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Cinnamon (Cinnamomum Species)
Cinnamon (Cinnamomum Species) Donald G. Barceloux, MD History Cinnamon has been used as a spice for thousands of years; several references to it are found in the Bible. In Egypt, cinnamon was a spice used in embalming fluid. In Ayurvedic medicine, cinnamon bark was used as an antiemetic, antidiarrheal, antiflatulent, and general stimulant. The Portuguese found cinnamon trees growing in Sri Lanka (Ceylon) during the early 16th century; they subsequently imported cinnamon to Europe during the 16th and 17th centuries. The Dutch occupied Sri Lanka in the mid-17th century until the British captured the island in 1796. The East India Company then became the main exporter of cinnamon to Europe. The Dutch cultivated cinnamon in Java, and the exports of Ceylon cinnamon decreased as a result of heavy export duties. Nevertheless, Sri Lanka is the only regular supplier of cinnamon bark and leaf oils. The food industry prefers Ceylon cinnamon, but pharmaceutical manufacturers use both oils from Ceylon cinnamon (cinnamon oil) and from Chinese cinnamon (cassia oil) interchangeably. China is the main exporter of cassia oil.
Botanical Description The genus Cinnamomum comprises over 250 aromatic evergreen trees and shrubs, primarily located in Asia and Australia. Common Name: Cinnamon, Ceylon cinnamon Scientific Name: Cinnamomum verum J. Presl (Cinnamomum zeylanicum Blume, Laurus cinnamomum L.) Botanical Family: Lauraceae (laurel family) Physical Description: Large evergreen trees with young branches that are smooth and brown. The leaves are opposite, leathery, ovate to broadly ovate with three (and rarely, five) prominent veins. Young leaves are This article was published in: Barceloux DG. Medical Toxicology of Natural Substances: Foods, Fungi, Medicinal Herbs, Toxic Plants, and Venomous Animals. Hoboken, NJ: John Wiley & Sons, 2008. pp. 39-43. Copyright © 2008 by John Wiley & Sons, Inc. Reprinted with permission of John Wiley & Sons, Inc. Dis Mon 2009;55:327-335 0011-5029/2009 $36.00 ⫹ 0 doi:10.1016/j.disamonth.2009.03.003 DM, June 2009
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reddish and later turn dark green. Small, pale yellow flowers are borne in axillary or terminal panicles. The fruit is a fleshy, ovoid drupe, which contains one seed and turns dark purple or black when ripe. Distribution and Ecology: Ceylon cinnamon is an indigenous tree of Sri Lanka and southwestern India. Common Name: Cassia, Chinese cinnamon, false cinnamon, cassia lignea, bastard cinnamon, cassia bark, cassia-bark tree, Chinese cassia, Saigon cinnamon Scientific Name: Cinnamomum aromaticum Nees (Cinnamomum cassia Nees ex Blume, Cinnamomum cassia J. Presl) Botanical Family: Lauraceae (laurel family) Physical Description: This slender, evergreen tree grows up to 65 ft (20 meters) high. Young branches are smooth and brown. The leaves are subopposite, slender, lanceolate or oblanceolate with three prominent veins. These leaves are reddish when young and dark green when mature. The small, white flowers are borne in axillary or terminal panicles. The fruit is a green, fleshy, globose drupe, which contains one seed and turns dark purple or black when mature. This fruit is similar in size to a small olive. Distribution and Ecology: Chinese cinnamon is an indigenous bush in the mountains of southern China, and cultivation for cassia oil production now occurs primarily in the southern Chinese provinces of Guangxi (Kwangsi) and Guangdong (Kwangtung). Other similar species occur on the Indonesian islands of Sumatra and Java [C. burmannii (Nees & T. Nees) Blume, Indonesia cassia], in Vietnam (C. loureiroi Nees, Vietnamese cassia), and in India and Nepal [C. tamala (Buch.-Ham.) Nees & Eberm., Indian cassia]. Commercial cultivation of these cassia species occurs in all of these areas.
