Noni

• How It Works

  Noni showed anticancer effects in laboratory studies, but results from human studies are lacking.

  The juice of the noni fruit has been traditionally used in Polynesian cultures as an anticancer agent. Scientists have isolated a fraction from noni juice that is rich in complex sugars. This fraction, alone and in conjunction with chemotherapy drugs, is able to increase the survival of laboratory mice that have been implanted with lung cancer. Scientists are unsure exactly how noni exerts this effect, but observe that it enhances certain aspects of the immune system. Furthermore, noni juice acts as an antioxidant and slows the transformation of normal cells to cancer cells in animal studies.

• Purported Uses
  • To treat cancer
    Laboratory studies in human cell lines and animals show that noni extracts have anticancer effects both when used alone and with chemotherapy drugs. However, there is no proof from clinical trials that the same effect occurs in humans, although a preliminary study is underway.
  • To treat diabetes
    Although some compounds in noni have antidiabetic properties in the lab, there is no clinical evidence to support this use. In addition, noni fruit is rich in complex sugars and therefore may worsen medical conditions associated with high blood sugar levels.
  • To lower high blood pressure
    No scientific evidence supports this use.
  • As an immune stimulant
    Laboratory studies show that noni juice enhances certain aspects of the immune system, but these results are not always transferable to the human body. There is no proof from clinical trials that these effects occur in humans.
  • As an analgesic
    One study in laboratory mice supports this use, but there is no proof from clinical trials that the same effect occurs in humans.
• Do Not Take If
  • You have renal insufficiency: Noni is high in potassium content.
  • You have diabetes: Noni juice has a high sugar content.
  • You are taking potassium-sparing diuretics, angiotensin converting enzyme (ACE) inhibitors, or angiotensin receptor blockers.
  • You are undergoing chemotherapy or radiation therapy: Noni has antioxidant effects and can interfere with treatment.
  • You are taking blood-thinning medications such as coumadin: Noni juice can reduce their effectiveness.
  • You are taking antiepileptic drugs such as phenytoin: Noni juice may reduce its effectiveness.
  • You are taking drugs to increase the motility of the stomach and intestine. Noni has similar activity and may affect the absorption of other drugs or increase their adverse effects.
  • You are taking UGT (Uridine 5’-diphospho-glucuronosyltransferase) substrate drugs: Noni may increase the risk of side effects of these drugs.
• Side Effects

  Case reports

  • Kidney failure and dangerously high potassium levels in the blood resulting from noni juice use.
  • Liver failure requiring transplants: In a 29-year-old man with prior liver inflammation following ingestion of 1.5 liters of noni juice over 3 weeks and a 56-year-old who regularly consumed noni juice and other products.
  • Acute hepatitis: In a 62-year-old woman after consuming 2 liters of noni juice over 3 months. She recovered after stopping noni juice intake.
  • Coumadin resistance: In a 41-year-old woman following concurrent intake of noni juice. Symptoms improved after treatment and discontinuation of noni juice.
  • Reduced effectiveness of phenytoin: In a 49-year-old man with epilepsy who also ingested noni fruit juice daily. The effectiveness of phenytoin therapy was restored when he stopped his noni juice regimen.

  However, a company-sponsored study showed that dose-related adverse effects are minimal in a noni product.

• Scientific Name

  Morinda citrifolia

• Clinical Summary

  Noni is an evergreen plant found throughout Polynesia. It bears fleshy yellow-white fruit and is used in traditional medicine for wound healing, infections, diarrhea, skin conditions, and as a tonic. It is also cultivated in Hawaii and other Polynesian islands and is marketed worldwide. Fresh or fermented juices are available as drinks while capsules, pills, and powders are sold as dietary supplements.

