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Cinnamomum Zeylanicum

and Cinnamomum Aromaticum

Marybeth Missenda
Tai Sophia Institute
Compiled October 11, 2011

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SCIENTIFIC NAMES:
Cinnamomum zeylanicum Nees,
Cinnamomum verum J.S. Presl (McGuffin,Kartesz,Leung & Tucker 2000
p39,183),( Teuscher, 2006)
The name Cinnamomum verum J.S. Presl refers to the cultivated varieties of C.
zeylanicum.
Cinnamomum cassia , Cinnamomum aromaticum Nees(McGuffin,Kartesz,Leung &
Tucker 2000 p39,183),

Family: Lauraceae (USDA Plants Database, 2011)

COMMON NAMES:
Cinnamomum zeylanicum:
Ceylon Cinnamon (Osol & Farrar, 1955), (Teuscher, 2006)
Zimt, Ceylon-Zimt, Kaneel, Canellier, Canella de Ceylon. (Teuscher, 2006)
Dalchini, ecorce de cannelier de Ceylon, echter, gujerati-dalchini, kannel, kuei-pi,
kurundu, kulit, kayumanis, obchoei, tamalpatra, wild cinnamon. (Braun&Cohen, 2010)
Tvak (ayurvedic name) ( McGuffin, Kartesz, Leung, Tucker, 2000)
True Cinnamon ( McGuffin, Kartesz, Leung, Tucker, 2000)

Cinnamomum cassia Blume.


Bastard Cinnamon, Chinese Cinnamon (Natural Medicine Comprehensive Database ,
8/12/2011), (Osol & Farrar 1955)

Canela de Cassia, Canela Molida, Canelle Batarde, Cannelle Cassia,


Cannelle de Ceylan, Cannelle de Chine, Cannelle de Cochinchine, Cannelle de Padang,
Cannelle de Saigon, Cannelier Casse, Canton Cassia, Casse, Casse Odorante, Cassia,
Cassia Aromaticum, Cassia Bark, Cassia Lignea, , Cinnamomi Cassiae Cortex,
Cinnamomum, Cinnamon, Cinnamon Essential Oil, Cinnamon Flos, Cinnamoni Cortex,
Cinnamonomi Cortex, Cortex Cinnamomi, corce de Cassia, False Cinnamon, Fausse
Cannelle, Gui Zhi, Huile Essentielle de Cannelle, Keishi, Laurier des Indes, Nees,
Ramulus Cinnamomi, Sthula Tvak, Taja, Zimbluten. (Natural Medicine Comprehensive
Database , 8/12/2011)

Dalchini, guipi, kannan, keihi, keishi, lavanga-pattai, lurundu, macrophyllos cassia, bark
tree, Siagon cinnamon, saleekha, taj,took,Viet Nam cinnamon. (Braun& Cohen, 2010).

Pinyin Names:
Rou gui (bark ) ( McGuffin, Kartesz, Leung,& Tucker, 2000), (Braun& Cohen, 2010).
Gui zhi (twig) ( McGuffin, Kartesz, Leung, Tucker, 2000)
Gu xn, guan gu ( Bensky & Gamble, 1993)

Japanese: Nikkei ( Bensky & Gamble, 1993)


Korean: yukkye ( Bensky & Gamble, 1993)

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DEFINITION

Cinnamomum zeylanicum

Inner bark of the shoots (Osol&Farrar, 1955) (Felter & Lloyd, 1898 p 558)
Dried inner bark of the shoots grown on cut stock or trunk bark freed from the underlying
parenchyma (Braun & Cohen, 2010)
Oil extracted from bark containing not less than 55% and not more than 68% cinnamic
aldehyde B.P (Osol & Farrar, 1955)
The dried bark from young shoots from which the outer cork has been removed is
preferred (Wichtl, 2004)
Dried inner bark from the shoots of coppiced trees (Youngken, 1948)
The bark is obtained from trees in Ceylon which are cultivated to form slender shoots
with little or no astringent cork (Youngken, 1948). The trees are allowed to grow for 4
to 5 years before their shoots are harvested (Youngken, 1948). Shoots from older trees
come from 2 year old root suckers and are cut during the rainy season ( Wichtl, 2004)
(Youngken, 1948).

Cinnamomum cassia
Inner bark (Osol& Farrar, 1955)
Oil extracted from the leaves and twigs , containing not less than 80% of aldehydes ,
U.S.P.(Osol& Farrar, 1955), ( Youngken, 1948)
Harvested September to October from trees that are at least 7 years old (Bensky &
Gamble , 1993 p301)

The trees are cultivated in the provinces of Kwangi and Kwangtung in southeast China.
The bark is harvested from adventitious shoots after the tree is 5 to 7 years old. The
leaves, leaf stalks and twigs are harvested and distilled into Oil of Cinnamon U.S.P.
(Youngken, 1948).

IDENTIFICATION:

Botanical:
C.zeylanicum
Habitat:
Ceylon
Botanical description:
The tree is an evergreen up to 10 m tall with black- brown bark. The young
branchlets are gray in color. The fruit is black when mature
(Xiwen,Jie,Puhua,Fanan, Hongbin & Van der Werff, 2008).

Cultivation and Harvesting:


Cultivated primarily in Guangdong and Taiwan. The tree is native to Sri Lanka
(Xiwen,Jie,Puhua,Fanan, Hongbin & Van der Werff, 2008)

Native to South and Southeast Asia and cultivated in Sri Lanka. (Wichtl, 2004)

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C.cassia
Habitat:
Southeastern China, possibly Cochin China (Youngken, 1948)
Botanical description:
Distinguishing characteristics from other species of Cinnamomum are the
transverse veins which are inconspicuously abaxial (Xiwen,Jie,Puhua,Fanan,
Hongbin & Van der Werff, 2008).

A medium size evergreen tree with aromatic leaves which are shiny green on the
upper surface. Underneath the leaves are glaucous and reticulate (Youngken,
1948)
The flowers are small, yellowish-white and arranged in loose, silky clusters.
(Youngken, 1948).
The fruit is ellipsoid in shape and black-purple in color when mature
(Xiwen,Jie,Puhua,Fanan, Hongbin & Van der Werff, 2008).
Cultivation and Harvesting:
The trees were believed to originate from Southern China
(Xiwen,Jie,Puhua,Fanan, Hongbin & Van der Werff, 2008). Today they are
cultivated in tropical and subtropical areas of Fujian, Guangdong, Guangxi,
Guizhou, Hainan, Taiwan and Yunnan. Cultivation is also occurring in India,
Indonesia, Laos, Malaysia, Thailand and Vietnam. (Xiwen,Jie,Puhua,Fanan,
Hongbin & Van der Werff, 2008)

Macroscopic

C. zeylanicum

Long closely rolled quills, composed of eight or more layers of paper thin bark.
Paler than C.cassia in color. The outer surface is smooth ,pale brown and marked
with wavy lines of bast-bundles( The Pharmacopoeia of the United States of
America, 1890), (Wichtl,2004). Inner surface is striated darker brown in color
and fractures with short-splinters (The Pharmacopoeia of the United States of
America, 1890 p 94).

The powder is light brown or light yellowish- brown in color (Youngken, 1948).

C.cassia

Yellowish-brown quills with a rough outer surface (The Pharmacopoeia of the


United States of America, 1890 p 94).

