Kidney toxicity related to herbs and dietary supplements: Online table of case reports. Part 3 of 5 series

doi:10.1016/j.fct.2016.07.024

Food and Chemical Toxicology

Volume 107, Part A, September 2017, Pages 502-519

https://doi.org/10.1016/j.fct.2016.07.024 Get rights and content

Abstract

Background

No tabular summary of potentially life-threatening, kidney-toxic dietary supplements (DS; includes herbs) based on PubMed case reports is currently available online and continually updated to forewarn United States consumers, clinicians, and companies manufacturing DS. The purpose of this review was to create an online research summary table of kidney toxicity case reports related to DS.

Methods

Documented PubMed case reports (1966 to May 2016, and cross-referencing) of DS appearing to contribute to kidney toxicity were listed in “DS Toxic Tables.” Keywords included “herb” or “dietary supplement” combined with “kidney” to generate an overview list, and possibly “toxicity” to narrow the selection. Case reports were excluded if they involved herb combinations (some exceptions), Chinese herb mixtures, teas of mixed herb contents, mushrooms, poisonous plants, self-harm, excessive doses (except vitamins/minerals), legal or illegal drugs, drug-herbal interactions, and confounders of drugs or diseases. Since commercial DS often include a combination of ingredients, they were treated separately; so were foods. A few foods with kidney-toxic effects were listed in a fourth table. The spectrum of herbal or DS-induced kidney injuries included kidney stones, nephritis, nephrotic syndrome, necrosis, acute kidney injury (AKI; previously known as acute renal failure [ARF]), chronic kidney disease, kidney transplant, and death.

Results

Approximately 7 herbs (minus 4 no longer for sale) and 10 dietary supplements (minus 3 excluded due to excessive doses + germanium that is no longer sold) have been related to kidney injury case reports published in PubMed (+crosslisting) in the last 50 + years (1966 to May 2016). The implicated herbs include Chinese yew (Taxus celbica) extract, impila (Callilepis laureola), morning cypress (Cupressus funebris Endl), St. John's wort (Hypericum perforatum), thundergod vine (Tripterygium wilfordii hook F), tribulus (Tribulus terrestris) and wormwood (Artemisia herba-alba). No longer sold in the United States are chocolate vine or mu tong (Caulis aristolochiae), guang fang ji (Aristolochia fangchi), ma huang (Ephedra sinica), and Tenshin Tokishigyaku-ka-goshuyu-shokyo-to. The DS include bile (sheep), chlorella, chromium (Cr), CKLS, creatine, gallbladder (fish), glucosamine, hydrazine, N.O.-Xplode, Spanish fly, and excess intakes of vitamins A, C, and D. Germanium (Ge) is not available for sale. The top two DS with the largest number of reported publications, but not always case reports, in descending order, were the aristolochic acid-containing herbs guang fang ji (mistaken identity) and chocolate vine or mu tong. The remaining DS featured one to three publications over a 50+ year period. Numerous case reports were reported for kidney-toxic foods: djenkol bean, gallbladders (carp fish, pufferfish, & snake), and star fruit (only in chronic kidney disease patients), and uncooked yam powder or juice.

Conclusion

This online “DS Toxic Table” provides clinicians, consumers, and manufacturers with a list of herbs that could potentially contribute to kidney injuries.

Introduction

This is the third of five review articles investigating dietary supplements (DS; includes herbs): Article one covers DS definitions, usage, efficacy and safety, and an overview of DS regulation in the United States; and articles two through five cover DS medical case reports in tabular form related to liver toxicity, kidney toxicity, heart toxicity, and cancer (Brown, 2017a, Brown, 2017b, Brown, 2017c, Brown, 2017d, Brown, 2016e). Interest in complementary and alternative medicine (CAM), also known as functional, integrative, traditional, or holistic medicine, continues to grow, but “natural” is not always safe. Although the majority of botanical products appear inherently safe (Marcus and Grollman, 2002), and some have demonstrated efficacy, this review focuses on the potentially life-threatening DS that increase kidney risk as detected through PubMed case reports. Case reports do not always demonstrate causation or association, but reoccurrences raise concerns (Haaz et al., 2006). In this review, the selected kidney toxicities are defined, the literature search methods employed are described, and a summary table of the results along with a brief discussion of selected DS are presented.

