Clinical Efficacy of Australian Eucalyptus and Lemon scent Tea Tree Essential Oils for Head Lice Treatment

  • Australian Eucalyptus (Eucalyptus globulus, Myrtaceae)
  • Lemon-scent Tea Tree (Leptospermum petersonii, Myrtaceae)
  • Head Lice

Head lice infestation, most often seen in children aged 3 to 14 years, causes itching and discomfort, as well as parental anxiety, embarrassment, and school absences. The use of treatments containing neurotoxins has caused safety concerns and has led to resistant lice populations. Alternative treatments have been developed for improved efficacy and concerns about the use of neurotoxins. These authors conducted a multicenter, randomized, parallel-group trial to compare the safety and efficacy of head lice treatments of Australian eucalyptus (Eucalyptus globulus, Myrtaceae) oil and lemon-scent tea tree (Leptospermum petersonii, Myrtaceae) oil (EO/LP) with a neurotoxic mousse containing pyrethrins and piperonyl butoxide (P/PB) in children (trial 1). In trial 2, a single-blind, open trial, the authors studied the efficacy of the EO/LP solution in killing head lice after a single application. Skin irritancy and sensitivity tests were conducted in both adults and children, and the efficacy of EO/LP solution in killing live lice and louse eggs was tested in vitro.

Conducted in Queensland, Australia, the study included male and female schoolchildren up to grade 7 who had live head lice in their hair or on their scalp upon visual inspection and dry-combing with head lice comb.

The EO/LP treatment used was MOOV Head Lice Solution (Ego Pharmaceuticals Pty Ltd; Braeside, Victoria, Australia), which contained 11% per weight eucalyptus oil and 1% per weight lemon-scent tea tree oil. The P/PB treatment was Banlice® Mousse (Pfizer Consumer Healthcare Group; West Ryde, New South Wales, Australia), which contained 1.65 mg/g pyrethrins and 16.5 mg/g piperonyl butoxide.

The EO/LP solution was applied 3 times – on days 0, 7, and 14. Although the P/PB mousse manufacturer recommended only 1 treatment, the mousse was applied twice – on days 0 and 7 – as recommended by the Therapeutic Goods Administration of Australia. The technicians applying the treatments were not blinded because of the physical and smell differences between the treatments; however, the assessment technicians, subjects, and parents did not know which treatment was being used.

The intention-to-treat (ITT) population, which included all randomly assigned subjects before treatment, was used to determine the safety and efficacy. Subjects included in the per-protocol (PP) population were those who completed all treatments of the EO/LP solution or the P/PB mousse. Subjects’ siblings who had lice were treated in the same manner as the subjects and were enrolled in the trial. Siblings with no head lice but with evidence of recent infestation underwent wet-combing. Any adverse effects were recorded at each study visit.

Of the 97 subjects in the ITT population, 76 met the requirements for the PP analysis. Subjects did not meet the PP requirements for the following reasons: 1 did not receive the required dose, 3 used alternative head lice treatments during the trial, 15 failed to comply with sibling control criteria, 1 failed to appear on day 21, and 1 withdrew due to an adverse event. Of the PP population, 40 received the EO/LP solution and 36 received the P/PB mousse.

Analysis of the PP population revealed a significant between-group difference in cure rate at 7 days, with 83% of the EO/LP group cured compared with 36% of the P/PB group (P<0.0001). On day 1, no significant differences were seen in cure rate between the 2 groups. In the ITT subjects, at day 7, 71% in the EO/LP group were cured compared with 33% in the P/PB group (P=0.0002). No significant between-group difference in cure rate was observed on day 1.

Of the 97 subjects who received at least 1 treatment, 21 adverse effects were reported in 13 subjects; the 18 adverse effects reported in the EO/LP group included transient mild to moderate sensations such as itchiness, stinging, or burning lasting no more than 5 minutes and requiring no treatment. The 3 adverse effects in the P/PB group included 1 crawling and 2 stinging sensations.

In trial 2, on day 0, 11 subjects with live lice received treatment with the EO/LP solution. The authors report that after the single EO/LP application, the 1,418 head lice collected were considered dead as they were wet-combed out of the hair. Upon examination 30 minutes after combing, all lice were confirmed dead.

For the skin irritation and sensitivity study, a patch containing the EO/LP solution was applied to the skin of the back for 24 hours every Monday, Wednesday, and Friday for 3 consecutive weeks. Then, 10 to 14 days afterward, 1 challenge or retest dose was applied to a previously unexposed test site and assessed 24 and 48 hours later. Fifty-three of the 56 adult subjects enrolled in this study completed it; 3 withdrew for reasons unrelated to the study protocol. The authors report that no erythema, edema or adverse effects were observed.

For the pediatric testing for skin irritation or sensitivity, 20 children aged 6 months to 4 years were examined on the scalp, face, and neck, and then the EO/LP solution was applied on days 0, 7, and 14. The subjects were evaluated after each application and again 24 hours after the last application. The authors report that no test-related irritation was observed, and no safety-related comments were made by any subjects or their parents.

In testing the in vitro efficacy of the EO/LP solution, the authors observed that no louse eggs hatched for 10 days after a 10-second immersion in the solution. Following immersion in the control (purified water) treatment, 24% of the eggs hatched after 7 days, 76% after 8 days, 92% after 9 days, and 92% after 10 days. Other findings revealed that 60 minutes after a 10-minute exposure to the EO/LP solution, 100% of the body lice were moribund or dead; all the body lice immersed in water were alive. The authors conclude that compared with the water treatment, the EO/LP solution was 100% effective in killing lice (P<0.0001).

The authors attribute the treatment failures seen in 7 of the 40 subjects in the EO/LP group in trial 1 to the fact that some lice or some eggs survived any 1 of the 3 treatments or that re-infestation occurred. After observing the results of the in vitro studies revealing “that the EO/LP solution is 100% ovicidal after only a 10-s immersion, it is more likely that the treatment failures are due to re-infestation,” they write.

The authors conclude that “the EO/LP solution contains a proprietary combination of essential oils that has been shown to be safe and effective in eliminating head lice in Australia,” and because the solution is both volatile and quickly effective, “it is unlikely to cause the development of head lice resistance in the community.”

Resource:

Greive KA, Barnes TM. The efficacy of Australian essential oils for the treatment of head lice infestation in children: a randomized controlled trial. Australas J Dermatol. March 7, 2017; [epub ahead of print]. doi: 10.1111/ajd.12626.

 

Flow Injection Mass Spectrometry, Proton Nuclear Magnetic Resonance, and DNA Sequencing Can All Distinguish Black Cohosh from Likely Adulterants

Harnly J, Chen P, Sun J, et al. Comparison of flow injection MS, NMR, and DNA sequencing: methods for identification and authentication of black cohosh (Actaea racemosa). Planta Med. February 2016;82(3):250-262. doi: 10.1055/s-0035-1558113.

Authentication and correct identification of botanicals in dietary supplements are critical for a number of reasons, not the least of which is potential harm from the inclusion of undesirable species. The process of identification may be complicated by material processing, variable preparation methods, and the existence of very similar related species. Current methods for identification of botanicals include morphological identification, DNA sequencing, and phytochemical and metabolic fingerprinting. As black cohosh (Actaea racemosa syn. Cimicifuga racemosa, Ranunculaceae) is a popular medicinal plant, adulteration is increasingly common. This basic research study coupled two methods of phytochemical fingerprinting, flow injection mass spectrometry (FIMS) and proton nuclear magnetic resonance (1H NMR), with DNA sequencing to determine how well they could identify different species of Actaea before and after processing.

Root samples from various species of Actaea were procured from American Herbal Pharmacopoeia (AHP), Scotts Valley, California; Strategic Sourcing, Inc., Banner Elk, North Carolina; The North Carolina Arboretum Germplasm Repository (TNCAGR), Asheville, North Carolina; National Institutes of Standards and Technology, Gaithersburg, Maryland; and from Chinese commercial sources. Liquids, tablets, and capsules were bought from local stores in Maryland, and additional samples were obtained from the United States Department of Agriculture, Washington D.C. The roots and commercial samples were authenticated using DNA sequencing at AuthenTechnologies LLC; Richmond, California. DNA sequences from the nuclear ribosomal internal transcribed spacer (ITS) region and the chloroplast psbA-trnH intergenic spacer, obtained by polymerase chain reaction (PCR) and Sanger capillary sequencing, were used for authentication by comparing them to the reference sequences. To prepare samples for FIMS, root material, tablets, and contents of capsules were powdered and extracted in 70:30 methanol:water, sonicated, centrifuged, diluted 1:10 with methanol, and filtered. Liquid extracts were combined with 70:30 methanol:water and treated as described above. To prepare for NMR, samples were dissolved in dimethyl sulfoxide-d6 containing 0.47 mM 4,4-dimethyl-4-silapentane-1-sulfonic acid, vortexed, sonicated, and centrifuged.

Each sample was run on FIMS five times, with random sample order each time; most samples were run once for NMR. Raw data were exported into various computer programs for analysis. Data were normalized to unit vector length (this metric incorporates the sum of squares) and analyzed using principal component analysis (PCA, an analysis that displays data based on greatest variation) and four multivariate analysis methods, especially soft independent modeling of class analogy (SIMCA, an analysis based on modeling that fits a model to a single class, which is explained to be useful for authentication). Both methods of analysis were used to assess whether FIMS or NMR could distinguish various Actaea species. Because of the complexity of PCA plots in including all samples, the authors chose to analyze the data from only the following five American species: black cohosh, bugbane (A. cimicifuga), baneberry (A. pachypoda), American bugbane (A. podocarpa), and red baneberry (A. rubra).

In analyses of both FIMS and NMR data, samples of black cohosh generally clustered separately from other species; some analyses portray it as most similar to baneberry, suggesting a close relation, and more distant from other species. One sample of black cohosh was found to occur outside the black cohosh cluster, and one sample of baneberry clustered with black cohosh; repeated analyses starting from new raw material had the same result. Significant phytochemical variation was observed within species; in the FIMS analysis, samples from multiple sites supplied by TNCAGR clustered according to the site of origin. The authors noted that the potential causes of geographically correlated variation include not only genetic differences and environmental influences on the plants but variation in the presence of endophytic fungi, which are suspected of producing some of the secondary compounds in black cohosh. The models for FIMS and NMR were validated using bootstrap analysis, despite the authors’ concern about limited sample size. It was found that FIMS had a sensitivity of 91.4% and NMR had a sensitivity of 91.7%, with specificities of 100% for both. Overall, it was concluded that both FIMS and NMR are appropriate techniques for distinguishing the five species of Actaea, with sensitivity to the phytochemical composition.

For North American samples of multiple species, putative identities according to DNA sequencing were generally consistent with the AHP identification, although sequencing quality problems sometimes precluded identification. The two samples that seemed to be outliers (black cohosh and baneberry) in the FIMS and NMR analyses had DNA sequences consistent with the stated identity. This suggests that the species are biologically complex species with morphological or chemical variations greater than the genetic variations. Very few of the geographically diverse black cohosh samples from TNCAGR, which were subjected to chemical analysis, were included in DNA analyses.

Root samples procured from China were stated to belong to four different species;

nuclear ribosomal DNA (nrDNA) and chloroplast DNA (cpDNA) sequences indicated that the majority of samples, including one purported sample of A. racemosa, were Chinese cimicifuga (A. dahurica) and one was A. brachycarpa, while two contained non-Actaea spp. plant material and another had only fungal DNA amplified. All of these, as well as some North American Actaea spp. samples were said to be “mixtures” according to ITS data, and to some extent according to psbA-trnH data; it appears that this simply means that more than one ITS sequence variant was present in some samples, while other samples may contain hybrid plant material. DNA analysis confirmed that four of the seven capsule supplements purchased locally contained black cohosh, while one contained A. brachycarpa; the other two had no detectable Actaea spp. DNA (one had no DNA and the other had rice [Oryza sativa, Poaceae] DNA or excipient DNA only). Liquid extract supplements were not analyzed with DNA sequencing since they were not expected to contain retrievable DNA. In summary, the FIMS and NMR analyses showed diverse chemical profiles that were different from any of the raw materials tested, which is presumably due to differences in processing and extraction methods or systematic geographical variations. Moreover, the DNA sequencing of roots could be used for identification of Actaea species and also for validating the discrepancies that might arise in the chemical fingerprinting methods.

In conclusion, the three methods outlined here may be useful to aid in authentication of black cohosh in commerce and identify possible adulterants. However, more experimentation and adjustment of methods would be necessary to analyze finished botanical supplements.

Bulletin on Adulteration of Scutellaria lateriflora

Goal:

The goal of this bulletin is to provide timely information and/or updates on issues of adulteration of Scutellaria lateriflora to the international herbal products industry and extended natural products community in general.

1 General Information

1.1 Common name: Skullcap3

1.2 Other common names:

English: Blue skullcap, helmet flower, hoodwort, European or greater skullcap, Quaker bonnet, mad-dog skullcap, mad weed, scullcap, Virginia skullcap4

French: Scutellaire, scutellaire latériflore, scutellaire de Virginie, toque, toque casquée5

German: Helmkraut, seitenblütiges Helmkraut5

Italian: Scutellaria

Spanish: Escutelaria, escutelaria de Virginia

1.3 Accepted Latin binomial: Scutellaria lateriflora L.6,7

1.4 Synonyms: Cassida lateriflora (L.) Moench; Scutellaria polybotrya Bernh.6,7

1.5 Botanical family: Lamiaceae (formerly Labiatae)

1.6 Plant part and form: The flowering aerial parts of S. lateriflora are used fresh, or dried as an infusion, as a tincture, or in the form of a fluid extract.1 Suggested daily dosages vary depending on the author and correspond to 0.25-12 g of dried aboveground flowering parts.1,8,9

1.7 General use(s): Traditionally, skullcap is used to help relieve nervousness and anxiety, as a sleep aid (mainly for stress-related cases of insomnia), or as an antispasmodic.1,7,8

2 Market

2.1 Importance in the trade: Skullcap is not a widely traded botanical commodity. In 2001, approximately 16 tons (35,000 pounds) of material were reportedly harvested and sold worldwide.10 No statistics on more recent volumes of harvested skullcap material could be identified in the published literature. The limited popularity of the herb is also shown by recent sales data from the United States (Table1), where it ranked between #99 and #107 of all single herbal dietary supplements in the Natural retail channel, and between #149 and #157 in the Mainstream Multi-Outlet retail channel. (T. Smith e-mail to S. Gafner, September 2, 2015 and September 3, 2015)

Table 1: Sales data for skullcap dietary supplements from 2012-2014.