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Microscopic

Histology of the bark:

The pericycle contains almost continuous bands of stone cells among which are
small groups of pericyclic fibers with thick slightly lignified walls. (Youngken,
1948)

The Phloem is a broad zone with medullary-rays one to two cells in width. These
contain either starch or raphides of calcium oxalate. The parenchyma cells of
each phloem contain either starch, raphides or reddish brown contents. Bast
fibers are scattered around the parenchyma with oil cells and mucilage cells.
(Youngken, 1948)

The starch grains in C. zeylanicum are less abundant and smaller than those found
in C. cassia (Youngken, 1948)

Wichtl (2004) notes that authentication microscopically is based on its long


slender phloem fibers which appear brighter in polarized light. Very fine calcium
oxalate needles in the parenchyma will be visible. The stone cells are thickened
throughout. Cork and lignified cork are clear indicators of adulteration of
Cinnamon and should be absent from official drug.

C.cassia can be distinguished from C. zeylanicum by its thicker bark (1-2mm) and
the presences of cork with inner layers of lignified stone cells. (Wicht, 2004)

TLC Identification:

C.zeylanicum

The qualitative assay is based on purity tests including the identification of trans-
cinnamic aldehyde, eugenol and trans-2-methoxycinnamaldehyde. Adulterations
usually contain more than 0.03% coumarin which in the official drug is below
0.0008%. C. cassia will have a larger percentage of coumarin. (Wichtl, 2004)

Chemical

Essential Oils:

Cinnamomum zeylanicum: 0.2-2.5% (max 4%)(Teuscher, 2006), (Dewick, 2001)

Cinnamic aldehyde (42-82%)


Eugenol (1-11%)
Cinnamic alcholol (up to 8%)
Cinnamic acid ( up to 10%)

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Cinnamyl acetate, -methoxycinnamic aldehyde, benzyl benzoate, linalool
and safrole (up to 2%)
- Leaves can contain 55-95% eugenol and only small amounts of cinnamic aldehyde
(Teuscher, 2006).
- The flower essential oils are primarily cinnamyl acetate (42%) (Teuscher, 2006)
- There are significant regional differences in chemical constituents. Northeast India
barks essential oil contains 85% benzylbenzoate (Teuscher, 2006)
whereas Madagascar barks essential oil contains 74% eugenol and only
4% cinnamic aldehyde (Teuscher, 2006)
-B.P. states that the oil is soluble in three parts 70% alcholol (Osol & Farrar, 1955)

Cinnamomum cassia
Cinnamaldehyde (70-90%) (Dewick, 2001)
2-methoxycinnamaldehyde (12%) (Dewick, 2001)
Cinnamic aldehyde (C6H5CH:CH CHO) (Felter & Lloyd, 1898 p 559)
Eugenol ( discovered by Holmes in 1890) (Felter & Lloyd, 1898 p 559)
Cinnamic acid (Felter & Lloyd, 1898 p 559)
Phellandrene (Pole, 2006)

Other Chemicals found in both species :


Proanthocyanidins : Mono-linked tri-to pentamers 2% (Teuscher, 2006)
-A red pigment linked to superoxide anion scavenging. (Pengelly,2004)
Phenolcarboxulic acids: Protocatechuic acid(Teuscher, 2006)
Diterpenes: Cinnzeylanol, Cinnzeylanin, Acetylcinnzeylanol (Teuscher, 2006)
Sterols: -Sitosterol (Teuscher, 2006)
Sugar alcohols : Mannitol (up to 1.8%) (Teuscher, 2006)
Mucilage: Arabinoxylans (2-4%), glucans (Teuscher, 2006)
Starch: 5-10% (Teuscher, 2006)
Water: ~ 16% ( Osol & Farrar, 1955 p 330)

Standards and Tests:


Cinnamon bark should contains not more than trace amounts of lignified cork cells, few
starch grains exceeding 10 micrometers in diameter and no fibers over 30 micrometers in
breath. It must contain less than 2% of foreign organic matter and acid-insoluble
ash(Osol & Farrar, 1955).

The two species differ primarily in their eugenol and coumarin content. With C.
zeylanicum having more eugenol than C.cassia. Coumarin is only found in the C.cassia
species (Braun & Cohen, 2010) (WHO Monographs, 2011), (Mills, 1991), (Bone, 2003).

Cinnamic aldehyde increases while cinnamic acetate decreases during storage (Teuscher,
2006).

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TASTE /ODOR/ ENERGETICS:

Taste:
Chinese: acrid, sweet (Bensky & Gamble , 1993 p301) (Chen & Chen, 2004)
Ayurvedic: Pungent, sweet, astringent (Pole, 2006)
Eclectic/ Phytomedical: sweet. (Osol& Farrar 1955), (Grieve, 1971)
Biomedical: C. zeylanium and C. cassia are delicate and warm in taste compared to C.
loureirii which has a stronger more pungent flavor. (Youngken, 1948)
Spicy and burning ( Wichtl, 2004)

Odor:
fragrant .(Osol& Farrar 1955), (Grieve, 1971)
Warmly aromatic .(Osol & Farrar 1955)

Energetics:
Chinese: hot (Bensky & Gamble , 1993 p301) , (Chen &Chen, 2004)
Dry, stimulating, restoring, solidifying (Holmes,1997)
Warms the kidneys and fortifies the yang (Bensky & Gamble , 1993 p301)
Leads the fire back to its source (Bensky & Gamble , 1993 p301)
Treats a pattern of illusionary heat with true cold ( heat above/cold below)
(Bensky & Gamble , 1993 p301)
Pure Yang energy (Chen &Chen, 2004)

Ayuvedic: Hot with a sweet post-digestive effect (Pole,2006)


Dry, light, penetrating (Pole, 2006)

Eclectics: Warming cordial effect on the stomach. (Osol & Farrar 1955)

KEY PHYSIOLOGICAL ACTIONS:


Pharmacologic Actions
Antibacterial (Braun& Cohen, 2010)
Evidence category C -Unclear or Conflicting Scientific Evidence (Natural
Standard , 2011)
Antidiarrheal (Duguous,Seely, Perri, Cooley, Forelli,Mills& Koren, 2007)
Anti-inflammatory (Braun & Cohen, 2010)
Antineoplastic (Duguous,Seely, Perri, Cooley, Forelli,Mills& Koren, 2007)
Evidence category C -Unclear or Conflicting Scientific Evidence (Natural
Standard , 2011)
Antioxidant (Braun & Cohen, 2010)
Evidence category C -Unclear or Conflicting Scientific Evidence (Natural
Standard , 2011)
Antispasmotic (Braun & Cohen, 2010)
Fungicide (Braun& Cohen, 2010)
Evidence category C -Unclear or Conflicting Scientific Evidence (Natural
Standard , 2011)

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Hypoglycemic (Braun & Cohen, 2010)
Evidence category C -Unclear or Conflicting Scientific Evidence (Natural
Standard , 2011)
Immunmodulatory (Duguous,Seely, Perri, Cooley, Forelli,Mills& Koren, 2007)

Nervous system stimulant (Duguous,Seely, Perri, Cooley, Forelli,Mills& Koren, 2007)

Traditional Actions
Abortifacient (Natural Standard, 2011)
Astringent (Bone,2003), (Osol& Farrar 1955 p 330), (Felter & Lloyd, 1898 p 560)

Antipyretic ( Duke, J 2003 CRC Handbook of Medicinal Spices)


Carminative (Bone, 2003), (Osol& Farrar, 1955 p330), (Felter&Lloyd, 1898 p560)

Diaphoretic ( Duke, J 2003 CRC Handbook of Medicinal Spices)


Antidiarrhea (Osol & Farrar, 1955)
Digestive, (Bone, 2003)
Emmenagogue (Natural Standard, 2011), (Felter & Lloyd, 1898 p 560)

Germicidal (Felter 1922, p304)


Stimulant (Osol& Farrar 1955 p 330), (Felter 1922 p 304), (Felter & Lloyd, 1898 p 560)

Encourages the generation of qi and blood (Bensky & Gamble , 1993 p301)

Cinnamon oil was added to syrups in a concentration of 1 to 10,000 to prevent mold


growth. (Osol &Farrar, 1955)

