Cinnamon and Health

Abstract

Cinnamon has been used as a spice and as traditional herbal medicine for centuries. The available in vitro and animal in vivo evidence suggests that cinnamon has anti-inflammatory, antimicrobial, antioxidant, antitumor, cardiovascular, cholesterol-lowering, and immunomodulatory effects. In vitro studies have demonstrated that cinnamon may act as an insulin mimetic, to potentiate insulin activity or to stimulate cellular glucose metabolism. Furthermore, animal studies have demonstrated strong hypoglycemic properties. However, there are only very few well-controlled clinical studies, a fact that limits the conclusions that can be made about the potential health benefits of cinnamon for free-living humans. The use of cinnamon as an adjunct to the treatment of type 2 diabetes mellitus is the most promising area, but further research is needed before definitive recommendations can be made.

Full text

Critical Reviews in Food Science and Nutrition
, 50:822–834 (2010)
Copyright C
 Taylor and Francis Group, LLC
ISSN: 1040-8398 print / 1549-7852 online
DOI: 10.1080/10408390902773052
Cinnamon and Health
JOERG GRUENWALD,1JANINE FREDER,2and NICOLE ARMBRUESTER1
1Analyze & realize ag, Berlin, Germany
2Science in Writing & Consulting, Glienicke/Nordbahn, Germany
Cinnamon has been used as a spice and as traditional herbal medicine for centuries. The available in vitro and animal in vivo
evidence suggests that cinnamon has anti-inflammatory, antimicrobial, antioxidant, antitumor, cardiovascular, cholesterol-
lowering, and immunomodulatory effects. In vitro studies have demonstrated that cinnamon may act as an insulin mimetic,
to potentiate insulin activity or to stimulate cellular glucose metabolism. Furthermore, animal studies have demonstrated
strong hypoglycemic properties. However, there are only very few well-controlled clinical studies, a fact that limits the
conclusions that can be made about the potential health benefits of cinnamon for free-living humans. The use of cinnamon
as an adjunct to the treatment of type 2 diabetes mellitus is the most promising area, but further research is needed before
definitive recommendations can be made.
Keywords Cinnamomum, spice, insulin, diabetes, cinnamon
INTRODUCTION
The purpose of this paper is to provide a comprehensive sum-
mary of the current scientific literature on the effect of cinnamon
on several physiological and health-related conditions.
Cinnamon has been used as a spice in several cultures for
centuries. In addition to its culinary uses, cinnamon has been
employed as a stomachic and carminative for gastrointestinal
complaints as well as other ailments and is still used for these
conditions in many countries (Teuscher, 2003). The German
Commission E and the European Scientific Cooperative on Phy-
totherapy (ESCOP) approved two medicinal herbs of the genus
Cinnamomum:C. zeylanicum (Blumenthal et al., 1998a; Eu-
ropean Scientific Cooperative on Phytotherapy, 2003) and C.
cassia (Blumenthal et al., 1998b). The bark is the only part
of these plants that is used as a spice or for medical purposes
(Cinnamomi cortex) (Blumenthal et al., 1998a; 1998b).
The volatile oils obtained from the bark, leaf, and root
bark of Cinnamomum zeylanicum and C. cassia vary signifi-
cantly in chemical composition which suggests that they vary
in their pharmacological effects as well (Shen et al., 2002;
Wijesekera, 1978). These oils of three different plant parts pos-
sess the same array of monoterpene hydrocarbons in different
proportions. However, each oil has a different primary con-
stituent: cinnamaldehyde (in the bark oil), eugenol (in the leaf
oil), or camphor (in the root-bark oil).
Address correspondence to: Nicole Armbruester, analyze & realize ag,
Waldseeweg 6, Berlin13467, Germany. Tel.: +49 (0)30 4000 8154; Fax: +49
(0)30 4000 8454. E-mail: na@a-r.ag
Three of the main components of the essential oil obtained
from the bark of C. zeylanicum are trans-cinnamaldehyde,
eugenol, and linalool, which, according to Chericoni et al.
(2005) represent 82.5% of the total composition. Trans-
cinnamaldehyde, the major component of C. zeylanicum bark
oil, accounts for approximately 49.9% (Singh et al. 2007) to
62.8% (Simic et al., 2004) of the total amount. Cinnamalde-
hyde and eugenol also are the major components of cinnamon
extract (Usta et al., 2002; 2003). The dried stem bark of C. cas-
sia contains four characteristic components—cinnamaldehyde,
cinnamic acid, cinnamyl alcohol, and coumarin. He et al. (2005)
identified high contents of cinnamaldehyde (13.01–56.93 mg/g)
in C. cassia bark. Friedman et al. (2000) found that eugenol
and linalool in foods are stable to heat, unlike pure cinnamalde-
hyde, which undergoes a temperature-dependent transformation
to benzaldehyde under the influence of heat starting at approxi-
mately 60◦C.
According to the U. S. Department of Agriculture (USDA)
Economic Research Services, 1,797,000 pounds of cinnamon
were imported into the U.S. for consumption in 2005.
DATA AND METHODS
An extensive database search was performed using the
databases PubMed, MEDLINE, EMBASE, BIOSIS, TOXLINE
and Google Scholar. Search terms used were as follows: “cin-
namon,” “Cinnamomum,” “cinnam∗” combined with “anti-
inflammatory,” “antioxidant,” “antiviral,” “viral,” “cancer,”
“cholesterol,” “dietary,” “diabetes,” “heart,” “immunomodul∗,”
822
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CINNAMON AND HEALTH 823
“Alzheimer,” “Parkinson.” Species of the genus Cinnamomum
other than C. zeylanicum (syn. C. verum) and C. cassia were ex-
cluded as well as most studies on plant parts other than the bark.
Retrieved abstracts were searched manually and more than 200
articles relevant to the efficacy of C. zeylanicum and C. cassia
were evaluated.
Results
Summary of Human Trials
Few human trials have been published that investigated the
efficacy of cinnamon on physiological parameters and health-
related conditions. However, recent in vitro and in vivo research
has discovered new properties of C zeylanicum and C. cassia,
which may be of interest for clinical use. The treatment of
diabetes (type 2) has been investigated in several clinical trials
(Blevins et al., 2007; Khan et al., 2003; Mangold et al., 2006;
Suppapitiporn et al., 2006; Vanschoonbeek et al., 2006) and
is probably the most well-documented health benefit of this
spice for humans. Nevertheless, additional research is needed
to determine whether cinnamon can help control this disease in
free-living patients. Furthermore, some evidence suggests that
cinnamon may be effective in the supportive treatment of cancer,
infectious diseases, and complaints associated with modern life
style due to its anti-inflammatory, antimicrobial, antioxidant,
and blood pressure-lowering effects. Unfortunately, human data
in this area is limited. One trial on Helicobacter pylori infection
(Nir et al., 2000) yielded negative results for cinnamon ingested
at daily doses of 80 mg as did a pilot trial (Quale et al., 1996)
on candidiasis in HIV-patients (daily dosage of cinnamon not
reported).