Channel 2012 2013 2014
Rank Sales [US$] Rank Sales [US$] Rank Sales [US$]
Naturala 107 556,856 106 577,065 99 625,734
Mainstream Multi-Outletb n/a 19,355 157 22,735 149 27,997

aAccording to SPINS (SPINS does not track Whole Foods Market sales, which is a major natural products retailer in the US)

bAccording to SPINS/IRI (the Mainstream Multi-Outlet channel was formerly known as food, drug and mass market channel [FDM], exclusive of possible sales at Walmart)
n/a: not available
Source: T. Smith (American Botanical Council) e-mail September 2, 2015 and September 3, 2015

2.2 Supply sources: Most supplies on the North American market appear to be obtained from cultivated sources both in the United States (e.g., Minnesota, Missouri, North Carolina, Oregon, and Washington) and internationally (e.g., Chile, Costa Rica, and Mexico).11 According to a report for the Australian government, Australian growers formerly supplied skullcap, but production halted after 2003 when global prices dropped and local growers were not able to compete with the prices from abroad.12 The majority of the skullcap used in products sold in Australia is now imported (Hans Wohlmuth e-mail to S. Gafner, January 19, 2015). There is some commercial material available that is harvested in the wild in North America, but the majority (85% according to a report from 2001) is obtained from cultivation.10

2.3 Raw material forms: In the United States, many companies that manufacture products containing properly authenticated skullcap grow it themselves.11 Bulk skullcap raw material is mainly sold as cut and sifted, in form of a teabag cut, or as powdered aboveground parts, which may be more susceptible to adulteration, since the distinct features for macroscopic identification are no longer recognizable.

2.4 Market dynamics: In 2001, an estimated 16 tons of skullcap were harvested and sold on world markets at a price of US $9-13/kg.10 Since the cessation of production in Australia, prices for imported skullcap from North America have been gradually increasing and reached Australian (AUD) $42/kg (US $31/kg based on the exchange rate from June 1, 2006) for organic crops and AUD 25-30/kg (US $19-22/kg) for conventional crops in 2006.12 Based on a 2008 newsletter of the Australian raw material supplier Network Nutrition, growers in the United States have experienced issues with cultivation due to difficulties with seed germination, crop failure, and various other issues. This has led to a shortage in raw material and the appearance of material where skullcap was substituted with other species of Scutellaria.13 In recent years, the demand for skullcap has been has been subject to fluctuations but overall trended flat or was slightly increasing. Currently, growers under contract can obtain between US $18-19/kg for conventional and US $24-29/kg for certified organic skullcap (E. Fletcher e-mail to S. Gafner, January 20, 2015; L. Ballard oral communication to S. Gafner, January 28, 2015). Pricing for the consumer is in the range of US $43-47/kg for conventionally-grown herb and US $70-110/kg for organically grown skullcap, according to an informal survey, by co-author of this Bulletin (SG), of smaller companies that had listed pricing on the Internet.

  1. Adulteration

3.1 Known adulterants: Canada germander (Teucrium canadense, Lamiaceae); germander (T. chamaedrys); Scutellaria spp., e.g., Alpine skullcap (S. alpina), Chinese skullcap (S. baicalensis), hoary skullcap (S. incana), heartleaf skullcap (S. ovata), and marsh skullcap (S. galericulata).1,8

3.2 Sources of information confirming adulteration: The most comprehensive review on adulteration of skullcap has been published by Foster in HerbalGram for the ABC-AHP-NCNPR Botanical Adulterants Program.2 Other sources for information on skullcap adulteration include the American Herbal Pharmacopoeia monograph on Scutellaria lateriflora by Upton et al.,1 and the PhD thesis by Brock.8 Some of the adulteration seems to be due to the sale of mislabeled seed material, e.g., the inadvertent cultivation of S. incana in North America, or of S. ovata in the United Kingdom. 1,8 Leroy Ballard, president at Nature’s Cathedral, Inc., an American grower and supplier of native American medicinal plants, commented that there are still between 1350 and 1800 kg (3000 and 4000 lbs) of S. incana sold as “Scutellaria spp.” in the United States, but most of this material is exported overseas. (L. Ballard oral communication to S. Gafner, January 28, 2015). According to Brock, it is not clear how much of the skullcap material used by herbalists in the UK is actually S. ovata.8 Further evidence of ongoing adulteration of skullcap products available in the US market is demonstrated by the results from a study in 2011 by researchers at the United States Department of Agriculture, where 5 out of 13 commercial dietary supplements from US manufacturers purchased on the Internet were adulterated, reportedly with Canada germander and Chinese skullcap.14 [Note: The original publication does not state the source of the purchased products, but one of the authors has confirmed that they were from American (US) manufacturers. (P. Chen e-mail to S. Gafner, September 4, 2015)] Adulteration of commercially sold skullcap raw material with germander (species not identified) was also reported in 2012 by Walker and Applequist.15 Germander was formerly sold routinely as a bulk botanical in the United States but it is no longer offered by most herbal suppliers in the North American market (L. Ballard oral communication to S. Gafner, January 28, 2015).

3.3 Accidental or intentional adulteration: As indicated above, some of the adulterated material on the market may be due to rare accidental misidentification when material is harvested in the wild, or the cultivation of crops where the seeds have been mislabeled, which is likely the case for some of the adulteration with other species from the genus Scutellaria (except adulteration with Chinese skullcap, S. baicalensis, which does not grow in the same geographical area as S. lateriflora). The reasons behind the adulteration of skullcap with germander species is a matter of debate. Some experts suggest that it is accidental, but it is now believed that at least part of the adulteration is deliberate since the Teucriumspecies have a heavier dry weight than skullcap and therefore, a much higher yield is obtained when harvesting germander (E. Fletcher e-mail to S. Gafner , January 20, 2015; A. Chandra, e-mail to S. Gafner, January 23, 2015).12,16 Nomenclatural confusion may also play a roles, as pink skullcap is a common name applied to Canada germander.2

3.4 Frequency of occurrence: There is no comprehensive published study on the frequency of skullcap adulteration. The only study looking at the adulteration of skullcap dietary supplements included a limited amount of samples (n = 13) from manufacturers in the United States purchased over the Internet.14 In this study, 38% of the samples were found to be adulterated. On the other hand, a study looking at whole or minimally processed skullcap raw materials (n = 10) purchased from vendors within the United States, did not find any adulterated material, although the authors of the study specify that they “have seen a recent sample of commercial skullcap, not included within this study, that was over 50% Teucrium”.15 Similarly, a study investigating the authenticity of 11 commercial dietary supplements (10 extracts and one product made with crude powdered material) sold in the United States, using species-specific DNA primers, concluded that all nine samples from which DNA was obtained contained S. lateriflora. Two samples, including the product made with powdered raw herb, did not contain DNA of sufficient quality to determine the identity of the material (D. Harbaugh Reynaud e-mail to S. Gafner, January 14, 2016). No chemical assays were performed on these samples to confirm the results.

3.5 Possible safety/therapeutic issues: Substitution of S. lateriflora was a prominent issue in 2002 due to an Australian herbal product’s being implicated in the death of a patient due to liver failure.17According to the label, the herbal product contained kava (Piper methysticum, Piperaceae), passionflower (Passiflora incarnata, Passifloraceae) and skullcap. The authors of the case report suggested that the liver failure was possibly due to the ingestion of kava, a botanical that has been linked to rare occurrences of liver toxicity.18 However, the causative agent for the death of the Australian patient was never confirmed. The Australian Therapeutics Goods Administration (TGA) analyzed the product and determined that it did not contain skullcap. Some of the known skullcap adulterants, Teucrium species are known to cause liver injury in humans.19 The hepatotoxicity in Teucrium has been ascribed to the diterpenoid fraction.20 The liver toxicity of germander is influenced by a number of factors, including the diet, the type of germander preparation, and possibly genetic factors.21,22 In contrast to many of the germander neo-clerodane diterpenes, those with a tetrahydrofuran moiety did not show hepatotoxic effects. The neo-clerodane diterpenes isolated from skullcap by Bruno et al.23 are different since they are substituted with either a dihydrofuran-fused tetrahydrofuran moiety or a fused tetrahydrofuran-γ-lactone ring. The detection of these specific diterpenes may offer a way to uncover adulteration, although subsequent studies failed to detect diterpenes in skullcap.24,25

The root of Chinese skullcap (S. baicalensis) is widely used in Traditional Chinese Medicine. There are some reports of allergic reactions, diarrhea, and stomach discomfort after ingestion or injection of Chinese skullcap.26 There are also a small number of case reports that have linked Chinese skullcap to liver injury,27,28 but this implication is based on previous reports where causality between Chinese skullcap ingestion and liver injury reportedly has not been established,29 or on case reports implicating a proprietary mixture of flavonoids from Chinese skullcap, catechins from betelnut palm (Areca catechu, Arecaceae), and zinc bisglycinate sold as a medical food under the brand name Limbrel® (Primus Pharmaceuticals, Phoenix, AZ).28 Aboveground parts of barbed skullcap (S. barbata), a skullcap species native to China, are similarly used and theoretically could be substituted for S. lateriflora, though this has not been formally reported. Since S. lateriflora does not grow naturally in China, and based on current knowledge, is not generally cultivated there, there is a greater likelihood that attempts by companies to procure S. lateriflora from Chinese suppliers could result in use of Chinese species.

The substitution of skullcap with material from other species of Scutellaria does not pose an apparent safety risk, although the data on use in humans with the adulterating species is more limited. Scutellaria galericulata, which is also used in herbal medicine, is believed to have similar actions and indications as S. lateriflora.16 The ethnobotanical use of S. galericulata and S. incana in North America is described by Moerman.30 Scutellaria galericulata herb has been used by the Delaware tribe of Native Americans as a gastrointestinal aid and a laxative. The Ojibwe tribe used the aboveground parts for heart trouble.Scutellaria incana decoctions were used by the Cherokee as abortifacient, to treat diarrhea, against breast pain and as a gynecological aid, but ethnobotanical research suggests that Native American tribes used the root of the plant rather than the aboveground parts.30 In addition, the chemical composition of these species, with the exception of the flavonoids, has not been established in detail.

3.6 Analytical methods to detect adulteration: Confirmation of species identity and purity may be achieved by organoleptic methods, if conducted by qualified personnel (e.g., a botanist) for plant material in its whole form. For establishing the identity of cut or powdered raw material, a combination of a physical assessment test (e.g., macroscopic or microscopic) with chemical identification methods or a suitable genetic approach is considered appropriate. Results from a paper using species-specific primers to authenticate commercial skullcap supplements had a success rate of finding skullcap DNA in nine out of 11 products (82%) with the remainder not containing any identifiable DNA. Chromatographic methods, such as high-performance thin-layer chromatography (HPTLC) and high-performance liquid chromatography (HPLC), can be used for chemical characterization of raw material and extracts. A comprehensive evaluation of publicly available methods for the authentication of skullcap and detection of adulterants in skullcap, the Skullcap Laboratory Guidance Document, is available through the ABC-AHP-NCNPR Botanical Adulterations Program website.31

3.7 Perspectives: Industry expert Steven Foster, president of Steven Foster Group, Inc., believes that “there is no accidental misidentification of Teucrium canadense as Scutellaria lateriflora. That is a myth. One can easily harvest a pick-up truck load of T. canadense in a morning, whereas one would be hard-pressed to harvest a few pounds of any Scutellaria spp. from any wild habitat anywhere in the United States in a day. The adulteration of Scutellaria lateriflora with Teucrium canadense is pure and simple ‘under the radar’ economic adulteration.” (S. Foster, e-mail to S. Gafner, January 28, 2015)

4 Conclusions

Based on a survey in the United Kingdom,32 skullcap is a highly regarded medicinal herb with herbal medicine practitioners. It has remained relatively popular in the United States as a botanical to treat anxiety and stress-related conditions.1 The substitution of skullcap with germander species is particularly deplorable because of the known toxicity of species of plants in the genus Teucrium. Such adulteration is easily detected by a variety of analytical methods, a detailed report of which is available in the Skullcap Laboratory Guidance Document,31 and as such, the potentially dangerous presence of Teucrium material labelled as skullcap in botanical raw materials or finished products cannot be excused.