Exposure Sources Cinnamon leaf and bark are spices and sources of cinnamon oil, primarily from the Cinnamomum verum J. Presl (Ceylon cinnamon). However, most of products are extracted from cinnamon trees cultivated at altitudes up to about 1500 ft (460 meters). Cortex cinnamomi is the dried inner bark of shoots from Cinnamomum verum J. Presl or the stripped trunk bark of Cinnamomum cassia Blume. Cinnamomum aromaticum Nees (Chinese cinnamon) is the main source of internationally traded cassia oil, which is a distillate from a mixture of leaves, twigs, and bark fragments. Limited commercial production of cassia oil occurs in 328
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other regions including Indonesia [C. burmannii (Nees & T. Nees) Blume], Vietnam (Cinnamomum loureiroi Nees), and India [C. tamala (Buch.-Ham.) Nees & Eberm.]. Commercial production of cinnamon usually begins about 3-4 years after planting and pruning of the stems to force the growth of young stems. These stems are cut during the rainy season to facilitate the peeling of the bark. After scraping the outer skin of the bark, workers rub off the bark with a brass block. The bark is then split from end to end with a special round knife. The long strips of bark are then formed into the familiar compound quills (cinnamon) or hollow quills (cassia) of the spices that are stuffed with fragments of bark and then dried. Bleaching with sulfur dioxide disinfects the material and imparts a golden hue to the quills.
Uses Traditional. The herbal use of cinnamon includes application as an astringent, germicide, and antispasmodic. Cinnamon was one of the early treatments for chronic bronchitis.1 Other traditional uses include the treatment of impotence, frigidity, dyspnea, inflammation of the eye, leukorrhea, vaginitis, rheumatism, and neuralgia, as well as wounds and toothaches.2 Current. Cinnamon bark oil has a delicate aroma along with a sweet, pungent taste that results in use primarily as a flavoring in dental and pharmaceutical preparations, seasonings, sauces, baked goods, drinks, and tobacco. Investigational uses of cinnamon bark include use as a hypoglycemic and cholesterol lowering agent,3 promotion of wound healing,4 antimicrobial agent,5 and an antiinflammatory compound.6 The flavoring agent cinnamaldehyde in cinnamon oil is added to toothpaste to mask the taste of pyrophosphate, which is an unpleasant tasting compound that inhibits plaque calcification by interrupting the conversion of amorphous calcium phosphate to hydroxyapatite. The skin sensitizing properties of cinnamon bark oil limits use of this essential oil in cosmetic and other topical products.7 Cinnamon leaf oil has a warm, spicy, and somewhat harsh odor that lacks the smooth consistency of cinnamon bark oil. Major uses of this essential oil include as flavoring in seasonings and a fragrance in soaps and insecticides. Cinnamon leaf oil is also a source for eugenol. Cassia oil is used medicinally as a carminative, antidiarrheal, antimicrobial, and antiemetic. Traditional uses for dried cassia include digestive complaints such as flatulence, colic, dyspepsia, diarrhea, and nausea, as well as colds, influenza, fevers, arthritis, and rheumatism. The major commercial uses of cassia oil are the flavoring of cola-type drinks DM, June 2009
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FIG 1. Chemical structure of cinnamaldehyde.
and, to a lesser extent, bakery goods, sauces, confectionery products, and liquors. Like cinnamon bark oil, the use of cassia oil in topical preparations is limited by its skin-sensitizing properties. Cassia oil is a constituent of tiger balm. Smoking cessation products frequently involve the use of candies, chewing gum, or fresheners that often contain cinnamon flavoring. A few clinical studies suggest that cinnamon supplementation may lower blood glucose concentrations in patients with diabetes type 2; however, the sample sizes of these studies were small and there are inadequate data to recommend the regular use of cinnamon in diabetic patients.8 Regulatory Status. In the United States, cinnamon has GRAS (generally recognized as safe) status as a food additive.
