Supplement induced liver injuries – the overview

Supplements containing green tea extract are the subject of many reports of liver toxicity. Several cases of liver toxicity have also association with green tea “infusions.” There is only one reported case of liver toxicity from drinking brewed green tea.  

A number of reports suggest kava, often taken for anxiety or insomnia, may cause liver damage (Sarris, Aust N Z J Psychiatry 2011). Occasionally, liver damage has been reported even with normal doses. For this reason, some countries have banned the sale of kava – although it is still available in the U.S.  

Three cases of acute hepatitis have been reported with the use of CLA (conjugated linoleic acid) supplements – which are used for slimming.

Several cases of liver failure, one of which required a liver transplant, have been linked with drinking noni, although it was not conclusively determined that noni was the cause.

Too much vitamin A can cause liver damage, as can high doses of niacin. (Be aware that energy drinks and shots often contain high doses of niacin, and a case of acute hepatitis due to excessive intake of niacin from energy drinks has been reported.)

Like prescription statins, red yeast rice (which naturally contains lovastatin) can alter liver function.

High doses of CBD (cannabidiol) may cause abnormal results on liver-function tests. (CBD has also been reported to cause elevated liver enzymes in dogs)…

Source: https://www.consumerlab.com/answers/which-supplements-can-cause-liver-toxicity/liver-toxicity/;

The liver is the first line of defense against toxins that enter the body. It removes them from the bloodstream before they can reach other organs and be harmful. That doesn’t mean the liver is able to process toxins without any ill effects; some substances will do harm to the liver. In only rare cases does the long-term use of medications cause cirrhosis of the liver or chronic liver damage.
However, there are medications and supplements that when taken alone, or mixed with other medications or substances, can cause liver damage.
Liver damage or injury from use or overuse of medications or supplements may be a challenge to diagnose.
Often the cause of a drug-induced liver disease is quite apparent to physicians, but in some cases, other causes for liver disease, such as hepatitis, cancer, metabolic disease, or vascular disease, may need to be ruled out first.
The medication or supplement that is suspected to be the cause of the liver damage will need to be stopped in order to confirm the diagnosis.
The signs and symptoms of liver damage or injury from medications should be taken seriously and investigated right away. These include:
Abdominal pain and swelling
Disorientation or confusion
Fever
Jaundice (yellow eyes and skin, dark urine)
Nausea and Vomiting
Severe fatigue or sleepiness

https://www.thailandmedical.news/news/common-drugs-and-supplements-that-can-cause-liver-damage

Herb induced liver injury (HILI) and drug induced liver injury (DILI) share the common characteristic of chemical compounds as their causative agents, which were either produced by the plant or synthetic processes. Both, natural and synthetic chemicals are foreign products to the body and need metabolic degradation to be eliminated. During this process, hepatotoxic metabolites may be generated causing liver injury in susceptible patients. There is uncertainty, whether risk factors such as high lipophilicity or high daily and cumulative doses play a pathogenetic role for HILI, as these are under discussion for DILI. It is also often unclear, whether a HILI case has an idiosyncratic or an intrinsic background. Treatment with herbs of Western medicine or traditional Chinese medicine (TCM) rarely causes elevated liver tests (LT). However, HILI can develop to acute liver failure requiring liver transplantation in single cases. HILI is a diagnosis of exclusion, because clinical features of HILI are not specific as they are also found in many other liver diseases unrelated to herbal use. In strikingly increased liver tests signifying severe liver injury, herbal use has to be stopped. To establish HILI as the cause of liver damage, RUCAM (Roussel Uclaf Causality Assessment Method) is a useful tool. Diagnostic problems may emerge when alternative causes were not carefully excluded and the correct therapy is withheld. Future strategies should focus on RUCAM based causality assessment in suspected HILI cases and more regulatory efforts to provide all herbal medicines and herbal dietary supplements used as medicine with strict regulatory surveillance, considering them as herbal drugs and ascertaining an appropriate risk benefit balance.

Listing compilation of TCM herbs and herbal products with reported hepatotoxicity.

