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Bioactivities of Cinnamon in relation to health: A Review.

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Abstract

Cinnamon is the oldest spice and has been used by several cultural practices for centuries. In addition to its culinary uses, cinnamon possesses a rising popularity due to many stated health benefits. Out of the large number of cinnamon species available, Cinnamomum aromaticum (Cassia) and Cinnamomum zeylanicum have been subjected to extensive research. Available in vitro and in vivo evidence indicates that cinnamon may have multiple health benefits, mainly in relation to hypoglycaemic activity. Furthermore, the therapeutic potential of cinnamon is stated also to be brought about by its anti-microbial, anti-fungal, antiviral, antioxidant, anti-tumour, blood pressure-lowering, cholesterol and lipid-lowering and gastro-protective properties. This article provides a summary of the scientific literature available on both C. aromaticum and C. zeylanicum. All studies reported here have used cinnamon bark and its products. Although almost all the animal models have indicated a pronounced anti-diabetic activity of both cinnamon species, conflicting results were observed with regard to the few clinical trials available. Therefore, the necessity of evaluating the effects of cinnamon for its therapeutic potential through well-defined and adequately powered randomized controlled clinical trials is emphasized, before recommendations are made for the use of cinnamon as an effective treatment for humans. Keywords: Cinnamomum zeylanicum, Cinnamomum aromaticum, Cassia, blood glucose, cholesterol
Bioactivity of cinnamon with special emphasis on diabetes mellitus:
A review
THUSHARI BANDARA
1
, INOKA ULUWADUGE
2
, & E. R. JANSZ
3
1
Allied Health Sciences Degree Programme, Faculty of Medicine, University of Ruhuna, Galle, Sri Lanka,
2
Medical Laboratory
Sciences, Department of Medical Education, Faculty of Medical Sciences, University of Sri Jayewardenepura, Nugegoda,
Sri Lanka, and
3
University of Sri Jayewardenepura, Nugegoda, Sri Lanka
Abstract
Cinnamon is the oldest spice and has been used by several cultural practices for centuries. In addition to its culinary uses,
cinnamon possesses a rising popularity due to many stated health benefits. Out of the large number of cinnamon species
available, Cinnamomum aromaticum (Cassia) and Cinnamomum zeylanicum have been subjected to extensive research. Available
in vitro and in vivo evidence indicates that cinnamon may have multiple health benefits, mainly in relation to hypoglycaemic
activity. Furthermore, the therapeutic potential of cinnamon is stated also to be brought about by its anti-microbial, anti-fungal,
antiviral, antioxidant, anti-tumour, blood pressure-lowering, cholesterol and lipid-lowering and gastro-protective properties.
This article provides a summary of the scientific literature available on both C. aromaticum and C.zeylanicum. All studies
reported here have used cinnamon bark and its products. Although almost all the animal models have indicated a pronounced
anti-diabetic activity of both cinnamon species, conflicting results were observed with regard to the few clinical trials available.
Therefore, the necessity of evaluating the effects of cinnamon for its therapeutic potential through well-defined and adequately
powered randomized controlled clinical trials is emphasized, before recommendations are made for the use of cinnamon as an
effective treatment for humans.
Keywords: Cinnamomum zeylanicum,Cinnamomum aromaticum, Cassia, blood glucose, cholesterol
Introduction
Cinnamon is one of the well-known and oldest spices,
which has been used for centuries in several cultures
(Gruenwald et al. 2010). Chinese literature 4000 years
ago has cited the traditional use of cinnamon in
naturopathic medicine (Qin et al. 2003). It has been
traditionally used in Ayurvedic and Chinese medicine
as a treatment for diabetes (Modak et al. 2007).
Cinnamon was reported to be employed as a stomachic
and carminative for gastrointestinal complaints as well
as other ailments in many countries (Teuscher 2003).
About250speciesareincludedinthegenus
Cinnamomum (Lauraceae). These species are shrubs
and small to medium-sized trees (Jantan et al. 1995)
and found in tropical rain forests where they grow at
various altitudes from highland slopes to lowland
forests and occur in both marshy places and on
well-drained soils. The four principal Cinnamomum
species are Cinnamomum zeylanicum (C.verum:‘True
cinnamon’, Sri Lanka cinnamon or Ceylon cinnamon),
C.loureirii (SaigoncinnamonorVietnamesecinnamon),
C.burmanni (Korintje or Indonesian cinnamon) and
(Cinnamomum aromaticum (Cassia or Chinese cinna-
mon). The bark of mainly C.aromaticum and
C.zeylanicum enters the trade as cinnamon, although
the European Union has labelled C.aromaticum as Cassia.
