INTRODUCTION

Melissa officinalis, commonly called lemon balm,¹ is an erect, herbaceous perennial that grows to about three feet (1 m) in height. The species has sparsely pubescent, toothed leaves,² which have a fragrance and flavor reminiscent of lemon (Citrus × limon, Rutaceae). Unlike many members of the mint family, lemon balm does not have invasive roots. The small, yellow to pinkish-white flowers produce four tiny seeds, which germinate easily and are primarily responsible for the plant’s vigorous dispersion.

The genus Melissa is small and includes only four accepted species (M. officinalis, M. axillaris, M. flava, and M. yunnanensis).³ Melissa officinalis has three main subspecies that have been differentiated (ssp. officinalis, ssp. altissima, and ssp. inodora⁴) and at least 15 named cultivars.⁵ Based on composition of the essential oil, at least three chemotypes have been identified: citral-, germacrene- and caryophyllene-types.⁶

The genus Melissa originated in the Mediterranean to western and central Asian regions.⁴ Lemon balm leaf is wild-collected on a commercial scale in parts of eastern Europe,^7,8 southern Europe,^9-11 and western Asia.¹² The commercial supply of cultivated lemon balm comes mainly from eastern Europe,^4,13,14 southern Europe,^4,10,15-17 western Europe,^4,18-20 northern Africa,²¹ North America,⁴ and South America.⁴

Most of the certified organic lemon balm in the global market originates from Albania (wild-collected), Bulgaria (wild-collected), Egypt (cultivated), Turkey (cultivated), the United Kingdom (cultivated), and the United States (cultivated).²² There are also producers of certified fair trade lemon balm in Egypt.²¹

HISTORY AND CULTURAL SIGNIFICANCE

The genus name Melissa is derived from the Greek μελισσο (melisso), meaning “bee,” which refers to the strong attraction that bees have to M. officinalis.⁴ Swedish botanist Carl Linnaeus first assigned the genus Melissa in 1737.²³ While referred to as “melissa” in the European Pharmacopoeia,²⁴ the preferred standardized common name in the United States is “lemon balm,” according to the second edition of the American Herbal Products Association’s Herbs of Commerce.¹

One of the earliest known descriptions of lemon balm appeared in Historia Plantarum by Greek philosopher and botanist Theophrastus of Eresus (372-287 BCE). Lemon balm remains were detected in a rodent nest inside a hollow bronze statue of a champion athlete of Greek origin excavated from the northern Adriatic Sea — probably the cargo of a Roman ship — that dates back to the Classical period (first century BCE to second century CE).²⁵ In the 10th century, lemon balm was introduced to Spain by the occupying Moors and was later brought to central Europe by Benedictine monks. In her book Physica, written between 1151 and 1158, Benedictine abbess Hildegard von Bingen (1098-1179) described medicinal uses of lemon balm.²⁶ It is believed that the original idea of “Carmelite Water” (Eau de Carmélite, also known as “Spirit of Melissa”) may be traced back to around the year 1200, when Christian hermits, who began living in caves on Mount Carmel after the Crusaders retook Haifa, first realized the therapeutic properties of lemon balm.²⁷ Lemon balm is among the 165 medicinal plant species used in Carinthian monastic medicine of the High Middle Ages (1001-1300), and it is still cultivated today at Carinthian monasteries in Austria.²⁸

By the 16th century, lemon balm was being grown in several European countries.²⁶ In his 1543 herbal New Kreüterbuch, botanist and physician Leonhart Fuchs (1501-1566) wrote that “Melissen” and “Honigblum” were the traditional names used because of the honey bee’s special love and desire for the flowers of lemon balm to make honey.²⁹

In France, lemon balm cultivation began around 1611 in monastery gardens, where a process for distilling lemon balm water was developed by the Discalced Carmelites* in Paris, and Eau de Carmélite became a popular remedy for treating toothache, syncope (fainting), and anxiety. A century later, in 1710, the Discalced Carmelites in Venice began to produce their version of Acqua di Melissa, but decided to use Dracocephalum moldavica (syn. M. moldavica) instead of M. officinalis.³⁰ At the end of the 18th century, during a church-hostile phase of the French Revolution, two Carmelite nuns fled Paris to take refuge at a German monastery in Baden-Baden and brought with them their secret recipe for Eau de Carmélite. In this way, the French tradition carried on in Germany where the name of the elixir changed to Melissengeist. The method of preparing Melissengeist was known by only the two nuns, who took an oath to pass it on to an initiated successor only when one of them died. In 2003, the sisters of the Holy Sepulcher of Baden-Baden came to an agreement with the sisters of Monastère du Carmel Notre Dame de l’Unité in Develier, Switzerland, to transfer the rights to manufacture the formula. The transfer took two years and required formal consent of the Archbishop of Freiburg (the legal owner of the formula) and authorization from the Swiss Alcohol Board for the manufacture of alcoholic beverages.³¹

In 1984, the German Commission E approved the use of lemon balm leaf, prepared as an herbal infusion, dry extract or fluidextract, as a nonprescription medicine for treating nervous sleeping disorders and functional gastrointestinal complaints.³² In 1997, the European Scientific Cooperative on Phytotherapy (ESCOP) indicated lemon balm internally for tenseness, restlessness, irritability, and for treatment of minor digestive issues, as well as externally for cold sores (herpes labialis).³³ Since then, national labeling standards monographs of European Union (EU) member states, such as those of the German Commission E, have been superseded by monographs of the European Medicines Agency (EMA).

