Bitter Bottle Gourd (Lagenaria siceraria) Toxicity

The Journal of Emergency Medicine, Vol. -, No. -, pp. 1–4, 2013 Copyright Ó 2013 Elsevier Inc. Printed in the USA. All rights reserved 0736-4679/$ - see front matter

http://dx.doi.org/10.1016/j.jemermed.2013.08.106

Selected Topics: Toxicology BITTER BOTTLE GOURD (LAGENARIA SICERARIA) TOXICITY Cynthia H. Ho, MD,* Michael G. Ho, MD,† Shin-Pin Ho, MD,‡ and Helen H. Ho, MD§ *Los Angeles County + University of Southern California Medical Center, Departments of Internal Medicine and Pediatrics, University of Southern California, Los Angeles, California, †Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, ‡Henry Mayo Newhall Memorial Hospital, Newhall, California, and §Department of Emergency Medicine, White Memorial Medical Center, Los Angeles, California Reprint Address: Cynthia H. Ho, MD, Departments of Internal Medicine and Pediatrics, University of Southern California, 2020 Zonal Avenue, IRD Room 109, Los Angeles, CA 90033

, Abstract—Background: Bottle gourd (Lagenaria siceraria) is an edible plant in the Cucurbitaceae family. When extremely bitter, ingestion of bottle gourd can cause rapid onset diarrhea, vomiting, gastrointestinal bleeding, and hypotension due to release of a substance named cucurbitacin. Objective: Our aim was to increase physician awareness of cucurbitacin poisoning in order to facilitate accurate diagnosis and appropriate management. Case Report: Five adult patients presented with nausea, vomiting, and diarrhea within 5 to 25 min of ingesting cooked bitter bottle gourd. One patient developed severe diarrhea, hematemesis, and hypotension requiring hospitalization. All patients improved within a few days with intravenous fluids and proton pump inhibitors. To our knowledge, this is the first reported group of patients with toxicity due to ingestion of bottle gourd in the United States (US). Conclusions: Physicians should be suspicious of cucurbitacin toxicity in patients who present with symptoms within minutes of ingestion of a plant in the Cucurbitaceae family. Patients should be asked if the plant tasted unusually bitter. The most common symptoms include diarrhea and hematemesis. More than half of patients develop hypotension. There is no known antidote for bottle gourd poisoning; treatment is supportive. Proton pump inhibitors should be given to patients with gastrointestinal mucosal injury. Ó 2013 Elsevier Inc.

INTRODUCTION Bottle gourd (Lagenaria siceraria) is a plant widely grown and ingested in India and Sri Lanka. Practitioners of Ayurveda, or ‘‘life-knowledge’’ in Sanskrit, believe that drinking fresh bottle gourd juice, called lauki in Hindi, can treat hyperlipidemia, liver disease, depression, hair loss, and constipation. Indeed, studies of animal models suggest that bottle gourd may have a potential role in the treatment of cancer, depression, toxininduced liver injury, and dyslipidemia (1 4). In the United States (US), bottle gourds are primarily sold to crafting enthusiasts who use the gourds to make bowls, birdhouses, containers, and decorative figurines. With the increasing practice of complementary and alternative medicine, many Americans are treating their ailments with plant and herb preparations (5). Although many of these preparations have potential therapeutic properties, controversy surrounds Ayurveda because of adulteration of preparations, lack of standardized dosing, and improper identification of plants. Our case report represents the first known cases of toxicity due to ingestion of bitter bottle gourd in the US. CASE REPORT

, Keywords—Cucurbitaceae; cucurbitacin; hematemesis; food-borne illness; food poisoning

A family of five adults presented to the emergency department (ED) within 30 min of eating cooked bottle

RECEIVED: 16 April 2013; FINAL SUBMISSION RECEIVED: 27 July 2013; ACCEPTED: 18 August 2013 1

