Eaton A, Tran T. Author Angie Eaton, Pharm.D

m o r e
t h a n
j u s t
a
f l a v o r i n g
Eaton A, Tran T.
Author
Angie Eaton, Pharm.D.
P.O BOX 6450 Malibu, CA 90264 - USA
805-988-8851 - USA / CANADA
+1-805-988-8851 - from outside USA
W W W . T R I P P E R . C O M
a g e n t
Cinnamon – more than just a flavoring agent
Introduction
Cinnamon is noted for its most popular use as a spice.
As one of the oldest spices known, it was mentioned in
the Bible and was used as a beverage flavoring,
medicine and also as an embalming agent. Cinnamon
was treasured during this period and it was considered
more precious than gold. During this time, cinnamon
received attention in China, which is reflected in one of
the earliest books on Chinese botanical medicine, dated
around 2700 B.C. ²In medieval Europe cinnamon was know
as a staple ingredient in many recipes. It is impossible to
obtain the strong, sweet and inviting aroma of cinnamon
Cinnamomum burmanni¹
bread and cookies without cinnamon; however, it is more than just another flavoring
agent, it is considered an herbal medicine as one of the fifty Chinese fundamental
herbs.
Plant Origin
Traveling to the North Pacific Ocean to visit China the world’s
fourth largest country after Russia, Canada and USA, China is
the home of the gigantic and beautiful Mount Everest which is
located in southwestern China. China is the native home land
of Cinnamomum cassia, a species closely related to Cinnamo
³
mum zeylanicum. 4 Cinnamomum is the genus of both species
from the family of Lauraceae.
Cinnamomum cassia, also known as Cinnamomum
aromaticum, comes from a tree that grows up to 10-15 meter tall with grayish bark which
is specifically harvested to be used as a spice and flavoring agent. Characteristically
different from true cinnamon, dried cassia bark is thicker, harder and rougher in texture
and is available commercially in powder and dried whole bark forms.
Uses and Pharmacological Effects
Anti-microbial
Historically, cinnamon had been used to combat GI
disorders such as diarrhea, dyspepsia and Helicobacter
pylori (H. pylori). 6 The antimicrobial effect of cinnamon
was identified in a laboratory experiment in which pure
Cinnamomum cassia extract, mainly composed of the
active
ingredient
cinnamaldehyde,
was
tested
on
isolated strains of bacteria including gram-positive Staphy
5
lococcus aurus, gram-negative Escherichia coli, Enterobacter aerogenes, Proteus vulgaris,
Pseudomonas aeruginosa, Vibrio cholerae, Vibrio parahaemolyticuas and Samonella
typhymurium. The anti-microbial effect resulted in a minimum inhibition concentration
(MIC) of cinnamomum cassia extract ranged from 75 mcg/ml to 600 mcg/ml on these
various isolations of bacteria. 7 However, conflicting data was obtained in human study, a
randomized and controlled pilot clinical trial of fifteen patients aged 16 to 79 years who
had a positive Campylobacter urease test (CUT) for H. pylori. Each patient in the controlled group received twice daily 40mg of ethanol extract of cinnamon for four weeks;
the control group received plain 95% ethanol. With urea breath tests as the measurement of efficacy, the mean urea breath test before and after the study for the treated
group were 22.1 and 24.4; the mean urea breath test before and after the study for the
controlled group were 23.9 and 25.9. Conclusively, this study found that 40mg of
cinnamon extract given twice daily was ineffective in eradicating H. pylori. 8
Anti-inflammatory
Although, cinnamon historically had not been used to treat inflammatory disorders, its
anti-inflammatory effect was demonstrated experimentally. Specifically, Cinnamomum
cassia was used to investigate the anti-inflammatory effect on nitric oxide (NO) and
Nuclear factor kappa-b (NF-kappa-B). Both substances have been implicated in
inflammation. In acute and chronic inflammation, there is an increase NO production;
nitric oxide promotes vasodilatation resulting in increased vascular permeability and
edema.
