Sunday, 9 December 2018

Beavers sighted in Italy after almost 500 years By Il Globo Editorial Team Published December 7, 2018 The European beaver has been spotted in Italy for the first time in almost 500 years. The male beaver has been spotted several times in the last week. (Photo: ANSA/Renato Pontarini) Camera traps captured images of a male beaver in the forests of Tarvisiano, in the north-eastern region of Friuli-Venezia Giulia which shares a border with both Austria and Slovenia. The beaver, who seems to be a lone ranger, has been caught on camera several times over the past week. Wildlife experts suspect he crossed the border to Italy from Austria. Locals believed the area had a visitor when they noticed unusual tracks on the ground and marks on branches, so they contacted conservation experts from the University of Turin, who then set up hidden cameras in the area. Researchers have nicknamed the historic creature “Ponta” in honour of Renato Pontarini, the photographer who first caught him on camera. The cute critter’s new name also refers to the bridges that beavers are famous for creating, as the word ponte is the Italian for “bridge”. European beavers were once common from Britain to China, but were hunted to near extinction for their fur and castoreum, an anal secretion the animals use to mark their territories, which – believe it or not – was once used to add scent to perfume and flavour to food. While the species has been successfully reintroduced in parts of its former habitat, including in Croatia, it remained extinct in Italy from the 16th century until now. Il Globo Editorial Team By Il Globo Editorial Team

First ethnobotanical inventory and phytochemical analysis of plant species used by indigenous people living in the Maromizaha forest, Madagascar.

J Ethnopharmacol. 2018 Dec 3. pii: S0378-8741(18)30255-1. doi: 10.1016/j.jep.2018.12.002. [Epub ahead of print] Riondato I1, Donno D2, Roman A3, Razafintsalama VE4, Petit T5, Mellano MG2, Torti V3, De Biaggi M2, Rakotoniaina EN6, Giacoma C3, Beccaro GL2. Author information 1 Department of Agriculture, Forestry and Food Science, University of Torino, Torino, Italy. Electronic address: 2 Department of Agriculture, Forestry and Food Science, University of Torino, Torino, Italy. 3 Department of Life Sciences and Systems Biology, University of Torino, Torino, Italy. 4 Centre National d'Application de Recherches Pharmaceutiques, Antananarivo, Madagascar. 5 Laboratoire de Chimie des Substances Naturelles et des Sciences des Aliments, Université de La Réunion, La Réunion, France; Département Génie Biologique, IUT, Université de La Réunion, La Réunion, France. 6 Département de Biologie et Écologie Végétales, Université d'Antananarivo, Antananarivo, Madagascar; Institute Malgaches des Recherches Appliqués, Antananarivo, Madagascar. Abstract ETHNOPHARMACOLOGICAL RELEVANCE: Characterized by one of the highest rates of endemism and biodiversity in the world, Madagascar provides a wide variety of medicinal plants, that could represent a potential source of new drugs. The main aim of this study was to investigate the potential medicinal properties of the plant species used by indigenous people in Maromizaha forest and to provide the first ethnobotanical inventory of the area. MATERIALS AND METHODS: Data were collected through open semi-structured interviews with local informants, the reported plants were collected and identified to create a specimen herbarium. Informant Consensus Factor (ICF) was calculated for each ailment category mentioned in the use-reports. A selection of seven medicinal plants was submitted to phytochemical and antimicrobial analysis. The results were discussed and compared with those described in ethnobotanical and pharmacological literature. RESULTS: One hundred and three villagers were interviewed and a total of 509 use-reports were recorded. Information on 117 plant species belonging to 57 botanical families were provided. 12 categories of indigenous uses were recognized, among them the higher ICF values were recorded for cardiovascular complaints (0.75), general and unspecific diseases (0.74), digestive disorders (0.69), and diseases of the skin (0.55). The traditional medicinal uses of 18 species (15 endemic) were described for the first time. In total, 22 different bioactive compounds were identified; polyphenols, monoterpenes, organic acids, and vitamin C were observed in the chemical composition of all the analyzed samples. Macaranga perrieri showed the highest values of both total polyphenolic compounds and antioxidant activity. Antimicrobial activity was observed in leaf and bark extracts of Dilobeia thouarsii. CONCLUSION: These results confirmed the importance of investigating the traditional use of plant species, suggesting the crucial role of ethnobotanical studies for rural development, biodiversity conservation, and the sustainable use of plant resources in the studied area. Copyright © 2018. Published by Elsevier B.V. KEYWORDS: Antimicrobial activity; Ascorbic acid; BENZOIC ACIDS; CATECHINS; CINNAMIC ACIDS; Caffeic acid; Castalagin; Catechin; Chlorogenic acid; Citric acid; Coumaric acid; Dehydroascorbic acid; Dilobeia thouarsii; Ellagic acid; Epicatechin; Ethnobotany; FLAVONOLS; Ferulic acid; Gallic acid; Hyperoside; Isoquercitrin; Limonene; MONOTERPENES; Macaranga perrieri; Malic acid; Medicinal plants; ORGANIC ACIDS; Oxalic acid; Phellandrene; Phytochemicals; Quercetin; Quercitrin; Quinic acid; Rutin; Sabinene; Succinic acid; TANNINS; Tartaric acid; Terpinolene; VITAMINS; Vescalagin; Vitamin C; γ-Terpinene

Polycyclic and organochlorine hydrocarbons in sediments of the northern South China Sea.

Mar Pollut Bull. 2018 Dec;137:668-676. doi: 10.1016/j.marpolbul.2018.10.039. Epub 2018 Nov 15. Kaiser D1, Schulz-Bull DE2, Waniek JJ3. Author information 1 Leibniz Institute for Baltic Sea Research Warnemünde, 18119 Rostock, Germany. Electronic address: 2 Leibniz Institute for Baltic Sea Research Warnemünde, 18119 Rostock, Germany. Electronic address: 3 Leibniz Institute for Baltic Sea Research Warnemünde, 18119 Rostock, Germany. Electronic address: Abstract We investigated the concentration distribution and composition of organic pollutants in sediments of the shelf and the deep northern South China Sea (NSCS). Concentrations of polycyclic aromatic hydrocarbons (Σ15PAH; 10.69-66.45 ng g-1), Dichlorodiphenyltrichloroethane (Σ4DDT; 0-0.82 ng g-1), and polychlorinated biphenyls (Σ24PCB; 0-0.12 ng g-1) are below established sediment quality guidelines, suggesting no environmental risk. Surprisingly, concentrations increase from the shelf to the deep NSCS, and are higher in the east of the study area. The organic pollutant composition indicates PAH mainly derived from pyrogenic sources, and mostly degraded DDT and PCB. However, in the deep NSCS, considerable contribution of petrogenic PAH, low chlorinated PCB and p,p'-DDT suggest more recent input from different sources compared to the shelf. From these results we infer that organic pollution in the NSCS does not originate from the Pearl River Estuary but from the NE SCS, SW of Taiwan. KEYWORDS: Organic pollution; Sediment; Source appointment; South China Sea

The effect of covering material on the yield, quality and chemical composition of greenhouse grown tomato fruit.

J Sci Food Agric. 2018 Dec 3. doi: 10.1002/jsfa.9519. [Epub ahead of print] Petropoulos SA1, Fernandes Â2, Katsoulas N3, Barros L2, Ferreira ICFR2. Author information 1 Laboratory of Vegetable Production, University of Thessaly, Fytokou Street, 38446 N. Ionia, Magnissia Greece. 2 Centro de Investigação de Montanha (CIMO), Instituto Politécnico de Bragança, Campus de Santa Apolónia, 5300-253, Bragança, Portugal. 3 Laboratory of Agricultural Constructions and Environmental Control, University of Thessaly, Fytokou Street, 38446 N. Ionia, Magnissia Greece. Abstract BACKGROUND: During the last decades, greenhouse technology for horticultural crops has focused on retaining optimum conditions within the greenhouse environment that could allow to finding the compromise between maximum yields and minimum production costs. The aim of the present manuscript was to evaluate the effect of three greenhouse covering materials and five harvesting dates on the yield and quality parameters of hydroponically produced tomato fruit, as well as on energy consumption. RESULTS: Plants had a higher growth rate at early stages for S-PE cover material, while differences were minimized at later stages. Tocopherols content was the highest for ID-PE material and harvesting later than 170 days after transplanting (DAT), while sugars content (fructose and glucose) was the highest for S-PE material and 157 DAT. Organic acids content was the highest at early harvestings, especially for 7-PE and S-PE cover materials, while it exhibited decreasing trends at later harvesting dates. Antioxidant properties showed a varied response to cover materials and harvesting dates, while β-carotene, carotenoids, and chlorophylls were the highest for 7-PE material. CONCLUSION: In conclusion, the results showed that both cover materials and harvesting date may affect significantly tomato fruit quality, especially sugars and organic acids contents which are associated with fruit taste, as well as tocopherols which contribute to antioxidant properties and pigments that are associated with fruit ripening and earliness of marketable maturity. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved. KEYWORDS: Solanum lycopersicum L.; antioxidant activity; carotenoids; cover materials; double layer films; tomato fruit PMID: 30511352 DOI: 10.1002/jsfa.9519

Hibiscus extract, vegetable proteases and Commiphora myrrha are useful to prevent symptomatic UTI episode in patients affected by recurrent uncomplicated urinary tract infections.

Arch Ital Urol Androl. 2018 Sep 30;90(3):203-207. doi: 10.4081/aiua.2018.3.203. Cai T1, Tiscione D, Cocci A, Puglisi M, Cito G, Malossini G, Palmieri A. Author information 1 Department of Urology, Santa Chiara Regional Hospital, Trento. Abstract OBJECTIVE: To evaluate the efficacy of a combination of Hibiscus extract, vegetable proteases and Commiphora myrrha extract in the prophylaxis of symptomatic episode in women affected by recurrent urinary tract infections (rUTIs). MATERIALS AND METHODS: In this phase II clinical trial, all patients with history and diagnosis of rUTI were enrolled. All patients underwent the following treatment schedule: 1 tablet in the morning and 1 tablet in the evening for 7 days and, then, 1 tablet in the evening for 10 days (1 cycle every each month, for 6 months) of a combination of Hibiscus extract, vegetable proteases and Commiphora myrrha extract. At the baseline, all patients underwent urologic visit with quality of life (QoL) questionnaires and mid-stream urine culture. After 3 and 6 months, all patients underwent urologic visit, urine culture and QoL questionnaires evaluation. RESULTS: Fifty-five women were enrolled (mean age 49.3; range: 28-61). At the enrollment time, the most common pathogen was Escherichia coli (63.7%). The median number of UTI per 6 months was 5 (IQR: 4-9). At the end of the second follow-up evaluation, 25 women did not reported any symptomatic episode of UTI (49%), 18 reported less than 2 episodes (35.3%), while 8 reported more than 2 episodes (15.7%). However, at the first and second follow-up evaluation the clinical statistically significant improvement (QoL) was reported by 38/51 (74.5%) (p < 0.001 from baseline) and 43/51 (84.3%) (p < 0.001 from baseline) women, respectively. The median number of UTI decreased to 2 (IQR: 0-3). At the end of the follow-up period, 30/51 had sterile urine (58.8%), while 21/51 (41.2%) reported a transition from symptomatic UTI to asymptomatic bacteriuria. CONCLUSIONS: In conclusion, this treatment, in motivated patients, is able to prevent symptomatic UTI symptomatic episode and improve patient's QoL. KEYWORDS: Ellirose; Myrliq; Protelix; Serrazimes; Urinary tract infection; antibiotic stewardship; plant extracts; treatment. PMID: 30362679 DOI: 10.4081/aiua.2018.3.203 Free full text

Double-blind placebo-controlled randomized clinical trial of ginger ( Zingiber officinale Rosc.) addition in migraine acute treatment.

