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Home , Fish oil, Shark liver oil

LETTER TO EDITOR September-October, Vol. 11 No.5, 2012: 728-730

Shark : hidden dangers

Serta Kilincalp,* Murat Deveci,* Omer Basar,* Fuat Ekiz,* Sahin Coban,* Osman Yuksel

* Department of Gastroenterology, Diskapi Yildirim Beyazit Education and Research Hospital, Ankara, Turkey.

Dear Editor: examination was only remarkable for jaundice of the sclera and skin. An estimated 80% of the world population uses Liver function tests on admission revealed: alani- herbal and supplementary medicines. Herbal toxici- ne aminotransferase (ALT) 1,102 U/L (reference ty due to herbal products is a rare but well-known range 0-49), aspartate aminotransferase (AST) adverse event.1 However less is known about the 908 U/L (0-34), alkaline phosphatase (ALP) 248 U/L effects of other phytotherapics. Among these is (0-270), γ-glutamyl transferase (GGT) 265 U/L liver oil, a popular over-the-counter Asian (0-61), total bilirubin 9.2 mg/dL (0-1.2), direct bili- and Mediterranean folk remedy, which has been in rubin 6.3 mg/dL (0-0.2), and serum albumin 3.5 g/dL use for over 40 years as both a therapeutic and pre- (3.4-4.8). These highly abnormal results indicated ventive agent.1 that the patient was suffering from acute toxic hepatitis. A case of severe acute hepatitis caused by inges- Results of other biochemical tests, including tion of capsules is presented. No seve- serum creatinine, blood urea nitrogen, , po- re side effects in dosages of 500 mg three times a day tassium, , and , were in nor- prescribed for its immunomodulatory effects have mal limits. A complete blood cell count revealed previously been recorded. hemoglobin 13.1 g/dL, white blood cell count 4.8 x A 31-year-old woman was admitted to our Gas- 103/mm3, and platelet count 140 x 10³ cells/mL.2 Di- troenterology Department. Preliminary physical fferential white blood cell count was normal. examination revealed that she was suffering from Erythrocyte sedimentation rate was 19 mm/h, and jaundice, pruritus, new onset malaise and abdomi- prothrombin time was 16.1seconds (10.5-14.5). Uri- nal discomfort. In her medical history she denoted ne analysis revealed 2+ bilirubin and urobilinogens, that she had been taking shark liver oil capsules, 2 respectively. Creatinine clearance was 102 mL/min, times a day for two weeks. Her malaise and abdomi- 24 h urinery excretion was 18 µg/24 h (10- nal discomfort began at the end of the first week of 30),3 serum and iron binding capacity were treatment and progressed slowly over a 1-week pe- normal, and the ferritin level was 303 ng/mL (13- riod, she was also suffering from jaundince and pru- 400). ritis that began on the tenth day of treatment. She Negative results were received from tests for vi- stopped taking shark liver oil capsules and consul- ral hepatitis (hepatitis A virus IgM, hepatitis B virus ted our department.5 She said she had not consumed surface antigen and core antibody, hepatitis C any alcohol, any herbal or folk remedies, or any virus by polymerase chain reaction, and cytomega- other over-the-counter agents. No environmental is- lovirus and Epstein-Barr virus IgM), autoimmune sues were identified. She had no history of liver di- hepatitis (antinuclear antibody, anti–smooth muscle sease, elevated liver enzyme levels, jaundice, antibody, and serum γ-globulin), and Wilson’ disease. gastrointestinal bleeding, or ascites; no family his- In the abdominal ultrasonography, liver paren- tory of liver disease; and no other risk factors for li- chyma was homogeneous and the edges were regu- ver disease. Vital signs were normal. Physical lar, the vertical size of liver was 13 cm and spleen was 13 cm. Liver biopsy was not performed because of the acute-toxic hepatitis situation. Correspondence and reprint request: Serta Kilincalp, M.D. These unusual findings led us to suspect that the Anittepe mah, Isik sok 22/5, Cankaya, Ankara, Turkey recorded consumption of shark liver oil capsules had Ph.: +90 312 596 3085 led to the high toxic levels in the liver. When shark E-mail: [email protected] liver oil tablets were no longer taken, an immediate Manuscript received: October 31, 2011. improvement in the patient’s condition was seen. Li- Manuscript accepted: December 21, 2011. ver enzymes reduced rapidly and were at completely 729 Shark liver oil: hidden dangers. , 2012; 11 (5): 728-730 +1 +1 +0 +2 +0 Points 15 days +1 ≤ rus. EBV: Epstein-Barr virus. HAV: hepatitis econd exposure - causes of group I ruled out +0 55 years uses ruled out ≥ to 90 days 1 to 15 days +2 50% improvement 8 days +3 15 days Hepatocellular First exposure S < 5 or > 90 days≤ > 15 days +1 Alcohol Age Worsening or < 50% improvement 30 daysTime to onset incompatibleTime to onset compatible but with unknown reactionTime to onset compatible but known reactionRole proved in this caseNone or information not available -1 -2 -2 +0 +0 -3 > 50% improvement 30 daysNo information Fewer than 4 causes of group I ruled outNondrug cause highly probable +2 -2 -3 Reaction published but unlabeledReaction labeled in product’s characteristicsDoubling of ALT with the drug aloneDoubling of ALT with the drugs already givenat the time of first reaction Increase of ALT but less than the first administration +2 +1 +2 +1 +3 Reaction unknown diseases, EBV)] hepatotoxicity 0, excluded; 1-2, unlikely; 3-5, possible; 6-8, probable; 8, highly probable. ALT: alanine aminotransferase. CMV: cytomegalovi ≤ Causality assessment in hepatotoxicity by drugs and dietary supplements. Type of liver injury Time of onset the event Time from drug intake until reaction onset 5 Course of the reaction > Time from drug withdrawal until reaction onset Risk factors Concomitant therapy Exclusion of non drug-related causes:ca All a) Group I (HBV, HAV, HCV, alcoholism, acute recent hypotension history,hepatobiliary sonography of liver vessels)b) Group II [complications of underlying other viral causes (VZV, HSV, CMV, Previous information on 4 or 5 The 6 causes of group I ruled out +1 Response to re-administration Table 1. Total points/causality: A virus. HBV: hepatitis B virus. HCV: C HSV: herpes simplex VZV: varicella zoster 730 Kilincalp S, et al. , 2012; 11 (5): 728-730

