Weight gain is a frequent problem in perimenopausal and postmenopausal women. Cimicifuga racemosa (CR) is a popular treatment option for menopausal symptoms. The aim of this review was to investigate whether there is scientific evidence that CR causes weight gain. We searched our database for medically confirmed, spontaneous adverse events regarding weight gain, literature for case reports and randomized controlled trials. Thirty cases in total were spontaneously reported in 15 years. The causality was not considered certain/likely in any of the cases. A nurse (consumer) assessed the causality as possible. Only one case was published in the literature. However, no change in body fat composition was reported, and the causality seems unlikely. Of the 31 identified studies, 17 were double-blind placebo-controlled, five were double-blind reference-controlled and nine were open reference-controlled. In total, 1839 women were treated with CR for up to 12 months. Two studies reported weight gain as an adverse event; however, no significant differences in weight changes were observed between the groups. One case of weight gain (about 2 kg) was reported, but the authors did not specify in which treatment group. In conclusion, this study provides no scientific evidence that the use of Cimicifuga racemosa causes weight gain in menopausal women.

Herbal medicines like Esberitox (TOX, wild indigo root stock, echinacea root, thuja tips and leaves) are used to treat common colds. Several randomized, controlled trials (RCT) document the efficacy and safety of TOX in this indication. So far its efficacy and safety has not been evaluated meta-analytically. We included individual patient data from all 825 patients from 3 RCTs. 693 patients had been treated with TOX, 132 with placebo (PLA) (7-9 days). All symptom scores were adjusted to baseline and meta-analyzed regarding area under the curve (AUC), time to response (≥50% decrease of symptom score), response rate and duration of the cold. The AUCs of the rhinitis score were 19.05 with TOX superior to 20.57 with PLA (p=0.020), bronchitis score 14.92 versus 16.16 (p=0.039) and well-being 208.4 versus 216.4 (p=0.008). Response rates were higher in TOX than PLA in all scores. The times to response showed an acceleration of the healing process of rhinitis (1.5 days, p=0.049), bronchitis (2 days) and pain (2 days, p=0.008). The duration of the cold was shortened by TOX by up to 2.3 days. The ADR-rate did not differ significantly (2.7% vs. 1.5%, p=0.41). Tolerability was good to very good in 98.4% (TOX) and 99.2% (PLA) (p=0.34). In conclusion, this meta-analysis confirmed the efficacy and tolerability of Esberitox at a higher level of evidence. It accelerates the improvement of cold symptoms by up to 2 days and shortens the duration of colds by up to 2.3 days.

Background: The unique extract of a mixture of Baptisiae tinctoriae radix, Echinaceae pallidae/purpureae radix and Thujae occidentalis herba alleviates the typical symptoms of the common cold and shortens the duration of the disease. Purpose: The risk-benefit ratio of a concentrated formulation of this herbal extract was investigated under everyday conditions. Study design: Pharmacy-based, non-interventional, multicenter, open, uncontrolled study registered at DRKS00011068. Methods: For 10 days, patients completed a diary questionnaire rating the severity of each common cold symptom on a 10-point scale. For evaluation, symptoms were combined into the scores "overall severity", "rhinitis", "bronchitis" and "general symptoms". Cox models were used to evaluate the influence of covariates on the time of stable improvement. Results: In total 955 patients (12 to 90 years) were analyzed; 85% assessed the efficacy as good or very good. Response (improvement of the overall severity by at least 50%) was reached at median day 5 (95% CImedian 5-5). General symptoms abated faster than the other complaints. The percentage of predominantly moderate or severe symptoms to predominantly mild or absent symptoms reversed on day 3.9 (interpolation). Results of adolescents and adults did not differ (p = .6013; HR = 0.918). Concomitant medication did not boost the effect of the herbal remedy. Early start of treatment of the cold accelerated the recovery (p = .0486; HR = 0.814). Thirty-four cases of adverse events were self-recorded in the diaries; none of them were serious. The tolerability was assessed as "good or very good" by 98% of the patients. Conclusion: The benefit-risk assessment of this herbal extract clearly remains positive. This non-interventional study accords with and shows transferability of the results of previous placebo-controlled studies with this extract in a real-life setting.

