Finding out the truth about noni juice, in contrast to the widely available claims and sales pitches, is elusive and challenging. One reason is that many noni researchers who submit papers in support and/or defense of the product disclose financial affiliations with noni products.1,2,3,4,5 A quote by Keith I. Block, M.D., editor-in-chief of "Integrative Cancer Therapies," sums up the problem well: "A significant trend in contemporary herbal medicine has been the movement of traditional medicines of indigenous peoples directly into international commerce, often with little scientific exploration before widespread marketing."6 This lack of evidence leaves unanswered questions about the actual health value of noni, the advantages of one product over another, as well as the dangers noni ingestion may pose to consumers. Concerns about safety even led the European Union to ban the marketing of noni because of unknown safety in the late 1990s.7 Representatives from Tahitian Noni International Inc., the largest noni juice company and research center, insist that "not all noni liquid dietary supplements are created equal," and that their product is safe.8 Product Consistency They are certainly correct on the first count, and the benefits and risks involved with one noni supplement may differ widely from another, based on manufacturing techniques, growing techniques, and added vitamins, electrolytes, sweeteners and derivatives.9,10 Juice concentrations can vary from 10 percent to 96 percent between products.11 Currently, no means exist by which independent analyzers can determine the quality and authenticity of noni juice.12 Fortunately, the buzz about noni has inspired more researchers to respond to the need for rigorous evaluation of noni's risks and benefits. Current Research Brian Issell, M.D., an oncologist, internist and director of clinical sciences at the University of Hawaii's Cancer Research Center, is conducting a Phase I clinical study on noni, funded initially by the National Institutes of Health and then by the Hawaii Community Foundation. Eligible patients have advanced cancer but no suitable conventional treatment options. Issell and his colleagues are working to determine the maximum tolerable dose that can provide anti-cancer effects while optimizing quality of life. Noting the "incredible commercialization" associated with noni products, Issell remarked: "We need to know if it helps more than harms people."13 Issell and his fellow researchers are also tracking interactions and adverse effects from the 500 mg capsules.14 Early reports suggest that patients may have improved quality of life at higher doses. Noni Basics The species name for noni is Morinda citrifolia. The noni fruit resembles a "grenade,"15 or a green potato covered with "pineapple-like spots."16 The mature fruit "has a foul taste and soapy smell."17 Known also as "Indian mulberry," this small evergreen tree is a native to Australia and Southeast Asia and reached Hawaiian soil long ago.18 Cancer or Fungal Therapy Pacific Islanders, Australian aborigines and Asians have viewed noni as both a food and healing remedy for over a thousand years.19 They sought the plant for its fruit, leaves, bark and roots for the treatment of diabetes, diarrhea, hypertension, pain, skin wounds, topical infections and malaria.20 The claims for noni extend further, to cancer treatment and its prevention. Noni polysaccharides reportedly provide immunomodulatory or immune-enhancing benefits when combined with certain chemotherapy preparations (DNA-alkylating agents, DNA-intercalators, topo-isomerase inhibitors, mitotic inhibitors, and anti-metabolites).21 Anti-tumor properties deliver a 25 percent to 45 percent "cure rate" for the sarcoma 180 ascites tumor in mice.22 One study suggests that noni demonstrates tumor cell-selective anti-proliferative effects.23 Insofar as its anti-fungal value, noni interferes with serum-induced formation of filamentous structures in Candida albicans and inhibits germination of Aspergillus nidulans, yielding potentially effective herbal treatment options in cases of candidiasis and aspergillosis.24 Other Qualities Noni may be cardioprotective by reducing risk of atherosclerosis and lowering blood pressure. The extract up-regulates the low-density lipoprotein (LDL) receptor, thereby accelerating LDL clearance from the circulation.25 A Japanese study indicated that noni juice strongly inhibited the activity of angiotensin I converting enzyme.26 An even more recent added application for noni includes wrinkle protection in human skin.27 Some of the most widely studied noni constituents for cancer prevention include anthraquinones. Both the fruit and root contain an anthraquinone (2-methoxy-1,3,6-trihydroxyanthraquinone) that demonstrates "extremely potent" quinine reductase (QR) inducing activity.28 The capacity of this noni anthraquinone to induce QR activity was almost 40 times stronger than a comparison positive control, l-sulforaphane, a cancer chemopreventive compound first isolated from broccoli.29 Some place QR, a phase II enzyme, in the "cancer chemopreventive" category on account of its capacity to readily metabolize and promote excretion of oxidative and electrophilic molecules before they damage cellular macromolecules such as DNA.30 Furthermore, QR helps alpha-tocopherol and coenzyme Q remain reduced and as such has earned QR inducers the title, "indirect antioxidants." Side Effects of Noni Three potential drawbacks to noni have appeared in the literature. These include coumadin resistance from one preparation supplemented with vitamin K,31 hyperkalemia in patients with compromised renal function,32 and hepatotoxicity. The hepatotoxicity may be the most problematic, as even otherwise healthy individuals have become ill on noni. Three reports of liver damage after noni ingestion were published in 2005. In all three cases, the authors found a temporal relationship between noni juice ingestion and liver injury, and they postulated that the anthraquinones in noni may have contributed to the toxicity.33,34 An extensive ruling-out process of other potential causes of acute hepatitis led them to the conclusion of herbal hepatotoxicity associated with noni juice. In one case, a 29-year-old man with a history of toxic hepatitis developed sub-acute liver failure necessitating emergency liver transplant. This followed ingestion of a combination of 1.5 liters of Tahitian noni over the preceding three weeks, and a nine-day course of a Chinese herbal mixture containing bupleurum, pinellia, scutellaria, codonopsis, licorice, schizonepeta and peony.35 An additional hepatotoxic effect may have occurred in the first case due to the concomitant administration of Chinese herbs. In the second case, a 62 year-old woman with no history of liver disease experienced a self-limiting case of acute hepatitis after consuming 2 liters of Tahitian Noni juice over three months. In the third case, a 45-year-old man, again with no history of liver disease, presented with a 2-week history of malaise, nausea, anorexia, fatigue and shortness of breath, which started after ingesting noni juice for three weeks preceding presentation. Laboratory evaluation indicated highly elevated transaminases and elevated lactate dehydrogenase. Discontinuation of the product resolved the condition within one month.36 Research and development representatives from Tahitian Noni International, a 9-year-old multi-level marketing company that in 2005 surpassed $3 billion in total sales,37 submitted rebuttals to the aforementioned case reports.38,39 In their letters to the editor, they defended the safety of noni juice, citing unpublished data from a human clinical study as well as animal toxicity tests in rats. In addition, they question the relevance of anthraquinones insofar as causing liver damage in the three reported cases, claiming that, "M. citrifolia anthraquinones occur in quantities too small to be of any toxicological significance. Further, these do not have chemical structures capable of being reduced to reactive anthrone radicals, which were implicated in previous cases of herbal hepatotoxicity."40 Veterinary Use Many holistic veterinarians have been selling noni for pets for years. On a multilevel marketing training website, one veterinarian's testimonial asserts in boldface that "more than 90 percent of the time the animals have responded well." He continues, "I have found that noni is the most wonderful substance a doctor can use in this line of work. In all my 35 years of practicing traditional and holistic veterinary medicine, I haven't seen any other product that is as versatile as noni juice. If I were banished to a remote island and could only bring one health product, it would definitely be noni juice."41 Dr. Robinson, DVM, DO, MS, Dipl. ABMA, FAAMA, is an assistant professor in complementary and alternative medicine in the department of clinical sciences at Colorado State University. <HOME>
