Clinical Toxicology, 38(1), 63–66 (2000)

Toxicity of Passiflora incarnata L.

Clinical Toxicology Downloaded from informahealthcare.com by York University Libraries on 10/04/13

Alex A. Fisher; Patrick Purcell; David G. Le Couteur

The Canberra Hospital, Garran, Australia (AAF); Therapeutic Goods

Administration, Symonston, Australia (PP); The Canberra Clinical School of the
University of Sydney, Garran, Australia (AAF; DGLC)

ABSTRACT
For personal use only.

Background: Herbal medicines may have significant adverse effects which are
not suspected or recognized. Case Report: A 34-year-old female developed se-
vere nausea, vomiting, drowsiness, prolonged QTc, and episodes of nonsus-
tained ventricular tachycardia following self-administration of a herbal rem-
edy, Passiflora incarnata L., at therapeutic doses. The possible association of
symptoms with passiflora was not recognized for several days. She required
hospital admission for cardiac monitoring and intravenous fluid therapy. Con-
clusions: Passiflora incarnata was associated with significant adverse effects in
this patient. It is important to ask specifically about the use of herbal medicines
in patients with undiagnosed illnesses.

INTRODUCTION We report a case of significant cardiovascular and gas-

Herbal remedies are an increasingly popular form of
therapy.1,2 Although promoted as natural and free from
adverse effects, herbal remedies may have serious toxic-
ity.2,3 As a result, there has been debate on whether herbal
remedies should undergo assessment of safety and effi-
cacy before being licensed for sale as a therapeutic prod-
uct.2,3 In view of these trends it is important that informa-
tion about the efficacy and toxicity of herbal products are
recognized and reported.
trointestinal toxicity following self-administration of
therapeutic doses of a herbal medication, Sedacalm . Ac-
cording to the manufacturer, 1 tablet contains an extract
of Passiflora incarnata L. (Figure 1) equivalent to 500
mg of the active ingredients. The therapeutic dose is
500–1000 mg 3 times daily.4,5 Passiflora is said to possess
sedative, hypnotic, antispasmodic, and anodyne proper-
ties. Traditionally, passiflora has been used for the treat-
ment of neuralgia, generalized seizures, hysteria, nervous
tachycardia, spasmodic asthma, and insomnia.5

Correspondence: Dr. David Le Couteur, The Canberra Clinical School of the University of Sydney, The Canberra Hospital, Yamba
Drive, Garran ACT 2605, Australia. Tel: 612/6-244-3602; Fax: 612/6-244-4036; E-mail: david_le_couteur@dpa.act.gov.au