Chinese NameBotanical Names, Ingredients
● Ai YeArtemisia argyi
● An Shu LingLycopodium serratum or rarely, Corydalis speciesPanax ginseng, Pseudo ginseng, or two species of Stephania
● Bai FangAngelica sinensisCyperus rotundus, Ginseng, Ligusticum wallichiiPaeonia albaRehmannia glutinosa
● Bai Shi WanAtractylisCarthamus tinctoriusDalbergia odoriferaDioscorea bulbiferaGlycyrrhizaLithospermum erythrorhizonPaeonia suffruticosaPolygonum multiflorumPsoralea corylifoliaSalvia miltiorrhizaEndoconcha sepiaeGanoderma lucidum (mushroom)
● Bi Ma ZiRhicinus communisChaenomelesCodonopsis pilosulaNotopterygiumPolygonum multiflorumRehmanniaSchisandra
● Bo HeMentha haplocalyx
● Bo Ye Qing Niu DanTinospora crispa
●Bofu Tsu Sho SanAngelicaAtractylisCnidiumGardeniaEphedraForsythiaGlycyrrhhizaGypsum fibrosumLedebouriellaMenthaPaeoniaPlatycodonRheumSchizonepetaScutellariaZingiber; Kadinum (talcum powder), sodium sulfuricum
● Boh Gol ZheePsoralea corylifolia
● Cang Er ZiXanthium sibiricum
● Chang ShanDichora febrifuga Lour
● Chai HuBupleurum falcatum
● ChasoCamellia sinensisCassia tora (syn. Senna), CrataegusN-nitroso-fenfluramine
● Chi R YunBreynia officinalis
● Chinese herbal mixtures (various)Dictamnus dasycarpusGentiana scabraHedyotis diffusaPaeonia suffructicosaParis polyphyllaRehmannia glutinosa, Smilax glabraSophora subprostrataAngelica sinensisBupleurum chineseDictamnus dasycarpusPaeonia suffructiosaPhilodendron chineseSaposhnikovia divaricata,Shisandra chinesisShizonepeta tenuifoliaTribulus terrestrisCocculus trilobusDictamnus dasycarpusEurysolen gracilisGlycyrrhizaLophatherumPaeoniaPotentillaRehmannia glutinosaAlisma plantago aquaticaArtemisia capillarisBupleurum, Chrysanthemum morifoliumCircumaGardenia jasminoidisGentiana scabraGlycyrrhizaMagnoliaPaeoniaPlantago asiaticaSaussurea lappa
● Chuan Lian ZiMelia toosendan
● Ci Wu JiaAcanthopanax senticosus
● Da Chai Hu TangBupleurum falcatumGinsengGlycyrrhiza glabraPinelliaScutellariaZingiber officinaleZizyphus jujuba
● Da HuangRheum palmatum
● Du HuoAngelica archangelica
● Fu Fang Qing Dai WanAngelica dahurica, Isatis indigotica (Indigo naturalis), Massa medicata fermentata (yeast), Salvia milthiorrhizaSmilax glabra
● Gan CaoGlycyrrhiza uralensis, syn. Liquorice
● Ge GenPueraria lobata, syn. Arrowroot
● He Huan PiAlbizia julibrissin
● Ho Shou WuPolygonum multiflorum, syn. He Shou Wu
● Hu Bohe YouMentha pulegium, syn. Pennyroyal oil
● Hu ZhangPolygonum cuspidatum
● Huang QinScutellaria baicalensis
● Huang Yao ZiDioscorea bulbifera
● Hwang Geun ChoCorydalis speciosa
● Ji Gu CaoAbrus cantoniensis
● Ji JiChloranthus serratus
● Ji Xue CaoCentella asiatica, syn. Gotu Kola
● JigujaHovenia dulcis
● Jin Bu HuanLycopodium serratum or rarely, Corydalis speciesPanax ginseng, Pseudo ginseng, or two species of Stephania
● Jue Ming ZiCassia obtusifolia, syn. Senna
● KamishoyosanAngelica sinensisAtractylodes raceaBupleurum falcatumGardeniaGlycyrrhiza glabraMentha haplocalyxMoutanPaeonia albaSclerotium Poriae CocosZingiber officinale
● KudzuPueraria thunbergiana
● Ku Lian ZiMelia azedarach
● Lei Gong TengTripterygium wilfordii Hook
● Long Dan Xie Gan TangAcebiaAlismaAngelica sinensisBupleurumGardeniaGentianaGlycyrrhizaPlantagoRehmanniaScutellaria
● Lu ChaCamellia sinensis, syn. Chinese green tea
● Ma HuangEphedra sinica
● Mao Guo Tian Jie CaiHeliotropium lasiocarpum
● OnshidoAloeCamellia sinensisCrataegus, Gynostemma pentaphyllum makinoRaphanusN-nitroso-fenfluramine
● Qian Li GuangSenecio scandens
● Ren ShenPanax ginseng
● Sairei ToAlismaAtractylisBupleurumCinnamomumGinsengGlycyrrhizaPinelliaPolyporusPoriaScutellariaZingiberZizyphus
● Shan ChiGynura segetum
● Shang LuPhytolacca acinosa
● Shen MinBlack cohosh, Burdock, Cayenne pepper, Ginkgo biloba, Horse chestnut, Piper nigrumPolygonum multiflorumuva ursi; biotin, collagen (hydrolyzed), niacin, pantothenic acid, silica (from plant sources), soy isoflavones, vitamin A, vitamin B6
 Shi CanTeucrium chamaedrys, syn. Germander
● Shi Liu PiPericarpium granati
● ShouWu PianAchyranthes bidentataCuscuta chinensisEclipta prostrataLigustrum lucidumLonicera japonicaMorus albaPolygonum multiflorumPsoralea corylifoliaRehmannia glutinosaRosa aevigatSesemum indicumSiegesbeckia orientalis
● Tian Hua FenTrichosanthes kirilowii
● White floodQian Ceng Ta (Huperzia serrata), Wu Zhu Yu Evodia rutaecarpa); beet root, caffein, cocoa bean, vinpocetine (from Vinca plant); acesulfame potassium, calcium silicate, carnitine tartrate, Carno-Syn® beta-alanine, citrulline, cryptoxanthin, folic acid, gamma-aminobutyric acid (GABA), glucuronolactone, selenium, L-norvaline, L-tyrosine, lutein, malic acid, ornithine, potassium gluconate, sucralose, sugar cane, watermelon flavor, zeaxanthin
● Wu Bei ZiGalla chinensis
● Xi ShuCamptotheca acuminata
● Xian Si ZiAbrus Precatorius
● Xiao Chai Hu TangBupleurum falcatumGinsengGlycyrrhiza glabraPinellia tuberScutellaria baicalensisZingiber officinaleZizyphus jujuba
● Yin Chen HaoArtemisia capillaris
● ZexieAlisma orientalis
● Zhen Chu CaoPhyllanthus urinaria