A quality standards monograph for “Melissa Leaf” first entered the European Pharmacopoeia (PhEur) in the 2000 supplement to the 1997 third edition,³⁴ and subsequently a monograph for “Melissa Leaf Dry Extract” was added to the sixth supplement to the sixth edition (PhEur 6.6) in 2010. Both monographs have remained official through the current ninth edition published in July 2016.²⁴ In 2004, a comprehensive monograph (quality and therapeutics) for “Folium Melissae” was added to volume two of the WHO Monographs on Selected Medicinal Plants,³⁵ and, in 2010, a monograph was included in the WHO Monographs on Medicinal Plants Commonly Used in the Newly Independent States (NIS).³⁶ In 2007, the EMA published a labeling standards monograph, which was later superseded by a 2013 revised monograph.³⁷

After the passage of the EU Directive on Traditional Herbal Medicinal Products (THMPD) of 2004, the first product in Europe to be issued a product registration under the new framework was Klosterfrau^† Melissengeist (M.C.M. Klosterfrau Vertriebs GmbH; Cologne, Germany), issued by the German Federal Institute for Drugs and Medical Devices (BfArM) in December 2005.³⁸

CURRENT AUTHORIZED USES IN COSMETICS, FOODS, AND MEDICINES

In the United States, the Food and Drug Administration (FDA) classifies “balm (lemon balm)” as Generally Recognized as Safe (GRAS) for use as a spice, natural seasoning, or flavoring.³⁹ FDA also classifies essential oils and natural extractives (including distillates) of lemon balm as GRAS for use in food products.⁴⁰ Lemon balm is also permitted 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 conforms with current Good Manufacturing Practices (cGMPs) for dietary supplements.⁴¹

For herbal medicinal product companies in the EU or in non-EU countries where the PhEur is an official compendium (e.g., Australia and Canada), the aforementioned PhEur quality monographs can be used as the basis for active ingredient specifications. Registered Traditional Herbal Medicinal Products (THMPs) composed of PhEur-quality lemon balm and prepared as herbal teas, liquid extracts, or as solid dosage forms containing dry extract, may be labeled and marketed “for relief of mild symptoms of mental stress and to aid sleep” or “for symptomatic treatment of mild gastrointestinal complaints including bloating and flatulence.”³⁷

For use in cosmetic products, the European Commission Health and Consumers Directorate lists “Melissa Officinalis Leaf Extract” and “Melissa Officinalis Leaf Water” (aqueous solution of the steam distillates obtained from the leaves) for skin-conditioning function, and “Melissa Officinalis Leaf Oil” (volatile oil obtained from the leaves and tops) for masking, perfuming, and tonic functions.⁴²

MODERN RESEARCH

Chemical constituents found in M. officinalis include antioxidant phenolic acids, with rosmarinic acid (a caffeic acid derivative) as the major compound; flavonoids (e.g., luteolin-3’-O-glucuronide)⁴³; and essential oil (with citronellal, neral, and geranial as the most abundant constituents)^33,44; among others.

In vitro and in vivo studies have shown lemon balm and its essential oil to have anti-anxiety,⁴⁵ anti-inflammatory, analgesic,⁴⁶ antibacterial, antiviral,^47-53 antiproliferative, radical scavenging,^54,55 sedative,^45,56 thyroid-inhibiting,⁵⁷ hypoglycemic, anti-diabetic (glucokinase-stimulating),⁵⁸ antigenotoxic, antimutagenic,⁵⁹ immunostimulating,⁶⁰ and anticonvulsive properties.^61,62

A number of clinical studies have shown various positive outcomes when M. officinalis is used in combination with other herbs. These include the following: promoting sleep (with valerian [Valeriana officinalis, Caprifoliaceae])^63,64; treating restlessness in children (with valerian)⁶⁴; stimulating alpha1 electrical brain activity (with lavender [Lavandula spp., Lamiaceae], hops [Humulus lupulus, Cannabaceae], and oat [Avena sativa, Poaceae])⁶⁵; treating infantile colic (with German chamomile [Matricaria chamomilla, Asteraceae] and fennel [Foeniculum vulgare, Apiaceae])⁶⁶; reducing oxidative stress (with cinnamon [Cinnamomum zeylanicum, Lauraceae])⁶⁷ and laboratory-induced stress (with valerian)⁶⁸; treating dyspepsia (in STW 5^‡ [Steigerwald Arzneimittelwerk GmbH; Darmstadt, Germany])⁶⁹; treating abdominal pain and bloating in patients with irritable bowel syndrome (with spearmint [Mentha spicata, Lamiaceae] and coriander [Coriandrum sativum, Apiaceae]).⁷⁰

Unfortunately, despite the approved uses of lemon balm based on its long history in traditional medicine, there are few high-quality clinical studies on M. officinalis alone.