Cephalalgia. 2018 Jan 1:333102418776016. doi: 10.1177/0333102418776016. [Epub ahead of print] Martins LB1, Rodrigues AMDS1, Rodrigues DF1, Dos Santos LC1, Teixeira AL2, Ferreira AVM1. Author information 1 1 Department of Nutrition, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. 2 2 Department of Internal Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. Abstract Background Previous studies have demonstrated the analgesic effects of ginger in different conditions, but evidence about its efficacy in migraine treatment is scarce. Objective This study aimed to evaluate the potential of ginger to improve acute migraine as an add-on strategy to standard treatment. Methods A double-blind placebo-controlled randomized clinical trial in the emergency room of a general hospital was conducted. Patients who sought medical care at the time of migraine attack were enrolled in this study. Only adults with episodic migraine (one to six migraine attacks per month) with or without aura were included. Sixty participants were randomized into two groups in which they received 400 mg of ginger extract (5% active ingredient) or placebo (cellulose), in addition to an intravenous drug (100 mg of ketoprofen) to treat the migraine attack. Patients filled a headache diary before, 0.5 h, 1 h, 1.5 h and 2 h after the medication. Pain severity, functional status, migraine symptoms and treatment satisfaction were also recorded. Results Patients treated with ginger showed significantly better clinical response after 1 h ( p = 0.04), 1.5 h ( p = 0.01) and 2 h ( p = 0.04). Furthermore, ginger treatment promoted reduction in pain and improvement on functional status at all times assessed. Conclusions The addition of ginger to non-steroidal anti-inflammatory drugs may contribute to the treatment of migraine attack. This trial is registered at (NCT02568644). KEYWORDS: Migraine; complementary treatment; ginger; ketoprofen PMID: 29768938 DOI: 10.1177/0333102418776016

A Placebo-Controlled Double-Blind Study Demonstrates the Clinical Efficacy of a Novel Herbal Formulation for Relieving Joint Discomfort in Human Subjects with Osteoarthritis of Knee.

J Med Food. 2018 May;21(5):511-520. doi: 10.1089/jmf.2017.0065. Epub 2018 Apr 30. Karlapudi V1, Prasad Mungara AVV2, Sengupta K3, Davis BA4, Raychaudhuri SP5. Author information 1 1 Pujitha Hospital , Vijayawada, India . 2 2 Vijaya Super Speciality Hospital , SPSR Nellore, India . 3 3 Laila Nutraceuticals R&D Center , Vijayawada, India . 4 4 PLT Health Solutions, Inc. , Morristown, New Jersey, USA. 5 5 Department of Medicine, School of Medicine, University of California Davis , Davis, California, USA. Abstract LI73014F2 is a novel composition prepared from extracts of Terminalia chebula fruit, Curcuma longa rhizome, and Boswellia serrata gum resin with synergistic benefit in 5-Lipoxygenase (5-LOX) inhibition. This herbal composition with strong anti-5-LOX activity exhibited significant pain relief as indicated through improvements in weight-bearing capacity in a monosodium iodoacetate-induced osteoarthritis (OA) model of Sprague-Dawley rats. A 90-day randomized, placebo-controlled double-blind study evaluates the clinical efficacy and tolerability of LI73014F2 in the management of symptoms of OA of the knee (Clinical Trial Registration No. CTRI/2014/01/004338). Subjects, (n = 105), were randomized into three groups: placebo (n = 35), 200 mg/day of LI73014F2 (n = 35), and 400 mg/day of LI73014F2 (n = 35). All study participants were evaluated for pain and physical function by using standard tools, that is, Visual Analog Scale, Lequesne's Functional Index, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at the baseline (day 0) and on day 14 ± 3, 30 ± 3, 60 ± 3, and at the end of the study (day 90 ± 3). In addition, routine examinations on biochemical parameters in serum, urine, and hematological parameters were conducted on each visit to assess the safety of the study material. At the end of the trial period, LI73014F2 conferred significant pain relief, improved physical function, and quality of life in OA patients. In conclusion, preclinical and clinical data together strongly suggest that the herbal formulation LI73014F2 is a safe and effective intervention for management of joint discomfort, demonstrating efficacy as early as 14 days. KEYWORDS: Boswellia serrata; Curcuma longa; T. chebula; osteoarthritis PMID: 29708818 DOI: 10.1089/jmf.2017.0065 [Indexed for MEDLINE]

Re: Aloe Vera Juice Improves Thyroid Function in Patients with Subclinical Hypothyroidism

Aloe Vera (Aloe vera syn. A. barbadensis, Asphodelaceae) Thyroid Function Hashimoto's Thyroiditis Subclinical Hypothyroidism Date: 11-30-2018 HC# 051836-605 Metro D, Cernaro V, Papa M, Benvenga S. Marked improvement of thyroid function and autoimmunity by Aloe barbadensis Miller juice in patients with subclinical hypothyroidism. J Clin Transl Endocrinol. February 2018;11:18-25. doi: 10.1016/j.jcte.2018.01.003. The leaves of aloe vera (Aloe vera syn. A. barbadensis, Asphodelaceae) contain more than 200 phytochemical substances, including vitamins, minerals, amino acids, active enzymes, anthraquinones, sterols, lignin, saponins, and salicylic acids. Among its amino acids, the most abundant one is arginine; the rarest one is tyrosine, a precursor to thyroid hormones T4 (thyroxine) and T3 (triiodothyronine). These authors examined the effects of aloe vera juice (AVJ) in women with Hashimoto's thyroiditis (HT)-related subclinical hypothyroidism (SCH) and high levels of thyroperoxidase auto-antibodies (TPOAb). The personal experience of one of the authors who had a history of HT-related SCH prompted this study. She began drinking 50 mL of AVJ in the morning on an empty stomach as a skin soother and laxative. After three months and more so after six months, she observed remarkable improvements in her thyroid function. Recruited for this study were women aged 30 to 55 years with HT-associated SCH (thyrotropin [TSH] >4.0 mU/L and high levels of TPOAb) who had not been treated with levothyroxine or supplements. The 30 women aged 20 to 55 years who were enrolled in the study drank 50 mL of AVJ each morning on an empty stomach for nine months. Thyroid function tests, including serum TSH, T3, T4, and TPOAb, were measured at baseline, at 90 ± 3 days (three months), and at 180 ± 3 days (nine months). All 30 women completed the study. The product used in the study was 100% Aloe Vera2 juice (ZUCCARI; Trento, Italy); 100 mL of the juice contains nonpasteurized and noncarbon-filtered AVJ and pulp (49.8 g), 0.2 g fats (0% saturated), 1.2 g carbohydrates, no proteins, and 0.06 g minerals. The juice also contains citric acid as an acidifier and the preservatives sodium benzoate and potassium sorbate. For comparison, the authors used a database of the Interdepartmental Program of Molecular & Clinical Endocrinology and Women's Endocrine Health at University Hospital of Messina, Italy, to identify a group of women with HT who were not using thyroid hormone replacement therapy or supplementation with nutraceuticals. The authors matched the 30 aloe vera-treated women in their study with 15 women from the database who had SCH, were of comparable age, and had similar baseline levels of serum TSH and TPOAb; those 15 women served as a control group. The biochemical indices, which were similar in both groups at baseline, did not change over time in the control group. In the AVJ group, at the end of month three, improvements were seen in TPOAb, which decreased by 24% (P=0.00034), and T4, which increased by 15% (P=0.0073). T3 decreased by 16%. Serum TSH decreased as expected (by 42%) and by three times more than the 15% increase in serum T4. The three-fold greater change (60%) in TSH was also observed at six months, in response to a further increase (24%) in serum T4. After nine months, TPOAb levels continued to decrease (by 56%), TSH was lower (by 62%), and T4 had increased by 26%. The levels of T3 did not decrease further by the end of month nine compared with month three; thus, the T4-T3 ratio continued to increase. At the end of three months, 83% of patients in the AVJ group had normal thyroid function (TSH ≤4.0 mU/L). At the end of month nine, 100% or 83% of women had normal thyroid function, depending on TSH threshold. At the end of the study, all participants in the control group continued to have SCH, with a TSH >4.0 mU/L. No adverse effects were reported during the study. A search of PubMed on September 30, 2017 revealed only a letter to the editor reporting on a single patient1 and one paper on male mice2 describing the effects of aloe vera on thyroid function. Several studies have examined the effects of selenium in patients with autoimmune thyroiditis because of its role in endocrine and immune functions and modulation of the inflammatory response. Investigators report variable effects on serum TPOAb levels after supplementation with selenium for one to 12 months in patients with HT. More consistent and overall greater improvements were observed with the use of selenomethionine, the organic and more bioavailable form of selenium. The findings of the current study are comparable, if not superior, to those reported in studies using selenium alone or combined with myo-inositol. The authors conclude that the daily intake of 50 mL AVJ for nine months restored normal thyroid function in women with HT-related SCH. The authors declare no conflicts of interest. —Shari Henson References 1Pigatto PG, Guzzi G. Aloe linked to thyroid dysfunction. Arch Med Res. September-October 2005;36(5):608. 2Kar A, Panda S, Bharti S. Relative efficacy of three medicinal plant extracts in the alteration of thyroid hormone concentrations in male mice. J Ethnopharmacol. July 2002;81(2):281-285

Re: A Review of Herbal Treatments for Viral Respiratory Tract Infections

Viral Respiratory Infections Antiviral Herbs Date: 11-30-2018 HC# 041844-605 Yarnell E. Herbs for viral respiratory infections. Altern Complement Ther. February 2018;24(1):35-43. Viral respiratory infections (VRIs) like the common cold, viral pharyngitis, acute bronchitis, and influenza (flu) are among the most common human illnesses. Annual vaccines for flu lack acceptance and have variable efficacy. There are no vaccines for other VRIs, and the flu vaccine cannot prevent them. Conventional treatments for VRIs are generally lacking; even neuramidase inhibitors (e.g., oseltamivir, zanamivir) are only marginally effective, with substantial adverse effects (AEs). Antibiotics do not affect viruses; nonetheless, lacking effective conventional medicines, patient demand for antibiotics continues, contributing to bacterial resistance. Many herbal medicines are used to prevent and treat VRIs. Some are backed by research; others, by traditional use; some, by both. Generally, no one herb can resolve VRIs. Multi-herb treatments tailored to the patient are most effective. Yarnell discusses a range of herbs useful for treating and/or preventing VRIs, adding his insights as a clinician. Many herbs act directly against the viruses that cause VRIs and have broad clinical efficacy. Those tested against a range of organisms and viruses have been found to act against most. Listed are garlic (Allium sativum, Amaryllidaceae), licorice (Glycyrrhiza spp., Fabaceae) bloody crane's-bill (Geranium sanguineum, Geraniaceae), Umckaloabo (Pelargonium sidoides, Geraniaceae), Japanese honeysuckle (Lonicera japonica, Caprifoliaceae), black elderberry (Sambucus nigra, Adoxaceae) fruit, and others from diverse plant families. Black elderberry fruit and flower have been shown in clinical trials to reduce severity and duration of flu symptoms. A proprietary formula (BNO1016; Sinupret; Bionorica SE; Neumarkt, Germany) uses a combination of black elderberry flower, vervain (Verbena officinalis, Verbenaceae), cowslip (Primula veris, Primulaceae), Rumex spp. (Polygonaceae), and yellow gentian (Gentiana lutea, Gentianaceae). The formula is active against parainfluenza, respiratory syncytial virus (RSV), rhinovirus, and adenovirus in vitro and has been shown to modulate inflammation in rodents. Randomized, placebo-controlled clinical trials (RCTs) in patients with VRIs also document BNO1016's efficacy. RCTs included children and adults, with minimal AEs. The formula is also effective for allergies, sometimes clinically indistinguishable from VRIs. Among other anti-viral species, both andrographis (Andrographis paniculata, Acanthaceae) and Umckaloabo have been found more effective than placebo, as well as safe, in meta-analyses of RCTs. Yarnell also discusses two ephedra-based anti-viral remedies. Má huáng tāng, a traditional Chinese medicine (TCM) formula with ephedra (Ephedra sinica, Ephedraceae) and three other herbs, was first described for use in "cold damage diseases" in 220 CE. Its historical use against flu has been validated in modern studies. A variant, antiwei formula, adds three more herbs to the mix. In a Chinese RCT of 480 adults with flu (n=125) or flu-like illness (n=355), symptom duration and severity were significantly less in those who took antiwei formula compared to placebo. In these trials of ephedra medicines, AEs were uncommon and mild. Plant families and species with known inflammation- and immuno-modulating effects, as well as anti-viral activity, include an Apiaceae group (oshá [Ligusticum spp.], lomatium [Lomatium dissectum], and western sweet cicely [Osmorhiza occidentalis]). Oshá and related species are used worldwide for colds and flu. Ligusticum spp. produce a known anti-viral compound, (Z)-ligustilide. A Lamiaceae group includes sage (Salvia officinalis), white sage (S. apiana), thyme (Thymus spp.)*, rosemary (Rosmarinus officinalis), and heal-all (Prunella vulgaris). An "evergreen" group spans three Pinaceae (pine [Pinus spp.], fir [Abies spp.], and spruce [Picea spp.]) and two Cupressaceae (cedar [Thuja spp.] and juniper (Juniperus spp.]) genera. Their resin and branch tips are antiviral and inflammation modulating, with an affinity for the respiratory tract. Evergreens are highly sustainable herbal sources. Since herbs in these three groups are immunomodulatory, their ability to also regulate inflammation reduces risks of worsening symptoms through a "cytokine storm." Lomatium lowers production of CXCL10, highly associated with cytokine storms in severe flu. Other herbs reduce production of CCL5, another cytokine storm participant. Diterpenoids in rosemary and sage inhibit many such cytokines. Echinacea (Echinacea angustifolia, Asteraceae), a North American traditional VRI remedy, is an example of how poorly-informed research can harm the reputation of a useful herb. Studies have used extracts, dosages, durations, and means of administration with little or no traditional basis. When low doses at short duration proved ineffective, succeeding trials used even lower doses, citing poor results as proof of echinacea's uselessness. Many used other Echinacea spp., alone or with E. angustifolia. While all Echinacea spp. show inflammation-modulating effects in VRI models in vitro, E. angustifolia is considered superior. Echinacea products must be gargled for their topical numbing effect, useful in pharyngeal pain. Yarnell's base formula for acute VRIs includes E. angustifolia, lomatium, heal-all, licorice, and pokeweed (Phytolacca americana, Phytolaccaceae), the latter a lymphagogue. For patients with confirmed flu, elderberry fruit should be added; for those with fever >103°F, febrifuge herbs. Other herbs can help patients without fever, those with bothersome coughs (wet and dry), or sore throat. Botanical extracts with significant potential to prevent VRIs include Asian ginseng (Panax ginseng, Araliaceae), American ginseng (P. quinquefolius), green tea (Camellia sinensis, Theaceae), and garlic. Given that many safe herbs can prevent and treat VRIs, the author urges "large-scale adoption" of these remedies. —Mariann Garner-Wizard * In an RCT in patients with acute bronchitis, a combination of thyme and ivy (Hedera helix, Araliaceae) leaf reduced coughing significantly more than placebo.