Section snippets

Definition

The types of kidney dysfunctions considered in this review are shown in Table 1. The major risk factors for one of the most serious forms of kidney injury, chronic kidney disease, are diabetes mellitus, high blood pressure, heart disease, and a family history of kidney failure (NIH-a, 2014).

The kidney is highly susceptible to toxic insults, and drugs are a common source of acute kidney injury (Garella, 1993, Naughton, 2008). Researchers have suggested that drugs are responsible for as much as

Prevalence in Africa

The patients most vulnerable to kidney injuries are the elderly, and people in Africa who use traditional medicines. In Africa, herbal medicine accounts for approximately 30–35% of all acute kidney injury cases (Akpan and Ekrikpo, 2015). Contributing to this problem is the possible reliance on herbal medicines whose compositions are closely guarded secrets that lead to questionable substitutions (Gold, 1980). In South Africa, up to 80% of the black community in certain regions uses folk

Methods

Documented PubMed case reports (1966 to May 2016, and cross-referencing) of DS appearing to contribute to kidney toxicity were listed in “DS Toxic Tables.” The broad search included the keywords of “plant extracts” or “plant preparations” with “kidney” and “toxicity” (“human” species filter always selected). The narrowed search included the keywords of “herb” or “dietary supplement” combined with “kidney” to generate an overview list, and possibly “toxicity” to narrow the selection. Specific

Results

Approximately 7 herbs (minus 4 no longer for sale and depicted in grey shading in Table 3) and 10 dietary supplements (minus 3 excluded due to excessive doses + germanium that is no longer sold) have been related to kidney injury case reports published in PubMed (+crosslisting) in the last 50+ years (1966 to May 2016). The implicated herbs listed in Table 3 include Chinese yew (Taxus celbica) extract, impila (Callilepis laureola), morning cypress (Cupressus funebris Endl), St. John's wort (

Conclusion

Some researchers maintain “the presumptive belief in some therapeutic efficacy of botanicals as evidenced by a long history of use in traditional medicine,” and “the absence of serious adverse effects, also as evidenced by a long history of use in traditional medicine” (Schiff et al., 2006). Other reviews have listed certain DS that may be protective of the kidneys (Lien et al., 2012, Wojcikowski et al., 2004, Wojcikowski et al., 2006). As always, until more information is available, it appears

Herbs

•
Approximately 7 herbs (minus 4 no longer sold) were related to kidney injury case reports published in PubMed (+crosslisting) in the last 50+ years (1966 to May 2016).
•
Herbs include, but are not limited to Chinese yew (Taxus celbica) extract, chocolate vine or mu tong (Caulis aristolochiae), guang fang ji (Aristolochia fangchi), impila (Callilepis laureola), ma huang (Ephedra sinica), morning cypress (Cupressus funebris Endl), St. John's wort (Hypericum perforatum), Tenshin

Conflict of interest/Caveat

Amy Brown is CEO of Natural Remedy Labs, LLC, and has served as an expert witness in herb and dietary supplement cases. The names, formulations and corporate name and/or ownership of DS may change, so any identification in this publication may no longer apply.

References (238)

B.A. Adesunloye
Acute renal failure due to the herbal remedy CKLS
Am. J. Med.
(2003 Oct 15)
T. Asaka et al.
Germanium intoxication with sensory ataxia
J. Neurol. Sci.
(1995)
M. Auxiliadora-Martins et al.
Severe encephalopathy after ingestion of star fruit juice in a patient with chronic renal failure admitted to the intensive care unit
Heart Lung
(2010)
A. Awada et al.
Deep non-reactive reversible coma after a Mediterranean neurotoxic fish poisoning
Rev. Neurol. Paris.
(2010)
V. Bandara et al.
A review of the natural history, toxinology, diagnosis and clinical management of Nerium oleander (common oleander) and Thevetia peruviana (yellow oleander) poisoning
Toxicon
(2010)
J.J. Blau
Ephedrine nephrolithiasis associated with chronic ephedrine abuse
J. Urol.
(1998 Sep)
A.C. Brown
An overview of herb and dietary supplement efficacy, safety, and government regulations in the United Sates with suggested improvements. Part 1 of 5 series
Food Chem. Toxicol.
(2017)
A.C. Brown
Liver toxicity related to herbs and dietary supplements: online table of medical case reports. Part 2 of 5 series
Food Chem. Toxicol.
(2017)
A.C. Brown
Kidney toxicity related to herbs and dietary supplements: online table of medical case reports. Part 3 of 5 series
Food Chem. Toxicol
(2017)
P.P. But et al.
Chinese-herb nephropathy
Lancet
(1999)