A randomized, double-blind, placebo-controlled (RDBPC) study (N = 58) published in 2016 evaluated the effect of lemon balm on patients with borderline hyperlipidemia. Outpatients with total serum cholesterol ranging from 200-260 mg/dL, low-density lipoprotein (LDL) levels ranging from 100-160 mg/dL, and/or serum triglycerides ranging from 150-300 mg/dL were randomly assigned to take 1,000 mg encapsulated lemon balm leaf powder (500 mg per capsule; no further information provided) or placebo three times per day after meals over two months. Participants were advised not to change their diet, and their daily intake of carbohydrates, protein, fiber, and fat were recorded via two 24-hour dietary recall questionnaires at the beginning and end of the study. No statistical differences were found within or between groups regarding dietary intake. The lemon balm group experienced a significant decrease in mg/dL of LDL cholesterol (139.64 ± 19.06 to 125.68 ± 22.62) compared to the placebo group (129.90 ± 17.94 to 131.07 ± 21.21). While there were no significant differences between groups in levels of total cholesterol, fasting blood glucose, high-density lipoprotein (HDL), triglycerides, creatinine, or alanine transaminase (ALT) at the end of the study, the lemon balm group did not experience the higher LDL:HDL ratio (a risk factor for atherosclerosis and coronary heart disease) that was seen in the placebo group. According to the authors, this suggests that lemon balm may provide protection against atherosclerosis and coronary heart disease. Additionally, the lemon balm group experienced a significant change in levels of aspartate transaminase (AST; 23.64 ± 7.36 U/L to 22.30 ± 6.56 U/L) compared to the placebo group (20.27 ± 5.76 U/L to 22.50 ± 6.00 U/L). Since increased levels of AST are correlated with liver damage, this study suggests that lemon balm may have the ability to improve liver health, although the observed decrease is not likely to have a clinically relevant impact.⁴⁴

Another RDBPC study explored the effect of lemon balm on heart palpitations, an indication for lemon balm in traditional Iranian medicine. Participants (N = 55) with “an unpleasant sensation in the heart or awareness of heartbeat as their main complaint” were randomly assigned to take 500 mg encapsulated lemon balm dry water extract powder (powdered dry leaves infused in 1,000 mL boiling water, filtered, then freeze dried; no additional information provided) or placebo twice daily for 14 days. At the end of the two-week period, palpitation episodes, based on patients’ diaries, had decreased by 36.8% in the lemon balm group, compared to a decrease of 4.19% in the placebo group. Moreover, the lemon balm group had fewer participants with anxiety and insomnia at the end of the study than the placebo group (decreases of 42.8% vs. 18.2%, respectively). Change in pain intensity between the two groups was not significant.⁷¹

A 2015 RDBPC study (N = 100) investigated the effect of lemon balm on the intensity of premenstrual syndrome (PMS) symptoms in high school girls in Shiraz, Iran, over the course of three menstrual cycles. Participants with PMS Screening Tool scores greater than 20 (considered “average symptoms”) were randomly assigned to receive 1,200 mg per day of lemon balm essence (600 mg capsules made in the pharmacology department of the Shiraz University of Medical Sciences in Shiraz, Iran) or placebo. The test group experienced significant reductions in PMS symptom intensity scores from the onset of the study (42.56 + 15.73) at one month (32.72 ± 13.24), two months (30.02 ± 12.08), and three months (13.90 ± 10.22). The placebo group experienced non-significant reductions in intensity of PMS symptoms, which the authors suggest may be attributable to the placebo effect.⁷²

A randomized, single-blind study (N = 43) in 2016 compared lemon balm to the nonsteroidal anti-inflammatory drug (NSAID) mefenamic acid for their ability to relieve dysmenorrhea (i.e., pain associated with menstruation). From the onset of the menstrual period until the third day of menstruation, women with moderate-to-severe primary dysmenorrhea were randomly assigned to drink one cup of lemon balm tea made from tea bags (Golchai Co.; Alborz, Iran; no additional information provided) or take 250 mg of mefenamic acid (Razak Laboratories Co.; Tehran, Iran) every eight hours until pain was relieved. Both groups experienced decreases in pain intensity and duration over three menstrual cycles, but the lemon balm group experienced a greater decrease in pain intensity (5.61 ± 1.125 to 3.166 ± 0.632) than the mefenamic acid group (6.13 ± 1.38 to 4.095 ± 1.70). The authors recognize that the study’s findings are limited by the small sample size and short follow-up period.⁷³

Published in 2003, one RDBPC study investigated the efficacy of lemon balm for treating mild-to-moderate Alzheimer’s disease (AD) over four months. Patients (N = 42; 65-80 years old) with scores of 12 or greater on the AD Assessment Scale (ADAS-cog) and 2 or less on the Clinical Dementia Rating-Sum of Boxes (CDR-SB) scale were randomly assigned to receive 60 drops per day of lemon balm extract (1:1 in 45% alcohol, standardized to contain at least 500 µg citral/mL; no additional information provided) or placebo. After four months, the lemon balm group experienced a significant improvement in cognition compared to placebo in both the ADAS-cog (-6.4 vs. 5.60, respectively) and the CDR-SB scores (-1.92 vs. 1.03, respectively). The authors state that while lemon balm may be effective in treating mild-to-moderate AD, further studies with larger sample sizes are needed to confirm lemon balm’s efficacy. The authors also list the short follow-up period as a limitation, but it is unclear from the paper if there was a follow-up period at all.⁷⁴