Food as Medicine: Buckwheat

HerbalEGram: Volume 15, Issue 10, October 2018 (Fagopyrum esculentum; F. tataricum, Polygonaceae) By Jenny Pereza and Hannah Baumanb a ABC Education Coordinator b HerbalGram Associate Editor Editor’s Note: Each month, HerbalEGram highlights a conventional food and briefly explores its history, traditional uses, nutritional profile, and modern medicinal research. We also feature a nutritious recipe for an easy-to-prepare dish with each article to encourage readers to experience the extensive benefits of these whole foods. With this series, we hope our readers will gain a new appreciation for the foods they see at the supermarket and frequently include in their diets. We would like to acknowledge ABC Chief Science Officer Stefan Gafner, PhD, for his contributions to this project. Overview Buckwheat (Fagopyrum esculentum and F. tataricum) belongs to the Polygonaceae, or knotweed, family, a plant family with 40 known genera and approximately 1,200 species, which includes other edible plants such as common sorrel (Rumex acetosa) and rhubarb (Rheum rhabarbarum).1,2 Plants in this family have polygonum, or “many knees,” referring to the swollen nodes of the leaf stems.1 Commercially, buckwheat is grown for its fruits, leaves, and flowers that are obtained from either Fagopyrum esculentum, often referred to as common or sweet buckwheat, or F. tataricum, known as Tartary or bitter buckwheat.2-6 Both species are annual herbaceous plants that grow erect from a single hollow stem, which is succulent and smooth except at its characteristic swollen nodes.4 The plant grows rapidly to an average height of 1-3 feet and has soft, heart-shaped leaves and clustered groups of five small white to dark pink petal-like sepals.4,7 Its small dry fruits, botanically known as achenes, are grey to black and have a distinct triangular shape, a hard shell, and a starchy endosperm inside.7 These achenes are known commercially as “groats.” Despite its common name, buckwheat does not belong to the cereal grain family (Poaceae) but is considered a pseudocereal due to its similarities to wheat (Triticum aestivum, Poaceae) in terms of chemical characteristics and dietary uses.3 However, buckwheat does not contain gluten. The name buckwheat comes from the Dutch boekweit (boeke: “beech” and weite: “wheat”), which describes the resemblance of buckwheat seeds to beech (Fagus spp., Fagaceae) nuts as well as the wheat-like nature of buckwheat flour.7,8 Phytochemicals and Constituents Buckwheat groats and flour are considered important nutritional foods because of their high levels of protein, polyphenols, and minerals.5 Starch is the major nutritional component of buckwheat seed. The groats are high in B vitamins, including thiamin (B1), riboflavin (B2), and pyridoxine (B6), and they provide an array of minerals such as potassium, calcium, magnesium, zinc, copper, manganese, and selenium.3 In fact, buckwheat is considered a very good source of dietary magnesium, which is required for healthy nerves and muscles, and contains considerably more calcium than most cereal grains.8,9 Buckwheat’s fatty acid profile and total dietary fiber content is also considered superior to cereal grains.3 However, the high fiber content (17.8%) of buckwheat impedes the digestibility of its proteins.4 The protein content in buckwheat groats is well-balanced and extremely high compared to true cereal grains, and it has a biological value above 90%.3,6 (Biological value is a measure of how much protein is absorbed and integrated into the human body.) Buckwheat contains all nine essential amino acids and is particularly high in lysine, an amino acid found in limited quantities in cereal grains.3,4,8 Buckwheat also contains high amounts of arginine, tryptophan, and thiamine-binding proteins (TBPs), which act to stabilize and enhance the biological activity of thiamine.3 Foods that contain TBPs can be used to prevent dietary thiamine deficiencies.2,3 Despite the high protein content of buckwheat groats, the presence of trypsin inhibitors, fiber, and tannins lowers enzymatic availability, which can impede digestion and absorption of protein.3 The high antioxidant capacity and flavonoid content of buckwheat groats qualify buckwheat and buckwheat-enriched products as functional foods.3 Buckwheat groats are rich in antioxidant compounds, including glutathione, and have a very high polyphenol content, including catechins and flavonoids (e.g., rutin and quercetin).2,3 Rutin and quercetin are biosynthesized by plants in order to protect themselves from UV radiation, diseases, and predators.10 Buckwheat is among a few other field-grown crops that contain rutin, which is considered to be an important component of a heart-healthy diet.3,4 The leaves of buckwheat contain the highest amount of rutin in the plant.10 Tartary buckwheat contains more rutin than common buckwheat.2 Rutin has significant antioxidant and anti-inflammatory effects, and may also have antidiabetic and anti-hypertensive effects.2-4 Consuming 100 g (3.5 oz) of buckwheat flour or grains delivers roughly 10% of the daily therapeutic dose of rutin, which is considered to be between 180 and 350 mg.5 Buckwheat’s rutin levels decrease when exposed to heat; however, quercetin levels remain stable when heated. Although heat-treatment results in lower rutin levels in buckwheat breads and noodles, they are still considered nutrient-dense compared to raw flour.5 Historical and Commercial Uses Buckwheat, grown mainly for its groats, has been cultivated in China for at least 1,000 years.4,5 Buckwheat initially spread to Asia, reaching Japan 3,000 years ago from northern China via the Korean Peninsula.4 Buckwheat cultivation then spread to the Middle East and subsequently to Europe and Russia during the Middle Ages.7 From Europe, buckwheat arrived in North America in the 1600s, and early immigrants cultivated buckwheat on cleared lands to smother weeds and build soil.4,8 Today, Russia and China are the biggest producers of buckwheat globally.2,6 In traditional Chinese medicine (TCM), the leaf of the Tartary buckwheat is used to treat choking, ulcers, and hypertension, and to cleanse wounds. The flavonoid-rich leaves are also considered a nutritious food used to improve vision and hearing.4 Buckwheat is considered blood-building and detoxifying as it neutralizes acidic metabolic waste, and it is a staple of macrobiotic diets.9 In Nepal, Tartary buckwheat leaves are consumed to alleviate stomach disorders.4 Buckwheat groats are prepared raw or roasted, whole or powdered.11 To process buckwheat, the hulls enclosing the seeds are removed, and the seeds are typically roasted.3,11 Raw, hulled buckwheat seeds have a subtle flavor, while roasted, hulled buckwheat has an earthy, nutty flavor.8,11 Roasted, cooked groats have the consistency of porridge and are the basis of kasha, a traditional Russian dish cooked and served much like rice.7,11 In medieval Russia, the word kasha meant “meal” or “feast,” which referred to the belief that no meal was complete without buckwheat.9 Buckwheat flour is made from unroasted groats and typically includes a mixture of both hulled and unhulled buckwheat seeds. Depending on the amount hulled and unhulled seeds, buckwheat flour is graded light, medium, or dark.9 Unhulled buckwheat seed flour is the darkest in color and most nutritious, while flour made from hulled ground groats is the lightest in color and contains fewer nutrients.8,9 Buckwheat flour is used by a variety of diverse cultures, alone or as an ingredient in pancakes, French crepes, Southeast Asian unleavened breads (chapattis) and fried snacks (pakora), as well as Japanese soba noodles.4,7 To prevent rancidity, buckwheat seeds are stored with hulls and de-hulled shortly before use.4 A balanced amino acid profile can be achieved by mixing buckwheat with cereal grains, which are typically low in lysine.4 In Europe, buckwheat bread is gaining popularity as a nutrient-dense, antioxidant rich, gluten-free alternative to common cereal grains.5 Food science studies indicate that making wheat bread with 15% buckwheat flour functionally enhances its nutrient content and natural antioxidant capacity without compromising texture or flavor.3 In Europe and North America, buckwheat flour is typically blended with wheat flour to prepare pancakes, biscuits, noodles, and cereals.3 Aromatic buckwheat flowers provide both pollen and nectar for honeybees.3,8,11 Because honey production comes late in the season when other nectar sources are scarce, buckwheat is an important warm-weather, late-season crop for honeybees.4,11 Buckwheat honey has dark color, a distinct spiced flavor, and confirmed health benefits (see “Buckwheat Honey” section below).3 Modern Research A Gluten-free ‘Grain’ Unlike wheat, barley (Hordeum vulgare, Poaceae), and rye (Secale cereale, Poaceae), buckwheat grains lack α-gliadin and are low in prolamins (seed storage proteins that act as food antigens).3 These factors make buckwheat a healthy alternative for individuals with Celiac disease or non-Celiac gluten sensitivity (NCGS). Celiac disease is an autoimmune disease with both genetic and environmental components.3 Chronic intestinal inflammation can lead to malabsorption of several important nutrients, including iron and folate, which can lead to anemia and other ill effects.3 Strict adherence to a gluten-free diet is crucial to effectively treating Celiac disease and other gluten-sensitive individuals.3 A randomized, crossover trial with two intervention phases was conducted on 19 patients with NCGS over a period of 12 weeks.12 Participants either consumed a diet that consisted of buckwheat products or maintained their normal gluten-free diet without buckwheat supplementation. During the intervention period, those consuming buckwheat products experienced not only a significant reduction in the severity of abdominal pain and bloating, but also a significant increase in blood levels of magnesium and a reduction in pro-inflammatory cytokines.12 Type 2 Diabetes Dietary approaches are highly recommended for managing chronic diseases like type 2 diabetes mellitus (T2DM) and its associated cardiovascular, renal, and ocular complications.13 In many places where buckwheat is cultivated, it is traditionally used as both a food and a medicine. For example, in Taiwan and China, Tartary buckwheat is consumed daily to treat T2DM.5 Regular consumption of buckwheat products is strongly correlated with lower incidence of hyperglycemia and improved glucose tolerance.6 Buckwheat contains D-chiro-inositol (DCI), which is a primary mediator of insulin metabolism and has the ability to enhance glucose utilization and decrease blood pressure, plasma triglycerides, and glucose concentrations.6 Replacing or partially substituting buckwheat flour for white rice or wheat flour is a practical approach to disease management for patients with T2DM and those with a high risk of developing T2DM.13 Among all of the grains, buckwheat has the longest gastrointestinal transit time, which is associated with stabilized blood sugar levels and feelings of satiety.9 In a four-week clinical trial, 165 participants with T2DM who consumed Tartary buckwheat (> 110 g/d) experienced a 2.85% reduction in insulin, a 6.3% reduction in total cholesterol levels, and a 7.0% decrease in low-density lipoprotein (LDL) levels compared with the control group.13 Additionally, those who consumed buckwheat as part of their staple diet had a 15% increase in daily protein intake and a 25% increase in daily dietary fiber intake compared to baseline.13 A small clinical study of analyzed the effects on glucose and insulin on 10 healthy volunteers who consumed a single dose of boiled buckwheat groats, bread enriched with 50% buckwheat flour, or white wheat bread on separate days. Data showed that postprandial blood glucose and insulin production were lower when the subjects consumed buckwheat, especially buckwheat groats, than when the subjects consumed white wheat bread.2 Cardiovascular Health The bioflavanoids in green buckwheat tea may play a role in improving circulatory health.9,10 Rutin, for example, has been shown to increase the elasticity of blood vessels and arteries, enhance peripheral circulation, lower the risk of atherosclerosis and hypertension, and reduce capillary fragility.2-4,10 Two other compounds in buckwheat — γ-aminobutyric acid (GABA) and 2”-hydroxynicotianamine (H2N) — have been shown to possess blood pressure-reducing activity in vitro and in animals, possibly by inhibiting the action of angiotensin converting enzyme (ACE)-inhibitors.2,6 The use of buckwheat leaf and flower tea was investigated for its effects on leg adema in a randomized, double-blind, placebo-controlled trial of 67 patients with chronic venous insufficiency. Individuals who consumed buckwheat tea reported significant improvements in edema symptoms and less discomfort.5 Other studies have reported a rise in serum quercetin levels after consuming buckwheat tea, which may contributing to its potential anti-inflammatory and antioxidant effects.10 Buckwheat has also been studied for its ability to reduce unhealthy cholesterol levels including LDL and very low density lipoproteins.6 Buckwheat’s high fiber content helps lower cholesterol by increasing fecal excretion of sterols and decreasing absorption of dietary cholesterol.6,13 In a 2011 randomized, double-blind, placebo-controlled crossover study, 62 healthy volunteers were divided into two groups that consumed four cookies daily for four weeks. The active group received cookies enriched with buckwheat flour, and the control group were given cookies contained no buckwheat flour. After two weeks, the groups switched cookie types.2 The participants in the active group experienced significant decreases in levels of total cholesterol and myeloperoxidase (MPO), an enzyme that contributes to oxidative stress and inflammation.2 Oral Health In many traditional cultures, the seeds, roots, and bark of polyphenol-rich herbs are powdered and used as natural antibacterial and anti-inflammatory toothpowders to maintain oral hygiene and gum health. A clinical study reported a 62% improvement in periodontitis and bleeding gums in patients who brushed their teeth twice daily with Tartary buckwheat flour toothpowders.4 The improvements in gum tissue integrity were attributed to buckwheat’s vitamin and mineral contents, as well as the protective anti-inflammatory effects of rutin and quercetin.4 Buckwheat Honey Buckwheat honey provides antioxidant and antibacterial protection similar to New Zealand’s Manuka honey and has been studied for its powerful internal and external healing properties.14 Despite its own therapeutic benefits, buckwheat honey is not widely consumed due to its dark amber color and its strongly spiced odor and malty flavor.14 The flavor, composition, and biological activities of honey vary upon type of botanical forage and geographical location. Research indicates that dark-colored honey contains higher levels of phenolic compounds and has, therefore, a more potent antibacterial and antioxidant capacity.14 Higher mineral content in honey is also associated with a darker color and stronger flavor. Buckwheat honey has a higher protein content than most honeys and delivers more iron, calcium, magnesium, manganese, and zinc.14 A 2007 clinical study of 105 children with acute nocturnal cough due to upper respiratory illness were randomly assigned to one of three groups: an active group given a single nocturnal dose of buckwheat honey, an active control group given single nocturnal dose of artificial honey-flavored dextromethorphan (an over-the-counter antitussive), or the control group which received no treatment.15 Results indicated that the group treated with buckwheat honey had significantly greater symptom relief (reduced cough severity, and frequency while improving child’s sleep quality) than participants in the other two groups.15 In vitro, both Manuka and buckwheat honey have been shown to inhibit Staphylococcus aureus, a bacteria that causes a wide range of common skin infections and life-threatening illnesses such as pneumonia and sepsis.14 Studies by Zhou et al. have demonstrated buckwheat honey’s ability to prevent hydroxyl radical-induced DNA damage through its inherent antioxidant components.2 Consumer Considerations Buckwheat’s nutritional, dietetic, and therapeutic properties make it an important global food crop to cultivate especially as access to arable land and water become more challenging.2 Compared to cereal grains, buckwheat requires fewer soil nutrients and less water, and has the additional benefits of naturally suppressing weeds, improving soil health, fostering beneficial insects, and providing forage for livestock and poultry.2,7,11 Due to its very high protein content, buckwheat complements cereal grains and helps provide a more complete protein when combined with typical cereal grains and flours.8 Consuming buckwheat or buckwheat-containing foods frequently and in high amounts can cause IgE antibody-mediated allergic reactions.2 Additionally, it is important to be aware that buckwheat sprouts, despite their growing popularity, contain napthodianthrones, more specifically the fagopyrins that can cause photosensitization or skin irritation after sunlight exposure.5 Buckwheat sprouts should not be consumed in excess by poultry, livestock, or humans.5 Consumers should be aware that gluten-free products tend to be deficient in B vitamins, calcium, iron, zinc, magnesium, and fiber while also containing higher amounts of added sugar or fat.12 The dietary use of pseudocereals, like buckwheat, could improve dietary intake of protein, iron, calcium, and fiber.12 Nutrient Profile16 Macronutrient Profile: (Per 100 grams buckwheat groats) 343 calories 13.3 g protein 71.5 g carbohydrate 3.4 g fat Secondary Metabolites: (Per 100 grams buckwheat groats) Excellent source of: Manganese: 1.3 mg (56.5% DV) Magnesium: 231 mg (55% DV) Dietary Fiber: 10 g (33% DV) Riboflavin: 0.43 mg (33% DV) Niacin: 7.02 mg (43.9% DV) Phosphorus: 347 mg (27.8% DV) Very good source of: Vitamin B6: 0.21 mg (12.4% DV) Iron: 2.2 mg (12.2% DV) Good source of: Potassium: 460 mg (9.8% DV) Thiamin: 0.101 mg (8.4% DV) Folate: 30 mcg (7.5% DV) Also provides: Calcium: 18 mg (1.4% DV) DV = Daily Value as established by the US Food and Drug Administration, based on a 2,000-calorie diet. Recipe: Kasha Cereal9 Ingredients: 1 cup buckwheat groats 4-5 cups boiling water 1/2 onion, diced (optional) Salt to taste Directions: Place all ingredients in a large pot and bring to a boil. Cover, reduce heat to low, and simmer for 30 minutes until soft. Photo credit: Buckwheat (Fagopyrum esculentum) All photos ©2018 Steven Foster References Elpel T. Botany in a Day: The Patterns Method of Plant Identification. Pony, MT: HOPS Press LLC; 2004. Gimenez-Bastida JA, Zielinski H. Buckwheat as a functional food and its effects on health. J Agr Food Chem. 2015;63:7896-7913. Wronkowska M, Soral-Smietana M, Krupa-Kozak U. Buckwheat, as a food component of a high nutritional value, used in the prophylaxis of gastrointestinal disease. Eur J Plant Sci Biotech. 2010;4(Special Issue 1):64-70. Campbell CG. Buckwheat (Fagopyrum esculentum). International Plant Genetic Resources Institute. 1997. Kade Research Ltd. Morden, Manitoba, Canada. Kreft M. Buckwheat phenolic metabolites in health and disease. Nutr Res Rev. 2016;29:30-39. Zhang ZL, Zhou ML, Tang Y, et al. Bioactive compounds in functional buckwheat food. Food Res Int. 2012;49:389-395. Van Wyk B. Food Plants of the World: An Illustrated Guide. Portland, OR: Timber Press; 2006. Murray M, Pizzorno J. The Encyclopedia of Healing Foods. New York, NY: Atria Books; 2005. Pitchford P. Healing with Whole Foods: Oriental Traditions and Modern Nutrition. Berkeley, CA: North Atlantic Books; 1993. Kreft I, Fabjan N, Germ M. Rutin in buckwheat – Protection of plants and its importance for the production of function food. Fagopyrum. 2003;20:7-11. Buckwheat. Encyclopedia Britannica website. Available at: Accessed on October 2, 2018. Dinu M, Macchia D, Pagliai G, et al. Symptomatic efficacy of buckwheat products in Non-Celiac Gluten Sensitivity (NCGS). Asian Pac J Clin Nutr. 2017;26(4):630-636. Qiu J, Liu Y, Yue T, et al. Dietary Tartary buckwheat intake attenuates insulin resistance and improves lipid profiles in patients with type 2 diabetes: a randomized controlled trial. Nutr Res. 2016;36:1392-1401. Deng J, Liu R, Lu Q, et al. Biochemical properties, antibacterial and cellular antioxidant activities of buckwheat honey in comparison to Manuka honey. Food Chem. 2018;252:243-249. Paul IM. Therapeutic options for acute cough due to upper respiratory infections in children. Lung. 2012;190:41-44. Agricultural Research Service. National Nutrient Database for Standard Reference Legacy Release. United States Department of Agriculture website. April 2018. Available at: Accessed October 5, 2018.