Endocrine therapy in breast cancer survivors can cause severe climacteric' symptoms, which may compromise therapy adherence. To determine whether such symptoms can be treated with herbal medication containing black cohosh in the form of isopropanolic Cimicifuga racemosa extract (iCR) alone or in fixed combination with St John's wort (Hypericum perforatum [HP]) (iCR+HP), a systematic literature search was conducted. Results were viewed in relation to experimental data and metabolism of endocrine therapies. Most breast cancer survivors receiving endocrine therapy experienced reductions in climacteric symptoms under iCR/iCR+HP. Tamoxifen's interference potential may be countered by using higher iCR doses or iCR+HP. No estrogen-like effects at the breast or on hormones were seen. After breast cancer, even if receiving tamoxifen, patients using iCR/iCR+HP had significantly increased recurrence-free survival rates compared to non-users. These results are substantiated by experimental data demonstrating antiproliferative and anti-invasive effects of iCR in breast cancer cells and enhancement of the antineoplastic effects of tamoxifen. There are no known clinical interactions for iCR and HP with endocrine therapies. The HP extract used in iCR+HP did not exhibit any clinically relevant interaction potential. In conclusion, with its positive benefit-risk profile, iCR/iCR+HP may offer a safe non-hormonal therapeutic option for breast cancer survivors receiving endocrine therapy.

Anderson et al. in 2015 presented two case reports of Baptisia poisoning ( 1 Anderson M.J. Kurtycz D.I. Cline J.R. Baptisia poisoning: a new and toxic look-alike in the neighborhood. J Emerg Med. 2015; 48: 39-42 Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar ). An 85-year-old woman and her daughter (48 years old) presented to the Emergency Department with gastrointestinal complaints and dizziness after they had eaten plant material that they had collected from a municipal rain garden. The ingested plant material was identified to be Baptisia australis. The authors found on the Internet numerous herbal supplements containing Baptisia as a remedy for upper respiratory infections (URI), and discussed the poisoning of Baptisia without specification or special consideration of the botanical variety ( 1 Anderson M.J. Kurtycz D.I. Cline J.R. Baptisia poisoning: a new and toxic look-alike in the neighborhood. J Emerg Med. 2015; 48: 39-42 Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar ). Baptisia Poisoning: A New and Toxic Look-alike in the NeighborhoodJournal of Emergency MedicineVol. 48Issue 1PreviewBaptisia is commonly found in residential gardens as an ornamental plant, in municipal “rain gardens” for water control, as well as in native and restored prairie habitat. Cytisine, an alkaloid with nicotinic acetylcholine receptor agonist properties, is a component of Baptisia. Full-Text PDF

Die Blätter von Arctostaphylos uva-ursi (Bärentraubenblätter) werden traditionell zu Behandlung von Harnwegsinfektionen angewendet. Durch Metabolisierung in der Leber entsteht aus dem Hauptwirkstoff (Arbutin) Hydrochinon (HQ), welches im Rahmen einer Phase-II-Reaktion zügig konjugiert wird. Lediglich ein kleiner Anteil verbleibt als freies HQ, dessen potenzielle Mutagenität in der Literatur immer wieder diskutiert wird.

Menopause, a natural process of aging, remains asymptomatic for few women while 50–85% of women worldwide experience disabling symptoms, which significantly affect their well-being and quality of life.

Uva-ursi folium (bearberry leaf) has been traditionally used to treat symptoms of lower urinary tract infections. The most representative constituent of this herbal drug is arbutin that is rapidly absorbed in the small intestine and undergoes hepatic conjugation to form hydroquinone (HQ) conjugates. As free HQ is crucial for the safety of the herbal preparation, we reviewed published and unpublished experimental and human studies to clarify some outdated assumptions and to support the safety of therapeutic daily doses of Uva-ursi folium extract. Specifically, data on pharmacokinetics and the human exposure of arbutin and HQ were reviewed. A therapeutic recommended human daily dose of bearberry leaf extract (420 mg hydroquinone derivatives calculated as anhydrous arbutin) liberates free HQ in urine at a maximum exposure level of 11 µg/kg body weight (bw)/d. By means of an experimental no observed effect level value, a permitted daily exposure dose below which there is a negligible risk to human health was estimated for free HQ (100 µg/kg bw/d). Dietary sources of arbutin/HQ that are regularly consumed long term by humans generate comparable free HQ exposure levels. There is no direct evidence, regarding human data, supporting the fact that free HQ causes convulsion, hepatotoxicity, nephrotoxicity, or promotion of tumors in humans. Free HQ had no activity promoting pancreatic, bladder, stomach, or liver carcinogenesis. In conclusion, under the recommended use conditions Uva-ursi folium is a safe therapeutic option for treating lower urinary tract infections.