One RDBPC study published in 2002 evaluated the effectiveness of lemon balm essential oil (LBEO) for managing agitation in patients with severe dementia. Patients with clinically significant agitation related to severe dementia (N = 72, mean age = 78.5 ± 8.1 years), who continued to use prescribed psychotropic medications during the study, were randomly assigned to receive treatment with LBEO lotion or placebo (sunflower [Helianthus spp., Asteraceae] oil lotion). The LBEO was obtained from G. Baldwin & Co. (London, England) and contained 22% citronellal, 18% caryophyllene, 7% neral, 7% geraniol, 3% geranyl acetate, and 4% citronallal. The test preparation was made by adding 10% by weight LBEO to a base lotion containing almond (Prunus dulcis, Rosaceae) oil, glycerine, stearic acid, cetearyl alcohol, and tocopheryl acetate. Over a four-week period, a measured dose of 0.16-0.17 g was applied for one to two minutes to the patient’s face and arms twice a day for a total of six doses per day. To achieve blinding, two residential facilities were used and participants in each facility were given either the active treatment or placebo.

By the end of the study, the lemon balm group had experienced a 35% decrease from baseline in agitation on the Cohen-Mansfield Agitation Inventory (CMAI), compared to an 11% decrease in the placebo group, a significant between-group difference. Additionally, 21 of 36 subjects (58%) in the active treatment group experienced a clinically significant improvement in agitation (defined as a 30% improvement) compared to only five of 36 (14%) in the placebo group. Moreover, the lemon balm group experienced a significant reduction in the amount of time spent socially withdrawn and a significant increase in the amount of time participating in constructive activities. The authors propose several hypotheses for the success of the treatment: physiological effect(s) of the LBEO terpenes; concentration of the monoterpene citronellal in the hippocampus after administration; increased social contact between staff and subjects; the fragrance having a placebo effect on subjects (considered unlikely as patients with severe dementia commonly have an impaired sense of smell); and the fragrance having an impact on the caregivers’ reporting. However, the authors believe that none of these hypotheses taken individually can explain the magnitude of improvement in the active treatment group, and they recommend further multicenter studies to confirm and elucidate their findings.⁷⁵

FUTURE OUTLOOK

Although classified as a protected species in Croatia,⁷⁶ the International Union for Conservation of Nature (IUCN) European Red List of Medicinal Plants assigns M. officinalis to the conservation category of least concern, meaning that the species is not threatened in Europe.⁷⁷ However, the situation is different in parts of Asia. In Iran, wild M. officinalis is reportedly threatened due to habitat destruction, land use changes, and overharvesting.⁷⁸ In Armenia, field studies on changes in distribution and structure of wild M. officinalis populations were carried out from 2006 to 2009.⁷⁹ A related eco-geographic survey of population dynamics of wild M. officinalis was conducted from 2007 to 2011.⁸⁰ While historical data had shown that wild M. officinalis populations were widely distributed in northern and central regions of Armenia, nearly half of the populations no longer existed in the previously cited locations. There is also evidence that the distribution of M. officinalis is expanding in southern Armenia. Current models predict that vulnerability of wild populations in central and northern Armenia will increase due to anthropogenic threats (e.g., poor land management, deforestation, livestock overpopulation, and unsustainable wild-collection methods) and climate change (e.g., more frequent early spring frosts and abrupt weather changes).⁸¹

One of the biggest markets for lemon balm is Germany, where the average annual demand is about 1.5 million kg (3.307 million lbs). While Germany imports most of its lemon balm supply, about 20% is grown in Germany on about 120 hectares (296.5 acres).⁸² There are approximately 38 hectares (94 acres) of lemon balm cultivation in neighboring France.¹⁹ Bulgaria remains one of the main producers and exporters of both wild-collected and cultivated lemon balm with an annual average export volume of 330,629 kg (728,912 lbs) Folium Melissae (leaf), plus another 118,840 kg (261,997 lbs) of Herba Melissae (aerial parts), and 11,400 kg (25,132 lbs) of Herba Melissae Stipites (stem).⁸³ In 2015, Bulgaria had about 410 hectares (1,013 acres) of lemon balm cultivation with an overall yield of 550,000 kg (1.212 million lbs).⁸⁴ Albania exports about 350,000 kg (771,618 lbs) of wild-collected lemon balm annually.¹⁰ Hungary has an estimated 200-250 hectares (494-618 acres) of lemon balm cultivation with an annual production of up to 300,000 kg (661,387 lbs).⁸⁵ In the United States, there are many small- to medium-sized organic lemon balm growers in several states, including California, Oregon, Washington, Vermont, Maine, and New York.²²

There are no indications that the demand for lemon balm for use in herbal medicinal products, herbal dietary supplements, foods, and beverages will decrease. Although lemon balm is now cultivated in many countries worldwide, the main production areas and highest demand remain in Europe, especially Germany. There is evidence that both cultivated and wild-collected lemon balm are increasingly being produced according to international sustainability standards, such as organic and fair trade. The production and market scenario appear stable.

—Gayle Engels and Josef Brinckmann

* The Order of the Discalced Carmelites, founded in 1562, is a mendicant monastic order (i.e., dependent on charity) of the Roman Catholic Church. “Discalced” comes from the Latin word for “barefoot.”