Grape Seed Vitis vinifera

Family: Vitaceae by Gayle Engels, Josef Brinckmann HerbalGram. 2018; American Botanical Council INTRODUCTION The Vitaceae or grape family includes about 900 species in 15 genera. About 70 interfertile (capable of interbreeding) species compose the genus Vitis. Of these, V. vinifera is the best known, as well as the most culturally and economically important.1 Vitis vinifera originated in central Asia, but it now occurs in many regions of the world as a result of extensive cultivation and escape.2 It is a perennial liana (woody, climbing vine) that climbs with coiled tendrils. Grapes were among the first fruits to be domesticated thousands of years ago, and there are currently an estimated 10,000 cultivars of this single species. The domesticated subspecies V. vinifera subsp. vinifera (syn. V. vinifera subsp. sativa, or V. sativa) is monoecious (hermaphroditic), having both male and female reproductive organs in a single individual. It descended from a wild ancestor V. vinifera subsp. sylvestris (syn. V. sylvestris), which is dioecious — having male and female reproductive organs in separate individuals. The subspecies sylvestris now occurs in the wild from the Atlantic coast of southwestern Europe to Tajikistan and the western Himalayas in central and southern Asia.3 More than 90% of the world production of grapes is from V. vinifera.4 However, other Vitis species, including V. berlandieri, V. riparia, and V. rupestris, are used as germplasm resources to breed rootstock for improved resistance against fungal diseases.5 Other Vitis species used for wine production, in particular V. labrusca, also provide seed material for the production of grape seed extract (GSE*).6 GSEs typically are produced from dried or fresh grape seeds that are obtained as a byproduct of the juice and wine industries. First, the grape seeds are extracted using a solvent (e.g., water, or mixtures of water with ethanol or acetone) and then filtered and subjected to further processing in order to produce GSE that contains anywhere from 50% to 90% phenolic compounds.7 There is also a pharmacopeial GSE called “Grape Seeds Oligomeric Proanthocyanidins,” defined in the United States Pharmacopeia (USP) as the fraction of an extract of the ripe seeds of V. vinifera containing not less than 75.0% oligomeric proanthocyanidins (OPCs).8 HISTORY AND CULTURAL SIGNIFICANCE The Latin genus name Vitis means “grape vine,” while the species name vinifera means “produces wine” or “wine bearing’” and is related to the Latin terms vinum (“wine”) and vinea (“vineyard”).9 The words “wine,” vin (French), and Wein (German) stem from the ancient Greek term (oinos) and the Latin term vinum.10 Swedish botanist Carl Linnaeus (1707-1778) included Vitis vinifera in his 1749 work Materia Medica and described its occurrence as “orbis totus temperatus” (global, temperate). For therapeutic use, he did not describe the seed but rather the leaf (as Vitis Folia), stating that it was used to treat stranguria (slow, painful urination) and tussis (cough).11 Grape is considered a “cultural keystone species” and is associated with divinities and rituals, evidenced by representations on artifacts of ancient cultures of the Mediterranean.12 Archaeobotanical evidence of Vitis species is mainly in the form of waterlogged, mineralized, and charred seeds. It is difficult to determine whether these seeds originated from wild or cultivated plants13 because the seeds of V. vinifera subsp. sylvestris (wild) and V. vinifera subsp. vinifera (cultivated), for example, are morphologically very similar.14 Domestication of the cultivated grape reportedly took place between the seventh and the fourth millennia BCE in the Caucasus region (between the Black Sea and the Caspian Sea) in present-day Georgia, Armenia, and Azerbaijan,5,15 where the crop exhibits high genetic diversity. From the Caucasus, cultivation is believed to have spread to Mesopotamia and Egypt and then throughout the Mediterranean16 and beyond. Approximately 9,000-year-old grape pips (seeds) found in the southern Caucasus provide the earliest known archaeological evidence of grape cultivation.17 Based on botanical, ampelographic (the science concerned with identification and classification of grape vines), archaeological, paleontological, historical, ethnographical, and linguistic studies, Georgia is recognized as one of the earliest sites of grape domestication.18 Today, the most widely cultivated species in Georgia are V. vinifera and V. labrusca and their varieties, including V. labrusca var. izabella (purple), V. vinifera var. Rkatsiteli (white), and V. vinifera var. Saperavi (red). The fermented grape seed residue byproduct of these species are being studied in Georgia as potential source materials for commercial production of GSE.6 While there are well-documented traditional medicinal uses of other plant parts of V. vinifera — for example, the dried leaf (pharmacopeial name: Vitis viniferae folium),19 the dried fruit or raisin (Uvae passae or Vitis viniferae fructus), and processed forms such as wine (Vinum)20 — extraction of the seed for functional, nutritional, or therapeutic uses is a relatively new innovation. Development of GSE traces back to research begun in the late 1940s, although commercial products did not appear until the 1970s. In 1947, French scientist Jack Arthur Masquelier (1922-2009) extracted a colorless fraction from peanut (Arachis hypogaea, Fabaceae) skin, proposing that its major components were oligomers of flavan-3-ol units (e.g., (+)-catechin or (-)-epicatechin), which today are classified as oligomeric flavan-3-ols. Over the decades, this led to research into other potential sources of the compounds, including pine (Pinus spp., Pinaceae) bark and grape seed. By 1970, Masquelier had isolated these flavanols from grape seeds21 and applied for a patent for his extraction process, which was granted to his company, Société Civile d’Investigations Pharmacologiques d’Aquitaine (SCIPA), in 1972 by the French National Institute of Industrial Property (INPI).22 Today, GSE is used as a component of dietary supplement products and natural health products for venous insufficiency (in which veins have problems sending blood from the legs back to the heart), to promote wound healing, and to reduce inflammation.23 It is also used as a functional food additive and cosmetic ingredient. In 2003, San Joaquin Valley Concentrates (Fresno, California) submitted a Generally Recognized as Safe (GRAS) notice to the US Food and Drug Administration (FDA) for a GSE to be used as an antioxidant or emulsifier component of food products at levels ranging from 0.01% to 0.08%. The FDA responded that it had no questions regarding San Joaquin’s conclusion that GSE is GRAS under the intended conditions of use.24 In the same year, Polyphenolics, Inc. (Madera, California) submitted a GRAS notice for GSE and grape pomace extract (GPE) for use as antioxidants in certain fruit beverages at a concentration of up to 210 parts per million (alone or in combination with other ingredients). Again, the FDA had no questions regarding Polyphenolics’ conclusion that GSE and GPE are GRAS under the intended conditions of use.25 Subsequently, in 2007, Polyphenolics, Inc. requested and received an independent GRAS extension expert opinion that justified increasing the concentration in beverages to up to 845 mg/L (200 mg/8 oz). Enovita, a GSE from Indena (Milan, Italy), is also GRAS as per an independent GRAS assessment and conclusion (G. Ris email to T. Smith, June 18, 2018). In 2008, a new dietary supplement quality standards monograph titled “Grape Seeds Oligomeric Proanthocyanidins” was proposed for entry into the USP. A draft monograph was published in the Pharmacopeial Forum for public comment,26 after which the final monograph became official in the 33rd revision of the USP in 2010.27 In 2012, the company Nutrilinks Sarl (Lausanne, Switzerland) submitted an application to the European Food Safety Authority (EFSA) for an opinion on scientific substantiation of its proposed health claim for GSE related to maintenance of normal venous blood flow. The subject of its application was a dry extract obtained by extraction of grape seeds with ethanol and ethyl acetate, and subsequent evaporation, filtration, concentration, and spray-drying, standardized to total polyphenol content (minimum 35% of gallic acid, catechins, and epicatechins, and minimum 7% of procyanidin dimers B1, B2, B3, and B4). The EFSA concluded that the data did not establish a cause-and-effect relationship between the consumption of this GSE and maintenance of normal venous blood flow.28 Another application by the same company was submitted to the EFSA in 2012 for an opinion on scientific substantiation of a health claim for its GSE related to the elimination of excess water in the body. The EFSA panel concluded that the applicant’s proposed claim statement (“helps to drain the body in case of water accumulation”) in the context of “normal venous circulation in the legs” refers to the maintenance of normal venous blood flow, and that a claim for GSE and maintenance of normal venous blood flow had already been assessed and rejected.29 CURRENT AUTHORIZED USES IN COSMETICS, FOODS, AND MEDICINES In the United States, GSE is classified as GRAS for certain limited food uses and appears on the FDA’s list of “Substances Added to Food” (formerly “Everything Added to Food in the United States,” or EAFUS).30 GSE may also be used as a component of dietary supplement products, which require FDA notification within 30 days of marketing if a structure-function claim is made and product manufacturing that adheres to current Good Manufacturing Practices (cGMPs).31 In Canada, GSE standardized to 80-85% OPCs is regulated as an active ingredient of licensed natural health products (NHPs), which require pre-marketing authorization from the Natural and Non-prescription Health Products Directorate (NNHPD). Depending on the dosage and strength, labels of licensed GSE NHPs may carry one or both of the following claim statements: “Source of antioxidants for the maintenance of good health” and “Helps to relieve symptoms related to non-complicated chronic venous insufficiency (CVI), such as sensation of swelling, heaviness and tingling of the legs.”32 In the European Union, different types of GSE are listed as components of cosmetic products and are used for various functions (e.g., antidandruff, antimicrobial, antioxidant, oral care, skin-protecting, and UV-absorbing functions). “Oleoyl GSE” (obtained by the reaction of oleoyl chloride with GSE), “Propyl Oleoyl GSE” (obtained by the reaction of oleoyl chloride with the propyl ether of GSE), and “Undecylenoyl GSE” (obtained by the reaction of GSE with undecylenoyl chloride) are all used for antioxidant function; “Palmitoyl GSE” (GSE reaction products with hexadecanoyl chloride) is used for skin-conditioning function; and “Sodium GSE Phosphate” (sodium salt of a complex mixture of esters of phosphoric acid and GSE) is used for antioxidant and skin-conditioning functions.33 MODERN RESEARCH Proanthocyanidins (PACs) are the major chemical compounds in GSEs. The PAC content of GSEs typically comprises 5-30% monomers (including catechins, epicatechins, and other flavan-3-ol monomers), 17-63% oligomers,† and 11-39% polymers (and their gallic acid esters). GSEs contain primarily B-type PACs (flavan-3-ol polymers where the units are linked by a single bond). The large number of grape varieties used to make GSEs accounts for the varied concentrations of bioactive chemical compounds in the seeds.7,34 There are a number of clinical studies on various GSEs for numerous