Severe Hepatotoxicity Associated With a N‐nitrosofenfluramine‐containing Weight‐loss Supplement: Report of Three Cases

Kawaguchi, Takumi; Harada, Masaru; Arimatsu, Hidetoshi; Nagata, Shuichiro; Koga, Yuriko; Kuwahara, Reiichiro; Hisamochi, Akiko; Hino, Teruko; Taniguchi, Eitaro; Kumemura, Hiroto; Hanada, Shinichiro; Maeyama, Michiko; Koga, Hironori; Tomiyasu, Nobuo; Toyomasu, H; Kawaguchi, Motonari; Kage, Masayoshi; Kumashiro, Ryukichi; Tanikawa, Kyuichi; Sata, Michio

doi:10.1111/j.1440-1746.2003.03200.x

Cited by 20 publications

(6 citation statements)

References 3 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To test this hypothesis, the prevalence of CYP2C19 polymorphisms was examined in affected individuals; CYP2C19 is involved in N ‐nitrosofenfluramine metabolism. One of two Japanese patients tested carried the CYP2C19 poor metabolizer phenotype 14 . While this observation is consistent with the concept of a genetically determined reaction, it should be noted that up to 14% of the Japanese general population carry this metabolic variant.…”

Section: Resultssupporting

confidence: 79%

“…While this observation is consistent with the concept of a genetically determined reaction, it should be noted that up to 14% of the Japanese general population carry this metabolic variant. Further, acute hepatitis associated with Sennomotokounou has been documented in persons also carrying the CYP2C19 extensive metabolizer phenotype 14 . Therefore, a definitive relationship with a specific cytochrome polymorphism remains to be established.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Hepatotoxic slimming aids and other herbal hepatotoxins

Chitturi

Farrell

2008

J of Gastro and Hepatol

View full text Add to dashboard Cite

Perceptions of safety and/or cultural mores prompt individuals to seek herbal slimming aids in preference to conventional dietary, physical activity and medication-based protocols. In recent years, terpenoid-containing dietary supplements have been implicated in causing severe and sometimes fatal hepatotoxicity. Teucrium polium (germander) was the first of these herbal products to be clearly linked to cases of acute liver failure. Subsequently, similar hepatotoxicity has been observed with other members of the Teucrium genus. While diterpenoid-derived reactive metabolites are central to germander hepatotoxicity, it may also be that the hepatic effects of compounds such as Sho-saiko-to, Centella asiatica and Black cohosh are linked to their triterpenoid content. Other nonterpenoid-containing herbal remedies marketed for weight reduction have been causally associated with significant liver injury. Important among these are preparations containing N-nitrosofenfluramine, usnic acid and ephedra alkaloids. Finally, we review recent data on known and emerging hepatotoxins such as Boh-Gol-Zhee, Kava, pyrrolizidine alkaloids and Shou-Wu-Pian. Better public and physician awareness through health education, early recognition and management of herbal toxicity and tighter regulation of complementary/alternative medicine systems are required to minimize the dangers of herbal product use.

show abstract

Section: Resultssupporting

confidence: 79%

Section: Resultsmentioning

confidence: 99%

Hepatotoxic slimming aids and other herbal hepatotoxins

Chitturi

Farrell

2008

J of Gastro and Hepatol

View full text Add to dashboard Cite

show abstract

“…Cytochrome P450 is most commonly responsible for hepatic metabolism of drugs, and genetic polymorphisms in cytochrome P450 genes have previously be shown to result in toxic accumulation of certain drugs or metabolites. For example, toxicity associated with weight-loss supplements containing N- nitrofenfluramine has been associated with cytochrome CYP2C19 phenotypes[23]. Mitochondrial injury, suggesting of toxic accumulation of N-nitrofenfluramine, was associated with a poor metabolizer phenotype; while, mitochondrial injury was absent in extensive metabolizers of the drug.…”

Section: Discussionmentioning

confidence: 99%

Dangerous dietary supplements:Garcinia cambogia-associated hepatic failure requiring transplantation

Lunsford¹,

Bodzin²,

Reino³

et al. 2016

WJG

View full text Add to dashboard Cite

Commercial dietary supplements are marketed as a panacea for the morbidly obese seeking sustainable weight-loss. Unfortunately, many claims cited by supplements are unsupported and inadequately regulated. Most concerning, however, are the associated harmful side effects, often unrecognized by consumers. Garcinia cambogia extract and Garcinia cambogia containing products are some of the most popular dietary supplements currently marketed for weight loss. Here, we report the first known case of fulminant hepatic failure associated with this dietary supplement. One active ingredient in this supplement is hydroxycitric acid, an active ingredient also found in weight-loss supplements banned by the Food and Drug Administration in 2009 for hepatotoxicity. Heightened awareness of the dangers of dietary supplements such as Garcinia cambogia is imperative to prevent hepatoxicity and potential fulminant hepatic failure in additional patients.

show abstract

“…Excessive intake of N -nitroso-fenfluramine, which is generally used as a food supplement, has hepatotoxic effects [26,27]. Rapid depletion of ATP by impaired mitochondrial function and induction of DNA damage by the production of alkyl cations are thought to be the mechanism of N -nitroso-fenfluramine-induced cell death [28].…”

Section: Resultsmentioning

confidence: 99%

Evaluation of drug-induced tissue injury by measuring alanine aminotransferase (ALT) activity in silkworm hemolymph

Inagaki

Matsumoto

Kataoka

et al. 2012

BMC Pharmacol Toxicol

View full text Add to dashboard Cite

BackgroundOur previous studies suggest silkworms can be used as model animals instead of mammals in pharmacologic studies to develop novel therapeutic medicines. We examined the usefulness of the silkworm larvae Bombyx mori as an animal model for evaluating tissue injury induced by various cytotoxic drugs. Drugs that induce hepatotoxic effects in mammals were injected into the silkworm hemocoel, and alanine aminotransferase (ALT) activity was measured in the hemolymph 1 day later.ResultsInjection of CCl4 into the hemocoel led to an increase in ALT activity. The increase in ALT activity was attenuated by pretreatment with N-acetyl-L-cysteine. Injection of benzoic acid derivatives, ferric sulfate, sodium valproate, tetracycline, amiodarone hydrochloride, methyldopa, ketoconazole, pemoline (Betanamin), N-nitroso-fenfluramine, and D-galactosamine also increased ALT activity.ConclusionsThese findings indicate that silkworms are useful for evaluating the effects of chemicals that induce tissue injury in mammals.

show abstract

Severe Hepatotoxicity Associated With a N‐nitrosofenfluramine‐containing Weight‐loss Supplement: Report of Three Cases

Cited by 20 publications

References 3 publications

Hepatotoxic slimming aids and other herbal hepatotoxins

Hepatotoxic slimming aids and other herbal hepatotoxins

Dangerous dietary supplements:Garcinia cambogia-associated hepatic failure requiring transplantation

Evaluation of drug-induced tissue injury by measuring alanine aminotransferase (ALT) activity in silkworm hemolymph

Contact Info

Product

Resources

About