Dose-response trials are of paramount importance, as the
clinical studies on the hypoglycemic properties of cinnamon
have shown. The studies which did not yield statistically sig-
nificant results were carried out with a daily dose of ≤1.5gof
cinnamon. Significant positive effects were only found in studies
utilizing 3 to 6 g of cinnamon daily. One teaspoonful of cinna-
mon powder weighs approximately 1.5 g. It seems reasonable
that up to 2 teaspoons of this spice could easily be integrated
into a normal diet.
Preclinical and Clinical Evidence
Anti-inflammatory properties. The studies cited in this sec-
tion refer to the ability of cinnamon to affect inflammation, e.g.,
by counteracting the cyclooxygenase (COX) enzyme. Studies
dealing with related mechanisms of action are cited in the ap-
propriate sections—for example, the antioxidant activity may
influence the immunomodulary properties of a drug, which in
turn may cause an anti-inflammatory effect.
The inhibitors of prostaglandin biosynthesis and nitric oxide
production are potential anti-inflammatory and cancer chemo-
preventive agents. Cinnamomum cassia extracts showed potent
inhibition of cyclooxygenase-2 (COX-2) activity in lipopolysac-
charide (LPS)-induced mouse macrophage RAW264.7 cells
(Hong et al., 2002). The main constituents of cinnamon,
eugenol, and cinnamaldehyde, were found to inhibit COX-2
in vitro in a rapid semi-homogeneous COX-2 enzymatic assay
(Huss et al., 2002).
The redox sensitive, pro-inflammatory nuclear transcrip-
tion factor NF-kappaB plays a key role in inflammation. Cin-
namaldehyde derivatives based on 2-hydroxycinnamaldehyde
isolated from the bark of C. cassia significantly inhibited
lipopolysaccharide (LPS)-induced nitric oxide (NO) produc-
tion and NF-kappaB transcriptional activity in a dose-dependent
manner (Lee et al., 2005). 2-Hydroxycinnamaldehyde had the
strongest inhibitory effect on NO production among the cinna-
maledhyde derivatives through inhibition of NF-kappaB activa-
tion, and thus could be used as an anti-inflammatory agent due
to its antioxidant properties.
Kim et al. (2007) recently examined cinnamaldehyde
further for its molecular modulation of inflammatory NF-
kappaB activation via the redox-related NF-kappaB/IχB kinases
(NIK/IKK) and mitogen-activated protein kinase (MAPK) path-
ways through the reduction of oxidative stress. Results show
that age-related NF-kappaB activation upregulated NF-kappaB
targeting genes, inflammatory iNOS, and COX-2, all of which
were effectively inhibited by cinnamaldehyde. Cinnamaldehyde
furthermore inhibited the activation of NF-kappaB via three
signal transduction pathways—NIK/IKK, extracellular signal-
regulated kinases, and p38 MAPK. It is likely that the antiox-
idative effect of cinnamaldehyde and the restoration of redox
balance are responsible for its anti-inflammatory action.
As this section has suggested, the bark of C. cassia,
probably due to its cinnamaldehyde content, demonstrates clear
anti-inflammatory properties in vitro. Additional information is
provided below in the sections on “antioxidant properties” and
“immunomodulatory properties.”
Antimicrobial Properties
Antibacterial properties. Spices have been traditionally used
since ancient times for their antiseptic and disinfectant prop-
erties. De et al. (1999) carried out a preliminary screening for
antimicrobial activities of 35 different Indian spices. Cinnamon,
among others, has potent antimicrobial activity against the test
organisms Bacillus subtilis and Escherichia coli.
Cinnamon bark oil as well as cinnamaldehyde and eugenol
showed potent antibacterial effects against Bacillus cereus,
Campylobacter jejuni, Enterococcus faecalis, Escherichia coli,
Listeria monocytogenes, Haemophilus influenzae, Salmonella
choleraesuis, S. enterica, Pseudomonas aeruginosa, Staphy-
lococcus aureus, Streptococcus pneumoniae, and S. pyogenes,
as well as Yersinia enterocolitica (Friedman et al., 2002;
Inouye et al., 2001; L´
opez et al., 2005; Smith-Palmer et al.,
1998). In general, Gram-positive bacteria were more sensitive
to inhibition by the plant essential oil than Gram-negative
bacteria. Campylobacter jejuni was the most resistant
of the bacteria investigated (Smith-Palmer et al., 1998).
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824 J. GRUENWALD ET AL.
Cinnamaldehyde showed the strongest antibacterial effective-
ness of the constituents examined (L´
opez et al., 2007).
Oussalah et al. (2006) studied the mechanism of the an-
timicrobial action of the essential oil of C. cassia against cell
membranes and walls of bacteria by measurement of intracellu-
lar pH and ATP concentration, the release of cell constituents,
and electronic microscopy of the cells when the essential oil at
its minimum inhibitory concentration was in contact with E. coli
and L. monocytogenes. A significantly (p≤0.05) higher cell
constituent release compared to untreated controls was observed
in the supernatant when E. coli and L. monocytogenes cells were
treated with C. cassia oil. The oil reduced the intracellular pH of
E. coli and decreased the intracellular pH of L. monocytogenes
significantly (p≤0.05 for both). Electronic microscopy obser-
vations revealed that the cell membrane of both treated bacteria
was significantly damaged. These results suggest that the cyto-
plasmic membrane is involved in the toxic action of essential
oils. Senhaji et al. (2007) found that in the presence of 0.05% of
the essential oil from C. zeylanicum,mostofE. coli cells were
killed after 30 min, suggesting that the antimicrobial activity of
essential oil is bactericidal.
Aqueous and ethanolic C. cassia extracts exhibited strong
inhibitory effects on collagenolytic activity of Porphyromonas
gingivalis (Osawa et al., 1991). These extracts are effective in
reducing the pathogenicity of periodontopathic bacteria. The
extracts of C. cassia also had relatively strong anti-cytotoxic
activity. Azumi et al. (1997) found a substance in cinnamon
bark that inhibits the activity of bacterial endotoxin (LPS). Fur-
thermore, the inhibitor abrogated the pyrogenicity of the LPS.
Watt et al. (2007), however, found no antibacterial activity in
C. zeylanicum tincture using luminescent bacterial biosensors
(E. coli strains).
Antifungal properties. The essential oils of several Cin-
namomum species have been shown to have anticandidal
(Candida albicans, C. glabrata) and antidermatophytic (Mi-
crosporum canis, Trichophyton mentagrophytes, T. rubrum)
activity in vitro (Mastura et al., 1999). The essential oil
of the leaves of C. zeylanicum demonstrated only modest
antifungal properties. However, according to Simic et al.
(2004), the essential oil of C. zeylanicum (plant part not
specified) showed the strongest antifungal activity compared
to Aniba roaeodora, Laurus nobilis and Sassafras albidum
against 17 micromycetes (Aspergillus niger, A. ochraceus, A.
versicolor, A. flavus, A. terreus, Alternaria alternata, Aure-
obasidium pullulans, Penicillium ochrochloron, P. funiculo-
sum, Cladosporium cladosporioides, C. Fulvium, Trichoderma
viride, Fusarium tricinctum, F. sprortrichoides, Phoma mac-
donaldii, Phomopsis helianthi, Mucor mucedo)in vitro. Trans-
cinnamaldehyde was the most active component in the oil of C.
zeylanicum.