  In vitro and animal studies suggest that noni extracts and its constituents have antibacterial ⁽³²⁾, antifungal ^(14) (33), anti-inflammatory ⁽³⁴⁾, antidiabetic ⁽³⁵⁾, hepatoprotective ^(36) (37), prokinetic ⁽³⁸⁾, antitumor ⁽³⁹⁾, and immunomodulatory ^{(3) (7) (8) (17) (18)} properties. Noni also inhibits low-density-lipoprotein oxidation and may be useful in preventing arteriosclerosis ⁽¹⁵⁾. It improved memory in animal models of impairment ⁽⁴⁰⁾ and activated cell-mediated immunity ⁽⁴¹⁾. Glycosides, iridoids, and other constituents isolated from the fruits and leaves have demonstrated antioxidant effects ^{(12) (13) (42) (43)}. In addition, a >5% concentration of noni juice was shown to have antiangiogenic properties in an ex vivo assay ⁽¹⁶⁾ , and cervical cancer cell lines treated with 10% noni altered oxidative stress markers and DNA repair gene expression ^(44) (45).

  In human studies, a noni extract was shown to be effective in reducing incidence of early postoperative nausea ⁽²⁹⁾. Consumption of noni juice alleviated cigarette smoke-induced dyslipidemia ⁽³⁰⁾. Morinda citrifolia should not be confused with Morinda officinalis, also known as Ba Ji Tian, commonly used in Chinese medicine.

• Purported Uses
  • Cancer treatment
  • Diabetes
  • Health maintenance
  • Hypertension
  • Immunostimulation
  • Pain
• Mechanism of Action

  Glycosides isolated from noni juice inhibit AP-1 transactivation and cell transformation in mouse epidermal JB6 cell lines ⁽²⁾. Antidiabetic characteristics of some noni compounds are attributed to inhibition of the protein tyrosine phosphatase 1B enzyme ⁽³⁵⁾. Anti-inflammatory activity in noni extract was attributed to quercetin ⁽³⁴⁾. In addition, noni juice exhibited antioxidant effects by reducing aromatic DNA adducts ^(5) (19).

  In animal models, an aqueous extract of noni root produced a central analgesic effect that was antagonized by naloxone ⁽⁶⁾. Hepatoprotective effects occur through regulation of lipid homeostasis, antioxidant status, and anti-inflammatory responses ^(36) (37). The primary iridoid deacetylasperulosidic acid may exert antioxidant effects by increasing superoxide dismutase activity ⁽⁴²⁾. Scopoletin and rutin in noni may be responsible for antidopaminergic and antiadrenergic effects ⁽⁴⁶⁾. Scopoletin also stimulates gastrointestinal motility by acting as a 5-HT4 receptor agonist ⁽³⁸⁾. Treatment with noni extract prevented memory impairment through increased brain energy metabolism, cholinergic neurotransmission, brain-derived neurotrophic factor, and antioxidative activity ⁽⁴⁰⁾.

  When combined with suboptimal doses of certain chemotherapy agents, polysaccharides from noni improved survival time and curative effects ⁽⁴⁾. Apoptotic effects occur via upregulation of p53 and proapoptotic Bax proteins, as well as downregulation of the antiapoptotic Bcl-2, Bcl-XL proteins and survivin. Increase in caspase 9 and 3 was also reported, which suggests involvement of the intrinsic mitochondrial pathway ⁽³¹⁾. In cervical cancer cell lines, malondialdehyde levels were significantly reduced when treated with noni, alone or in combination with cisplatin alone ⁽⁴⁴⁾. The antitumor effects of damnacanthal from noni are attributed to its inhibitory effects on the HGF/c-Met axis in human hepatocellular carcinoma cells, with decreases in Akt phosphorylation and matrix metalloproteinase-2 secretion ⁽³⁹⁾. Noni extract induced apoptosis, G1/S phase cell-cycle arrest, and decreased intracellular ROS generation and mitochondrial membrane potential in breast cancer cells ⁽⁴⁷⁾.

