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ADRAC

An adverse reaction to the herbal medication milk thistle (Silybum marianum)

MJA 1999; 170: 218-219
 

Introduction	There is widespread use of herbal and other complementary medicines in Australia.1 Many people believe that these products are "natural" and therefore free from side effects, but this is not necessarily the case. Various adverse reactions can occur.2 A recent publication has suggested that adverse drug reactions to herbal remedies are even more under-reported than those to conventional over-the-counter (OTC) medicines.3 The Adverse Drug Reactions Advisory Committee (ADRAC) receives and analyses reports of adverse drug reactions to complementary medicines as well as to prescribed and OTC medications, and has published reports on adverse reactions to royal jelly, chaparral and Kombucha tea.4-7
Case	A report of a severe reaction in association with milk thistle has recently been received. A 57-year-old woman presented with a two-month history of intermittent episodes of sweating, nausea, colicky abdominal pain, fluid diarrhoea, vomiting, weakness and collapse. The episodes could last up to 24 hours, but she felt completely well between attacks. The episodes were not related to food or to any obvious activity. She had been taking ethinyloestradiol and amitriptyline. The patient had no abnormalities on examination, with a regular pulse rate of 80 beats/minute and only a 6 mmHg postural drop in blood pressure. Neurological examination was normal. Differential diagnoses considered were phaeochromocytoma, carcinoid syndrome and thyrotoxicosis. She was admitted to hospital for investigation one day after an attack. Investigations revealed an initial minor elevation of urea and haemoglobin level, and raised white cell count, which were believed to be due to dehydration and reverted to normal without therapy. All other tests, including thyroid function, blood glucose level, urinary free catechol level and 5-hydroxyindolacetic acid levels, were normal and her erythrocyte sedimentation rate was 15 mm/hour. She was then questioned further about any changes to her routine in the previous two months. She admitted that she had started taking Microgenics Herbals Milk Thistle Vegicaps (Aust L 56929; Optimum Healthcare Pty Ltd) for headaches and liver cleansing exactly two months previously. On the day before admission to hospital she had taken a capsule a few hours before the onset of symptoms. On reflection, she thought that all the attacks had occurred after taking the capsules. She ceased taking milk thistle and had no further symptoms. A few weeks later she took another capsule and experienced a violent reaction similar to the one causing hospital admission.
Comment	Milk Thistle Vegicaps contain Silybum marianum (commonly known as milk thistle), a plant which is native to southern Europe, southern Russia, Asia Minor and North Africa. It now grows naturally in Australia, but the drug is largely obtained from cultivated plants. The active constituents of Silybum marianum fruit include a group of flavonolignans known collectively as silymarin.8 Silymarin consists of four isomers, with silybin accounting for 50% of the total. These substances have been studied both in vitro and in vivo and found to have antioxidant properties and to protect against light-induced skin cancer.9,10 They are also hepatoprotective in rodents. In humans, silymarin has been used to protect against poisoning with the toxic mushroom Amanita phalloides, and as both prophylaxis and treatment for liver disease.11 Silymarin has been studied in a number of prospective clinical trials.12,13 Its efficacy in liver disease is still debated, but a recent overview indicated that no serious side effects have been reported.14 The present case report describes a severe and time-associated reaction to milk thistle capsules confirmed on rechallenge. It is, however, quite possible that the problem was caused not by silybin, but by some other substance contained in the capsules. Drew and Myers point out a number of ways in which medications can cause problems because of extrinsic effects unrelated to the intended active ingredient.2 These idiosyncratic reactions are just as likely to occur with complementary medicines as with more conventional medications. ADRAC has received only two previous reports in association with milk thistle. In one, an 83-year-old man was found to be thrombocytopenic. The relation with taking milk thistle was uncertain. In the other report, a woman developed abdominal pains, nausea, listlessness and insomnia after taking milk thistle. The important message for health professionals is to take a full drug history from patients, particularly when unusual symptoms occur. It is necessary to ask directly about herbal and alternative substances as well as prescribed and OTC medications. If there is any suspicion that an adverse drug reaction has occurred it should be reported to ADRAC on a "blue card", where it will be reviewed by the Committee, collated and compared with other reactions related to complementary medicines.
References	McLennan AH, Wilson DH, Taylor AW. Prevalence and cost of alternative medicine in Australia. Lancet 1996; 347: 569-572. Drew AK, Myers SP. Safety issues in herbal medicine: implications for the health professions. Med J Aust 1997; 166: 538-541. Barnes J, Mills SY, Abbot NC, et al. Different standards for reporting ADRs to herbal remedies and conventional OTC medicines: face-to-face interviews with 515 users of herbal remedies. Br J Clin Pharmacol 1998; 45: 496-500. Bullock RJ, Rohan A, Straatmans J-A. Fatal royal jelly-induced asthma [letter]. Med J Aust 1994; 160: 44. Smith BC, Desmond PV. Acute hepatitis induced by ingestion of the herbal medication chaparral [case report]. Aust N Z J Med 1993; 23: 526. ADRAC. Harmless herbals? Aust Adv Drug React Bull 1993; 12: 11. ADRAC. Kombucha tea. Aust Adv Drug React Bull 1997; 16: 6. Bisset NG, Wichtl M. Herbal drugs and phytopharmaceuticals. A handbook for practice on a scientific basis. Boca Raton, Fla: CRC Press, 1994; 121-125. Basaga H, Poli G, Tekkaya C, Aras I. Free radical scavenging and antioxidative properties of silibin complexes on microsomal lipid peroxidation. Cell Biochem Funct 1997; 15: 27-33. Katiyar SK, Norman NJ, Muktar H, Agarwal R. Protective effects of silymarin against photocarcinogenesis in a mouse skin model. J Natl Cancer Inst 1997; 89: 556-566. Hruby K, Csomos G, Furhmann M, Thaler H. Chemotherapy of Amanita phalloides poisoning with intravenous silibinin. Hum Toxicol 1983; 2: 183-195. Ferenci P, Frank H, Benda L, et al. Treatment with silymarin decreases mortality in patients with cirrhosis of the liver. Hepatology 1984; 4: 1093. Pares A, Planas R, Torres M, et al. Effects of silymarin in alcoholic patients with cirrhosis of the liver: results of a controlled, double-blind, randomised and multicentre trial. J Hepatol 1998; 28: 615-621. Flora K, Hahn M, Rosen H, Benner K. Milk thistle (Silybum marianum) for the therapy of liver disease. Am J Gastroenterol 1998; 93: 139-143. Adverse Drug Reactions Advisory Committee PO Box 100, Woden, ACT 2606 ©MJA 1998 Make a comment
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