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DRUG RECORD

 

NONI

(MORINDA CITRIFOLIA)

OVERVIEW
Noni

 

Introduction

Noni is a tropic fruit tree, the juice, roots, stems, bark, leaves and flowers of which have been used as medicinal remedies in Polynesia for centuries and recently in the Western world for a wide range of medical problems from cancer and diabetes to AIDs.  A small number of isolated case reports of clinically apparent liver injury have been attributed to noni.

 

Background

Morinda citrifolia is a small, tropic fruit tree commonly known as Indian Mulberry, Ba Ji Tian or Noni which has been used as a food and an herbal remedy for centuries in Polynesia and Southeast Asia.  Recently, noni has been introduced into Western herbal medicine as a “tropic fruit with 101 medical uses”, and widely advertised and sold on the internet for a wide range of disorders including cancer, diabetes, depression, chronic fatigue, AIDS and senility.  Active components in noni are many and include flavonoids, glycosides, vitamins, anthraquinones and polyunsaturated fatty acids.  Studies in vitro and in animal models suggest that the active components are polysaccharide rich substances which have antitumor effects in vitro.  In clinical trials, however, noni has yet to be proven to have anticancer activity.  Noni juice has been marketed in the United States since 1996 and was approved as a “novel food” by the European Commission in 2003.  While considered safe, several case reports of adverse events attributed to use of noni have appeared, although often criticized because of lack of chemical analysis of the actual product to exclude misidentification and contamination.

 

Hepatotoxicity

Several case reports have suggested that noni may account for some cases of idiosyncratic acute liver injury, although the association was weak in many cases.  The latency to onset ranged from 2 to 8 weeks and the clinical features resembled acute hepatitis with a hepatocellular pattern of serum enzyme elevations.  Immunoallergic features (rash, fever, eosinophilia) were not present, but some patients had high levels of autoantibodies.  Nevertheless, the liver injury resolved rapidly once noni was discontinued and other features of autoimmunity were not present.

 

Mechanism of Injury

The mechanism of hepatotoxicity of noni is unknown.  Extracts of the noni fruit have multiple components, including low levels of anthraquinones which are often cited as being hepatotoxic.  However, the cases of noni associated liver injury have had all of the characteristics of idiosyncratic liver injury rather than direct toxicity, and in vitro and in vivo studies of noni have not demonstrated evidence of intrinsic hepatotoxicity.

 

Outcome and Management

Hepatotoxicity attributed to noni juice has occasionally been severe and led to acute liver failure, which in at least one case necessitated emergency liver transplantation.  Rechallenge studies have not been reported.

Other Names:  Morinda citrifolia, Indian mulberry, Ba Ji Tian, Cheese fruit, Tahitian Noni Juice®, Xeronine

 

Drug Class:  Herbal and Dietary Supplements

 

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REPRESENTATIVE TRADE NAMES
Noni – Generic

 

DRUG CLASS
Herbal and Dietary Supplements

 

SUMMARY INFORMATION

Fact Sheet at National Center for Complementary and Integrative Health, NIH

 

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DRUG CAS REGISTRY NUMBER MOLECULAR FORMULA STRUCTURE
Noni 84929-68-0 Herbal mixture Not applicable

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REFERENCES
Noni

 

References updated: 07 February 2014

  1. Zimmerman HJ. Unconventional drugs. Miscellaneous drugs and diagnostic chemicals. In, Zimmerman, HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott,1999: pp. 731-4.  (Expert review of hepatotoxicity published in 1999; noni is not discussed).

  2. Seeff L, Stickel F, Navarro VJ. Hepatotoxicity of herbals and dietary supplements. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd ed. Amsterdam: Elsevier, 2013, pp. 631-58.  (Review of hepatotoxicity of herbal and dietary supplements [HDS] mentions that noni jucie has been implicated in cases of hepatitis and acute liver failure).

  3. Noni. In, PDR for Herbal Medicines. 4th ed. Montvale, New Jersey: Thomson Healthcare Inc. 2007, pp 604-5.  (Compilation of short monographs on herbal medications and dietary supplements).

  4. Wang MY, West BJ, Jensen CJ, Nowichi D, Su C, Palu AK, Anderson G. Morinda citrifolia(noni): a literature review and recent advances in Noni research. Acta Pharmacologica Sinica 2002; 23: 1127-41. PubMed Citation  (Extensive review of the literature on in vitro and in vivo effects of noni as well as studies in animals and humans which demonstrated lack of toxicity).

  5. Pittler MH, Ernest E. Systematic review: hepatotoxic events associated with herbal medicinal products. Aliment Pharmacol Ther 2003; 18: 451-71. PubMed Citation  (Systematic review of published cases of hepatotoxicity due to herbal medications listing 52 case reports or case series; noni is not listed or mentioned).