R. Carbajal et al.

Case report: boldo (Peumus boldus) and tacrolimus interaction in a renal transplant patient

Transpl. Proc.

(2014)

C. Cassinotto et al.

MRI findings in star-fruit intoxication

J Neuroradiol.

(2008)

J.M. Chang et al.

Fatal outcome after ingestion of star fruit (Averrhoa carambola) in uremic patients

Am. J. Kidney Dis.

(2000)

C.L. Chen et al.

Acute oxalate nephropathy after ingestion of star fruit

Am. J. Kidney Dis.

(2001)

W.C. Chou et al.

Hypovolemic shock and mortality after ingestion of Tripterygium wilfordii hook F.: a case report

Int. J. Cardiol.

(1995)

L.N. Cossey et al.

Oxalate nephropathy and intravenous vitamin C

Am. J. Kidney Dis.

(2013)

J.P. Cosyns et al.

Urothelial lesions in Chinese herb nephropathy

Am. J. Kidney Dis.

(1999)

M. Depierreux et al.

Pathological aspects of a newly described nephropathy related to the prolonged use of Chinese herbs

Am. J. Kidney Dis.

(1994)

J.R. Diamond et al.

Acute interstitial nephritis following following use of tung shueh pills

Am. J. Kidney Dis.

(1994)

J. Foote et al.

Medicinal herb use and the renal patient

J. Ren. Nutr.

(1998)

G. Gillerot et al.

Aristolochic acid nephropathy and the peritoneum: functional, structural, and molecular studies

Kidney Int.

(2003)

F. Granado-Lorencio et al.

Hypercalcemia, hypervitaminosis A and 3-epi-25-OH-D3 levels after consumption of an “over the counter” vitamin D remedy. a case report

Food Chem. Toxicol.

(2012)

J.Y. Guh et al.

Herbal therapy is associated with the risk of CKD in adults not using analgesics in Taiwan

Am. J. Kidney Dis.

(2007)

D.F. Hwang et al.

Tetrodotoxin poisoning

Adv. Food Nutr. Res.

(2007)

Q.T. Islam et al.

Puffer fish poisoning in Bangladesh: clinical and toxicological results from large outbreaks in 2008

Trans. R. Soc. Trop. Med. Hyg.

(2011)

C. Isnard Bagnis et al.

Herbs and the kidney

Am. J. Kidney Dis.

(2004)

V. Jha et al.

Nephropathy associated with animal, plant, and chemical toxins in the tropics

Semin. Nephrol.

(2003)

V. Jha et al.

Natural medicines causing acute kidney injury

Semin. Nephrol.

(2008)

S.M. Ji et al.

Clinical trial of Tripterygium Wilfordii Hook F. in human kidney transplantation in China

Transpl. Proc.

(2006)

D.Y. Acık et al.

Management of Chenopodium polyspermum toxicity with plasma exchange and hemodialysis

J. Clin. Apher.

(2012)

T. Akiyasu et al.

A case report of acute renal failure associated with bee pollen contained in nutritional supplements

Ther. Apher. Dial.

(2010)

E.E. Akpan et al.

Acute renal failure induced by Chinese herbal medicine in Nigeria

Case Rep. Med.

(2015)

A.M. Alkhunaizi et al.

Secondary oxalosis: a cause of delayed recovery of renal function in the setting of acute renal failure

J. Am. Soc. Nephrol.

(1996)

T. Allard et al.

Mechanisms of herb-induced nephrotoxicity

Curr. Med. Chem.

(2013)

S.H. Allen et al.