Singh et al. (1995) identified cinnamic aldehyde as the active
fungitoxic constituent of C. zeylanicum bark oil. The fungitoxic
properties of the vapors of the oil/active constituent were es-
tablished against fungi involved in respiratory tract infections
(mycoses), i.e., Aspergillus niger, A. fumigatus, A. nidulans A.
flavus, Candida albicans, C. tropicalis, C. pseudotropicalis, and
Histoplasma capsulatum. The authors concluded that these in-
halable vapors appear to approach the ideal chemotherapy for
respiratory tract mycoses.
Cinnamon oil demonstrated inhibitory activity against As-
pergillus flavus, A. parasiticus, A. ochraceus, Fusarium monil-
iforme, F. graminearum and F. proliferatum as well as Saccha-
romyces cerevisiae in several further studies (De et al., 1999;
Soliman and Badeaa, 2002; Ranasinghe et al., 2002; Bartine and
Tantaoui-Elaraki, 1997; Velluti et al., 2003; Velluti et al., 2004).
Furthermore, oils obtained from C. zeylanicum were found to
be most active in vitro tested against dermatophyte strains iso-
lated from patients with dermatophytosis inhibiting 80% of the
dermatophyte strains tested (Lima et al., 1993).
Oral candidiasis is a frequent occurance in patients with HIV-
infection. Treatment of this condition with an oral azole is gener-
ally effective. However, fluconazole-resistant Candida species
are an emerging problem. C. zeylanicum shows in vitro activity
against fluconazole-resistant and -susceptible Candida isolates
(Quale et al., 1996).
CLINICAL TRIALS
Quale et al. (1996) conducted a pilot study in five patients
with HIV infection and oral candidiasis to investigate the activity
of cinnamon (Cinnamomum zeylanicum) against fluconazole-
resistant and –susceptible Candida isolates. All patients studied
had pseudomembranous candida infection confirmed by culture.
Patients were given eight lozenges of a cinnamon candy daily
(no further information given). The commercially available ex-
tract was administered for one week. Three of the five patients
had improvement of their oral candidiasis (no further details
given). The pilot study was neither randomized nor blinded,
and the sample size was very small. Further clinical trials will
be necessary to determine the usefulness of cinnamon for the
treatment of mucosal candidiasis.
Antiviral Properties
ACinnamomum cassia bark extract was highly effective
against HIV-1 and HIV-2 replication in terms of inhibition of
virus-induced cytopathogenicity in MT-4 cells infected with
HIV (Premanathan et al., 2000). Cinnamaldehyde derived from
cinnamon bark has an inhibitory effect on the growth of in-
fluenza A/PR/8 virus in vitro (Madin-Darby canine kidney cells)
and in vivo (mice infected with the lung-adapted PR-8 virus;
Hayashi et al., 2007).
The available in vitro data demonstrate that C. cassia bark oil
as well as aqueous and ethanolic extracts have potent antibac-
terial and highly effective antiviral properties against Gram-
positive and Gram-negative bacteria as well as HI- and influenza
virus, respectively. These properties have not been reported for
C. zeylanicum, even though the two cinnamon species have
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CINNAMON AND HEALTH 825
similar constituents. The essential oil of C. zeylanicum,how-
ever, demonstrated potent antifungal activity. Further in vitro
and in vivo research in addition to human data is needed to
confirm the antimicrobial properties of cinnamon in free-living
individuals.
Antioxidant Properties
Spices and vegetables possess antioxidant activity that can
reduce lipid peroxidation in biological systems (Shobana and
Naidu, 2000). Reactive oxygen species have been implicated in
a range of human diseases such as atherosclerosis and certain
cancers (Halliwell, 2007). Oxidative processes generally play a
key role in inflammatory and immune processes. As oxidative
stress has been implicated in the pathogenesis of many human
diseases, the use of antioxidants in pharmacology is widely
studied (Clark, 2002). Dragland et al. (2003) found very high
concentrations of antioxidants (i.e., >75 mmol/100 g) in the
medicinal herb Cinnamomi cortex. The authors speculate that
several of the effects of this herb are mediated by their antioxi-
dant activities.
A water and alcoholic extract (1:1) of cinnamon showed sig-
nificant inhibition of lipoxygenase-dependent enzymatic lipid
peroxidation in an in vitro lipid peroxidation assay (Shobana
and Naidu, 2000). Etheric, methanolic, and aqueous cinnamon
extracts, inhibited in vitro oxidation in a beta-carotene/linoleic
acid system (Mancini-Filho et al., 1998).
Ethanol extracts of dry bark of C. cassia exhibited a greater
inhibition of lipid peroxidation of rat liver homogenate in vitro
than alpha-tocopherol, high superoxide anion scavenging activ-
ity, strong anti-superoxide formation activity (P <0.05), and ex-
cellent antioxidant activity in enzymatic and nonenzymatic liver
tissue oxidative systems (Lin et al., 2003). Cinnamon exhibited
a higher percentage of inhibition of oxidation than butylated
hydroxyanisole, butylated hydroxytoluene, and propyl gallate
as tested by the lipid peroxidation assay (Murcia et al., 2004).
Cinnamomi cortex also has inhibitory effects on lipid perox-
idation and protein oxidative modification by copper (Toda,
2003).
Cinnamon oil exhibited superoxide dismutase (SOD)-like
activity measured by the inhibition of pyrogallol autoxidation
that is catalyzed by the superoxide radical (Kim et al., 1995).
The volatile extracts of cinnamon showed moderate antioxi-
dant activities in the aldehyde/carboxylic acid assay and in the
conjugated diene assay (Lee and Shibamoto, 2002).
The essential oil obtained from the bark of C. zeylanicum and
three of its main components, eugenol, (E)-cinnamaldehyde,
and linalool, were tested in two in vitro models of peroxynitrite-
induced nitration and lipid peroxidation. The essential oil and
eugenol showed very powerful activities. (E)-cinnamaldehyde
and linalool were completely inactive (Chericoni et al., 2005).
However, C. cassia bark-derived trans-cinnamaldehyde showed
potent inhibitory effects on NO production in RAW 264.7 cells,
determined through the evaluation of NO production and expres-
sion of inducible nitric oxide. Little or no activity was observed
for cinnamic acid and eugenol (Lee et al., 2002).
Several flavonoids obtained from cinnamon that were re-
ported to exhibit antioxidant and free radical scavenging activi-
ties were tested for their 1,1-diphenyl-2-picrylhydrazyl (DPPH)
radical scavenging activity (Okawa et al., 2001). Recently,
Prakash et al. (2007) found strong free radical-scavenging ac-
tivities in the bark of C. zeylanicum as indicated by a very low
inhibitory concentration value, efficiency concentration value
(DPPH), and reducing power value (ascorbic acid equivalents)
as well as a reasonably high value of anti-radical power. These
findings confirm earlier results by Shan et al. (2005), which
indicate very strong activity for C. zeylanicum and a relatively
high activity for C. cassia.
