European Elder

Sambucus nigra, L.

Family: Caprifoliaceae

INTRODUCTION

European elder (Sambucus nigra, Caprifoliaceae), also known as black elder¹ and elderberry, is a deciduous tree that grows to 30 feet and is native to Europe, northern Africa, and western Asia.² It has flat-topped clusters of small, creamy-white flowers in early summer, followed by large, drooping bunches of purplish-black, juicy drupes (commonly referred to as berries) in late summer or early fall.^2,3

Both the elder flower and berry are used medicinally. Most of the elder flower in commerce is collected from the wild, mainly from Albania,⁴ Bosnia-Herzegovina, Bulgaria, Croatia, Romania,⁵ Hungary, Macedonia,⁶ Poland,⁷ Russia,⁸ Serbia, and Montenegro.⁹ Elderberries also are wild-collected in the aforementioned countries, but there are several distinct cultivars grown in commercial orchards, particularly in Austria (e.g., mainly the “Haschberg,” “Rubin,” and “Tattin” varieties), Denmark (e.g., “Sambu,” “Sampo,” “Samdal,” “Samyl,” “Allesoe,” and “Korsör”), and Germany (e.g., “Haschberg,” “Sambu,” “Sampo,” “Samyl,” and “Haidegg 13”). Due to successful auto-vegetative propagation, regular yields, and high coloring matter content, “Haschberg” is the chief variety cultivated in both Austria and Germany.¹⁰

For the sake of convenience, European elder will be referred to as elder in this article, and the plant part under discussion will be specified.

HISTORY AND CULTURAL SIGNIFICANCE

The genus Sambucus contains more than 20 species, many with similar chemical constituents to S. nigra. One such species, American elder (S. canadensis), is a fast-growing, deciduous North American shrub that can reach up to 12 feet with flowers and berries similar to S. nigra.^1,3 While this species was used by Native American tribes and as a folk remedy in some of the same ways as S. nigra, it will not be discussed in this article for reasons set forth below in the Modern Research section.

The use of elder as a medicine dates back to antiquity, according to the writings of Hippocrates (ca. 470-410 BCE), Pliny the Elder (ca. 23-79 CE), and Dioscorides (ca. 40-90 CE).¹¹ The word elder is derived from the Anglo-Saxon word æld, meaning “fire,” because one could start a fire by blowing through its young, hollow branches.¹² Historically, medicinal uses for European elder could be found in Italian, Dutch, Portuguese, Croat-Slovak, German, Austrian, Swiss, and Hungarian pharmacopeias.¹³

Of interesting historical note, in Anatomi Sambuci: The Anatomy of the Elder, written in 1677, the physician Martin Blochwich described medicines made from the various parts of elder, including a berry tincture, extract (or essence), wine, spirits (fermentation), syrup, tragea (powdered elderberry kernels), and rob (a thickened juice made from the berries, either with or without sugar), as well as seed oil.¹⁴ He also noted elder flower-derived preserves, syrup or honey, water and spirits, vinegar and oxymel (vinegar and honey), wine, and oil. Additionally, Blochwich elaborated upon powder, preserves, and syrup that could be made from the buds or sprouts of the plant, and also medicines that could be made with the leaves, middle bark, roots, pith, and fungus, including those in the form of water, syrup, oils, and liniments. Lastly, he chronicled making a “salt and its spirit” by reducing the entire plant to ashes over an open fire, pouring boiling water over it, and again reducing it over a low fire. This process produced the salt from which the spirit was then made. Blochwich then addressed the many ways in which these elder preparations were used alone (some of which might seem quite strange to the modern reader) and in combination with other “medicines” that are now known to be toxic. Common ailments these elder preparations were used to treat include headache, toothache, eye conditions, facial blemishes, mouth and throat conditions, cough, asthma, hoarseness, fever, smallpox, measles, stomach and intestinal conditions, stones, arthritis, menstrual complaints, inflammation, edema, and burns. Some of the more unusual conditions treated include deliria and affections (in combination with lily water, rose water, and opium); melancholy (by provoking vomiting); epilepsy (using an elder amulet worn over the heart); apoplexy and palsy (by vigorous rubbing of the extremities with elder spirit); protection from plague (by carrying and smelling an elder vinegar-soaked sponge in a hollow juniper-wood globe); and wound healing (by drinking wine that had elder leaves pounded into it, followed by a poultice of elder kernel oil, Venice turpentine, and verdigris [a poisonous green pigment caused by the action of acetic acid on copper]).

