Cassia Cinnamon in Diabetes Mellitus Type 2

By Craig Schneider, MD and Ted Wissink, MD. Dr. Schneider is Director of Integrative Medicine, Department of Family Medicine, Maine Medical Center in Portland. Dr. Wissink is a Fellow in the Integrative Family Medicine Program at Maine Medical Center and University of Arizona (Tucson); they report no financial relationships relevant to this field of study.

Cinnamon is aromatic, tasty, and sweet, but does it play a role in treating diabetes?; in vitro and animal studies are promising. Recent media reports are glowing, but how good is the evidence supporting the use of cinnamon in glycemic control and diabetes mellitus? The few clinical trials available are conflicting.

History and Traditional Use

There are many different species and types of cinnamon. Several are gastronomic, others ornamental, and some are considered medicinal. Cinnamon is found across a multitude of culinary traditions, and it has been used in traditional medicine formulae for multiple purposes, especially for its carminative (anti-gas) properties, to aid digestion and improve appetite. In East Asia, one traditional use has been in the treatment of diabetes mellitus.1 In the West, Cinnamomum verum (Ceylon cinnamon) and Cassia cinnamon are the types most commonly used. Cinnamon sold as a culinary spice is often a mixture of more than one type. Cassia cinnamon shows up in toothpaste, mouthwashes, and gargles, as well as flavoring for foods and beverages. This article will focus on Cassia cinnamon. It is worth noting that when samples of cinnamon from different geographic sources and commercial preparations were compared by Anderson and colleagues for their insulin-like activities, they reported similar activity among the different samples.2

Botany and Pharmacology

Cassia cinnamon, also known as Cinnamomum aromaticum or Chinese cinnamon, is a member of the Lauraceae family. The genus name Cinnamomum may be from Arabic, Hebrew, or Malay language origins, and its species name, Cassia, is believed to derive from the Greek Kassia meaning to strip off the bark.2 Chinese medical texts trace its use back to at least 2700 B.C.2 Cassia cinnamon is a medium-sized evergreen tree native to China and Vietnam but now cultivated across Asia and other subtropical locales. Both bark and flower are cultivated. Volatile oils from Cassia cinnamon bark contain cinnamaldehyde, cinnamic acid, cinnamyl alcohol, and coumarin.3

Mechanism of Action

In vitro studies of Cassia cinnamon demonstrate multiple mechanisms of action. Cinnamaldehyde from Cassia cinnamon has antibacterial, immunomodulating, antioxidant, and antitumor activity.4,5 Aqueous extracts appear to increase glycogen synthetase, glucose uptake, and glucose oxidation in vitro.6 Cinnamomum has been demonstrated to have insulin-enhancing activity.7,8 Polyphenolic polymers found in Cassia cinnamon appear to potentiate the action of insulin by increasing phosphorylation of insulin receptors, resulting in enhanced insulin sensitivity.9 Cassia has been shown to stimulate insulin release and lower blood glucose during a glucose tolerance test in vivo.10

Clinical Studies

There are four relatively small, randomized, double-blind, placebo-controlled studies that have looked at the effects of Cassia cinnamon in patients with type 2 diabetes. The results are conflicting. In 2003, Khan and colleagues7 reported findings from a study of 6 groups of 10 Pakistani patients (30 men and 30 women aged 52.2 ± 6.3 years) with type 2 diabetes who consumed 1, 3, and 6 grams of cinnamon or placebo (wheat flour) daily, taken after meals for a period of 40 days. From days 41-60, neither cinnamon nor placebo were given. Fasting glucose levels after 20 days were only significantly lower in the group receiving 6g of cinnamon daily but, at 40 days, each group consuming cinnamon had a significant (P < .05) reduction in fasting serum glucose (18-29%), triglyceride level (23-30%), LDL (7-27%), and total cholesterol (12-26%). No difference was found from baseline in the placebo groups. There was no evidence of a dose response, as all three cinnamon groups showed similar effects. However, in the 20-day period following the intervention, when neither cinnamon nor placebo were given, significant improvements were maintained only in the groups receiving lower doses. No dropouts were reported, and compliance was excellent. There were no reports of adverse or toxic effects, even at the highest dose of Cassia cinnamon. This study has been criticized for several limitations, including inadequate description of Cassia standardization, randomization, and blinding protocols, and a failure to utilize intention-to-treat analysis.