Animal Studies
Dhuley (1999) assessed the antioxidant properties of C.
zeylanicum in vivo through the measurement of hepatic and
cardiac antioxidant enzymes, glutathione (GSH) content and
lipid conjugated dienes in rats fed a high fat diet containing
10% cinnamon. The antioxidant enzyme activities were
significantly enhanced whereas the GSH content was markedly
restored in rats fed a high-fat diet containing spices. In addition,
cinnamon partially counteracted the primary products of lipid
peroxidation (i.e., increase in lipid conjugated dienes and
hydroperoxides) in this system. These observations suggest that
this spice exerts antioxidant protection through its ability to
activate antioxidant enzymes. C. cassia pretreatment decreased
liver cytochrome P450 content, but increased GSH content
and the activity of the glutathione-dependent antioxidant
enzymes glutathione S-transferase, glutathione reductase, and
glutathione peroxidase. Hence, the antimutagenic potential of
C. cassia could be attributed to its modulatory effect on the
xenobiotic bioactivation and detoxification processes.
High fructose feeding in normal rats facilitates oxidative
damage. Suganthi et al. (2007) evaluated a spice mixture con-
taining 1.0 g/100 g of cinnamon bark for its effect on oxida-
tive stress markers and antioxidant potential in tissues of high
fructose-fed insulin-resistant rats. Administration of the spice
mixture along with dietary fructose reduced the levels of perox-
idation markers in tissues and improved the antioxidant status
compared to rats receiving dietary fructose alone.
In conclusion, numerous in vitro studies and one in vivo trial
demonstrate the antioxidant potential of Cinnamomum cassia
and C. zeylanicum. However, the in vivo data are scarce and
no human data are available to confirm the beneficial effects of
cinnamon with respect to its antioxidant properties. Halvorsen
et al. (2006) generated a ranked food table with values for total
content of redox-active compounds (i.e., antioxidants). Ground
cinnamon ranked fourth with regard to total antioxidant content
(17.647 mM/100 g) but was not among the 50 foods with the
highest antioxidant contents per serving size. Based on the work
of Wu et al. (2004), the USDA published the oxygen radical
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826 J. GRUENWALD ET AL.
absorbance capacity (ORAC) of selected foods. Both lipophilic
(L-ORAC) and hydrophilic (H-ORAC) antioxidant capacities
were determined. Ground cinnamon had values of 34.53 µMof
Trolox equivalent (TE)/g and 2640.83 µM TE/g for L- and H-
ORAC, respectively. Total ORAC was 2675.36 µM TE/g. These
data show that cinnamon used as a spice has potentially high
antioxidant content, and can contribute to the total antioxidant
content of the diet.
Antitumor Properties
As has been stated above, antitumor and anti-cancer prop-
erties of a substance are closely related to its antioxidant and
immunomodulatory properties. Studies on the antioxidant and
immunomodulatory properties of C. zeylanicum and C. cassia
may imply antitumor properties. However, additional studies
on cinnamon bark and its main constituent cinnamaldehyde are
needed in order to investigate their precise antitumor properties.
Ka et al. (2003) investigated the effects of cinnamaldehyde on
the cytotoxicity, induction of apoptosis and putative pathways of
its actions in human promyelocytic leukemia cells. Cinnamalde-
hyde was a potent inducer of apoptosis in these studies. The
authors concluded that the anticancer effects of cinnamalde-
hyde result from induction of reactive oxygen species (ROS)-
mediated mitochondrial permeability transition and resultant
cytochrome C release. Nishida et al. (2003) found that C. cassia
induced death of HL-60 cells as demonstrated by the reduc-
tion of mitochondrial transmembrane potential and increased
caspase-3 activity. According to the authors, the apoptosis in-
duced by C. cassia occurred via the mitochondrial route and
the apoptosis-conducting mechanism acted through a cascade
involving caspase-3.
Kwon et al. (1998) synthesized cinnamaldehydes and re-
lated compounds from various cinnamic acids based on the
2-hydroxycinnamaldehyde isolated from the bark of C. cassia.
Cinnamic acid, cinnamates, and cinnamyl alcohols did not show
cytotoxicity against several human solid tumor cells. HCT15 and
SK-MEL-2 cells, however, were much more sensitive to these
cinnamaldehyde analogues. Cytotoxicity of the saturated alde-
hydes was much weaker compared to their unsaturated counter-
parts.
Matrix metalloproteinase-9 (MMP-9) degrades type IV colla-
gen, the major structural component of the basement membrane
and the extra cellular membrane (Seo et al., 2005). The activity
of this enzyme is found to be elevated in tumor tissues. The
hexane and chloroform fractions as well as water extracts of
C. cassia showed a weak inhibitory effect on MMP-9 activity.
However, a strong MMP-9 inhibition was found in the butanol
fraction of C. cassia.
2-Hydroxycinnamaldehyde (HCA) and 2-benzoyloxy-
cinnamaldehyde (BCA) isolated from C. cassia strongly in-
hibited in vitro growth of 29 kinds of human cancer cells and
in vivo growth of SW-620 human tumor xenograft without loss
of body weight in nude mice (Lee et al., 1999). HCA pre-
vented adherence of SW-620 cells to the culture surface but did
not inhibit oncogenic K-Ras processing, implying its antitumor
mechanisms are at the cellular level.
Haranaka et al. (1985) suggested that one mechanism un-
derlying the antitumor activity of Cinnamomi cortex is based
on stimulation of the reticuloendothelial system (RES) and is
closely related to tumor necrosis factor (TNF) production. The
drug was given to DDY mice in drinking water before and af-
ter transplantation of Ehrlich tumors. A good survival rate was
found in the group administered Cinnamomi cortex. Relatively
high levels of TNF activity were noted in the group given cin-
namon. The TNF capacity for production broadly paralleled the
survival rate of the mice transplanted to Ehrlich tumors.
Abraham et al. (1998) assessed antigenotoxic effects and
changes in glutathione S-transferase (GST) activity in mice
after oral co-administration of urethane (URE), a carcino-
genic substance, with an aqueous extract of cinnamon. The
results of the genotoxicity assay (micronucleus test) demon-
strated dose-related antigenotoxic effects after URE was co-
administered with the extract. Furthermore, an aqueous extract
prepared from cinnamon seemed to interact with phosphory-
lation/dephosphorylation signaling activities in three myeloid
cell lines (Jurkat, Wurzburg, and U937), thus reducing cellu-
lar proliferation and blocking the G2/M phase of the cell cycle
(Schoene et al., 2005).
Furthermore, C. cassia exerted significant antimutagenic ef-
fects against benzo[a]pyrene and cyclophosphamide in mice
pretreated with the plant extract as shown by the Ames test, the
bone marrow chromosomal aberration assay, and the micronu-
cleus test (Sharma et al., 2001).
In conclusion, the available in vitro and in vivo data suggest
that cinnamon has antitumor properties that are probably related
to its antioxidant activity.
