Severe Hepatotoxicity Associated with the Dietary Supplement LipoKinetix

Favreau, Joya T.

doi:10.7326/0003-4819-136-8-200204160-00008

Cited by 176 publications

(107 citation statements)

References 12 publications

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“…1,7,8,12,22,23 In contrast, the current (+)-UA feeding study in sheep suggests a primary myotoxic effect in ruminants. This discrepancy is not surprising considering the differences in monogastric versus ruminant physiology.…”

Section: Discussioncontrasting

confidence: 72%

Toxicity of the Lichen Secondary Metabolite (+)-Usnic Acid in Domestic Sheep

et al. 2008

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Abstract. Toxicity following ingestion of the vagrant, foliose lichen Xanthoparmelia chlorochroa was identified as the putative etiology in the death of an estimated 400-500 elk on the Red Rim-Daley Wildlife Habitat Management Area in Wyoming during the winter of 2004. A single, unsubstantiated report in 1939 attributed toxicity of X. chlorochroa in cattle and sheep to usnic acid, a common lichen secondary metabolite. To test the hypothesis that usnic acid is the proximate cause of death in animals poisoned by lichen, domestic sheep were dosed PO with (+)-usnic acid. Clinical signs in symptomatic ewes included lethargy, anorexia, and signs indicative of abdominal discomfort. Serum creatine kinase, aspartate aminotransferase, and lactate dehydrogenase activities were considerably elevated in symptomatic sheep. Similarly, only symptomatic ewes exhibited appreciable postmortem lesions consisting of severe degenerative appendicular skeletal myopathy. The median toxic dose (ED 50 ) of (+)-usnic acid in domestic sheep was estimated to be between 485 and 647 mg/kg/day for 7 days.

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Section: Discussioncontrasting

confidence: 72%

Toxicity of the Lichen Secondary Metabolite (+)-Usnic Acid in Domestic Sheep

et al. 2008

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“…For instance, usnic acid, a dietary supplement promoted for weight loss, was linked to 21 reported cases of hepatotoxicity, seven of which resulted in complete liver failure (Favreau et al, 2002;Frankos, 2005). As such, the FDA issued a warning against using supplements containing usnic acid.…”

Section: Discussionmentioning

confidence: 99%

In Vitro Hepatotoxicity and Cytochrome P450 Induction and Inhibition Characteristics of Carnosic Acid, a Dietary Supplement with Antiadipogenic Properties

Dickmann¹,

VandenBrink²,

Lin³

2012

Drug Metab Dispos

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ABSTRACT:Carnosic acid is a phenolic diterpene isolated from rosemary (Rosmarinus officinalis), which may have anticancer, antiadipogenic, and anti-inflammatory properties. Recently, carnosic acid was shown to prevent weight gain and hepatic steatosis in a mouse model of obesity and type II diabetes. Based on these results, carnosic acid has been suggested as a potential treatment for obesity and nonalcoholic fatty liver disease; however, little is known about the safety of carnosic acid at doses needed to elicit a pharmacological effect. For this reason, hepatotoxicity and cytochrome P450 inhibition and induction studies were performed in primary human hepatocytes and microsomes. Measuring cellular ATP, carnosic acid showed a dose-dependent increase in hepatotoxicity with an EC 50 value of 94.8 ؎ 36.7 M in three human hepatocyte donors without a concurrent increase in the apoptosis markers caspase-3/7. In human liver microsomes, carnosic acid did not exhibit significant time-dependent inhibition for any of the cytochrome P450 enzymes investigated, although it did inhibit CYP2C9-and CYP3A4-catalyzed reactions with K i values of 9.2 and 4.3 M, respectively. Carnosic acid also induced CYP2B6 and CYP3A4 mRNA and enzyme activity in a dose-dependent manner. At 10 M, carnosic acid increased CYP2B6 enzyme activity 61.6 and 49.3% in two donors compared with phenobarbital, and it increased CYP3A enzyme activity 82.6 and 142% compared with rifampicin. These results indicate the potential for drug interactions with carnosic acid and illustrate the need for an appropriate safety assessment before being used as a weight loss supplement.

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“…49 In two models of inflammation "an acute rat paw edema and a chronic rat cotton pellet with 100 mg/kg oral dose", the antiinflammatory action of (+)-UA was similar to ibuprofen with a similar dose. 50 Another study reported that usnic acid protects lipopolysaccharide produced mice acute lung injury by alleviating the inflammatory reactions and oxidative stress. Assessment of the anti-inflammat o ry action showed that usnic acid mitigated the expression of: "tumor necrosis factor alpha (TNF-a), interleukin-6 (IL-6), interleukin-8 (IL-8) and macrophage inflammat o ry protein-2 (MIP-2)".…”

Section: Usnic Acid As Antiinflmmatory Agentmentioning

confidence: 99%

Usnic acid biological activity: history, evaluation and usage

Alahmadi

2017

Int J Basic Clin Pharmacol

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Since Usnic acid (UA) was isolated from lichen metabolite in 1844, a lot of studies were conducted on it and now it became commercially available in the market. Its wide availability in different lichen species, being isolated easily, and high purity of the isolated product make it an excellent base for producing new pharmaceuticals. In this review the different usage of UA was summarized. It was utilized as an antioxidant, anti-proliferative, antimicrobial and antiprotozoal, larvicidal and insecticidal, antifungal, antiviral, algicidal, anti-inflammatory, pain-relieving and antipyretic agent. Many adverse effects were associated with using usnic acid, especially at high dose, including; hepatotoxicity, genotoxicity, allergenicity, side effects on the cardiovascular system and adipocytes of fatty tissue. This review aimed to throw the light on the updated biological activities, effectiveness and safety and usage of usnic acid during the last decade.

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Severe Hepatotoxicity Associated with the Dietary Supplement LipoKinetix

Abstract: The use of LipoKinetix may be associated with hepatotoxicity. Despite extensive evaluations, no other cause for hepatotoxicity could be identified in the seven patients studied.

Cited by 176 publications

References 12 publications

Toxicity of the Lichen Secondary Metabolite (+)-Usnic Acid in Domestic Sheep

Toxicity of the Lichen Secondary Metabolite (+)-Usnic Acid in Domestic Sheep

In Vitro Hepatotoxicity and Cytochrome P450 Induction and Inhibition Characteristics of Carnosic Acid, a Dietary Supplement with Antiadipogenic Properties

Usnic acid biological activity: history, evaluation and usage

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