5 References

  1. Upton R, Graff A, Soria T, Swisher D. American Herbal Pharmacopoeia and Therapeutic Compendium: Skullcap Aerial Parts: Scutellaria lateriflora L.: Standards of Analysis, Quality Control and Therapeutics. Scotts Valley, CA: American Herbal Pharmacopoeia; 2009.
  2. Foster S. Adulteration of skullcap with American germander. HerbalGram. 2012:(93);34-41. Available at: http://cms.herbalgram.org/herbalgram/issue93/FEAT_skullgerm.html. Accessed April 21, 2016.
  3. McGuffin M, Kartesz JT, Leung AY, Tucker AO. American Herbal Products Association’s Herbs of Commerce. 2nd ed. Silver Spring, MD: American Herbal Products Association; 2000.
  4. Gruenwald J, Brendler T, Jaenicke C, et al. (eds). PDR for Herbal Medicines, 2nd ed. Montvale, NY: Medical Economics Co; 2000:678.
  5. The Plant List. Version 1.1 (September 2013). Available at: http://www.theplantlist.org. Accessed April 21, 2016.
  6. List PH, Hörhammer L. Scutellaria. In: Hager’s Handbuch der Pharmazeutischen Praxis, Volume 6. Berlin: Springer Verlag; 1979:339-341.
  7. Tropicos.org. Missouri Botanical Garden. Available at: http://www.tropicos.org. Accessed April 21, 2016.
  8. Brock CA. American skullcap (Scutellaria lateriflora L.): a study on its effects on mood in healthy volunteers. PhD thesis. London: University of Westminster; 2012. Available at: http://westminsterresearch.wmin.ac.uk/12194/1/Christine_BROCK.pdf. Accessed April 21, 2016.
  9. Health Canada: Natural Health Products Ingredients Database. Skullcap. Available at: http://webprod.hc-sc.gc.ca/nhpid-bdipsn/monoReq.do?id=159. Accessed April 21, 2016.
  10. Greenfield J, Davis JM. Medicinal Herb Production Guide: Skullcap (Scutellaria lateriflora L.). Chapel Hill, NC: North Carolina Consortium on Natural Medicines; 2004.
  11. Upton R. Skullcap Scutellaria lateriflora L.: An American nervine. J Herb Med. 2012;2(3):76-96.
  12. Yap G. Prospects for medicinal herbs: Assessment of market potential for selected medicinal herb products (Valerian, Arnica, Skullcap, Echinacea, Goldenseal). Barton, Australia: RIRDC. 2006.
  13. Gorman R. Buyer Beware: Scutellaria lateriflora. In: Nutralink. Network Nutrition Pty Ltd, Australia. 2008. Available at: http://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=1&ved=0CCAQFjAA&url=http%3A%2F%2Fnetworknutrition.com.au%2Fcontent.cfm%3FLive%3D0%26ContentType%3DContent%26ContentID%3D84%26TEI%3D150%26TLI%3D0&ei=SEvJVMOXLu3GsQS0p4G4CQ&usg=AFQjCNFc5twJHGECqPA0znGIXbB62biP3Q&sig2=d4U1iWtoAjBOTAZvJU3MxA. Accessed April 21, 2016.
  14. Sun J, Chen P. A flow-injection mass spectrometry fingerprinting method for authentication and quality assessment of Scutellaria lateriflora-based dietary supplements. Anal Bioanal Chem.2011;401(5):1577-1584.
  15. Walker KM, Applequist WL. Adulteration of selected unprocessed botanicals in the U.S. retail herbal trade. Econ Bot. 2012;66(4):321-327.
  16. Wills RBH, Stuart DL. Generation of high quality Australian skullcap products. Barton, Australia: RIRDC. 2004. Available from: http://www.rirdc.gov.au/reports/EOI/04-020.pdf. Accessed April 21, 2016.
  17. Gow PJ, Connelly NJ, Hill RL, Crowley P, Angus PW. Fatal fulminant hepatic failure induced by a natural therapy containing kava. Med J Aust. 2003;178(9):442-443.
  18. Teschke R, Sarris J, Schweitzer I. Kava hepatotoxicity in traditional and modern use: the presumed Pacific kava paradox hypothesis revisited. Brit J Clin Pharmacol. 2012;73(2):170-174.
  19. Laliberte L, Villeneuve JP, 1996. Hepatitis after the use of germander, a herbal remedy. Can Med Assoc J. 1996;154(11):1689-1692.Opinion of the Scientific Committee on Food on teucrin A, major component of hydroalcoholic extracts of Teucrium chamaedrys (wild germander).
  20. European Commission, Health & Consumer Protection Directorate General. Opinion of the Scientific Committee on Food on teucrin A, major component of hydroalcoholic extracts of Teucrium chamaedrys (wild germander). Brussels, Belgium. 2003. Available at: http://ec.europa.eu/food/fs/sc/scf/out173_en.pdf. Accessed April 21, 2016.
  21. Nencini C, Galluzzi P, Pippi F, Menchiari A, Micheli L. Hepatotoxicity of Teucrium chamaedrys L. decoction: Role of difference in the harvesting area and preparation method. Ind J Pharmacol. 2014;46(2):181-184.
  22. Zhou S, Koh HL, Gao Y, Gong ZY, Lee EJ. Herbal bioactivation: The good, the bad and the ugly. Life Sci. 2004;74(8):935-968.
  23. Bruno M, Cruciata M, Bondi ML, et al. Neo-clerodane diterpenoids from Scutellaria lateriflora.Phytochemistry. 1998;48(4):687-691.
  24. Lin LZ, Harnly JM, Upton R. Comparison of the phenolic component profiles of skullcap (Scutellaria lateriflora) and germander (Teucrium canadense and T. chamaedrys), a potentially hepatotoxic adulterant. Phytochem Anal. 2009;20(4):298-306.
  25. Li J, Wang YH, Smillie TJ, Khan IA. Identification of phenolic compounds from Scutellaria laterifloraby liquid chromatography with ultraviolet photodiode array and electrospray ionization tandem mass spectrometry. J Pharm Biomed Anal. 2012;63:120-127.
  26. Gardner Z, McGuffin M (eds). American Herbal Products Association’s Botanical Safety Handbook. 2nded. Boca Raton, FL: CRC Press; 2013.
  27. Teschke R, Wolff A, Frenzel C, Schulze J. Herbal hepatotoxicity–an update on traditional Chinese medicine preparations. Aliment Pharmacol Ther. 2014;40:32-50.
  28. Chalasani N, Vuppalanchi R, Navarro VJ, et al. Acute liver injury due to Flavocoxid (limbrel), a medical food for osteoarthritis. A case series. Ann Intern Med. 2013;156: 857-860.
  29. Dhanasekaran R, Owens V, Sanchez W. Chinese skullcap in move free arthritis supplement causes drug induced liver injury and pulmonary infiltrates. Case Reports Hepatol. 2013;2013:965092.
  30. Moerman DE. Native American Ethnobotany. Portland, OR: Timber Press; 1988.
  31. Gafner S. Skullcap Adulteration Laboratory Guidance Document. Austin, TX: ABC-AHP-NCNPR Botanical Adulterants Program. 2015. Available at: http://cms.herbalgram.org/BAP/LGD/SkullcapLabGuidanceDocument.html. Accessed January 15, 2016.
  32. Brock C, Whitehouse J, Tewfik I, Towell T. The use of Scutellaria lateriflora: A pilot survey amongst herbal medicine practitioners. J Herb Med. 2012;2(2):34-41.

Bulletin on Adulteration of Hydrastis canadensis root and rhizome

Goal:

The goal of this bulletin is to provide information and/or updates on issues regarding adulteration of goldenseal (Hydrastis Canadensis) root to the international herbal industry and extended natural products community in general. It is intended to present the available data on the occurrence of adulteration, the market situation, and consequences for the consumer and the industry.

1 General Information

1.1 Common name: Goldenseal1,2

1.2 Other common names:

English: Yellow root, yellow puccoon, ground raspberry, wild curcuma*, Indian dye, eye root, eye balm, Indian paint, jaundice root, Warnera3,4

French: Hydraste du Canada, hydraste, fard inolien, framboise de terre, sceau d’or5

German: Goldsiegelwurzel, Kanadische Gelbwurz, Kanadische Orangenwurzel5

Italian: Idraste, radice gialla6

Spanish: Hidrastis, hidrastis de Canadá, raíz de oro, scello de oro5

1.3 Accepted Latin binomial: Hydrastis canadensis7,8

1.4 Botanical family: Ranunculaceae

1.5 Plant part and form: Whole fresh or dry roots and rhizomes, powdered dry roots and rhizomes, hydroalcoholic and glycerin-water extracts and powdered dry extracts.9,10 Dried whole or powdered roots and rhizomes complying with the United States Pharmacopeia (USP) are required to contain not less than 2.0% of hydrastine and not less than 2.5% berberine.10

1.6 General use(s): Native American tribes used goldenseal root and rhizome preparations as eye washes, treatments for skin disorders, bitter tonics, and for respiratory ailments and the infectious diseases brought by European settlers.11 The plant was included in The American Eclectic Materia Medica and Therapeutics12 and King’s American Dispensatory,13 which increased its use substantially among Eclectic physicians for infections, mouth ulcers, and thrush, inflamed mucous membranes, chronic gonorrhea, jaundice, gastrointestinal complaints, as a bitter tonic and as a uterine tonic. Goldenseal preparations are now used as antimicrobial agents to treat infections of the mucosal membrane, including mouth, upper respiratory tract, gastrointestinal tract, eyes, vagina, as well as for wounds.9

 

2 Market

2.1 Importance of the trade: Echinacea-goldenseal combination dietary supplements were ranked #15 in sales in the natural food channel in the United States in 2013 and in 2014 (Table 1), with estimated sales exceeding $5 million in 2014. Sales in the Mainstream Multi-Outlet retail channel (excluding sales data from Walmart and Club stores in 2013 and 2014, which were not available) were lower, with echinacea-goldenseal products ranking between #41 and #53. (T. Smith [American Botanical Council] e-mail to S. Gafner, September 2, 2015, and September 3, 2015)14,15

Goldenseal root/rhizome-only supplements did not rank in the top 50 best-selling herbal supplements in the natural food channel or the Mainstream Multi-Outlet retail channel from 2012-2014 (Table 2).

Table 1: Sales data for echinacea-goldenseal dietary supplements from 2012-2014. 

Channel 2012 2013 2014
Rank Sales [US$] Rank Sales [US$] Rank Sales [US$]
Naturala 18 4,400,290 15 4,824,801 15 5,116,708
Mainstream Multi-Outletb 41 2,665,724 53 1,697,591 53 1,566,916

Table 2: Sales data for goldenseal-only dietary supplements from 2012-2014.

Channel 2012 2013 2014
Rank Sales [US$] Rank Sales [US$] Rank Sales [US$]
Naturala 68 1,046,775 70 1,111,038 69 1,110,546
Mainstream Multi-Outletb 60 1,287, 453 106 217,617 102 207,312

aAccording to SPINS (SPINS does not track Whole Foods Market sales, which is a major natural products retailer in the US)
bAccording to SPINS/IRI (the Mainstream Multi-Outlet channel was formerly known as food, drug and mass market channel [FDM]; possible sales at Walmart and Club stores are excluded in 2013 and 2014)
n/a: not available
Source: T. Smith (American Botanical Council) e-mail September 2, 2015, and September 3, 2015

2.2 Supply sources: Historically, the majority of the goldenseal root and rhizome on the market has come from the wild-harvested material, with Kentucky and Tennessee as the major producers. Other states along the Appalachian Mountains and in the northeastern United States provide additional supplies.9 There is no credible evidence that H. Canadensis is cultivated commercially outside of the United States and Canada.

2.3 Conservation status: In 1997 goldenseal was listed on Appendix II of the Convention on International Trade in Endangered Species of Wild Fauna and Flora,17 which also controls global trade and markets for H. Canadensis.18 Several states consider H. Canadensis in need of conservation: Pennsylvania lists the plant as vulnerable, at high risk of endangerment in the wild; Maryland, Michigan and New York list the plant as threatened, at risk of extinction in the wild sometime in the near future; Connecticut, Georgia, Massachusetts, Minnesota, New Jersey and Vermont list the plant as endangered, at high risk of extinction in the wild; North Carolina and Tennessee list the plant as endangered with special concern, at critically high risk of extinction in the wild.19

2.4 Raw material forms: Bulk goldenseal root and rhizome raw material is sold as whole roots and rhizomes (fresh or dry), cut and sifted, or as a powder.

2.5 Market dynamics: Despite a general trend of price increases since 1986, the costs vary considerably from year to year. Prices per kg paid to collectors of dried wild goldenseal root and rhizome ranged from the US $44–$77 between 1996 and 2005, and $77 wild to $110 for organic woods-cultivated material for the same time frame.20 The price per kg of dried wild root and rhizome peaked at $77 in 2001, dropping to $44 per kg in 2005, and fluctuating between $44–55 per kg through 2010.21 In its tonnage report, the American Herbal Products Association (AHPA) reported an average yearly harvest of 10 metric tons (MT) of cultivated compared to 30 MT of wild-harvested dry goldenseal root and rhizome between 2004 and 2010. The amounts of fresh goldenseal root and rhizome have remained below one MT in the same timeframe. Generally, the quantities of goldenseal root and rhizome harvested between 2004 and 2010 have been relatively steady.22

3 Adulteration

3.1 Historical adulterants: At the height of the Eclectic medical movement in the United States during the early 1900s, the price of goldenseal had risen to the point that several plant species were being used as economic adulterants on a regular basis; these included goldthread or coptis (Coptis spp., Ranunculaceae), yellow root (Xanthorrhiza simplicissima, Ranunculaceae), European peony (Paeonia Officinalis, Paeoniaceae),and twin leaf (Jeffersonia diphylla, Berberidaceae).23,24 The adulteration of goldenseal with Virginia snakeroot (Aristolochia serpentaria, Aristolochiaceae), which is of concern due to its content of nephrotoxic and carcinogenic aristolochic acids, was initially documented in 1892 and described again in 1900.25 However, there are no reported cases of adulteration with Virginia snakeroot in recent times. Additional historical adulterants and contaminants of goldenseal that have been documented include Athyrium filix-femina (Athyriaceae), Stylophorum diphyllum (Papaveraceae), Cypripedium calceolus(Orchidaceae), Collinsonia canadensis (Lamiaceae), Trillium spp. (Melanthiaceae), Caulophyllum thalictroides (Berberidaceae), and Polygala senega (Polygalaceae) as admixtures or contaminants.26 It is unlikely that adulteration is occurring with these species in commerce today.