Objective: Black cohosh, a popular herbal treatment for menopausal symptoms, has been implicated in a number of hepatotoxicity case reports. The purpose of this investigation was to analyze data gained from clinical trials on the effect of black cohosh on liver function. Methods: A meta-analysis of randomized, double-blind, and controlled clinical trials was conducted. These studies primarily evaluated the efficacy and safety of the isopropanolic black cohosh extract (iCR) in perimenopausal and postmenopausal women. Raw data on liver function values of aspartate aminotransferase, alanine aminotransferase, and &ggr;-glutamyltranspeptidase were considered in this analysis, if these data at baseline and after 3 to 6 months of treatment were available. Standard methods of descriptive statistics were used in this analysis. Results: Five studies involving a total of 1,117 women were included in the meta-analyses. A total of 1,020 women (test population = 517 and reference population = 503) completed the studies. Perimenopausal and postmenopausal women (40-60 y) were treated daily with iCR (corresponding to 40-128 mg drug) for 3 to 6 months. The meta-analyses of the standardized mean differences in the "test" versus "reference" showed no significant effects and no differences between double-blind, placebo-controlled and other trials. The overall fixed effect ± SEM was 0.055 ± 0.062 (P = 0.37) for aspartate aminotransferase and 0.063 ± 0.062 (P = 0.31) for alanine aminotransferase. The nonsignificant effects concerned the overall analyses of all included studies as well as the proportion of placebo-controlled studies. Conclusions: The results of this meta-analysis of five randomized, double-blind, and controlled clinical trials showed no evidence that iCR has any adverse effect on liver function.

Aim: Documentation on safety and tolerability of Esberitox® tablets (Thujae occidentalis herba, Echinaceae radix, Baptisiae tinctoriae radix; formerly Esberitox® N) in a group of children from 4–11 years of age treated for viral cold diseases.

TO THE EDITOR: The recent case report by Chow and colleagues raises questions about the causal link between black cohosh use and hepatotoxicity. The authors state that the patient had no history of “significant alcohol consumption”, but a presumably related adverse drug reaction report avail­ able from the Therapeutic Goods Adminis­ tration reveals her alcohol use was “3–4 units [of] alcohol per day, [with] 1–2 alco­ hol-free days per week”. Alcohol misuse is a known risk factor for severe liver disease, as is gastric bypass surgery for obesity, also in the patient’s history. Unfortunately, because histological examination of the liver 6 weeks after first presentation found no recognisable residual hepatocytes, the diag­ noses of alcoholic steatohepatitis, non-alco­ holic fatty liver disease and non-alcoholic steatohepatitis cannot be excluded. Without this, the specific conclusion of the liver biopsy that the “Massive hepatocellular necrosis [was] associated with herbal medi­ cation” cannot be substantiated. The patient “was not taking any other medications, including other herbal prepa­ rations”, but the use of multivitamins was disclosed, without further information on ingredients, indication, dosage and duration of use. Notably, an overdose of vitamin A can cause severe liver disease. Finally, discontinuation of black cohosh failed to reduce the patient’s bilirubin levels, suggesting ongoing liver cell destruction by the as-yet unknown agent. Chow et al state “Extensive investigations to exclude other causes of acute liver failure gave negative results”. It is unclear whether rare liver diseases were excluded, notably herpes infection, which has been reported to cause severe herpetic hepatitis. Nor was polymer­ ase chain reaction testing performed for hepatitis viruses. The authors mentioned other published case reports of hepatotoxicity potentially linked with black cohosh. A recent assess­ ment of 42 cases by the European Medicines Agency (EMEA) concluded that most were insufficiently documented, or were otherwise inappropriate for analysis. A case in the United States initially described as “probable” (> 1000% of the recommended dosage of black cohosh), based on the report that the patient “did not drink alcohol or use illicit drugs and was not taking any medications”, was later corrected. The patient testified under oath that she drank wine regularly and used other drugs, and a US court judged there was no evidence to establish that black cohosh had caused her liver disease. There is no apparent credible evidence that black cohosh caused liver failure in the patient described by Chow et al. A daily alcohol consumption of 30–40 g should be considered principally in any causality assessment. In addition, idiopathic reasons, rare or unclear liver diseases, and other medications should be considered as possi­ ble causes. Even in patients with liver disease who consume little or no alcohol and have no exposure to other toxic agents, the cause of the disease remains unclear in up to 30%. In view of this, reliable and sufficient reporting of adverse drug reactions is a necessary precondition to any reliable assessment of causality.