The bark of cinnamon is widely used as a spice. It is
used in cookery as a condiment and flavouring
material. It is used in the preparation of chocolate, in
many desserts recipes (apple pie, doughnuts and
cinnamon buns), spicy candies, tea, hot cocoa and
liqueurs (especially in Mexico, the main importer of
true cinnamon). In the Middle East, it is often used in
savoury dishes of chicken and lamb. In the United
States, cinnamon (mainly cassia) and sugar are often
ISSN 0963-7486 print/ISSN 1465-3478 online q2011 Informa UK, Ltd.
DOI: 10.3109/09637486.2011.627849
Correspondence: T. Bandara, Allied Health Sciences Degree Programme, Faculty of Medicine, University of Ruhuna, Galle, Sri Lanka.
Tel: þ94 91 2222314. Fax þ94 91 2222314. E-mail: wvthush@yahoo.com
International Jour nal of Food Sciences and Nutrition,
2011; Early Online: 1–7
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used to flavour cereals, bread-based dishes and fruits.
Cinnamon is further used in pickling. Cinnamon
powder is used as a spice in Persian cuisine in a variety
of thick soups, drinks and sweets. It is also used in
‘Sambar powder’ or ‘BisiBelebath powder’ in Karna-
taka, in India. It has a rich aroma and tastes unique.
Cinnamon is used as an insect repellent. It has been
found that cinnamon leaf oil is very effective in killing
mosquito larvae. The medicinal value of cinnamon is
brought about by its anti-microbial, anti-fungal,
antiviral, antioxidant, anti-tumour, blood pressure-
lowering, cholesterol and lipid-lowering, hypoglycae-
mic and gastro-protective properties. Cinnamon has
traditionally been used to treat toothache and fight bad
breath and its regular use is believed to stave off the
common cold and aids digestion. More than 600
formulations of cinnamon are mentioned in Indian
traditional medicine (Ayurveda). It is stated to be useful
in conditions such as flatulence, piles, amenorrhoea,
diarrhoea, toothache, amoebiasis, heart diseases, fever,
cough, cold, headache, etc. but statements are mainly
based on folklore with little clinical trials.
This paper aims to provide a comprehensive
summary of the scientific literature on the effects of
cinnamon species on health centred on its hypogly-
caemic activity.
Methodology of search
A database search was carried out using the databases
PubMed, Medline and Google Scholar. ‘cinnamon’,
‘cinnamomum’, ‘cinnamomum zeylanicum’, ‘cinna-
momum cassia’, cinnamon combines with ‘blood
glucose’, ‘cholesterol’, ‘hypoglycaemic’, ‘anti-
microbial’, ‘anti-oxidant’, ‘anti-tumour’, ‘lipid low-
ering’, ‘cholesterol lowering’ and ‘diabetes’ were the
search terms used. The literature search was confined
to articles in the English language. Due to inability to
access the full articles of some studies, only their
abstracts were evaluated.
Published findings
An interest in the therapeutic potential of cinnamon
has been growing for almost 20 years (Khan et al.
1990). Both C.aromaticum and C.zeylanicum possess
numerous health benefits. Extensive literature is
available on C.aromaticum while the biological
activities of C.zeylanicum have not been studied in
any great detail up to now.
Animal studies on unspecified cinnamon
Hypoglycaemic properties
A major problem in the literature is that many
publications do not specify the species used. Most
of them are related to the anti-diabetic and lipid-
lowering activities. Khan et al. (1990) have shown the
insulin-sensitizing property of ‘cinnamon’ in the rat
epididymal fat cell assay. Berrio et al. (1992) have used
the insulin secretary effect of ‘cinnamon’ to evaluate
the influence of bovine serum albumin on insulin
activity. According to Jarvill-Taylor et al. (2001) a
hydroxychalcone derived from ‘cinnamon’ could
function as a mimetic for insulin in adipocytes. Results
of the research conducted by Qin et al. (2003) have
suggested that ‘cinnamon’ extract would improve
insulin action via enhancing glucose uptake in vivo at
least in part through an insulin signalling pathway in
skeletal muscles. Research conducted in 2004 by the
same group has suggested that early administration of
‘cinnamon extract’ to high-fructose diet-fed rats
prevents the development of insulin resistance at
least in part by enhancing insulin signalling.
Several animal experiments were conducted in 2010
to evaluate the anti-diabetic effects of ‘cinnamon’.
Ping et al. (2010) have reported that cinnamon oil
could significantly reduce the fasting blood glucose in
diabetic mice. The effects of ‘cinnamon extract’ on
insulin resistance and body composition have been
studied by Couturier et al. (2010) using Wistar rats of
induced metabolic syndrome. Their results also
concluded that ‘cinnamon’ alters the body compo-
sition in association with improved insulin sensitivity.