• Contraindications
  • Patients with renal insufficiency should consume noni juice with caution due to high potassium content ⁽⁷⁾.
  • Patients with diabetes should consume noni juice with caution due to high sugar content.
• Adverse Reactions

  Case reports

  • Hepatotoxicity, some acute, following consumption of noni juice products ^{(9) (10) (22) (23) (24) (26)}.
  • Acute liver failure requiring a transplant: In a 56-year-old woman without previous liver disease who regularly consumed noni juice and other products, the combination of products was suggested as the probable cause ⁽⁴⁸⁾.
  • Hyperkalemia ⁽⁷⁾ due to high potassium content.
  • Resistance to coumadin: In a 41-year-old woman following concurrent intake of noni juice. Symptoms improved after treatment and discontinuing noni juice ⁽²⁵⁾.
  • Reduced effectiveness of phenytoin: In a 49-year-old man with epilepsy treated with phenytoin who also took noni fruit juice daily. Despite medication adherence, sub-therapeutic phenytoin levels persisted resulting in poor seizure control that could be traced to the concurrent ingestion of noni ⁽⁴⁹⁾.

  However, a company-sponsored study suggests that dose-related adverse effects are minimal in a noni product ⁽²⁰⁾.

• Herb-Drug Interactions

  Chemotherapy or radiation therapy: The antioxidant effects of noni products may decrease the activity of some chemotherapeutic agents ⁽²¹⁾ or radiation therapy.
  Coumadin: Noni juice was reported to antagonize the effects of coumadin ⁽²⁵⁾.
  Antiepileptic drugs (phenytoin): Noni may reduce effectiveness of these drugs ⁽⁴⁹⁾.
  Potassium-sparing diuretics, angiotensin converting enzyme (ACE) inhibitors, or angiotensin receptor blockers: Noni is high in potassium ⁽⁷⁾.
  Prokinetic drugs: Noni may have additive effects and may affect the absorption rate of other drugs ⁽³⁸⁾.
  UGT (Uridine 5’-diphospho-glucuronosyltransferase) substrate drugs: Noni modulates UGT enzymes in vitro and may increase the side effects of drugs metabolized by them ⁽²⁸⁾.

• References

  1. FDA warning letter. http://www.fda.gov/NewsEvents/Testimony/ucm114985.htm. Accessed June 6,2013.

  2. Liu G, et al. Two novel glycosides from the fruits of Morinda citrifolia (noni) inhibit AP-1 transactivation and cell transformation in the mouse epidermal JB6 cell line. Cancer Res 2001;61:5749-56.

  3. Hirazumi A, et al. Immunomodulation contributes to the anticancer activity of Morinda citrifolia (noni) fruit juice. Proc West Pharmacol Soc 1996;39:7-9.

  4. Hirazumi A, Furusawa E. An immunomodulatory polysaccharide-rich substance from the fruit juice of Morinda citrifolia (noni) with antitumour activity. Phytother Res 1999;13:380-7.

  5. Wang MY, Su C. Cancer preventative effect of Morinda citrifolia (noni). Ann N Y Acad Sci 2001;952:161-8.

  6. Younos C, et al. Analgesic and behavioural effects of Morinda citrifolia. Planta Med 1990;56:430-4.

  7. Mueller BA, et al. Noni juice (Morinda citrifolia): hidden potential for hyperkalemia? Am J Kidney Dis 2000;35:310-2.

  8. Hirazumi A, et al. Anticancer activity of Morinda citrifolia (noni) on intraperitoneally implanted Lewis lung carcinoma in syngeneic mice. Proc West Pharmacol Soc 1994;37:145-6.

  9. Stadlbauer V, et al. Hepatotoxicity of NONI juice: Report of two cases. World J Gastroenterol. 2005;11(30):4758-60.

  10. Millionig G, Stadlmann S, Vogel W. Herbal hepatotoxicity: acute hepatitis caused by a Noni preparation (Morinda citrifolia). Eur J Gastroenterol Hepatol. 2005; 17(4):445-7.

  11. Study of Noni in Cancer Patients. http://www.clinicaltrials.gov/ct2/show/NCT00033878?term=noni&rank=1. Accessed June 6, 2013.