3.2 Recent adulterants: Over the past 20–30 years, economic adulterants have reappeared in goldenseal products,27-29 based in part on the erroneous use of goldenseal to negate illicit drug testing in the 1980s.30 The adulterating species include Japanese goldthread (Coptis japonica), yellow root (Xanthorrhizasimplicissima), Oregon grape (Mahonia aquifolium, Berberidaceae), celandine (Chelidonium majus, Papaveraceae), barberry (Berberis spp., Berberidaceae), and yellow dock (Rumex spp., Polygonaceae) root.2,9,27 There is a single case of the sale of other root materials labeled as goldenseal, e.g., plantain (Plantago spp., Plantaginaceae) root, nettle (Urtica dioica, Urticaceae) root, or passionflower (Passiflora incarnata, Passifloraceae) root colored with a yellow dye, as reported on the website of an analytical laboratory.31

Historically, market pricing for H. Canadensis has displayed instability.20 As noted above, over the more recent 15 years the price has ranged between $44-110/kg for dry root and rhizome material. Assuming that the relatively higher goldenseal price level drives intentional economic adulteration, the addition and/or substitution with several of the adulterating plant species would represent substantial cost savings to an unscrupulous supplier. Over the past 20 years, dried roots of the species Mahonia have sold at $6.1-$8.8 per kg and Berberis at $7.3-14.30 per kg. Over the past 10 years, the price/kg of adulterating species ranged as follows: celandine $3.7-6.9, barberry $5.6-19.3, yellow dock imported $9.5-10.1 and domestically grown $12.9-14.8. (S. Yeager [Mountain Rose Herbs] e-mail, August 25, 2015) The price/kg for Coptis spp. was approximate $14.1 per kg in 2011 and $11.0/kg in 2015.32

3.3 Sources of information supporting confirmation of adulteration: Goldenseal adulteration can be detected through the presence or absence of several alkaloids, namely the presence of berberine, canadine, hydrastine, and hydrastinine, and the absence of palmatine.9 Although most species used as adulterants contain berberine, the alkaloids hydrastine and canadine are unique to goldenseal.9 The presence of palmatine is indicative of adulteration by Coptis spp., the most common adulterant of goldenseal.27 An analysis of several dietary supplement products marketed as goldenseal root extract using the AOAC official method 2008.04-2008, a high-performance liquid chromatography (HPLC) method for the analysis of goldenseal material, revealed that several products contained palmatine.33

A validated HPLC-mass spectrometry (MS) method was used to analyze H. Canadensis root from three suppliers along with the common adulterants – Coptis spp. root, M. aquifolium root, Berberis spp. bark, and C. majus herb.29 Of the three commercial lots that were purchased, all contained the expected goldenseal alkaloids: hydrastinine berberastine, tetrahydroberberastine, canadaline, berberine, hydrastine, and canadine. However, one product contained additional alkaloids not associated with goldenseal – palmatine, coptisine, and jatrorrhizine – thus suggesting admixture of an adulterating species. Avula et al. used an ultra-high-performance liquid chromatography (UHPLC) method to detect the non-goldenseal constituents palmatine, coptisine, and jatrorrhizine in a commercial goldenseal product.34 An emerging adulterant problem stems from the use of goldenseal leaf material, which contains both berberine and hydrastine, but in a different ratio from goldenseal root.27

 

A recent report by a company specializing in DNA-based species identification analyzed several off-the-shelf goldenseal products, including those from a company described as “a major manufacturer.” The company used their proprietary ConfirmIDNATM method, a DNA barcoding method using universal primers, to identify plantain root, nettle root, or passionflower root rather than goldenseal. In addition, the product was colored with a yellow dye.31 No additional tests were carried out to confirm these findings.

Although this publication is focused on H. Canadensis root, commercial trade in H. Canadensis leaf does occur. Dried leaf harvest for the years 2004-2010 was estimated to range from 3.5-8.5 MT.22 During that time the price was approximate $2.2-11.0/kg (E. Burkhart [Pennsylvania State University] e-mail, September 21, 2012). Goldenseal leaf is an article of commerce, and there are allegations of its use as a low-cost adulterant.27 Actual evidence of non-declared goldenseal leaf as an adulterant to goldenseal root/rhizome is rare. One analysis of hydrastine and berberine in goldenseal leaf found levels of these alkaloids ranging at 0.27-0.29% and 0.36-0.39%, respectively, while levels in the root were 2.25-3.32% and 2.61-3.75%, respectively. As part of this 2002 study, three commercial echinacea/goldenseal products were tested with one containing only berberine in the expected range of goldenseal-derived isoquinoline alkaloids, which may indicate an adulterant species was used. Another contained very low alkaloid content suggesting possible leaf adulteration.29

 

3.4 Accidental or intentional adulteration: Historically as well as recently, the use of adulterating species appears to be motivated primarily by economic gain,24-29 particularly when bulk goldenseal root is selling for up to $110 per kg.

3.5 Frequency of occurrence: There is no comprehensive study on the frequency of goldenseal adulteration. One analysis in 2003 of three lots of purchased commercial goldenseal root powder found goldenseal alkaloids hydrastinine, berberastine, tetrahydroberberastine, canadaline, berberine, hydrastine, and canadine in all samples, while only one sample from a single supplier also contained palmatine, coptisine, and jatrorrhizine, presumably indicating that adulteration with coptis occurred in that one sample.29

3.6 Possible therapeutic/safety issues: Although no systematic investigation into human toxic effects associated with the use of Berberis spp., Coptis spp., or M. aquifolium could be found, no other spontaneous or anecdotal reports of adverse effects could be found. The second edition of the American Herbal Products Association’s Botanical Safety Handbook (BSH2) lists B. Vulgaris and C. Chinensis as class 2b safety ingredients, meaning that these botanicals should not be used during pregnancy. The safety concerns in the BSH2 are based on studies using pure berberine, and may not directly apply to extracts made from barberry or coptis. Mahonia aquifolium, which also contains berberine, is presented as a safety class 1 ingredient, which is a botanical that is considered to be safe when used appropriately. Nevertheless, use of Oregon grape during pregnancy is not recommended. In addition, all berberine-containing plants are not recommended for use during lactation.35

Case studies of Chelidonium majus herb in Germany have associated consumption of the herb with liver toxicity. Ad hoc causality assessments in 22 spontaneous cases employing a liver-specific, standardized, quantitative assessment method (Council for International Organizations of Medical Sciences) found causality to be highly probable (n = 2), probable (n = 6), possible (n = 10), unlikely (n = 1), and excluded (n = 3). The pattern of liver injury was observed predominantly among female consumers. The average treatment was 36.4 days, and the latency period until first symptoms and jaundice was 29.8 and 35.6 days, respectively. The study did not identify which of the constituents were responsible for the liver injury.36 No product analysis was conducted and manufacturer observance of cGMP (current Good Manufacturing Practices) was assumed. As such, it is unknown if adulterated products impacted the reported adverse effects.

3.7 Analytical methods to detect adulteration: Brown and Roman conducted a multi-laboratory collaborative study utilizing an HPLC-ultraviolet (UV) detection method, previously validated using AOAC International single-laboratory validation guidelines, to measure hydrastine and berberine in goldenseal root raw materials, extracts, and dietary supplements at concentrations of 0.4 to 6% (w/w). In addition to the quantification of berberine and hydrastine, the method also detected the presence of palmatine, an indicator of adulteration with Coptis spp.33 Based on the results of the study the method was subsequently adopted as AOAC official method 2008.04-2008.37 Weber et al., generated different alkaloid profiles for H. Canadensis root and two berberine-containing Coptis species using a validated HPLC-MS method.38 Kamath and colleagues investigated alkaloid compositions of H. Canadensis, American goldthread (C. trifolia) and coptis (C. Chinensis). They determined that the spectrum of alkaloids in C. Chinensis was different from those in H. Canadensis and C. trifolia, showing that the alkaloid fingerprint was suitable to distinguish the species.39 Another HPLC-MS method was shown to separate 10 analytes (berbamine, berberine, canadine, chelerythrine, coptisine, hydrastinine, hydrastine, jatrorrhizine, palmatine, and sanguinarine) from six different plant species (H. Canadensis, Coptis japonica, B. vulgaris, Chelidonium majus, M. aquifolium andS. Canadensis), allowing analysts to quantify the presence of adulterants at concentrations as low as 5%.40More recently, a UPLC method with UV detection was used to identify the non-goldenseal constituents palmatine, coptisine, and jatrorrhizine in a commercial goldenseal product.34

Govindan and Govindan developed a thin-layer chromatography (TLC) method to detect hydrastine, hydrastinine, and berberine of several goldenseal preparations.41 Their analysis identified three samples containing only berberine and one sample that contained none of the alkaloids, potentially indicating economic adulteration. The results of the TLC analysis were confirmed by subsequent HPLC tests.41 The American Herbal Pharmacopoeia adopted a validated high-performance TLC (HPTLC) method that simultaneously detects palmatine, which is found in adulterants, plus berberine, hydrastine, and hydrastinine. Upton noted the usefulness of hydrastinine as a reliable marker for old or poor quality H. Canadensis, since it is formed as a degradation product of hydrastine.42 Finally, a TLC/desorption electrospray ionization (DESI)-MS method was shown to detect non-goldenseal alkaloids from adulterants in goldenseal products.43

Several official compendial methods exist that may also be applied to adulterant detection, including theEuropean Pharmacopoeia44 and the United States Pharmacopeia–National Formulary.45 Criteria to perform identification using macroscopic and microscopic examinations of goldenseal rhizome and root are presented in several references.42,44,45 In addition to the macroscopic and microscopic characteristics of goldenseal, the AHP monograph also lists such characteristics for Oregon grape, Coptis spp., yellow dock, and yellow root.42

Other, unique analytical systems have been developed that detect both major and minor H. canadensis alkaloids. These methods, including capillary electrophoresis-mass spectrometry (CE-MS),46 pH-zone-refining counter-current chromatography (CCC),47 shift subtracted Raman spectroscopy (SSRS),48 and an enzyme-linked immunosorbent assay (ELISA) linked to an HPLC,49 may be adapted for the detection of adulterants.

4 Conclusions: Habitat destruction in some areas of the eastern United States, goldenseal’s native range, has decreased the availability of this important medicinal plant. Pricing pressure has historically increased the incentive for economically motivated adulteration of goldenseal root. Although the actual extent of adulteration of goldenseal root and rhizome in the current market is not clear, a number of authenticated methods exist to detect such adulteration, including some that have been validated.

*Although it has sometimes been called wild Curcuma, goldenseal should not be confused with turmeric root (Curcuma longa, Zingiberaceae).

5 References

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  34. Avula B, Wang YH, Khan IA. Quantitative determination of alkaloids from the roots of Hydrastis Canadensis L. and dietary supplements using ultra-performance liquid chromatography with UV detection. J AOAC Int. 2012;95(5):1398-1405.
  35. Gardner Z, McGuffin M, eds. American Herbal Products Association’s Botanical Safety Handbook. 2nd ed. Boca Raton, FL: CRC Press; 2013:155-159.
  36. Teschke R, Glass X, Schulze J. Herbal hepatotoxicity by Greater Celandine (Chelidonium majus): Causality assessment of 22 spontaneous reports. RTP. 2011: 61(i3):282-291.
  37. Official Method 2008.04-2008, Hydrastine and berberine in goldenseal raw materials, extracts and dietary supplements. Official Methods of Analysis of AOAC International, 19th ed. Gaithersuburg, MD: AOAC International; 2012.
  38. Weber HA, Zart, MK, Hodges AE, et al. Method validation for determination of alkaloid content in goldenseal root powder. 2002; J AOAC Int 86:476.
  39. Kamath S, Skeels M, Pai A. Significant differences in the alkaloid content of Coptis Chinensis (Huanglian), from its related American species. Chinese Medicine. 2009;4:17.
  40. Tims MC. The chemical ecology of Hydrastis Canadensis L. (Ranunculaceae): Effects of root isoquinoline alkaloids on the Hydrastis endophyte, Fusarium oxysporum. 2006. Available at: http://drum.lib.umd.edu/handle/1903/4052. Accessed July 17, 2015.
  41. Govindan M, Govindan G. A convenient method for the determination of the quality of goldenseal. Fitoterapia. 2000;71(3):232-235.
  42. Upton R. American Herbal Pharmacopoeia and Therapeutic Compendium: Goldenseal root. Hydrastis Canadensis. Santa Cruz, CA: American Herbal Pharmacopoeia. 2001.
  43. Van Berkel GJ, Tomkins BA, Kertesz V. Thin-layer chromatography/desorption electrospray ionization mass spectrometry: investigation of goldenseal alkaloids. Anal Chem. 2007;79(7):2778-2789.
  44. The European Directorate for the Quality of Medicines & HealthCare. European Pharmacopoeia (EP 8.7). Hydrastis rhizoma. Strasbourg, France: Council of Europe; 2015.2963.
  45. United States Pharmacopeial Convention. Goldenseal. In: USP 39-NF 34. Rockville, MD: United States Pharmacopeial Convention. 2016.
  46. Sturm S, Stuppner H. Analysis of isoquinoline alkaloids in medicinal plants by capillary electrophoresis—mass spectrometry. Electrophoresis. 1998;19(16‐17): 3026-3032.
  47. Chadwick LR, Wu CD, Kinghorn AD. Isolation of alkaloids from goldenseal (Hydrastis Canadensis rhizomes) using pH-zone-refining countercurrent chromatography. J Liq Chromatogr Rel Technol. 2001; 2445-2453;24(16):2445-2453.
  48. Bell SE, Bourguignon ESO, Dennis AC, Fields JA, McGarvey JJ, Seddon KR. Identification of dyes on ancient Chinese paper samples using the subtracted shifted Raman spectroscopy method. Anal Chem. 2000;72:234-239.
  49. Kim JS, Tanaka H, Shoyama Y. Immunoquantitative analysis for berberine and its related compounds using monoclonal antibodies in herbal medicines. Analyst. 2003;129(1):87-91.

Bulletin on Adulteration of Bilberry (Vaccinium myrtillus) Extracts

Goal:

The goal of this bulletin is to provide timely information and/or updates on issues of adulteration of bilberry extract to the international herbal industry and extended natural products community in general.

1 General Information

1.1 Common name: Bilberry3

1.2 Other common names:

English: European blueberry, whortleberry, huckleberry4

Chinese: Hei guo yue ju (黑果越桔)

French: Myrtille, ambroche, ambreselle, brimbelle, gueule-noire, raisin des bois, vigne des montagnes

German: Heidelbeere, Blaubeere, Schwarzbeere, Waldbeere, Bickbeere, Moosbeere

Italian: Mirtillo, ampulette, asaire, bagole, baggiole, cesarelle, giasine, lambrune, mirtillo nero, murucule

Spanish: Arándano azul, mirtilo

1.3 Accepted Latin binomial: Vaccinium myrtillus L.5,6

1.4 Synonyms: Vaccinium myrtillus var. oreophilum (Rydb.) Dorn, Vaccinium myrtillus subsp. oreophilum (Rydb.) Á. Löve, D. Löve & B.M. Kapoor, Vaccinium oreophilum Rydb.5

1.5 Botanical family: Ericaceae

1.6 Plant part and form: Bilberry extracts are made from fresh bilberry fruit.1 The extracts are often standardized to 25% anthocyanidins or 36% anthocyanins. Products that claim these levels of compounds may in actuality contain the same amount as the differences are most often due to different quantitative values obtained from using different analytical techniques. In the case of bilberry, high-performance liquid chromatography (HPLC) provides a lower quantitative value than ultraviolet-visible spectrophotometry (UV/Vis).7 Also found on the market are bilberry leaf extracts, or combinations of bilberry fruit and leaf extracts. Extracts made entirely from bilberry leaves and properly labeled as such are not within the scope of this document.