Principal Toxins Chemical Composition Volatile oils are distilled products from the bark, leaves, flowers, or buds of Cinnamomum species, and the chemical composition of these oils varies depending on the part of the plant used for the distillation process. Cinnamon bark and leaf oil are steam distillation products obtained from the inner bark and leaves, respectively, of Ceylon cinnamon (Cinnamomum verum).9 Other sources of cinnamon include Japanese cinnamon, Java cinnamon, and Taiwan cinnamon. Most of the chemical constituents of the essential oils from cinnamon are monoterpenes, sesquiterpenes, and related oxygen derivatives of these two types of compounds. The major monoterpene hydrocarbons in volatile components of cinnamon extracts are ␣-pinene, camphene, and limonene.10 The main constituent of cinnamon bark oil is cinnamaldehyde (Fig 1), whereas eugenol is the main constituent (ie, about 81-85%) of cinnamon leaf oil.11 A commercial sample of essential oils from Cinnamomum verum contained approximately 63% cinnamaldehyde, 8% limonene, 7% eugenol, 5.5% cinnamaldehyde propylene, and ⬍1-2% of a variety of terpenoid compounds (␣-pinene, camphene) as measured by gas chromatography/mass spectrometry.5 Cinnamon leaf oil 330
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TABlE 1. Some physical properties of cinnamaldehyde Physical Property
Value
Melting point Boiling point log P (octanol-water) Water solubility Henry’s Law Constant Atmospheric OH rate constant
⬃7.50°C 246°C 1.9 1420 mg/L (25°C) 1.60 E-06 atm m3/mole (25°C) 3.79 E-11 cm3 molecule/sec (25°C)
contains a variety of constituents including eugenol (CAS RN: 97-53-0, C10H12O2) and cinnamaldehyde (CAS RN: 104-55-2, C9H8O), which is a local mucous and dermal membrane irritant. In a study of the essential oils from leaves of Cinnamomum osmophloeum (Taiwan cinnamon), terpenoid compounds accounted for approximately 90% of the chemical compounds with 1,8-cineole, spathulenol, santolina triene, and caryophyllene oxide being the most common compounds.6 The essential oils from leaves of Cinnamomum species accounts for about 0.5% dry weight. Analysis of a steam-distilled volatile oil from cinnamon fruit stalks yielded 27 compounds with cinnamyl acetate (36.59%) and caryophyllene (22.36%) being the major components.12 Analysis of the hydro-distilled volatile oil from buds of Cinnamomum verum (C. zeylanicum) yielded terpene hydrocarbons (78%) and oxygenated terpenoids (9%) with the sesquiterpenes, ␣-bergamotene (27%) and ␣-copaene (23%), being the most common compounds.13 Minor compounds included ␣-humulene, ␣-muurolene, and ␦-cadinenes. The volatile oil of the buds contains more monoterpene and sesquiterpene compounds than oils from the flowers and fruits, whereas the concentration of trans-cinnamyl acetate is much higher in the volatile oils from flowers and fruit than from the buds. A study of cinnamon essential oil from C. verum grown in Madagascar indicated that the major constituent was trans-cinnamaldehyde (41.3%).14 Cassia oil is extracted from the leaves, bark, twigs, and stalks of C. cassia by steam distillation.
Physicochemical Properties Cinnamon leaf oil has a fragrant odor and a very pungent taste. Experimental studies suggest that cinnamon has some mosquito larvicidal activity15 and some antibacterial properties when added to certain food products.16 However, there is no conclusive evidence that the antimicrobial properties of cinnamon produce clinically efficacious results.17 Table 1 lists some of the physical properties of cinnamaldehyde. DM, June 2009
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Dose Response Medicinal Use. The average daily dose of the crude drug (cortex cinnamomi) is 2-4 g or 0.05-0.2 g of the essential oil. Toxicity. The ingestion of an estimated 60 mL of cinnamon oil was associated with burning sensation in the gastrointestinal tract along with lethargy, double vision, vomiting, and lightheadedness.18 The symptoms resolved spontaneously within 5 hours with no complications.