  12. Su BN, et al. Chemical constituents of the fruits of Morinda citrifolia (Noni) and their antioxidant activity. J Nat Prod 2005 68(4):592-5.

  13. Sang S, et al. Flavonol glycosides and novel iridoid glycoside from the leaves of Morinda citrifolia. J Agric Food Chem 2001 49(9):4478-81.

  14. Banerjee S, et al. An Extract of Morinda citrifolia Interferes with the Serum-Induced Formation of Filamentous Structures in Candida albicans and Inhibits Germination of Aspergillus nidulans. Am J Chin Med 2006; 34(3):503-9.

  15. Kamiya K, et al. Chemical constituents of Morinda citrifolia fruits inhibit copper-induced low-density lipoprotein oxidation. J Agric Food Chem 2004; 52(19): 5843-8.

  16. Hornick CA, et al. Inhibition of angiogenic initiation and disruption of newly established human vascular networks by juice from Morinda citrifolia (noni). Angiogenesis 2003; 6(2):143-9.

  17. Arpornsuwan T, Punjanon T. Tumor cell-selective antiproliferative effect of the extract from Morinda citrifolia fruits. Phytother Res 2006; 20(6):515-7.

  18. Furusawa E, et al. Antitumour potential of a polysaccharide-rich substance from the fruit juice of Morinda citrifolia (Noni) on sarcoma 180 ascites tumour in mice. Phytother Res 2003; 17(10):1158-64.

  19. Wang MY, Peng L, Lutfiyya MN, et al. Morinda citrifolia (noni) reduces cancer risk in current smokers by decreasing aromatic DNA adducts. Nutr Cancer. 2009;61(5):634-9.

  20. West BJ, White LD, Jensen CJ, Palu AK. A double-blind clinical safety study of noni fruit juice. Pac Health Dialog. 2009 Nov;15(2):21-32.

  21. Santiago K, Gaikwad A, Coffer L, et al. Evaluation of the Hepatic Metabolism and Antitumor Activity of Noni Juice (Morinda citrifolia L.) in Combination with Chemotherapy. Journal of the Society for Integrative Oncology. Vol 8, No 3 (Summer), 2010: p. 89.

  22. 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 Jan;7(1):19-24.

  23. 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(2-3):167-70.

  24. 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 Sep;103(9):2406-7.

  25. Carr ME, Klotz J, Bergeron M. Coumadin resistance and the vitamin supplement “Noni”. Am J Hematol. 2004 Sep;77(1):103.

  26. 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 Feb;52(2):222-4.

  27. Engdal S, Nilsen OG. In vitro inhibition of CYP3A4 by herbal remedies frequently used by cancer patients. Phytother Res. 2009 Jul;23(7):906-12.

  28. Mohamed ME, Frye RF. Effects of herbal supplements on drug glucuronidation. Review of clinical, animal, and in vitro studies. Planta Med. 2011 Mar;77(4):311-21.

  29. Prapaitrakool S, Itharat A. Morinda citrifolia Linn. for prevention of postoperative nausea and vomiting. J Med Assoc Thai. 2010 Dec;93 Suppl 7:S204-9.

  30. Wang MY, Peng L, Weidenbacher-Hoper V, et al. Noni juice improves serum lipid profiles and other risk markers in cigarette smokers. ScientificWorldJournal. 2012;2012:594657.

  31. Gupta RK, Banerjee A, Pathak S, Sharma C, Singh N. Induction of mitochondrial-mediated apoptosis by Morinda citrifolia (Noni) in human cervical cancer cells. Asian Pac J Cancer Prev. 2013;14(1):237-42.

  32. Kumarasamy B, Manipal S, Duraisamy P, et al. Role of aqueous extract of Morinda citrifolia (Indian noni) ripe fruits in inhibiting dental caries-causing streptococcus mutans and streptococcus mitis. J Dent (Tehran). Nov 2014;11(6):703-710.

  33. Murugan DD, Mohamed Z, Barani K, et al. Anti-fungal activity of Morinda citrifolia (noni) extracts against Candida albicans: an in vitro study. ScientificWorldJournal. Mar-Apr 2014;25(2):188-190.