Calcinosis and metastatic calcification due to vitamin D intoxication. A case report and review

Horm. Res.

(1992)

S. Aloui et al.

An exceptional case of acute renal failure: is there a renal toxicity of Artemisia herba-alba?

Ren. Fail.

(2010)

D.M. Alscher et al.

Drug interaction of herbal tea containing St. John's wort with cyclosporine

Transpl. Int.

(2003 Jul)

Anonymous

St. John's Wort linked to kidney rejection

Nephrol. News Issues

(2000)

A. Anık et al.

Acute vitamin D intoxication possibly due to faulty production of a multivitamin preparation

J. Clin. Res. Pediatr. Endocrinol.

(2013)

T. Araki et al.

Vitamin D intoxication with severe hypercalcemia due to manufacturing and labeling errors of two dietary supplements made in the United States

J. Clin. Endocrinol. Metab.

(2011)

M. Asakawa et al.

Food poisonings by ingestion of cyprinid fish

Toxins (Basel)

(2014)

V.K. Audimoolam et al.

Acute interstitial nephritis induced by glucosamine

Nephrol. Dial. Transpl.

(2006)

J. Bacchetta et al.

Non-drug-induced nephrotoxicity

Pediatr. Nephrol.

(2009)

G.W. Barone et al.

Herbal supplements: a potential for drug interactions in transplant recipients

Transplantation

(2001)

F. Barrueto et al.

Acute vitamin D intoxication in a child

Pediatrics

(2005)

A.B. Beköz et al.

Consequences of the increasing prevalence of the poisonous Lagocephalus sceleratus in southern Turkey

Emerg. Med. J.

(2013)

D.A. Bell et al.

Prolonged vitamin D intoxication: presentation, pathogenesis and progress

Intern Med. J.

(2013)

V. Biniaz et al.

Effect of vitamin C supplementation on serum uric acid in patients undergoing hemodialysis: a randomized controlled trial

Iran. J. Kidney Dis.

(2014)

K. Boubaker et al.

Acute renal failure by ingestion of Euphorbia paralias

Saudi J. Kidney Dis. Transpl.

(2013)

A.C. Brown

Heart toxicity related to herbs and dietary supplements: online table of medical case reports. Part 4 of 5 series

(2017)

