2406

Letters to the Editor

aids. We have now demonstrated that the diagnosis can be

made easily by direct visualization during enteroscopy, using
balloon-enteroscopy. The latest innovation in this field has
been the introduction of a single-balloon enteroscope. This
device is easier to handle and should facilitate the spread of
this technology.
In conclusion, small bowel diverticulitis can now be detected directly by enteroscopy.
Andreas Leodolter, M.D.
Dietmar Zielinski, M.D.
Daniela Borkenstein, M.D.
Manfred Crone, M.D.
Jochen Labenz, M.D.
Faculty of Medicine, University of Duisburg/Essen
Ev. Jung-Stilling Hospital
Siegen, Germany

REFERENCES
1. Miller RE, McCabe RE, Salomon PF, et al. Surgical complications of small bowel diverticula exclusive of Meckels.
Ann Surg 1970;171:20210.
2. Lee RE, Finby N. Jejunal and ileal diverticulosis. AMA Arch
Intern Med 1958;102:97102.
3. Macari M, Faust M, Liang H, et al. CT of jejunal diverticulitis: Imaging findings, differential diagnosis, and clinical management. Clin Radiol 2007;62:
737.
4. Kassahun WT, Fangmann J, Harms J, et al. Complicated small-bowel diverticulosis: A case report and review of the literature. World J Gastroenterol 2007;13:2240
2.
5. Kamal A, Gerson LB. Jejunal diverticulosis diagnosed by double-balloon enteroscopy. Gastrointest Endosc
2006;63:864.
6. Kita H, Yamamoto H. Double-balloon endoscopy for the diagnosis and treatment of small intestinal disease. Best Pract
Res Clin Gastroenterol 2006;20:17994.

Herbal Does Not At All Mean

Innocuous: The Sixth Case of
Hepatotoxicity Associated With
Morinda Citrifolia (Noni)
TO THE EDITOR: Up to two-thirds of the population report using complementary and alternative self-medication
(1) without consulting health-care professionals (2). We are
concerned about this since we have seen two cases of hepatotoxicity related to the consumption of noni juice (Morinda
citrifolia), one of which required liver transplantation (3).
Three further cases have been reported in the literature to date
(46). We herein report another patient with hepatotoxicity
related to the ingestion of noni juice and provide a summary
of all cases reported to date in order to make hepatologists
aware of the potential of noni juice to cause liver damage.
Our patient is a 43-yr-old white male who was diagnosed
with a gliobastoma in September 2007 after suffering two

seizures. He underwent surgery and was scheduled for radiation and chemotherapy in early December 2007. To aid his
recovery, he started to drink noni juice (Tahitian Noni, Tahitian Noni International UK Ltd, London, UK) in the recommended dose of 20 mL twice daily. Two weeks later, routine
prechemotherapy blood tests were performed; these revealed
elevated transaminases: aspartate-aminotransferase (AST)
192 U/L (normal <35U/L), and alanine-aminotransferase
(ALT) 516 U/L (normal <45U/L). Bilirubin remained normal (0.58 mg/dL [normal 0.11.2 mg/dL]). Liver function
tests had, however, been completely normal 3 days before
the patient started to drink noni juice (AST 17 U/L, ALT
34 U/L) and the patient did not report any symptoms at that
time. He had had no liver-related problems in the past and
had abstained totally from alcohol following the diagnosis of
gliobastoma; previously he had consumed an occasional glass
of wine. Viral hepatitis, autoimmune hepatitis, hemochromatosis, 1-antitrypsin deficiency, and Wilsons disease were
ruled out. The patient was treated with levetiracetam (500
mg twice daily) for his tumor-related epilepsy. Since liver
function tests were normal after 3 weeks therapy with levetiracetam (see above), we did not consider this medication to
be the cause of the deranged transaminases. Transaminases
dropped as soon as the patient stopped drinking noni juice.
After 6 wk, AST had decreased to 34 U/L and ALT to 70
U/L. The patient remained on treatment with levetiracetam
throughout this period. A liver biopsy was not taken because
of the patients rapid recovery.
Drug-related hepatotoxicity is the most frequent reason
for postmarketing warnings or drug withdrawal, since hepatotoxicity is such a rare event that premarketing studies often fail to detect it (7). Herbal hepatotoxicity is even more
difficult to diagnose: herbal preparations are sold over the
counter; patients do not consider them to be medication and
so do not report their use (7). Scoring systems have been
developed to assess the likelihood that a drug will cause hepatic toxicity. The two most common ones are the CIOMS
(Council for International Organizations of Medical Sciences) score (8) and the Maria & Victorino score (9). Both
scores in our case gave the result probable (CIOMS +8,
Maria & Victorino +14). So far, the mechanism of noniinduced hepatotoxicity is only speculative. Anthraquinones,
which are known to be hepatotoxic (10) and have been
found in the fruit of Morinda citrifolia, have come under
suspicion (11, 12).
With this case report, we would like to increase awareness
of herbal hepatotoxicity, especially related to the use of noni
juice. Although this case shows the mildest clinical presentation reported so far, the occurrence of hepatotoxicity most
likely related to the ingestion of noni juice had important implications for our patient, because chemotherapy could not be
started as planned and had to be delayed by 4 wk. We think
that six reported cases are more than just chance and would
like to emphasize the importance of a detailed history including self-medication when patients present with unexplained
high transaminases. We also hope that health authorities will