  34. Huang HL, Liu CT, Chou MC, et al. Noni (Morinda citrifolia L.) Fruit Extracts Improve Colon Microflora and Exert Anti-Inflammatory Activities in Caco-2 Cells. J Med Food. Jun 2015;18(6):663-676.

  35. Nguyen PH, Yang JL, Uddin MN, et al. Protein tyrosine phosphatase 1B (PTP1B) inhibitors from Morinda citrifolia (Noni) and their insulin mimetic activity. J Nat Prod. Nov 22 2013;76(11):2080-2087.

  36. Chang YY, Lin YL, Yang DJ, et al. Hepatoprotection of noni juice against chronic alcohol consumption: lipid homeostasis, antioxidation, alcohol clearance, and anti-inflammation. J Agric Food Chem. Nov 20 2013;61(46):11016-11024.

  37. Lin YL, Chang YY, Yang DJ, et al. Beneficial effects of noni (Morinda citrifolia L.) juice on livers of high-fat dietary hamsters. Food Chem. Sep 1 2013;140(1-2):31-38.

  38. Nima S, Kasiwong S, Ridtitid W, et al. Gastrokinetic activity of Morinda citrifolia aqueous fruit extract and its possible mechanism of action in human and rat models. J Ethnopharmacol. Jul 13 2012;142(2):354-361.

  39. Garcia-Vilas JA, Quesada AR, Medina MA. Damnacanthal, a noni anthraquinone, inhibits c-Met and is a potent antitumor compound against Hep G2 human hepatocellular carcinoma cells. Sci Rep. 2015;5:8021.

  40. Pachauri SD, Verma PR, Dwivedi AK, et al. Ameliorative effect of Noni fruit extract on streptozotocin-induced memory impairment in mice. Behav Pharmacol. Aug 2013;24(4):307-319.

  41. Murata K, Abe Y, Futamura-Masudaa M, et al. Activation of cell-mediated immunity by Morinda citrifolia fruit extract and its constituents. Nat Prod Commun. Apr 2014;9(4):445-450.

  42. Ma DL, Chen M, Su CX, et al. In vivo antioxidant activity of deacetylasperulosidic Acid in noni. J Anal Methods Chem. 2013;2013:804504.

  43. Su BN, Pawlus AD, Jung HA, et al. Chemical constituents of the fruits of Morinda citrifolia (Noni) and their antioxidant activity. J Nat Prod. Apr 2005;68(4):592-595.

  44. Gupta RK, Singh N. Morinda citrifolia (Noni) alters oxidative stress marker and antioxidant activity in cervical cancer cell lines. Asian Pac J Cancer Prev. 2013;14(8):4603-4606.

  45. Gupta RK, Bajpai D, Singh N. Influence of Morinda citrifolia (Noni) on Expression of DNA Repair Genes in Cervical Cancer Cells. Asian Pac J Cancer Prev. 2015;16(8):3457-3461.

  46. Pandy V, Narasingam M, Kunasegaran T. Effect of noni (Morinda citrifolia Linn.) fruit and its bioactive principles scopoletin and rutin on rat vas deferens contractility: an ex vivo study. 2014;2014:909586.

  47. Sharma K, Pachauri SD, Khandelwal K, et al. Anticancer Effects of Extracts from the Fruit of Morinda Citrifolia (Noni) in Breast Cancer Cell Lines. Drug Res (Stuttg). Jul 9 2015.

  48. Garrido-Gallego F, Munoz-Gomez R, Munoz-Codoceo C, et al. Acute liver failure in a patient consuming Herbalife products and Noni juice. Rev Esp Enferm Dig. Apr 2015;107(4):247-248.

  49. Kang YC, Chen MH, Lai SL. Potentially Unsafe Herb-drug Interactions Between a Commercial Product of Noni Juice and Phenytoin- A Case Report. Acta Neurol Taiwan. Jun 2015;24(2):43-46.