Pancreatitis in a woman taking an herbal supplement.

Abstract: A healthy woman developed pancreatitis after starting a popular herbal supplement designed to boost female libido. Following cessation of the herbal supplement, her enzymes quickly normalized. The patient had no risk factors for pancreatitis and anatomic obstruction was later ruled out. The contents of the supplement and their history of side effects are reviewed. As several of the ingredients are estrogenic in nature, this may have contributed to the patient's reaction. Physicians should remember to take a careful history regarding the usage of supplements and alternative medicines.

Key Words: herbal supplements, pancreatitis, herbal toxicity

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Pancreatitis is usually caused by ingestion of a toxin such as alcohol or by mechanical obstruction, but there are very few documented cases of pancreatitis caused by an herbal supplement. We present the case of a woman who developed acute pancreatitis after a one week history of herbal supplementation with a product that claimed to enhance libido.

Case Report

A 28-year-old female presented to the emergency department complaining of gradually increasing right upper quadrant pain for two days. She did not relate it to meals, and had no nausea, diarrhea, or dysuria. She was in good health, did not drink, and had no evidence of an ongoing viral infection. She did smoke 1/2 pack of cigarettes per day and had been on Depo-Provera for the last two years. Upon further questioning, she shyly admitted starting a popular supplement a week earlier--Avlimil Proprietary Blend, which claims to enhance a woman's "libido, sexual feeling, and sexual response." (1)

Physical examination revealed only diffuse pain to deep palpation of the right upper quadrant. An ultrasound revealed no biliary obstruction; acute abdominal series was also normal. Amylase and lipase levels were elevated, but her triglyceride and calcium levels were not. After she stopped the supplement, her enzyme levels gradually returned to normal without any other intervention (Table 1). A follow-up dedicated computed tomography scan performed six months later (delayed due to hurricane season) failed to reveal any anatomic source of obstruction. After obtaining consent, the patient agreed to try taking the supplement again one year later. Upon rechallenge with the supplement, the patient did not develop the same symptoms.

Discussion

Reports of pancreatitis due to herbal supplements are rare. A fatal pancreatic abscess developed in a 67-year-old man with type 2 diabetes who was taking a concoction containing Nux vomica and Rhus toxicodendron. (2) A 34-year-old man presented with an acute case of pancreatitis, which was ascribed to a mixture of 19 different ingredients including Ranuculaceae and juniper. (3)

Several of the ingredients in Avlimil contain plant phytoestrogens that bind to estrogen receptors and thus affect estrogen metabolism. Several case reports in the literature implicate increased estrogen levels in the contribution of pancreatitis, (4) including one very interesting case in which a man taking estrogen for a sex-change procedure developed pancreatitis. (5) Black cohosh, red clover, kudzu root and Valeriana root all have a weakly estrogenic effect that could influence pancreatitis. Valeriana has also been linked to liver toxicity (6) (Table 2).

Unfortunately, we cannot explain why rechallenge with the product a year later failed to reproduce the effect. It should be noted that the FDA has pursued numerous cases against herbal purveyors who have secretly tainted their libido enhancement products with prescription drugs such as Viagra and Cialis, (7) and there is no real quality control in preparing these concoctions.

Conclusion

The sales of this product have reached $110 million in its first year and spawned a host of copycat competitors. It has a slick marketing campaign that cleverly mimics those of bona fide medications; leading one to suppose it is an FDA-approved prescription medication. Its choice of ingredients is mystifying at best. For example, it claims that damiana has been proven to boost libido, but the only studies implying this have noted a slight increase in copulatory frequency and testosterone levels in male lab rats. The other ingredients seem to have been chosen for their purported stimulant effect. The study they sponsored which backs up their claims to efficacy was not properly blinded, randomized, nor cross controlled, contained only 49 participants and the results were based on self-reporting only. Most significantly, the lead researcher has said of the study that he "... would probably take [it] back, if I could." (8)

The mechanisms that can contribute to idiopathic pancreatitis are poorly understood. Likewise, female sexual dysfunction is a condition where little clinical research has been directed despite indications of its prevalence. As is the case in so many areas, when the traditional medical community offers little assistance, people may turn to supplement purveyors to seek relief, and the unregulated herbal industry is notoriously unscrupulous in taking their money with little concern for the consequences.