Toxicokinetics There are few human toxicokinetic data for the constituents in cinnamon oil. Rodent studies indicate that the major metabolic pathway of o-methoxycinnamaldehyde involves oxidation to the corresponding cinnamic and phenylpropionic acids with subsequent urinary excretion of benzoic and hippuric acids.19
Clinical Response Most case reports of toxicity from cinnamon oil involve local irritation and allergic reactions to cinnamon oil as a constituent of personal hygiene (toilet soaps, mouthwash, toothpaste, perfumes, mud baths),20 beverages (colas, vermouth, bitters), or baking products.21-23 Allergic reactions include contact dermatitis, perioral dermatitis, cheilitis, stomatitis, gingivitis, glossitis, chronic lichenoid mucositis, contact urticaria,24 and rarely immediate hypersensitivity reactions (asthma, urticaria).25,26 Clinical manifestations of intraoral reactions include pain, swelling, erythema, ulcerations, fissures, vesicles, and white patches.27 These reactions are local, and distal skin involvement is rare.28 Occupational allergic contact dermatitis from spices is rare, and typically involves the hands.29 More common food sensitizers include carrot, cucumber, tomato, melon, fish, potato, orange, green pepper, onion, red cherry, and garlic. Cinnamon oil contains local mucous membrane irritants such as cinnamaldehyde and cinnamic acid. Prolonged skin contact (48 hours) from a cinnamon oil spill produced superficial partial-thickness burns.30 Chronic use of cinnamonflavored gum can produce submucosal inflammation and alteration of the surface epidermis resembling oral leukoplakia, manifest on biopsy by acanthosis, hyperkeratosis, parakeratosis, plasma cell infiltration, fibrosis of the lamina, and focal atypia.31 These changes are not pathognomonic for cinnamon-induced mucositis. The differential diagnosis of chronic mucositis associated with hypersensitivity to cinnamon includes local trauma, smokeless tobacco keratosis (snuff dipper’s lesion), hyperkeratosis, lichen planus, lupus erythematosus, candidiasis, premalignant lesions, lichenoid mucositis, and carcinoma. 332
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The severity of the local mucosal reaction depends on the duration of cinnamon-gum chewing. In contrast to the diffuse gingival reaction associated with cinnamon-flavored toothpaste, oral lesions associated with gum chewing occur on the lateral border of the free tongue or adjacent buccal mucosa. Sequelae of contact dermatitis associated with cinnamon include desquamation and hyperpigmentation.32 Although a case report associated the development of squamous cell carcinoma of the tongue with prolonged use of cinnamon gum,33 the International Agency for Research on Cancer (IARC) and the US National Toxicology Program do not list cinnamon as a potential carcinogen. School-aged children abuse cinnamon oil by sucking on toothpicks or fingers dipped in the oil.34 Reported effects include facial flushing, sensation of warmth, and intraoral hyperesthesias. Although nausea and abdominal pain may occur, systemic symptoms do not usually result from this type of exposure. Ingestion of cinnamon oil may cause central nervous system depression, predisposing the patient to aspiration pneumonia.
Diagnostic Testing Analytical methods for the identification of the constituents of cinnamon oil include high performance liquid chromatography35 and gas chromatography/mass spectrometry.10,36
Treatment Treatment is supportive. Patients with leukoplakia after chronic use of cinnamon-containing gums should be observed for resolution after cessation of use. Persistent oral lesions should be evaluated for oral cancer.
REFERENCES 1. 2. 3. 4. 5.
Ziment I. History of the treatment of chronic bronchitis. Respiration 1991;58(suppl 1):37-42. World Health Organization. WHO monographs on selected medicinal plants. Vol. 1. Geneva: World Health Organization, 1999. Khan A, Khattak KN, Safdar M, et al. Cinnamon improves glucose and lipids of people with type 2 diabetes. Diabetes Care 2003;26:3215-8. Kamath JV, Rana AC, Chowdhury AR. Pro-healing effect of Cinnamomum zeylanicum bark. Phytother Res 2003;17:970-2. Simic A, Sokovic MD, Ristic M, et al. The chemical composition of some Lauraceae essential oils and their antifungal activities. Phytother Res 2004;18: 713-7.