Lipid-lowering properties
Ping et al. (2010) have observed significant declines in
plasma C-peptide, serum triglycerides, total choles-
terol and blood urea nitrogen with a significantly
increased serum high-density lipoprotein levels, after
35 days of treatment of ‘cinnamon’ oil to diabetic mice.
Effects of ‘cinnamon extract’ on the regulation of
plasma levels of adipose-derived factors and
expression of multiple genes related to carbohydrate
metabolism and lipogenesis in adipose tissue in
fructose-fed rats have also been studied (Qin et al.
2010). Results of this study have suggested that
cinnamon extract could effectively ameliorate the
circulating levels of adipokines partially mediated via
regulation of the expression of multiple genes involved
in insulin sensitivity and lipogenesis in the epididymal
adipose tissue. The effects of ‘cinnamon extract’ on
postprandial apolipoprotein B-48 production in
fructose-fed rats and the secretion of apo B-48 in
freshly isolated intestinal enterocytes of fructose-fed
hamsters have been studied (Qin et al. 2009a,b). The
results of this study have shown that cinnamon
improves the postprandial overproduction of intestinal
apo B-48-containing lipoproteins by ameliorating
intestinal insulin resistance and therefore may be
beneficial in the control of lipid metabolism. Further-
more, the effect of ‘cinnamon extract’ on TNF-
alpha-induced intestinal apo-B-48 overproduction
by Qin et al. (2009a,b) have suggested that a water
extract of ‘cinnamon’ reverses TNF-alpha-induced
overproduction of intestinal apoB48 by regulating
T. Bandara et al.2
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gene expression involving inflammatory, insulin and
lipoprotein signalling pathways. Therefore, it has been
concluded that ‘cinnamon’ could improve inflam-
mation-related intestinal dyslipidaemia.
Animal studies on Cinnamomum aromaticum
Hypoglycaemic properties
Verspohl et al. (2005) have studied the anti-diabetic
effect of both cinnamon species in vivo and in vitro.
They have used the bark extracts of both cinnamon
species and evaluated the blood glucose and plasma
insulin levels in rats. This study has concluded that
cassia extract is superior to that of the C.zeylanicum
extract. They have observed an elevation of insulin
secretion by using insulin-secreting cell lines and
have concluded the direct anti-diabetic potency of
C.aromaticum extract.
Kim and Choung (2010) evaluated the anti-
hyperglycaemic and insulin-sensitizing activities of
C.aromaticum bark extract in C57BL/Ks db/db mice
by measuring the blood glucose levels and serum
insulin levels. Results of this study have shown that
C.aromaticum extract significantly increases the
insulin sensitivity and improves hyperglycaemia.
Lipid-lowering properties
Kim and Choung (2010) have also studied the effects
of C.aromaticum bark extract on adiponectin levels,
serum and hepatic lipids, PPARalpha mRNA
expression in liver and PPARgamma mRNA
expression in adipose tissue in C57BL/Ks db/db
mice. Their study has concluded that C.aromaticum
extract significantly reduces serum and hepatic lipids
and improves hyperlipidaemia possibly by regulating
the PPAR-mediated glucose and lipid metabolism.
Other bioactivities
C.aromaticum also exhibits anti-inflammatory and
cancer chemo-protective potential. C.aromaticum
bark extracts has shown potent inhibition of cyclo-
oxygenase-2 activity in lipopolysaccharide-induced
mouse macrophage cells (Hong et al. 2002). Further-
more, cinnamaldehyde derivatives isolated from the
bark of C.aromaticum has significantly inhibited
lipopolysaccharide-induced nitric oxide production
and NF-kappaB transcriptional activity in a dose-
dependent manner (Lee et al. 2005).
Oussalah et al. (2006) have studied the mechanism
of the anti-microbial action of the essential oil of
C.aromaticum against cell membranes and walls of
bacteria by measurement of intracellular pH and
ATP concentration. Results have suggested that the
action on the cytoplasmic membrane is involved in
the toxic action.
According to Premanathan et al. (2000)
C.aromaticum bark extract is highly effective against
HIV-1 and HIV-2 replication in terms of inhibition
of virus-induced cytopathogenicity in MT-4 cells
infected with HIV.
Lin et al. (2003) have found that ethanol extracts
of dry bark of C.aromaticum exhibit a greater
inhibition of lipid peroxidation of rat liver homogenate
in vitro than alpha-tocopherol, high superoxide anion
scavenging activity, strong anti-superoxide formation
activity (P,0.05) and excellent antioxidant activity
in enzymatic and non-enzymatic liver tissue oxidative
systems.