In 2006, Vanschoonbeek and colleagues11 studied 25 overweight, postmenopausal Dutch women with type 2 diabetes who were either on oral antiglycemic drugs or whose diabetes was diet-controlled. The women were given a baseline oral glucose tolerance test (OGTT), and glycosylated hemoglobin (HBA1c) and fasting blood lipid profiles (FLP) were obtained. They were then divided into two groups: 12 patients consumed 1500 mg of cinnamon daily and 12 patients consumed a reportedly indistinguishable placebo (wheat grass) daily for 6 weeks. The OGTT, HBA1c, and FLP were repeated after 2 and 6 weeks of supplementation. At both 2 and 6 weeks, there were no differences found in fasting glucose, HBA1c, or FLP from baseline compared with placebo. All subjects tolerated the treatment well. No allergies or adverse or toxic effects were reported. As with the Khan study, this trial also lacked an adequate description of Cassia standardization of the product used, randomization and blinding protocols, and employed a small study population.

In 2006, Mang and colleagues12 reported on 79 German patients with type 2 diabetes in a 4-month double-blind, randomized, controlled trial. Rather than using cinnamon, an aqueous cinnamon extract was utilized in an attempt to reduce the potential risk of adverse effects, such as coagulopathy or allergic reaction, by limiting the content of coumarins and essential oils in the extract. Patients were randomized to cinnamon extract (equivalent to 1 gram of cinnamon) or placebo 3 times daily with meals. Twenty-three percent of patients were diet controlled, while the remainder were using sulfonylurea, metformin, thiazolidinediones, or a combination of these agents. Approximately half the participants were also taking antihypertensive medications, and 20% were on antihyperlipidemics. Fasting glucose, HbA1c, and lipids were measured at baseline and again after 4 months. Fasting glucose was reduced significantly by approximately 10 % in the cinnamon extract group (average 147 mg/dL) compared to the placebo group (average 167 mg/dL) P = 0.046. There were no other significant differences detected. No allergies or adverse or toxic effects were reported. In addition to using a cinnamon extract rather than Cassia cinnamon, as in other trials, a limitation of this study is its small sample size and lack of intention-to-treat analysis.12

In 2007, the first randomized, controlled trial of Cassia cinnamon in the United States was reported by Blevins and colleagues.13 Sixty subjects were randomized to receive either Cassia cinnamon 500 mg capsules twice daily with meals or a wheat flour placebo. Fasting glucose, cholesterol, insulin levels, and HBA1c were measured at baseline and again after 3 months. Participants were divided equally by gender and included Caucasians 68%, Native Americans 16%, African Americans 7 %, Hispanics 4 %, and Asians 2 %. More than 75% of participants in the cinnamon group were also taking medications for diabetes (three-quarters were on metformin, one-third on thiazolidinediones), and over half were on lipid lowering medications (statins). No significant changes were noted in any of the parameters measured.13 This was a small study, but it did use intention-to-treat analysis.

A single-blind, randomized, placebo-control trial evaluating the effect of Cassia cinnamon powder 1.5 grams 3 times daily in type 2 diabetes found reductions of fasting glucose and HBA1c in both the cinnamon and placebo groups in a Thai population over a 3-month period; there was no statistical significance between them. Again, no adverse effects were noted.14

Adverse Effects

In the United States, Cassia cinnamon has generally been recognized as safe (GRAS) status. Orally, it is generally well-tolerated. Clinical trials lasting as long as 4 months have not identified significant side effects.15 No interactions with medications were observed in the available clinical trials looking at Cassia and type 2 diabetes where patients were also taking sulfonylurea drugs, metformin, and/or thiazolidiones. There have been reports of allergic reactions to cinnamaldehyde.16 Cassia contains coumarin, a substance demonstrated to cause hepatotoxicity in rodent models. There is concern that very high doses might do the same in humans; however, coumarin exposure from natural dietary sources is considered safe for most people.17 Nevertheless, it seems reasonable to use caution when using Cassia cinnamon in patients with liver disease or who take other potentially liver-damaging medications and/or dietary supplements.

