Chinese red rice-induced myopathy.

Abstract: A middle-aged man presented with joint pain and muscle weakness that had begun 2 months before presentation. Three months before presentation, he had begun to take the herbal preparation Chinese red rice. Laboratory testing revealed a moderately elevated creatine phosphokinase level. Symptoms and laboratory abnormalities resolved with discontinuation of the Chinese red rice. Eight months later, he resumed the product and his creatine phosphokinase level rose again. Lovastatin is a naturally occurring component of Chinese red rice and was the probable cause of his myopathy.

Key Words: Chinese red rice, herbal, lovastatin, myopathy

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Herbal product use is increasing in popularity in the United States. (1) Herbal remedies are used to prevent and to alleviate symptoms of disease. (2) In 1999, the Centers for Disease Control and Prevention reported that 10% of adults used herbal preparations and 29% used some form of complementary or alternative medicine. (3) Herbal preparations are easily obtainable by the general public at most health food stores. Information regarding their use is widespread on the Internet. Herbal preparations are not required to meet the standards of other proprietary drugs, because they are marketed as dietary supplements. (3) It is a challenge for most medical professionals to maintain a working knowledge of contents and adverse effects of the various herbal preparations on the market today. However, some herbal preparations can have clinically significant adverse effects. For example, the Chinese herb Aristolochia fangchi has been reported to increase urothelial carcinoma among patients with end-stage Chinese herb nephropathy. (4) One case report described proximal muscle weakness associated with the ingestion of an herb purchased in Mexico that contained triamcinolone. (5) We report a case of symptomatic myopathy associated with the use of Chinese red rice.

Discussion

Chinese red rice was first used to make rice wine and as a food preservative during the Tang Dynasty in AD 800. (6) It is used to help improve blood circulation and decrease cholesterol and triglycerides. (6), (7) The main active ingredients in Chinese red rice are hydroxymethylglutaryl coenzyme reductase inhibitors, primarily lovastatin (also referred to as monacolin K or mevinolin). (6), (7) Some studies have shown a significant decrease in total cholesterol and reductions in low-density lipoprotein and triglycerides after 8 weeks of treatment with Chinese red rice compared with placebo. (6), (7) During and after the 8-week trial, there were no reported adverse events using the Chinese red rice. (6)

Chinese red rice has been documented to cause anaphylactic reactions, gastritis, abdominal discomfort, and elevated liver enzymes. (7) Because Chinese red rice does contain the ingredient lovastatin, it may pose the risk of rhabdomyolysis, liver damage, and kidney toxicity. (8) Patients who take this herbal supplement could develop symptoms of weakness, muscle pain, and illnesses similar to those caused by viruses. (8) However, none of those adverse reactions caused by hydroxymethylglutaryl coenzyme reductase inhibitors have been reported in association with Chinese red rice ingestion. (7)

Because the patient was also taking ginseng, its role in his symptoms must be considered. Ginseng is used in the United States to increase resistance to daily stress. (9) The main constituents of ginseng marketed in the United States are the ginsenosides or panoxosides. (9) Ginsenoside Rb-1 is found primarily in U.S. ginseng and reportedly decreases blood pressure, helps enhance gastrointestinal motility, and has an ulcer-protective effect. (9)

Although ginseng seems to have broad medicinal uses, there have been reported adverse reactions, including amenorrhea, mastalgia, and postmenopausal bleeding in women. (10) One small French study showed an increase in the CPK levels of guinea pigs that were administered ginseng in comparison with those administered placebo. (11) No human cases of myopathy have been reported.

The present case provides strong anecdotal evidence for a cause-and-effect relationship between the ingestion of Chinese red rice and the development of myopathy. The patient developed symptoms and laboratory findings of a myopathy after beginning to ingest Chinese red rice. These symptoms completely resolved after discontinuation. With resumption of Chinese red rice consumption, the patient's CPK level increased again. Although we cannot entirely exclude the possibility that his symptoms were related to the use of ginseng, ginseng-related myopathy has not been reported in humans. Furthermore, it is biologically plausible that Chinese red rice could cause myopathy, because it contains lovastatin.

Conclusion

This case illustrates two important points. First, physicians should be aware of all substances that their patients are using, not just prescription drugs. Herbal substances can have significant clinical relevance. Second, physicians should be aware that Chinese red rice can cause a clinically significant myopathy. In a patient who presents with myopathy, Chinese red rice should be considered a potential cause.

[ILLUSTRATION OMITTED]

Accepted August 11, 2003.

References

(1.) Cupp MJ. Herbal remedies: Adverse effects and drug interactions. Am Fam Physician 1999;59:1239-1245.

(2.) Eisenberg DM, Kessler RC, Foster C, et al. Unconventional medicine in the United States: Prevalence, costs, and patterns of use. N Engl J Med 1993;328:246-252.