1.7 General use(s): The indications for bilberry fruit include the symptomatic treatment of dysmenorrhea associated with premenstrual syndrome, circulatory disorders in patients with capillary leakage or peripheral vascular insufficiency, and ophthalmic disorders.1,4,8 In addition, bilberry fruit is used topically for mild inflammations of the oral mucosa.4,8


2 Market

2.1 Importance in the trade: In the United States, bilberry was among the top 20 herbal supplements between 2007 and 2012 in the food, drug and mass market with annual sales above US $1.4 million in this channel.9-13 The market volume has been fairly steady in recent years (D. Stanek oral communication, January 23, 2015).

2.2 Supply sources: Commercial bilberries are sourced mainly from Scandinavian and Eastern European countries. The World Blueberry Acreage & Production report lists Poland as the major producer of bilberry, followed by Russia, Ukraine and Scandinavia. Commercial bilberry for the production of bilberry extracts is sourced mainly from Eastern European (Lithuania, Romania, Poland, Russia and Ukraine) and Scandinavian (Sweden, Finland, Norway) countries, but also from France, Italy, and the Netherlands. (D. Stanek oral communication, January 23, 2015; E. M. Martinelli e-mail, November 16, 2015)

2.3 Raw material forms: Bilberry extracts are prepared from fresh berries that are frozen and then extracted with aqueous ethanol or aqueous methanol, and further concentrated according to the manufacturer’s proprietary processes. Generally, the extract yield is approximately 100 times lower than the initial weight of raw material, i.e., 1 kg of fresh bilberry will provide ca. 10 grams of bilberry dry extract (D. Stanek oral communication, January 23, 2015). Dry extract materials using other manufacturing processes are also available.

2.4 Market dynamics: Tracking the bilberry harvest volume is difficult as the fruit is generally harvested by local people (i.e., wildcrafted) who then sell the fruit to brokers. A report from the North American Blueberry Council indicates that the total harvest for wild Vaccinium species (mostly bilberry, but other Vaccinium species, e.g., bog bilberry [V. uliginosum], are collected as well) in Europe was 11,340 metric tons (25 million lbs.) in 2008, 7,710 metric tons (17 million lbs.) in 2010, and 19,500 metric tons (43 million lbs.) in 2012.14

For 2012, the harvest in Poland was around 10,000 metric tons, but the harvest was mainly destined for the domestic market for confectionary and baked goods. Russia, Ukraine, and Scandinavia provided at least an additional 6,000 metric tons to the overall harvest.14 According to the report, the harvest in 2012 was particularly strong despite unfavorable weather conditions; since the economy was depressed in European countries, many people harvested wild blueberries for additional revenue.


3 Adulteration

3.1 Known adulterants: Materials that are used to adulterate bilberry extracts typically have an intensive dark blue color, such as anthocyanidin-containing extracts or red food coloring such as amaranth dye (FD&C Red 2, E 123). Anthocyanidin-rich extracts known to be used as substitute for bilberry include those from bog bilberry (Vaccinium uliginosum), lingonberry (V. vitis-idaea), blueberry species (V. angustifolium, V. corymbosum, V. floribundum), cranberry (V. oxycoccos and V. macrocarpon), raspberries (Rubus spp., Rosaceae), wild cherry (Prunus avium, Rosaceae), black chokeberry (Aronia melanocarpa, Rosaceae), European elder (Sambucus nigra, Adoxaceae) berry, black soybean (Glycine max, Fabaceae) hull, black rice (Oryza sativa, Poaceae), and mulberry species (Morus australis, M. nigra, Moraceae).2,15-18

The common names “blueberry” and “wild blueberry” have different meanings depending on the geographical location. In the US dietary supplement trade, the name “blueberry” is restricted to three species, Vaccinium angustifolium, V. corymbosum, and V. pallidum.3 In Europe, V. myrtillus is often called blueberry, though bilberry is the English word which refers to this species in the trade.3 The hybrid cultivated blueberries from which the majority of the commercial food supply is derived are generally called blueberries. North American wild blueberry, common blueberry, common lowbush blueberry, low sweet blueberry, and lowbush blueberry refer to V. angustifolium which grows in the Northeastern U.S. and is commercially harvested in its habitat. Velvet leaf blueberry (V. myrtilloides) is also traded as “wild blueberry,” and is mostly wild-harvested in the Canadian maritime provinces. It is safe to assume that “wild blueberry” in a commercial sense refers to both V. angustifolium and V. myrtilloides (Steven Foster, e-mail, July 1, 2015).

3.2 Sources of information confirming adulteration: There have been a number of publications on bilberry adulteration, such as the reviews by Foster and Blumenthal,2 Giacomelli et al.,16 Upton et al.,1 the presentation by Pace et al.,19 and the doctoral thesis by Primetta.20 Foster and Blumenthal distinguish between the deliberate adulteration of bilberry extracts by addition of extracts from anthocyanin-rich sources such as blueberry, cranberry, European elder, sweet cherry, and others, and the adulteration occurring in the markets in China, where extracts of lingonberry and bog bilberry are wild-harvested and offered as “homemade Chinese bilberry” and “Chinese domestic bilberry” extracts at prices as low as $10/kg.2 This is in contrast to the much more expensive authentic bilberry extract (see section 3.3 below). Two additional studies regarding adulteration of commercial bilberry extracts were published in 2013 and 2014.15,21 The investigation into the quality of 20 dietary supplements purchased in a store or over the Internet in Japan by ultra-high-performance liquid chromatography (UHPLC) with detection by visible light at 535 nm provided evidence for adulteration in one sample. The product in question was labeled to contain a mixture of bilberry and black currant (Ribes nigrum, Grossulariaceae) extracts, but instead consisted entirely of black currant.21 Gardana et al. analyzed 26 commercial bilberry materials including 14 bulk extracts, six food supplements, and six juices by UV/Vis spectrophotometry and by UHPLC using a photodiode array detector (DAD). The samples were purchased either directly from the supplier (bulk extracts), or from herbal shops and local markets in Italy. The authors found an admixture of black mulberry in five samples (two extracts, three food supplements), and substitution of bilberry with chokeberry in two extracts and with a material tentatively identified as blackberry (Rubus spp.) in one extract. One food supplement did not contain any anthocyanins at all. Five of the juices were consistent with products made from bilberry fruit, while one juice did not contain measurable amounts of anthocyanins.15

3.3 Accidental or intentional adulteration: The limited supply and high commodity prices of bilberry raw materials have created an incentive for economically-motivated adulteration. In 2015 authentic bilberry extracts sold for a price of US $600-800/kg extract (D. Stanek oral communication, January 23, 2015). More easily accessible anthocyanin-containing fruit species can be collected in larger amounts than bilberry in a comparatively short time since many of these are readily available from cultivated rather than more expensive wild sources. The fruit from these other species can be made into extracts at a significantly lower cost than bilberry and can be priced below bilberry market rates while producing a profit for the producer/seller.

3.4 Frequency of occurrence: There are very little data on the extent of adulteration of commercial bilberry extracts and dietary supplements. A presentation by Pace et al. suggested that “adulteration of bilberry is rampant”;19 Roberto Pace, PhD, Director of Quality Control at Indena S.p.A. (Milan, Italy), the world’s leading marketer of bilberry extract whose use has been confirmed in clinical trials, commented that “bilberry is one of the most economically adulterated ingredients of the health food market” (R. Pace oral communication, November 5, 2015). As noted above, one study included results of 20 commercial products purchased in Japan, with only 13 of the products labeled to contain bilberry. Of these 13 products, one was found to be entirely composed of black currant, while the remainder did contain authentic bilberry.21 Another study looked at bilberry extracts from different manufacturers and supplements purchased on local markets in Italy. The results indicated that six out of 14 extracts and four out of six supplements were adulterated.15 Lee analyzed 15 commercial bilberry supplements purchased in the states of Washington and Idaho in the United States. Five products contained authentic bilberry material, and two samples could not be evaluated because they were composed of a mixture of anthocyanin-containing fruits, including bilberry. The remaining eight products were found to be adulterated.18 Based on the limited published data available, it is not possible to come to any conclusions about the frequency of bilberry adulteration, but it is accurate to say that it is not uncommon.

3.5 Possible safety/therapeutic issues: Most of the known adulterants of bilberry have a long-standing history of safe use in food and therefore do not represent a safety concern. However, adulteration of bilberry extracts with amaranth dye is of possible safety concern. Amaranth dye has been prohibited for use by the US Food and Drug Administration (FDA) since 1976 due to concerns about carcinogenicity, which are mainly based on two controversial studies in rats.22,23 The use of amaranth dye is still permitted in Europe but is limited to 0.15 mg/kg per day.24 Most botanical adulterants are cultivated plants and might be potentially contaminated by pesticides, largely used in the growing of berries. Conversely, pesticides are not an issue with wild-harvested bilberry.

3.6 Analytical methods to detect adulteration: The most suitable way to authenticate bilberry extracts and detect adulteration is by chemical analysis based on the specific anthocyanin fingerprint using either high-performance thin layer chromatography (HPTLC) or high-performance liquid chromatography (HPLC) with ultraviolet/visible (UV/Vis) and/or mass spectrometric (MS) detection. The monograph of the United States Pharmacopeia (USP)26 recommends use of HPLC, while that of the American Herbal Pharmacopoeia (AHP)1 and European Pharmacopoeia (EP)27 utilize the UV/Vis method after adequate identification tests have been performedThe use of UV/Vis spectrophotometry alone will allow measurement of total anthocyanins in bilberry extracts, but is not specific enough as an identity test. It can be applied as a quantitative tool only after the identity of the raw material has been assured. A comprehensive evaluation of 39 publicly available methods for the authentication and detection of adulterants in bilberry extracts, the Bilberry Extract Laboratory Guidance Document, is available through the ABC-AHP-NCNPR Botanical Adulterants Program.25

3.7 Perspectives: Don Stanek, US Sales Director at Linnea Inc., a European producer of bilberry extract, commented that adulteration of bilberry extracts is likely to persist, since the authentic material is so expensive (oral communication, January 23, 2015). Furthermore, explains Giovanni Appendino, PhD, professor of pharmaceutical sciences at the University ofEastern Piedmont (Novara, Italy) and consultant to Indena, the leading producer of bilberry extract, the price of the berries is subjected to significant variations due to the effect of climate on the labor-intensive harvest (e-mail, July 20, 2015).


4 Conclusions:
The adulteration of bilberry extracts continues to afflict the natural products industry. Since the raw material is harvested in the wild, the control of the supply chain is more challenging and adequate testing of the incoming raw material is crucial. Test methods outlined, e.g., in the USP,26 the EP,27 or in the AHP1 are able to detect adulteration of bilberry extracts and should be in place in every quality control laboratory to prevent manufacturers of bilberry extract products from becoming victims of companies providing fraudulent ingredients.


5 References

  1. Upton R, Graff A, Petrone C, Swisher D. American Herbal Pharmacopoeia and Therapeutic Compendium: Bilberry Fruit. Vaccinium myrtillus L.: Standards of Analysis, Quality Control and Therapeutics. Scotts Valley, CA: American Herbal Pharmacopoeia; 2001.
  2. Foster S, Blumenthal. The adulteration of commercial bilberry extracts. HerbalGram. 2012;96:63-74. Available at: http://cms.herbalgram.org/herbalgram/issue96/hg96-feat-bilberry.html. Accessed February 14, 2015.
  3. McGuffin M, Kartesz JT, Leung AY, Tucker AO. American Herbal Products Association’s Herbs of Commerce. 2nd ed. Silver Spring, MD: American Herbal Products Association; 2000.
  4. Blumenthal M, Goldberg A, Brinckmann J (eds). Herbal Medicine: Expanded Commission E Monographs. Austin, TX: American Botanical Council; Newton, MA: Integrative Medicine Communications; 2000:16-21.
  5. The Plant List. Version 1.1 (September 2013). Available at: http://www.theplantlist.org. Accessed February 24, 2015.
  6. Tropicos.org. Missouri Botanical Garden. Available at: http://www.tropicos.org. Accessed February 24, 2015.
  7. Artaria C, Pace R, Maramaldi G, Appendino G. Different brands of bilberry extract: A comparison of selected components. Nutrafoods. 2007;6:13-18.
  8. World Health Organization: WHO monographs on selected plants, Volume 4. Fructus Myrtilli. WHO Press 2009;210-225.
  9. Cavaliere C, Rea P, Blumenthal M. Herbal supplement sales in United States show growth in all channels.HerbalGram. 2008;78:60-63. Available at: http://cms.herbalgram.org/herbalgram/issue78/article3263.html. Accessed February 14, 2015.
  10. Cavaliere C, Rea P, Lynch ME, Blumenthal M. Herbal supplement sales experience slight increase in 2008.HerbalGram. 2009;82:58-61. Available at: http://cms.herbalgram.org/herbalgram/issue82/article3400.html. Accessed February 14, 2015.
  11. Cavaliere C, Rea P, Lynch ME, Blumenthal M. Herbal supplement sales rise in all channels in 2009. HerbalGram.2010;86:62-65. Available at: http://cms.herbalgram.org/herbalgram/issue86/article3530.html. Accessed February 14, 2015.
  12. Blumenthal M, Lindstrom A, Lynch ME, Rea P. Herbs sales continue growth – up 3.3% in 2010. HerbalGram.2011;90:64-67. Available at: http://cms.herbalgram.org/herbalgram/issue90/MarketReport.html. Accessed February 14, 2015.
  13. Blumenthal M, Lindstrom A, Ooyen C, Lynch ME. Herb supplement sales increase 4.5% in 2011. HerbalGram.2012;95:60-64. Available at: http://cms.herbalgram.org/herbalgram/issue95/hg95-mktrpt.html. Accessed February 14, 2015.
  14. Brazelton C. 2012 World Blueberry Acreage and Production Report. North American Blueberry Council. 2013.
  15. Gardana C, Ciappellano S, Marinoni L, Fachechi C, Simonetti P. Bilberry adulteration: identification and chemical profiling of anthocyanins by different analytical methods. J Agric Food Chem. 2014;62(45):10998-11004.
  16. Giacomelli L, Appendino G, Franceschi F, Togni S, Pace R. Omne Ignotum pro Magnifico: characterization of commercial Bilberry extracts to fight adulteration. Eur Rev Med Pharmacol Sci. 2014;18(24):3948-3953.
  17. Filippini R, Piovan A, Caniato R. Substitution of Vaccinium myrtillus L. for Aronia melanocarpa (Michx.) Elliott in acommercial batch. Plant Biosyst. 2011;145(1):175-181.
  18. Lee J. Anthocyanin analyses of Vaccinium fruit dietary supplements. Food Sci Nutr. 2016. doi: 10.1002/fsn3.339.
  19. Pace R, Morazzoni P, Appendino G. Omne ignotum pro magnifico: Getting bilberry out of the adulteration swamp. Talk presented at: 9th Oxford International Conference on the Science of Botanicals; April 14, 2010; Oxford, MS.
  20. Primetta A. Phenolic compounds in the berries of the selected Vaccinium species – the potential for authenticity analyses. PhD thesis. Kuopio, Finland: University of Eastern Finland; 2014.
  21. Yamamoto M, Yamaura K, Ishiwatari M, et al. Degradation index for quality evaluation of commercial dietary supplements of bilberry extract. J Food Sci. 2013;78:S477–S483.
  22. Andrianova MM. Carcinogenous properties of red food pigments – amaranth, SX purple and 4R purple, Vop. Pitan. 1970;29:61-65.
  23. Baigusheva MM. Carcinogenic properties of the amaranth paste, Vop. Pitan. 1968:27:46-50.
  24. European Food Safety Authority. Scientific Opinion on the re-evaluation of Amaranth (E 123) as a food additive. EFSA Journal. 2010;8(7):1649.
  25. Gafner S. Bilberry Extract Adulteration Laboratory Guidance Document. ABC-AHP-NCNPR Botanical Adulterants Program, Austin, TX. 2015. http://cms.herbalgram.org/BAP/LGD/BilberryLabGuidanceDocument.html. Accessed August 25, 2015.
  26. United States Pharmacopeial Convention. Powdered Bilberry Extract. In: USP 37-NF 32. Rockville, MD: United States Pharmacopeial Convention. 2014.
  27. The European Directorate for the Quality of Medicines. European Pharmacopoeia (EP 7.5). Myrtilli fructus recentis extractum siccum raffinatum et normatum. Strasbourg, France: Council of Europe; 2012:1130-1132.