Conclusions

Herbal use is highly appreciated around the world to treat various health conditions. Many herbal products are easily accessible via the internet and thus can escape regulatory surveillance. Concomitantly, herb induced liver injury emerges as a clinical problem and can evolve into acute liver failure in rare cases. Clinical signs are often non-specific and there is no diagnostic feature that delineates HILI from alternative causes of liver damage. Therefore, the diagnosis of HILI is one of exclusion and the RUCAM score can aid the clinician to establish causality. Furthermore, assessment according to RUCAM facilitates evaluation of published cases and provides useful information for authorities to regulate the marketing of herbal products. Clinical studies to evaluate the benefit/risk balance of herbal drugs are encouraged. Finally, all herbal products and herbal dietary supplements used as medicine should be under a more strict regulatory surveillance, considering these products as herbal drugs.

Source: Frenzel C, Teschke R. Herbal Hepatotoxicity: Clinical Characteristics and Listing Compilation. Int J Mol Sci. 2016 Apr 27;17(5):588. doi: 10.3390/ijms17050588. PMID: 27128912; PMCID: PMC4881436.

Background: Herbal and dietary supplements are commonly used throughout the World. There is a tendency for underreporting their ingestion by patients and the magnitude of their use is underrecognised by Physicians. Herbal hepatotoxicity is not uncommonly encountered, but the precise incidence and manifestations have not been well characterised.

Aims: To review the epidemiology, presentation and diagnosis of herbal hepatotoxicity. This review will mainly discuss single ingredients and complex mixtures of herbs marketed under a single label.

Methods: A Medline search was undertaken to identify relevant literature using search terms including ‘herbal’, ‘herbs’, ‘dietary supplement’, ‘liver injury’, ‘hepatitis’ and ‘hepatotoxicity’. Furthermore, we scanned the reference lists of the primary and review articles to identify publications not retrieved by electronic searches.