References

1. Avlimil Website. Available at: http://www.avlimil.com/avlimilblend.html. Accessed November 22, 2006.

2. Barquro J, Romero J, Redondo Lopez JM, et al. [Fatal acute pancreatitis in a patient who received a homepathic treatment.] Med Clin (Bare) 2004;122:318-319.

3. Kerr HD, Yarborough GW. Pancreatitis following ingestion of a homeopathic preparation. N Engl J Med 1986;314:1642-1643.

4. Blake ED, Pitcher ME. Estrogen-related pancreatitis in the setting of normal plasma lipids: case report. Menopause 2003;10:99-101.

5. Perego E, Scaini A, Romano F, et al. Estrogen-induced severe acute pancreatitis in a male. J Pancreas 2004;5:353-356.

6. Bagheri H, et al. Fulminant hepatic failure after herbal medicine ingestion in children. Therapie 1998;53:77-83.

7. FDA Public Health Advisory. Available at: http://www.fda.gov/bbs/topics/ANSWERS/2003/ANS01235.html. Accessed November 22, 2006.

8. James Blum, PhD, quoted by Bryan Reid. Bed Medicine? Washington Post, July 29, 2003, p HE01.

David Lesser, MD, CDR MC, USN, and Paul Hillesheim, DO, LT MC, USN

From the US Naval Hospital, Pensacola, FL.

Reprint requests to David Lesser, MD, CDR MC, USN, US Naval Hospital, 6000 Highway 98 West, Pensacola, FL 32512. Email: [e-mail]

Accepted August 21, 2006.

RELATED ARTICLE: Key Points

* The side effects of most herbal supplements are poorly understood.

* A toxin may be the cause of idiopathic pancreatitis when anatomic obstruction has been ruled out.

* The use of herbal supplements is growing rapidly and their use may have unintended results.

Table 1. Normalization of patient's enzymes after stopping supplement
(all values U/L)

                                  Day 0  Day 5  Day 10

Lipase                            1972   435    289
Amylase                            354   100     78
ALT (alanine aminotransferase)     342    70     32
AST (aspartate aminotransferase)   173    17     17

Table 2. Avlimil[TM] ingredients and some of their side effects

Trifolium pretense (red clover extract)
  High in isoflavones and phytoestrogens which bind to estrogen
    receptors
Pueraria montana (kudzu root)
  Isoflavones affect estrogen metabolism by weakly binding to estrogen
    receptors
Capsicum annum (capsicum pepper)
  Believed to have stimulant effects
Salvia officinalis (sage leaf)
  Believed to regulate blood circulation, has been used to reduce hot
    flashes
Glycyrrhiza glabra (licorice root)
  Used in a wide variety of herbal products for stress relief and
    increased energy. Also noted to have some mineral corticoid as well
    as estrogen-like properties. Has been linked to hypokalemia, sodium
    retention and hypertension
Turnera diffusa (damiana leaf)
  Used as an aphrodisiac for its testosterone-like properties in lab
    studies
Morella cerifera (bayberry fruit)
  Used to boost memory
Actaea racemosa (black cohosh)
  Phytoestrogen, traditionally used for postmenopausal and menstrual
    symptoms. Purported to "balance" a woman's estrogen level it
    actually has been shown to have antiestrogenic properties. Most
    common side effect is GI upset
Zingiber officinale (ginger root)
  Used for its purported stimulant and antiemetic properties
Rubus idaeus (red raspberry leaf)
  Phytoestrogens bind to estrogen receptors
Valeriana officinalis (Valeriana root)
  Noted to be hepatotoxic, it has been used for its purported sleep aid
    benefit