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gourd. The family, first-generation Chinese-American, consisted of a 64-year-old woman, her 64-year-old husband, 74-year-old brother-in-law, 72-year-old sister, and 52-year-old sister-in-law. During dinner, they ingested a dish containing cooked bottle gourd. The bottle gourd was grown in their backyard from seeds purchased at a craft store (Figure 1). Everyone noted the extremely bitter taste of the bottle gourd after one bite of the dish. All family members were healthy and denied history of previous gastrointestinal illness, anticoagulant, or nonsteroidal anti-inflammatory drug use. Within 3 to 25 min of consuming the bottle gourd, all five adults developed a sensation of gastric fullness and nausea, followed by sudden onset abdominal cramping, fecal urgency, tenesmus, and diarrhea. Diarrhea was described as watery for three patients. Two patients developed bloody diarrhea. Two patients developed vomiting that progressed to hematemesis within several hours. All five patients were managed supportively with intravenous crystalloids. After 3 h, they were discharged home with odansetron as needed for nausea and vomiting and instructions to continue oral rehydration. One day after eating the bottle gourd, all patients continued to experience anorexia and frequent watery diarrhea, more than 30 episodes each. They returned to

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the ED for worsening nausea and dehydration. Clinical features are shown in Table 1. Patient 1, 2, 4, and 5 were treated in the emergency department. Over 6 h, they were each given 2 3 L of intravenous 0.9% sodium chloride solution with improvement of symptoms and the ability to tolerate a liquid diet. Patient 3 ate the largest quantity of bitter bottle gourd. Interestingly, despite noting the bitter taste of the gourd, he reported eating several bites because he did not want to insult his sister-in-law, who had prepared the meal. He was hospitalized for severe dehydration, hypotension, and persistent tachycardia that continued despite fluid resuscitation with 3 L 0.9% NaCl solution. In our cases, the severity of illness was dose dependent and correlated with the amount of cucurbitacin ingested. On arrival to the hospital ward, Patient 3’s vital signs were as follows: temperature 36.9 C (98.4 F), pulse 121 beats/min, blood pressure 93/66 mm Hg, respirations 20 breaths/min, and oxygen saturation 98%. He appeared awake and oriented but fatigued and had several episodes of vomiting and diarrhea during the initial examination. He had mild generalized edema, most prominent in his face and extremities. Abdomen was mildly tender on palpation. Laboratory values were as follows: white blood cells 13,100/mm3, hemoglobin 14.8 g/dL, platelets 164,000/ mm3, sodium 142 mEq/L, potassium 3.4 mEq/L, chloride 114 mEq/L, bicarbonate 19 mEq/L, creatinine 0.7 mg/dL, aspartate aminotransferase (AST) 24 U/L, alanine aminotransferase (ALT) 20 U/L, and albumin 3 g/dL. During his hospital stay, he received a total of 6 L intravenous crystalloids and 60 mEq potassium supplementation. Vomiting subsided by the second day of illness but diarrhea continued for 5 days. He was discharged after 2 days in the hospital. He was seen by a gastroenterologist and was advised to complete a 2-week course of omeprazole. DISCUSSION

Figure 1. Bottle gourd, ‘‘speckled swan’’ variety, ingested by our patients.

Bottle gourds are members of the Cucurbitaceae family of plants. Other plants in the family include cucumber, zucchini, eggplant, squash, pumpkin, and bitter melon. These plants produce cucurbitacin, a pheromone that protects the plants from insects and herbivores (6). The bitter taste of the substance prevents poisoning in humans. When bottle gourds are grown under environmental stress, such as extreme temperatures and poor soil quality, they produce higher levels of cucurbitacins. Plants that are over-ripened also produce more cucurbitacins (7). Compared with other Cucurbitaceae, bottle gourds have unusually elevated levels of cucurbitacins, in particular, types B, D, G, and H. Cucurbitacins are triterpenoid substances; they are hydrophobic derivatives of triterpenes (C30H48), which are

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Table 1. Clinical Features of Our Patients 1 Day after Ingestion of Bitter Bottle Gourd Patient 1 2 3 4 5

Age (y)

Sex

Latent Period (min)

Amount Ingested

Abdominal Pain

Vomiting

Diarrhea

BP (mm Hg)

HR (bpm)

Time to Recovery (d)

74 72 64 64 52

M F M F F

20 25 3 5 15

1 bite 1 bite 6 bites 1 bite 1 bite

+ + + + +

+ + (hematemesis) -

+ (bloody) + + (bloody) + +

123/72 120/68 98/62 115/81 102/53

105 96 112 104 98

4 4 5 4 3

BP = blood pressure; bpm = beats per minute; F = female; HR = heart rate; M = male.