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Chao LK, Hua K-F, Hsu H-Y, et al. Study on the antiinflammatory activity of essential oil from leaves of Cinnamomum osmophloeum. J Agric Food Chem 2005;53:7274-8. Hartmann K, Hunzelmann N. Allergic contact dermatitis from cinnamon as an odour-neutralizing agent in shoe insoles. Contact Dermatitis 2004;50:253-4. Pham AQ, Kourlas H, Pham DQ. Cinnamon supplementation in patients with type 2 diabetes mellitus. Pharmacotherapy 2007;27:595-9. Mino Y, Ota N. Inorganic chemical approaches to pharmacognosy. V. X-ray fluorescence spectrometric studies on the inorganic constituents of crude drugs. (3). On the cinnamoni cortex. Chem Pharm Bull (Tokyo) 1990;38:709-13. Miyazawa M, Hashimoto Y, Taniguchi Y, et al. Headspace constituents of the tree remain of Cinnamomum camphora. Nat Prod Lett 2001;15:63-9. Mallavarapu GR, Ramesh S, Chandrasekhara RS, et al. Investigation of the essential oil of cinnamon leaf grown at Bangalore and Hyderabad. Flavour Fragrance J 1995;10:239-42. Jayaprakasha GK, Rao LJ, Sakariah KK. Volatile constituents from Cinnamomum zeylanicum fruit stalks and their antioxidant activities. J Agric Food Chem 2003;51:4344-8. Jayaprakasha GK, Rao LJ, Sakariah KK. Chemical composition of volatile oil from Cinnamomum zeylanicum buds. Z Naturforsch 2003;57:990-3. Mollenbeck S, Konig T, Schreier P, et al. Chemical composition and analysis of enantiomers of essential oils from Madagascar. Flavour Fragrance J 1997;12:63-9. Cheng SS, Liu JY, Tsai KH, et al. Chemical composition and mosquito larvicidal activity of essential oils from leaves of different Cinnamomum osmophloeum provenances. J Agric Food Chem 2004;52:4395-400. Yuste J, Fung DY. Inactivation of Salmonella typhimurium and Escherichia coli O157:H7 in apple juice by a combination of nisin and cinnamon. J Food Prot 2004;67:371-7. Martin KW, Ernst E. Herbal medicines for treatment of bacterial infections: a review of controlled clinical trials. J Antimicrob Chemother 2003;51:241-6. Pilapil VR. Toxic manifestations of cinnamon oil ingestion in a child. Clin Pediatr 1989;28:276. Samuelsen OB, Brenna J, Solheim E, et al. Metabolism of the cinnamon constituent o-methoxycinnamaldehyde in the rat. Xenobiotica 1986;16:845-52. Garcia-Abujeta JL, de Larramendi CH, Berna JP, et al. Mud bath dermatitis due to cinnamon oil. Contact Dermatitis 2005;52:234. Calnan CD. Cinnamon dermatitis from an ointment. Contact Dermatitis 1976;2: 167-70. Sainio EL, Kanerva L. Contact allergens in toothpastes and a review of their hypersensitivity. Contact Dermatitis 1995;33:100-5. Nixon R. Cinnamon allergy in a baker. Australas J Dermatol 1995;36:4. Kirton V. Contact urticaria and cinnamic aldehyde. Contact Dermatitis 1978;4: 374-5. Lamey PJ, Lewis MA, Rees TD, et al. Sensitivity reaction to the cinnamonaldehyde component of toothpaste. Br Dent J 1990;168:115-8. Uragoda CG. Asthma and other symptoms in cinnamon workers. Br J Ind Med 1984;41:224-7. DM, June 2009
27. 28. 29. 30. 31. 32. 33.
34. 35. 36.
Jacob SE, Steele T. Tongue erosions and diet cola. Ear Nose Throat J 2007;86: 232-3. Drake TE, Maibach HI. Allergic contact dermatitis and stomatitis caused by a cinnamic aldehyde-flavored toothpaste. Arch Dermatol 1976;112:202-3. Kanerva L, Estlander T, Jolanki R. Occupational allergic contact dermatitis from spices. Contact Dermatitis 1996;35:157-62. Sparks T. Cinnamon oil burn. West J Med 1985;142:835. Mihail RC. Oral leukoplakia caused by cinnamon food allergy. J Otolaryngol 1992;21:366-7. Garcia-Abujeta JL, de Larramendi CH, Berna JP, et al. Mud bath dermatitis due to cinnamon oil. Contact Dermatitis 2005;52:234. Westra WH, McMurray JS, Califano J, et al. Squamous cell carcinoma of the tongue associated with cinnamon gum use: a case report. Head Neck 1998;20: 430-3. Perry PA, Dean BS, Krenzelok EP. Cinnamon oil abuse by adolescents. Vet Hum Toxicol 1990;32:162-4. Sagara K, Oshima T, Yoshida T, et al. Determination of Cinnamomi cortex by high-performance liquid chromatography. J Chromatogr 1987;409:365-70. Jayaprakasha GK, Jagan Mohan Rao L, Sakariah KK. Chemical composition of the flower oil of Cinnamomum zeylanicum Blume. J Agric Food Chem 2000;48: 4294-5.
