US Pharm. 2007;32(12)38-42.
It is impossible to obtain the
strong, sweet, and inviting aroma of cinnamon bread and cookies without
cinnamon; however, cinnamon is more than just another flavoring agent. One of
today's most popular spices, it is also one of the oldest known flavorings. In
medieval Europe, cinnamon was known as a staple ingredient in many recipes.
Cinnamon was also cited in the Bible and was used in ancient times as a
beverage flavoring, medicine, and even as an embalming agent. Cinnamon was
treasured during this period, considered more precious than gold. During this
time, cinnamon received attention in China, evidenced by its inclusion in one
of the earliest books on Chinese botanical medicine, dated around 2700 B.C.
1 Even today, cinnamon is considered one of the 50 Chinese fundamental
medicinal herbs.
Plant Origin
The world's fourth
largest country after Russia, Canada, and the United States, China is the home
of the gigantic and beautiful Mount Everest, which is located in the
southwest. China is the native home land of Cinnamomum cassia, a
species closely related to Cinnamomum zeylanicum.2
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 to 15 meters tall with grayish bark and is
harvested specifically 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
Antimicrobial:
Historically, cinnamon had been used to combat gastrointestinal disorders
such as diarrhea, dyspepsia, and Helicobacter pylori (H pylori).
3 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 Staphylococcus aurus, gram-negative
Escherichia coli, Enterobacter aerogenes, Proteus vulgaris,
Pseudomonas aeruginosa, Vibrio cholerae, Vibrio parahaemolyticuas
, and Samonella typhymurium. The antimicrobial effect resulted in a
minimum inhibition concentration (MIC) of cinnamomum cassia extract
ranging from 75 mcg/mL to 600 mcg/mL on these various bacteria.4
However, conflicting data was obtained in a randomized, controlled pilot
clinical trial of 15 patients ages 16 to 79 who had a positive Campylobacter
urease test for H pylori. Each patient in the control group received 40
mg of ethanol extract of cinnamon twice daily 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, respectively; the mean urea breath test before and
after the study for the controlled group were 23.9 and 25.9, respectively.
This conclusive study found that 40 mg of cinnamon extract given twice daily
was ineffective in eradicating H pylori.1,5
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-kB). Both substances have been implicated in inflammation. In acute and
chronic inflammation, there is an increased production of NO, which promotes
vasodilatation and results in increased vascular permeability and edema.
Nitric oxide also activates COX-2 enzyme involving in the biosynthetic pathway
of inflammatory prostaglandins.2,6 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 NO production and
transcriptional activity of NF-kB, thereby contributing to its
anti-inflammatory qualities.7
Antifungal:
Cinnamon oil has been reported as an antifungal agent, although current
efficacy of cinnamon oil's fungicidal effect has not been tested in clinical
trials. Experimentally, promising results on its antifungal activity were
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 pulmonary cryptococcosis or
cryptococcocal meningitis.7 It was found that the phenolic compound
in cinnamon oil identified as eugenol is responsible for its fungitoxic
activity.8 Cinnamon oil's 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, entering the respiratory tract of
patients with AIDS or with immunocrompromised conditions to cause
Aspergillosis.9 Seventy-five botanical essential oils, including
Cinnamomum zeylanicum and Cinnamomum cassia, were tested for the
inhibition of hyphal growth and spore formation on inoculated agar with A.
niger incubated at 28?C for 48 hours. Among the 75 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 versus 50 and 45 for
Cinnamomum zeylanicum and Cinnamomum cassia, respectively.10
Antioxidant:
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 (OPC), a class
of bioflavonoid, opened a new area of research on its antioxidative effect.
Through agriculture research, type A and type B oligomeric proanthocyanidins
were identified in cinnamon spice via mass spectrometer analysis.
Additionally, it was found that over 84% to 90% of OPC found in cinnamon spice
were type A OPC.11 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 2 is a metabolic disorder that will affect an estimated
25.4 million of people in 2011, 32.6 million people in 2021, and 37.11 million
people in 2031.12 It is characterized by impaired glucose
metabolism and peripheral insulin resistance; symptoms are hyperglycemia,
polydipsia, polyphagia, and polyuria. Glycemic control is the key in slowing
disease progression as well as preventing peripheral neuropathy, nephropathy,
and retinopathy. It places affected individuals at high risk for
atherosclerotic coronary artery disease, mucocutaneous fungal infections, and
bacterial foot infections. Nonpharmacological treatment approaches are
lifestyle modifications such as aerobic exercise and healthy food choices.