substances that can be found in plant resins, vegetable oils, and perfumes (8). These substances have promising roles in pharmacology; in particular, they have been shown in vitro and in vivo to have anti-tumorigenic and cytotoxic effects on breast, prostate, brain, and hematologic cancers by inducing apoptosis and cell cycle arrest (3,4). Cucurbitacin B inhibits cellular signaling pathways, such as the JAK/STAT pathway, and is a promising target for cancer therapy (Figure 2) (3). Cucurbitacin D enhances capillary permeability, which leads to persistent hypotension and capillary leak syndrome in animal models (9). Patient 3’s presentation with hypotension despite fluid resuscitation, generalized edema, and hypoalbuminemia was consistent with capillary leak syndrome. In vitro studies suggest that cucurbitacins inhibit binding of cortisol to the glucocorticoid receptor in a dose-dependent manner (9). These mechanisms might explain why patients with bottle gourd toxicity develop hypotension. Previous case reports and case series have described significant systemic and gastrointestinal effects of bottle

Figure 2. Structure of cucurbitacin B.

gourd toxicity (10,11). Symptoms occur within minutes to 1 h of ingestion. Diarrhea and hematemesis are the most common symptoms (10). Hypotension occurs in up to one half of patients (10). Three deaths have been reported in India related to bottle gourd toxicity. Laboratory abnormalities previously described include elevated AST and ALT between 200 and 400 IU/L and low serum albumin (10). Four of our patients did not have serum laboratory values drawn. Patient 3, our most severe case, had hypoalbuminemia but normal AST and ALT values. Gastrointestinal injury can vary from hyperemia to erosions and ulcerations of the esophagus, stomach, and duodenum. Gastrointestinal mucosal damage likely occurs due to a combination of the cytotoxic effect of cucurbitacins and gut hypoperfusion. Outbreaks of cucurbitacin poisoning have been described. In 1984, an outbreak of 202 cases of poisoning in California was attributed to bitter zucchini (12). In 1994, more than 100 school children in London developed gastrointestinal illness (13). The outbreak was initially attributed to mass hysteria; however, further investigations suggested an association with the ingestion

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of cucumbers served at lunch. Similar to our patients, onset of symptoms was within 1 h of ingestion. Management of bitter bottle gourd toxicity is largely supportive, with intravenous crystalloids. Vasoactive medications for blood pressure support may be needed in severe cases. Injury to the gastrointestinal mucosa should be treated with proton pump inhibitors (10). Symptoms resolve within 1 week and gastrointestinal damage resolves within 2 weeks (10). To our knowledge, our case report represents the first cases of bottle gourd toxicity described in the US. Although foodborne illness due to a bacterial preformed toxin was included in the differential diagnosis, the rapid onset within 3 25 min of ingestion of the bottle gourd was highly suspicious for cucurbitacin toxicity. Food poisoning, or foodborne illness, from enterotoxins produced by Staphylococcus aureus and Bacillus cereus typically have a longer time to onset of symptoms (1 6 h and 10 16 h, respectively) (14). In addition, symptoms typically resolve within 24 to 48 h vs. to 2 7 days with cucurbitacin toxicity (14). Limitations Because treatment is supportive, there is little utility in measuring serum or urine cucurbitacin concentrations. Diagnosis of cucurbitacin toxicity remains a clinical diagnosis, and confirmatory tests are not available at this time. Limited information is available about the adverse effects of bottle gourd ingestion and potential interaction with other drugs. CONCLUSIONS Bottle gourds are edible plants that are consumed primarily in South Asian countries. The fresh juice is consumed by practitioners of Ayurveda for its medicinal properties. However, these plants contain abnormally high levels of cucurbitacins and can be potentially toxic. Physicians should be suspicious of cucurbitacin toxicity in patients who present with symptoms within 1 h of ingestion of a plant in the cucurbitaceae family. Patients should be asked if the plant tasted unusually bitter. Very small amounts of ingestion can lead to significant symptoms. Toxicity can lead to dehydration and gastrointestinal injury. Early recognition of cucurbitacin toxicity

and differentiation from food poisoning from toxinmediated illness from S. aureus and B. cereus is important because up to 50% of cases develop hypotension requiring support with vasoactive medications. Severity may be related to amount of cucurbitacin ingested. There is no known antidote for bottle gourd poisoning; treatment is supportive. Proton pump inhibitors should be considered, given the association with significant gastrointestinal mucosal injury.

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