Animal studies on Cinnamomum zeylanicum
Hypoglycaemic properties
Roffey et al. (2006) have found that water extract of
C.zeylanicum has insulin-mimetic action in adipo-
cytes in terms of glucose uptake. They have used
3T3-L1 adipocytes for their study. However, they
have reported that the secretion of adiponectin was
adversely affected concurrently.
Subash Babu et al. (2007) have studied the effects of
cinnamaldehyde from C.zeylanicum on blood glucose
levels of streptozotocin-induced diabetic rats. Bio-
assay-guided fractionation has been used for isolation
and purification of putative compounds. They found a
significant decline in plasma glucose and glycosylated
haemoglobin. Furthermore, there had been a signifi-
cant increment in plasma insulin and hepatic glycogen
levels after the treatment period. At the same time
cinnamaldehyde was able to restore the altered plasma
enzyme (aspartate aminotransferase, alanine amino-
transferase, lactate dehydrogenase, alkaline phospha-
tase and acid phosphatase) levels to near normal
levels. This study has confirmed the definite hypogly-
caemic effects of C.zeylanicum in STZ-induced
diabetic rats.
Effects of cinnamaldehyde from C.zeylanicum
on transcriptional regulation of pyruvate kinase,
phosphoenolpyruvate carboxykinase and GLUT4
translocation have been studied in experimental
diabetic rats (Anand et al. 2010). Oral administration
of cinnamaldehyde (20 mg/kg BW) for 2 months
significantly improved the hepatic and muscle glyco-
gen content. Further in vitro incubation of pancreatic
islets with cinnamaldehyde (CND) has been shown
to enhance the insulin release in comparison to
glibenclamide. The insulinotropic effect of CND has
been found to increase the glucose uptake through
glucose transporter (GLUT4) translocation in peri-
pheral tissues. This treatment has also showed a
significant improvement in altered enzyme activities of
pyruvate kinase and phosphoenolpyruvate carboxyki-
nase and their mRNA expression levels. These results
indicate the therapeutic potential of C.zeylanicum as a
candidate for the treatment of diabetes.
Bioactivity of cinnamon 3
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The ameliorative effect of the cinnamon oil from
C.zeylanicum on the early stages of diabetic nephro-
pathy has also studied. Cinnamon oil has been
extracted by hydro-distillation of the dried bark.
The results have shown that cinnamon can confer
a dose-dependent significant protection against
alloxan-induced renal damage (Mishra et al. 2010).
Lipid-lowering properties
Subash Babu et al. (2007) have further studied the
effects of cinnamaldehyde from C.zeylanicum on lipid
levels of streptozotocin-induced diabetic rats. They
have observed a significant reduction in serum total
cholesterol and triglyceride levels. Furthermore, there
had been a significant increment in plasma high-
density lipoprotein cholesterol levels after the treat-
ment period.
Antioxidant properties
It has been suggested that antioxidant properties of
both C.zeylanicum and C.aromaticum could influence
diabetic complications. The polyphenolic compounds
found in both species have demonstrated the reduction
of oxidative stress in dose-dependent manner through
inhibition of 5-lipoxygenase enzyme (Anderson et al.
2004). Dudonne
´et al. (2009) have also found a high
level of antioxidant properties in C.zeylanicum and
postulated that it would be a good source of natural
antioxidants.
Human studies on unspecified cinnamon
It has been reported that ingestion of 6 g of ‘cinnamon’
bark together with rice pudding has reduced the
postprandial blood glucose and gastric emptying rate
(GER) in healthy subjects (Hlebowicz et al. 2007).
Human studies on Cinnamomum aromaticum
Hypoglycaemic properties
Khan et al. (2003) have investigated the effects of
C.aromaticum (finely ground and capsulated bark) on
blood glucose levels of the patients with type 2
diabetes. They have included a total of 60 patients in
this study. This study has indicated that the intake of 1,
3or6gofC.aromaticum per day could reduce serum
glucose levels significantly (by 18 29%) after 40 days.
They have suggested that inclusion of cinnamon to the
diet of the patients with type 2 diabetes would reduce
the risk factors associated with diabetes and cardio-
vascular diseases.
Mang et al. (2006) have studied the effect of cassia
on plasma glucose and HbA
1
c in type 2 diabetics.
They have used an aqueous cinnamon purified extract.
For this double-blind study, a total of 79 type 2
diabetic patients who are not on insulin therapy but
treated with oral anti-diabetic drugs were included.
Their results have indicated a significant difference in
the mean absolute and percentages between the pre-
and post-intervention fasting plasma glucose levels of
the cinnamon and placebo groups. There had been a
significantly higher reduction in the cinnamon
group (10.3%) than in the placebo group (3.4%).
