farmacy2.pl?1228 Hedrick, U.P. (ed.) 1972. Sturtevant's Edible Plants of the World. NY, NY: Dover Publications, Inc., 1972. Downloaded from: www.swsbm.com/ Ho CK, Huang YL, Chen CC. Garcinone E, a xanthone derivative, has potent cytotoxic effect against hepatocellular carcinoma cell lines. Planta Med. 2002 Nov;68(11):975-9. Matsumoto K, Akao Y, Kobayashi E, Ohguchi K, Ito T, Tanaka T, Iinuma M, Nozawa Y. Induction of apoptosis by xanthones from mangosteen in human leukemia cell lines. J Nat Prod. 2003 Aug;66(8):1124-7. Moongkarndi P, Kosem N, Kaslungka S, Luanratana O, Pongpan N, Neungton N. Antiproliferation, antioxidation and induction of apoptosis by Garcinia mangostana (mangosteen) on SKBR3 human breast cancer cell line. J Ethnopharmacol. 2004 Jan;90(1):161-6. Morton, Julia F. Mangosteen. In: Fruits of Warm Climates. Self-published. Miami, FL, 1987, pp. 301-304. ISBN: 0-9610184-1-0 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. 2002 Jan 1;63(1):73-9. ORAC value of Sunsweet prunes: http://www.sunsweetdryers.com/Sunsweet.htm Recio, M. C., Rios, J. L., and Villar, A., A review of some antimicrobial compounds isolated from medicinal plants reported in the literature 1978-1988, Phytotherapy Research. 1989:3(4)117-125. Shankaranarayan D, Gopalakrishnan C, Kameswaran L. Pharmacological profile of mangostin and its derivatives. Arch Int Pharmacodyn Ther. 1979 Jun;239(2):257-69.