Conclusions

Cinnamon has a long and varied history of worldwide use. In East Asia, one use has been for the treatment of diabetes mellitus. Cinnamon has gained recognition in the West because of in vitro findings of insulin-potentiating effects. Recently, enormous media attention followed positive findings of the Kahn et al study, and a number of nutritional supplements containing cinnamon, and marketed toward healthy maintenance of blood sugars, have come onto the market. A recent internet query on "cinnamon and diabetes" generated 907,000 "hits." But is cinnamon beneficial in this setting? Available clinical trials present conflicting evidence about the effects of cinnamon supplementation in patients with type 2 diabetes, and "solid" proof remains to be established.

One key difference between the double-blind, placebo-controlled studies is that only women were included in the negative trial by Vanschoonbeek et al,11 while Khan et al,7 Mang et al,12 and Belvins et al13 included both male and female subjects. Another distinction involved the types of diabetes medications taken by patients enrolled in the studies. Khan et al7 included patients taking sulfonylureas, while Vanshoonbeek et al11 included patients taking sulfonylureas, metformin, and/or thiazolidiones. Mang et al12 included those taking antihypertensive and antihyperlipidemic medications, and Blevins et al13 included participants on metformin, thiazolidinediones, and lipid-lowering drugs.

There were also significant differences in baseline values of fasting glucose and HBA1C between the studies. Khan et al7 used patients with an average baseline (FBG = 232mg/dL) and did not measure HBA1C (although this would appear to translate to an HBA1c of between 8-9). The other three studies all used patients with more tightly controlled diabetes. Vanshoonbeek et al11 patients had an average FBG = 149 and HBA1C = 7.25, Mang et al12 patients had an average FBG = 161 and HBA1C = 6.79, and Blevins et al13 patients had an average FBG = 139 and HBA1C = 7.15. Mang et al12 and Khan et al,7 observed a 10% and 30% reduction in FBG, respectively, while the other two studies found no significant differences for either FBG or HBA1C. Each of these clinical trials are important initial attempts to expand on the in vitro research into the effects of Cassia cinnamon. Although each study has its limitations, the reduction in fasting serum glucose, triglyceride, total cholesterol, and LDL cholesterol levels found by Khan et al,7 and the reduction in FBG found by Mang,12 are intriguing.

Cinnamon could easily be incorporated into diabetic patients' daily diet without contributing to their caloric intake, and is a familiar and well-tolerated culinary spice for people around the world. The fact that no allergies or adverse or toxic effects were reported in any study lasting up to 4 months also makes Cassia cinnamon likely to be safe for diabetic patients to try as adjunctive therapy. Patients with a history of liver disease or on medications/supplements that have the potential to cause liver damage would benefit from close monitoring when using cinnamon.

Recommendations:

Despite the positive press and supportive in vitro trials on cinnamon, larger and longer-term studies are needed to more clearly determine whether, and in what dose, Cassia cinnamon has a beneficial effect on blood glucose and related cardiac risk factors in diabetic patients. In the meantime, for diabetic patients wishing to try Cassia cinnamon in addition to their current regimen, let them know that most studies have used between 1 and 6 grams daily, and that a half-teaspoon of store bought Cassia cinnamon approximates 1 gram.15

References

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11. Vanschoonbeek K, et al. Cinnamon supplementation does not improve glycemic control in postmenopausal type 2 diabetes patients. J Nutr. 2006;136:977-980.

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13. Blevins SM, et al. Effect of Cinnamon on glucose and lipid levels in non-insulin dependent type 2 diabetes mellitus. Diabetes Care. 2007.

14. Suppapitiporn S, et al. The effect of cinnamon cassia powder in type 2 diabetes mellitus. J Med Assoc Thai. 2006;89 Suppl 3:S200-S205.

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16. De Benito V, Alzaga R. Occupational allergic contact dermatitis from cassia (Chinese cinnamon) as a flavouring agent in coffee. Contact Dermatitis. 1999; 40:165.

17. Felter SP, et al. A safety assessment of coumarin taking into account species-specificity of toxicokinetics. Food Chem Toxicol. 2006;44:462-475.