Adulterants Bulletin ~ Arnica Montana

Arnica Montana

Goal: The goal of this bulletin is to provide timely information and/or updates on issues of adulteration of Arnica montana flower to the international herbal products industry and extended natural products community in general. It is intended to present the available data on the occurrence of adulteration, the market situation, and consequences for the consumer and the industry.

arnica11 General Information

1.1 Common name: Arnica1

1.2 Other common names:

English: Leopard’s bane, European arnica, mountain tobacco, wolfsbane2

Chinese: Shan jin hua (山金花)3

French: Arnica, arnique, bétoine des montagnes, herbe aux chutes, souci des alpes, tabac des Vosges2

German: Arnika, Berg-Wohlverleih, Engeltrank, Fallkraut, Wohlverleih, Wolfsblume2

Italian: Arnica2

Spanish: Arnica, tobaco de montana2

1.3 Accepted Latin binomial: Arnica montana1

1.4 Botanical family: Asteraceae

1.5 Plant part and form: Arnica bulk raw material is usually sold as dried whole flowers, or in the form of dried flower extracts. Arnica tinctures (usually made with 50-70% aqueous ethanol) are sold for external use or as dietary supplements, although arnica is not recommended for oral use according to theAmerican Herbal Products Association’s Botanical Safety Handbook, 2nd ed., the European Medicines Agency’s (EMA) draft Community Herbal Monograph, and the monographs on Arnica Flower by the European Scientific Cooperative on Phytotherapy (ESCOP) and the German Commission E.4-7 An exception is the use of arnica flower preparations in homeopathy, where highly diluted arnica tinctures in liquid form or tablets are popular. The predominant galenic form for arnica is as an ointment or a gel made with various concentrations of arnica tincture. Arnica ointments are sold mainly as homeopathic remedies (although in most preparations, the arnica tincture is undiluted), or as herbal ointments in combination with other ingredients. Arnica is also a popular ingredient in massage oils and in cosmetic preparations.

1.6 General use(s): Traditionally, arnica tinctures, gels, creams, and ointments containing arnica oil, tinctures, or liquid extracts (liquid extracts are made using a 1:20 ratio of fresh flowers to 50% aqueous ethanol) are used topically for the relief of bruises, sprains, and localized muscular pain.6 The World Health Organization monograph lists the treatment of pain and inflammation (bruises and other types of injuries leading to hematomas [localized bleeds visible under the surface of the skin]) resulting from minor injuries and accidents, and the treatment of inflammation of the oral mucous membranes, insect bites, and superficial phlebitis as indications for arnica.8 The essential oil, flower water or extracts of arnica are used in the cosmetic industry as a fragrance, or as a skin-conditioning agent.9

2 Market

2.1 Importance of the trade: The use of arnica as an ingredient in dietary supplements is not extensive, as it is not recommended for internal use.4,5 Ingestion of non-homeopathic arnica preparations can result in cardiac, pulmonary, and uterine toxicity (see section 3.5 below), and can cause gastrointestinal disorders.5,10 However, the herb is popular as an ingredient in ointments and gels. According to the market research company SPINS, sales of arnica in the herbal category (according to SPINS, herbal tinctures, e.g., arnica tinctures labeled “for external use only”, and loose herbs do not have to bear a dietary supplement statement on their labels to be captured under the herbal category) have been increasing between 2012 and 2014 (Table 1), with ca. 65–75% of sales in the Mainstream Multi-Outlet retail channel in the United States, where arnica ranked between #83 and #113. (T. Smith [American Botanical Council] e-mail, September 2, 2015, and September 3, 2015). Sales of topical arnica ointments and gels were in the range of US $15–25 million in the years 2013–2015 (Table 2), with a healthy year-to-year sales increase (K. Kawa [SPINS] e-mail, February 25, 2016, and February 29, 2016). The ranking of topical arnica preparations compared to other homeopathic products is not available.

Channel 2012 2013 2014
Rank Sales [US$] Rank Sales [US$] Rank Sales [US$]
Naturala 189 59,044 182 85,813 176 125,246
Mainstream Multi-Outletb 102 135,583 113 161,936 83 384,485

Table 1: Sales data for arnica (including bulk herbs and tinctures) in the herbal category in the United States from 2012-2014.

Channel 2012 2013 2014 2015
Naturala 3,814,350 4,112,825 4,257,750 4,184,862
Mainstream Multi-Outletb n/a 12,281,389 16,770,345 18,710,056

Table 2: Sales [in US$] data for topical arnica preparations (sold as homeopathic remedies) in the United States from 2012-2015.

aAccording to SPINS (SPINS does not track sales at Whole Foods Market, which is a major natural products retailer in the US, health professionals, or other outlets without scanners
bAccording to SPINS (the Mainstream Multi-Outlet channel was formerly known as food, drug, and mass market channel [FDM], exclusive of sales at Walmart)
n/a: not available
Source: T. Smith (American Botanical Council) e-mail, September 2, 2015, and September 3, 2015; K. Kawa (SPINS) e-mail, February 25, 2016, and February 29, 2016.

2.2 Supply sources: Arnica montana is native to Europe; its range extends from Scandinavia across central Europe to Spain and Portugal, and eastward to the Balkan peninsula, Poland, Romania, Ukraine, and southern Russia. A report from 1998 suggests that Europe alone uses ca. 50 metric tons of dried arnica flowers (equivalent to 250–350 tons of fresh flowers) per year.11 The same harvest volume is also cited in 2010 by Cropwatch, an independent organization assessing the status of threatened medicinal and aromatic plants.12 The most commercial material is obtained from collections in the wild in Romania, Spain, and countries of the western Balkans.13,14 Cultivation is possible but is difficult and more costly than the collection in the wild.14 Results of an assessment of the arnica supply chain, commissioned by the World Wildlife Fund, were published in 2006. According to these data, harvesters received €0.28/kg (1€ was equivalent to US $1.18-1.32 in 2006) for fresh arnica flowers, while intermediary collectors obtained €0.38/kg. After drying, arnica flowers were sold for ca. €10/kg to wholesale manufacturers. Prices at wholesale reached €25-28/kg, depending on the market (domestic versus export).15 These prices are in line with wholesale prices in 2006 from Australia, where material sold for the US $28–40/kg. In the past years, prices for sustainably wildcrafted bulk arnica flowers (minimum quantity of 500 kg) varied from €20 to €40/kg (US$22.5 to $45/kg based on the exchange rate on June 15, 2016) for Central European material and from €30 to €50/kg (US$34 to $57/kg) for Spanish material, depending on year and supplier (K.W. Quirin [Flavex] e-mail communication, May 25, 2016).

2.3 Raw material forms: Bulk arnica raw material is sold mainly as whole dried flowers. Other plant parts, e.g., the whole herb and the roots, are also sold. However, whole arnica herb or roots are not within the scope of this document.

2.4 Market dynamics: According to sales data from the past four years (Tables 1 and 2), there has been a steady increase in sales of arnica-based products in the United States. Sales data from other countries are not available. Pricing for the consumer is in the range of US $99-216/kg for whole dried arnica flowers, according to an informal survey of smaller companies in the United States and Germany that had pricing listed on the internet, conducted for this Bulletin (SG). Dried whole flowers of A. chamissionis and false, or Mexican, arnica (Heterotheca inuloides, Asteraceae), were listed at the US $74-117/kg and US $18-37/kg, respectively.

3 Adulteration

3.1 Known adulterants: Currently, A. Montana is the only official species listed in the European Pharmacopoeia.16 However, other Arnica species, i.e., A. Angustifolia, A. chamissonis, A. chamissonissubsp. foliosa, A. cordifolia, A. latifolia, and A. sororia, may legally be sold in the United States under the Standardized Common Name of “arnica”, according to the second edition of the American Herbal Products Association’s Herbs of Commerce. North America has the greatest natural diversity of Arnica species with 26 of 29 species within the genus.17 The most common adulteration-related issue in the arnica trade is the replacement of arnica flowers with flowers of so-called “Mexican arnica” (predominantly Heterotheca spp.). In addition, other species known as “arnica”, especially in the Southern United States and Mexico, are offered on the market. These species include members of the Asteraceae (Gaillardia spp., Grindelia spp.,Helenium mexicanum, Heterotheca leptoglossa, H. subaxillaris, Jefea pringlei, Neurolaena lobata,Pseudogynoxys spp., Tithonia diversifolia, Trixis angustifolia, T. inula, T. radialis, Verbesina crocata, V. pinnatifida), and Loasaceae (Mentzelia conzattii).18,19 Adulteration with other yellow-flowering species of the Asteraceae (Calendula officinalis, Cota tinctoria, Doronicum pardalianches, and Inula britannica) is reported in older textbooks, but a mixture of these species with arnica flowers has not been reported in the current market.20

3.2 Sources of information supporting confirmation of adulteration: Adulteration of arnica with H. inuloides was noted in the mid-twentieth-century pharmacognostic literature.21 European literature states that it had been frequent in the 1990s.22-24 A 2012 study of bulk herbs sold by online retailers and two stores in the St. Louis, Missouri area reported that of 11 samples of unprocessed whole “arnica flower” obtained from US-based vendors of bulk herbs, six were Heterotheca rather than genuine arnica.25

3.2 Accidental or intentional adulteration: Due to overharvesting, arnica has been protected in a number of European countries, but populations are still in decline.26,27 The relatively high price of A. montana flowers, compared to H. inuloides, has provided an incentive for economically-motivated adulteration. At the same time, other species of Arnica, or members of the family Asteraceae colloquially known as arnica, are interchangeably used by local herbalists for the same benefits as A. montana. In addition, A. chamissonis subsp. foliosa was approved by the German Commission E in 1984 as a substitute for A. montana for external use in preparations for treating muscle and joint injuries, and for inflammation of the oral cavity and the throat.5 However, the species A. chamissonis subsp. foliosa is currently not included in the European Pharmacopoeia.16

3.4 Frequency of occurrence: There is no comprehensive published study on the frequency of arnica adulteration, but information from limited publications to date indicates that adulteration is common.

3.5 Possible safety/therapeutic issues: Adulteration of arnica with H. inuloides is economic in nature and creates no apparent safety concern. Traditional uses of the latter are similar to those of the former. However, H. inuloides is also used internally without the cautions regarding toxicity that are usually expressed for arnica,28,29 which is contraindicated for ingestion.4,30

Heterotheca inuloides contains cytotoxic compounds, but a recent study reported that a dose of 2,000 mg/kg of the predominant sesquiterpene, 7-hydroxy-3,4-dihydrocadalene, was required to produce evidence of acute toxicity in mice.31 The occurrence of allergic reactions and contact dermatitis after topical administration of arnica is well documented,4,32 but a comprehensive literature search has not revealed any such adverse event description for H. inuloides.

