Toxicity of Dietary supplement used for weight reduction contaminated with adulterants

2. Toxicity of Dietary supplement used for weight reduction contaminated with adulterants

3. Sahar Y. Issa1,2, Essam M. Hafez 1, 3 ,Maha K. Al-Mazroua2 ,Asmaa S. Al-Banna1, Heba A. Hussain1,Mohammed G. Saad4 & Mohammed Al-Omran2 (1) Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Alexandria University, Egypt.(2 ) Dammam poison control center, (3) Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Minya University, (4) KFSH-D

4. Introduction Nowadays, dietary supplements’ consumption, especially those of plant origin, have been gaining more popularity among consumers owing to misbelieve that they are natural products posing no risks to human health. In many regions of the world, dietary supplements are legally considered as special categories of food.

5. Introduction Among the safety issues, comes adulteration by the illegal addition of pharmaceutical substances or their analogues, since unscrupulous producers can falsify these products to provide for quick effects and to increase their profits and sales.

7. Case presentation • A 40-years old male presented to the emergency department (ED) confused and excited with oliguria and discolouration of urine output (dark urine). • The patient was on a non-pharmacological traditional herbal remedy for 28 days before hospitalization, as recommended by a local herbalist to reduce his body weight. • The patient had no previous history of any suicidal attempts, drug overdose, or substance abuse.

8. Introduction • On Admission: • Blood pressure : 145/78 mmHg; • Pulse: 73/min; • Body temperature: 38.2° C. • Heart, lungs, abdomen, eyes and extremities were unremarkable . • CT brain and ECG showed normal findings.

9. Lab works Hb and hematocrit levels were 10.5 gm and 42.8% consequentively. WBC count was 23800/cu mm with a normal differentiation. The platelet count was 127000/cu mm. ESR was 17mm/hour; fibrinogen level, 169 mg/dl. The urine was dark brown with a pH of 6.8 and specific gravity of 1.035. Urine showed Proteinuria 4+, urine occult blood 2+, granular casts.

10. The urine output volume was 400 ml per day. • Blood pH was 7.2. • Serum electrolyte values were as following ; Na; 140 mEq/L, K; 5.3 mEq/l, cl; 93 mEq/l and bicarbonate 20.2 mEq/l. • Other laboratory values were BUN; 58 mg/dl, creatinine 5.1 mg/dl, glucose 161 mg/dl, albumin 4.5 g/dl, calcium 6.4 mg/dl, inorganic phosphate ll.8 mg/dl, uric acid 23.8 mg/dl, CPK 43785 U/l. • Both aspartate aminotransferase (AST) 3920 U/l, and alanine aminotransferase ALT4105 U/l.

11. Serum myoglobin value was remarkably elevated to 53,000 ng/ml (normal range less than 60 ng/dl)and urine myoglobin was 400,000 ng/ml (normal negative). Abdominal ultrasonography using Toshiba Xario 200 apparatusrevealed slightly enlarged kidneys without evidence of ureteral dilatation and enlarged liver with fatty changes. The following tests were negative: antistreptolsin O titre (ASO) titre, rheumatoid factor (RF), antinucleotid antigen (ANA), hepatitis antigen, and Human immunodeficiency virus (HIV).

12. Introduction Blood and urine samples of the patient were screened for drugs, DOA; (Amphetamine, barbiturates, benzodiazepine, cannabis, cocaine, and opiates), using ARCHITECT system c4000, model i1000 SR by ABBOTT LABORATORIES. Amphetamine was detected by IA in the given urine samples. Further confirmatory analysis was done using Gas Chromatography Mass spectrometer GC-MS–QP 2010, Shimadzu and the results were confirmed as positive for amphetamine metabolites Fig .(1)

14. Using Gas Chromatography- Head space trace GC ultra model K0C33B730000000, Milano, Italy; Ethanol and Methanol, alcohols and hydrocarbons were not detected in the given blood and urine samples. The analyses of the powder remedy using Gas Chromatography Mass spectrometer GC-MS–QP 2010, Shimadzu. , revealed Anethole, β-Elemene, γ-Elemene and amphetamine metabolites.

