Review of Abnormal Laboratory Test Results (part 4)

Abnormal Laboratory Test Results Due to Toxic Effects of Herbal Medicines

Kava-Kava and Abnormal Liver Function Test Results. Kava is an herbal sedative with a purported antianxiety or calming effect. Kava is prepared from a South Pacific plant (Piper mesthysticum). The main bioactive compounds include yangonin, desmethoxyyangonin, 11-methoxyyangonin, kavain, and dihydroxykavin. These components are present in the lipid-soluble kava extract or kava resin.

Kava can have additive effects with central nervous system depressants. A patient who was taking alprazolam (Xanax), cimetidine, and terazosin became lethargic and disoriented after ingesting kava. Kava lactones can inhibit cytochrome P-450 activities and have a potential for interaction with drugs that are metabolized by the liver. Heavy consumption of kava has been associated with increased concentrations of -glutamyltransferase. Escher et al described a case in which severe hepatitis was associated with kava use. A 50-year-old man took 3 to 4 kava capsules daily for 2 months (maximum recommended dose, 3 capsules). Liver function tests showed 60- to 70-fold increases in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) concentrations. Blood tests were negative for hepatitis, cytomegalovirus, and HIV. The patient eventually received a liver transplant. Because of the potential for toxic effects on the liver, the FDA warned the public against the use of kava-kava.

Chaparral and Abnormal Liver Function Test Results. Chaparral can be found in health food stores as capsules and tablets and is used as an antioxidant and an anticancer herbal product. Leaves, stems, and bark also are available in bulk for brewing tea. Chaparral-associated hepatitis has been reported. A 45-year-old woman who took 160 mg/d of chaparral for 10 weeks sought care because of jaundice, anorexia, fatigue, nausea, and vomiting. The results of liver enzyme and other liver function tests were abnormally high (ALT, 1,611 U/L; AST, 957 U/L; alkaline phosphatase, 265 U/L; g-glutamyltransferase, 993 U/L; and bilirubin, 11.6 mg/dL [198 µmol/L]). Viral hepatitis, cytomegalovirus, and Epstein-Barr virus were ruled out. Liver biopsy showed acute inflammation with neutrophil and lymphoplasmacytic infiltration, hepatic disarray, and necrosis. Gordon et al reported a case in which hepatitis developed in a 60-year-old woman owing to the use of chaparral for 10 months. Despite aggressive therapy, the condition of the patient deteriorated, and she required orthotopic liver transplantation. Other cases of toxic effects on the liver due to chaparral have been reported. The FDA has warned the public about the dangers of consuming chaparral.

Mistletoe and Liver Damage. Mistletoe is a parasitic evergreen plant that lives on trees such as oaks, elms, firs, pines, and apple. Mistletoe was used in folk medicine as a digestive aid, heart tonic, and sedative. Mistletoe berries are poisonous. In a 49-year-old woman with nausea, general malaise, and dull abdominal pain, the results of liver function tests suggested hepatitis (ALT, 123 U/L; lactate dehydrogenase, 395 U/L; AST, 250 U/L). Liver biopsy also suggested hepatitis. However, all serologic tests for hepatitis were negative. The patient had drug-induced hepatitis probably due to mistletoe.

Germander and Elevated Liver Enzyme Levels. Germander has been used as a remedy for weight loss and as a general tonic. Germander tea is made from the aerial parts of the plant and has been in use for centuries. Capsules made from germander powder also are available in health food stores. Twenty-six cases of germander-induced hepatotoxicity have been reported in Europe. A 55-year-old woman taking 1,600 mg per day of germander became jaundiced after 6 months. Laboratory results were as follows: bilirubin concentration, 13.9 mg/dL (238 µmol/L); AST, 1,180 U/L; ALT, 1,500 U/L; alkaline phosphatase, 164 U/L. Serologic tests for all types of hepatitis were negative. A liver biopsy suggested drug-induced hepatitis. Germander therapy was discontinued, and the hepatitis resolved in 2 months. Acute cholestatic hepatitis with the transient appearance of antimitochondrial antibody also has been reported due to germander.

Comfrey and Liver Damage. The regular use of comfrey is a potential health risk owing to the presence of pyrrolizidine alkaloids. These alkaloids have hepatotoxic effects in animals and humans and also induce tumors in animals. Ridker et al documented hepatic veno-occlusive disease associated with consumption of comfrey roots. Long-term studies in animals have confirmed the carcinogenicity of comfrey in animal models. A study showed that phenobarbital induced the metabolism of pyrrolizidine alkaloids to a lethal metabolite. Stickel and Seitz commented on serious hazards associated with the use of comfrey.