Traditionally, numerous ailments have been treated by elderberry including dysentery and diarrhea. It also was used to induce perspiration in order to remove toxins and increase resistance to illness.¹³ Currently, elderberries are used to treat symptoms associated with colds, flu, and in feverish conditions as a diaphoretic (an agent that increases perspiration).^12,15,16 The expressed juice of the berries, as well as extracts and dried juice concentrates, are used as components of oral ingestion products like medicated syrups and tablets, as well as topical application products like lozenges and skincare products.¹⁰ The fresh ripe berries are used in juices, jams, marmalades, liqueurs and dessert wines, and also as a coloring agent in beverages, foods, and textiles.¹⁰

Elder flowers are used as a diuretic, laxative, and diaphoretic.^12,17 Additionally, they are used as an astringent for the skin and in treating rheumatism, usually as an infusion (tea) or in a poultice.¹⁸ The dried flowers of elder are used in European traditional herbal medicinal products mainly in the form of herbal teas, liquid extracts, and tinctures.¹⁹ The German Commission E approved elder flower — administered as fluid extract, herbal tea, or tincture — for common cold symptoms in 1986.²⁰ In 1992, the British Herbal Medicine Association published an elder flower monograph in its British Herbal Compendium, specifying the forms of herbal tea infusion (drunk hot), liquid extract (1:1, 25% ethanol), and tincture (1:5, 25% ethanol) for treating feverish common cold conditions.²¹ Elder flower water also has been used in eye and skin moisturizers, and flower extracts are used in perfumery.¹⁸

Both elderberry and elder flower extracts are used as flavorings in food products, alcoholic  (bitters and vermouth) and nonalcoholic beverages, and confectionary items.¹⁸

CURRENT AUTHORIZED USES IN COSMETICS, FOODS, AND MEDICINES

In 2008, the European Medicines Agency (EMA) published a final labeling standards monograph on elder flower (as herbal tea for oral use, liquid extract [1:1, 25% V/V ethanol], or tincture [1:5, 25% V/V ethanol]), which superseded existing monographs of EU national authorities for the registration and marketing authorization of traditional herbal medicinal products that contain elder. The authorized therapeutic indication is “for the relief of early symptoms of common cold.”²²

One prerequisite of registration is that the quality of the herbal material complies with the corresponding quality standards monograph of the European Pharmacopoeia (Sambuci flos PhEur), which, for example, requires the dried flowers to contain a minimum of 0.80% flavonoids, expressed as isoquercitroside.²³ In European countries, elder flower also is found as an active ingredient of clinically tested polypreparations such as Sinupret^® (Bionorica SE, Neumarkt, Germany), a licensed herbal medicinal product sold only in pharmacies and indicated for acute and chronic inflammation of the paranasal sinuses. (Sinupret also contains primrose [Primula veris, Primulaceae] flowers with calyx, common sorrel [Rumex acetosa, Polygonaceae] herb, European vervain [Verbena officinalis, Verbenaceae] herb, and gentian [Gentiana lutea, Gentianaceae] root.²⁴) In the United Kingdom, aqueous liquid extract (1:1) of elder flower is an active ingredient of Cold and Flu Relief by Potter’s Herbals (Wigan, UK; founded by Henry Potter in 1812), a registered traditional herbal medicinal product available without prescription from pharmacies and other retail outlets with the authorized therapeutic indication “used to relieve the symptoms of colds and flu, chills and sore throats.”²⁵ (Potter’s Cold and Flu Relief also contains ethanolic liquid extracts [1:1] of hemlock spruce [Pinus canadensis, Pinaceae] needle and bayberry [Myrica cerifera, Myricaceae] bark.)