  6. Millonig G, Stadlmann S, Vogel W. Herbal hepatotoxicity: acute hepatitis caused by a Noni preparation(Morinda citrifolia). Eur J Gastroenterol Hepatol 2005; 17: 445-7. PubMed Citation  (45 year old man developed malaise and chest discomfort a few weeks after starting noni juice [bilirubin 0.8 mg/dL, ALT 1995 U/L, GGT 539 U/L], with resolution within 1 month of stopping).

  7. Stadlbauer V, Fickert P, Lackner C, Schmerlaib J, Krisper P, Trauner M, Stauber RE. Hepatotoxicity of NONI juice: report of two cases. World J Gastroenterol 2005; 11: 4758-60. PubMed Citation  (2 cases from Austria: 29 year old man developed acute liver failure after taking 1.5 L of noni juice over 3 weeks and various Chinese herbs for 7 days [bilirubin 45.3 mg/dL, ALT 1626 U/L, INR 1.4], undergoing liver transplantation 6 days later; 62 year old woman developed vomiting and diarrhea 2 months after ingesting noni juice daily for 3 months [bilirubin 2.9 mg/dL, ALT 2381 U/L, Alk P 292 U/L], resolving over next 9 months).

  8. West BJ, Jensen CJ, Westendorf J. Noni juice is not hepatotoxic. World J Gastroenterol 2006; 12: 3616-9. PubMed Citation  (Letter in response to Millonig [2005] and Stadlbauer [2005] questioning the link of the liver injury to noni juice intake, and reviewing studies of safety of noni in animals and man which showed no evidence of direct hepatotoxicity).

  9. Yuce B, Gulberg V, Diebold J, Gerbes AL. Hepatitis induced by Noni juice from Morinda citrifolia: a rare cause of hepatotoxicity or the tip of the iceberg? Digestion 2006; 73: 167-70. PubMed Citation  (24 year old woman with multiple sclerosis on beta interferon developed jaundice 4 weeks after starting noni juice [bilirubin 5.3 rising to 43.5 mg/dL, ALT 1538 to 3648 U/L, GGT 110 U/L], resolving in 4 weeks after stopping noni and 5 weeks after stopping beta interferon).

  10. West BJ. Hepatotoxicity from interferon-beta, not noni juice. Digestion 2006; 74: 47-8; author reply 48. PubMed Citation  (Letter in response to Yuce [2006] suggesting that the liver injury was more likely due to beta interferon than noni).

  11. López-Cepero Andrada JM, Lerma Castilla S, Fernández Olvera MD, Amaya Vidal A. [Hepatotoxicity caused by a Noni(Morinda citrifolia) preparation]. Rev Esp Enferm Dig 2007; 99: 179-81. Spanish. PubMed Citation  (33 year old woman developed jaundice a few weeks after starting daily use of noni juice during travel to Ecuador [bilirubin 8.1 mg/dL, ALT 2740 U/L, Alk P 205 U/L, prothrombin 58%], resolving rapidly upon stopping the herbal).

  12. West BJ, Berrio LF. [Tahitian Noni juice is not hepatotoxic]. Rev Esp Enferm Dig 2007; 99: 737-8; author reply 738. Spanish. PubMed Citation  (Letter in response to Lopez-Cepero Andrada [2007] questioning the role of noni juice in the liver injury, because of the lack of anti-HEV testing and lack of verification of the purity and identity of noni in the product).

  13. Potterat O, Hamburger M. Morinda citrifolia(Noni) fruit—phytochemistry, pharmacology, safety. Planta Med 2007; 73: 191-9. PubMed Citation  (Review of the history, phytochemistry, pharmacology, animal and clinical studies and safety of noni; 4 case reports of hepatotoxicity have been reported, but review by the European Food Safety Authority “concluded that there was no convincing evidence for a causal relationship”).

  14. García-Cortés M, Borraz Y, Lucena MI, Peláez G, Salmerón J, Diago M, Martínez-Sierra MC, et al. Liver injury induced by “natural remedies”: an analysis of cases submitted to the Spanish Liver Toxicity Registry. Rev Esp Enferm Dig 2008; 100: 688-95. PubMed Citation  (Among 521 cases of drug induced liver injury submitted to Spanish registry, 13 [2%] were due to herbals, but none were attributed to noni juice).

  15. Stadlbauer V, Weiss S, Payer F, Stauber RE. Herbal does not at all mean innocuous: the sixth case of hepatotoxicity associated with morinda citrifolia(noni). Am J Gastroenterol 2008; 103: 2406-7. PubMed Citation  (43 year old man with glioblastoma developed elevated liver tests two weeks after starting noni juice [ALT rising from 34 to 516 U/L with normal bilirubin], resolving when noni juice was stopped).