KEY CONSTITUENTS:

Cyclic Aldehydes:
Cinnamaldehyde (E.S.C.O.P., 2003)
Cinnamic Aldehyde (Pengelly, 2004),(Iwaoka,Hashimoto,Koizumi,Yu,&Okabe, 2010)
Benzaldehyde (Duke, J 2003 CRC Handbook of Medicinal Spices)

Proanthocyandins:
Procyanidin B-2 (Natural Standard, 2011)
Procyanidin B-3 (Natural Standard, 2011)

Phenylpropanoid:
Eugenol (Pengelly, 2004)

Terpenes:
Caraphyllene (Braun & Cohen, 2010)
1,8 cineole (Braun & Cohen, 2010)

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Flavanoids:
Quercetin (Natural Standard, 2011)
Kaempferol (Natural Standard, 2011)
Luteolin (Natural Standard, 2011)
Pelargonidin (Natural Standard, 2011)

Polyphenol:
methylhydroxy-chalcone polymer (MHCP) (Pham, Kourlas,Pham, 2007)

Figure 1. Structure of a class of water-soluble cinnamon polyphenol compounds that


display insulin-potentiating and antioxidant activities. One tetramer and four type A
trimers have been isolated from cinnamon and all were shown to have in vitro insulin-
potentiating activity(Qin,Panickar, and Anderson, 2010)

Benzopyrone:
Coumarin (primarily in C. cassia) (WHO Monographs, 2011)

PHARMACOLOGY:
Antibacterial and Antifungal Effects:
There are a number of in vitro studies exploring the antimicrobial effects of cinnamon oil
(Bensky & Gamble, 1993 p301). Niu , Afre and Gilbert (2006) demonstrated that low
concentrations of cinnamaldehyde inhibited selected quorum sensing promoters which show
promise inhibiting the ability of Escherichia coli and Pseudomonas to form biofilms. This was
further demonstrated by Nuryastuti et al (2009) whose study confirmed that cinnamon oil was
effective in detaching and killing Staphylococcus epidermidis from their biofilms. Early in vitro
studies from Lee and Ahn (1998) showed that Cinnamomum cassia (Blume) was a potent
inhibitor of the pathogenic bacterias Clostridium perfringens, and Bacteroides fragilis with
little effect on beneficial bacterial in the human gastrointestinal tract including Bifidobacterium
longum and Lactobacillus acidophilus.

Cinnamon extracts have also demonstrated activity against Campylobacter jejuni,


Listeria monocytogens, Bacillus subtilis, Salmonella spp, Morganella morganii, Bacillus cereus,
respiratory bacterial like Streptococcus pyrogenes, Haemophilus influenzae, and Porphyromonas
gingivalis in vitro (Natural Standard, 2011). Chinese studies have also demonstrated inhibitory
effects on many gram positive bacteria (Chen & Chen, 2004). The purposed mechanisms of
actions include inhibition of glucose uptake or utilization by bacteria, effects on membrane
permeability or even motility in the case of E. coli (Natural Standard, 2011). Cinnamon bark oil
has also demonstrated an inhibitory effect on bacterial which can lead to periodontal disease

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(Braun and Cohen, 2010). Unfortunately oral application of cinnamon oil has led to a number of
adverse effects which will be discussed later in this monograph. As a result this application
should be used with caution.

The antibacterial effects are of significance in light of the increasing bacterial resistance
to currently available antibiotics. Cinnamon has been combined with currently available
antibiotics including clindamycin and has demonstrated a synergistic effect (Natural Standard,
2011). In vitro studies with C. cassia has shown significant inhibition of Helicobacter pylori
which was greater than or equal to a number of commonly used antibiotics (Braun and Cohen,
2010).

Studies have also shown the antifungal properties of C.cassia. One such study showed
Cinnamomum cassia oils ability to potentiate amphotericin Bs inhibitory effect on Candida
albicans. This would suggest promise in being able to reduce the dosage of amphotericin B and
potentially reduce the risks of the adverse effects of this toxic medication (Braun and Cohen,
2010). Since this was an in vitro study more research is needed to demonstrate this synergy in
vivo. Other antifungal studies have focused on food storage and preventing spoilage (Cohen and
Braun, 2010).

Anticancer/Antitumor Effect:
A number of the active constituents in cinnamon have demonstrated antitumor and
antimutagenic effects in vitro (Natural Standard, 2011). Suggested mechanisms of action include
apoptosis, stimulation of the reticuloendothelial system and tumor necrosis factor production,
reduction of mitochondrial transmembrane potential, increase of caspase-3 activity, the arrest of
cell cycle progression, induction of ROS-mediated mitochondrial permeability with resultant
cytochrome c release, blocking protein synthesis through trapping sulfhydryl-containing amino
acids, inhibition of angiogenesis and inhibitory effects against metalloproteinase-2,
metalloproteinase-9 (Natural Standard , 2011) ( Braun and Cohen, 2010). Cinnamomum cassia
has demonstrated strong inhibition of in vitro growth of 29 kinds of human cancer cells and in
vivo growth of SW-620 human tumor in mice (Natural Standard, 2011).

Antidiabetic Effects:
Pharmacological studies suggest that cinnamon has short lived improvements in glucose
and insulin metabolism (Natural Standard, 2011). The hypoglycemic effect demonstrated in
animal studies is a potentiation of insulin by the up-regulation of glucose by adipocytes and the
insulin-regulated glucose utilization, suggesting the reduction of insulin resistance (Natural
Standard, 2011). One mechanism of action suggested by in vivo studies is that cinnamon
increases glucose uptake through enhancement of the nitric oxide pathway in the skeletal muscle
(Natural Standard,2011). Based on human evidence, cinnamon reduced postprandial serum
insulin and increased glucagon-like peptide 1 (GLP-1) concentrations without significantly
affecting blood glucose, glucose-dependent insulinotropic polypeptide (GIP), the ghrelin
concentration, satiety or gastric emptying rates (Natural Standard, 2011). When it was mixed
with rice pudding in one study, delays in gastric emptying were seen however (Natural Standard,
2011).

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Initial studies identified Methylhydroxy-chalcone polymer as the active component
which was thought to stimulate insulin receptor kinase, leading to autophosphorylation of the
insulin receptor substrate. This action results in increased glucose uptake in adipocytes. Other
studies found that the active component was water soluble whereas Methylhydroxy-chalcone
polymer is not. The water soluble polyphenolic type-A polymer, brings into question which
substance has the biological activity (Pham,Kourias, Pham 2007).

Antilipemic Effects:
Cinnamomum zeylanicum significantly decreased serum total cholesterol and triglyceride
concentrations and increased HDL-cholesterol levels in animal studies (Natural Standards,
2011). Cinnamate was compared to the medication lovastatin and found to have a greater
impact on increasing HDL levels (Natural Standard, 2011). The proposed mechanism is that
postprandial hypertriglycerides and overproduction of apoB48 may be inhibited by cinnamon
extracts by improving insulin sensitivity of the intestinal enterocytes (Natural Standard, 2011).
Cinnamate may not be the only active component in cinnamon which decreases total serum
cholesterol. A study in rats showed that cinnamaldehyde had the same effect (Natural Standard,
2011).