^† Klosterfrau, literally translated as “cloister woman,” is a German term for “nun.”

^‡ STW 5 is a combination herbal product that also contains bitter candytuft (Iberis amara, Brassicaceae), angelica (Angelica archangelica, Apiaceae), milk thistle (Silybum marianum, Asteraceae), caraway (Carum carvi, Apiaceae), celandine (Chelidonium majus, Papaveraceae), licorice (Glycyrrhiza glabra, Fabaceae), German chamomile, and peppermint (Mentha × piperita, Lamiaceae).

References

1. McGuffin M, Kartesz JT, Leung AY, Tucker AO. American Herbal Products Association’s Herbs of Commerce. 2nd ed. Silver Springs, MD: American Herbal Products Association; 2000.
2. Applequist W. The Identification of Medicinal Plants: A Handbook of the Morphology of Botanicals in Commerce. St. Louis, MO: Missouri Botanical Garden; 2006.
3. The Plant List (2013). Version 1.1. 2013. Available at: www.theplantlist.org/tpl1.1/search?q=Melissa. Accessed April 15, 2017.
4. Bomme U, Honermeier B, Hoppe B, Kittler J, Lohwasser U, Marthe F. Melisse (Melissa officinalis L.). In: Hoppe B, ed. Handbuch des Arznei- und Gewürzpflanzenbaus, Band 5. Bernburg: Verein für Arznei- und Gewürzpflanzen SALUPLANTA e.V. Bernburg; 2013:151-173.
5. Heine H, Eger H, Franz C, Blüthner W-D, Hoppe K. Sortenwesen und Sortenübersicht Arznei- und Gewürzpflanzen. In: Verein für Arznei- und Gewürzpflanzen SALUPLANTA e.V. Bernburg, ed. Handbuch des Arznei- und Gewürzpflanzenbaus, Band I. Bernburg: Verein für Arznei- und Gewürzpflanzen SALUPLANTA e.V. Bernburg; 2009.
6. Kittler J, Krüger H, Schütze W, et al. Charakterisierung unterschiedlicher Genpools der Melisse (Melissa officinalis) als Basis für die Entwicklung von züchterisch wertvollem Ausgangsmaterial. In: Humboldt-Universität zu Berlin, ed. 6. Fachtagung Arznei- und Gewürzpflanzen. Berlin: Deutscher Fachausschuß für Arznei-, Gewürz- und Aromapflanzen; 2011.
7. Bakalski Co. Ltd. List of Wild Collected Organic Herbs, season 2010. Available at: www.bakalskico.com/products/organic-wild-collected-herbs.html Accessed April 15, 2017.
8. Viola Ltd. List of Wild Collected Organic Herbs. Available at: www.viola.bg/LISTOFWILDCOLLECTED2009.pdf. Accessed April 16, 2017.
9. AgroHerbAl sh.p.k. Products. Available at: www.agroherbal.net/products-natural-biologic-organic-agroherbal.html. Accessed April 16, 2017.
10. Kathe W, Honnef S, Heym A. Medicinal and Aromatic Plants in Albania, Bosnia-Herzegovina, Bulgaria, Croatia and Romania. Bonn, Germany: Bundesamt für Naturschutz (BfN);2003.
11. Brinckmann JA, Huggins K, Gardner ZE. Managing Natural Resources for Sustainable Livelihoods: Threats to the Future of Sustainable Wild Collection and Field Experience with Implementation of the FairWild Standard for Medicinal Plants. International Journal on Biodiversity Watch. 2014;3:13-29.
12. ANTARAM PC. Medicinal herbs and herbal teas. Yerevan, Armenia: ANTARAM PC; 2017.
13. Bernáth J, Németh E. Main fields of research activity on medicinal and aromatic plant species in Hungary in relation to the ECPGR “priority list”. In: Lipman E, ed. Report of a Working Group on Medicinal and Aromatic Plants. Second Meeting, 16‑18 December 2004, Strumica, Macedonia FYR / Third Meeting, 26–28 June 2007, Olomouc, Czech Republic. Rome, Italy: Bioversity International; 2009:115-128.
14. Węglarz Z, Geszprych A. The status of medicinal and aromatic plants in Poland. In: Baričevič D, Bernáth J, Maggioni L, Lipman E, eds. Report of a Working Group on Medicinal and Aromatic Plants. First meeting, 12-14 September 2002, Gozd Martuljek, Slovenia. Rome, Italy: International Plant Genetic Resources Institute; 2004:96-105.
15. Foreign Trade Chamber of Bosnia and Herzegovina. Catalogue: Medicinal & Aromatic Plants | Mushrooms | Forest Fruits | Honey. Sarajevo: USAID/Sida FARMA; 2014.
16. Albinspekt. Organic Certificate: Annex C - Processed products - Agroproduct shpk - List of certified products. 2017. Available at: http://albinspekt.com/site.OLD/wp-content/uploads/2017/01/Annex-C_List-of-products-AP-170124.pdf. Accessed April 18, 2017.
17. Zivanovic ST, Stevanetic S, Ceranic S, Zivanovic T. Trends in production of raw medicinal and aromatic plants in Serbia. Paper presented at: Fifth International Scientific Agricultural Symposium “Agrosym 2014” - Jahorina, Bosnia and Herzegovina, October 23-26, 2014.
18. Kainz W. Medicinal and aromatic plants in Austria – status 2007. In: Lipman E, ed. Report of a Working Group on Medicinal and Aromatic Plants. Second Meeting, 16‑18 December 2004, Strumica, Macedonia FYR / Third Meeting, 26–28 June 2007, Olomouc, Czech Republic. Rome, Italy: Bioversity International; 2009:45-58.