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Evaluation of packaging, labels, and some physicochemical properties of herbal antimalarial products on the Ghanaian market
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Malaria is a parasitic disease that is endemic in tropical areas and can be life-threatening. There has been a decrease in the prevalence of malaria in Ghana but the burden of the disease is still high in the country. Many Ghanaians depend on herbal products for malaria treatment. This study aimed to survey and evaluate commercial herbal antimalarials in the Volta Region of Ghana.
A survey of finished herbal antimalarials was done at herbal shops, pharmacies, and over-the-counter medicine seller shops. Products available on shelves were purchased and their details were recorded, after which they were examined using a visual inspection tool. The density, pH, and extract weight per dose of each sample were also determined.
Thirty-four liquid formulations (A-1–34) containing 1–9 different herbs were found. The majority of the product labels had errors in consumer age classifications. Unconventional ways of stating doses were found on two products (A-13, “tot”; A-19, cupful). Six products did not have dosing devices. No duration of treatment was indicated on 24 products. Dose errors were found on A-14 and A-22. Samples A-17 and A-28 did not have registration or batch numbers. Product A-28 did not have its herbs listed on it and was indicated for persons aged 3–8 years at a dose of 45 mL. The relative density range for the products was 0.997–1.015. From the pH investigation, no product was extremely erosive; however, 10 samples were deemed erosive (pH, 3.0–3.99), whereas 24 were minimally erosive (pH, ≥4.0). The extract weight per dose volume (20–90 mL) was 0.048–1.766 g, indicating that unit dose capsules or tablets could be formulated from the products.
The findings clearly show that Ghanaian authorities responsible for regulating herbal products must enforce guidelines for the formulation, label details, and sale of antimalarial products. Additionally, the unpleasant taste of liquid herbal mixtures can affect patient compliance and dosing convenience; therefore, it is recommended that oral solid dosage forms of herbal antimalarials are produced as alternatives to the liquid mixtures.
Antidiabetic effects of polyherbal mixture made of Centaurium erythraea, Cichorium intybus and Potentilla erecta
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The polyherbal mixture made of Centaurium erythraea aerial parts and Cichorium intybus roots and Potentilla erecta rhizomes has been used for centuries to treat both the primary and secondary complications of diabetes.
As a continuation of our search for the most effective herbal mixture used as an ethnopharmacological remedy for diabetes, this study aimed to compare the in vitro biological activities of this polyherbal mixture and its individual ingredients, and, most importantly, to validate the ethnopharmacological value of the herbal mixture through evaluation of its phytochemical composition, its potential in vivo toxicity and its effect on diabetes complications.
Phytochemical analysis was performed using HPLC-UV. Antioxidant activity was estimated via the DPPH test. Potential cytotoxicity/anticytotoxicity was assessed using an in vitro RBCs antihemolytic assay and an in vivo sub-chronic oral toxicity method. Antidiabetic activity was evaluated using an in vitro α-amylase inhibition assay and in vivo using a chemically induced diabetic rat model.
The HPLC-UV analysis revealed the presence of p-hydroxybenzoic acid, p-hydroxybenzoic acid derivative, catechin, five catechin derivatives, epicatechin, isoquercetin, hyperoside, rutin, four quercetin derivatives, caffeic acid, and four caffeic acid derivatives in the polyherbal mixture decoction. Treatment with the decoction has shown no toxic effects. The antioxidant and cytoprotective activities of the polyherbal mixture were higher than the reference's ones. Its antidiabetic activity was high in both in vitro and in vivo studies. Fourteen days of treatment with the decoction (15 g/kg) completely normalized blood glucose levels of diabetic animals, while treatments with insulin and glimepiride only slightly lowered glycemic values. In addition, lipid status of treated animals as well as levels of serum AST, ALT, ALP, creatinine, urea and MDA were completely normalized. In addition, the polyherbal mixture completely restored the histopathological changes of the liver, kidneys and all four Cornu ammonis regions of the hippocampus.
The polyherbal mixture was effective in the prevention of both primary and secondary diabetic complications such as hyperlipidemia, increased lipid peroxidation, non-alcoholic fatty liver disease, nephropathy and neurodegeneration.
Study on toxicity/efficacy related substances and metabolic mechanism of Tripterygium wilfordii Hook. f based on O2LPS correlation analysis
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TwHF was found to have a protective effect on the kidney of RA rats and an injurious effect on the kidney of normal rats at a dose of 11.25 g/kg/d. The UPLC-Q-TOF/MS technique was used to identify 34 components in TwHF extracts; 23 components and 57 metabolites were identified in the administered rats. O2PLS screened three substances as both toxic and pharmacodynamic components of TwHF, namely 3,5-dimethoxyphenyl-2-propenl-ol, kaurane-16,19,20-triol, and demethylzeylasteral + O, and found that these three components may exert nephrotoxic effects via the nicotinic acid and nicotinamide metabolic pathways and nephroprotective effects via the tryptophan metabolic pathway.
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Development of nucleotide signatures for common poisonous organisms provides a new strategy for food poisoning diagnosis