However, no significant differences were observed
regarding HbA
1
c concluding a moderate effect of
C.aromaticum in reducing fasting plasma glucose
levels in diabetic patients.
Suppapitiporn et al. (2006) have investigated the
effect of cinnamon cassia powder in type 2 diabetic
patients. Sixty type 2 diabetic patients were included
in this study. The patients were on their conventional
metformin and sulphonylurea treatment. The treat-
ment period was for 12 weeks. Their results have
indicated that the treatment was ineffective in
reducing fasting blood glucose or HbA
1
c. Vanschoon-
beek et al. (2006) have estimated the effects of
C.aromaticum supplementation on insulin sensitivity
and/or glucose tolerance in 25 postmenopausal
patients with type 2 diabetes. The test group has
been treated with 1.5 g of cinnamon per day over a
period of 6 weeks. This study has concluded that
cinnamon supplementation could not improve whole-
body insulin sensitivity or oral glucose tolerance in
postmenopausal patients with type 2 diabetes.
Furthermore, Blenin et al. (2007) have reported that
ingestion of cassia at a dose of 1 g daily for a period of 3
months could not produce any significant change in
fasting glucose, HbA
1
c or insulin levels. This is reported
to be the first study conducted in the United States to
evaluate the effect of cinnamon on type 2 diabetes.
Solomon and Blanin (2007) have investigated the
effect of cassia on lean healthy male volunteers. They
have included only eight male volunteers in this study.
It has been found that cassia ingestion (3 g/day) could
significantly reduce the total plasma glucose responses
to oral glucose ingestion. They have concluded that
cassia supplementation may be important to in vivo
glycaemic control and insulin sensitivity in humans.
According to them, its effects are lost following
cessation of treatment.
Naturally occurring substances such as chromium
and polyphenols have been shown to improve the
insulin sensitivity (Anderson 2008). These com-
pounds could exert similar effects on insulin signalling
and glucose control (Anderson 2008). Cinnamon
polyphenols activate insulin receptors by increasing
their tyrosine phosphorylation activity and by decreas-
ing phosphatase activity that inactivates the insulin
receptor (Imparl-Radosevich et al. 1998). Based on
these facts, Anderson (2008) has suggested that some
of the beneficial effects brought about by cinnamon in
relation to blood glucose lowering in humans are due
to polyphenols in cinnamon.
However, a review article published by Baker et al.
(2008) has concluded that cinnamon does not appear
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to improve fasting blood glucose or HbA
1
c in patients
with either type 1 or type 2 diabetes.
Hlebowicz et al. (2009) have re-investigated the
effects of 1 and 3 g C.aromaticum on gastric emptying,
satiety, and postprandial blood glucose, insulin,
glucose-dependent insulinotropic polypeptide,
glucagon-like peptide 1 and ghrelin concentrations in
healthy subjects. This study has indicated that the
ingestion of 3 g of cinnamon reduced postprandial
serum insulin and increased glucagon-like peptide-1
concentrations without affecting postprandial GER,
satiety or blood glucose, glucose-dependent insulino-
tropic polypeptide, or ghrelin concentrations in
healthy subjects. This study has also shown a
relationship between the amount of cinnamon
consumed and the decrease in insulin concentrations
in healthy subjects and concluded that higher doses of
cinnamon are required to influence GER and
postprandial blood glucose concentrations (Hlebowicz
et al. 2009).
Akilen et al. (2010) have conducted a prospective,
randomized, placebo-controlled, double-blind clinical
trial to determine the effects of cassia powder in type 2
diabetic patients. Fifty-eight type 2 diabetic patients
have included in the study. It has been observed
that intake of 2 g of cinnamon for 12 weeks could
significantly reduce HbA
1
c, systolic blood pressure
and diastolic blood pressure among poorly controlled
type 2 diabetes patients. This study has concluded
that cinnamon could be considered an additional
dietary supplement option to regulate blood glucose
and blood pressure levels along with conventional
medications to treat type 2 diabetes.
Lipid-lowering properties
Khan et al. (2003) have investigated the effects
of C.aromaticum on lipids of patients with type 2
diabetes. This study has indicated that the intake of 1,
3or6gofC.aromaticum per day could reduce
serum triglyceride, Low density lipoprotein (LDL)
cholesterol and total cholesterol levels significantly.