In 2011, the EMA called for scientific data to be used by its Committee on Herbal Medicinal Products for assessment work toward the establishment of a community herbal monograph and/or community list entry for elderberries (Sambuci fructus).²⁶ Presently, there are also some elderberry-containing food supplement products in the European market, such as Wellion Diabasic^® tablets (MED TRUST; Lichtenwörth, Austria), a dietetic food supplement labeled for special medical needs of diabetic patients with disease-related nutrient deficiencies.²⁷ Another example is the enzyme complex and herbal preparation Snorin^® tablets (VitaBasix^®; Maastricht, the Netherlands), labeled for chronic snoring whose cause is not determined to be anatomic after other causes (obesity, alcoholism, chronic tonsillitis, or sinusitis) have been excluded.²⁸

Concerning use of elder in cosmetic products, the European Commission Health and Consumers Directorate lists “Sambucus Nigra Fruit Extract” for astringent (contracts the skin) function and “Sambucus Nigra Fruit Juice” for both astringent and skin-conditioning functions. “Sambucus Nigra Flower,” “Sambucus Nigra Flower Juice” (juice expressed from the flower), and “Sambucus Nigra Flower Water” (aqueous solution of the steam distillate obtained from the flowers) are approved for use as skin-conditioning ingredients, while “Sambucus Nigra Flower Extract” is listed for refreshing (imparts a pleasant freshness to the skin), skin-conditioning, soothing (helps lightening discomfort of the skin or of the scalp), and tonic (produces an invigorating sensation on skin and hair) functions.²⁹

In the United States, elder tree leaf is classified as a Generally Recognized as Safe (GRAS) natural flavoring substance, although its use is limited to only alcoholic beverages and not to exceed 25 ppm (parts per million) prussic acid in the natural flavor ingredient.³⁰ The essential oil or natural extractives (including distillates) of elder flower are GRAS flavoring agents in food products.³¹ Elderberry and elder flower also are permitted as dietary supplement components in the United States, requiring Food and Drug Administration notification within 30 days of marketing a product (if a “structure-function” claim is made). In Canada, they are regulated as active ingredients of licensed natural health products (NHPs) requiring pre-market authorization from the Natural Health Products Directorate. As one example, Sambucol^®* Original Lozenges (Healthcare Brands International Ltd., Surrey, UK), an elderberry preparation, is a licensed NHP indicated for reducing severity of flu symptoms (aches and pains, cough, congestion) and shortening duration of influenza A and B viruses.³² Elder flower preparations, such as Gaia Garden Herbals Elder Flowers Tincture (Flora Manufacturing & Distributing Ltd.; Burnaby, Canada), are licensed NHPs with the authorized therapeutic indication “as a diaphoretic in conditions requiring fever management, including the common cold and influenza and for sinusitis and chronic nasal catarrh [inflammation of mucus membranes] with deafness.”³³

MODERN RESEARCH

Numerous in vivo and in vitro laboratory studies have assessed elder flowers and berries for antibacterial, anticancer, anti-inflammatory, antimicrobial, antiproliferative, antiviral, antioxidant, and immunomodulating activity, as well as chemopreventive and cytotoxic potential, cellular uptake, burn healing, insulin-simulating and insulin-releasing actions, anti-angiogenic (inhibiting the growth of blood vessels) activity, cardioprotective activity, and antihypertensive properties. Human clinical studies support the traditional use of and laboratory findings on elderberry and flower.

During the 2009 flu season, a short-term, randomized, double-blind, placebo-controlled pilot study was conducted on 64 volunteers suffering from three or more flu-like symptoms (coughing, fever, headache, muscle aches, and/or nasal congestion and mucosal discharge) for less than 24 hours.³⁴ The patients were randomized into two groups of 32 and administered four doses of 175 mg proprietary elderberry extract (HerbalScience Singapore Pte. Ltd.; standardized and enriched in phenolic acids, polyphenolics, and a broad diversity of other flavonoids)³⁵ or placebo daily for two days. After 48 hours, the elderberry group reported a significant reduction in symptoms with 28% of volunteers being symptom free. The symptoms of the patients in the placebo group were either unchanged or worse.

In 2004, a randomized, double-blind, placebo-controlled study (n=60) demonstrated the safety and efficacy of Sambucol in the treatment of influenza.³⁶ Patients with influenza type A or B received 15 ml Sambucol or placebo four times per day. Flu symptoms decreased significantly in the elder group by the third or fourth day versus seven-to-eight days in the placebo group. Treatment was initiated within 48 hours of symptom onset and the authors suggested that the elder preparation might have been even more effective with earlier intervention.

