Cinnamon–More Than Just a Flavoring Agent

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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