Mang et al. (2006) have also studied the effect of cassia
extract on serum lipids in type 2 diabetics. They have
found that the treatment with cassia extract could not
affect the lipid profiles of type 2 diabetic patients
significantly. Suppapitiporn et al. (2006) have also
reported that the treatment of cassia powder in type 2
diabetic patients was ineffective in reducing serum
lipid levels. Vanschoonbeek et al. (2006) have
estimated the effects of C.aromaticum supplemen-
tation on lipid profiles in postmenopausal patients
with type 2 diabetes. This study has concluded that
cinnamon supplementation could not modulate blood
lipid profile in postmenopausal patients with type 2
diabetes. Furthermore, a review article published by
Baker et al. (2008) has concluded that cinnamon does
not appear to improve lipid parameters either in type 1
or type 2 diabetic patients.
Antioxidant properties
The antioxidant effect of cassia extract (a dried
aqueous extract) has been analysed in patients with
impaired fasting blood glucose that are overweight
and obese (Roussel et al. 2009). Twenty-two subjects
have been included in this study. The treatment used
was 250 mg of cinnamon extract twice a day for a
period of 12 weeks. They have measured the plasma
malondialdehyde concentration, plasma antioxidant
status, erythrocyte Cu Zn superoxide activity and
erythrocyte glutathione peroxidase activity. This study
has supported the hypothesis that ingestion of cassia
could reduce the risk factors associated with diabetes
and cardiovascular diseases due to its antioxidant
properties.
Human studies on Cinnamomum zeylanicum
Quale et al. (1996) have conducted a pilot study to
investigate the activity of C.zeylanicum against
fluconazole resistant and -susceptible Candida iso-
lates. They used a small sample size (five patients with
HIV infection and oral candidiasis). Subjects had
confirmed pseudomembranous candida infection.
Patients have been treated with eight lozenges of a
cinnamon candy daily and three of the five patients
had improvement of their oral candidiasis.
Data of the human studies on the effects of
C.zeylanicum were not found in relation to hypo-
glycaemic and lipid-lowering potentials.
Chemical composition of cinnamon species
Volatile oils obtained from the leaf, bark and root bark
of C.zeylanicum and C.aromaticum have reported to be
varying significantly in chemical composition. Hence,
it is obvious that there must be variations in their
pharmacological effects (Wijesekera 1978; Shen et al.
2002). The oils of three different parts of the plant
possess the same array of monoterpene hydrocarbons
in different proportions. However, in bark oil the
primary constituent is cinnamaldehyde which is
about 95% in cassia and 40 65% in C.zeylanicum
(Wijesekera 1978). According to Chericoni et al.
(2005), the other components of the bark of
C.zeylanicum are eugenol and linalool with as many
as 50 other volatile substances. Cinnamaldehyde and
eugenol have also been found to be the major
components of cinnamon extract (Usta et al. 2003).
The stem bark of C.aromaticum contains in addition
cinnamic acid, cinnamyl alcohol and coumarin
(Gruenwald et al. 2010).
Cinnamon toxicity due to coumarin
Coumarin is a natural substance, a known phyto-
chemical found in cinnamon, which can cause liver
and kidney damage in rats, mice and in a proportion
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of the human population, when tolerable daily intake
(TDI) was exceeded (Lungarini et al. 2008; Woehrlin
et al. 2010). TDI for coumarin is 0.1 mg/kg body
weight (Abraham et al. 2010). The chemical compo-
sition of the C.zeylanicum and C.cassia is markedly
different, with respect to their coumarin levels.
According to Miller et al. 1995, coumarin concen-
tration of C.zeylanicum is below the detection
limit to 190 mg/kg, whereas in cassia the level is
700 –12,230 mg/kg.
Discussion
The documented health benefits of cinnamon appear
to be its glucose-lowering activity. In addition,
cinnamon possesses anti-microbial, anti-fungal,
antiviral, antioxidant, anti-tumour, blood pressure-
lowering, cholesterol and lipid-lowering properties.
Research on the anti-diabetic activity of cinnamon
extends over a period of 20 years. Much more
literature is available on cassia and lesser number of
publications are available on C.zeylanicum which is
known to be the ‘true cinnamon’ (endemic Sri Lankan
species). Therefore, comparison is difficult. The
potential glucose-lowering effect and the underlining
pharmacological mechanisms of cinnamon species
have been studied in vitro and in vivo animal studies.
Almost all the animal models have indicated a
pronounced anti-diabetic activity. However, conflict-
ing results were reported with regard to the few clinical
trials available. This leaves room for considerable
doubt. The variability of results of the available
publications could be due to the species used, the
sampling techniques (collection, storage and method
of grinding, etc.), methodological differences of
extractions, differences in the controls used and their
glucose-lowering drugs, the cinnamon dose adminis-
tered, duration of the treatment, the number and type
of the patients included and their inclusion and
exclusion criteria, baseline blood glucose levels, body
mass index that has a bearing on both hypoglycaemic
and hypolipidaemic effects and the ethnicity of the
patients. Furthermore, the climatic and edaphic
features of the point of collection of samples may
affect the bioactivity and very often these details have
not specified. In the case of C.zeylanicum in Sri Lanka,
there are different grades and the bioactivity can be
varied with different grades. The ethnicities of patients
will naturally give different genetic factors that may
influence the effects of cinnamon doses even when all
the other parameters are kept well under control. The
other major failure in cinnamon research is the
absence of dose curves.