Immune System Effects:


In vitro studies have demonstrated inhibition of cyclooxygenase activity, specifically
COX-2 and prostaglandin formation with Cinnamon bark oil (E.S.C.O.P, 2004), (Natural
Standard, 2011). Cinnamaldehyde also inhibits 5-lipoxygenase resulting in reductions of
leukotrienes (Natural Standard, 2011). Histamine inhibition has been seen with ethanol extracts
of cinnamon but not aqueous extracts (Corren, J., Lemay, M., Lin, Y., Rozga, L., & Randolph, R.
,2008). Nagi, Shimazawa, Matsuura and Koda (1982) also found that cinnamon caused
inhibition of histamine release and demonstrated anti-complement action and inhibition of
complement dependent allergic reactions. Other inflammatory pathways affected by cinnamon
include the antagonism of TRPA1, the suppression of tumor necrosis factor (TNF)-induced
signaling pathways and the activation of NFkappB and IRF3, resulting in reduced expression of
inflammatory cytokines (Natural Standard, 2011).

Cardiovascular Effects
The Chinese have observed that the intravenous administration of cinnamon bark causes
marked reduction in blood pressure, heart rate, and blood vessel resistance. It also causes
peripheral vasodilation (Chen & Chen, 2004). These effects were short lived with the
cardiovascular system returning to normal within 15 minutes (Chen &Chen, 2004). These
effects on the cardiovascular system were also demonstrated with oral use in animal studies by
Wang in 1983 (Ravindran, Babu and Shylaja, 2004).

Gastrointestinal Effects:
The Chinese have found that cinnamon oil has a mild stimulating effect on the gastrointestinal
system, causing increases in saliva and gastric acid(Chen & Chen, 2004). It also enhances
digestive function and relieves intestinal spasms and pain (Chen &Chen, 2004). Animal in vivo
studies have demonstrated inhibition of stomach motility in dogs and rats exhibiting carminative
activity (E.S.C.O.P., 2004), (Braun& Cohen, 2010). Simulation models also suggest cinnamon
oil has antifoaming activity and may be effective for flatulence (Braun & Cohen, 2010).

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Other Effects:
Cinnamon has mild diaphorectic effects primarily due to its vasodilatory action
(Ravindran, Babu and Shylaja, 2004). Aqueous cinnamon extracts have also inhibited tau
aggregation, filament formation and improvements in cognitive behavior in animal models with
aggressive Alzheimers disease (Natural Standard, 2011).

PHARMACOKINETICS
Absorption:
Researchers in Japan investigated the oral bioavailability of procyanidin B-2 and
procyanidin B-3 isolated from Cinnamomum cassia in rats showing a peak at 20 minutes for
procyanidin B-2 and 40 minutes for procyanidin B-3. Plasma concentrations of both
procyanidins disappeared within 3 hours (Tanaka et al, 2003). Keller (1992) found that
Cinnamaldehyde is poorly absorbed through the skin.

Metabolism:
Animal studies have demonstrated rapid metabolism of o-methoxycinnamaldehyde with
no evidence of conjugation with glutathione in rats. (Samuelsen, Brenna, Solheim, and Scheline,
1986). The major pathway involved was oxidation to cinnamic and phenylpropionic acids
(Natural Standard,2011). An extract of cinnamon induced substrate binding with cytochrome
P-450 in vitro with rat (E.S.C.O.P., 2004). O-methoxycinnamaldehyde was identified as an
inhibitor of drugs metabolized by cytochrome P-450 1A2 (CYP 1A2) and cytochrome P-450
2E1( CYP 2E1) (Natural Standard, 2011). A constituent of cinnamon extract, 5'-hydroxy-5-
hydroxymethyl-4'',5''-methylenedioxy-1,2,3,4-dibenzo-1,3,5-cycloheptatriene, has been shown to
inhibit CYP3A4 in vitro (Natural Standard, 2011).

Excretion:
Constituents in cinnamon were found to be excreted via the kidneys and have been
recovered in the urine (Natural Standard, 2011). Cinnamic acid and phenylpropionic acid are
primarily excreted as glycine conjugates in the urine (Natural Standard, 2011). The excretion of
these metabolites was 91% in 24 hours and 98% in 48 hours (Natural Standard, 2011).

Traditional Use:

The Eclectic Specific Indication for Specific Cinnamon (an alcoholic solution of the oil)
was for passive hemorrhages of the uterus, bowels, stomach and urinary tract (Felter, 1922
p304), (Fyfe and Scudder, 1909). They observed that cinnamon had a direct effect on uterine
contractions (Fyfe and Scudder, 1909). Scudder claimed to have arrested post-partum
hemorrhage with cinnamon oil even during severe hemorrhage (Fyfe and Scudder, 1909). There
was also limited use for less severe cases of hemoptysis (Fyfe and Scudder, 1909). Other uses
included treating nausea, diarrhea, vomiting, flatulence, colic and stomach cramps (Felter &
Lloyd, 1898 p 560).

The eclectic physicians typically added cinnamon to a number of their formulas to


improve the flavor of unpalatable herbs (Felter & Lloyd , 1898 p560) as well as to minimize the
griping caused by purgative remedies (Fyfe and Scudder, 1909). Felter recommended small

12
doses for acute diarrhea and larger doses if the patient had chronic non-inflammatory and non-
febrile diarrhea. (Felter, 1922 p305).Cautions limiting its daily use for long periods were
published in 1922 when they began seeing long-term use causing mouth irritation, stomach
revolt and taste recoil (Felter, 1922 p 305).

The people of Lebanon use cinnamon for colds and rheumatism in addition to decreasing
slobbering in children and the elderly (Duke, J 2003 CRC handbook of Medicinal Spices).

In Ayurvedic medicine, cinnamon is considered an aphrodisiac and has been used as a


general and cardiac tonic (Duke J 2003 CRC handbook of Medicinal Spices.). Other uses
include treating bronchitis, diarrhea, dyspepsia, flatulence, vomiting, itching, parched mouth,
worms, and rectal and urinary disease(Duke J 2003 CRC handbook of Medicinal
Spices),(Nadkarni, 1982) . The crystalline cinnamic acid is considered antitubercular (Nadkarni,
1982). Cinnamon oil is considered a stimulant of uterine muscle and is used in menorrhagia and
difficulties in labor (Nadkarni, 1982).

In Chinese medicine it is a classic assistant remedy which boosts the actions of other
herbs. It can give a stimulant tweak to formulas for cold, deficiency and congestion. Examples
include:
Uterus cold syndromes: Juniper berry, Pennyroyal and Blue Cohosh root.
Debility (Qi tonic): Elecampane root and Thyme
Deficient heart or lung: Rosemary or Hyssop
Deficient intestines (Spleen) Yang patterns: Calamus, prickly ash bark and cardamom
pod (Holmes, 1997)

Clinical Trials:

There have been a number of clinical trials testing cinnamon for a variety of its
indications but the majority of the studies have focused on its effects on diabetes. Five (5)
clinical trials evaluating the effectiveness of Cinnamon on Diabetes were reviewed by this
author. One trial by Altschuller, Casella, MacKenzie and Curtis (2007) evaluated the effects of
Cinnamon on type 1 diabetes and the other 4 studies looked at its effect on type 2 diabetes
(Khan,Safdar,Khan,Khattak,&Anderson, 2003),( Mang et al, 2006), (Vanschoonbeek,
Thomassen, Senden, Wodzig, & van Loon,2006),(Blevins,Leyva, Brown, Wright, Scofield &
Aston, 2007). Khan, Safdar, Khan ,Khattak and Andersons (2003) study was a landmark study
which many have attempted to replicate. Their study was done in Pakistan with a poorly
controlled patient population with type 2 diabetes. No studies to date have been able to
reproduce the results Khan et al accomplished in their 2003 study.
The following table summarizes each of the studies reviewed and discusses the
limitations of each study. Two literature searches were also reviewed.