Letters to the Editor

2407

Table 1. Reports on Noni-Related Hepatotoxicity

Duration
of
Case Sex Age Ingestion

Amount
Ingested

Delay Between
Ingestion
and Onset
of Symptoms

Male

45 Few
1 glass per
weeks
day

Few weeks

Male

29 3 weeks 1.5 L

3 weeks

Female 62 4 months 2 L

4 weeks

Female 24 4 weeks 1-1.5L

3 weeks

Female 33 2 weeks Not stated

1 weeks

Male

43 2 weeks 2 20 ml
per day

2 weeks

Laboratory
Tests
(Maximum)

Concomitant
Medication

AST 604 U/l

ALT 1995 U/l
bilirubin 0.82
mg/dL
AST 1557 U/L
ALT 1626 U/L
bilirubin 45.3
UL/
ASL 2020 U/L
ALT 3570 U/L
bilirubin 3.9
mg(dL
AST 2818 U/l
ALT 3648 U/l
bilirubin 43.5
mg/dL
AST 3382 U/L
ALT 2740 U/L
Bilirubin 8.1
mg/dL
AST 192 U/L
ALT 516 U/L
Bilirubin 0.58
mg/dL

consider these reports when assessing the risk of novel food

and add appropriate warnings to the labels of such products.
Vanessa Stadlbauer, M.D.1
Sabine Weiss, M.D.2
Franz Payer, M.D.2
Rudolf E. Stauber, M.D.1
Departments of 1 Internal Medicine and
Neurology, Medical University of Graz
Graz, Austria

7.
8.

9.
10.

REFERENCES
1. Kessler RC, Davis RB, Foster DF, et al. Long-term trends in
the use of complementary and alternative medical therapies
in the United States. Ann Intern Med 2001;135:2628.
2. Saydah SH, Eberhardt MS. Use of complementary and
alternative medicine among adults with chronic diseases: United States 2002. J Altern Complement Med
2006;12:80512.
3. Stadlbauer V, Fickert P, Lackner C, et al. Hepatotoxicity
of NONI juice: Report of two cases. World J Gastroenterol
2005;11:475860.
4. Yuce B, Gulberg V, Diebold J, et 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.
5. Millonig G, Stadlmann S, Vogel W. Herbal hepatotoxicity:
Acute hepatitis caused by a Noni preparation (Morinda
citrifolia). Eur J Gastroenterol Hepatol 2005;17:4457.
6. Lopez-Cepero Andrada JM, Lerma Castilla S, Fernan-

11.

12.

Outcome

Presentation

Reference

None

Spontaneous
recovery

Malaise,
thoracic
discomfort

(5)

Chinese herbs

Liver transplantation

Acute liver
failure

(3)

None

Spontaneous
recovery

Diarrhea

(3)

Interferon
beta-1a

Spontaneous
recovery

Subacute liver
failure

(4)

None

Spontaneous
recovery

Levetiracetam

Spontaneous
recovery

Abdominal
(6)
pain, nausea,
vomiting,
anorexia
Routine
This report
laboratory
check-up

dez Olvera MD, et al. Hepatotoxicity caused by a Noni

(Morinda citrifolia) preparation. Rev Esp Enferm Dig
2007;99:17981.
Stickel F, Patsenker E, Schuppan D. Herbal hepatotoxicity.
J Hepatol 2005;43:90110.
Danan G, Benichou C. Causality assessment of adverse
reactions to drugsI. A novel method based on the conclusions of international consensus meetings: Application to drug-induced liver injuries. J Clin Epidemiol
1993;46:132330.
Maria VA, Victorino RM. Development and validation of
a clinical scale for the diagnosis of drug-induced hepatitis.
Hepatology 1997;26:6649.
Bironaite D, Ollinger K. The hepatotoxicity of rhein involves impairment of mitochondrial functions. Chem Biol
Interact 1997;103:3550.
Pawlus AD, Su BN, Keller WJ, et al. An anthraquinone
with potent quinone reductase-inducing activity and other
constituents of the fruits of Morinda citrifolia (noni). J Nat
Prod 2005;68:17202.
Kamiya K, Tanaka Y, Endang H, et al. New anthraquinone
and iridoid from the fruits of Morinda citrifolia. Chem
Pharm Bull (Tokyo) 2005;53:15979.

An Unusual Cause of Colonic

Obstruction
TO THE EDITOR: Medications with anticholinergic properties have long been recognized as having numerous side
effects, including urinary retention, constipation, decreased
secretion, and tachycardia (1, 2). The differential diagnosis
of acute colonic obstruction has traditionally been relatively