15. Fluid replacement and furosemide were started intravenously but urine output remained low. On the second day of hospitalization, the BUN level was 82 mg/dl and the serum creatinine level was 8.7 mg/dl. Haemodialysis was started. • After third session of haemodialysis, On the 8th day of hospitalization, the urine volume started gradually to increase and consciousness level recovered. Eighteen days post admission, BUN and creatinine values were 36 mg/dl and 2.1 mg/dl, and the haemodialysis was discontinued.

16. Discussion • Anorexigenic drugs, like amphetamines, are sometimes added illegally as aids to reduce voluntary food intake despite of their side effects. • Amphetamine administration induces disturbances in the hormonal balance, metabolism, and function of many organs and tissues. • In humans, several toxic side effects were reported in the literature, namely hyperthermia, disseminated intravascular coagulation, strokes and acute renal failure.

17. The most identifiable clinical effects of amphetamines result from the release of catecholamines, especially dopamine and norepinephrine, from the presynaptic terminals. • Common features of amphetamine toxicity include tachycardia, dysrhythmias, hypertension, hyperthermia, agitation, delirium, seizures, hyperreflexia, diaphoresis, tachypnea, and rhabdomyolysis.

18. Nephrotoxicity secondary to the use of amphetamine, and more recently ‘Ecstasy’, has been described, often in association with fibrinolysis leading to disseminated intravascular coagulation, (DIC) and hyperpyrexia. • Acute renal failure may be caused directly by the drug, by microvascular obstruction secondary to DIC, rhabdomyolysis , myoglobinuria, systemic hypotension or hyperpyrexia

19. Hepatocellular damage was reported after both acute and chronic amphetamine abuse. • Direct toxic effects, hypotension, hepatotoxic contaminants, hepatic vasoconstriction, lipid peroxidation, occult viral causes, and necrotizing angiitis were postulated as causes of amphetamine-induced hepatocellular toxicity. • Also, immune mediated mechanisms might play a role in amphetamine induced liver damage. Auto immune hepatitis like injury resolving spontaneously on drug withdrawal might be seen.

20. Rhabdomyolysis patients typically presents with muscle pain and tenderness, and is found to be in acute renal failure with hyperkalaemia, hyperphosphataemia, and raised creatine kinase. Myoglobin and granular casts are found in the urine. • Due to increased public awareness, drug abusers are becoming aware of the risk of dehydration and often drink large quantities of water after taking ecstasy to try to prevent this.

21. As a consequence, cases of hyponatraemia, catatonic states and cerebral oedema have occurred.   • The dilutional hyponatraemia, due to excessive fluid ingestion, may involve inappropriate antidiuretic hormone secretion.  • Rhabdomyolysis may be asymptomatic or present with muscle weakness or myalgias and creatinine phosphokinase (CPK) elevations.

22. More severe cases may include electrolyte imbalances and acute renal injury. • Rhabdomyolysis can be caused by trauma, extreme physical exertion, electrolyte imbalances, or certain medications. • Reports of Complementary and alternative medicine (CAM) reported acute rhabdomyolysis as a leading cause to renal dysfunction.

23. Myoglobinuria can be caused by rhabdomyolysis, due to remarkable elevation of muscle enzymes and serum myoglobin. • The mechanisms of rhabdomyolysis include: prolonged immobility, decreased muscle perfusion, coagulopathy, systemic hypotension and hyperpyrexia. • Decreased muscle perfusion led to ischemic and edemateous state. Such factors contributed to depression of muscle metabolism and rhabdomyolysis

24. Conclusion In conclusion, dietary supplements’ consumption, especially those of plant origin, has been gaining more popularity among consumers owing to misbelieve that they are natural products posing no risks to human health. In many regions of the world, dietary supplements are legally considered as special categories of food, thus are not popularly being submitted to any safety assessment prior to their commercialization, which needs further regulations.