In a previous placebo-controlled, double-blind study conducted in 1995 on 27 patients with influenza symptoms for 24 hours or less, patients received either Sambucol or placebo daily for three days (two tablespoons per day for children five-to-11 years of age and four tablespoons per day for adults 12 years and older).³⁷ Within two days, 93.3% of the elderberry group experienced a significant improvement in symptoms, and complete resolution was achieved by 90% of the group within two to three days. The placebo group did not experience similar improvement or resolution until day six.

A 2004 randomized, double-blind, placebo-controlled study investigated the effect of elderberry juice on cholesterol, triglyceride concentrations, and antioxidant status in young volunteers.³⁸ In the first arm of the study, 34 participants took three daily doses of 400 mg encapsulated spray-dried elderberry juice (Iprona; Lana, Italy; 10% anthocyanins, equal to 5 ml elderberry juice, processed first by ultra filtration after which the liquid extract is spray dried to a powder using maltodextrin as the carrier), or placebo for two weeks. A subgroup continued for another week to test for resistance to oxidation of low-density lipoprotein (LDL) cholesterol. There was a small, statistically insignificant change in cholesterol in the elderberry group (from 199 to 190 mg/dl) compared to placebo (from 192 to 196 mg/dl). Resistance to copper-induced oxidation of LDL did not change within the three weeks. In the second arm of the study, six participants took a single dose of 50 ml elderberry juice with a high-fat breakfast, and no significant post-meal triglyceride concentrations were observed. The authors stated that low-dose, spray-dried elderberry extract has a minor effect on serum lipids and antioxidative capacity, but that further studies employing higher, nutritionally relevant doses might affect significant postprandial serum lipids.

Based on evidence supporting the cardioprotective role of anthocyanins, a 2009 parallel-designed, randomized, placebo-controlled study was conducted to examine the effect of chronic anthocyanin consumption on biomarkers of cardiovascular disease (CVD) risk and kidney function.³⁹ Healthy postmenopausal volunteers (n=52) consumed 500 mg per day elderberry anthocyanins (Artemis International; Fort Wayne, IN; 125 mg cyanidin-3-glucoside, extraction method not stated) or placebo for 12 weeks. No significant change in biomarkers of CVD risk was observed and liver and kidney function remained within clinically acceptable ranges. The authors stated that while their findings are consistent with two previous studies that are not directly comparable (elderberry and cranberry [Vaccinium macrocarpon, Ericaceae] juices), their findings are inconsistent with two previous studies that showed reduction in CVD biomarkers (using Bing cherry [Prunus avium, Rosaceae] anthocyanins) and inflammatory markers (bilberries [Vaccinium myrtillus, Ericaceae] and blackcurrants [Ribes nigrum, Grossulariaceae]). They explained that differences in study design may explain the inconsistent results because the participants in their trial had lower levels of CVD risk than participants in the other study populations. They also suggested that the difference in inflammatory markers could be a result of this study’s examination of high levels of anthocyanin intake over a short period of time rather than long-term intake of anthocyanin-rich foods.

Studies have been conducted on elder in combination with other plant materials investigating their usefulness in a variety of conditions. A 2009 monograph by the American Botanical Council on Sinupret concluded that the “scientific and clinical literature supported [its] pharmacological mechanisms of mucolytic, secretolytic, anti-inflammatory, antibacterial, antiviral, and immunological activity, some of which has been documented in open-label and randomized, controlled human clinical trials.”²⁴

A small, randomized, crossover, placebo-controlled, single-blinded study performed in 2010 evaluated the laxative efficacy of a combination product that has been available in Brazil since 1926.⁴⁰ The product contains fruits of anise (Pimpenella anisum, Apiaceae) and fennel (Foeniculum vulgare, Apiaceae), as well as flowers of elder and senna (Cassia angustifolia, Fabaceae) (Laboratórios Klein; Porto Alegre, Brazil; described only as a “homogeneous mixture of dried botanicals”). Each of the 20 patients with chronic constipation who participated in the study received the compound as a tea (15 g infused for five minutes in 1,500 ml boiling water) or placebo for five days. Following a washout period of nine days during which the patients were free to use other laxatives, the treatment was reversed in the two groups. The number of evacuations in the group receiving the combination tea increased during the use of the tea and significant differences were observed as of the second day of treatment. No adverse effects were observed.

