The effects of immunostimulatory herbal supplements on autoimmune skin diseases.

The use of herbal supplements that promise to improve immune health has gained popularity among dermatology patients. However, there is little to no evidence that herbal supplements improve dermatologic conditions. Several in vitro and in vivo studies have shown that Spirulina platensis, Aphanizomenon flos-aqua, Chlorella, Echinacea, and alfalfa activate immune cells via certain cytokines and chemokines. Case reports suggest the association of ingesting immunostimulatory herbs and the clinical onset or flares of diseases characterized by an exaggerated immune response such as lupus erythematosus, dermatomyositis, and autoimmune blistering disorders. Therefore, it is imperative to investigate the prevalence of herbal supplement use in this patient population. In addition, in vitro studies should examine the underlying mechanisms by which herbs stimulate immune pathways that are already overactive in autoimmune patients.

Analysis of spontaneous adverse drug reactions to echinacea, valerian, black cohosh and ginkgo in Australia from 2000 to 2015.

OBJECTIVE: Assessing adverse drug reactions (ADRs) is a proven method to estimate the safety of medicines. The ADRs to herbal medicines in Australia (and by inference, the safety of herbal medicines in Australia) remain unknown. This study examines spontaneous ADR cases to four of the most popular herbs in Australia from 2000 to 2015: echinacea (Echinacea purpurea), valerian (Valeriana officinalis), black cohosh (Actaea racemosa) and ginkgo (Ginkgo biloba). METHODS: ADRs of echinacea, valerian, black cohosh and ginkgo reported to the Australian Therapeutic Goods Administration (TGA) between 2000 and 2015 were obtained from the TGA database. Data were collated and analysed according to age, sex, severity, type of ADR and body system affected. Statistics were calculated using GraphPad Prism software. RESULTS: Most ADRs were mild or moderate. However, every herbal medicine was associated with life-threatening ADRs. In each life-threatening case, the herbal medicine was taken concomitantly with prescription medications. Black cohosh was associated with a significant number of severe ADRs (30.3% of the total), with 39.4% of these ADRs being associated with abnormal hepatic function, hepatitis or hepatotoxicity. CONCLUSION: This study highlights the lack of public awareness with regard to herb-drug interactions, since most of the severe ADRs involved a herb-drug interaction.

Review and Assessment of Medicinal Safety Data of Orally Used Echinacea Preparations.

Echinacea purpurea, Echinacea angustifoli and Echinacea pallida are frequently used as medicinal plants. Besides asking for evidence on their efficacy, there is an increasing interest for safety data. This review systematically presents the available literature on drug interactions, contraindications, adverse events, duration of use, and safety of use in pregnant and nursing women, and assesses the safety profile of corresponding Echinacea preparations. It is noteworthy that all safety data reported are as product specific as the pharmacological or efficacy data are. In pharmacokinetic herb-drug interaction studies performed in vivo, no significant inhibitions of human CYP2D6 and CYP3A4 isoforms have been found after the administration of standardized E. purpurea preparations. However, contradictory results exist in studies using liver microsomes. Adverse events reported during clinical trials following administration of Echinacea spp. mono-preparations were generally mild and mostly without causality. Due to published long term studies with continuous ingestion of different Echinacea preparations up to 6 month with no reported toxicological concerns, Echinacea can be recommended also for long-term use. Moreover, the contraindications in cases of autoimmune diseases and immune-suppression are questionable, since lipophilic Echinacea preparations containing alkamides suppress cellular immune responses, and beneficial effects in autoimmunity were reported. The same applies for the use during pregnancy. Although there has been some impact reported on embryonic angiogenesis in mice, no association with an increased risk for major or minor malformations during organogenesis was found in a literature review. Altogether, the different evaluated Echinacea preparations are well-tolerated herbal medicines in the management in children and adults alike.

Contact dermatitis as an adverse reaction to some topically used European herbal medicinal products - part 2: Echinacea purpurea-Lavandula angustifolia.

This review focuses on contact dermatitis as an adverse effect of a selection of topically used herbal medicinal products for which the European Medicines Agency has completed an evaluation up to the end of November 2013 and for which a Community herbal monograph has been produced. Part 2: Echinacea purpurea Moench-Lavandula angustifolia Mill.

Echinacea for treating the common cold: a randomized trial.

