Acute toxic hepatitis and acute renal failure in diabetic patients using raw sheep bile as an unconventional remedy for diabetes

Recent reports of acute hepatic and renal toxicity in Asians who drank raw bile from fish (grass carp) in the United States suggested a potential danger to diabetic patients in southwestern Saudi Arabia who had been advised by a traditional healer to drink raw sheep bile as a cure for diabetes. To assess the possibility that raw sheep bile was also toxic we investigated this practice in Al-Wadein village (population 5640) in the Asir.

From the 73 diabetic patients using two village Primary Health Care Centers, 30 who had used traditional medicine for diabetes were selected. We interviewed these diabetics about underlying illnesses, drinking bile and illnesses that immediately followed. From medical records we obtained serum chemistries taken over the year before the bile exposure (baseline), immediately after, and two months after bile exposure.

Fourteen of the 30 diabetics (age 53 to 78) who had used traditional medicine (including five on dialysis for chronic renal failure) reported that they had tried drinking sheep's bile to cure diabetes once during a four year period. This was done during the Eid holidays when slaughter of sheep was common and bile readily available. Two patients drank a minimum of 15 ml of bile while those who could tolerate it drank as much as 210 ml of bile over one to seven consecutive days. All 14 drank from 15 to 30 ml of bile after awakening in the morning before breakfast.

All 14 patients developed nausea and anorexia immediately after drinking the bile and the 12 who drank more than 15 ml also developed vomiting with diarrhea (six with blood) within 36 hours. All remained afebrile. All 14 sought medical treatment and 12 were hospitalized for gastrointestinal symptomatology during the week after drinking bile. One became oliguric and another comatose but none died.

Stool cultures on 13 yielded no pathogens. After (<1 week) drinking bile mean serum ALT was 295 U/l compared to a baseline of 27 U/I (P<0.001, paired t-test). Serum bilirubin, AST and alkaline phosphatase showed similar elevations. Attending physicians evaluated all patients for hepatitis infection. However, anti-HAV IgM, HBsAg and anti HCV were all negative. Patients also showed evidence of renal toxicity. Following exposure, the mean BUN was 144 mg/100m1 compared to a baseline of 77 mg/100 ml (P<0.001, paired t-test) and the mean creatinine was 6 mg/100m1 compared to a baseline of 0.9 mg/100m1 (P<0.001, paired t-test). Since several had underlying diabetic renal disease attending physicians had not further evaluated renal function. There was a dose response effect both serum ALT (r=0.88, 95%, CI 0.76 to 0.96), and creatinine (r=0.63, 95% CI 0.34 to 0.81) increased in a direct linear relationship in proportion to an increasing dose of bile. (Figure 1.) All biochemical indicators of hepatic and renal toxicity returned to baseline levels two months after the acute illness. Mean baseline ALT, AST, alkaline phosphatase, serum bilirubin BUN, serum creatinine and blood glucose of the 14 who drank bile and 16 who did not drink bile were the same. All patients had stopped insulin or oral antidiabetic medications during the bile treatment. Following exposure, the mean blood glucose (random blood sugar) was 253 mg/100 ml compared to a baseline of 196 (p<0.01, paired t-test). However, serum glucose did not increase, nor was it otherwise related to the amount of bile drunk.

The similarity of the reaction of these diabetic patients to sheep bile and the toxicity described from carp bile suggests a common toxic component of bile.[1,2) However, smaller quantities of carp bile than sheep bile were involved. The hepatotoxic and nephrotoxic components of carp bile have been shown to be in fractions of bile containing principally bile salts and bile acids.[3] In humans, bile salts will cause diarrhea in disease states that allow bile salts to reach the colon.[4] Hydrophobic bile salts are also known as cytotoxins.[5] Bile salts are conserved through an enterohepatic circulation with reabsorbtion in the ileum. Since they are recycled six times in 24 hours the total bile salt pool in the human is relatively small. Thus, the amounts of sheep bile drunk by these diabetic patients could potentially contain sufficient cytotoxic bile salts to overload this enterohepatic circulation and produce the observed toxicity.

As illustrated by this investigation, unconventional treatment can present a danger to the patient by direct toxicity. In this investigation the patients also neglected their prescribed antidiabetic medication, and demonstrated poor control of blood sugar. Even if unconventional medicines are effective the preparations are not standardized, so incorrect dosing is a common problem. The scope of this investigation was limited to only one village. However, the healer who promoted this remedy had disseminated his message widely. Thus, the sheep bile remedy and other potentially dangerous practices may be widespread. Physicians in Saudi Arabia should routinely question patients about unconventional therapy and report any suspect toxicity or other adverse events from these therapies. In order to define the extent of the bile remedy, physicians are asked to identify and report to the Ministry of Health any incident involving the drinking of bile for the treatment of any condition.