conditions and functions, such as atherosclerosis prevention,35,36 chronic periodontitis,37 climacteric syndrome,35 estrogen levels,38 hyperlipidemia,36,39,40 hypertension,41,42 idiopathic male infertility,43 leg swelling during prolonged sitting,44 liver function,45 oxidative stress and reperfusion injury caused by cardiopulmonary bypass surgery,46 postprandial oxidative stress and inflammation in persons with metabolic syndrome,47 postprandial blood glucose,48 renal failure in chronic kidney disease,49 antioxidant capacity and lipid peroxidation in type 2 diabetes mellitus,50 and skin protection from UV radiation.51 Most of these studies are of varying degrees of quality and, while they all show some positive outcomes, they are either preliminary studies; were not randomized, double-blind, and placebo-controlled (RDBPC); did not explain randomization, blinding, or withdrawals; and/or had a very small study population. One recent RDBPC study investigated the effects of GSE supplementation on oxidative stress and metabolic profiles of female volleyball players. Forty healthy volunteers (14-24 years old) were randomly assigned to take 300 mg GSE (formulated by Barij Essence Pharmaceutical Co.; Kashan, Iran; no additional information provided) or placebo twice a day, with lunch and dinner, for eight weeks. Participants kept dietary records on one weekend day and two weekdays, and physical activity records on weeks two, four, and six of the study. Fasting blood samples were obtained before and after the intervention and centrifuged, and the total antioxidant capacity (TAC), total glutathione (GSH, an antioxidant), malondialdehyde (MDA, a marker of oxidative stress), nitrous oxide (NO), creatine phosphokinase (CPK), fasting plasma glucose (FPG), serum triglycerides, serum insulin, and very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and total cholesterol levels were measured. The GSE group experienced a significant increase in GSH compared to placebo, and a significant decrease in MDA compared to placebo. Additionally, GSE supplementation resulted in decreased serum insulin concentrations, decreased scores on the homeostasis model assessment for insulin resistance index, and increased scores on the quantitative insulin sensitivity check index compared to placebo, all of which are considered beneficial effects on insulin metabolism. There were no significant changes in CPK, TAC, NO, FPG, or serum lipid concentrations compared to placebo.52 Two meta-analyses have reported on clinical studies investigating the effects of GSE on cardiovascular risk markers. The first, conducted in 2011, included nine randomized, controlled trials published between 2000 and 2009 (N = 390) that focused on at least one of the following: systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate, triglycerides, C-reactive protein (CRP), or total, LDL-, or HDL-cholesterol. This meta-analysis concluded that GSE supplementation was associated with significantly lowered SBP and heart rate with no significant effects on DBP, CRP, or serum lipid levels. While the reduction in SBP was modest compared to that seen with prescription antihypertensive drugs, it may still be meaningful since it is estimated that “every 3 mm Hg reduction in SBP could reduce the risk of all-cause mortality by 4%, mortality after stroke by 8%, and mortality after coronary artery disease by 5%.” The authors opined that GSE might have cardioprotective effects beyond SBP and heart rate reductions, and that larger studies should be done evaluating different dosages of GSE with longer follow-up durations.53 A more recent meta-analysis from 2016 included 12 articles (16 randomized trials, N = 810) that analyzed the effects of GSE on blood pressure over at least two weeks. Of the 16 clinical trials, four studied GSE’s effects in patients with prehypertension and stage 1 hypertension, four included healthy subjects, three in patients with metabolic syndrome, two in patients with hypertension, two in women with at least one menopausal symptom, and one in patients with above-average vascular risk. Overall, GSE was associated with significant changes in SBP and DBP. Significant decreases in SBP and DBP occurred more often in subjects under 50 years of age, while significant decreases in SBP alone occurred in obese subjects and patients with metabolic syndrome. Additionally, the authors identified study design, randomization, and baseline blood pressure as possible causes of heterogeneity (variability between the studies). Therefore, they recommend confirmation of their findings through a “large-scale, long-term, multiple-dose randomized controlled trial, especially among hypertensive patients.”54 At least seven clinical trials have studied GSE in combination with other ingredients for a variety of uses. Five of these addressed skin conditions. One found that skin radiance (e.g., for pink and olive skin tones) was significantly improved with six weeks of oral treatment with 150 mg per day of SkinAx2 (a product containing GSE, superoxide dismutase-rich melon [Cucumis melo var. cantalupensis, Cucurbitaceae] concentrate, vitamin C, and zinc; Activ’Inside; Libourne, France).55 Another oral supplement with 27.5 mg GSE, 210 mg biomarine complex, 54 mg vitamin C, 4 mg zinc, and 28.76 mg tomato (Solanum lycopersicum, Solanaceae) extract (Imedeen Man.Age.Ment; Ferrosan Laboratórios S/A; Copenhagen, Denmark) taken twice a day for 30 days improved skin hydration, dermal ultrasound density, reduction of skin pH, and overall signs of skin aging in men.56 Likewise, an oral supplement (Imedeen Time Perfection; Ferrosan S/A; Copenhagen, Denmark) with 105 mg BioMarine Complex, 14.8 mg LycoPhence GS (lycopene and GSE), and 30 mg acerola (Malpighia spp., Malpighiaceae) taken for 120 days was associated with improvements in skin hydration and pH, ultrasound density, and a histological increment of collagen and elastic fibers.57 An SPF 30 sunscreen containing GSE, vitamins E and C, and ubiquinone (Dr. Peter Hansen R&D; Stada; Bad Vilbel, Germany) effectively protected the subjects’ skin against infrared A radiation.58 Finally, a nonsteroidal topical cream (MD2011001; no other information provided) containing GSE, vitamin E, and epigallocatechin gallate (EGCG) provided a faster and statistically significant improvement in atopic dermatitis in patients who used it for 28 days, compared to placebo.59 One RDBPC study investigated the benefits of a nutritional supplement in low-income patients recently diagnosed with hyperlipidemia (N = 191; 18-65 years old). Subjects were randomly assigned to receive a placebo or a proprietary phytonutrient supplement (PreLipid; Preventions Meds, Inc.; Lebanon, NJ; no additional information provided) containing red yeast rice (a product of a yeast [Monascus purpureus, Elaphomycetaceae] grown on white rice [Oryza sativa, Poaceae]) powder, GS powder, niacin, folic acid, and black pepper (Piper nigrum, Piperaceae) powder. Subjects taking PreLipid experienced significant reductions in LDL-C and non-HDL-C at 12 weeks compared to placebo.60 Another RDBPC study investigated the effects of 150 mg GSE (MegaNatural BP; Polyphenolics; Madera, CA) in a fruit juice blend (provided by Coca-Cola) on blood pressure and metabolic indices in men and women with prehypertension (N = 28; 25-65 years old). Subjects were randomly assigned to take placebo or 300 mg GSE/juice blend per day in two doses for 12 weeks. By week six, the GSE group experienced significantly reduced SBP (5.6%) and DBP (4.7%) compared to placebo. The higher the subjects’ baseline BP, the greater the reduction they experienced; in some cases, subjects taking the GSE/juice blend experienced nearly double the SPB and DBP reduction of those in the placebo group. While not significant, fasting insulin and insulin sensitivity of subjects in the GSE/juice blend group tended to improve after six weeks.61 FUTURE OUTLOOK The International Union for Conservation of Nature (IUCN) assigns wild V. vinifera to the conservation category of Least Concern (LC), meaning that the species is not considered to be threatened.2 In any case, GSE is produced from seeds of the widely cultivated grape that is used for production of juices and wines worldwide. Nonetheless, long-term survival of crop wild relatives remains critical for preserving genetic diversity. Some wild grape species are becoming threatened in Europe due to habitat loss, competition with alien grape species, and intensive deforestation.62 Perhaps the biggest concern is economic adulteration of GSE, which has a direct impact on its safety and efficacy. In 2016, the American Botanical Council (ABC)-American Herbal Pharmacopoeia (AHP)-National Center for Natural Products Research (NCNPR) Botanical Adulterants Prevention Program published a Botanical Adulterants Bulletin on GSE, reporting that “adulteration of GSE in commercial products appears to be a significant problem.” In one of the studies cited in the bulletin, samples of several commercial GSE products contained no GSE at all and were composed primarily of peanut skin extract. Although peanut skin extracts should not exhibit allergenic potential comparable to that of peanuts themselves (due to no protein content), allergenicity could still be possible due to contact with the peanut protein. Besides the obvious matter of consumer fraud, persons with peanut allergies who unwittingly consume these products could experience adverse reactions. Other known adulterants of GSE include pine bark, green tea (Camellia sinensis, Theaceae) extract, and other PAC-rich (e.g., propelargonidin-containing) extracts from non-grape seed sources.7 While GSE is a relatively new item of commerce, evidence that supports its various beneficial uses as a functional component of cosmetic, food, dietary supplement, and natural health products continues to grow. To ensure the safety and efficacy of GSE for its intended uses, all finished product brands and marketers should specify the production and procurement of only well-characterized GSE for use in consumer products. For example, the USP quality standards monograph Grape Seeds Oligomeric Proanthocyanidins provides a useful basis for a company to establish a scientifically valid specification with suitable tests and methods for verifying identity, composition, strength, and purity. —Gayle Engels and Josef Brinckmann * The acronym GSE should not be confused with the acronym GFSE, which refers to grapefruit (Citrus paradisi, Rutaceae) seed extract, an entirely different material. In some original publications on GFSE adulteration, the authors use “GSE” to refer to grapefruit seed extract. †The authors define oligomers as PACs that have 2-7 units. References Gavazzi F, Braglia L, Mastromauro F, Gianì S, Morello L, Breviario D. The tubulin-based-polymorphism method provides a simple and effective alternative to the genomic profiling of grape. PLOS ONE. 2016;11(9):e0163335. Participants of the FFI/IUCN SSC Central Asian regional tree Red Listing workshop B, Kyrgyzstan (11-13 July 2006). Vitis vinifera. The IUCN Red List of Threatened Species 2007: e.T63537A12687723. 