In 2008, authors of an observational study sought to obtain information on the compounds in a food supplement sold as a weight reduction aid to determine its short-term effectiveness and safety as an initiator of lifestyle change.⁴¹ While the name of the supplement was not stated, it consisted of elderberry juice supplemented with elder flower juice (concentrate based on 120 g fresh berries and extract of 3.9 g dried flowers), elder tablets (225 mg berry powder and 600 mg flower extract) three times per day, psyllium (Plantago arenaria, Plantaginaceae) two to three teaspoons each morning, and a dose of asparagus (Asparagus officinalis, Asparagaceae) tablets equivalent to 40.5 g dried asparagus per day. Participants (n=80) followed a 13-to-15 day protocol after which time their mean body mass index (BMI), weight, blood pressure, physical and emotional wellbeing, and quality of life had improved significantly. The authors stated that it remained to be established if any of the chemical constituents in the supplements contributed to the efficacy of the diet.

FUTURE OUTLOOK

For generations, European elder flower and elderberry preparations have been labeled and marketed as non-prescription herbal medicinal products available at most pharmacies and drugstores throughout Europe, as well as in countries where traditional European herbal medicines are licensed, listed, or registered (in particular, Australia, Canada, and New Zealand). In the United States, elder preparations are offered mainly as dietary supplements, although some, such as Sambucol Cold & Flu Relief, are listed homeopathic drug products. In recent years, new demand for elder is being driven, in part, by several alcoholic beverage brands offering certified organic elder flower and elderberry liqueurs, schnapps, spirits, and wines that have become trendy in both Europe and America. Moreover, non-alcoholic drinks — including the certified organic BIONADE^® (Peter Bier, Ostheim vor der Rhön) Elderberry flavor (entered EU market in 1996) — are sold in conventional, natural, and organic grocery stores throughout Europe and are popular on the menus of cafes, clubs, and bars. The elderberries used in BIONADE products are organically grown in Germany’s Rhön region (State of Hesse) and in Lower Franconia (State of Bavaria).

Elder (as elderberry) was the 18^th top-selling herbal dietary supplement in the Food, Drug, and Mass Market channel in the United States for 2011.⁴² A reported total of $797,915.00 in elderberry products was sold in that channel of trade, down almost 15 percent from 2010.

In a 2003 report, the estimated annual quantity of dried elder flowers wild-collected in Bosnia-Herzegovina was about 44 tons (five percent used domestically and 95 percent exported), and in Romania about 150 tons of elder flowers and 40 tons of elder fruits are wild-harvested annually.⁵ A 2010 report by the European Herb Growers Association (Europam) states that elder flowers and fruits remain among the highest volume wild-collected medicinal plants in both Bulgaria and Romania for export trade as well as for domestic herbal tea and phyto-pharmaceutical production.⁴³ An International Trade Centre study on certified organic wild-collected plants estimated that, in 2005, about 472 tons of elderberries, 19 tons of elder flowers, and six tons of elder leaves were collected according to an organic wild-crop harvesting practice standard.⁴⁴ Demand for European elder flower and fruit with sustainability certifications (e.g., Organic Wild and FairWild) appears to be increasing as evidenced by the fact that wild-collection firms are implementing ecological and social standards for elder harvesting in a number of countries, including Albania, Bosnia-Herzegovina, Hungary, Macedonia,⁶ Croatia, and the Ukraine.⁴⁵ In Croatia, about 75 percent of the wild-harvested elder flowers are traded in the local and national markets, and about 25 percent are exported.⁵

* Sambucol was the initial trade name for the elderberry extract made by Razei Bar Industries in Jerusalem, Israel. Razei Bar was purchased by Health Brands International Ltd. (a private equity company based in the United Kingdom) in 2007. Health Brands International sold the Sambucol rights to PharmaCare Labortories, a Sydney, Australia company, which now markets the brand in the United States.