19. Délégation nationale de FranceAgriMer Volx. Données et bilans: Filières plantes à parfum, aromatiques et médicinales Panorama 2015 / direction Marchés, études et prospective. Montreuil cedex: FranceAgriMer; 2016.
20. Organic Herb Trading Company. Online Price List. Available at: www.organicherbtrading.com/. Accessed April 18, 2017.
21. FLO-CERT GmbH Fairtrade customer search. Available at: www.flocert.net/fairtrade-services/fairtrade-certification/fairtrade-customer-search/. Accessed April 16, 2017.
22. Organic INTEGRITY Database. USDA, Agricultural Marketing Service; 2017. Available at: https://organic.ams.usda.gov/Integrity/. Accessed April 16, 2017.
23. Linnæi C. Genera plantarum :eorumque characteres naturales secundum numerum, figuram, situm, & proportionem omnium fructificationis partium. Batavorum Lugdunum [Leiden]: Conradum Wishoff; 1737.
24. European Pharmacopoeia Commission. European Pharmacopoeia Ninth Edition (PhEur 9.0). Strasbourg, France: European Directorate for the Quality of Medicines; 2016.
25. Šoštarić R, Kovačić D, Ćaleta M, Alegro A, Mitić B. The Croatian Apoxyomenos as a luxurious rodent nest: archaeobotanical and zoological analyses of organic material found inside the classical bronze statue. Vegetation History and Archaeobotany. 2007;17(3):289-295.
26. Teuscher E. Medicinal Spices: A Handbook of Culinary Herbs, Spices, Spice MIxtures and their Essential Oils. Stuttgart: Medpharm Scientific Publishers; 2006.
27. Heckelmann H. Maria Clementine Martin (1775-1843) Ordensfrau, “Quacksalberin,” Unternehmerin. Eine rechtshistorische Untersuchung aus neuen Quellen, Universität Regensburg; 2014.
28. Kartnig T, Piendl S. Arzneipflanzen und Arzneidrogen in der Klostermedizin in Kärnten einst und jetzt. Carinthia II, Klagenfurt. 2004;194(114):83–95.
29. Fuchs L. New Kreüterbuch / in welchem nit allein die gantz histori / das ist / namen / gestalt/ statt und Zeit der wachsung / natur / krafft un würkung / des meysten theyls der Kreuter so in Teutschen unnd andern Landen wachsen / mit dem besten vleiß beschrieben. Basel, Switzerland: Michael Isingrin; 1543.
30. Favero C, Favero G. The Discalced Carmelites in Venice - The Church of Santa Maria di Nazareth and the Monastery Garden. BIBLOS EDIZIONI, Cittadella (Pd), Italy; 2015.
31. Gönnheimer S. Schätze aus der Schulstiftung der Erzdiözese – Das Elexier der Karmeliterinnen. FORUM Schulstiftung. 2006;45:106-109.
32. 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 Monographs — Therapeutic Guide to Herbal Medicines. Austin, TX: American Botanical Council; Boston: Integrative Medicine Communication; 1998.
33. ESCOP. Melissae folium. Monographs on the Medicinal Uses of Plant Drugs. Exeter, UK: European Scientific Cooperative on Phytotherapy; 1997.
34. European Pharmacopoeia Commission. Europäisches Arzneibuch Nachtrag 2000. Stuttgart/Eschborn: Deutscher Apotheker Verlag/Govi-Verlag - Pharmazeutischer Verlag GmbH; 2000.
35. World Health Organization. WHO Monographs on Selected Medicinal Plants, Volume 2. Geneva: World Health Organization; 2002.
36. World Health Organization. WHO Monographs on Medicinal Plants Commonly Used in the Newly Independent States (NIS). Geneva, Switzerland: World Health Organization; 2010.
37. Committee on Herbal Medicinal Products (HMPC). Community herbal monograph on Melissa officinalis L., folium. London, UK: European Medicines Agency; 2013.
38. Deutsches Institut für Medizinische Dokumentation und Information (DIMDI). Gebrauchsinformation: Klosterfrau Melissengeist. In: PharmNet.Bund. Arzneimittel-Informationssystem. 2005; Available at: www.pharmnet-bund.de/dynamic/de/arzneimittel-informationssystem/index.html. Accessed April 16, 2017.
39. US Food and Drug Administration (FDA). § 182.10 Spices and other natural seasonings and flavorings. Code of Federal Regulations, Title 21 (21 CFR). Washington, DC: US Government Printing Office; 2016:474-475.
40. US Food and Drug Administration. § 182.20 Essential oils, oleoresins (solvent-free), and natural extractives (including distillates). In: Code of Federal Regulations (21 CFR). Washington, DC: US Government Printing Office; 2016.
41. 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.
42. Cosmetic Ingredients and Substances (CosIng®) Database. European Commission; 2017. Available at: http://ec.europa.eu/growth/tools-databases/cosing/. Accessed April 16, 2017.