BACKGROUND: Echinacea is widely used to treat the common cold. OBJECTIVE: To assess the potential benefits of echinacea as a treatment of common cold. DESIGN: Randomized, controlled trial. (ClinicalTrials.gov registration number: NCT00065715) SETTING: Dane County, Wisconsin. PATIENTS: 719 patients, aged 12 to 80 years, with new-onset common cold. INTERVENTION: Patients were assigned to 1 of 4 parallel groups: no pills, placebo pills (blinded), echinacea pills (blinded), or echinacea pills (unblinded, open-label). Echinacea groups received the equivalent of 10.2 g of dried echinacea root during the first 24 hours and 5.1 g during each of the next 4 days. Indistinguishable placebo tablets contained only inert ingredients. MEASUREMENTS: The primary outcome was the area under the curve for global severity, with severity assessed twice daily by self-report using the Wisconsin Upper Respiratory Symptom Survey, short version. Secondary outcomes included interleukin-8 levels and neutrophil counts from nasal wash, assessed at intake and 2 days later. RESULTS: Of the 719 patients enrolled, 713 completed the protocol. Mean age was 33.7 years, 64% were female, and 88% were white. Mean global severity was 236 and 258 for the blinded and unblinded echinacea groups, respectively; 264 for the blinded placebo group; and 286 for the no-pill group. A comparison of the 2 blinded groups showed a 28-point trend (95% CI, -69 to 13 points) toward benefit for echinacea (P = 0.089). Mean illness duration in the blinded and unblinded echinacea groups was 6.34 and 6.76 days, respectively, compared with 6.87 days in the blinded placebo group and 7.03 days in the no-pill group. A comparison of the blinded groups showed a nonsignificant 0.53-day (CI, -1.25 to 0.19 days) benefit (P = 0.075). Median change in interleukin-8 levels and neutrophil counts were also not statistically significant (30 ng/L and 1 cell/high-power field [hpf] in the no-pill group, 39 ng/L and 1 cell/hpf in the blinded placebo group, 58 ng/L and 2 cells/hpf in the blinded echinacea group, and 70 ng/L and 1 cell/hpf in the open-label echinacea group). LIMITATION: Higher-than-expected variability limited power to detect small benefits. CONCLUSION: Illness duration and severity were not statistically significant with echinacea compared with placebo. These results do not support the ability of this dose of the echinacea formulation to substantively change the course of the common cold. PRIMARY FUNDING SOURCE: National Center for Complementary and Alternative Medicine, National Institutes of Health.

Hypereosinophilia associated with echinacea use.

Echinacea, believed by herbal practitioners to enhance the immune system, is one of the most widely used herbal supplements in the United States. Like most herbal products, it lacks strict FDA regulation and more information is needed about its potential adverse reactions. Here, we report the case of a patient with eosinophilia of unclear etiology whose condition resolved after cessation of this supplement. We feel this likely represents an IgE-mediated allergic process to echinacea.

Usage of herbal medications in patients undergoing IVF treatment in an Irish infertility treatment unit.

BACKGROUND: Usage of herbal and complimentary medicines by patients presenting for procedures that require the use of anaesthetic agents is common. AIMS: To determine the prevalence of herbal medication usage among female patients attending for assisted reproduction procedures involving the use of sedative or hypnotic agents. METHODS: Questionnaire-based survey carried out over a 6-month period from January to July 2007. RESULTS: Forty-six percent of patients admitted regular use of herbal medications, with 38% of patients having taken herbal preparations in the 3-month period prior to their attendance for treatment. No patient taking herbal preparations had discussed the use of these products with the attending anaesthetist or fertility specialist prior to attending for the procedure. CONCLUSIONS: The usage of herbal medications with potential for serious adverse effects is high in this unique patient population. Education of both healthcare providers and patients is indicated.

Perioperative risks and benefits of herbal supplements in aesthetic surgery.

Most medications, herbal preparations, and nutraceutical supplements have notable effects on biochemical pathways and may influence wound healing, coagulation, and cardiovascular function. They can also interact with other drugs. A large portion of the data available regarding the effects of naturopathic medicines is anecdotal. Marketing of certain products may be misleading and potentially harmful, and quality control standards are highly variable. In order to ensure quality control and standardization of products, it is prudent to work with preparations manufactured by companies that adhere to pharmaceutical (good manufacturing practice [GMP]) standards. However, many of these higher-quality products are not readily available to the public over the counter. A large percentage of patients undergoing plastic surgery use one or more herbal medications, but the disclosure of such medications to allopathic providers is often incomplete. In addition, patients may not understand the importance of discontinuing such medications before surgery. The authors review research on the possible benefits and risks of commonly used herbal medications such as arnica montana, St. John's wort, bromelain, echinacea, ginkgo biloba, ephedra, valerian, and others, focusing on their potentially positive or negative impact during the perioperative period of aesthetic surgery. Good communication with surgical patients, including the administration of a presurgical questionnaire to help identify any use of herbal medications, is emphasized.

A critical evaluation of drug interactions with Echinacea spp.