REFERENCES

1.     McGuffin M, Kartesz JT, Leung AY, Tucker AO. American Herbal Products Association’s Herbs of Commerce, 2nd ed. Silver Spring, MD: American Herbal Products Association; 2000.

2.     Bown D. New Encyclopedia of Herbs and Their Uses. London: Dorling Kindersley Ltd.; 2001.

3.     Gilman EF, Watson DG. Sambucus Canadensis American Elder. Available at: http://edis.ifas.ufl.edu/pdffiles/ST/ST57800.pdf. Accessed November 16, 2012.

4.     Torres-Londoño P, Doka D, Becker H. Die Wildsammlung von Arznei- und Gewürzpflanzen in Albanien, untersucht an Beispielen aus dem Umland von Peshkopi (Region Dibër). Zeitschrift für Arznei & Gewürzpflanzen. 2008;13(4):153-160.

5.     Kathe W, Honnef S, Heym A. Medicinal and Aromatic Plants in Albania, Bosnia-Herzegovina, Bulgaria, Croatia and Romania. Bonn, Germany: German Federal Agency for Nature Conservation. 2003. Available at: www.bfn.de/fileadmin/MDB/documents/skript91.pdf. Accessed November 17, 2012.

6.     FairWild Foundation. FairWild-certified ingredients under production. Weinfelden, Switzerland, FairWild Foundation. December 2011. Available at: www.fairwild.org/publication-downloads/other-documents/FairWild_species_products_Dec2011.pdf. Accessed November 17, 2012.

7.     Łuczaj L, Szymański WM. Wild vascular plants gathered for consumption in the Polish countryside: a review. Journal of Ethnobiology and Ethnomedicine. 2007;3:17. doi:10.1186/1746-4269-3-17. Available at: www.ethnobiomed.com/content/pdf/1746-4269-3-17.pdf. Accessed November 17, 2012.

8.     Wichtl M, ed. Brinckmann JA, Lindenmaier MP, trans. Herbal Drugs and Phytopharmaceuticals, 3rd ed. Stuttgart: Medpharm GmbH Scientific Publishers; 2004.

9.     Donnelly R, Helberg U. Balkans Herbal Development Initiative—Phase 1 Final Summary Report—Serbia and Montenegro. Southeastern Europe Enterprise Development and The Corporate Citizenship Facility. 2003. Available at: www.ifc.org/ifcext/enviro.nsf/AttachmentsByTitle/art_CCF-HDISerbMont/$FILE/HDI%2BReport%2BSerbia%2Band%2BMontenegro.pdf. Accessed November 17, 2012.

10.  Möhler M, Blaschek W, Lohwasser U, Walther E. Holunder (Sambucus nigra L.). In: Hoppe B, et al. Handbuch des Arznei- und Gewürzpflanzenbaus, Band 4. Bernburg, Germany: Verein für Arznei- und Gewürzpflanzen SALUPLANTA e.V.  ; 551-561.

11.  Mumcuoglu M. Wonderful Sambucus: The Black Elderberry. Jerusalem: Shmuel Tal Printing Service; 1998.

12.  Grieve M. A Modern Herbal. Vol. 2. New York: Dover Publications; 1971.

13.  Lehman, H. Mathemathisch-naturwisssenschalichen Abteilung der Philosophischen Fakultät der Universität Basel. Zofingen: Graphische Anstalt Zofinger Tagblatt; 1935.

14.  Blochwich M. Anatomi Sambuci: The Anatomy of the Elder. Rev. ed. Jacobs A, Stipps F (eds.), Freund S (trans.). Lana, Italy: BerryPharma AG; 2010.

15.  Hoffman D. Medical Herbalism: The Science and Practice of Herbal Medicine. Rochester, VT: Healing Arts Press; 2003.

16.  Elliman W. Elderberry, flu contrary. Hadassah Magazine. 1994 Dec;40-41.

17.  Blumenthal M, Goldberg A, Brinckmann J, eds. Herbal Medicine: Expanded Commission E Monographs. Austin, TX: American Botanical Council; Newton, MA: Integrative Medicine Communications; 2000.