43. Herodež ŠS Hadolin M, Škerget M, Knez Ž. Solvent extraction study of antioxidants from balm (Melissa officinalis L.) leaves. Food Chem. 2003;80:275-282.
44. Jandaghi P, Noroozi M, Ardalani H, Alipour M. Lemon balm: A promising herbal therapy for patients with borderline hyperlipidemia–A randomized double-blind placebo-controlled clinical trial. Complement Ther Med. 2016;26:136-140.
45. Heinrich M, Barnes J, Gibbons S, Williamson EM. Fundamentals of Pharmacognosy and Phytotherapy. London, UK: Elsevier; 2012.
46. Birdane YO Büyükokuroglu M, Birdane FM, Cemek M, Yavuz H. Anti-inflammatory and antinociceptive effects of Melissa officinalis L. in rodents. Revue Med Vet. 2007;158(2):75-81.
47. Pourghanbari G, Nili H, Moattari A, Mohammadi A, Iraji A. Antiviral activity of the oseltamivir and Melissa officinalis L. essential oil against avian influenza A virus (H9N2). Virusdisease. 2016;27(2):170-178.
48. Astani A, Navid MH, Schnitzler P. Attachment and penetration of acyclovir-resistant herpes simplex virus are inhibited by Melissa officinalis extract. Phytother Res. 2014;28(10):1547-1552.
49. Astani A, Reichling J, Schnitzler P. Melissa officinalis extract inhibits attachment of herpes simplex virus in vitro. Chemotherapy. 2012;58(1):70-77.
50. Schnitzler P, Schuhmacher A, Astani A, Reichling J. Melissa officinalis oil affects infectivity of enveloped herpesviruses. Phytomedicine. 2008;15(9):734-740.
51. Mazzanti G, Battinelli L, Pompeo C, et al. Inhibitory activity of Melissa officinalis L. extract on Herpes simplex virus type 2 replication. Nat Prod Res. 2008;22(16):1433-1440.
52. Nolkemper S, Reichling J, Stintzing FC, Carle R, Schnitzler P. Antiviral effect of aqueous extracts from species of the Lamiaceae family against Herpes simplex virus type 1 and type 2 in vitro. Planta Med. 2006;72(15):1378-1382.
53. Allahverdiyev A, Duran N, Ozguven M, Koltas S. Antiviral activity of the volatile oils of Melissa officinalis L. against Herpes simplex virus type-2. Phytomedicine. 2004;11(7-8):657-661.
54. Čanadanović-Brunet J, Ćetković G, Djilas S, et al. Radical scavenging, antibacterial, and antiproliferative activities of Melissa officinalis L. extracts. Journal of Medicinal Food. 2008;11(1):133-143.
55. Jeziorek M, Wasek M. Free radical scavenging activity for infusions of 30 medicinal plants detected with electron paramagnetic resonance. Herba Polonica. 2008;54(1):7-14.
56. Soulimani R, Fleurentin J, Mortier F, Misslin R, Derrieu G, Pelt JM. Neurotropic action of the hydroalcoholic extract of Melissa officinalis in the mouse. Planta Med. 1991;57(2):105-109.
57. Santini F, Vitti P, Ceccarini G, et al. In vitro assay of thyroid disruptors affecting TSH-stimulated adenylate cyclase activity. J Endocrinol Invest. 2003;26(10):950-955.
58. Chung MJ, Cho SY, Bhuiyan MJ, Kim KH, Lee SJ. Anti-diabetic effects of lemon balm (Melissa officinalis) essential oil on glucose- and lipid-regulating enzymes in type 2 diabetic mice. Br J Nutr. 2010;104(2):180-188.
59. Cassettari de Carvalho N, Corrêa-Angeloni MJF, Leffa DD, Moreira J, et al. Evaluation of the genotoxic and antigenotoxic potential of Melissa officinalis in mice. Genetics and Molecular Biology. 2011;34(2):290-297.
60. Drozd J, Anuszewska E. The effect of the Melissa officinalis extract on immune response in mice. Acta Pol Pharm. 2003;60(6):467-470.
61. Hariry RE. Anticonvulsant effects of hydroalcoholic extract of Melissa officinalis on pentylenetetrazole (PTZ) model of convulsion in mice. J Med Plant Research. 2011;5(16):3803-3809.
62. Gorgich E, Komeili G, Zakeri Z, Ebrahimi S. Comparing anticonvulsive effect of Melissa officinalis hydro-alcohlic extract and phenytoin in rat. Journal of Health Scope. 2012;1(1):44-48.
63. Dressing H, Köhler S, Müller WE. Improvement of sleep quality with a high-dose valerian/lemon balm preparation: a placebo-controlled double-blind study. Psychopharmakotherapie. 1996;3:123-130.
64. Müller SF, Klement S. A combination of valerian and lemon balm is effective in the treatment of restlessness and dyssomnia in children. Phytomedicine. 2006;13(6):383-387.
65. Dimpfel W, Pischel I, Lehnfeld R. Effects of lozenge containing lavender oil, extracts from hops, lemon balm and oat on electrical brain activity of volunteers. Eur J Med Res. 2004;9(9):423-431.
66. Savino F, Cresi F, Castagno E, Silvestro L, Oggero R. A randomized double-blind placebo-controlled trial of a standardized extract of Matricariae recutita, Foeniculum vulgare and Melissa officinalis (ColiMil) in the treatment of breastfed colicky infants. Phytother Res. 2005;19(4):335-340.