63
Copyright  2000 by Marcel Dekker, Inc. www.dekker.com
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Clinical Toxicology Downloaded from informahealthcare.com by York University Libraries on 10/04/13
For personal use only.
Figure 1. Passiflora incarnata.
Case Report
A 34-year-old single mother took Sedacalm purchased
from a supermarket for stress. These had been prescribed
by a friend. She had been previously well apart from sur-
gery for removal of ovarian cysts and fibroids. She did
not smoke or drink alcohol.
After she had taken 3 tablets on the first day, she be-
came nauseated. On the second day after ingesting an-
other 4 tablets, she began vomiting profusely. She was
reviewed in an emergency department where it was noted
that she was afebrile with a pulse rate of 65 bpm. All
investigations including full blood count, electrolytes and
liver function tests, urine culture, and microscopy were
normal, and pregnancy test was negative. She was treated
for a presumed diagnosis of gastritis with metoclopram-
ide, prochlorperazine, droperidol, and ondansetron with
minimal improvement of nausea. She was unable to take
any more Sedacalm because of the vomiting. The follow-
ing day she returned to the hospital complaining of nau-
sea, vomiting, drowsiness, and fatigue. On this presenta-
tion, the history of Sedacalm ingestion was elicited.
REPRINTS
Fisher, Purcell, and Le Couteur
On physical examination, she was drowsy and mildly
dehydrated. She was afebrile with an irregular pulse rate
of 50 bpm and blood pressure of 180/90 mm Hg. Apart
from these findings, the rest of the examination was un-
remarkable. The electrocardiogram (ECG) revealed a
bradycardia with a rate of 43–52 bpm associated with
ventricular bigeminy and episodes of nonsustained ven-
tricular tachycardia (Figure 2a). The QT c interval was
0.539 seconds with nonspecific ST-T wave changes and
U waves more prominent in anterolateral leads (Figure
2b). Other investigations included leukocyte count
10.9 ⫻ 10 9 /mm3 (normal 4–11 ⫻ 10 9 /mm 3), sodium
140 mmol/L (normal 137–145 mmol/L), potassium 4.1
mmol/L (normal 3.5–5 mmol/L), creatinine 93 mmol/L
(normal 40–90 mmol/L), calcium 2.32 mmol/L (normal
2.10–2.55 mmol/L), and creatinine kinase 114 U/L (nor-
mal 10–200 U/L). Liver function tests were normal and
no digoxin activity was detected. She underwent cardiac
monitoring and was managed with intravenous fluids and
antiemetics. After 3 days, the vomiting had ceased and
she was discharged after her ECG including the QTc in-
terval had normalized. One week later, she reported com-
plete recovery from all symptoms.
A sample of Sedacalm taken by the patient was com-
pared with another batch of the product as well as a sam-
ple of Passiflora incarnata, digitoxin, and digoxin (Ther-
apeutics Goods Administration, Department of Health
and Aged Care). The tablets she had taken were found
to have similar chromatographic profiles to that of Pas-
siflora incarnata and other Sedacalm tablets. Neither di-
goxin nor digitoxin was detected.
DISCUSSION
The use of herbal remedies is widespread and increas-
ing. In the US, the annual sales of herbal treatments ex-
ceed $1.5 billion and this is increasing at a rate of 25%
per year.3 As many as 17% of adults report using herbal
remedies in the past year. However, because of lack of
standardization and licensing mechanisms, natural
remedies vary tremendously in content, quality, and
safety.3
In our patient, self-administration of a Passiflora in-
carnata herbal remedy for stress at therapeutic doses for
2 days was followed by severe nausea, prolonged vom-
iting, weakness, drowsiness, bradycardia, and ventricular
arrhythmia, including bigeminy and ventricular tachycar-
dia. The causality of the association is supported by the
clear temporal relationship between the use of the herbal
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Passiflora incarnata L.
Clinical Toxicology Downloaded from informahealthcare.com by York University Libraries on 10/04/13
(a)
For personal use only.
(b)
Figure 2. (a) Electrocardiogram on admission showing ventricular bigeminy and episodes of nonsustained ventricular tachycardia;
(b) Electrocardiogram on admission showing bradycardia with prolonged QT c interval, nonspecific ST and T wave changes, and U
waves.
product and the symptoms, the absence of any cardiovas-
cular or gastrointestinal comorbidities, the absence of any
other cause for this illness, and improvement with cessa-
tion of the remedy.
Passiflora incarnata (wild passionflower, maypop,
apricot vine, granadilla, passion vine) is a climbing plant
with white, blue, purple, or red flowers and yellow ovoid
fruit. It is indigenous to an area from southeast US to
Argentina and Brazil. The name passionflower dates back
to the 17th century when the mystery of a beautiful blos-
som out of an unassuming bud was compared to the Pas-
sion of Christ. Passiflora extract is prepared from the
REPRINTS
65
dried leaves, stems, and flowers. The main constituents
of the extract are flavonoids (e.g., vitexin, isovitexin, api-
genin, luteolin, isoorientin, schaftoside, isoschaftoside,
and swertisin).5 Passiflora contains harman alkaloids 6 but
the amount in most commercial preparations has been
questioned.7 For many years, passiflora has been used for
its alleged sedative, hypnotic, antispasmodic, antineural-
gic arid hypotensive action, and is now recommended to
treat nervous restlessness, tachycardia, anxiety, and in-
somnia.5
There are few reports of toxicity associated with pas-
siflora ingestion. No acute toxicity was observed after
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66
intraperitoneal injection in mice of doses greater than 900
mg/kg.8 In humans, a case of hypersensitivity with cut-
aneous vasculitis and urticara following ingestion of
tablets containing passiflora extract has been reported.9
Passiflora is associated with IgE-mediated occupational
asthma and rhinitis 10 and 5 patients required hospitaliza-
tion for reduced consciousness following passiflora in-
gestion.11 Thus, hypersensitivity and drowsiness appear
to be the major undesirable effects.
The mechanism for the toxic effects of Sedacalm in
our patient is not clear but could be attributed to the ac-
tions of the main flower ingredients, such as flavonoids
Clinical Toxicology Downloaded from informahealthcare.com by York University Libraries on 10/04/13
and harman alkaloids which have a wide variety of phar-
macological actions on the cardiovascular and central
nervous system. They induce bradycardia 12 and ventricu-
lar arrhythmias,13 interact with neurotransmitter metabo-
lism,8 and inhibit intestinal smooth muscle.14 These ac-
tions are consistent with the symptoms seen in our
patient. The question then arises as to why our patient
developed serious toxicity when the remedy is apparently
taken by many others without adverse effects. We hy-
pothesize that this patient had polymorphic variation of
xenobiotic metabolizing genes such as cytochrome P450
2D6.
For personal use only.
Finally, it is important to note that this patient did not
have a history of herbal remedy ingestion elicited until
her second presentation to the hospital after 3 days of
significant illness. This confirms the importance of
asking specifically about the use of herbal and other com-
plementary medicines in patients with undiagnosed dis-
eases.
SUMMARY
A 34-year-old female developed nausea, vomiting,
drowsiness, prolonged QT c, and ventricular arrhythmias
following self-administration of a herbal remedy con-
taining Passiflora incarnata for stress. This illness may
have been secondary to harman alkaloids found in Pas-
siflora incarnata.
REPRINTS
Fisher, Purcell, and Le Couteur
REFERENCES
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4. Blumenthal M. The Complete German Commission E
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12. Aarons DH, Rossi GV, Orzechowski RF. Cardiovascular
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Urakawa N. Inhibition of calcium channels by harmaline
and other harmala alkaloids in vascular and intestinal
smooth muscles. Brit J Pharmacol 1986;89:367–375.
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