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CLINICAL STUDIES:
Citation Study Purpose and Methods Outcome
Design
Khan,A.,Safdar,M.,Khan,M.,Kha prospective, Purpose: To determine whether there is The addition of Cinnamon led to a significant decrease in fasting serum
ttak,K.,& Anderson,R. (2003) randomized, a dose response of cinnamon on glucose levels without evidence of a dose response (18-29%). Serum
Cinnamon Improves Glucose and placebo-controlled, clinical variables associated with glucose levels were not significantly different in any of the three placebo
Lipids of People with Type 2 peer-reviewed group.
diabetes and cardiovascular diseases in
Diabetes. Diabetes Care clinical trials
26:3215-3218 people with type 2 diabetes
There was also a time dependent decrease in serum triglyceride levels in
all of the treatment arms (23-30%) only after 40 days of therapy. There
Method: Sixty (60) patients with fasting were no changes in serum triglyceride levels seen in any of the placebo
blood glucose levels between 140-400 arms.
mg/dl were randomly assigned to 6
different arms, 3 treatment arms and 3
placebo arms. Treatment arms Decreases in serum cholesterol in all three of the treatment arms were
consisted of 1gm, 3gm and 6 gms of an significant at 13-26% after the 40 days. Whereas only those taking 3gm
aqueous extract of Cinnamon and 6gm showed a decrease in LDL levels after 40 days (10-24%).
(Cinnamomum cassia). Each patient Decreases in those receiving 1 gm were not statistically significant but
received 40 days of either Cinnamon or they continued to decrease even during the washout period.
placebo followed by a 20 day washout
period. Fasting blood glucose levels, Limitations of this study included the small population size, and the
fasting triglyceride levels, and fasting applicability of fasting glucose levels versus hemoglobin A1C levels in
serum cholesterol levels were drawn on monitoring type 2 diabetes activity. Also of note is that the average
day 0, 20, 40 and 60. fasting glucose levels in all of the arms exceeded the recommendations of
125mg/dl even after treatment and demonstrated a poorly controlled
Compliance was measured by pill count. patient population.

Patients receiving insulin were excluded Insulin sensitivity, glucose tolerance, changes in blood insulin levels and
from the study and all patients actual A1C values were not reported in the study.
continued receiving their sulfonylurea
drug therapy throughout the study. Blinding was not discussed in the article. The investigators did put the
cinnamon and wheat flour in capsules to mask the taste creating an
Wheat flour was used as a placebo. To attempt to blind the participants. But there was no discussion of double
assist with blinding the Cinnamon and blinding.
Wheat flour were ground and put into
capsules. This study did not provide data on diet, BMI, ethnic mix or A1C.

14
Citation Study Purpose and Methods Outcome
Design
Roussel, A.M., Hininger, I., There were no significant changes observed in the placebo group. In the
Benaraba, R., Ziegenfuss, T.N., Prospective double- Cinnamon group a 10% decrease in fasting glucose levels which was
blind placebo Purpose: Study the effects of Cinnamon deemed to be significant although none of the serum levels were in the
Anderson, R.A., (2009)
controlled trial on oxidative stress markers and fasting hyperglycemic range at baseline or after 12 weeks. Of note the fasting
Antioxidant effects of a insulin level actually increased in the Cinnamon group. This increase was
blood glucose and insulin levels in
cinnamon extract in people with overweight and obese patients. not noted as significant although they reported as much as a 14 pmol/ml
impaired glucose that are increase over the 12 weeks (14.15 11.19). The average insulin level in
overweight or obese. J Am Coll the U.S., according to the NHANES III survey, is 8.8 uIU/mL for men
Method: Twenty-two (22) subjects with and 8.4 for women. Elevated fasting insulin levels increase the risk of
Nutr. 28(1):16-21 retrieved from fasting blood glucose between cardiovascular disease. All of the fasting insulin levels in this study, both
http://www.ncbi.nlm.nih.gov/pu 100mg/dl-125mg/dl, a BMI between 25- before and after the 12 weeks, exceeded the NHANES III
bmed/19571155?dopt=Abstract 45, and normal liver and kidney recommendations.
function were divided into one of two
on 8/14/2011
groups. The treatment group received
250mg of dried aqueous extract of This study focused on oxidative stress markers. All plasma oxidative
Cinnamon (Cinnamomum cassia) twice stress markers (MDA, SH, FRAP) significantly improved. The RBC
a day for 12 weeks. antioxidant enzymes, superoxide dismutase and GPx were not altered by
the supplementation.
Oxidative stress markers were measured
at the beginning of the study, at 6 weeks The study supports the inclusion of cinnamon extracts in the diet to
and after 12 weeks. These included improve the risk factors associated with diabetes and cardiovascular
plasma malodialdehyde (MDA), plasma disease in patients who are overweight or obese by potentiating insulin
thiol group oxidation (SH), Ferric and the decrease of free radical production.
Reducing Activity plasma levels
(FRAP) and antioxidant erythrocyte One of the limitations was that the cinnamon was provided by Integrity
enzyme activities as superoxide Nutraceuticals International who partially funded the study. This created a
dismutase (RBC SOD) and glutathione suggestion of bias.
peroxidase (GPx). Fasting blood
glucose levels and plasma insulin levels Another limitation includes the small number of subjects studied and the
were also monitored. missing patient demographic information. There was no discussion of
gender or race of the patients studied, making it difficult to extrapolate the
applicability to different patient populations.

Since the patient population studied had fasting blood glucose in the
prediabetic range (100-125mg/dl) the results of this study cannot be
extrapolated to patients with type 2 diabetes.

15
Citation Study Purpose and Methods Outcome
Design
Purpose: Study the effects of cinnamon More men than women were enrolled in the study ( 67.6% ) with a mean
prospective, on type 2 diabetes. age of 63 years. The fasting glucose levels in the treatment group were
Mang, B., Wolters, M., Schmitt, randomized, significantly reduced compared to baseline with the mean absolute and
double-blind, Methods: Sixty-five (65) patients with percentage differences between the treatment group and the placebo group
B., Kelb, K., Lichtinghagen,
placebo-controlled, type 2 diabetes mellitus currently being were significantly different. There were no significant or intergroup
R.,Stichtenoth, D.O., and Hahn, peer-reviewed differences of hemoglobin A1C, total cholesterol, LDL, HDL or
treated with antidiabetic medications
A. 2006. Effects of a cinnamon clinical trials triacyglycerol concentrations.
and diet were included in the study.
extract on plasma glucose, One cinnamon capsule containing
HbA1c, and serum lipids in 112mg of the aqueous cinnamon liquid No adverse effects were reported by participants in the treatment group.
diabetes mellitus type 2. Eur. J. purified extract TC112 (Cinnamomum
Clin. Invest. 36: 3404. cassia) equivalent to 1 gm of cinnamon This study observed a 10% reduction in fasting blood glucose levels. The
or an identical capsule containing investigators purposed that this lower reduction compared to Khan et al
doi:10.1111/j.1365- microcrystalline cellulose were given 3 (2003) results of 18-29% was due to lower initial fasting glucose levels
2362.2006.01629.x times a day with meals for 4 months to compared to the Pakistani diabetics. Suggesting that patients with poor
study participants. Compliance was glycemic control may benefit more from cinnamon intake.
measured by pill count.
This trial found no changes in the lipid profiles after intervention
Fasting blood glucose, low-density compared to baseline. The investigators suggested that the smaller
lipoprotein (LDL) and high-density decreases of fasting glucose in their study were not enough to result in
lipoprotein (HDL) cholesterol were improvements in lipid profiles.
measured at the start of the study and at
4 months.
This study used a liquid extract instead of powdered Cinnamon in order to
separate the lipophilic substances which have been linked to more adverse
effects including decreases in blood coagulation from the coumarin
component and allergic reactions linked to cinnamic aldehyde.

The main limitations of this study is the small population size and funding
provided by the manufacturer of the TC112 extract. It has also been
suggested by Pham et al (2007) that the limited number of fasting glucose
levels limited the observation of cinnamons effects. Of note also was
that the baseline A1C levels were already at goal before any intervention.