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DNA barcoding is widely used in toxic species authentication, but due to serious DNA degradation of forensic materials, the application of full-length barcode sequences in food poisoning diagnosis is greatly limited. Nucleotide signature, a shorter specific molecular marker, derived from traditional DNA barcoding has been proposed as an emerging tool of toxic species detection in deeply processed materials. In this study, to resolve the frequent food poisoning accidents with unknown origin, we envisioned developing a nucleotide signature data set of common poisonous organisms and combining high-throughput sequencing (HTS) to reveal the poisoning cause. Ninety-three individuals and 1093 DNA barcode sequences of twelve common poisonous plants, fish, mushrooms and their related species were collected. Through sequence alignment and screening, the nucleotide signatures were respectively developed and validated as their specific molecular markers. The sequence length varied from 19 bp to 38 bp. These fragments were conserved within the same species or genera, and the specificity between related species has been also demonstrated. To further evaluate the application potential of nucleotide signature in forensic diagnosis, simulated forensic specimens (SFS) containing different poisonous ingredients were sequenced by HTS with PCR-free libraries. As a result, the nucleotide signature was successfully captured from original HTS data without assembly and annotation, accompanied by a high detection sensitivity of 0.1 ng/µl in mixture system. Therefore, this method was suitable for the assay of forensic materials with serious DNA degradation. The present study undoubtedly provides a new perspective and strong support for the detection of toxic ingredients and the diagnosis of food poisoning.
Exploring the pharmacological mechanisms of Tripterygium wilfordii against diabetic kidney disease using network pharmacology and molecular docking
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Tripterygium wilfordii (TW), when formulated in traditional Chinese medicine (TCM), can effectively treat diabetic kidney disease (DKD). However, the pharmacological mechanism associated with its success has not yet been elucidated. The current work adopted network pharmacology and molecular docking for exploring TW-related mechanisms in treating DKD. Methods: In the present work, the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database was employed to obtain the effective components and candidate targets of TW. Additionally, this work utilized the UniProt protein database for screening and standardizing human-derived targets for effective components. The Cytoscape software was utilized to construct an effective component-target network for TW. Targets for DKD were acquired in the GEO, DisGeNET, GeneCards, and OMIM databases. Additionally, a Venn diagram was also plotted to select the possible targets of TW for treating DKD. Gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were conducted to explore the TW-related mechanism underlying DKD treatment. This work also built a protein-protein interaction (PPI) network based on the Cytoscape and String platform. Then, molecular docking was conducted in order to assess the affinity of key proteins for related compounds. Results: In total, 29 active components and 134 targets of TW were acquired, including 63 shared targets, which were identified as candidate therapeutic targets. Some key targets and important pathways were included in the effect of TW in treating DKD. Genes with higher degrees, including TNF and AKT1, were identified as hub genes of TW against DKD. Molecular docking showed that TNF and AKT1 bind well to the main components in TW (kaempferol, beta-sitosterol, triptolide, nobiletin, and stigmasterol).
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Herbal Remedies
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Since prehistoric times, humans have used natural products, such as plants, animals, microorganisms, and marine organisms in medicines to alleviate and treat illness. These remedies are often prescribed as part of traditional medicine, a discipline that has been built over the ages based on empirical knowledge that was passed down through the generations. Herbal remedies are aimed at wellness and general disease states, whereas conventional pharmaceuticals are directed at specific molecular disease targets.
Herbal remedies come from various sources where growth, harvesting, and storage conditions can alter the amount of the active ingredients substantially. In addition, fungal and other organic and inorganic contaminants add to the complexity of safety assessment. Sometimes adulterants are intentionally added for the purpose of efficacy.
Herbal remedies are labeled as mg of the plant, an extract (in mg or percent), or the active ingredient in mg, e.g., capsules containing 80 mg of the herb [Ginger root 750 mg], or capsules containing 80 mg of the active [Saint John's Wort 300 mg–0.3% hypericin], or as a straight concentration [CBD oil 2.5%] for the purpose of dosage. The therapeutic index for herbal remedies is large: the recommended doses for herbs are usually in milligrams per 70 kg person compared to toxicity experiments that require grams per kilogram for an effect. This does not mean that herbal remedies are innocuous, as most users are aware of the intrinsic hazard of some herbal remedies and risk of exposure, cigarette smoking, for example.
In toxicologic pathology, the organ of impact following herbal remedy overdose, like conventional pharmaceuticals, is usually the liver. However, toxicity can be seen in other organs such as the heart, following Digitalis exposure. Goldenseal root power [Hydrastis canadensis]), Gingko biloba extract [Ginkgo biloba], Riddelliine (pyrrolizidine alkaloid), Pulegone [Mentha sp.], Kava kava [Piper methysticum], and Indole-3-carbinol [Brassica sp.] are hepatotoxic at the doses given experimentally. In addition, some herbs have been classified as carcinogens based on experimental evidence. The International Agency for Research on Cancer (IARC) has reviewed the evidence for carcinogenic activity for four of these herbal remedies (Goldenseal, Gingko, Kava, and Pulegone), and classified them as “possibly carcinogenic to humans” (Group 2B) because of evidence for carcinogenic activity in two species or both sexes of the same rodent species.
Other target organs damaged during high exposure include the gastrointestinal tract: Aloe vera and Senna; kidney: Aloe vera, raw Garlic, Ginkgo, Kava kava, Pulegone, St John's wort, and Tobacco; heart: Ephedra; and the vascular system: Riddelliine pyrrolizidine alkaloid and Tobacco.
Milk thistle, Turmeric oleoresin, Green tea extract studies did not provide clear evidence for carcinogenic activity in rodent model systems nor did Marijuana, Chamomile, Coffee, Cocoa, Echinacea, Ephedra, Ginger, Ginseng, St. John's wort, and Turmeric.
The scope of this chapter is limited to herbal remedies. Other supplements will not be part of the discussion except to illustrate specific points regarding herbal remedies. In this chapter we explore the use of herbal remedies in medical treatment regimens, differentiate traditional from scientific knowledge and discovery, the issue of quality in herbal remedies, and the difficulties in obtaining precise dose–response data for safety and efficacy.