Nitric oxide also activates COX-2 enzyme involving in the biosynthetic pathway of
inflammatory prostaglandins. 9 NF-kB contributes to inflammation through induction of
transcription of genes coding for inflammatory mediators. It was found that cinnamaldehyde,
specifically 2’-hydroxycinnamaldehyde found in Cinnamomum cassia extract, exhibited
a dose-dependent inhibitory effect on nitric oxide production and transcriptional activity
of NF-kB thereby contributing to its anti-inflammatory effect. 10
Anti-fungal
Cinnamon oil has been reported as an anti-fungal agent,
although current efficacy of cinnamon oil fungicidal effect
has not been tested in clinical trials. Experimentally,promising
results on its antifungal activity were obtained as reported in
two in vitro studies of cinnamon oil on Cryptococcus neoformans and Aspergillus niger. Crytococcus neoformans is an
opportunistic fungal pathogen affecting the lungs or meninges of immunocompromised or AIDS patients causing pulmoCinnamomum cassia 11
nary cryptococcosis or cryptococcocal meningitis.10 It was
found that the phenolic compound in cinnamon oil identified
as eugenol is responsible for its fungitoxic activity.13 Cinnamon
oil antifungal property was again demonstrated in a more
recent in vitro study on Aspergillus niger (A. niger), an opportunistic fungal pathogen residing in the air and through inhalation of Aspergillus sp. spores they enter the respiratory tract to
cause Aspergillosis as seen in immunocompromised or AIDS
Cinnamomum zeylanicum 12
patients.14Seventy five botanical essential oils including Cinna
momum zeylanicum and Cinnamomum cassia were tested for the inhibition of hyphal
growth and spore formation on inoculated agar with A. niger incubated at 28ºC for 48
hours. Among the seventy five botanical essential oils used, Cinnamomum zeylanicum
and Cinnamomum cassia demonstrated maximal and superior results; the zone of
hyphal growth inhibition and zone of spore formation were 43 and 40 vs. 50 and 45 for
Cinnamomum zeylanicum and Cinnamomum cassia respectively.15
Anti-oxidant
Anti-oxidant
There is more to Cinnamon besides the antimicrobial,
anti-inflammatory and antifungal effects attributed to
cinnamaldehyde found in Cinnamomum cassia powder
and oil. The presence of oligomeric proanthocyanidins
electron
Free radical
(OPC), a class of bioflavonoid, opened a new area of
research on its antioxidative effect. Through agriculture
Anti-oxidant neutralizing a free radical 16
research, type A and type B oligomeric proanthocyanidins were identified in cinnamon
spice via massspectrometer analysis. Additionally, it was found that over 84-90% of OPC
17
found in cinnamon spice were type A OPC. However, there has not been a specific study
on the antioxidative effect of cinnamon alone. Antioxidants are essential to the human
body to neutralize free reactive oxygen species, also known as free radicals, to maintain
functional cellular membrane and structure. Furthermore, free radicals associated with
impaired glucose metabolism and antioxidants have been implicated in the regression
of diabetes mellitus.
Clinical Efficacy
Diabetes
Diabetes mellitus type II (NIDDM), a metabolic
disorder, which has been estimated to affect
25.4 million of people in 2011, 32.6 million in
2021 and 37.11 million in 2031.19 It is characterized by impaired glucose metabolism and
peripheral insulin resistance; symptoms are
hyperglycemia, polydipsia, polyphagia and
18
polyuria. Glycemic control is the key in slowing disease progression as well as preventing
peripheral neurophathy, nephropathy, and retinopathy. It places affected individuals at
high risk for atherosclerotic coronary artery disease, mucocutaneous fungal infections
and bacterial foot infections.
Non-pharmacological treatment approaches are life style modifications such as aerobic
exercise and diet by means of making healthy food choices. 20 Available prescription
pharmacological treatments are biguanide (Glucophage®), sulfonylureas (Glucotrol®,
Amaryl®, Diabeta®) thiazolidindiones (Actos®, Avandia®), α-glucosidase inhibitors
(Precose®, Glyset®), meglitinides (Starlix®, Prandin®) and various insulin preparations
such as aspart, lispro, regular, lente, ultralente, NPH, and glargine.21
Additionally, in 2005, FDA approved three new drugs Byetta®, Symlin®, and Levemir®
classified as incretin mimetics, amylino-mimetic and insulin determir. In 2006, FDA
approved Januvia® a dipeptidyl peptidase-4 (DPP-4) enzyme inhibitor and Exubera® an
22
insulin human [rDNA origin] inhalation. The list continues to lengthen as more drugs are
awaiting FDA approval such as Galvus®. Glucobetic® and Cinnulin PF® are over-thecounter nutraceutical products claiming beneficence for individuals with diabetes.
Glucobetic® active ingredients include vitamins and cinnamon bark extract. Cinnulin PF
contains aqueous extract of cinnamon.
Hypoglycemic effect through human studies
High Blood - Sugar
The quest for new treatments conDiabetic Reaction
tinues as the realm of research for
diabetes type II expands to nutra-
Normal Reaction
ceutical products. A pilot clinical
Normal Blood - Sugar Level
Low Blood -
Sugar 23
trial conducted in Pakistan to study
Hypoglycemic Reaction
the effect of cinnamon in type II
diabetic patients harvested successful results. It involved 60 subjects (30 men & 30
women) with type II diabetes, averaged age of 52.2 ± 6.32 years, fasting plasma
glucose ranged 140-400 mg/dl and were not on insulin or medicines for other health
conditions. Subjects were randomly assigned into three placebo groups and
three cinnamon groups in which they were given either 1, 3 or 6 grams of cinnamon
capsules (Cinnamomum cassia powder) daily for 40 days followed by 20 days wash-out
period. All subjects were allowed to continue taking sulfonylurea drugs during the study.
Plasma glucose, triglyceride, LDL, HDL and total cholesterol were measured at fasting
state before and after treatment.