16
Citation Study Purpose and Methods Outcome
Design
Vanschoonbeek, K., Thomassen, Prospective, Purpose: To Investigate the health Baseline characteristics, plasma hemoglobin A1C, fasting glucose levels,
B.J., Senden, J.M., Wodzig, placebo-controlled benefits of Cinnamon in insulin concentrations, insulin resistance, fasting plasma triacylglycerol,
double-blind, peer- postmenapausal women with type 2 LDL, HDL and total cholesterol did not differ between the two study
W.K.,& van Loon, L.J. 2006.
reviewed trail diabetes. groups. The investigators did not observe significant differences in any
Cinnamon supplementation parameter between the placebo or treatment arm. No adverse effects were
does not improve glycemic reported.
Methods: Twenty-five (25)
control in postmenopausal type postmenopausal women diagnosed with
2 diabetes patients.J. Nutr. 136: type 2 diabetes mellitus who were This study differed by Khan et al (2003) by adding nutritional
977980. PMID:16549460 currently receiving oral glucose standardization prior to laboratory measurements. Also this study
lowering agents. Participants were included only postmenopausal women.
assigned to a treatment group (n=13) or
placebo group (n=12) matched by age, This study was not randomized and limited by the small sample size
BMI, years since diagnosis with type 2 (underpowered). Another limitation was that the 6 week treatment period
diabetes, fasting blood glucose is considered too short. The American Dietetic Association recommends
concentrations and medications. a 2 to 3 month interval between A1C measurements.

The study period was 6-7 weeks. The American Diabetes Association. 2006. Standards of medical care in diabetes.
treatment arm involved supplementation Diabetes Care 29:S442.
with 500mg 3 times a day with meals of
Cinnamon (Cinnamomum cassia) and
the placebo arm with 500mg 3 times a
day with meals of wheat flour. The
study described the blinding process and
reported that the capsules were
indistinguishable by color, scent or
taste.

All subjects excluded food products


containing cinnamon from their diets.
Dietary food intake records were
obtained for 2 days before the baseline,
2 week and 6 week oral glucose
tolerance testing. And they received the
sane standardized meal the evening
before the trial ( 60% CHO, 28% fats
and 12% protein)

Compliance was monitored by pill


count on a weekly basis.

17
Citation Study Purpose and Methods Outcome
Design
Of the 72 patients enrolled in the study, 15 did not complete the 90 days
Prospective, double- of medication. This left 57 participants meaning the study was not
Altschuller,J.A.,Casella, blind, placebo- Purpose: To determine the effect of sufficiently powered based on their own study critieria.
controlled trial cinnamon on glycemic control among
S.J.,MacKenzie,T.A.,and Curtis,
K.M. 2007. The Effect of adolescents with type 1 diabetes. There was one adverse reaction of hives reported to the Cinnamon. This
patient was discontinued from the study. A second patient in the
Cinnamon on A1C Among
Methods: Study participants were Cinnamon arm experienced a hypoglycemic seizure during the trial. And
Adolescents with Type 1 one patient experienced stomach pains on the placebo arm, possible due
randomized to receive either 1 gram of
Diabetes. Diabetes Care. 30(4): Cinnamon in a capsule or an equivalent to lactose intolerance.
813-816 Retrieved from appearing capsule containing lactulose.
http://care.diabetesjournals.org The investigators admitted that the Mean final A1C levels and mean change in A1C was not statistically
/content/30/4/813.full.pdf+html capsules looked similar but that some of significant in either the placebo or Cinnamon arm. Furthermore there was
the participants could discern no statistically significant change in the amount of daily insulin used by
differences between the them. either arm. The patients in the Cinnamon arm did report 39% more
hypoglycemic episodes than the placebo group but it did not reach
Inclusion criteria were 1) type 1 statistical significance.
diabetes for >= 18 months 2) aged 13-
18 years , 3) presentation to the clinic The investigators believed that the absences of endogenous insulin in type
for routine care, 4) no hospital 1 diabetes might be a reason for the negative results. It is believed that
admissions 12 months before enrollment Cinnamon may act by stimulating endogenous insulin production. (Kim,
5) accessible by phone and 6) not Hyun, and Choung, 2007)
pregnant.
Limitations of this study included the low dosage of cinnamon studied,
Participants were instructed to take one and the investigators did not reach power for their study. They also did
capsule daily and keep a log of their not discuss in their article what species of cinnamon was use not whether
total daily insulin dose. Compliances it was an extract or whole herb.
was measured by remaining pill count at
the end of the study. This study highlights the uncertainty of the mechanism of action of
Cinnamon
A1C levels were obtained at baseline
and after 90 days.

It was deemed necessary to obtain a


power of 80% to detect a reduction in
A1C at 3 months. This was calculated
to be 64 subjects with 32 in each arm. A
total of 72 subjects participated with an
estimated dropout rate of 10%.

18
Citation Study Purpose and Methods Outcome
Design
Sixty (60) patients were randomized into the study with 43 completing the
study. This study had an even distribution of both men and women as
Prospective, Purpose: To recreate Khan et al(2003) well as tracking the ethnic mix of the participants. Not all of the
randomized, study using a Western population. participants were taking diabetic medications, with an uneven distribution
Blevins, S.M., Leyva, M.J., double-blind of these patients in the placebo group (30) versus the cinnamon group (3).
placebo control trial Those taking lipid-lowering medications were equally distributed into
Brown, J.,Wright, J., Scofield, Methods: Inclusion criteria was patients each study group.
R.H., and Aston, C.E.,2007 with type 2 diabetes. Patients who were
Diabtese Care . 30(9): 2236-2238 using insulin, consuming nondietary
cinnamon supplementation, had A1C The investigators found no statistically significant differences between the
less than 6% and acute illness were cinnamon and placebo groups in any of the measured parameters from
excluded. baseline and levels drawn after 3 months.

Participants were stratified by sex and Limits of the study include that due to drop outs power wasnt met.
randomized to receive with cinnamon
(Cinnamomum cassia) capsules or
placebo (Wheat flour) capsules. Each
capsule contained 500mg of product.
The dose was one capsule twice a day
with breakfast and dinner.

At baseline, 1 , 2, and 3 months fasting


glucose, cholesterol (total, LDL and
HDL), triglyceride and insulin levels
were recorded. A1C was measured at
baseline and at 3 months. Diet was
monitored using 3-day food journals.
Pham, A.Q., Kourlas, H.,Pharm, literature search MEDLINE search (1966-August 2006), Two prospective, randomized, double-blind, placebo-controlled, peer-
D.Q. 2007. Cinnamon EMBASE (1980-August 2006), reviewed clinical trials evaluating the efficacy of cinnamon
International Pharmaceutical Abstracts supplementation with type 2 diabetes and one prospective placebo-
Supplementation in Patients
(1970-August 2006) and Iowa Drug controlled, peer-reviewed trial were reviewed.
with Type 2 Diabetes Mellitus. Information Service (1966-August
Pharmacotherapy 27 (4): 595- 2006). References from articles and
599 Available from clinical trials were reviewed but no
http://pharmacotherapyjournal. abstracts were reviewed.
org/doi/abs/10.1592/phco.27.4.
595