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Botanical Description The genus Cinnamomum comprises over 250 aromatic evergreen trees and shrubs, primarily located in Asia and Australia. Common Name: Cinnamon, Ceylon cinnamon Scientific Name: Cinnamomum verum J. Presl (Cinnamomum zeylanicum Blume, Laurus cinnamomum L.) Botanical Family: Lauraceae (laurel family) Physical Description: Large evergreen trees with young branches that are smooth and brown. The leaves are opposite, leathery, ovate to broadly ovate with three (and rarely, five) prominent veins. Young leaves are This article was published in: Barceloux DG. Medical Toxicology of Natural Substances: Foods, Fungi, Medicinal Herbs, Toxic Plants, and Venomous Animals. Hoboken, NJ: John Wiley & Sons, 2008. pp. 39-43. Copyright © 2008 by John Wiley & Sons, Inc. Reprinted with permission of John Wiley & Sons, Inc. Dis Mon 2009;55:327-335 0011-5029/2009 $36.00 ⫹ 0 doi:10.1016/j.disamonth.2009.03.003 DM, June 2009
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reddish and later turn dark green. Small, pale yellow flowers are borne in axillary or terminal panicles. The fruit is a fleshy, ovoid drupe, which contains one seed and turns dark purple or black when ripe. Distribution and Ecology: Ceylon cinnamon is an indigenous tree of Sri Lanka and southwestern India. Common Name: Cassia, Chinese cinnamon, false cinnamon, cassia lignea, bastard cinnamon, cassia bark, cassia-bark tree, Chinese cassia, Saigon cinnamon Scientific Name: Cinnamomum aromaticum Nees (Cinnamomum cassia Nees ex Blume, Cinnamomum cassia J. Presl) Botanical Family: Lauraceae (laurel family) Physical Description: This slender, evergreen tree grows up to 65 ft (20 meters) high. Young branches are smooth and brown. The leaves are subopposite, slender, lanceolate or oblanceolate with three prominent veins. These leaves are reddish when young and dark green when mature. The small, white flowers are borne in axillary or terminal panicles. The fruit is a green, fleshy, globose drupe, which contains one seed and turns dark purple or black when mature. This fruit is similar in size to a small olive. Distribution and Ecology: Chinese cinnamon is an indigenous bush in the mountains of southern China, and cultivation for cassia oil production now occurs primarily in the southern Chinese provinces of Guangxi (Kwangsi) and Guangdong (Kwangtung). Other similar species occur on the Indonesian islands of Sumatra and Java [C. burmannii (Nees & T. Nees) Blume, Indonesia cassia], in Vietnam (C. loureiroi Nees, Vietnamese cassia), and in India and Nepal [C. tamala (Buch.-Ham.) Nees & Eberm., Indian cassia]. Commercial cultivation of these cassia species occurs in all of these areas.
Exposure Sources Cinnamon leaf and bark are spices and sources of cinnamon oil, primarily from the Cinnamomum verum J. Presl (Ceylon cinnamon). However, most of products are extracted from cinnamon trees cultivated at altitudes up to about 1500 ft (460 meters). Cortex cinnamomi is the dried inner bark of shoots from Cinnamomum verum J. Presl or the stripped trunk bark of Cinnamomum cassia Blume. Cinnamomum aromaticum Nees (Chinese cinnamon) is the main source of internationally traded cassia oil, which is a distillate from a mixture of leaves, twigs, and bark fragments. Limited commercial production of cassia oil occurs in 328
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other regions including Indonesia [C. burmannii (Nees & T. Nees) Blume], Vietnam (Cinnamomum loureiroi Nees), and India [C. tamala (Buch.-Ham.) Nees & Eberm.]. Commercial production of cinnamon usually begins about 3-4 years after planting and pruning of the stems to force the growth of young stems. These stems are cut during the rainy season to facilitate the peeling of the bark. After scraping the outer skin of the bark, workers rub off the bark with a brass block. The bark is then split from end to end with a special round knife. The long strips of bark are then formed into the familiar compound quills (cinnamon) or hollow quills (cassia) of the spices that are stuffed with fragments of bark and then dried. Bleaching with sulfur dioxide disinfects the material and imparts a golden hue to the quills.
Uses Traditional. The herbal use of cinnamon includes application as an astringent, germicide, and antispasmodic. Cinnamon was one of the early treatments for chronic bronchitis.1 Other traditional uses include the treatment of impotence, frigidity, dyspnea, inflammation of the eye, leukorrhea, vaginitis, rheumatism, and neuralgia, as well as wounds and toothaches.2 Current. Cinnamon bark oil has a delicate aroma along with a sweet, pungent taste that results in use primarily as a flavoring in dental and pharmaceutical preparations, seasonings, sauces, baked goods, drinks, and tobacco. Investigational uses of cinnamon bark include use as a hypoglycemic and cholesterol lowering agent,3 promotion of wound healing,4 antimicrobial agent,5 and an antiinflammatory compound.6 The flavoring agent cinnamaldehyde in cinnamon oil is added to toothpaste to mask the taste of pyrophosphate, which is an unpleasant tasting compound that inhibits plaque calcification by interrupting the conversion of amorphous calcium phosphate to hydroxyapatite. The skin sensitizing properties of cinnamon bark oil limits use of this essential oil in cosmetic and other topical products.7 Cinnamon leaf oil has a warm, spicy, and somewhat harsh odor that lacks the smooth consistency of cinnamon bark oil. Major uses of this essential oil include as flavoring in seasonings and a fragrance in soaps and insecticides. Cinnamon leaf oil is also a source for eugenol. Cassia oil is used medicinally as a carminative, antidiarrheal, antimicrobial, and antiemetic. Traditional uses for dried cassia include digestive complaints such as flatulence, colic, dyspepsia, diarrhea, and nausea, as well as colds, influenza, fevers, arthritis, and rheumatism. The major commercial uses of cassia oil are the flavoring of cola-type drinks DM, June 2009
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FIG 1. Chemical structure of cinnamaldehyde.