Results: The incidence rates of herbal hepatotoxicity are largely unknown. The clinical presentation and severity can be highly variable, ranging from mild hepatitis to acute hepatic failure requiring transplantation. Scoring systems for the causality assessment of drug-induced liver injury may be helpful, but have not been validated for herbal hepatotoxicity. Hepatotoxicity features of commonly used herbal products, such as Ayurvedic and Chinese herbs, black cohosh, chaparral, germander, greater celandine, green tea, Herbalife, Hydroxycut, kava, pennyroyal, pyrrolizidine alkaloids, skullcap, and usnic acid, have been individually reviewed. Furthermore, clinically significant herb-drug interactions are also discussed.

Conclusions: A number of herbal medicinal products are associated with a spectrum of hepatotoxicity events. Advances in the understanding of the pathogenesis and the risks involved are needed to improve herbal medicine safety.

Source: Bunchorntavakul C, Reddy KR. Review article: herbal and dietary supplement hepatotoxicity. Aliment Pharmacol Ther. 2013 Jan;37(1):3-17. doi: 10.1111/apt.12109. Epub 2012 Nov 5. PMID: 23121117.

The increase in the use of herbal and dietary supplements (HDS) over the last decades has been accompanied with an increase in the reports of HDS associated hepatotoxicity. The spectrum of HDS induced liver injury is diverse and the outcome may vary from transient liver test elevations to fulminant hepatic failure resulting in death or requiring liver transplantation. There are no validated standardized tools to establish the diagnosis, but some HDS products do have a typical clinical signature that may help to identify HDS induced liver injury.

Use and mechanism of specific HDS products

HerbalsCommon useMechanism and commentsReferences
Anabolic steroidsbodybuilding,
weight training, or
athletics
unknown(40)
Black cohosh
(Cimicifuga/Actaea
racemosa)
joint aches,
myalgia and
menopausal
symptoms
unknown
possibly adultrated with Actaea
pachypoda Ell. (white cohosh) and
Actaea podocarpa DC. (yellow
cohosh)
(46)
Chaparral (Larrea
tridentata)
antioxidant
properties, anti-
inflammatory,
liver disease, skin
disorders
unknown
possibly, interference with cyclo-
oxygenase or CYP450, estrogen-like
activity
(84)
Green tea extracts
(Camellia sinensis)
weight lossepigallocatechin gallate (EGCG)
toxicity is possibly heightened in
individuals with a genetic
predisposition
(54)
Pyrrolizidine
alkaloids/Comfrey
(Senecio,
Symphytum)
natural home
remedy
hepatic sinusoidal cells are
damaged, ultimately resulting in
sinusoidal obstruction syndrome
(5564)
Germander
(Teucrium
chamaedrys)
dyspepsia,
obesity, diabetes
and abdominal
colic
CYP3A4 dependent alkylation of
microsomal protein leading to
autoantibody formation
(4749)
Greater celandine
(Chelidonium majus)
dyspepsiaunknown(85)
Kava Kava (Piper
methysticum)
gall bladder
disease, biliary
colic,
cholelithiasis, and
jaundice
immunoallergic and idiosyncratic
factors, including CYP2D6 deficiency
(6566)
Mistletoe (Viscum
Album)
asthma, infertility,
hypertension
mistletoe lectins have
immunostimulating properties and a
strong dose-dependent cytotoxic
activity
(86)
Pennyroyal (Mentha
pulegium, Hedeoma
pulegoides)
abortifacientoxidation of pulegone by cytochrome
P450 into menthofuran, depletion of
glutathione
(87)
Skullcap (Scutellaria
baicalensis)
arthritic
symptoms
CYP3A dependent apoptosis
demonstrated in isolated rat
hepatocytes
(8082)
Jin Bu Huansedation,
analgesic
adulteration with other plant genera(38)
Ma huangstimulant, weight
loss
idiosyncratic ephidrine alkaloid
toxicity
(88)

Use and mechanism of specific HDS proprietary mixes

Proprietary
mixes
Common useMechanism and commentsReference
s
Herbalifeweight-loss or
improvement of
well-being
wide range of different products with
listed and unlisted ingredients

hepatotoxicity potentially due to
contamination with Bacillus subtilis in
some cases
(39)
OxyELITE Proweight losshepatotoxicity emerged after
reformulation with synthetic aegeline

product was recalled
(1824)
Hydroxycutweight lossdifferent products, changing
formulations

voluntarily recalled in 2009
(79)
Move Free
Advanced
See skullcaptable 1(8082)
SlimQuickweight loss, see
green tea extracts
table 1
(54)