18.  Leung A, Foster S. Encyclopedia of Common Natural Ingredients Used in Food Drugs, and Cosmetics, 2nd ed. New York: John Wiley & Sons; 1996.

19.  European Medicines Agency (EMA) Committee on Herbal Medicinal Products (HMPC). Community Herbal Monograph on Sambucus nigra L., flos. London, UK: EMA. 2008. Available at: www.ema.europa.eu/docs/en_GB/document_library/Herbal_-_Community_herbal_monograph/2009/12/WC500018233.pdf. Accessed November 17, 2012.

20.  Blumenthal M, Busse WR, Goldberg A, Gruenwald J, Hall T, Riggins CW, Rister RS, eds. Klein S, Rister RS, trans. The Complete German Commission E Monographs¾Therapeutic Guide to Herbal Medicines. Austin, TX: American Botanical Council; Boston: Integrative Medicine Communication; 1998.

21.  Bradley PR, ed. British Herbal Compendium: A Handbook of Scientific Information on Widely Used Plant Drugs, Vol. 1. Bournemouth, UK: British Herbal Medicine Association. 1992;84-86.

22.  European Medicines Agency (EMA) Committee on Herbal Medicinal Products (HMPC). Community Herbal Monograph on Sambucus nigra L., flos. London, UK: EMA. 2008. Available at: www.ema.europa.eu/docs/en_GB/document_library/Herbal_-_Community_herbal_monograph/2009/12/WC500018233.pdf. Accessed November 17, 2012.

23.  European Pharmacopoeia Commission. European Pharmacopoeia, 7th ed. (PhEur 7.0). Strasbourg, France: European Directorate for the Quality of Medicines. 2011;1117-1118.

24.  Oliff HS, Blumenthal M. American Botanical Council Proprietary Botanical Product Scientific and Clinical Monograph for Sinupret®. Austin, Texas: American Botanical Council; 2009.

25.  Medicines and Healthcare products Regulatory Agency (MHRA). Potter’s Cold and Flu Relief – THR: 00250/0224. London, UK: MHRA; May 8, 2012. Available at: www.mhra.gov.uk/home/groups/par/documents/websiteresources/con171949.pdf. Accessed November 17, 2012.

26.  European Medicines Agency (EMA) Committee on Herbal Medicinal Products (HMPC). Call for scientific data for use in HMPC assessment work on Sambucus nigra L., fructus. London, UK: EMA. October 15, 2011. Available at: www.ema.europa.eu/docs/en_GB/document_library/Herbal_-_Call_for_data/2011/10/WC500116585.pdf. Accessed November 17, 2012.

27.  Weißenbacher SM. Edelholunder - Gesundheit durch die Kraft der Pflanzenstoffe. Wellbion Journal für Diabetiker und Fachpersonal. 2006;1:24-25. Available at: www.wellion.at/_pdf/4c3b2508200c2.pdf. Accessed November 17, 2012.

28.  VitaBasix® by LHP Inc. Product Information: Snorin®. Maastricht, The Netherlands: LHP Inc. July 2011. Available at: www.vitabasix.com/fileadmin/content/produktInfoPDFs/enPDF/Produktinfo_Snorin_EN.pdf. Accessed November 17, 2012.

29.  European Commission Health & Consumers Directorate. Cosmetic Ingredients and Substances (CosIng®) Database. Brussels, Belgium: European Commission. Available at: http://ec.europa.eu/consumers/cosmetics/cosing/. Accessed November 17, 2012.

30.  Food and Drug Administration. 21CFR §172.510 Natural flavoring substances and natural substances used in conjunction with flavors. In: Code of Federal Regulations. Washington, DC: National Archives and Records Administration; 2012. Available at: www.gpo.gov/fdsys/pkg/CFR-2012-title21-vol3/pdf/CFR-2012-title21-vol3-sec172-510.pdf. Accessed November 17, 2012.

31.  Food and Drug Administration. 21CFR §582.20: Essential oils, oleoresins (solvent-free), and natural extractives (including distillates). In: Code of Federal Regulations. Washington, DC: National Archives and Records Administration; 2012. Available at: www.gpo.gov/fdsys/pkg/CFR-2012-title21-vol6/pdf/CFR-2012-title21-vol6-sec582-20.pdf. Accessed November 17, 2012.