(3.) Straus SE. Herbal medicines: What's in the bottle? N Engl J Med 2002; 347:1997-1998 (comment).

(4.) Nortier JL, Martinez MC, Schmeiser HH, et al. Urothelial carcinoma associated with the use of a Chinese herb (Aristolochia fangchi). N Engl J Med 2000;342:1686-1692.

(5.) Capobianco DJ, Brazis PW, Fox TP. Proximal muscle weakness induced by herbs. N Engl J Med 1993;329:1430 (letter).

(6.) Heber D, Yip I, Ashley JM, et al. Cholesterol-lowering effects of a proprietary Chinese red-yeast-rice dietary supplement. Am J Clin Nutr 1999;69:231-236.

(7.) Natural Medicines Comprehensive Database (on-line subscriber database). Red yeast. Available at: http://www.naturaldatabase.com/default.asp?. Accessed September 25, 2003.

(8.) WholeHealthMD, Reference Library. Red yeast rice. Available at: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10054,00.html. Accessed September 25, 2003.

(9.) Devitt M. Complementary care in the U.K.: Study finds high use of herbal medicine and acupuncture. Acupuncture Today 2000 Sep;1(9). Available at: http://www.acupuncturetoday.com/archives2000/sep/09camuk.html. Accessed September 25, 2003.

(10.) NutritionFocus web site. Wild American ginseng (click "Herbs" link under "Nutrition/Supplementation" heading on home page, then click on "Wild American ginseng" link). Available at: http://www.nutritionfocus.com/. Accessed September 25, 2003.

(11.) Anonymous. Ginseng: Muscle damage? [in Swedish]. Lakartidningen 1988;85(36):2875.

RELATED ARTICLE: Key Points

* Patients commonly use herbal products.

* Some herbal products possess clinically significant toxicity.

* In the present case, ingestion of Chinese red rice was associated with the development of a symptomatic myopathy that resolved with its discontinuation.

* Lovastatin is a naturally occurring ingredient of this preparation.

RELATED ARTICLE: Case Report

A 50-year-old white man presented to his primary care physician with a complaint of joint pain and muscle weakness. The patient had been well until approximately 2 months earlier, when he had developed pain in his left wrist and muscle discomfort in his left forearm. The muscle discomfort subsequently involved the right upper extremity. At presentation, the patient complained of diffuse body aching, upper-extremity weakness, and stiffness in his lower back. He denied acute injuries, insect bite, rashes, or recent travel. Cold weather exacerbated the symptoms, and a nonsteroidal agent helped minimally. The patient denied any infectious symptoms such as fever, chills, cough, or dysuria. There were no complaints of nausea, vomiting, or diarrhea.

His pertinent medical and social history included hypertension, mild hypercholesterolemia, anxiety, tobacco abuse, and occasional alcohol use. The patient had no family history of muscle diseases or problems. At the time of presentation, the patient was taking quinapril, clonazepam, rofecoxib, paroxetine, ginseng, and Chinese red rice. He had been taking quinapril and clonazepam for years, the rofecoxib for approximately 1 month, and the herbal supplements for 3 months.

The physical examination revealed a healthy-appearing man in no distress. His vital signs were normal. There was minimal edema of the metacarpophalangeal joint of the first digit of his left hand. During range-of-motion testing, the patient had difficulty in extending his upper extremities. His muscle strength in his hands was decreased to 4/5 bilaterally. He had normal strength testing with his upper arms, forearms, and lower extremities. There was no edema, erythema, or reproducible muscle tenderness with palpation of the upper and lower extremities. No pain was elicited with percussion of his spine. The upper- and lower-extremity pulses were normal, and he had good capillary refill. Crepitus was noted in his knees bilaterally with extension.

All laboratory tests (complete blood count, basic metabolic panel, liver function studies, thyroid-stimulating hormone, erythrocyte sedimentation rate, antinuclear antibody, rheumatoid factor, and creatinine phosphokinase [CPK]) were normal, except for a CPK level of 358 IU/L (normal range, 30-160 IU/L). According to the patient, the only new medications in his regimen were the over-the-counter herbal preparations, which he had started taking approximately 4 weeks before developing his symptoms, and rofecoxib, which he had started taking after the onset of symptoms. He was instructed to stop taking both ginseng and Chinese red rice. At the 3-week follow-up visit, his complaints of muscle weakness and joint pain had resolved completely. The CPK was rechecked and had decreased to 179 IU/L. Eight months later, the patient resumed Chinese red rice, and his CPK increased again, to 212 IU/L.

Dena James Smith, DO, and Kenneth E. Olive, MD

From the Department of Internal Medicine, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN.

Copyright [C] 2003 by The Southern Medical Association

0038-4348/03/9612-1265