Blood Pressure-Lowering Properties
Cinnamomum cassia bark affects the blood and cardiovascu-
lar system (Chen 1981). The cardiovascular properties of cin-
namon are closely connected to its effects on blood lipids and
glucose metabolism. Many agents (nutrients, nutraceuticals, and
drugs) that enhance insulin sensitivity and/or reduce circulating
insulin concentrations also lower blood pressure (Preuss et al.,
2006). Cinnamon (8% w/w) in the diet reduced the systolic
blood pressure of spontaneously hypertensive rats (SHR) eat-
ing sucrose-containing diets to virtually the same levels as SHR
consuming diets containing non sucrose. The presence of cin-
namon in the diet also decreased the systolic blood pressure
of SHR consuming a non sucrose-containing diet, suggesting
that cinnamon reduces more than just sucrose-induced blood
pressure elevations.
Cinnamomum cassia bark increases the level of atrial natri-
uretic factor (ANF) in the plasma of mice (Zhou et al., 1995).
ANF acts to reduce the water, sodium, and adipose loads on the
circulatory system, thereby reducing blood pressure. ANF was
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CINNAMON AND HEALTH 827
significantly higher in the plasma of mice after giving C. cassia
orally, compared with control (p<0.001).
In conclusion, available in vivo data strongly support the
hypothesis that cinnamon lowers systolic blood pressure in ex-
perimental animals.
Cholesterol- and Lipid-Lowering Properties
Several spices, e.g. garlic or ginger, have been shown to
have beneficial hypolipidemic or hypocholesterolemic proper-
ties (Sambaiah and Srinivasan, 1991). In a study undertaken
to screen several spices, C. zeylanicum did not lower serum or
liver cholesterol concentrations of rats when included in the diet
at about 5-fold the normal human intake level (i.e., 0.05% of
the diet). In contrast, cholesterol concentrations were increased
by 25% in cinnamon fed animals (Sambaiah and Srinivasan,
1991). However, hypocholesterolemic effects were reported in a
very recent study conducted to isolate and identify the putative
antidiabetic compounds of C. zeylanicum based on bioassay-
guided fractionation. It was found that cinnamaldehyde signif-
icantly (p<0.05) decreased plasma glucose concentration in
a dose-dependent manner (63.29%) compared to the control in
streptozotocin-induced male diabetic Wistar rats (Subash Babu
et al., 2007). The results of this study indicate that cinnamalde-
hyde possesses hypolipidemic effects in streptozotocin-induced
diabetic rats.
Kim et al. (2006a) demonstrated the effect of C. cassia extract
on blood lipids in an in vivo study. HDL-cholesterol concentra-
tions were significantly higher (p<0.01) in mice fed with
cinnamon extract, and the concentrations of triglyceride and in-
testinal alpha-glycosidase activity were significantly lower (p<
0.01), after 6 weeks. These results suggest that cinnamon extract
has a regulatory role in blood lipids and it may also exert a blood
glucose-suppressing effect by improving insulin sensitivity or
slowing absorption of carbohydrates in the small intestine.
In conclusion, several in vivo studies strongly suggest that
C. zeylanicum and C. cassia have cholesterol-lowering proper-
ties. Khan et al. (2003) determined whether cinnamon improves
blood glucose, triglyceride, total cholesterol, HDL cholesterol,
and LDL cholesterol levels in people with type 2 diabetes (see
“Hypoglycemic properties (including diabetes (type 1, type 2))”
below). After 40 days, 1, 3, or 6 g of cinnamon daily reduced
mean fasting serum glucose (18–29%), triglyceride (23–30%),
LDL cholesterol (7–27%), and total cholesterol (12–26%) lev-
els; no significant changes were noted in the placebo groups.
Changes in HDL cholesterol were not significant. However,
more clinical trials, especially with healthy volunteers and peo-
ple suffering from hyperlipidemia, are needed to confirm the
cholesterol- and lipid-lowering effects for humans.
Gastroprotective Properties (including H. pylori Infection)
Helicobacter pylori has been associated with the pathogen-
esis of antral gastritis, duodenal ulcer, and gastric lymphoma,
and the eradication of this organism has been shown to reverse
or prevent relapse of these diseases. Antimicrobials employed
in the eradication of H. pylori are not without adverse effects
(Chiba et al., 1992). Newer treatment modalities, therefore, are
required (Nir et al., 2000).
Cinnamon extract (from methylene chloride) inhibited H. py-
lori growth at a concentration range typical of common antibi-
otics (Tabak et al., 1999). The efficiency of cinnamon extracts in
liquid medium and its resistance to low pH levels may enhance
its effect in an environment such as the human stomach.
Animal Studies
Tanaka et al. (1989) showed that 3-(2-hydroxyphenyl)-
propanoic acid and its O-glucoside isolated from the stem
bark of C. cassia prevented serotonin-induced ulcerogenesis
in rats after per oral (p.o.) administration. The former com-
pound, administered orally or parenterally to rats at a remark-
ably low dose (40 µg/kg body weight), also inhibited gastric
ulcers induced by phenylbutazone, ethanol, and water immer-
sion stress. The authors suggest that the antiulcerogenicity of
3-(2-hydroxyphenyl)-propanoic acid may be due to cytoprotec-
tion comparable to prostaglandin E2.
Clinical Trials
A pilot study (Nir et al., 2000) was conducted to test the ac-
tivity of an alcoholic extract of cinnamon in a group of patients
infected with H. pylori (see Table 1). This study found that cin-
namon extract, at a concentration of 80 mg/day as a single agent,
was ineffective in eradicating H. pylori. The authors concluded
that a combination of cinnamon with other antimicrobials, or
a higher concentration of cinnamon extract may have had an
effect. Further studies are needed to test this hypothesis.
An in vivo study (Tanaka et al., 1989) supports the hypothesis
that cinnamon may have gastroprotective properties via inhibi-
tion of gastric ulcers. However, despite the positive outcomes
of an in vitro study (Tabak et al., 1999), there is no direct evi-
dence to suggest that cinnamon can affect H. pylori infection in
humans.
Hypoglycemic Properties (including Diabetes (type 1, type 2))
Diabetes mellitus is the sixth leading cause of death in the
United States where it affects an estimated 20.8 million peo-
ple (Chase and McQueen, 2007). The prevalence of adult onset
(type 2) diabetes greatly exceeds that of juvenile onset (type
1) diabetes in this population (Pham et al., 2007). Over the
past several years, the effectiveness of cinnamon supplemen-
tation for the management of diabetes has received world-
wide media attention. Several in vitro (Anderson et al., 2004;
Berrio et al., 1992; Broadhurst et al., 2000; Cao et al., 2007;
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Tab l e 1 Clinical trials of cinnamon extracts (Cinnamomum zeylanicum, C. cassia)
Disease Study
design
No. of patients Dosage Duration Main result Facility Reference
Oral candidiasis Pilot study 5 with HIV
infection
— 1 week Three of the five patients had improvement
of their oral candidiasis (no further
details given).
Department of Veterans
Affairs Medical Center
at Brooklyn, New
York, U.S.A.