2007; Accessed April 25, 2018. Jiang H-E, Zhang Y-B, Li X, et al. Evidence for early viticulture in China: proof of a grapevine (Vitis vinifera L., Vitaceae) in the Yanghai Tombs, Xinjiang. J Arch Sci. 2009;36(7):1458-1465. Mencarelli F, Bellincontro A, DiRenzo G. In: Mejía D, ed. Grape: Post-Harvest Operations. INPhO – Post-harvest Compendium. Rome, Italy: Food and Agriculture Organization of the United Nations; 2005. Terral J-F, Tabard E, Bouby L, et al. Evolution and history of grapevine (Vitis vinifera) under domestication: new morphometric perspectives to understand seed domestication syndrome and reveal origins of ancient European cultivars. Ann Bot. 2010;105(3):443-455. Goloshvili T, Badridze G, Akhalkatsi M. Characterization of grape seed extracts of native to Georgia varieties of Vitis vinifera L. Pak J Bot. 2018;50(1):245-250. Kupina S, Gafner S. Grape seed extract. Botanical Adulterants Bulletin. April 2016. Accessed April 25, 2018. United States Pharmacopeial Convention. United States Pharmacopoeia, Fortieth Revision (USP 40). Rockville, MD: United States Pharmacopeial Convention; 2017. Havlíková L. In vino veritas... Is there truth in wine? Drinking and intemperance in Great Moravian and Early Czech legislation (Antique traditions in the Byzantine and Slavonic world). Byzantinoslavica. 2014;72(1-2):98-121. Estreicher SK. Wine. In: Bagnall RS, Brodersen K, Champion CB, Erskine A, Huebner SR, eds. The Encyclopedia of Ancient History. John Wiley & Sons, Ltd; 2015:1-6. Linné Cv. Materia medica, liber I : De plantis, digestus secundum genera, loca, nomina, qualitates, vires, differentias, durationes, simplicia, modos, usus, synonyma, culturas, præparata, potentias, composita. Amstelædami: Apud J. Wetstenium; 1749. Savo V, Kumbaric A, Caneva G. Grapevine (Vitis vinifera L.) symbolism in the ancient Euro-Mediterranean cultures. Econ Bot. 2016;70(2):190-197. Cappellini E, Gilbert MTP, Geuna F, et al. A multidisciplinary study of archaeological grape seeds. Naturwissenschaften. 2010;97(2):205-217. Ucchesu M, Orrù M, Grillo O, et al. Predictive method for correct identification of archaeological charred grape seeds: support for advances in knowledge of grape domestication process. PLOS ONE. 2016;11(2):e0149814. Gasparyan S. Vitis collections in Armenia. In: Maul E, Eiras Dias JE, Kaserer H, et al., eds. Report of a Working Group on Vitis. First Meeting, 12-14 June 2003, Palić, Serbia and Montenegro. Rome, Italy: Bioversity International; 2008:54-56. Aversano R, Basile B, Buonincontri MP, et al. Dating the beginning of the Roman viticultural model in the Western Mediterranean: The case study of Chianti (Central Italy). PLoS ONE. 2017;12(11):e0186298. Accessed April 25, 2018. Ayala FJ. Elixir of life: In vino veritas. Proc Natl Acad Sci USA. 2011;108(9):3457-3458. Chkhartishvili N. Implementation in Georgia of the project on “Conservation and sustainable use of grapevine genetic resources in the Caucasus and Northern Black Sea region.” In: Maul E, Eiras Dias JE, Kaserer H, et al., eds. Report of a Working Group on Vitis. First Meeting, 12-14 June 2003, Palić, Serbia and Montenegro. Rome, Italy: Bioversity International 2008:152-154. Committee on Herbal Medicinal Products (HMPC). European Union herbal monograph on Vitis vinifera L., folium. London, UK: European Medicines Agency; 2017. Wood GB, Bache F. The Dispensatory of the United States of America. Philadelphia, PA: Grigg & Elliot; 1833. Weseler AR, Bast A. Masquelier’s grape seed extract: from basic flavonoid research to a well-characterized food supplement with health benefits. Nutr J. 2017;16(1):5. Masquelier J, Michaud J, Inventors; Société Civile d’Investigations Pharmacologiques d’Aquitaine, assignee. Procédé d’extraction des oligomères flavonoliques totaux des végétaux et produits obtenus. 1972-01-28. National Center for Complementary and Integrative Health (NCCIH). Grape Seed Extract. NCCIH Publication No.: D370. Updated: September 2016. Accessed April 25, 2018. US Food and Drug Administration. Agency Response Letter GRAS Notice No. GRN 000124. Silver Spring, MD: US Food and Drug Administration, CFSAN/Office of Food Additive Safety;August 1, 2003. US Food and Drug Administration. Agency Response Letter GRAS Notice No. GRN 000125. Silver Spring, MD US Food and Drug Administration, CFSAN/Office of Food Additive Safety; August 18, 2003. United States Pharmacopeial Convention. 34(3) In-Process Revision: Grape Seeds Oligomeric Proanthocyanidins. Pharm Forum. 2008;34(3):659. United States Pharmacopeial Convention. The United States Pharmacopeia. The National Formulary. USP 33 - NF 28 Reissue. New and Revised Official Text Since the Second Supplement to USP 32-NF 27. Rockville, MD: The United States Pharmacopeial Convention; 2010. EFSA Panel on Dietetic Products NaAN. Scientific Opinion on the substantiation of a health claim related to Vitis vinifera L. seeds extract and maintenance of normal venous blood flow pursuant to Article 13(5) of Regulation (EC) No 1924/2006. EFSA Journal. 2012a;10(12):2996. EFSA Panel on Dietetic Products NaAN. Scientific Opinion on the substantiation of a health claim related to Vitis vinifera L. seeds extract and “helps to drain the body in case of water accumulation” pursuant to Article 13(5) of Regulation (EC) No 1924/2006. EFSA Journal. 2012b;10(12):2998. Substances Added to Food (formerly EAFUS). 2013. Accessed April 25, 2018. US Food and Drug Administration. 21 CFR Part 111 Current Good Manufacturing Practice in Manufacturing, Packaging, Labeling, or Holding Operations for Dietary Supplements; Final Rule. Federal Register. 2007;72(121):34752-34958. Natural and Non-prescription Health Products Directorate. Monograph: Grape Seed Extract. Ottawa, ON: Health Canada; 2009. Cosmetic ingredient (CosIng) database. 2018. Accessed April 25, 2018. Ma ZF, Zhang H. Phytochemical constituents, health benefits, and industrial applications of grape seeds: A mini-review. Antioxidants (Basel). September 15, 2017;6(3). Kirichenko TV, Myasoedova VA, Orekhova VA, et al. Phytoestrogen-rich natural preparation for treatment of climacteric syndrome and atherosclerosis prevention in perimenopausal women. Phytother Res. 2017;31(8):1209-1214. Razavi SM, Gholamin S, Eskandari A, et al. Red grape seed extract improves lipid profiles and decreases oxidized low-density lipoprotein in patients with mild hyperlipidemia. Journal of Medicinal Food. 2013;16(3):255-258. Rayyan M, Terkawi T, Abdo H, et al. Efficacy of grape seed extract gel in the treatment of chronic periodontitis: A randomized clinical study. J Investig Clin Dent. 2018;9(2):e12318. Wahner-Roedler DL, Bauer BA, Loehrer LL, Cha SS, Hoskin TL, Olson JE. The effect of grape seed extract on estrogen levels of postmenopausal women: a pilot study. J Diet Suppl. 2014;11(2):184-197. Argani H, Ghorbanihaghjo A, Vatankhahan H, Rashtchizadeh N, Raeisi S, Ilghami H. The effect of red grape seed extract on serum paraoxonase activity in patients with mild to moderate hyperlipidemia. Sao Paulo Med J. 2016;134(3):234-239. Sano A, Uchida R, Saito M, et al. Beneficial effects of grape seed extract on malondialdehyde-modified LDL. J Nutr Sci Vitaminol (Tokyo). 2007;53(2):174-182. Kim JK, Kim KA, Choi HM, Park SK, Stebbins CL. Grape seed extract supplementation attenuates the blood pressure response to exercise in prehypertensive men. Journal of Medicinal Food. 2018;21(5):445-453. Belcaro G, Ledda A, Hu S, Cesarone MR, Feragalli B, Dugal M. Grape seed procyanidins in pre- and mild hypertension: a registry study. Evid Based Complement Alternat Med. 2013;2013. Soleimani M, Masoumi N. The effect of grape seed extract on semen oxidative stress markers in men with idiopathic infertility: a cross-sectional before-after study. Nepho-Urology Monthly. 2017;9(5):e13837. Sano A, Tokutake S, Seo A. Proanthocyanidin-rich grape seed extract reduces leg swelling in healthy women during prolonged sitting. J Sci Food Agric. 2013;93(3):457-462. Khoshbaten M, Aliasgarzadeh A, Masnadi K, et al. Grape seed extract to improve liver function in patients with nonalcoholic fatty liver change. Saudi J Gastroenterol. 2010;16(3):194-197. Safaei N, Babaei H, Azarfarin R, Jodati AR, Yaghoubi A, Sheikhalizadeh MA. Comparative effect of grape seed extract (Vitis vinifera) and ascorbic acid in oxidative stress induced by on-pump coronary artery bypass surgery. Ann Card Anaesth. 2017;20(1):45-51. Edirisinghe I, Randolph J, Cheema M, et al. Effect of grape seed extract on postprandial oxidative status and metabolic responses in men and women with the metabolic syndrome – randomized, cross-over, placebo-controlled study. Funcional Foods in Health and Disease. 2012;2(12):508-521. Sapwarobol S, Adisakwattana S, Changpeng S, Ratanawachirin W, Tanruttanawong K, Boonyarit W. Postprandial blood glucose response to grape seed extract in healthy participants: A pilot study. Pharmacogn Mag. 2012;8(31):192-196. Turki K, Charradi K, Boukhalfa H, Belha JM, Limam F, Aouani E. Grape seed powder improves renal failure of chronic kidney disease patients. EXCLI Journal. 2016;15:424-433. Pourghassem-Gargari B AS, Babaei H, Aliasgarzadeh A, Pourabdollahi P. Effect of supplementation with grape seed (Vitis vinifera) extract on antioxidant status and lipid peroxidation in patient with type II diabetes. J Med Plant Research. 2011;5(10):2029-2034. Yuan XY, Liu W, Hao JC, Gu WJ, Zhao YS. Topical grape seed proanthocyandin extract reduces sunburn cells and mutant p53 positive epidermal cell formation, and prevents depletion of Langerhans cells in an acute sunburn model. Photomed Laser Surg. 2012;30(1):20-25. Taghizadeh M, Malekian E, Memarzadeh MR, Mohammadi AA, Asemi Z. Grape seed extract supplementation and the effects on the biomarkers of oxidative stress and metabolic profiles in female volleyball players: A randomized, double-blind, placebo-controlled clinical trial. Iran Red Crescent Med J. 2016;18(9):e31314. Feringa HH, Laskey DA, Dickson JE, Coleman CI. The effect of grape seed extract on cardiovascular risk markers: a meta-analysis of randomized controlled trials. J Am Diet Assoc. 2011;111(8):1173-1181. Zhang H, Liu S, Li L, et al. The impact of grape seed extract treatment on blood pressure changes: A meta-analysis of 16 randomized controlled trials. Medicine (Baltimore). 2016;95(33):e4247. Dumoulin M, Gaudout D, Lemaire B. Clinical effects of an oral supplement rich in antioxidants on skin radiance in women. Clin Cosmet Investig Dermatol. 2016;9:315-324. Costa A, Pegas Pereira ES, Assumpcao EC, et al. Assessment of clinical effects and safety of an oral supplement based on marine protein, vitamin C, grape seed extract, zinc, and tomato extract in the improvement of visible signs of skin aging in men. Clin Cosmet Investig Dermatol. 2015;8:319-328. Costa A, Lindmark L, Arruda LH, et al. Clinical, biometric and ultrasound assessment of the effects of daily use of a nutraceutical composed of lycopene, acerola extract, grape seed extract and BioMarine Complex in photoaged human skin. An Bras Dermatol. 2012;87(1):52-61. Grether-Beck S, Marini A, Jaenicke T, Krutmann J. Effective photoprotection of human skin against infrared A radiation by topically applied antioxidants: results from a vehicle controlled, double-blind, randomized study. Photochem Photobiol. 2015;91(1):248-250. Patrizi A, Raone B, Neri I, et al. Randomized, controlled, double-blind clinical study evaluating the safety and efficacy of MD2011001 cream in mild-to-moderate atopic dermatitis of the face and neck in children, adolescents and adults. J Dermatolog Treat. 2016;27(4):346-350. Kasliwal RR, Bansal M, Gupta R, et al. ESSENS dyslipidemia: A placebo-controlled, randomized study of a nutritional supplement containing red yeast rice in subjects with newly diagnosed dyslipidemia. Nutrition. 2016;32(7-8):767-776. Park E, Edirisinghe I, Choy YY, Waterhouse A, Burton-Freeman B. Effects of grape seed extract beverage on blood pressure and metabolic indices in individuals with pre-hypertension: a randomised, double-blinded, two-arm, parallel, placebo-controlled trial. Br J Nutr. 2016;115(2):226-238. Bodor P, Höhn M, Pedryk A, et al. Conservation value of the native Hungarian wild grape (Vitis sylvestris Gmel.) evaluated by microsatellite markers. Vitis. 2010;49(1):23-27.