13 Available pharmacologic treatments include a biguanide,
sulfonylureas, thiazolinidinees, alpha-glucosidase inhibitors, meglitinides,
and various insulin preparations.14 Additionally, in 2005 the FDA
approved three new drugs, Byetta, Symlin, and Levemir, classified as incretin
mimetic, amylino-mimetic, and insulin determir, respectively. In 2006, FDA
approved Januvia, a dipeptidyl peptidase-4 enzyme inhibitor, and Exubera, an
insulin human [rDNA origin] inhalation.15 The list continues to
lengthen as more drugs are awaiting FDA approval including Galvus, Glucobetic,
and Cinnulin PF, OTC nutraceutical products claiming beneficence for
individuals with diabetes. Glucobetic's active ingredients
include vitamins and cinnamon bark extract. Cinnulin PF contains aqueous
extract of cinnamon.
Hypoglycemic Effect
Through Human Studies: The quest for new treatments continues as the
realm of research for type 2 diabetes expands to nutraceutical products. A
pilot clinical trial conducted in Pakistan to study the effect of cinnamon in
patients with type 2 diabetes harvested successful results. The study involved
60 subjects (30 men and 30 women) with type 2 diabetes, average age of 52.2 ±
6.32 years, fasting plasma glucose of 140-400 mg/dL, and not taking 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 g of cinnamon capsules (Cinnamomum cassia powder) daily for
40 days followed by a 20-day wash-out period. All subjects were allowed to
continue taking sulfonylurea drugs during the study. Plasma glucose,
triglyceride, low-density lipoprotein (LDL), high-density lipoprotein (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, the 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-day 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 2 diabetes and that inclusion of
cinnamon into daily diet may be beneficial to the remainder of the population.
16
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 postintervention, between cinnamon treated and
placebo groups. Mang et al. hypothesized that cinnamon improves glycosylated
hemoglobin (HbA1c), fasting blood glucose (FBG), LDL, HDL, total cholesterol
(TC), and triglycerides (TG) in type 2 diabetes. This hypothesis was tested in
a double-blind study that took place in Hannover, Germany, enrolling 79
subjects (44 men and 21 women) with type 2 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 antidiabetic 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 a placebo
group or a cinnamon group, taking one capsule of aqueous cinnamon extract (
Cinnamomum cassia) equivalent to 1 g of cinnamon given three times daily
with a meal for four months. Postintervention results showed a significant
difference in the mean percentage of fasting plasma glucose in the cinnamon
group (10.3% ± 13.2%) compared to the placebo group (3.37% ± 14.2%); the
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
compared to the Khan et al. findings and that the 10% reduction in fasting
glucose was not sufficient to observe a difference in lipoprotein levels.
17
Although, the plasma
glucose–lowering effect of cinnamon remained consistent based on the 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 2 diabetes. All subjects were allowed to continue antidiabetic
medications (sulfonylureas, metformin, thiazolidinediones or combination
therapy) or diet alone during the six weeks of study. Subject were randomized
to either placebo or treatment group, which received cinnamon capsules (
Cinnamomum cassia) 1500 mg/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, two weeks,
and six 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 two weeks and six weeks of treatment.18
Safety Profile
Cinnamon does
contain a measurable amount of goitrogens, oxalates, or purines and is not
known to cause food allergies.1 Consumption of large quantities of
cinnamon bark and moderate intake of cinnamon oil has been shown to have an
increased effect 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 centralized sedation will
occur.3 A case of generalized contact dermatitis has been reported
after a therapeutic mud bath with cinnamon essential oil.19
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 oral allergies.20
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.
References
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3. Cinnamon [monograph on Stat!Ref]. The review of natural products. St. Louis, MO: Wolters Kluwer Health, Inc.; 2007.
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13. American Diabetes Association Web site. Available at: www.diabetes.org/type-2-diabetes.jsp. Accessed February 26, 2007.
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18. Vanschoonbeek K, Thomassen BW, Seden JM, et al. Cinnamon supplementation does not improve glycemic control in postmenopausal type 2 diabetes patients. J Nutr. 2006;136:977-80.
19. Garcia-Abujeta JL, Larramendi C, Berna J, et al. Mud bath dermatitis due to cinnamon oil. Contact Dermatitis . 2005;52:234.
20. Rossi S, Greenburg M. Intraoral contact allergy: A literature review and case reports. JADA. 1998;129:1435-1441.
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