Joseph M. Betz, PhD Linda Anderson, PhD Mark I. Avigan, MD Joanne Barnes, PhD Norman R. Farnsworth, PhD Barbro Gerdén, MD Leigh Henderson, MS Edward J. Kennelly, PhD Uwe Koetter, PhD Stephanie Lessard, MS Tieraona Low Dog, MD, PhD Michelle McLaughlin, BS Belal Naser, MD Ruediger G. W. Osmers, MD, PhD Linda S. Pellicore, PhD John R. Senior, PhD Richard B. van Breemen, PhD Wolfgang Wuttke, MD John H. Cardellina II, PhD

Photosensitivity of the skin is a known side effect of St. John's Wort (SJW). In an open, phase one clinical trial (GCP) the effect of an ethanolic (60% V/V) SJW extract (Esbericum® capsule) on dermal photosensitivity was evaluated by determination of the minimal erythema dose (MED) before and after 2 weeks of therapy. Each of the volunteers received 3 capsules (60mg SJW dry extract (3.5–6:1)/capsule) twice daily (7.00 a.m./p.m.). At days –2 and 14, solar simulated skin irradiation was performed with a Dermalight® Erythemtester (285–350 nm) to determine and analyse MEDpre and MEDpost (paired t-test, Wilcoxon test). Photoreaction and symptoms of skin reaction were evalutated respectively 24h after irradiation using validated rating scales. Changes in pre-post MED values resulted in a mean difference of 2.30 mJ/cm2 (–8.25%) (two-sided paired t-test; p=0.2617). This non-significant result is confirmed by the 95% CI (–6.45 to 1.86mJ/cm2) and indicates no relevant increase in dermal photosensitivity of the SJW-extract in Esbericum® capsule. This is a further contribution to the good safety profile of this SJW-extract.

The aim of this study was to verify the efficacy and safety of an herbal medication containing an extract of a mixture of Baptisiae tinctoriae radix, Echinaceae pallidae/purpureae radix and Thujae occidentalis herba (SB-TOX) in the treatment of upper respiratory tract infections (URIs), and to test whether SB-TOX's clinical efficacy is dose dependent. A total of 91 adults (mean age 42.1±13.0 years) were randomised to receive 19.2 mg of SB-TOX (n=31), 9.6 mg SB-TOX (n=29) or placebo (n=31) three times daily for 3–12 days. Since a "running nose" is the main symptom of a common cold, the total number of facial tissues used throughout the clinical duration of their cold was the primary efficacy parameter. In the intention-to-treat analysis, this total number of tissues decreased with increasing extract dose. The slope across groups according to the Jonckheere test was significant (p=0.0259). In the high-dose group, the standardised effect size Δ/SD was 0.46 compared with placebo. Time to relevant improvement in cold symptoms (measured as the time until less than 30 tissues per day were used) was 1.1 days (95% CI 0.52; 1.67), 0.76 days (95% CI 0.28; 1.24) and 0.52 days (95% CI 0.22; 0.82) in the placebo, low-dose and high-dose groups, respectively (pLogRank=0.0175). No adverse events were reported. This study demonstrates the efficacy and safety of SB-TOX in the treatment of URIs, and that its efficacy is dose dependent.

Arbor vitae (Thuja occidentalis L.) is a native European tree widely used in homeopathy and evidence-based phytotherapy. Many reviews and monographs have been published on the herbal substance's description, mode of action and clinical use. However, no comprehensive evidence-based review is available. Therefore, our aim was to search MEDLINE databases and survey manufacturers for further details or unpublished data. This review presents the botany, ethnobotany and phytochemistry, especially the different contents of essential oil (Thujone) in relation to different extraction procedures of this medicinal plant. Thuja's antiviral action and immunopharmacological potential, such as stimulatory and co-stimulatory effects on cytokine and antibody production and activation of macrophages and other immunocompetent cells, have been evaluated in numerous in vitro and in vivo investigations. Although no controlled trials have been conducted on Thuja occ alone, many clinical studies have been performed with a herbal medicinal product containing a special extract of Thuja occ and other immunostimulants, demonstrating its therapeutic efficacy and safety in respiratory tract infections.