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Invited reviewKidney toxicity related to herbs and dietary supplements: Online table of case reports. Part 3 of 5 series

Abstract

Background

Methods

Results

Conclusion

Introduction

Section snippets

Definition

Prevalence in Africa

Methods

Results

Conclusion

Herbs

Conflict of interest/Caveat

Am. J. Med.

J. Neurol. Sci.

Heart Lung

Rev. Neurol. Paris.

Toxicon

J. Urol.

Food Chem. Toxicol.

Food Chem. Toxicol.

Food Chem. Toxicol

Lancet

Transpl. Proc.

J Neuroradiol.

Am. J. Kidney Dis.

Am. J. Kidney Dis.

Int. J. Cardiol.

Am. J. Kidney Dis.

Am. J. Kidney Dis.

Am. J. Kidney Dis.

Am. J. Kidney Dis.

J. Ren. Nutr.

Kidney Int.

Food Chem. Toxicol.

Am. J. Kidney Dis.

Adv. Food Nutr. Res.

Trans. R. Soc. Trop. Med. Hyg.

Am. J. Kidney Dis.

Semin. Nephrol.

Semin. Nephrol.

Transpl. Proc.

Management of Chenopodium polyspermum toxicity with plasma exchange and hemodialysis

J. Clin. Apher.

A case report of acute renal failure associated with bee pollen contained in nutritional supplements

Ther. Apher. Dial.

Acute renal failure induced by Chinese herbal medicine in Nigeria

Case Rep. Med.

Secondary oxalosis: a cause of delayed recovery of renal function in the setting of acute renal failure

J. Am. Soc. Nephrol.

Mechanisms of herb-induced nephrotoxicity

Curr. Med. Chem.

Calcinosis and metastatic calcification due to vitamin D intoxication. A case report and review

Horm. Res.

An exceptional case of acute renal failure: is there a renal toxicity of Artemisia herba-alba?

Ren. Fail.

Drug interaction of herbal tea containing St. John's wort with cyclosporine

Transpl. Int.

St. John's Wort linked to kidney rejection

Nephrol. News Issues

Acute vitamin D intoxication possibly due to faulty production of a multivitamin preparation

J. Clin. Res. Pediatr. Endocrinol.

Vitamin D intoxication with severe hypercalcemia due to manufacturing and labeling errors of two dietary supplements made in the United States

J. Clin. Endocrinol. Metab.

Food poisonings by ingestion of cyprinid fish

Toxins (Basel)

Acute interstitial nephritis induced by glucosamine

Nephrol. Dial. Transpl.

Non-drug-induced nephrotoxicity

Pediatr. Nephrol.

Herbal supplements: a potential for drug interactions in transplant recipients

Transplantation

Acute vitamin D intoxication in a child

Pediatrics

Consequences of the increasing prevalence of the poisonous Lagocephalus sceleratus in southern Turkey

Emerg. Med. J.

Prolonged vitamin D intoxication: presentation, pathogenesis and progress

Intern Med. J.

Invited review
Kidney toxicity related to herbs and dietary supplements: Online table of case reports. Part 3 of 5 series