19
Citation Study Purpose and Methods Outcome
Design
Therapeutic efficacy: Six (6) clinical trials were reported evaluating
Dugoua, J.,Seely, D., Perri,D., Literature search type 2 diabetes (3), Heliocobacter pylori infection (1), oral candidiasis in
Cooley, K., Forelli, T., Mills, E., Purpose: A systematic review of the HIV (1) and chronic salmonellosis (1).
and Koren, G., 2007. From type scientific literature pertaining to
2 diabetes to antioxidant activity: common and cassia cinnamon for Type 2 Diabetes (see previous reviews)
a systematic review of the safety evidence of their safety, efficacy and
and efficacy of common and pharmacological activity.
cassia cinnamon bark. Can. J. Mang et al 2007 ( Grade B1: strong scientific evidence)
Physiol. Pharmacol. 85: 837-847
The following databases were searched Khan et al 2003 (Grade B1: strong scientific evidence)
from their inception to August 2006:
Vanschoonbeek et al 2006 (Grade B2: Good scientific evidence)
MEDLINE, OLDMEDLINE,
Cumulative Index to Nursing & Allied
Health Literature (CINAHL), Cochrane Heliocobacter pylori infection
Database of Systematic Reviews,
Databse of Abstracts of Reviews of Nir et al 2000 (Grade B2) small randomized controlled pilot study
Effectiveness (DARE), Allied (n=23) which showed cinnamon alcoholic extract to be ineffective in
,Complementary Medicine (AMED), eradicating H.pylori. Statistical significance was not achieved. The
EMBASE and AltHealthWatch., investigators may have underpowered this study.
Complete German Commission E
Monographs by the American Botanical Oral candidiasis in HIV
Councel, Natural Database and Natural
Standards.
Quale et al 1996 : case series of 5 patients with HIV infection and oral
candidiasis who received Cinnamomun zeylanicum for 1 week. Three of
The MeSH terms used included : the 5 patients demonstrated improvements of their oral candidiasis.
cassia, cinnamon and
cinnamomum. Studies using
combination products were excluded. Chronic salmonellosis
Searches captured all preclinical and
clinical studies in addition to animal and Rosti and Gastaldi 2005 (Grade E: Indirect and/or clinical evidence) Case
in vitro studies to evaluate toxicology, presentation of an infant who was a chronic carrier of Salmonella
adverse effects and pharmacology of enteritidis. This patient was treated with ground Cinnamomum
cinnamon. zeylanicum 3-4 times a day for 1 month. At the end of the month the stool
culture results showed no growth of pathogens and remained negative at
both the second and third month followup.

20
Preparation and Dosage:
Dried Bark: Compound
1.5 4 g as an infusion (ESCOP, 2003),(Braun & Cohen, 2010)
1-6 g daily for 40 days (Roussel, Hininger, Benaraba, Ziegenfuss, cardamom
Anderson , 2009) tincture:
- teaspoonful in 1 cup of boiling water 2-3 times daily with 20 gm cardamom
meals. (Braun&Cohen,2010) seed
25 gm cinnamon
powder
Fluid Extract: 12 gm caraway
0.5-1ml up to three times a day (1:1 70% ethanol) (ESCOP, 2003) 5 gm cochineal
0.7-1.3ml three times a day (Braun&Cohen,2010)
Mix 50ml glycerin in
Aqueous extract: 950ml diluted alcohol
250mg capsules twice a day (equivalent to 5gm cinnamon powder
Mix powders in
(20:1 extract) (Natural Standard,2011).
750ml of menstrum
Cinnulin PF 250mg capsules have been standardized for then qs to 1000ml
doubly linked Type-A Polymers, specifically tetramers and
trimmers (What is Cinnulin PF, 2011) Dose= 2-8ml
Use : carminative but
Essential Oil: also as a vehicle
0.05-0.2ml diluted in carrier oil (Braun&Cohen, 2010)
(Osol & Farrar, 1955)
Traditional Dosing:
Cinnamon Water B.P.: 1-2 fluid ounces (Grieve, 1971)
Tincture of Cinnamon B.P.: to 1 drachm (Grieve, 1971)
Cinnamon Oil B.P.: to 3 drops (Grieve, 1971)
Comp.Powd.Arom. B.P.: 10-40 grains (Grieve, 1971)
Spirit B.P.: 5 to 20 drops (Grieve, 1971)
Specific Cinnamon: 5 to 30 drops ( Scudder,1870 p 13)

Special populations:
Reduce dosage for children proportional to age and body weight (ESCOP, 2003)
Use alcohol free in children (ESCOP, 2003)

SAFETY ISSUES
Contraindications:
Patients with known allergy or hypersensitivity to cinnamon, cinnamon bark oil or
cinnamaldehyde including members of the Lauraceae family or Balsam of Peru (case
studies) (ESCOP, 2003 p93), (Natural Standard, 2011)

Cinnamon is one of the 10 major food allergens. (case reports) (Natural Standard,2011)

Precautions:
Patients taking medications metabolized by cytochrome P450 (1A2 ,2E1 and 3A4) based
on in vitro studies (Natural Standard, 2011)

21
Patients with diabetes who are taking antidiabetic medications due to theoretical additive
effects with increased risk of hypoglycemia, based on in vitro, animal evidence (Natural
Standard, 2011). Although current clinical trials combined cinnamon with antidiabetic
medications there were no significant differences of hypoglycemic events in the
treatment arms and placebo arms (Khan,Safdar,Khan,Khattak,&Anderson, 2003),( Mang
et al, 2006), (Vanschoonbeek, Thomassen, Senden, Wodzig, & van
Loon,2006),(Blevins,Leyva, Brown, Wright, Scofield & Aston, 2007). No adverse drug
reactions were noted in any of the studies.

Patients with autoimmune diseases or who use immunosuppressants based on cinnamons


immunomodulatory effects in animal and in vitro studies (Natural Standards, 2011)

Patients with liver damage or who are taking hepatotoxic medications due to potential
additive effects of coumarin found in Cinnamomum cassia based on animal studies
(Natural Standard, 2011) and Safrole found in Cinnamomum zeylanicum (McGuffin,
Hobbs,Upton & Goldberg, 1997).

Use in pregnancy and lactation:


Only limited data is available suggesting it should not be used in pregnancy and lactation
without medical advice. (ESCOP, 2003 p93) Large doses in excess of those found in
dietary sources have possible abortifacient effects based on secondary sources (Natural
Standard, 2011).
Safrole, a minor constituent of Cinnamomum zeylanicum was shown to readily cross the
placenta in mice, as a result therapeutic doses of the oil should be avoided during
pregnancy (McGuffin, Hobbs,Upton & Goldberg, 1997).

Adverse Events:
Cinnamon is considered a class 2b: 2d herb not for long term use; do not exceed recommended
dose (McGuffin, Hobbs,Upton & Goldberg, 1997).

Case Reports:
Dermatitis, photodermatitis, stomatitis, glossitis, gingivitis, perioral dermatitis, perioral
leukoderma (simulating vitiligo), oral lesions, cheilitis, eczema, lip edema and irritation,
and depigmentation (Natural Standard, 2011)

Cinnamaldehyde may provoke orofacial granulomatosis, uticaria, dermatitis and


stomatitis. Squamous cell carcinoma of the tongue and speckled lesions following
exposure to cinnamon-flavored gum have been reported (Natural Standard, 2011)

Nausea and abdominal pain (Natural Standard, 2011)

Asthma , chronic respiratory symptoms have been seen in spice factory workers (Natural
Standard, 2011).

Altered state of consciousness in children and adolescents (Perry, P.A., Dean, B.S. &
Krenzelok, E.P. , 1990)

22
In vitro and Animal Studies: (Natural Standard, 2011)
Decrease in platelet count (animal study)
Hepatotoxicity (essential oil of Cinnamomum cassia and Cinnamomum zeylanicum)
Hyperoxaluria (secondary source- not based on human evidence)

Safrole is a minor component of Cinnamomum zeylanicum and has hepatotoxic,


carcinogenic and mutagenic potential. Safrole itself is not hepatotoxic or
hepatocarcinogenic, but its metabolites in the liver are known to be toxic. Of note is that
simultaneous enzymatic activities occur during Safroles metabolism, which acts in a
protective manner to detoxify the carcinogenic intermediates. It is the metabolites which
have not been deactivated by detoxification enzymes which can lead to problems
(McGuffin, Hobbs,Upton & Goldberg, 1997). Further investigation into the use of herbs
containing Safrole in patients with impairment of their detoxification pathways may shed
light on the management of minimizing toxic risks.