Kelp and Abnormal Thyroid Profile. Kelp (seaweed) tablets are available in health food stores and are used as a thyroid tonic, an anti-inflammatory, and a metabolic tonic. Kelp tablets are rich in vitamins and minerals but also contain a substantial amount of iodine (each tablet contains approximately 0.7 mg of iodine). A 72-year-old woman with no history of thyroid disease had the typical symptoms of hyperthyroidism. She had been taking 4 to 6 kelp tablets a day for 1 year. Her thyrotropin concentration was low (1.3 µIU/L); the total thyroxine level was 14.4 µg/dL (185.3 nmol/L; reference range, up to 12.4 µg/dL [160 nmol/L]); and the total triiodothyronine level was 284 ng/dL (4.38 nmol/L; reference range, 69-219 ng/dL [1.07-3.38 nmol/L]). After discontinuing the kelp tablets, her hyperthyroidism resolved, and thyroid function test results returned to normal (thyrotropin, 3.1 µIU/L; total thyroxine, 8.4 µg/dL [108.1 nmol/L]; total triiodothyronine, 140 ng/dL [2.15 nmol/L]).

Chromium and Hypoglycemic Herbs: Abnormally Low Glucose Concentrations. Athletes and body builders use chromium for improving performance. Chromium is a trace metal that has an effect on the glucose-insulin system. Bunner and McGinnis described a case in which a 29-year-old man was referred to the outpatient neuropsychiatry clinic because of his unusual behavior at work. The patient had been diagnosed with diabetes mellitus at the age of 20 years and was taking 9 U of NPH insulin (Humulin N) per day. His blood glucose concentrations ranged between 90 and 120 mg/dL (5.0-6.7 mmol/L). During the episode, he was agitated, and on admission to the hospital, his blood glucose concentration was 30 mg/dL (1.7 mmol/L). The patient was taking 200 to 300 µg of chromium 2 to 3 times per week for bodybuilding, and the hypoglycemic episode most likely was linked to chromium use. Anderson reviewed the effect of chromium on the glucose-insulin system in subjects with hypoglycemia, hyperglycemia, diabetes mellitus, and hyperlipidemia. Ginseng, whose activity has been attributed to 2% to 3% ginsenosides, has been associated with hypoglycemic properties. Fenugreek, ginger, nettle, sage, and devil's claw also can affect glucose levels. Karela has been shown to improve glucose tolerance.

Zhang et al reported that male subjects showed a significant reduction in the glucose concentration after taking garlic oil, but female subjects showed an increase. However, a small adverse effect on the lipid profile was observed in male subjects, while females had beneficial effects on the lipid profile following the use of garlic oil for 11 weeks.

Licorice and Hypokalemia. Fifty-nine licorice-induced hypokalemic myopathy cases have been reported. Laboratory findings include a mean serum potassium concentration of 1.98 mEq/L (1.98 mmol/L), a mean total creatine kinase concentration of 5,383 U/L, plasma aldosterone activity of 2.92 ng/dL (0.08 nmol/L), and a mean plasma renin activity of 0.17 ng/mL/h (0.13 · L-1 · h-1). Licorice-induced pseudoaldosteronism also has been reported.[64] Licorice contains glycyrrhizic acid, which inhibits the enzyme 11--hydroxysteroid dehydrogenase (converts cortisol to cortisone). Therefore, concentrations of cortisol may increase. Renin activity and aldosterone concentrations in serum usually decrease.

Lead Poisoning Due to Herbs: Abnormal Laboratory Test Results. Unexpected lead poisoning may occur owing to the use of herbal medicines contaminated with lead. Anderson et al reported a case of lead poisoning in a 23-year-old man with a 5-day history of severe, diffuse abdominal pain, vomiting, and diarrhea followed by constipation. The laboratory investigation showed elevated bilirubin and alanine transaminase concentrations, but the alkaline phosphatase activity was normal. The urinary porphyrin screen was positive, indicating the possibility of acute porphyria. Further investigation showed elevated concentrations of zinc protoporphyrin (145 µmol/L; reference range, <70 µmol/L) and lead (77 µg/dL [3.7 µmol/L]). The patient was taking an herb purchased in India. After discontinuation of the herbal medicine, his blood concentrations of lead and zinc protoporphyrin were reduced significantly. Wu et al reported 2 cases of lead poisoning due to the Chinese herbal medicine Cordyceps. One patient had a blood lead concentration of 130 µg/dL (6.3 µmol/L), and another patient had a lead concentration of 46 µg/dL (2.2 µmol/L). The lead content in the Chinese medicine was found to be as high as 20,000 ppm.