and, to a lesser extent, bakery goods, sauces, confectionery products, and liquors. Like cinnamon bark oil, the use of cassia oil in topical preparations is limited by its skin-sensitizing properties. Cassia oil is a constituent of tiger balm. Smoking cessation products frequently involve the use of candies, chewing gum, or fresheners that often contain cinnamon flavoring. A few clinical studies suggest that cinnamon supplementation may lower blood glucose concentrations in patients with diabetes type 2; however, the sample sizes of these studies were small and there are inadequate data to recommend the regular use of cinnamon in diabetic patients.8 Regulatory Status. In the United States, cinnamon has GRAS (generally recognized as safe) status as a food additive.
Principal Toxins Chemical Composition Volatile oils are distilled products from the bark, leaves, flowers, or buds of Cinnamomum species, and the chemical composition of these oils varies depending on the part of the plant used for the distillation process. Cinnamon bark and leaf oil are steam distillation products obtained from the inner bark and leaves, respectively, of Ceylon cinnamon (Cinnamomum verum).9 Other sources of cinnamon include Japanese cinnamon, Java cinnamon, and Taiwan cinnamon. Most of the chemical constituents of the essential oils from cinnamon are monoterpenes, sesquiterpenes, and related oxygen derivatives of these two types of compounds. The major monoterpene hydrocarbons in volatile components of cinnamon extracts are ␣-pinene, camphene, and limonene.10 The main constituent of cinnamon bark oil is cinnamaldehyde (Fig 1), whereas eugenol is the main constituent (ie, about 81-85%) of cinnamon leaf oil.11 A commercial sample of essential oils from Cinnamomum verum contained approximately 63% cinnamaldehyde, 8% limonene, 7% eugenol, 5.5% cinnamaldehyde propylene, and ⬍1-2% of a variety of terpenoid compounds (␣-pinene, camphene) as measured by gas chromatography/mass spectrometry.5 Cinnamon leaf oil 330
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TABlE 1. Some physical properties of cinnamaldehyde Physical Property
Value
Melting point Boiling point log P (octanol-water) Water solubility Henry’s Law Constant Atmospheric OH rate constant
⬃7.50°C 246°C 1.9 1420 mg/L (25°C) 1.60 E-06 atm m3/mole (25°C) 3.79 E-11 cm3 molecule/sec (25°C)
contains a variety of constituents including eugenol (CAS RN: 97-53-0, C10H12O2) and cinnamaldehyde (CAS RN: 104-55-2, C9H8O), which is a local mucous and dermal membrane irritant. In a study of the essential oils from leaves of Cinnamomum osmophloeum (Taiwan cinnamon), terpenoid compounds accounted for approximately 90% of the chemical compounds with 1,8-cineole, spathulenol, santolina triene, and caryophyllene oxide being the most common compounds.6 The essential oils from leaves of Cinnamomum species accounts for about 0.5% dry weight. Analysis of a steam-distilled volatile oil from cinnamon fruit stalks yielded 27 compounds with cinnamyl acetate (36.59%) and caryophyllene (22.36%) being the major components.12 Analysis of the hydro-distilled volatile oil from buds of Cinnamomum verum (C. zeylanicum) yielded terpene hydrocarbons (78%) and oxygenated terpenoids (9%) with the sesquiterpenes, ␣-bergamotene (27%) and ␣-copaene (23%), being the most common compounds.13 Minor compounds included ␣-humulene, ␣-muurolene, and ␦-cadinenes. The volatile oil of the buds contains more monoterpene and sesquiterpene compounds than oils from the flowers and fruits, whereas the concentration of trans-cinnamyl acetate is much higher in the volatile oils from flowers and fruit than from the buds. A study of cinnamon essential oil from C. verum grown in Madagascar indicated that the major constituent was trans-cinnamaldehyde (41.3%).14 Cassia oil is extracted from the leaves, bark, twigs, and stalks of C. cassia by steam distillation.