Potential drug interactions:


Interactions are based on pharmacological activity and are largely theoretical (Braun &Cohen,
2010). Clinicians should be aware of the potential interactions to ensure appropriate
management of therapy.

Additive Effects (Beneficial) (Natural Standard, 2011):


Alzheimers agents
Analgesics
Antibiotics
Antifungal agents
Antilipemic agents

Increased Risk of Adverse Reactions (Natural Standard, 2011):


Anticoagulants-increased risk of bleeding
Antiplatelets- increased risk of bleeding
Antidiabetic agents including insulin-increased risk of hypoglycemia
Antihypertensive agents- increased risk of hypotension

Medications which could cause additive hepatotoxic effects with cinnamon


include acetaminophen, amiodarone, carbamazepine, isoniazid, methotrexate,
methyldopa, fluconazole, itraconazole, erythromycin, valproic acid, divalproex
sodium and HMG-CoA reductase inhibitors including lovastatin, pravastatin and
simvastatin (Nilesh, Ozick,& Gbadehan, 2010).

Based on secondary sources cinnamon may slow the absorption and reduced
blood levels of Tetracycline (Natural Standard, 2011).

Cytochrome P450 (1A2 ,2E1 and 3A4) metabolized agents- risk of toxicity

23
Medications Metabolized by Cytochrome P450
1A21 2E12 3A4 (partial list)3
Alosetron (Lotronex) Acetaminophen Alfuzosin (Uroxatral)
Caffeine Chlorzoxazone Alprazolam (Xanax)
Clozapine (Clozaril) Cimetidine Budesonide
Flutamide (Eulexin) Disulfiram Carbamazepine (Tegretol)
Frovatriptan (Frova) Dorzolamide Colchicine
Melatonin Ethanol Cyclosporine (eg: Neoral)
Mexiletine (Mexitil) Isoniazid Dexamethasone
Mirtazapine (Remeron) Ondansetron Disopyramide (Norpace)
Olanzapine (Zyprexa) Propofol Ergotamine
Ramelteon (Rozerem) Ritonavir Fluticasone (Flovent)
Rasagiline (Azilect) Tamoxifen Lovastatin (Mevacor)
Ropinirole (Requip) Theophylline Methylprednisolone
Tacrine (Cognex) Volitile anesthetics (Halothan, Midazolam (oral)
Teflurane, Enflurane etc)
Theophylline Industrial solvents Pimozide (Orap)
(benzene,toluene ectc.)
Tizanidine (Zanaflex) Quinidine
Triamterene (Dyrenium) Repaglinide (Prandin)
Zolmitriptan (Zomig) Rifabutin (Mycobutin)
Sildenafil (Viagra)
Simvastatin (Zocor)
Tadalafil (Cialis)
Triazolam (Halcion)
Vardenafil (Levitra)
Vinblastine (Velban)
Vincristine (Oncovin)
1
(Get to Know an Enzyme: CYP1A2, 2007)
2
(Porubsky,Meneely&Scott, 2008)
3
(Get to Know an Enzyme: CYP3A4, 2007)

Herb-Herb Interactions:
Some common herbs which could cause additive hepatoxic effects with cinnamon
include chaparral, comfrey,DHEA, germander, kava, niacin, pennyroyal oil and
red yeast, Jin bu huan(Lycopodium serratum) (Nilesh, Ozick,& Gbadehan, 2010).
Toxicity:
Acute toxicity:

Acute poisoning of cinnamon oil can cause increased heart rate, nausea and vomiting,
acute pulmonary edema or respiratory stimulation and facial flushing (Perry, Dean, &
Krenzelok, 1990),( Cinnamon oil ;MSDS SLC5065, 2010)

Cinnamon bark oil : oral LD50 in rats = 4.16 g/kg and 3.4ml/kg (ESCOP, 2003 p 94),
(Braun&Cohen, 2010)

24
dermal LD50 in rabbits= 0.69ml/kg (Opdyke, 1975 ), (ESCOP, 2003 p94)

Cinnamon bark decoction (C. cassia)


LD50 for intravenous injection in mice= 18.48 1.8 g/kg (Chen& Chen, 2004)

Cinnamaldehyde
Derma LD50= doses greater than 0.2 grams/day or 15-20 grams of crude
herb.(ESCOP, 2003, p93)
Subacute or chronic toxicity:

Hepatotoxicity has been associated with coumarin found in C.cassia. A tolerable daily
intake has been set at 0.1mg/kg of coumarin per day
(Abraham,Whrlin,Lindtner,Heinemeyer &Lampen, 2010).

Fotland et al (2012) recently set an upper limit of dietary coumarin to 0.07mg/kg of body
weight / day based on a bench mark dose approach in humans.

Cinnamaldehyde added to the diet of rats for 16 weeks at 1% resulted in slight swelling
of hepatic cells and slight hyperkeratosis of the squamous portion of the stomach. No
effect was seen at lower concentrations. (ESCOP, 2003 p 94)

Mutagenicity, genotoxicity, and carcinogenicity:

Recent Ames test show mutagenic activity of cinnamon extracts, cinnamon bark oil and
cinnamaldehyde. (ESCOP, 2003 p94)

The bark oil also was mutagenic in the Bacillus subtilis DNA repair test. (ESCOP, 2003
p94)

Cinnamaldehyde and cinnamon bark oil gave positive results in chromosomal aberration
tests using Chinese hamster cell cultures as substrates. (ESCOP, 2003 p94)

Cinnamaldehyde showed genotoxic effects in Drosophilia test systems which was absent
from aqueous extracts. (ESCOP , 2003 p94)

Cinnamaldehyde and cinnamon extracts were cytotoxic in KB human carcinoma and


L1210 mouse leukaemia cell lines. (ESCOP, 2003 p94)

Overall the data n the mutagenicity and genotoxicity is insufficient to fully evaluate the
carcinogenic risk of cinnamon (ESCOP , 2003 p94)

Teratogenicity:

Evidence of teratogenicity from animal studies is contradictory. (Braun & Cohen, 2010)

25
One study demonstrated teratogenic effects of Cinnamaldehyde on chick embryos.
(ESCOP, 2003 p 94)

References

Abraham,K.,Whrlin,F.,Lindtner,O.,Heinemeyer,G.,and Lampen,A. (2010). Toxicology and risk


assessment of coumarin: Focus on human data. Mol.Nutr.Food Res. 54: 228-239 DOI
10.1002/mnfr.200900281

Altschuller,J.A.,Casella, S.J.,MacKenzie,T.A.,and Curtis, K.M. 2007. The Effect of Cinnamon


on A1C Among Adolescents with Type 1 Diabetes. Diabetes Care. 30(4): 813-816 Retrieved
from http://care.diabetesjournals.org/content/30/4/813.full.pdf+html

Bensky, D. & Gamble ,A. (compiled and translated) (1993). Chinese Herbal Medicine Materia
Medica (Revised Edition). Seattle Washington : Eastland Press Inc.

Bensky, D., Clavey, S., Stger, E. (2004) Chinese Herbal Medicine. Materia Medica . Third
Edition. Seattle, WA: Eastland Press, Inc.

Blevins, S.M., Leyva, M.J., Brown, J.,Wright, J., Scofield, R.H., and Aston, C.E.,2007 Diabtese
Care . 30(9): 2236-2238

Bone, K. (2003) A Clinical Guide to Blending Liquid Herbs: Herbal Formulations for the
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