Hepatotoxicity associated with specific HDS

Anabolics

Marketed anabolic steroids are generally synthetic chemicals and are not HDS as strictly defined.(1) However, they are typically included in the discussion of HILI. Liver injury due to ingestion of anabolic steroids/bodybuilding compounds has a very typical clinical presentation. It mostly involves young men involved in bodybuilding, weight training, or athletics who, despite modest liver enzyme elevations, present with marked jaundice and pruritus.(1540) It typically has a relatively mild course and completely resolves, albeit often slowly, after the cessation of the product. Pruritus may be debilitating. The use of anabolic steroids or enhancing products is often emphatically denied by the patient, yet the diagnosis can be made confidently based on the presentation and clinical course. Frequently, the patient does not return for a scheduled follow-up visit when feeling better (“Jay’s Law”a). Patients should be warned that the use of these agents may be illegal.

Black cohosh

Black cohosh (Cimicifuga/Actaea racemosa) is an herbal extract that was traditionally used by Native Americans to treat a wide variety of symptoms, including joint aches, myalgia and gynecologic symptoms. Today it is primarily used for the treatment of post-menopausal symptoms. The mechanism of action is unknown, but there have been reports on hepatotoxicity with and without autoimmune features,(4143) which has led to the publication of a cautionary statement by the US Dietary Supplement Information Expert Committee.(44) However, a more recent meta-analysis of five randomized, double-blind, controlled clinical trials found no evidence that isopropanolic extracts of black cohosh have any adverse effect on liver function.(45) Black cohosh has been known to be adulterated with other species of Actaea (Actaea pachypoda Ell. (white cohosh) and Actaea podocarpa DC. (yellow cohosh) from China which may be responsible for the hepatotoxicity reported.(46)

Germander

The blossoms of wall germander (Teucrium chamaedrys) have long been used in folk medicine in the Middle East and Mediterranean region as treatment for dyspepsia, obesity, diabetes and abdominal colic. Despite its wide use, it was found in the early 1990s that herbal preparations, in the form of tea or capsules, could cause significant liver injury. The injury is characterized by an hepatocellular pattern associated with marked jaundice, in the absence of immunoallergic or autoimmune features.(47) The latency to onset of injury is relatively short, usually within 30 days of starting the preparation. Although fatal cases and liver transplantation have been reported, the injury generally resolves after the cessation of the agent.(48) Re-exposure to germander leads to rapid recurrence of the injury.(47) The toxicity is thought to arise due to CYP3A4 activation of the component furan ring Teucrin A, which can then alkylate intracellular epoxide hydrolase, leading to formation of anti-microsomal epoxide hydrolase autoantibodies(49). It has been hypothesized that the anorexogenic properties of germander may actually relate to a mild hepatitis.

Green tea

Green tea (Camellia sinensis) contains polyphenols known as catechins (+-catechin, gallocatechin, epicatechin, epigallocatechin, epicatechin gallate, and epigallocatechin gallate). An intake of 2-3 cups of green tea per day will not generally lead to hepatotoxicity. However, HDS products such as SlimQuick, generally intended for weight loss may contain higher doses of GTE, which can induce hepatotoxicity.(5053) Epigallocatechin gallate (EGCG) is the most abundant green tea polyphenol, and is believed to be the most active and potent hepatotoxic component.(50) Genomic investigation in outbred mice identified genes that were associated with EGCG toxicity. There is a suggestion that analogous human genetic variants may be associated with susceptibility to GTE hepatotoxicity.(54)

Pyrrolizidine alkaloids

Pyrrolizidine alkaloids are found in a large number of plants, including several used as HDS. Among these are Senecio, and Symphytum (Comfrey) species. Sinusoidal obstruction syndrome (SOS, previously known as hepatic veno-occlusive disease) was first described in 1954 among Jamaicans drinking “bush teas” brewed from Senecio.(55) Reports from South Africa(56) (Senecio-contaminated bread), India (57) (Crotalaria-contaminated cereal), Afghanistan(58) (Heliotropium-contaminated wheat) and the southwestern United States(5961) (Comfrey used as HDS) have implicated pyrrolizidine alkaloids in SOS. Many reports describe the disease in children suggesting either an increased susceptibility or a dose effect.(62) Interestingly, the pulmonary vascular bed is also sensitive to the effects of pyrrolizidine alkaloids.(63) Sinosoidal obstruction syndrome may present as an acute, subacute or chronic liver injury characterized by weight gain, ascites and tender hepatomegaly. Hepatic sinusoidal cells appear to be the primary target of pyrrolizidine alkaloids. These cells are damaged and swell, impeding sinusoidal blood flow, inducing hemorrhage, and ultimately resulting in sinusoidal obstruction.(64)