  16. West BJ, Su CX, Jensen CJ. Hepatotoxicity and subchronic toxicity tests of Morinda citrifolia(noni) fruit. J Toxicol Sci 2009; 34: 581-5. PubMed Citation  (Noni extract was prepared from Tahitian noni fruits and tested for hepatotoxicity in vitro and in vivo; no toxicity found towards HepG2 cells or laboratory rats given a range of doses orally for up to 90 days).

  17. Jacobsson I, Jönsson AK, Gerdén B, Hägg S. Spontaneously reported adverse reactions in association with complementary and alternative medicine substances
    in Sweden. Pharmacoepidemiol Drug Saf 2009; 18: 1039-47. PubMed Citation  (Review of 778 spontaneous reports of adverse reactions to herbals to Swedish Registry; noni juice not mentioned).

  18. Reuben A, Koch DG, Lee WM; Acute Liver Failure Study Group. Drug-induced acute
    liver failure: results of a U.S. multicenter, prospective study. Hepatology 2010; 52: 2065-76. PubMed Citation  (Among 1198 patients with acute liver failure enrolled in a US prospective study between 1998 and 2007, 133 [11%] were attributed to drug induced liver injury of which 12 [9%] were due to herbals, but none were attributed to noni juice).

  19. Stickel F, Kessebohm K, Weimann R, Seitz HK. Review of liver injury associated with dietary supplements. Liver Int 2011; 31: 595-605. PubMed Citation  (Review of current understanding of liver injury from herbals and dietary supplements focusing upon Herbalife and Hydroxycut products, green tea, usnic acid, Noni juice, Chinese herbs, vitamin A and anabolic steroids; noni is not discussed).

  20. Yu EL, Sivagnanam M, Ellis L, Huang JS. Acute hepatotoxicity after ingestion of Morinda citrifolia (Noni Berry) juice in a 14-year-old boy. J Pediatr Gastroenterol Nutr 2011; 52: 222-4. PubMed Citation  (14 year old boy developed jaundice after having ingested 10 bottles of an antioxidant drink [containing green tea, aloe vera and noni] over the previous 2 months [bilirubin 4.4 rising to 12.3 mg/dL, ALT 2860 U/L, GGT 141 U/L, INR 1.7], resolving in 2 months).

  21. Jiménez-Encarnación E, Ríos G, Muñoz-Mirabal A, Vilá LM. Euforia-induced acute
    hepatitis in a patient with scleroderma. BMJ Case Rep 2012; 2012. PubMed Citation  (45 year old woman with systemic sclerosis developed jaundice 1 month after starting Euphoria, a combination herbal product whose ingredients included aloe vera, resveratrol, green tea, noni and several berries [bilirubin 17.7 mg/dL, ALT 837 U/L, Alk P 134 U/L], with slow recovery over the 18 months after stopping).

  22. Teschke R, Wolff A, Frenzel C, Schulze J, Eickhoff A. Herbal hepatotoxicity: a
    tabular compilation of reported cases. Liver Int 2012; 32: 1543-56. PubMed Citation  (A systematic compilation of all publications on the hepatotoxicity of specific herbals identified 185 publications on 60 different herbs, herbal drugs and supplements including 6 publications on noni). 

  23. Teschke R, Schulze J, Schwarzenboeck A, Eickhoff A, Frenzel C. Herbal hepatotoxicity: suspected cases assessed for alternative causes. Eur J Gastroenterol Hepatol 2013; 25: 1093-8. PubMed Citation  (Review of 23 publications of case series of liver injury attributed to herbals or dietary supplements found alternative causes to be "evident" in 49% of 573 cases).

  24. Bunchorntavakul C, Reddy KR. Review article: herbal and dietary supplement
    hepatotoxicity. Aliment Pharmacol Ther 2013; 37: 3-17. PubMed Citation  (Systematic review of literature on HDS associated liver injury mentions that noni has been associated with clinically apparent hepatotoxicity).

  25. Mrzljak A, Kosuta I, Skrtic A, Kanizaj TF, Vrhovac R. Drug-Induced Liver Injury Associated with Noni (Morinda citrifolia) Juice and Phenobarbital. Case Rep Gastroenterol 2013; 7: 19-24. PubMed Citation  (38 year old woman on phenobarbital for 9 months developed jaundice one week after starting noni juice [60 mL daily] [bilirubin 9.7 mg/dL, ALT 813 U/L, Alk P 532 U/L, INR 2.6], resolving within 6 months of stopping both noni and phenobarbital and with corticosteroid therapy).

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OTHER REFERENCE LINKS
Noni
  1. PubMed logoRecent References on Noni

  2. Clinical Trials logoTrials on Noni

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