Friday, 7 December 2018

It’s time to rethink letters of recommendation

They’re a waste of time, with little evidence they make a difference in decision-making. By RIMA WILKES & HOWARD RAMOS | DEC 07 2018 Writing letters of recommendation is a routine exercise for most faculty. Applications for graduate schools, scholarships, grants, awards and jobs all require letters, and writing each one takes precious time away from other work. There is little evidence that they make a difference in decision making and much evidence to show they contribute to inequities. Maybe it is time to ask, what is the point in all this? We might start by thinking about the pre-information-age origins of reference letters. Essentially, they were used to show that a person in the profession vouches for the candidate. Individuals writing and reading the letters usually knew, or at least were known to, each other. A letter of reference would have been necessary because other means of communication were not options. Publication was less of a metric and at the time it was difficult to send transcripts between institutions. Today, many people continue to hold reference letters in high esteem. The argument is often made that they offer valuable context to sterile and generic metrics, like grades, numbers of publications, awards and other “measurables.” They are said to help assessors better understand special circumstances, qualitative context and aspects missed by ‘hard’ metrics. The problem is that writing and reading letters uses up an extraordinary amount of time. To write a strong letter of support, one must know the student or colleague in detail, read their work, scour their CV, and give unique examples to write an original and personal letter. For some competitions this literally can take hours. For faculty, the time spent doing this could be spent in meaningful dialogue, reading, writing or pursuing grants, not to mention mentoring students. For students, every hour spent chasing down faculty for letters keeps them away from studying or working on other projects. In many cases, letters are needed at the last minute, adding an extra level of stress. In both cases, we also ought to consider that, for each application, multiple faculty are writing letters for the same competitions, amplifying the time spent and stress felt. Letters also take time to process for members of committees that need to read them. Increasingly, competitions have hundreds of applicants. Few of these applications will make the shortlist or get to the point where the detailed information and deep scrutiny that might be provided in letters is needed. Let us illustrate how much time letters take away from other work by examining the typical academic job application. In larger schools, a single job ad can have 100 or more applicants. Each ad asks candidates for three letters of reference and each letter is two to four pages single-spaced. For 100 applications, that totals somewhere between 600 to 1,200 pages of reading. All this effort might be warranted if letters really provided useful information not otherwise available. But is this really the case? Despite all the time and effort put into writing letters, the sheer volume of them means that most reviewers develop systems to parse information quickly. Usually only a handful of applications in the large pool of applicants is fully scrutinized – those that are hard to score by other methods and that are close to being considered. This means that most letters are never even read. When they are read, our experience is that most letters look and sound the same. Very few people write a bad letter, or even an honest one. There is intense competition for awards, for entrance to graduate programs, for postdocs, for faculty positions and for promotion. Why would professors write a negative or less-than-glowing letter given this context? Most people, if they don’t think highly of the person, will just say no to a letter request. More troubling is that research shows that letters of reference can maintain old boys’ clubs, privileging those who are well-networked and therefore leading to bias. Race, class, gender and nationality interact to shape the networks of who writes letters, who builds up the nerve to ask for them to be written in the first place, and how letters are written once a faculty member accepts to write one. Studies show that the content of letters is far too often biased against women, racialized people and others who are outsiders to the power structures of universities. So, what can be done? We could start by requesting fewer letters. In most situations it is more effective to simply ask for names of referees and their contact information. This would limit the letter writing to only those who are being seriously considered, saving countless hours of work for everyone. Or why not simply stop asking for letters altogether? Rima Wilkes is a professor of sociology at the University of British Columbia and former president of the Canadian Sociology Association. Howard Ramos is associate dean of research in the faculty of social sciences and a professor of sociology at Dalhousie University, and is also a former president of the Canadian Sociology Association.

Documentation and Consensus Analysis of Traditional Knowledge about Ethnoveterinary Medicinal Plants of Birbhum District, West Bengal (India)

Thursday, 6 December 2018

Complementary medicine use in the Australian population: Results of a nationally-representative cross-sectional survey