Effects were similar among the three cinnamon treated groups, the mean reduction in
blood glucose, triglyceride, LDL and total cholesterol levels were 18-29%, 23-30%,
7-27% and 12-26%, respectively; changes in these levels were not significant in the
placebo groups as well as HDL levels for all six groups. Interestingly, effects of cinnamon
lingered on after discontinuation. Khan et al reported that plasma glucose, triglyceride,
LDL and total cholesterol levels continued to remain lower than baseline during the 20
days wash-out period. Khan et al suggested that daily consumption of cinnamon may
not be necessary due to the observed sustained effects of cinnamon in studied subjects
with type II diabetes and that inclusion of cinnamon into daily diet may be beneficial to
the remainder of the population.24
The correlation between cinnamon and its effect on fasting plasma glucose becomes
stronger as a more recent pilot clinical trial reported significant difference in fasting
blood glucose, pre-intervention and post-intervention, between cinnamon treated and
placebo groups. Mang et al hypothesized that cinnamon improves HbA1c, FBG, LDL,
HDL, TC and TG in type II diabetes. This hypothesis was tested in a double blind study
which took place in Hannover, Germany, enrolling seventy nine subjects (44 men, 21
women) with type II diabetes; data evaluation was based on 65 subjects (14 were
excluded from the study). All subjects were not on insulin and were allowed to continue
anti-diabetic medications (27.7% metformin, 12.3% sulfonylureas, 4.6% glinides, 1.5 %
glitazones and 30.8% combination therapies) or diet. Subjects were randomly assigned
to placebo group or cinnamon group taking one capsule of aqueous cinnamon extract
(Cinnamomum cassia) equivalent to 1g of cinnamon given three times daily with a
meal for 4 months. Post-intervention results showed a significant difference in the mean
percentage of fasting plasma glucose in the cinnamon group (10.3 ± 13.2%) comparing to placebo group (3.37 ± 14.2%); cinnamon treated group obtained a greater
reduction in fasting plasma glucose. On the contrary, Mang et al found no significant
intergroup differences in HbA1c, LDL, HDL, TC and TG levels after treatment. Conclusively,
Mang et al acknowledged the moderate glucose lowering effect of aqueous cinnamon
extract comparing to Khan et al findings and that the 10% reduction in fasting glucose
was not sufficient enough to observe a difference in lipoprotein levels.25
Although, the plasma glucose lowering effect of cinnamon remained consistent based
on Khan et al and Mang et al studies, a solid ground has not yet established due to contradicting findings as Vanschoonbeek et al reported in their study (double blind, placebo
controlled) of cinnamon on 25 postmenopausal women with type II diabetes.
All subjects were allowed to continue antidiabetic medications (sulfonylureas, metformin,
thiazolidinediones or combination therapy) or diet alone during the 6 weeks of study.
Subject were randomized to either placebo or treatment group which received
cinnamon capsules (Cinnamomum cassia) 1500mg/day divided into three doses
administered after each main meal daily. Insulin sensitivity, oral glucose tolerance test,
HbA1c and lipid profiles were taken at fasting state before treatment, 2 weeks and 6
weeks after treatment. Vanschoonbeek et al found no significant differences in the levels
of fasting plasma glucose, insulin, HbA1c, LDL, HDL, TC and TG at 2 and 6 weeks of
treatment.26
Safety Profile
Cinnamon does contain a measurable amount of goitrogens,
oxalates, or purines and is not known to cause food allergies.
2
Consumption of large quantities of cinnamon bark and moderate
intake of cinnamon oil has been shown to have an increase on
various biological functions. An increased effect on heart rate,
intestinal motility, breathing, and perspiration via a chemical
stimulation of the vasomotor center has been reported. After a
period of increased function of these organs a period of central6
ized sedation will occur. A case of generalized contact dermati
27
28
tis has been reported after a therapeutic mud bath with cinnamon essential oil. Intraoral
cinnamon allergies have been reported with prolonged contact of cinnamon agents
such as cinnamon-flavored chewing gum and candies. The literature states that women
between the ages of 30 and 60 years old are most susceptible to cinnamon induced
oral allergies.29
Conclusion
Though cinnamon has been used for thousands of years, there is still more investigating
to do concerning its medicinal benefits. The effects of cinnamon have been seen from
brewing and from using ethanol extracts of the spice. An agent that is known for its sweet
flavoring characteristics, cinnamon also has many beneficial pharmacological effects in
the treatment of various disease states.
Sources :
1 Picture taken from Tripper pictures collection
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http://www.whfoods.com/genpage.php?tname=foodspice&dbid=68 . Accessed February 22, 2007.
3 Photograph taken from Tripper Group 2006 website. Available at:
http://www.tripper.com/photos.php?screen=5&cat=Company&sub=Photo%20Collections&photo=Cinnamon . Accessed March 5, 2007.
4. "Cassia." Wikipedia, The Free Encyclopedia. 15 Jan 2007, 22:34 UTC. Wikimedia Foundation, Inc. 18 Jan 2007 Available at:
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11 Photograph taken from Botanical.com website.Available at :http://www.botanical.com/botanical/mgmh/c/cassia31-l.jpg
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