Accurate information concerning drug-herb interactions is vital for both healthcare providers and patients. Unfortunately, many of the reviews on drug-herb interactions contain overstated or inaccurate information. To provide accurate information on drug-herb interactions healthcare providers must account for product verification, dosage, medicinal plant species, and plant part used. This critical review assessed the occurrence of drug interactions with one of the top selling botanical remedies, echinacea including Echinacea angustifolia, E. pallida, and E. purpurea. Only eight papers containing primary data relating to drug interactions were identified. Herbal remedies made from E. purpurea appear to have a low potential to generate cytochrome P450 (CYP 450) drug-herb interactions including CYP 450 1A2 (CYP1A2) and CYP 450 3A4 (CYP3A4). Currently there are no verifiable reports of drug-herb interactions with any echinacea product. However, further pharmacokinetic testing is necessary before conclusive statements can be made about echinacea drug-herb interactions. Given our findings, the estimated risk of taking echinacea products (1 in 100,000), the number of echinacea doses consumed yearly (> 10 million), the number of adverse events (< 100) and that the majority of use is short term, E. purpurea products (roots and/or aerial parts) do not appear to be a risk to consumers.

Application of FDA adverse event report data to the surveillance of dietary botanical supplements.

BACKGROUND: Concerns have been raised about the sufficiency of dietary botanical supplement (DBS) surveillance in the US. The Food and Drug Administration's Center for Food Safety and Applied Nutrition's Adverse Event Reporting System (CAERS) represents one of the few existing surveillance mechanisms, but it has not been well characterized with respect to DBS adverse effects. OBJECTIVE: To characterize data on DBSs associated with adverse event reports submitted to CAERS. METHODS: We requested and obtained CAERS data from 1999 to 2003 involving adverse effects associated with the 6 most frequently used DBSs: Echinacea, ginseng, garlic, Ginkgo biloba, St. John's wort, and peppermint. We summarized and characterized the adverse event reports received, focusing on the composition of the DBSs and the nature of associated adverse events. We also cross-referenced reported single-ingredient DBSs with corresponding available product information. A sample of CAERS cases associated with signal DBSs was also characterized in detail. RESULTS: CAERS reports involving ginseng DBSs were most frequently reported during the study period, whereas reports involving St. John's wort were the least frequently reported. Most CAERS reports involved multiple-ingredient DBSs, and 3-13% of reports involved multiple DBSs. Gastrointestinal and neurologic problems were the most common clinical outcomes among single-ingredient DBS-associated adverse events. CONCLUSIONS: CAERS surveillance of DBS adverse effects is potentially as effective as other passive surveillance methods, but the number of reports is relatively small, validation is incomplete, and some inconsistencies within reports were found. Reports in CAERS may underrepresent DBS adverse events associated with DBS consumption.

National surveillance of herbal dietary supplement exposures: the poison control center experience.

PURPOSE: The purpose of this report is to characterize reports to poison control centers (PCCs) involving two widely used herbal dietary supplements (HDSs), Echinacea, and St. John's wort (SJW). METHODS: We purchased data from the American Association of Poison Control Center's (AAPCC) toxic exposure surveillance system (TESS(R)) on reports made to PCCs in 2001 involving Echinacea or SJW. Analyses were limited to those cases in which Echinacea or SJW were the only associated products, and in which these HDSs were deemed primary to observed adverse effects. Descriptive statistics were generated for selected demographic and exposure-related variables. RESULTS: During 2001, PCCs were contacted regarding 406 exposures involving Echinacea and 356 exposures involving SJW. Most of the reported exposures for both HDSs occurred among children 5 years and younger, and the majority of exposures were coded as unintentional. For both HDSs, exposures among patients >/=20 years old were more likely to be associated with adverse effects. Intentional exposures accounted for 21% of SJW cases and 3% of Echinacea cases, with 13% of SJW exposures reported as 'suspected suicidal'. CONCLUSIONS: TESS represents a potentially important means of assessing and characterizing HDS-related adverse effects. Detailed studies validating the clinical events and outcomes of a sample of exposures reported to TESS(R) might offer substantial insights into adverse events (AEs) that could be systematically studied with other, established pharmacoepidemiological study designs.

Safety and efficacy of echinacea (Echinacea angustafolia, e. purpurea and e. pallida) during pregnancy and lactation.

BACKGROUND: There is a lack of basic knowledge on the part of both clinicians and patients as to the indications for use and safety of herbal medicines used in pregnancy and lactation. This is one article in a series that systematically reviews the evidence for commonly used herbs during pregnancy and lactation. OBJECTIVES: To systematically review the literature for evidence on the use, safety, and pharmacology of echinacea focusing on issues pertaining to pregnancy and lactation. METHODS: We searched 7 electronic databases and compiled data according to the grade of evidence found. RESULTS: There is good scientific evidence from a prospective cohort study that oral consumption of echinacea during the first trimester does not increase the risk for major malformations. Low-level evidence based on expert opinion shows that oral consumption of echinacea in recommended doses is safe for use during pregnancy and lactation. CONCLUSIONS: Echinacea is non-teratogenic when used during pregnancy. Caution with using Echinacea during lactation until further high quality human studies can determine its safety.