Published: 23 November 2018 Amie Steel, Erica McIntyre, Joanna Harnett, Hope Foley, Jon Adams, David Sibbritt, Jon Wardle & Jane Frawley Scientific Reportsvolume 8, Article number: 17325 (2018) | Download Citation Abstract In order to describe the prevalence and characteristics of complementary medicine (CM) practice and product use by Australians, we conducted a cross-sectional online survey with Australian adults aged 18 and over. Rates of consultation with CM practitioners, and use of CM products and practices were assessed. The sample (n = 2,019) was broadly representative of the Australian population. Prevalence of any CM use was 63.1%, with 36% consulting a CM practitioner and 52.8% using any CM product or practice. Bodywork therapists were the most commonly consulted CM practitioners (massage therapists 20.7%, chiropractors 12.6%, yoga teachers 8.9%) and homeopaths were the least commonly consulted (3.4%). Almost half of respondents (47.8%) used vitamin/mineral supplements, while relaxation techniques/meditation were the most common practice (15.8%). CM users were more likely to be female, have a chronic disease diagnosis, no private health insurance, a higher education level, and not be looking for work. Prevalence of CM use in Australia has remained consistently high, demonstrating that CM is an established part of contemporary health management practices within the general population. It is critical that health policy makers and health care providers acknowledge CM in their attempts to ensure optimal public health and patient outcomes. Introduction The use of complementary medicine (CM), defined as products and practices outside of the dominant medical paradigm1, is popular in many parts of the world2 and is recognised as a significant public health issue by the World Health Organisation3. CM is broadly classified into one of two categories, mind body practices (i.e. yoga, meditation) and natural products (i.e. vitamins, herbal medicines)1. The use of CM may be part of a self-management strategy or initiated and monitored under the guidance of a CM practitioner4. The most recent nationally representative investigation of Australian CM use and associated expenditure was conducted over a decade ago4. At that time, an estimated 70% of Australians had used at least one form of CM and 44.1% had visited a CM practitioner in the previous 12 months. The number of visits to CM practitioners was almost identical to the estimated number of visits to medical practitioners (69.3 million) and the annual expenditure on CM, was estimated to be 4.13 billion Australian dollars (US $3.12 billion). Well-educated, females aged 18–34 years with a higher than average income were the most common users of CM4. As the understanding of CM has evolved since this previous research, there is a need for contemporary data describing CM use to inform current and future health policy and practice in Australia. It is important to examine the amount of CM currently used in the community, along with the characteristics and drivers of this use, to ensure that appropriate public health policy can be developed to address any risks to the public associated with its use, and any benefits can be incorporated into health service delivery. This will also help to facilitate open discussions with patients about CM use that encourage disclosure and optimise patient care and safety. The objectives of this study are to obtain up-to date data regarding the prevalence and characteristics of CM practice and product use by Australians, and determine the predictors of CM use, using reliable and reproducible instruments and methodology. Methods Study design and setting A cross-sectional survey was administered online to an Australian population. Ethical approval for the study was obtained from the Human Research Ethics Committee at Endeavour College of Natural Health (#20170242) in accordance with the Declaration of Helsinki. The survey includes 241 survey items across five survey domains: demographics; health status; health service utilisation; complementary medicine literacy; and health information disclosure. This study represents the first, foundational analysis from the survey data. Participants Participants of this study were Australian adults aged 18 and over (N = 2,025) who were representative of the general population in gender, age and state of residence (Table 1). This study size was determined to provide sufficient statistical power for inferential analysis based upon previous rates of CM use reported in Australian studies5. Table 1 Sociodemographic characteristics of survey respondents (n = 2,019) compared with national data from the 2016 National Census10. Full size table Recruitment This study used purposive convenience sampling using a database of people who were registered to participate in research. Recruitment and data collection were conducted between 26 July and 28 August, 2017. Respondents who completed the survey received a small financial incentive based on the time taken to complete the survey. The financial incentive is a benefit of being a member of the research company’s (Qualtrics) database. Members of the database who met the inclusion criteria were emailed an invitation to participate in the online survey. Informed consent was obtained once respondents had read the information page presented prior to beginning the survey. The survey took approximately 15 minutes to complete. Data was screened for disengaged and missing responses. Six respondents were removed as their responses were unreliable (identified by discrepancies between responses, text responses incongruous with the corresponding question, lack of variance, and repeated patterns in the data), leaving 2,019 participants in the final data set. Instrument The survey consisted of 50 items covering demographics, health service utilisation (including use of complementary medicine), health status, health literacy and health communication. The study is a sub-analysis of a larger research project. The measures described below reflect those relevant to the objectives of this study. Demographics Survey items measured gender, age range (categorised in increments of ten years6, residential postcode, manageability on household income, highest level of education, private health insurance coverage, health care card status, employment status, and marital status. Health service and treatment utilisation Respondents were asked to provide information about their use of health services and products, including over the previous 12 months. Information about health services use was collected through a survey item which listed both conventional and CM practitioner groups. Details about treatments were measured through a survey item which listed both pharmaceutical (prescription and non-prescription) and non-pharmaceutical treatments. To avoid potential confusion resulting from unclear nomenclature, the terms ‘complementary medicine’ and ‘conventional medicine’ were not used. Items were based on the International Complementary and Alternative Medicine Questionnaire (I-CAM-Q), which was developed as a measure of CM use that could be used consistently across different populations7,8. Health status Health status was determined by a single item that asked respondents to describe their general health on a 5-point Likert scale ranging from ‘excellent’ to ‘poor’. Participants were also asked to identify whether they had been diagnosed in the last three years with a health condition from a list of 30 diseases including, but not limited to Australian National Health Priority Area9. Data analysis IBM SPSS Statistics Premium Edition Version 22 was used to analyse the data. Relevant variables were recoded to reflect a positive response direction. Binary variables (‘yes, I did use’ or ‘no, I did not use’) were created from categorical variables describing CM use, as well as confounders such as diagnosis with a chronic disease. Descriptive statistics were used to determine frequencies and percentages. Chi-square analysis was used to confirm the representativeness of the sample compared to 2016 Australian Census data10, and to test associations between demographic variables and CM use. Backwards stepwise logistic regression was used to control for confounding and determine the most parsimonious model for the likelihood of using any type of CM, any CM treatment, and any CM practitioner. Statistical significance was set at p = 0.05. Results Participant characteristics Table 1 summarises the sociodemographic characteristics of participants in comparison to Australian 2016 census data with no differences in age or gender and minor differences in locality; indicating the sample was broadly representative of the Australian population. Table 2 reports the association between any type of CM use and sociodemographic variables. There was a statistically significant association between gender and any CM use; more females (56.2%) compared to males (43.7%) used any type of CM. Table 2 Sociodemographic characteristics of survey respondents. Full size table Prevalence and frequency of health service and treatment use A total of 1,273 people (63.1%) used CM (either treatments or consulted practitioners), with 36% consulting with at least one CM practitioner and 52.8% using any CM product or practice. Bodywork therapists such as massage therapists, chiropractors and yoga teachers were the most commonly consulted CM practitioner (Table 3). The prevalence rate of consultations with an acupuncturist (7.9%), naturopath (6.2%), osteopath (5.4%) and TCM practitioner (5.3%) was comparable to each other. The prevalence rate for vitamin/mineral supplements use was the highest of all CM products (47.8%), while relaxation techniques or meditation was the most frequently reported CM practice (15.8%). Table 3 Prevalence and frequency of conventional and CM health service and treatment utilization. Full size table Characteristics of complementary medicine users Table 4 reports the results of the logistic regression models predicting the likelihood of each type of CM use. The model assessing the likelihood of demographic characteristics associated with any CM use (practitioner or treatment), was statistically significant, χ2(13) = 170.04, p < 0.001, and correctly classified 65.6% of cases. People without a chronic disease diagnosis, were less likely to use any type of CM (OR 0.49; p < 0.001). Those without private health insurance were more likely to use any type of CM compared to those with health insurance (OR 1.71; p < 0.001). Females were more likely than males to use any type of CM (OR 1.78; p < 0.001). There was a significant effect for education (p < 0.001); those with either a less than year 12, or year 12 or equivalent qualification were less likely to use any type of CM compared to those with a university degree. Employment status also had a significant influence on the model p = 0.003); full-time or part-time employment was more likely to influence any type of CM use, and those who were looking for work were less likely to use any type of CM compared to those not in the paid workforce. Table 4 Logistic regression predicting characteristics of individuals who use CM treatments (products or practices), consult with CM practitioners, and use any type of CM. Full size table The second logistic regression assessing the likelihood of consulting with a CM practitioner was statistically significant, χ2(14) = 190.81, p < 0.001, and correctly classified 67.7% of cases. Females were more likely to consult with a CM practitioner compared to males (OR 1.59, p < 0.001). People without a chronic disease diagnosis compared to those with a diagnosis, were less likely to consult with a CM practitioner (OR 0.57, p < 0.001). Those without private health insurance compared to those with health insurance were more likely to consult with a CM practitioner (OR 1.69, p < 0.001). Qualification has a significant effect on the model (p = 0.04); those with a qualification of either less than year 12, year 12 or equivalent were less likely to consult with CM practitioners compared to those with a university degree. All types of employment were more likely to influence any type of CM use compared to those not in the paid workforce, except looking for work p < 0.001). People in full time employment were 2.63 times more likely to consult with a CM practitioner. Finally, the logistic regression testing the likelihood of using any CM treatment (product or practice) was statistically significant, χ2(13) = 149.41, p < 0.001, and correctly classified 61.3% of cases. Females were more likely than males to use a CM treatment (OR 1.78, p < 0.001). People without a chronic disease diagnosis, were less likely to use a CM treatment compared to those with a diagnosis (OR 0.50, p < 0.001). In contrast, those without private health insurance were more likely to use a CM treatment compared to those with private health insurance (OR 1.39, p = 0.001). Level of qualification had a statistically significant influence on the model (p < 0.001); all levels of qualification were less likely to influence consultations with CM practitioners, compared to a university degree. Employment status also had a significant effect; people who were looking for work were less likely to use CM treatments compared to those not in the paid workforce (p = 0.03). Discussion Our study represents the first comprehensive examination of CM use by the Australian population using a nationally-representative survey for over a decade. The findings of this study suggest that two out of three Australians use some form of CM. This figure is consistent with previous studies indicating that high levels of CM use4 are a firmly entrenched aspect of the healthcare milieu in Australia, with prevalence and utilisation levels that are both significant and consistent. This study is not without limitations. The self-reported nature of the surveys exposes the data to the risk of responder and recall bias. However, previous research suggests this may not be such an issue for recall of events over a 12 month period particularly for recall of symptoms and conditions11. As the only items in our study where respondents were asked to recall health events which extended beyond a 12 month period related to diagnosis with or treatment for a chronic health condition (in the previous three years) it is not expected that this will have significantly affected the integrity of the survey data. Our data were also unable to provide insights into the health outcomes of CM. Despite these limitations, the nationally-representative sample importantly affords generalisability to the findings and as such this study has potential value to Australian policy makers, researchers and health professionals. Individuals in our study with a chronic disease diagnosis were more likely to use CM compared with the general population; a finding which was consistent across all categories of CM use examined. This finding concurs with previous Australian studies in discrete populations which suggested higher rates of CM utilisation among those with chronic or co-morbid conditions5. Chronic disease is a high priority in Australian health policy due to the substantive burden of disease and the associated complexity of health service needs for individuals with diagnosed chronic health complaints12. Persons with chronic conditions are known to be higher users of healthcare services more generally, and as such higher CM use may simply be a reflection of this broader phenomenon. However, it is also possible that people with chronic conditions are not having their healthcare needs met by conventional services and treatments, and are seeking CM use to supplement conventional care and address their unmet needs. In any case, the higher utilisation of CM by persons with increasingly complex health conditions and potential co-morbidities—combined with the fact that these patients are more likely to use a variety of healthcare approaches—presents a number of risks to the CM user13. These risks need to be managed both clinically (e.g. by ensuring medical providers actively inquire as to their patient’s CM use, as patients are more likely than not to be using some form of CM) and through appropriate policy (e.g. by ensuring appropriate levels of regulation). The finding that those without PHI were significantly more likely to use any type of CM, consult a CM practitioner, and use a CM treatment conflicts with findings from previous studies5. This finding is interesting because other factors that are traditionally associated with higher uptake of PHI – such as gender, income and education – are also associated with higher utilisation of CM5. However, many of these previous studies focused on whether PHI users specifically had ancillary cover – cover specific for CM and additional allied health services – which represents only a minority of policies14,15. This suggests that CM may not be a primary driver for PHI, which in Australia is focused largely on hospital coverage. This is further supported by findings when other therapies are similarly analysed, with higher use only found for specific policies rather than PHI more broadly (e.g. dental)15. Lack of uptake of CM-specific insurance may also indicate that CM users may not see value in PHI plans, which may be restrictive or incomplete (for example, PHI does not cover CM prescriptions), and prefer to use their discretionary healthcare spend to self-insure for these services rather than utilise PHI. Although the interface between CM and PHI has been the topic of considerable discussion16, findings such as these indicate that greater clarity is required to appropriately inform policy in this area. Our study found one third of Australians had consulted with a CM practitioner in the previous 12 months; a finding supported by previous research4. CM practitioners consulted most frequently appear to be body work and manual therapists such as massage therapist and chiropractors, confirming previous research. Practitioners for these health professions may be contributing significantly to the non-pharmacologic management of conditions such as back pain17,18, treatment options which have received additional attention where conventional approaches such as opioids have received increasing attention for uncertain effectiveness and safety19. The clearly articulated role for these CM professions for a limited range of conditions may partly explain these higher levels of utilisation. The use of these therapies for musculoskeletal conditions—but not other conditions—attracts a high level of support for referring practitioners as well as attracting a small number of subsidies for their services20,21. CM professions such as acupuncture and naturopathy, who report a broader scope of conditions treated22, were also identified as being used by a notable number of Australians in our study. While there is growing evidence suggesting effectiveness for acupuncture23,24,25,26 and for naturopathic care27,28 in a range of clinically important health conditions, lack of integration and variability in standards, regulation and research attention on these CM professions means that the impact these practitioners have on healthcare delivery remains largely unknown. Equally any difference in health outcomes from CM products or treatments when delivered by registered rather than unregistered health professionals have also been overlooked in the research to date. Ultimately, more research that explores the interface, interaction and effects of CM on conventional health care, and conventional health care on CM, is needed. Conclusion CM use in Australia has remained consistently high over the last decade despite ongoing developments in the evidence and policy environment surrounding health care utilisation. Consequently, it is critical that researchers, health policy makers and providers consider CM in relation to their investigations, interventions and attempts to provide optimal public health and patient care. Data Availability The datasets generated during and analysed during the current study are available from the corresponding author on reasonable request. Additional information Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. References 1. U. S. Department of Health and Human Services. Collection Development Manual of the National Library of Medicine (ed. National Institutes of Health) (National Library of Medicine, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, MD, 2004). 2. Coulter, I. D. & Willis, E. M. The rise and rise of complementary and alternative medicine: a sociological perspective. Med. J. Aust. 180, 587–590 (2004). PubMed Google Scholar 3. 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Google Scholar Download references Acknowledgements This study was funded by direct contributions from Endeavour College of Natural Health and the Australian Research Centre in Complementary and Integrative Medicine (University of Technology Sydney). HF was supported by an Australian Government Research Training Program Scholarship while working on this manuscript. JA was supported by an Australian Research Council Professorial Future Fellowship while working on this manuscript (Grant FT140100195). JW was supported by a National Health and Medical Research Council Translating Research into Practice Fellowship while working on this manuscript (Grant 1133136). JH’s academic position was supported by a philanthropic donation from Blackmores Pty Ltd during the course of this study. Author information Affiliations Australian Research Centre in Complementary and Integrative Medicine, Faculty of Health, University of Technology Sydney, Ultimo, NSW, Australia Amie Steel, Erica McIntyre, Joanna Harnett, Hope Foley, Jon Adams, David Sibbritt & Jon Wardle Discipline of Public Health, Faculty of Health, University of Technology Sydney, Ultimo, NSW, Australia Amie Steel, Erica McIntyre, Hope Foley, Jon Adams, David Sibbritt, Jon Wardle & Jane Frawley Endeavour College of Natural Health, Fortitude Valley, Brisbane, QLD, Australia Amie Steel & Hope Foley Faculty of Pharmacy, University of Sydney, Sydney, NSW, Australia Joanna Harnett Contributions All authors have made substantial contributions to this manuscript. A.S., J.H. and E.M. conceptualised the study and survey design. E.M. and H.F. managed the data cleaning and completed data analysis. All authors contributed to the drafting, critical revision and approved the manuscript. Competing Interests The authors declare no competing interests. Corresponding author Correspondence to Amie Steel. Rights and permissions Creative Commons BY Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit About this article Publication history Received 07 August 2018 Accepted 01 November 2018 Published 23 November 2018 DOI