Physicochemical Properties Cinnamon leaf oil has a fragrant odor and a very pungent taste. Experimental studies suggest that cinnamon has some mosquito larvicidal activity15 and some antibacterial properties when added to certain food products.16 However, there is no conclusive evidence that the antimicrobial properties of cinnamon produce clinically efficacious results.17 Table 1 lists some of the physical properties of cinnamaldehyde. DM, June 2009
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Dose Response Medicinal Use. The average daily dose of the crude drug (cortex cinnamomi) is 2-4 g or 0.05-0.2 g of the essential oil. Toxicity. The ingestion of an estimated 60 mL of cinnamon oil was associated with burning sensation in the gastrointestinal tract along with lethargy, double vision, vomiting, and lightheadedness.18 The symptoms resolved spontaneously within 5 hours with no complications.
Toxicokinetics There are few human toxicokinetic data for the constituents in cinnamon oil. Rodent studies indicate that the major metabolic pathway of o-methoxycinnamaldehyde involves oxidation to the corresponding cinnamic and phenylpropionic acids with subsequent urinary excretion of benzoic and hippuric acids.19
Clinical Response Most case reports of toxicity from cinnamon oil involve local irritation and allergic reactions to cinnamon oil as a constituent of personal hygiene (toilet soaps, mouthwash, toothpaste, perfumes, mud baths),20 beverages (colas, vermouth, bitters), or baking products.21-23 Allergic reactions include contact dermatitis, perioral dermatitis, cheilitis, stomatitis, gingivitis, glossitis, chronic lichenoid mucositis, contact urticaria,24 and rarely immediate hypersensitivity reactions (asthma, urticaria).25,26 Clinical manifestations of intraoral reactions include pain, swelling, erythema, ulcerations, fissures, vesicles, and white patches.27 These reactions are local, and distal skin involvement is rare.28 Occupational allergic contact dermatitis from spices is rare, and typically involves the hands.29 More common food sensitizers include carrot, cucumber, tomato, melon, fish, potato, orange, green pepper, onion, red cherry, and garlic. Cinnamon oil contains local mucous membrane irritants such as cinnamaldehyde and cinnamic acid. Prolonged skin contact (48 hours) from a cinnamon oil spill produced superficial partial-thickness burns.30 Chronic use of cinnamonflavored gum can produce submucosal inflammation and alteration of the surface epidermis resembling oral leukoplakia, manifest on biopsy by acanthosis, hyperkeratosis, parakeratosis, plasma cell infiltration, fibrosis of the lamina, and focal atypia.31 These changes are not pathognomonic for cinnamon-induced mucositis. The differential diagnosis of chronic mucositis associated with hypersensitivity to cinnamon includes local trauma, smokeless tobacco keratosis (snuff dipper’s lesion), hyperkeratosis, lichen planus, lupus erythematosus, candidiasis, premalignant lesions, lichenoid mucositis, and carcinoma. 332
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The severity of the local mucosal reaction depends on the duration of cinnamon-gum chewing. In contrast to the diffuse gingival reaction associated with cinnamon-flavored toothpaste, oral lesions associated with gum chewing occur on the lateral border of the free tongue or adjacent buccal mucosa. Sequelae of contact dermatitis associated with cinnamon include desquamation and hyperpigmentation.32 Although a case report associated the development of squamous cell carcinoma of the tongue with prolonged use of cinnamon gum,33 the International Agency for Research on Cancer (IARC) and the US National Toxicology Program do not list cinnamon as a potential carcinogen. School-aged children abuse cinnamon oil by sucking on toothpicks or fingers dipped in the oil.34 Reported effects include facial flushing, sensation of warmth, and intraoral hyperesthesias. Although nausea and abdominal pain may occur, systemic symptoms do not usually result from this type of exposure. Ingestion of cinnamon oil may cause central nervous system depression, predisposing the patient to aspiration pneumonia.
Diagnostic Testing Analytical methods for the identification of the constituents of cinnamon oil include high performance liquid chromatography35 and gas chromatography/mass spectrometry.10,36
Treatment Treatment is supportive. Patients with leukoplakia after chronic use of cinnamon-containing gums should be observed for resolution after cessation of use. Persistent oral lesions should be evaluated for oral cancer.
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