Kava kava

Kava kava (Piper methysticum) is used to treat anxiety and depressive disorders. However, numerous worldwide reports of fulminant hepatotoxicity, both hepatocellular and cholestatic, have led to the withdrawal of distribution licenses in the US, Europe and Australia.(6567) Both immunoallergic and idiosyncratic factors (including CYP2D6 deficiency), have been implicated. (6566)

Traditional Chinese Medicine

In the art of Traditional Chinese Medicine (TCM), specific herbs are selected in different preparations for their supposed properties to treat disease within the human body. TCMs have been used to treat conditions such as viral hepatitis for centuries. In China, currently, approximately 40% of cases of DILI are attributed to the use of TCMs, and have been responsible for cases of acute liver failure with associated coagulopathy.(6869)Go to:

Proprietary mixes

Herbalife

In 2004, a report by Elinav et al. implicated ingestion of Herbalife products in in 12 patients who developed DILI, manifest as acute fulminant hepatitis.(70) Herbalife products consist of a wide range of different mixtures, usually being taken for the purpose of weight loss or general well-being. Identified ingredients include Solidago gigantea, Ilex paraguariensis, Petroselinum crispum, Garcinia cambogia, Spiraea, Matricaria chamomilla, Liquiritia, Foeniculum amare, Humulus lupulus, Chromium and numerous others. Additionally, the proprietary formula of these products, contain a wide range of listed and unlisted ingredients, which makes it challenging to identify a single responsible component with any degree of certainty.(71) In the initial cohort of cases implicated, the injury resolved spontaneously in 11 of 12 (92%) patients; one patient with preexisting chronic hepatitis B died after undergoing liver transplantation. Three patients developed recurrent liver test abnormalities after resuming ingestion of Herbalife products. Since then, several reports have shown similar associations of HILI with Herbalife products, also suggesting contamination with Bacillus subtilis as a potential cause for its hepatotoxicity profile.(3972) Employees of Herbalife have aggressively criticized reports of Herbalife-associated hepatotoxicity (7374), but their criticisms have been effectively rebutted.(75)

OxyELITE Pro

Between February 2012 and February 2014 the FDA received 55 reports of liver disease in consumers of OxyELITE Pro. The typical clinical course consisted of a severe acute hepatitis pattern of injury with a median time to onset of 60 days. Hospitalization was required in 33 (60%) cases and liver transplantation in 3 (5%).(76) In early 2013 the formula of OxyELITE Pro had been changed, substituting 1,3-Dimethylamylamine, which had been associated with cardiovascular toxicity, with aegeline.(76) Early reports of liver injury were from Hawaii, where an initial cluster of 7 patients was reported to develop liver injury in the period between May and September 2013.(2477) Following this report, other cases were identified in an outbreak investigation performed by the Hawaii Department of Health, Centers for Disease Control and Prevention (CDC) and FDA.(77) The product was recalled and the manufacturer was required to discontinue the distribution of OxyELITE Pro.(18) Aegeline, derived from the bark of the Bael tree in India, has long been used as a traditional remedy but the component implicated in the OxyELITE Pro outbreak was synthetic.(36)

Hydroxycut

Hydroxycut products are generally marketed and used as a weight loss supplements. Two published case series implicated the use of some Hydroxycut products to the occurrence of liver injury, presenting predominantly with an hepatocellular pattern of injury and symptoms of jaundice, fatigue, nausea, vomiting, and abdominal pain.(7879) Several Hydroxycut products were voluntarily recalled in 2009, following a published FDA warning related to the use of Hydroxycut.(19)