Quale et al.,
1996
Helicobacter
pylori infection
Pilot study 23 80 mg/day 4 weeks The cinnamon extract was ineffective. Bnai Zion Medical
Center, Technion,
Haifa, Israel
Nir et al., 2000
Insulin resistance Pilot study
(RCT)
15 women with
polcystic
ovary
syndrome
999 mg/day 8 weeks Comparisons of post-treatment to baseline
insulin sensitivity indices using fasting
and 2-hour oral glucose tolerance tests
showed significant (p<0.05)
reductions in insulin resistance in the
cinnamon group but not in the placebo
group.
College of Physicians and
Surgeons, Columbia
University, New York,
New York, U.S.A.
Wang et al.,
2007
Adolescent type 1
diabetes
RCT 72 1 g/day 90 days No significant differences in final HbA1C,
change in HbA1C, total daily insulin
intake, or no. of hypoglycemic episodes
between the cinnamon and placebo
groups.
Dartmouth College,
Hanover, New
Hampshire, U.S.A.
Altschuler et al.,
2007
Type 2 diabetes RCT 60 1.5 g C.
cassia
powder
daily
12 weeks C. cassia powder did not significantly
reduce fasting plasma glucose, HbA1c
or serum lipid profile.
King Chulalongkorn
Memorial Hospital,
Bangkok, Thailand
Suppapitiporn
et al., 2006
Type 2 diabetes RCT 58 1 g/day 12 weeks No significant changes in fasting glucose,
lipid, HbA1c, or insulin levels.
University of Oklahoma,
Oklahoma City,
Oklahoma, U.S.A.
Blevins et al.,
2007
Type 2 diabetes RCT 25 post-
menopausal
women
1.5 g/day 6 weeks No interactions for plasma HbA1c, fasting
glucose, insulin concentrations, or
fasting blood lipid concentrations.
Maastricht University,
Maastricht, The
Netherlands
Vanschoonbeek
et al., 2006
Type 2 diabetes RCT 79 3 g
cinnamon
powder
daily
4 months There was a significantly (p=0.046)
higher reduction of fasting plasma
glucose concentration in the cinnamon
group (10.3%) than in the placebo group
(3.4%). No significant differences were
observed regarding HbA1C, and lipid
profiles.
University of Hannover,
Hannover, Germany
Mang et al.,
2006
Type 2 diabetes RCT 60 1-6 g/day 40 days Cinnamon reduced mean fasting serum
glucose (18–29%), triglyceride
(23–30%), LDL cholesterol (7–27%),
and total cholesterol (12–26%) levels (P
<0.05 for each). No significant changes
were noted in the placebo groups.
Changes in HDL cholesterol
concentrations were not significant.
NWFP Agricultural
University, Peshawar,
Pakistan
Khan et al.,
2003
828
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CINNAMON AND HEALTH 829
Imparl-Radosevich et al., 1998; Jarvill-Taylor et al., 2001; Khan
et al., 1990; Kim et al., 2006b; Kreydiyyeh et al., 2000; Lee,
2002; Roffey et al., 2006; Taher et al., 2004; Talpur et al., 2005)
and in vivo studies (Kannappan et al., 2006; Kim et al., 2006a;
2006b; Onderoglu et al., 1999; Qin et al., 2003; 2004; Subash
Babu et al., 2007; Verspohl et al., 2005) on the effects of cin-
namon on insulin resistance and glucose metabolism have been
published. Clinical trials investigating the effects of cinnamon in
healthy subjects (Hlebowitz et al., 2007; Solomon and Blannin,
2007) as well as the efficacy of cinnamon in the treatment of
diabetes mellitus type 1 and 2 (Altschuler et al., 2007; Blevins
et al., 2007; Khan et al., 2003; Mang et al., 2006; Suppapitiporn
et al., 2006; Vanschoonbeek et al., 2006) or insulin resistance
(Wang et al., 2007) have also been published (see below).
In Vitro Studies
In vitro studies conducted with extracts or constituents of
Cinnamomum zeylanicum or C. cassia have demonstrated that
cinnamon may act as an insulin mimetic, to potentiate insulin
activity or to stimulate cellular glucose metabolism.
The causes and control of type 2 diabetes mellitus are not
clear, but there is strong evidence that dietary factors are in-
volved in its regulation and prevention. Anderson et al. (2004)
isolated water-soluble polyphenol polymers from cinnamon that
increase insulin-dependent in vitro glucose metabolism roughly
20-fold and display antioxidant activity.
Insulin resistance and type 2 diabetes mellitus are rapidly
increasing throughout the world. Various combinations of es-
sential oils including cinnamon, cumin, fenugreek, and oregano
have been shown to enhance insulin sensitivity in in vitro exper-
iments. Talpur et al. (2005) found that the ability to alter systolic
blood pressure in rat models was the most sensitive early index
of insulin sensitivity. The combined essential oils lowered circu-
lating glucose concentrations and systolic blood pressure in both
Zucker fatty rats (a model of obesity and insulin resistance) and
SHR (a model of genetic hypertension), suggesting that these
natural products are capable of enhancing insulin sensitivity.
However, it is not possible to make specific conclusions regard-
ing the essential oil of cinnamon because only combinations of
essential oils were used in this study.
Kim et al. (2006b) looked for a new anti-diabetic com-
pound using derivatives of hydroxycinnamic acids puri-
fied from cinnamon. A naphthalenemethyl ester of 3,4-
dihydroxyhydrocinnamic acid (DHH105) showed the highest
glucose transport activity in vitro. According to the results re-
ceived from in vivo trials with diabetic C57BL/6 mice and
spontaneously diabetic ob/ob mice the authors conclude that
DHH105 lowers blood glucose levels through the enhancement
of glucose transport, mediated by an increase in insulin-receptor
signaling.
Roffey et al. (2006) examined the effects of an aqueous ex-
tract of C. zeylanicum on glucose uptake and adiponectin secre-
tion in 3T3-LI adipocytes in the presence or absence of insulin.
The results indicate that although aqueous cinnamon extract has
insulin-mimetic action in 3T3-LI adipocytes in terms of glu-
cose uptake, secretion of the antidiabetic hormone adiponectin
is adversely affected.
Jarvill-Taylor et al. (2001) investigated the ability of a hy-
droxychalcone from cinnamon to function as an insulin mimetic
in 3T3-LI adipocytes. Comparative experiments were performed
with the cinnamon methylhydroxychalcone polymer (MHCP)
and insulin with regard to glucose uptake, glycogen synthe-
sis, phosphatidylinositol-3-kinase dependency, glycogen syn-
thase activation, and glycogen synthase kinase-3beta activity, as
well as the phosphorylation state of the insulin receptor. MHCP
seems to be an effective mimetic of insulin and may be useful
in the treatment of insulin resistance.
Cao et al. (2007) showed that water-soluble cinnamon extract
and HPLC-purified cinnamon polyphenols with doubly-linked
procyanidin type-A polymers displayed insulin-like activity.