Hence, the necessity of evaluating the effects of
cinnamon for its therapeutic potentials through a well-
defined and adequately randomized controlled clinical
trial is emphasized, before recommending cinnamon
as an effective treatment for humans.
Conclusion
Based on the evidence in the literature which has a
number of details that are not mentioned, it appears
that cassia is more potent than C.zeylanicum with
regard to the lowering of blood glucose and its
hypolipidaemic effects. However, clearly triangular
clinical trials involving the most popular types of cassia
and C.zeylanicum, taking all precautions to ensure
that the history of sampling, sample preparation and
controls are taken into account are needed.
So far the data appear to indicate that cinnamaldehyde
may be the key compound in at least some of the
bioactivities of cinnamon. This may explain why cassia
mayappeartobemorepotentthanC.zeylanicum.
However, C.zeylanicum commands a premium price over
cassia in export market due to its more rounded flavour.
The recent studies on the relatively high coumarin
content of cassia unlike C.zeylanicum could also prove
to be a deciding factor in some western markets.
Therefore, it is also important that the work on
coumarin be repeated on all varieties of cassia and all
types of barks of C.zeylanicum in order to confirm
beyond any doubt the advantage of C.zeylanicum.
Declaration of interest: The authors report no
conflict of interest. The authors alone are responsible
for the content and writing of the paper.
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Article
Full-text available
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.
Article
To determine the blood glucose lowering effect of cinnamon on HbA1c, blood pressure and lipid profiles in people with type 2 diabetes. 58 type 2 diabetic patients (25 males and 33 females), aged 54.9 ± 9.8, treated only with hypoglycemic agents and with an HbA1c more than 7% were randomly assigned to receive either 2g of cinnamon or placebo daily for 12 weeks. After intervention, the mean HbA1c was significantly decreased (P<0.005) in the cinnamon group (8.22% to 7.86%) compared with placebo group (8.55% to 8.68%). Mean systolic and diastolic blood pressures (SBP and DBP) were also significantly reduced (P<0.001) after 12 weeks in the cinnamon group (SBP: 132.6 to 129.2 mmHg and DBP: 85.2 to 80.2 mmHg) compared with the placebo group (SBP: 134.5 to 134.9 mmHg and DBP: 86.8 to 86.1 mmHg). A significant reduction in fasting plasma glucose (FPG), waist circumference and body mass index (BMI) was observed at week 12 compared to baseline in the cinnamon group, however, the changes were not significant when compared to placebo group. There were no significant differences in serum lipid profiles of total cholesterol, triglycerides, HDL and LDL cholesterols neither between nor within the groups. Intake of 2g of cinnamon for 12 weeks significantly reduces the HbA1c, SBP and DBP among poorly controlled type 2 diabetes patients. Cinnamon supplementation could be considered as an additional dietary supplement option to regulate blood glucose and blood pressure levels along with conventional medications to treat type 2 diabetes mellitus.
Article
Coumarin is a flavoring which can cause hepatotoxicity in experimental animals and in a proportion of the human population. The tolerable daily intake (TDI) may be exceeded in consumers with high intake of cinnamon containing high levels of coumarin. The objective of this study was to determine these levels in cinnamon samples and to identify possible factors influencing them. A HPLC method to quantify coumarin and related constituents (cinnamaldehyde, cinnamic acid, cinnamyl alcohol, eugenol) in a single run was used. Results found in 47 cinnamon powder samples obtained from the German retail market confirmed high levels of coumarin in cassia cinnamon. A huge variation was observed in stick samples from two packages (range from below the limit of detection to about 10000 mg/kg). Cassia bark samples of five trees received directly from Indonesia were analyzed additionally. Interestingly, a high variation was observed in one of the trees, whereas no coumarin was detected in the samples of two other trees. In conclusion, coumarin levels in cassia cinnamon can vary widely even within a single tree.