32.  Health Canada Natural Health Products Directorate (NHPD). Sambucol® Original Lozenges, Natural Product Number (NPN): 80026276. In: Health Canada Licensed Natural Health Products Database. July 8, 2011. Available at: http://webprod3.hc-sc.gc.ca/lnhpd-bdpsnh/index-eng.jsp. Accessed November 17, 2012.

33.  Health Canada Natural Health Products Directorate (NHPD). Gaia Garden Herbals Elder Flowers Tincture, Natural Product Number (NPN): 80006307. In: Health Canada Licensed Natural Health Products Database. June 26, 2008. Available at: http://webprod3.hc-sc.gc.ca/lnhpd-bdpsnh/index-eng.jsp. Accessed November 17, 2012.

34.  Kong FK. Pilot clinical study on a proprietary elderberry extract: efficacy in addressing influenza symptoms. OJPK. 2009;5:32-43.

35.  Roschek W, Alberte RS. Pharmacokinetics of cyanidin and anti-Influenza phytonutrients in an elder berry extract determined by LC-MS and DART TOF-MS. Online Journal of Pharmacology and Pharmacokinetics. 2008;4:1-17.

36.  Zakay-Rones Z, Thom E, Wollan T, Wadstein J. Randomized study of the efficacy and safety of oral elderberry extract in the treatment of influenza A and B virus infections. J Int Med Res. 2004;32(2):132-140.

37.  Zakay-Rones Z, Farsano N, Zlotnik M, et al. Inhibition of several strains of influenza virus in vitro and reduction of symptoms by an elderberry extract (Sambucus nigra L.) during an outbreak of influenza B Panama. J Alt Comp Med. 1995;1(4):361-369.

38.  Murkovic M, Abuja PM, Bergmann AR, et al. Effects of elderberry juice on fasting and postprandial serum lipid and low-density lipoprotein oxidation in healthy volunteers: a randomized, double-blind, placebo-controlled study. Eur J Clin Nutr. 2004;58:244-249.

39.  Curtis PJ, Kroon PA, Hollands WJ, et al. Cardiovascular disease risk biomarkers and liver and kidney function are not altered in postmenopausal women after ingesting an elderberry extract rich in anthocyanins for 12 weeks. J Nutr. 2009;139:2266-2271.

40.  Picon PD, Picon RV, Costa AF. Randomized clinical trial of a phytotherapic compound containing Pimpinella anisum, Foeniculum vulgare, Sambucus nigra, and Cassia augustifolia [sic] for chronic constipation. BMC Complementary and Alternative Medicine. 2010;10:17. doi:10.1186/1472-6882-10-17.

41.  Chrubasik C, Maier T, Dawid C, et al. An observational study and quantification of the actives in a supplement with Sambucus nigra and Asparagus officinalis used for weight reduction. Phyto Res. 2008;22:913-918.

42.  Blumenthal M, Lindstrom A, Ooyen C, Lynch ME. Herb supplement sales increase 4.5% in 2011. HerbalGram. 2012;95:60-64.

43.  European Herb Growers Association (Europam). Production of Medicinal and Aromatic Plants in Europe Status 2010. Vienna, Austria: Europam. 2010. Available at: www.europam.net/index.php?option=com_content&view=article&id=6&Itemid=11. Accessed November 17, 2012.

44.  Censkowsky U, Helberg U, Nowack A, Steidle M. Overview of World Production and Marketing of Organic Wild Collected Products. Geneva, Switzerland: International Trade Centre UNCTAD/WTO. 2007. Available at: www.intracen.org/uploadedFiles/intracenorg/Content/Exporters/Sectors/Fair_trade_and_environmental_exports/Biodiversity/Overview_World_Production_Marketing_Organic_Wild_Collected_Products.pdf. Accessed November 17, 2012.

45.  Institut für Marktökologie (IMO). List of certified operators 2011/2012. Weinfelden, Switzerland: IMO. September 24, 2012. Available at: www.imo.ch/logicio/client/imo/file/clients/EU_List_of_certified_IMO_clients.pdf. Accessed November 17, 2012.