The effects of cinnamon on the protein and mRNA levels of
insulin receptor, glucose transporter 4, and tristetraprolin were
investigated in mouse 3T3-LI adipocytes. The results suggest
that cinnamon exhibits the potential to increase the amount of
proteins involved in insulin signaling, glucose transport, and the
anti-inflammatory/anti-angiogenesis response.
Taher et al. (2004) investigated the ability of cinnamon (C.
zeylanicum) extracts to stimulate preadipocytes of the cell line
3T3-L1 and studied the effect of cinnamon extracts as an al-
ternative to insulin in 3T3-LI adipocytes using the oil red O
staining method. Cinnamtannin B1 and water extracts of cin-
namon induced adipocyte differentiation of 3T3-L1 cells. The
authors concluded that cinnamtannin B1 or cinnamon water ex-
tracts can promote adipogenesis similar to insulin.
Cinnamon was highly active in the insulin-dependent uti-
lization of glucose using a rat epididymal adipocyte assay and
may therefore play a role in improving glucose and insulin
metabolism (Broadhurst et al., 2000). Cinnamon extracts have
furthermore been shown to potentiate the action of insulin in iso-
lated rat epididymal adipocytes (Berrio et al., 1992). Increased
activity of the insulin-stimulated utilization of glucose by the
extract in the absence of added insulin was observed.
Khan et al. (1990) investigated an unidentified factor that
potentiates the action of insulin in glucose metabolism in se-
lected foods and spices in the rat epididymal fat cell assay.
Cinnamon potentiated insulin activity by a factor of 4.3. These
results were confirmed by Imparl-Radosevic et al. (1998).
Bioactive compounds extracted from cinnamon potentiate in-
sulin activity, as measured by glucose oxidation in the rat
epididymal fat cell assay. Enzyme studies done in vitro sug-
gest that certain cinnamon compounds, like insulin, affect pro-
tein phosphorylation-dephosphorylation reactions in the intact
adipocyte.
Aldose reductase is an enzyme in carbohydrate metabolism
that converts glucose to its sugar alcohol form, sorbitol, us-
ing NADPH as the reducing agent. Lee (2002) prepared aldose
reductase from lenses of Sprague-Dawley male rat eyes. Cin-
namaldehyde effectively inhibited aldose reductase. Cinnamyl
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830 J. GRUENWALD ET AL.
alcohol, transcinnamic acid, and eugenol exhibited only weak
inhibition against aldose reductase. In comparison, quercitrin (a
glycoside formed from the flavonoid quercetin and the deoxy
sugar rhamnose) was 6 times more potent than cinnamaldehyde.
Finally, the aqueous extracts of cinnamon significantly low-
ered the absorption of alanine from the rat intestine. Alanine
is an important amino acid for gluconeogenesis; it is converted
back to pyruvate within the liver and used as a gluconeogenic
substrate (Kreydiyyeh et al., 2000).
Animal Studies
Verspohl et al. (2005) evaluated the in vivo effect of extracts
from C. cassia and C. zeylanicum on blood glucose and plasma
insulin concentrations in rats under various conditions. C. cassia
extract was superior to C. zeylanicum extract in this regard. A
decrease in blood glucose concentrations was observed in a
glucose tolerance test, whereas no such difference occurred in
rats that were not challenged by a glucose load. The elevation in
plasma insulin was direct since a stimulatory in vitro effect of
insulin release from INS-1 cells (an insulin secreting cell line)
was observed. Thus these data suggest that the C. cassia extract
has a direct antidiabetic potency.
Onderoglu et al. (1999) investigated the in vivo effects of
cinnamon bark on streptozotocin-induced tissue injury, and on
a variety of biochemical and haematological parameters in rats.
Streptozotocin is a naturally occurring chemical that is partic-
ularly toxic to the insulin-producing beta cells of the pancreas
in mammals. This compound is used in medical research to
produce an animal model for type 1 diabetes. The effects on
glycaemia were also evaluated in this series of experiments.
Long-term administration of cinnamon caused improvement in
tissue injury induced by streptozotocin treatment; however, no
effects on blood glucose concentrations were detected. These
data indicate that long-term use of cinnamon bark may possibly
provide benefit against diabetic conditions.
Treatment of streptozotocin-induced diabetic C57BL/6 mice
and spontaneously diabetic ob/ob mice with a naphthalen-
emethyl ester of 3,4-dihydroxyhydrocinnamic acid (DHH105)
decreased blood glucose concentrations to near normal (Kim
et al., 2006b). Cinnamaldehyde was administered for 45 days
to streptozotocin-induced male diabetic Wistar rats in order
to isolate and identify the putative antidiabetic compounds of
C. zeylanicum. Plasma glucose concentration was significantly
(p<0.05) decreased in a dose-dependent manner compared to
the control. In addition, oral administration of cinnamaldehyde
significantly decreased glycosylated hemoglobin (HbA1C),
a marker of mid-term glucose homeostasis, and at the same
time markedly increased plasma insulin and hepatic glycogen
concentrations (Subash Babu et al., 2007). Cinnamaldehyde
also restored altered plasma enzyme concentrations (aspartate
aminotransferase, alanine aminotransferase, lactate dehydro-
genase, alkaline phosphatase, and acid phosphatase) to near
normal levels.
Kim et al. (2006a) studied the anti-diabetic effect of Cin-
namomum cassia extract in a type 2 diabetic animal model
(C57BIKsj db/db). Within 6 weeks of administration, blood
glucose concentration was significantly decreased in a dose-
dependent manner (p<0.001). In addition, serum insulin
concentrations were significantly higher (p<0.01) and
intestinal alpha-glycosidase activity was significantly lower, af-
ter 6 weeks of administration. These results suggest that cin-
namon extract has a regulatory role in blood glucose home-
ostasis and may also exert a blood glucose-suppressing effect
by improving insulin sensitivity or slowing the absorption of
carbohydrates.
Qin et al. (2003) evaluated the effect of cinnamon extract
on insulin action in male Wistar rats utilizing the “hyperinsu-
linemic euglycemic clamp,” a technique measuring the amount
of glucose necessary to compensate for an increased insulin
level without causing hypoglycemia. Possible changes in in-
sulin signaling which occurred in skeletal muscle were fur-
ther analyzed. The results suggest that the cinnamon extract
improves insulin action via increasing glucose uptake in vivo,
possibly by enhancing the insulin-signaling pathway in skeletal
muscle.
Qin et al. (2004) fed normal male Wistar rats a high-fructose
diet (HFD) for three weeks with or without cinnamon extract
added to the drinking water in order to determine whether cinna-
mon extract would improve glucose utilization. In vivo glucose
utilization was again measured by the euglycemic clamp tech-
nique. Early administration of cinnamon extract to HFD-fed rats
seems to prevent the development of insulin resistance at least
in part by enhancing insulin signaling and possibly via the NO
pathway in skeletal muscle.
Kannappan et al. (2006) divided adult male albino rats into
five groups and fed either control or high fructose diets and
cinnamon bark extract for 60 days. The levels of glucose, in-
sulin, and protein-bound sugars were higher and activities of
enzymes of glucose metabolism were altered in high fructose
rats as compared to control animals. The levels were brought
back to near-normal when administered with cinnamon bark
extract. These findings indicate that cinnamon can improve glu-
cose metabolism in vivo in fructose-fed rats.