3.6 Analytical methods to detect adulteration: When present as whole dried flower, A. montana is readily distinguished from H. inuloides and C. officinalis using morphological characteristics.24,25 Arnica and calendula can also be differentiated using botanical microscopy.33,34 In addition, microscopic features to distinguish between A. montana and H. inuloides flowers have been detailed by Saukel.35 However, a literature search has not located a comparison of the microscopic characteristics of the various otherArnica spp. The HPTLC Association has published a high-performance thin-layer chromatography (HPTLC) method with criteria to distinguish A. montana from A. chamissonis, C. officinalis, and H. inuloides.36 A TLC method using the same solvent system is described in the European Pharmacopoeia.16 Chemical distinction among A. montana, A. chamissonis, and H. inuloides has also been achieved by Schröder and Merfort (1991) using high-performance liquid chromatography combined with mass spectrometry (HPLC-MS),37although more recent liquid chromatography methods to analyze flavonoids, caffeoylquinic acids, and sesquiterpene lactones are available.16,38-40 The sesquiterpene composition reportedly depends on the geographical origin of the flowers, with materials from Central Europe predominantly containing helenalin esters while flowers from Spain are characterized by the abundance of 11α,13-dihydrohelenalin esters.24,41Finally, DNA barcoding using the matK and rbcL sequences was performed to authenticate four dried crude materials labeled as “arnica” sold in yerberías and supermarkets in the Rio Grande Valley in Texas. The method could successfully distinguish authentic A. Montana from the commercial samples, which were identified as Grindelia spp., Heterotheca subaxillaris, Pseudogynoxys spp., and Trixis inula.19

4 Conclusions

Economic adulteration of arnica with less costly species, especially H. inuloides, remains an occurrence of which purchasers must be aware. Adulteration of arnica with H. inuloides is readily detected using macroscopic, microscopic, chemical analysis, and/or DNA analysis.

†The occasional common name ‘wolfsbane’ for arnica in some locations should not be confused with the more widespread use of the common name wolfsbane to refer to the toxic plants in the genusAconitum(Ranunculaceae).

Such undiluted tinctures in homeopathy are referred to as a ‘mother tincture’ and must conform to specifications for raw material and method of preparation found in officially recognized homeopathic pharmacopeias.

  • The first edition of the American Herbal Products Association’s Herbs of Commerce lists A. montana and A. latifolia as the only species in commerce with arnica as the common name. The first edition of Herbs of Commerce was incorporated by reference in the U.S. Food and Drug Administration’s (FDA) rules for labeling dietary supplements in 1997. This regulation was codified at 21 CFR 101.4 (h), but codification has not been updated to include the second edition of Herbs of Commerce.

5 References

  1. McGuffin M, Kartesz JT, Leung AY, Tucker AO. American Herbal Products Association’s Herbs of Commerce. 2nd ed. Silver Spring, MD: American Herbal Products Association; 2000.
  2. Ladner J. Arnica montana. In: Grassland species profile. Food and Agriculture Organization (FAO) of the United Nations website. Available at: http://www.fao.org/ag/agp/agpc/doc/gbase/data/pf000462.htm. Accessed March 17, 2016.
  3. Flora of China. eFloras.org website. Available at: http://www.efloras.org. Accessed March 17, 2016.
  4. Gardner Z, McGuffin M. American Herbal Products Association’s Botanical Safety Handbook. 2nd ed. Boca Raton, FL: CRC Press; 2013.
  5. Blumenthal M, Goldberg A, Brinckmann J, eds. Herbal Medicine: Expanded Commission E Monographs. Austin, TX: American Botanical Council; Newton, MA: Integrative Medicine Communications; 2000.
  6. European Medicines Agency: Draft community herbal monograph on Arnica montana L., flos. 2014. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/Herbal_-_Community_herbal_monograph/2013/08/WC500148263.pdf. Accessed March 17, 2016.
  7. Arnicae flos. European Scientific Cooperative on Phytotherapy. ESCOP Monographs. 2nd ed. New York: Thieme New York; 2003.
  8. World Health Organization. WHO Monographs on Selected Plants, Volume 3. Flos Arnicae. Geneva, Switzerland: WHO Press; 2007:77-87.
  9. European Commission Health & Consumers Directorate. Cosmetic Ingredients and Substances (CosIng®) Database. Brussels, Belgium: European Commission. Available at: http://ec.europa.eu/consumers/cosmetics/cosing. Accessed March 17, 2016.
  10. Schulz V, Hänsel R. Rationale Phytotherapie. 4th ed. Berlin, Germany: Springer-Verlag; 1999:324-325.
  11. Lange D. Europe’s medicinal and aromatic plants: their use, trade, and conservation. Cambridge, United Kingdom: TRAFFIC International; 1998:73.
  12. Burfield T. Arnica – Updated list of threatened aromatic plants used in the aroma & cosmetic industries, V1.21 Mar. 2010. Assembled from several Cropwatch sources. Published 2003-2010. Corrected and revised March 2010.
  13. Engels G, Brinckmann J. Arnica. HerbalGram. 2015;107:1-7.
  14. Kathe W. Conservation of Eastern-European medicinal plants: Arnica montana in Romania. In: Bogers RJ, Craker LE, Lange D, eds. Medicinal and Aromatic Plants, Agricultural, Commercial, Economic, Legal, Pharmacological and Social Aspects. Vol. 17. Dordrecht, The Netherlands: Springer-Verlag; 2006: 203-211.
  15. Michler B. Conservation of Eastern European medicinal plants: Arnica montana in Romania. Case study Gârda de Sus: Management plan. Surrey, United Kingdom: World Wildlife Fund; 2007.
  16. The European Directorate for the Quality of Medicines and HealthCare. European Pharmacopoeia(EP 8.4). Arnicae flos. Strasbourg, France: Council of Europe; 2014.
  17. Arnica. Flora of North America website. Available at: http://www.efloras.org/florataxon.aspx?flora_id=1&taxon_id=102636. Accessed July 5, 2016.
  18. Waizel-Bucay J, de Lourdes Cruz-Juárez M. Arnica montana L., planta medicinal europea con relevancia. Rev Mex Cienc Forest. 2014;5(25):98-109.
  19. Aguilar de Alba HG. Development of a DNA barcoding reference library for identification of medicinal plant materials used in the Rio Grande Valley in Texas: a representative case study usingArnica (Asteraceae). MSc thesis. Brownsville TX: the University of Texas at Brownsville, Dissertations in Biology; 2015. Available at: https://repositories.tdl.org/utb-ir/bitstream/handle/2152.6/703/Aguilar_Hector_%20Thesis_9-23-15.pdf?sequence=1&isAllowed=y. Accessed March 17, 2016.
  20. Merfort I, Willuhn G, Jerga C. Arnikablüten DAB9 – Reinheitsprüfung. Deutsche Apotheker Zeitung. 1990;130(18):980-984.
  21. Youngken H. Textbook of Pharmacognosy, 5th ed. Philadelphia, PA: The Blakiston Company; 1943.
  22. Schilcher H. Probleme bei der Beschaffung von Drogen mit Arzneibuchqualität. Pharm Ztg. 1981;126:2119-2128.
  23. Pietta PG, Mauri PL, Bruno A, Merfort I. MEKC as an improved method to detect falsifications in the flowers of Arnica montana and A. chamissonis. Planta Med. 1994;60:369-372.
  24. Willuhn G. Arnicae flos – Arnica flowers. In: Wichtl M, ed. Brinckmann JA, Lindenmaier MP, trans.Herbal Drugs and Phytopharmaceuticals. 3rd ed. Stuttgart: Medpharm GmbH Scientific Publishers; 2004:54-59.
  25. Walker K, Applequist W. Adulteration of selected unprocessed botanicals in the U.S. retail herbal trade. Econ Bot. 2014;66(4):321-327.
  26. Falniowski, A., Bazos, I., Hodálová, I., Lansdown, R, Petrova, A. 2013. Arnica montana. The IUCN Red List of Threatened Species 2013: e.T162327A5574104.Available at: http://dx.doi.org/10.2305/IUCN.UK.2011-1.RLTS.T162327A5574104.en. Accessed February 24, 2016.
  27. Cech R. Arnica and Arnica analogs. Journal of Medicinal Plant Conservation. 2013;6-7.
  28. González Elizondo M, López Enriquez IL, González Elizondo MS, Tena Flores JA. Plantas Medicinales del Estado de Durango y Zonas Aledañas. Tresguerras, Mexico: Instituto Politécnico Nacional; 2004.
  29. Moreno Uribe V, ed. Herbolaria y Tradición en la Región de Xico, Veracruz. [Xalapa, Mexico]: Consejo Veracruzano de Arte popular; 2004.
  30. Mills S, Bone K, eds. The Essential Guide to Herbal Safety. St. Louis, MO: Elsevier, Inc.; 2005:245-248.
  31. Rodriguez-Chávez JL, Coballase-Urrutia E, Sicilia-Argumedo G, Ramirez-Apan T, Delgado G. Toxicological evaluation of the natural products and some semisynthetic derivatives of Heterotheca inuloides Cass (Asteraceae). J Ethnopharmacol. 2015;175:256-265.
  32. Iannitti T, Morales-Medina JC, Bellavite P, Rottigni V, Palmieri B. Effectiveness and safety ofArnica Montana in post-surgical setting, pain and inflammation. Am J Ther. 2016;23(1):e184-e197.
  33. Upton R, Graff A, Jolliffe G, Länger R, Williamson E, eds. American Herbal Pharmacopoeia: Botanical Pharmacognosy – Microscopic Characterization of Botanical Medicines. Boca Raton, FL: CRC Press; 2011.
  34. Eschrich W, ed. Pulver-Atlas der Drogen. 7th ed. Stuttgart, Germany: Deutscher Apotheker Verlag; 1999:234-235.
  35. Saukel J. Pharmakobotanische Untersuchungen von Arzneidrogen III. Unterscheidungsmerkmale der Blütendrogen von Arnica montana L. und Heterotheca inuloides Cass. Sci Pharm. 1984;52:35-46.
  36. International Association for the Advancement of High-Performance Thin Layer Chromatography.Arnica montana (arnica flower). July 21, 2014. Available at: http://www.hptlc-association.org/methods.cfm. Accessed March 16, 2016.
  37. Schröder E, Merfort I. Thermospray liquid chromatographic/mass spectrometric studies of flavonol glycosides from Arnica montana and Arnica chamissionis extracts. Biol Mass Spectrom. 1991;20(1):11-20.
  38. Stefanache CP, Peter S, Meier B, Danila D, Tanase C, Wolfram E. Phytochemical composition ofArnicae flos from wild populations in the northern area of the Romanian eastern Carpathians. Rev Chim (Bucharest). 2015;66(5):784-787.
  39. Zheleva-Dimitrova DZ, Balabanova V, Gevrenova R, Doytchinova I, Vltkova A. Chemometrics-based approach in analysis of Arnicae flos. Phcog Mag. 2015;11:538-544.
  40. Lin LZ, Harnly JM. Identification of hydroxycinnamoyl quinic acids of arnica flowers and burdock roots using a standardized LC-DAD-ESI/MS profiling method. J Agric Food Chem. 2008;56(21):10105-10114.
  41. May P. Arnica flower CO2-extract – approved efficacy in topical treatment. Cosmetic Science Technology. 2013;1-6.

Comparison of Peppermint Oil and Mefenamic Acid for Relief of Dysmenorrhea Symptoms

Dysmenorrhea is associated with painful uterine contractions, nausea, vomiting, and diarrhea. Pain is thought to be caused by the release of prostaglandin F2α in the menstrual fluid. The main treatments are nonsteroidal anti-inflammatory drugs (NSAIDs), prostaglandin inhibitors, and contraceptive pills. NSAIDs can be effective in relieving dysmenorrhea but commonly cause adverse side effects and are contraindicated in some people. Mefenamic acid is a mild analgesic and fever-reducing NSAID used for relief of moderate short-term menstrual pain. Peppermint (Mentha × Piperita, Lamiaceae) exerts its effect on the myometrium contractile activity by inhibiting prostaglandin F2α and oxytocin and has also been shown to have an analgesic and anti-inflammatory effect.1,2 In addition, menthol, a primary constituent in mint, reduces vomiting and diarrhea.3,4 The goal of this study was to compare the effects of peppermint oil and the NSAID mefenamic acid for relief of dysmenorrhea symptoms.

A prospective, randomized, crossover study was conducted for 2 months with 122 single, female Iranian university students aged 18-25 years who already had primary dysmenorrhea. Group 1 received 3 peppermint oil capsules (Colpermin™; Tillotts Pharma AG; Rheinfelden, Switzerland) once a day for 3 days after menstruation started, followed by a washout period during the next menstrual cycle. The actual dosage of peppermint oil was not disclosed. [Note: The Colpermin website states that each gastro-resistant hard-gelatin capsule contains 187 mg of peppermint oil.5] Then, in the third menstrual cycle, patients were given 1 capsule containing 250 mg mefenamic acid (Ponstan®; Razak Laboratories Co.; Tehran, Iran) every 8 hours for 3 days. Group 2 received the same treatments in reverse order.

There was no significant difference in age, the number of days of menstruation, age at first menstruation, or dysmenorrhea interval between groups. Patients were given questionnaires after taking each treatment. Pain intensity was assessed through visual analog scale (VAS) and dysmenorrhea timing through the Cox menstrual symptom scale. Bleeding amount was measured using a pictorial blood assessment chart (PBAC). The VAS and Cox scale were answered at the beginning and end of each menstruation. PBAC was completed on menstruation days. Patients were allowed to take sedatives 1 hour after treatment, but they had to record the intensity and duration of their pain first.

Consumption of both mefenamic acid and peppermint oil significantly reduced the severity of pain (P<0.05), and there was no significant difference between the 2 treatments. Mefenamic acid and peppermint oil both significantly reduced duration of pain (P<0.05); however, duration of pain was more greatly reduced by mefenamic acid than peppermint oil (P<0.05). Mefenamic acid significantly reduced bleeding (P<0.05), while there was a slight (nonsignificant) increase in bleeding after peppermint oil treatment (P>0.05). There was no significant difference in nausea and vomiting with the use of mefenamic acid (P>0.05), but both were significantly decreased by peppermint oil (P<0.05). Peppermint oil also showed a significantly greater reduction in diarrhea compared to mefenamic acid (13.5% and 3.8% decrease, respectively; P<0.05). Both groups had similar significant decreases in analgesic use during treatment periods (P<0.05).

The findings of this study show that peppermint oil can reduce the duration and severity of menstrual cramps. Mefenamic acid has been studied as a drug treatment for dysmenorrhea; yet, the results of this study show that peppermint oil has similar effects to mefenamic acid while achieving the additional benefits of significantly reducing nausea and vomiting. Due to the complications of mefenamic acid (some of which include gastrointestinal bleeding, ulcers, flatulence, indigestion, and stomach pain), peppermint oil may be a preferred treatment. Researchers urge future studies on peppermint oil for treatment of dysmenorrhea symptoms and suggest the use of higher dosages or treatment during the luteal phase of the fertility cycle.