Article
The hypoglycemic effect of cinnamon oil (CO) in a type 2 diabetic animal model (KK-A(y) mice) was studied. The main component of CO was cinnamaldehyde, and other nineteen components were also determined. CO was administrated at doses of 25, 50 and 100mg/kg for 35 days. It was found that fasting blood glucose concentration was significantly decreased (P<0.05) with the 100mg/kg group (P<0.01) the most efficient compared with the diabetic control group. In addition, there was significant decrease in plasma C-peptide, serum triglyceride, total cholesterol and blood urea nitrogen levels while serum high density lipoprotein (HDL)-cholesterol levels were significantly increased after 35 days. Meanwhile, glucose tolerance was improved, and the immunoreactive of pancreatic islets beta-cells was promoted. These results suggest that CO had a regulative role in blood glucose level and lipids, and improved the function of pancreatic islets. Cinnamon oil may be useful in the treatment of type 2 diabetes mellitus.
Article
In previous study, the anti-diabetic effect of Cinnamomi Cassiae extract (Cinnamon bark: Lauraceae) in a type II diabetic animal model (C57BIKsj db/db) has been reported. To explore their mechanism of action, in present study, the effect of cinnamon extract on anti-hyperglycemia and anti-hyperlipidemia was evaluated by measuring the blood glucose levels, serum insulin, and adiponectin levels, serum and hepatic lipids, PPARalpha mRNA expression in liver and PPARgamma mRNA expression in adipose tissue, respectively. Male C57BIKs db/db mice were divided into a diabetic group and cinnamon extract treated group and examined for a period of 12 weeks (200 mg/kg, p.o). The fasting blood glucose and postprandial 2 h blood glucose levels in the cinnamon treated group were significantly lower than those in the control group (p < 0.01), whereas the serum insulin and adiponectin levels were significantly higher in the cinnamon treated group than in the control group (p < 0.05). The serum lipids and hepatic lipids were improved in the cinnamon administered group. Also the PPARalpha mRNA (liver) and PPARgamma mRNA (adipose tissue) expression levels were increased significantly in the cinnamon treated group (p < 0.05). Our results suggest that cinnamon extract significantly increases insulin sensitivity, reduces serum, and hepatic lipids, and improves hyperglycemia and hyperlipidemia possibly by regulating the PPAR-medicated glucose and lipid metabolism.
Article
Coumarin is a secondary phytochemical with hepatotoxic and carcinogenic properties. For the carcinogenic effect, a genotoxic mechanism was considered possible, but was discounted by the European Food Safety Authority in 2004 based on new evidence. This allowed the derivation of a tolerable daily intake (TDI) for the first time, and a value of 0.1 mg/kg body weight was arrived at based on animal hepatotoxicity data. However, clinical data on hepatotoxicity from patients treated with coumarin as medicinal drug is also available. This data revealed a subgroup of the human population being more susceptible for the hepatotoxic effect than the animal species investigated. The cause of the high susceptibility is currently unknown; possible mechanisms are discussed. Using the human data, a TDI of 0.1 mg/kg body weight was derived, confirming that of the European Food Safety Authority. Nutritional exposure may be considerably, and is mainly due to use of cassia cinnamon, which is a popular spice especially, used for cookies and sweet dishes. To estimate exposure to coumarin during the Christmas season in Germany, a telephone survey was performed with more than 1000 randomly selected persons. Heavy consumers of cassia cinnamon may reach a daily coumarin intake corresponding to the TDI.
Article
We reported earlier that dietary cinnamon extract (CE) improves systemic insulin sensitivity and dyslipidemia by enhancing insulin signaling. In the present study, we have examined the effects of CE on several biomarkers including plasma levels of adipose-derived adipokines, and the potential molecular mechanisms of CE in epididymal adipose tissue (EAT). In Wistar rats fed a high-fructose diet (HFD) to induce insulin resistance, supplementation with a CE (Cinnulin PF, 50 mg/kg daily) for 8 weeks reduced blood glucose, plasma insulin, triglycerides, total cholesterol, chylomicron-apoB48, VLDL-apoB100, and soluble CD36. CE also inhibited plasma retinol binding protein 4 (RBP4) and fatty acid binding protein 4 (FABP4) levels. CE-induced increases in plasma adiponectin were not significant. CE did not affect food intake, bodyweight, and EAT weight. In EAT, there were increases in the insulin receptor ( IR) and IR substrate 2 ( IRS2) mRNA, but CE-induced increases in mRNA expression of IRS1, phosphoinositide-3-kinase, AKT1, glucose transporters 1 and 4 , and glycogen synthase 1 expression and decreased trends in mRNA expression of glycogen synthase kinase 3beta were not statistically significant. CE also enhanced the mRNA levels of ADIPOQ, and inhibited sterol regulatory element binding protein-1c mRNA levels. mRNA and protein levels of fatty acid synthase and FABP4 were inhibited by CE and RBP4, and CD36 protein levels were also decreased by CE. These results suggest that CE effectively ameliorates circulating levels of adipokines partially mediated via regulation of the expression of multiple genes involved in insulin sensitivity and lipogenesis in the EAT.