HEALTHY SUBJECTS
As discussed above, in vivo studies in animals show that
cinnamon may have beneficial effects on glucose homeostasis;
therefore the aim of a study by Solomon and Blannin (2007) was
to further investigate this phenomenon in humans. Seven lean
healthy adult male volunteers underwent three oral glucose tol-
erance tests supplemented with a single dose of either a placebo
or 5 g of cinnamon using a randomized-crossover design. Cin-
namon ingestion reduced total plasma glucose responses to oral
glucose ingestion (–13% and –10% for cinnamon, p<0.05), as
well as improving insulin sensitivity as assessed by insulin sen-
sitivity index measures based on Matsuda’s model (p<0.05)
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CINNAMON AND HEALTH 831
compared with control. These data illustrate that cinnamon sup-
plementation may be important to in vivo glycaemic control and
insulin sensitivity in humans.
Hlebowitz et al. (2007) measured the effect of cinnamon on
gastric emptying rate (GER) in 14 healthy subjects in a crossover
experiment using standardized real-time ultrasonography. The
subjectswereexaminedafteran8hfastiftheyhadnormal
fasting blood glucose concentrations. GER was calculated 15–
90 min after ingestion of 300 g rice pudding (GER1) or 300 g rice
pudding and 6 g cinnamon (GER2). The addition of cinnamon
to the rice pudding significantly delayed gastric emptying and
lowered postprandial glucose response (p<0.05 for both). The
effect of cinnamon on satiety was not significant. This study
shows that the intake of 6 g cinnamon with rice pudding can
reduce postprandial blood glucose and delay gastric emptying
without affecting satiety. The inclusion of cinnamon in the diet
may lower postprandial glucose response; a change that is at
least partially explained by a delayed GER.
CLINICAL TRIALS
Seven clinical studies investigating the effect of cinnamon
on insulin resistance as well as type 1 and type 2 diabetes have
been published to date (see Table 1). Four did not report sta-
tistically significant beneficial effects (Altschuler et al., 2007;
Blevins et al., 2007; Suppapitiporn et al., 2006; Vanschoonbeek
et al., 2006) while the remaining three studies found such effects
(Khan et al., 2003; Mang et al., 2006; Wang et al., 2007).
In conclusion, the available in vitro and in vivo studies
strongly suggest that cinnamon has hypoglycemic properties.
However, the available human data are less consistent and indi-
cate that cinnamon may have modest effects on blood glucose
in subjects with type 2 diabetes. Additional evidence is needed
before the extent to which cinnamon can be used to prevent
and/or treat diabetes in humans is fully understood.
Immunomodulatory Properties
A study by Shan et al. (1999) showed that the extract of
C. cassia markedly stimulated human lymphocytes to prolifer-
ate in vitro. Kurokawa et al. (1998) characterized antipyretic
compounds from C. cassia. The antipyretic activity was sig-
nificantly correlated with interleukin-1alpha regulatory activity.
Reddy et al. (2004) found that an extract from the stem bark of
C. cassia had an inhibitory effect on LPS-induced activity of
NF-kappaB, a transcription factor regulating the expression of
inflammatory and immune genes. Trans-cinnamaldehyde and
2-methoxycinnamaldehyde were identified as the NF-kappaB
inhibitors.
Nagai et al. (1982) studied the anti-allergic action of an aque-
ous extract of C.cassiainvitro. Their results suggest that the
extract showed an anticomplement action and inhibited the com-
plement dependent allergic reaction.
Koh et al. (1998) studied two kinds of cinnamaldehyde
derivative, 2-hydroxycinnamaldehyde (HCA) and 2-benzoxy-
cinnamaldehyde (BCA), for their immunomodulatory effects in
aseriesofin vitro experiments. Treatment of mouse spleno-
cyte cultures with these cinnamaldehydes induced suppres-
sion of lymphoproliferation following both concavalin A and
lipopolysaccharide stimulation in a dose-dependent manner.
The results in this study suggest both derivatives inhibit the
lymphoproliferation and induce a T-cell differentiation through
the blockade of early steps in the signaling pathway leading to
cell growth.
Kanari et al. (1989) isolated a neutral polysaccharide, named
cinnaman AX (L-arabinose : D-xylose =4 : 3) from the dried
bark of C. cassia. The polysaccharide showed reticuloendothe-
lial system-potentiating activity in mice in a modified in vivo
carbon clearance test using zymosan as positive control.
In conclusion, the available in vitro and in vivo data demon-
strate that cinnamon has immunomodulatory properties. How-
ever, no human data are available to confirm this hypothesis in
free-living individuals.
DISCUSSION
Historically, the medicinal uses of spices were often indistin-
guishable from their culinary uses. The value of phytochemicals
in relation to human health has been recognized for centuries.
The constituents of herbs and spices can have complimentary
and overlapping actions, including reduction of inflammation,
antioxidant effects, modulation of detoxification enzymes, mod-
ulation of the immune system, and antibacterial and antiviral
effects. The available in vitro and animal in vivo trials on the
properties of Cinnamomum zeylanicum and C. cassia suggest
that this spice may have anti-inflammatory, antimicrobial, an-
tioxidant, antitumor, cardioprotective, cholesterol-lowering, hy-
poglycemic, and immunomodulatory effects. On the other hand,
there is little evidence that cinnamon has gastroprotective prop-
erties. The preponderance of available in vitro and in vivo data
suggest that cinnamon has health benefits. However, controlled
human studies will be necessary to determine whether these
effects have public health implications.
Most human research on cinnamon has been conducted to
establish whether this spice is suitable for the treatment of type
1 and/or type 2 diabetes mellitus. These results are conflicting,
but some evidence does exist to support this hypothesis.
The in vivo and in vitro studies on the topic of insulin resis-
tance and the insulin-mimetic actions of cinnamon, respectively,
have yielded consistently positive results. In addition, four of
the seven clinical studies published to date did not report sta-
tistically significant beneficial effects (Altschuler et al., 2007;
Blevins et al., 2007; Suppapitiporn et al., 2006; Vanschoonbeek
et al., 2006) while the remaining three studies found such effects
(Khan et al., 2003; Mang et al., 2006; Wang et al., 2007). The
negative studies employed 1–1.5 g of cinnamon as a daily dose,
whereas the studies with statistically significant results utilized
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832 J. GRUENWALD ET AL.
up to 6 g. As no dose-ranging studies were conducted, it is pos-
sible to estimate from the available data that ≥3 g cinnamon
daily may be effective. In addition, C. zeylanicum and C. cas-
sia may demonstrate slight differences in their pharmacological
effects so the source of cinnamon may be important. As noted
by Pham et al. (2007), further well-designed studies are needed
before recommendations can be made that cinnamon is effective
as treatment for type 2 diabetes mellitus. The available data do
not provide support for the hypothesis that cinnamon can be
used to treat type 1 or type 2 diabetes or to reduce the risk of
developing diabetes in healthy individuals.
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