67. Rashidi M, Malekirad AA, Abdollahi M, Habibollahi S, Dolatyari N, Narimani M. The effect of tea-cinnamon and Melissa officinalis L. aqueous extraction, on neuropsychology distress, biochemical and oxidative stress biomarkers in glass production workers. Health. 2014;6:2592-2601.
68. Kennedy DO, Little W, Haskell CF, Scholey AB. Anxiolytic effects of a combination of Melissa officinalis and Valeriana officinalis during laboratory induced stress. Phytother Res. 2006;20(2):96-102.
69. Rösch W, Liebregts T, Gundermann KJ, Vinson B, Holtmann G. Phytotherapy for functional dyspepsia: a review of the clinical evidence for the herbal preparation STW 5. Phytomedicine. 2006;13 Suppl 5:114-121.
70. Vejdani R, Shalmani HR, Mir-Fattahi M, et al. The efficacy of an herbal medicine, Carmint, on the relief of abdominal pain and bloating in patients with irritable bowel syndrome: a pilot study. Dig Dis Sci. 2006;51(8):1501-1507.
71. Alijaniha F, Naseri M, Afsharypuor S, et al. Heart palpitation relief with Melissa officinalis leaf extract: double blind, randomized, placebo controlled trial of efficacy and safety. Journal of Ethnopharmacology. 2015;164:378-384.
72. Akbarzadeh M, Dehghani M, Moshfeghy Z, Emamghoreishi M, Tavakoli P, Zare N. Effect of Melissa officinalis capsule on the intensity of premenstrual syndrome symptoms in high school girl students. Nurs Midwifery Stud. 2015;4(2):e27001.
73. Faranak SD, Parvin N. The effect of mefenamic acid and Melissa officinalis on primary dysmenorrhea: a randomized clinical trial study. International Journal of Pharmacognosy and Phytochemical Research. 2016;8(8):1286-1292.
74. Akhondzadeh S, Noroozian M, Mohammadi M, Ohadinia S, Jamshidi AH, Khani M. Melissa officinalis extract in the treatment of patients with mild to moderate Alzheimer’s disease: a double blind, randomised, placebo controlled trial. J Neurol Neurosurg Psychiatry. 2003;74(7):863-866.
75. Ballard CG, O’Brien JT, Reichelt K, Perry EK. Aromatherapy as a safe and effective treatment for the management of agitation in severe dementia: the results of a double-blind, placebo-controlled trial with Melissa. J Clin Psychiatry. 2002;63(7):553-558.
76. Sandev D, Mihelj D, Kovačić S. Meeting Target Eight – Ex situ conservation of Croatian threatened and statutorily protected plant species in the Botanical Garden of the Faculty of Science, University of Zagreb (Croatia). Natura Croatica. 2013;22(2):343–362.
77. Allen D, Bilz M, Leaman DJ, Miller RM, Timoshyna A, Window J. European Red List of Medicinal Plants. Luxembourg: Publications Office of the European Union; 2014.
78. Ghaffariyan S, Mohammadi SA, Aharizad S. DNA isolation protocol for the medicinal plant lemon balm (Melissa officinalis, Lamiaceae). Genet Mol Res. 2012;11(2):1049-1057.
79. Abrahamyan A. Changes in distribution and structure of wild Melissa officinalis L. populations during the last decade in Armenia and implications for conservation. Environment. Technology. Resources. Proceedings of the 8th International Scientific and Practical Conference. 2011;2:321-324.
80. Abrahamyan A, Barsevskis A, Melikyan A. Populations dynamics in sizes of wild Melissa officinalis L. (Lamiaceae) during the last decade in Armenia. Journal of Medicinal Plants Studies. 2015;3(1):21-26.
81. Abrahamyan A, Teilans A, Zorins A. Climate change impact on conservation status of wild Melissa officinalis L. (Lamiaceae) populations in Armenia. Paper presented at: First International Symposium on Medicinal, Aromatic and Nutraceutical Plants from Mountainous Areas (MAP-Mountain 2011), 6th – 9th July 2011, Saas-Fee, Switzerland.
82. Kästner U, Krüger H, Krähmer A, et al. Züchterische Bearbeitung von Melisse (Melissa officinalis). Paper presented at: 26. Bernburger Winterseminar Arznei- und Gewürzpflanzen - February 23-24, 2016; Bernburg.
83. Evstatieva L, Hardalova R, Stoyanova R. Medicinal plants in Bulgaria: diversity, legislation, conservation and trade. Phytologia Balcanica. 2007;13(3):415-427.
84. Boshnakova M. GAIN Report Number: BU1653. Bulgaria Organic Sector and Trade Update. Sofia: USDA Foreign Agricultural Service; 2016.
85. Non-food Group Department of Agricultural Chemical Technology Budapest University of Technology and Economics. Report from the Republic of Hungary. Budapest, Hungary: Interactive European Network for Industrial Crops and their Applications; 2002 (with updates in January 2004).