Move Free Advanced

Move Free Advanced is a widely distributed dietary supplement, sold over the counter in the United States for treatment of sore joints and to improve flexibility and mobility. The product contains glucosamine, chondroitin, hyaluronic acid, and proprietary Uniflex consisting of Chinese skullcap (Scutellaria baicalensis) and black catechu. In a 2010 report, the ingestion of Move Free was identified as a probable cause for the development of cholestatic hepatitis which resolved after discontinuation of the supplement.(80) In one patient, Move Free was not initially recognized as the agent responsible for the injury and the patient restarted the supplement, after which liver injury recurred. A liver biopsy performed at that time was consistent with acute drug induced liver injury.(81) In one patient, pulmonary infiltrates developed simultaneous with the hepatotoxicity and resolved completely with cessation of the supplement.(82) Diterpenoid compounds in Scutellaria baicalensis, have previously been shown to cause apoptosis in isolated rat hepatocytes, through reactive metabolites formed by CYP3A.(83)Go to:

Conclusion/summary

The increase in the use of herbal and dietary supplements (HDS) and a growing awareness of the potential for these agent to cause liver injury has been associated with an increase in reports of HDS associated hepatotoxicity. Limited regulatory oversight, inaccurate product labeling, adulterants and inconsistent sourcing of constituent ingredients may all contribute to the potential for toxicity. The spectrum of HDS induced liver injury is diverse and the outcome may vary from transient liver test abnormalities to acute hepatic failure requiring liver transplantation, or resulting in death. The most commonly implicated products include bodybuilding and weight loss products. There are no validated standardized tools to establish the diagnosis, but some HDS products do have a clear clinical signature that can make diagnosis almost certain. The keys to diagnosis are a high level of suspicion and a comprehensive workup to eliminate competing etiologies. Management is generally supportive and nonspecific.

Source: de Boer YS, Sherker AH. Herbal and Dietary Supplement-Induced Liver Injury. Clin Liver Dis. 2017 Feb;21(1):135-149. doi: 10.1016/j.cld.2016.08.010. Epub 2016 Oct 14. PMID: 27842768; PMCID: PMC5117680.

Globally, people are struggling with obesity. Many effective, non-conventional methods of weight reduction, such as herbal and natural dietary supplements, are increasingly being sought. Fat burners are believed to raise metabolism, burn more calories and hasten fat loss. Despite patient perceptions that herbal remedies are free of adverse effects, some supplements are associated with severe hepatotoxicity. The present report describes a young healthy woman who presented with fulminant hepatic failure requiring emergent liver transplantation caused by a dietary supplement and fat burner containing usnic acid, green tea and guggul tree extracts. Thorough investigation, including histopathological examination, revealed no other cause of hepatotoxicity. The present case adds to the increasing number of reports of hepatotoxicity associated with dietary supplements containing usnic acid, and highlights that herbal extracts from green tea or guggul tree may not be free of adverse effects. Until these products are more closely regulated and their advertising better scrutinized, physicians and patients should become more familiar with herbal products that are commonly used as weight loss supplements and recognize those that are potentially harmful.

Usnic acid is a component of nutritional supplements that are promoted for weight loss and have been associated with liver-related adverse events including mild hepatic toxicity, chemical hepatitis and liver failure requiring liver transplantation. It has been investigated for diverse uses as an antimicrobial, an anti-inflammatory, an antioxidant, an analgesic/antipyretic, an antiproliferative and as a natural supplement for weight loss. There are no adequate or well-controlled trials to substantiate any claims of effectiveness in humans for any indication

Another herbal remedy containing usnic acid – well known to be hepatotoxic – is kombucha tea. This is a beverage made by brewing kombucha mushrooms in sweet black tea 

Chinese green tea extracts are derivatives of the leaves of Camellia sinensis, which belongs to the aceae family. Green tea extracts have been marketed as effective weight-loss supplements, and for the prevention and cure of solid tumours. Although there is little scientific evidence supporting the effectiveness of green tea extracts, serious side effects, including acute liver failure, are increasingly being reported. Similar cases have been reported from France and Spain resulting in the removal of the green tea extract ‘Exolise’ from the market. Two cases of fulminant hepatic failure associated with green tea extracts have been reported. Mitochondrial toxicity and the formation of reactive oxygen species have been demonstrated with epigallocatechin-3-gallate, a key constituent of green tea extracts. The possibility of an allergic reaction to green tea itself has also been reported.

Source: Yellapu RK, Mittal V, Grewal P, Fiel M, Schiano T. Acute liver failure caused by ‘fat burners’ and dietary supplements: a case report and literature review. Can J Gastroenterol. 2011 Mar;25(3):157-60. doi: 10.1155/2011/174978. PMID: 21499580; PMCID: PMC3076034.

Be careful with supplements!

Coach Lucy

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