References

1Jalilzadeh-Amin G, Maham M. Evaluation of pulegone on transit time and castor oil induced diarrhea in rat. Pharmaceutical Sciences. 2013;19(3):77-82.

2Taher YA. Antinociceptive activity of Mentha piperita leaf aqueous extract in mice. Libyan J Med. 2012;7(1). doi: 10.3402/ljm.v7i0.16205.

3Hiki N, Kaminishi M, Hasunuma T, et al. A phase I study evaluating tolerability, pharmacokinetics, and preliminary efficacy of L-menthol in upper gastrointestinal endoscopy. Clin Pharmacol Ther. 2011;90(2):221-228.

4Alves JGB, de Brito Rde CCM, Cavalcanti TS. Effectiveness of Mentha piperita in the treatment of infantile colic: A crossover study. Evid Based Complement Alternat Med. 2012;2012:981352. doi: 10.1155/2012/981352.

5What does Colpermin™ contain? Colpermin website. Available at: http://www.colpermin.eu/about-colpermin-sup-tm-sup-/what-does-colpermin-sup-tm-sup-contain-. Updated October 2015. Accessed April 16, 2017.

Fennel ‘Safe and Effective’ for Easing Menopause Symptoms

Although a normal phase of a woman’s life, menopause can have a wide range of inconvenient symptoms. New research suggests fennel may help to relieve these symptoms, with little to no side effects.
Clinical trial shows fennel is a safe and effective treatment for menopause symptoms, with no side effects.

The symptoms of menopause range from changes in mood, period, or sex drive to sleep trouble, anxiety, depression, and the well-known hot flashes. This stage in a woman’s life can also increase the risk of health issues, such as osteoporosis or heart disease.

Physicians often recommend hormonal therapy (HT) for managing menopausal symptoms, as well as preserving bone density. However, the National Institute on Aging (NIA) caution against the health risks that HT often poses, including that of a heart attack, stroke, and breast cancer.

Additionally, the United States Food and Drug Administration (FDA) recommend that women take the smallest dose of HT for the shortest period of time possible.

Because of the adverse health effects associated with HT, many women turn to complementary, plant-based medicine for symptom relief during menopause. Plants such as red clover or soy contain phytoestrogens – substances similar to the estrogen produced by the human body but derived from plants.

However, the American Association of Clinical Endocrinologists (AACE) report that the efficacy of phytoestrogens in relieving menopause symptoms has been inconsistent.

But new research – published in Menopause, the journal of The North American Menopause Society (NAMS) – suggests that the phytoestrogens found in fennel help manage postmenopausal symptoms and pose no adverse effects.

Fennel – or Foeniculum vulgare Mill – is a herb known for its culinary and medicinal uses. Fennel is commonly used as a spice, and fennel tea is known to relieve indigestion or premenstrual cramps.

Fennel led to reduction in menopause symptoms

The new research consisted of a randomized, triple-blind trial – an experiment in which the details are kept secret from the participants, those administering the intervention, as well as the committee of researchers in charge of evaluating the outcomes of the experiment.

The study comprised of 90 Iranian women between 45 and 60 years old who lived in Tehran. The average age at which Iranian women get their menopause is younger than that of American women. The former is 48.2 years, compared with 51 years in the U.S.

Participants were administered capsules containing 100 milligrams of fennel every day, twice per day, for a period of 8 weeks. The participants were divided into two groups of 45 women: one that received the treatment and one that received placebo.

Using the Menopause Rating Scale (MRS), the researchers compared the results of the treatment group with those of the placebo group at 4, 8, and 10-week intervals after the intervention began.

Based on the participants’ responses, fennel was found to be “an effective and safe treatment to reduce menopausal symptoms in postmenopausal women without serious side effects.”

The study revealed significantly lower MRS scores in patients who had received the treatment compared with the placebo group.

In the treatment group, a Friedman test revealed significantly lower scores at 4, 8, and 10 weeks, compared with the baseline. In the placebo group, the same test found no significant differences.

This is one of the first clinical trials to investigate the effects of fennel on menopausal symptoms.

This small pilot study found that, on the basis of a Menopause Rating Scale, twice-daily consumption of fennel as a phytoestrogen improved menopause symptoms compared with an unusual minimal effect of placebo. A larger, longer, randomized study is still needed to help determine its long-term benefits and side effect profile.”

Dr. JoAnn Pinkerton, executive director of NAMS

Lavender: An Old World Herb That Has It All – The High Country Gardens Blog

At High Country Gardens our mission is to improve the earth one garden at a time by offering unique plants that are drought resistant or native.

Source: Lavender: An Old World Herb That Has It All – The High Country Gardens Blog

4 Bulk Herb Wholesalers You Can Trust

Consider these conscious companies when shopping for herbal ingredients.

Many of us like to take our health into our own hands and create our own herbal remedies such as tinctures, teas, salves, and oils. Of course, growing our own herbs is the absolute best way to get the freshest possible ingredients. But there are many reasons we might not be able to supply all of our own medicinal herbs, and that’s when we turn to bulk herb suppliers. When it comes to making medicinal products, though, it’s more important than ever that the herbs we source are high-quality, grown organically and harvested and handled by experts who know how to best maximize and retain the plants’ medicinal qualities.

The following Editors’ Picks are some of our very favorite suppliers of high-quality herbs grown, processed and distributed in conscientious ways. They all showcase a dedication to superior quality, whether growing their own herbs or developing long-standing relationships with trusted small farmers. In addition, these companies make it obvious that they value the people who work for them through innovative corporate policies. And they value their customers, too, answering every question promptly via phone, email or Facebook.

Frontier Co-op

Norway, Iowa
(800) 669-3275

Founded in 1976, Frontier Co-op is headquartered on 56 acres just outside Norway, Iowa, where its 145,000-square-foot facility houses its bulk herbs, seasonings, and spices. Owned by its 40,000 active co-op member-owners, Frontier Co-op offers a full line of natural and organic products, including bulk herbs and spices in addition to culinary spices, organic aromatherapy products and more. Frontier Co-op’s goal is to provide its customers with the highest quality organic and natural products while supporting and promoting social and environmental responsibility.

Find them on Facebook.

Ingredient Sourcing & Quality: Frontier was one of the first suppliers to actively advocate organic products and agriculture, carrying its first organic products in 1978 and becoming the first herb and spice manufacturer in the U.S. with certified organic processing. Frontier Co-op also offers farmers fair prices, dealing directly with growers whenever possible. Frontier’s comprehensive sustainable sourcing program, Well Earth, promotes the sustainable production of natural and organic products and creates partnerships built upon a mutual respect for quality botanicals and sound social and environmental principles. The Well Earth program is built on the sourcing expertise Frontier Co-op has gained in more than three decades of experience buying botanicals and meeting personally with growers all over the world. Frontier says, “The Well Earth program is good for our suppliers, their communities, the environment, our co-op and our customers.” Through this program, Frontier helps bring more organic, sustainable and ethically sourced products to the natural foods market, giving consumers the opportunity to use purchases to influence the way the world does business.

Responsibility: Frontier Co-op is committed to sustainability in the storage, processing, packaging and shipping of its products. Its operations practice water conservation; offset 100 percent of power use with renewable energy credits; recycle as much waste as possible; and offset the carbon generated from shipping. Frontier Co-op’s mission is “Nourish people and the planet. Always be fair.” To this end, Frontier Co-op donates 4 percent of its pre-tax sales to support sustainability and community development programs and to promote organic agriculture research, education, and practices in communities across the globe—this standard ranks Frontier among the top companies in the nation for yearly social giving as a percent of sales. Some of Frontier Co-op’s many causes include the Frontier Co-op Foundation, which supports social, educational and environmental causes; the Simply Organic 1% Fund, which supports organic agriculture through research, education and grower development; and the Aura Cacia Positive Change Project, which supports organizations that empower women to transform their lives. Through the Well Earth program, Frontier helps improve the communities where its farmers and growers live. In one recent example, Well Earth worked with its partners to bring expanded dental care services to 41 co-ops of farmers in the mountains around Coban, Guatemala, serving nearly 25,000 people.

Pacific Botanicals

Grants Pass, Oregon
(541) 479-7777

Pacific Botanicals is dedicated to empowering people everywhere to experience the miracle of good health. For more than 37 years, Pacific Botanicals has been growing certified organic medicinal herbs. Pacific Botanicals’ farm in Oregon’s Applegate Valley employs organic growing methods and beyond, saving seed from its own plants suited to the microclimate where they grow, feeding the soil with organic nutrients, and harvesting herbs at the peak of health. For those herbs the company does not grow on its farm, it turns into its network of worldwide certified organic farms and suppliers who understand its stringent quality requirements. Pacific Botanicals has become a leader in organic medicinal herb production through a passionate and uncompromising dedication to quality.

Ingredient Sourcing & Quality: As leaders in the field of providing herbal alternatives to conventional pharmaceutical medicines, Pacific Botanicals believes it must start with the finest chemical-free ingredients possible. The company views its farm, people, and processes not as a factory but rather as a living whole system. Recognizing that organic production integrates social, biological and mechanical practices that foster cycling of resources, promote ecological balance and conserve biodiversity, the Pacific Botanicals farm has many interwoven components—from the seeds to the soil, from the climate to the workers. Each piece of the farming process contributes to making something greater than the sum of its parts.

Responsibility: Pacific Botanicals is a good steward of the earth. Sustainability is the foundation of organic agriculture, and at Pacific Botanicals that means cooperating with the natural renewing and sustaining the power of the earth. The company works to build up its soil and protect its watershed. Its rigorous recycle/reuse program includes everything from recycling the bags in which herbs are received and composting earth-friendly paper towels to purchasing and adapting used equipment for farming and reusing cardboard boxes to ship out orders. The farm also has a 27 kW solar-electric system that supplies about 35 percent of the total electricity used to power its dryers, pumps, processing equipment and the owner’s personal residence.

Oregon’s Wild Harvest

Redmond, Oregon
(800) 316-6869

Founded in 1994 by a husband-and-wife team, Oregon’s Wild Harvest is a whole plant herbal supplement company headquartered in Redmond, Oregon. In harmony with its team of more than 40 farmers, scientists and quality assurance experts, Oregon’s Wild Harvest is dedicated to nurturing good, healthy soil and clean water and saving and replanting its non-GMO seeds on its three farms strategically located in distinct growing zones. With the well-being and care of its customers at heart, the company is committed to growing and procuring only the very highest-quality fresh, whole herbs, which are tested for optimum potency and prepared in small batches.

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Ingredient Sourcing & Quality: Oregon’s Wild Harvest offers 80 varieties of dried herbs and spices in whole, cut and sifted, and freshly milled powdered form. The company’s extensive assortment of bulk herbs is the same premium plant material that goes into all of its finished herbal products sold in natural foods stores around the country and online. All of its bulk herbs go through the same rigorous, in-house quality testing process as its bottled products to verify identity, purity, and potency. Oregon’s Wild Harvest grows many herbs on its certified organic and biodynamic farms. The company also sources from a community of trusted suppliers. Each bulk pouch has a lot number and date for identification and traceability. Herbs are stored in a temperature-controlled room, out of direct light and in the whole form, prior to processing. Each bulk bag is hand-filled to ensure the herbs remain in the whole form as much as possible to minimize essential oil loss. Oregon’s Wild Harvest’s hands-on, closed-loop approach gives the company maximum control over the identity, quality, potency and safety of all of its ingredients and the process itself every step of the way.

Responsibility: Oregon’s Wild Harvest says running an organic herb company requires land, energy, family, farmers, scientists, great partners and a lot of passion. Through its daily practices and operational decisions, Oregon’s Wild Harvest is dedicated to minimizing its impact on the planet. The responsibility starts with the company’s farms, which are dedicated to 100 percent non-GMO organic seed-saving and use Demeter Certified Biodynamic farming practices. The farms are also certified USDA Organic by Oregon Tilth and certified by Salmon-Safe, a nonprofit working to keep urban and agricultural watersheds clean enough for native salmon to spawn and thrive. More than 10 percent of the farm habitat is dedicated to pollinators. Oregon’s Wild Harvest sources the plants it doesn’t grow from growers and wildcrafters with the same high standards employed on the farm. The company also operates a resource-conscious production facility, purchasing carbon offsets via Clean Wind Green Tag, amounting to the equivalent of planting more than 5,400 trees each year. The office and manufacturing plant use 100 percent post-consumer recycled paper and recycle 100 percent of all plastic, glass, cardboard and paper.

Mountain Rose Herbs

Eugene, Oregon
(800) 879-3337

Mountain Rose Herbs offers an enormous selection of organic and fair-trade certified herbs, spices and seasoning blends from culinary traditions around the world. All products are fresh and potent thanks to the company’s dedication to supporting suppliers who use skillful growing, harvesting and drying practices.

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Ingredient Sourcing & Quality: Since 1987, Mountain Rose Herbs has been growing and offering high-quality certified organic herbs, teas and spices. Herbalist-owned and operated, the staff at Mountain Rose understands the importance of sourcing the most vibrant plants harvested at peak potency, dried and processed with expert care for making medicinal teas, tinctures, salves, infused oils and other medicinal preparations. Mountain Rose Herbs has built long-standing relationships with family farms in the Pacific Northwest, Appalachia and abroad to grow fair trade, organic crops that help sustain agricultural livelihoods around the world, as well as natural healing traditions. The company has an on-site Quality Control laboratory to analyze plant identity, test for macroscopic and microbial contaminants, and screen for heavy metals.

Responsibility: Not only is Mountain Rose a zero-waste company, Fair Trade Certified, solar-powered and the founder of a river restoration project, the company is also blazing trails to support medicinal plant conservation. Mountain Rose’s mission to preserve wild places and promote organic agriculture led the company to partner with the nonprofit United Plant Savers in support of the Forest Grown Program. This initiative fosters cultivation of native medicinal woodland crops in Appalachia, using third-party verification and organic certification to guarantee forest products most at risk of poaching—such as American ginseng—are grown and harvested in a sustainable and legal manner. The company is committed to its community and sponsors more than 30 educational events focused on herbal medicine and sustainable living, as well as 35 environmental nonprofit organizations each year.