1,200 10 2-4 ALT Recorded side effects have been negligible. In small trials, capsules up to 12 g/d (contai- 1,000 AST 8 ning 6 g/d n-3 polyunsaturated fatty acids) have T. bilirubin 800 been administered for more than 2 years without se- 6 mg/dL rious adverse events.4,6,7 Perhaps the most common

U/L 600 symptom causing discontinuation of fish oil supple- 4 ments is its “fishy taste” following eructation (bur- 400 ping). Although many people have taken shark liver oil, the issue of potential at the usual doses 200 2 has not been studied. 0 0 However a case of acute toxic hepatitis has been 01 2 8 shown to be related to the use of shark liver oil cap- Weeks sules. To our knowledge there have been no other Figure 1. Time course of liver function tests. reported cases of this kind. As a result, when presented with patients who have liver injury with no obvious cause, health care normal levels 8 weeks after the first admission. Ba- professionals should be vigilant in inquiring about sed on the labarotory findigs there was a hepatoce- the use of health supplements and alternative medi- llular type injury and the uptadated causality cines, including the use of shark liver oil. assessment in hepapoxicity by drugs and dietary su- blements scale (CIOMS) for his association was REFERENCES “probable” (score +7) (Table 1).8 The time course of the liver function tests is presented in figure 1.7-8 1. Stickel F, Patsenker E, Schuppan D. Herbal hepatotoxici- Shark liver oil has been found useful in adjuncti- ty. J Hepatology 2005; 43: 901-10. ve treatment of several types of . Fish 2. Berdel WE, Bausert WR, Weltzien HU, Modotell ML, Wid- mann KH, Munder PG. The influence of alkyl-lysophospholi- contain several active compounds that modify cell pids and lysophospholipid activated macrophages on the activity and influence various functions of the body. development of metastasis of 3-Lewis lung carcinoma. Eur Shark liver oils are rich in alkylglycerols and squa- J Cancer 1980; 16: 1199-204. lene, but contain relatively low amounts of n-3 po- 3. Finkelstein JB. do get cancer: few surprises in car- tilage research. J Natl Cancer Inst 2005; 97: 1562-3. lyunsaturated fatty acids. Virtually all species of 4. Deniau AL, Mosset P, Pédrono F, Mitre R, Le Bot D, Le- sharks are known to have an extraordinary resis- grand AB. Multiple beneficial health effects of natural tance to the growth of tumors. Several reports have alkylglycerols from shark liver oil. Mar Drugs 2010; 8: referred to an extremely low incidence of cancer in 2175-84. 5. Davidson BC, Rottanburg D, Prinz W, Cliff G. The influence sharks, some even stating that no cases of cancer in of shark liver oils on normal and transformed mammalian sharks have been recorded.3 cells in culture. In Vivo 2007; 21: 333-7. Shark liver oil has also been found useful in 6. Dosay-Akbulut M. The determination of the specific cha- treatment of conditions resulting from inadequate racteristics on the immunosurveilance against to cancer 2-4 formation in elasmobranches. Int J Cancer Res 2006; 2: immune response. Alkylglycerols may control im- 119-23. mune response possibly through modification of dia- 7. Sacks FM, Stone PH, Gibson CM, et al. Controlled trial of cylglycerol (DAG) and platelets to activating factor fish oil for regression of human coronary atherosclerosis. (PAF) production.6 Alkylglycerols and squalene, en- HARP Research Group. J Am Coll Cardiol 1995; 25: 1492. 8. Teschke R, Schwarzenboeck A, Hennermann KH. Causality hance antigen presentation and induction of inflam- assessment in hepatotoxicity by drugs and dietary suple- matory response.5,6 ments. Br J Clin Pharmacol 2008; 66: 758-66.