Abstract
Long known as a spice, cinnamon’s potential efficacy in the treatment of type 2 diabetes has been gaining interest. Evidence from animal models shows efficacy as an insulin mimetic and insulin sensitizing agent, in addition to other potential mechanisms of action. Human clinical data regarding its efficacy have shown inconsistent results but may be related to differentials in baseline glucose control, type of cinnamon used, and duration of study. Overall, a significant number of trials have shown cinnamon to be an effective option for lowering blood sugar in uncontrolled type 2 diabetics. Cinnamon’s reasonable cost, over-the-counter availability, and safety profile make it a relatively low-risk option for this population.
Cinnamon has been used medicinally in traditional Chinese culture for thousands of years.1,2 In addition to its use as a spice, cinnamon has been used to treat a variety of ailments such as headaches, loss of appetite, dyspepsia, the common cold, inflammation, wounds, nausea, and diarrhea.3-5 Cinnamon has also been used to treat the
All originating from the bark of trees native to South East Asia from the genus
In addition to its use as a spice, cinnamon has been used to treat a variety of ailments such as headaches, loss of appetite, dyspepsia, the common cold, inflammation, wounds, nausea, and diarrhea.
Within the past 10 years, numerous studies have analyzed cassia cinnamon in the treatment of type 2 diabetes. The purpose of this article is to describe cassia cinnamon, summarize the available evidence related to its effect on glycemic control, and discuss its clinical utility including dosage, side effects, precautions, and target treatment populations.
Potential Mechanisms of Action
Several rodent models and in vitro studies found that cinnamon may have the potential to decrease blood glucose and lipid levels through various mechanisms, some of which mimic the mechanisms of commonly used agents in Western medicine.6-16
Primarily, cinnamon has been shown to be an insulin mimetic.7-10 In vitro studies show that cinnamon increases cellular glucose uptake and glycogen synthesis in rats with high fructose diets.10,11 A trial in healthy human subjects found that cinnamon administration reduced postprandial serum insulin and increased glucagon-like peptide 1 (GLP-1) without significantly affecting blood glucose. 12 The decrease in serum insulin may indicate a decreased demand for insulin, likely due to enhanced glucose uptake, as discussed previously. The mechanism by which cinnamon increases GLP-1 is unknown, but its effects may be similar to the GLP-1 analogues exenatide and liraglutide, or the dipetidyl-peptidase 4 (DPP4) inhibitors sitagliptin, saxagliptin, and linagliptin.
Cinnamon may also be involved in the activation of peroxisome proliferator–activated receptors (PPAR)-γ and PPAR-α.3,13,14 Thiazolidinediones, including pioglitazone and rosiglitazone, target PPAR-γ and promote insulin sensitivity. The fibrate class of anti-hyperlipidemics target PPAR-α, which lowers plasma triglycerides and elevates plasma high-density lipoprotein cholesterol.
Finally, rodent models suggest that cinnamon may inhibit hepatic 3-hydroxy-3-methyl-glutaryl CoA reductase activity.15-17 This mechanism parallels that of the popular statin drug class.
Human Clinical Data
Human clinical studies analyzing the glycemic effects of cinnamon have varied results to date, although no large placebo controlled trials currently exist.1,17-22 A study by Lu et al compared 2 strengths of daily cinnamon extract supplementation with placebo.
2
The study included 66 Chinese type 2 diabetics treated with gliclazide (a sulfonylurea not marketed in the United States). Lu et al found statistically significant reductions in HbA1c in those receiving 360 mg of cassia cinnamon extract (−0.92%,
Another study by Khan et al looked at cinnamon supplementation in 60 type 2 diabetics treated with sulfonylureas. 18 The study found statistically significant decreases in mean fasting plasma glucose (FPG; 18% to 29%), triglycerides (23% to 30%), low-density lipoprotein cholesterol (7% to 27%), and total cholesterol (12% to 26%), following supplementation with either 1, 3, or 6 g of cassia cinnamon daily for 40 days. The significant change in FPG over time was similar across the 3 treatment doses while no change was seen in the placebo group.
Crawford conducted a randomized controlled trial simulating “usual care,” in which comorbid conditions, medication changes, and insulin use were allowed in the population.
22
It is one of the largest cinnamon trials to date with more than 100 individuals randomized. The study found that supplementation with 1 g of daily cassia cinnamon significantly lowered HbA1c by 0.83% (
In a study of 58 type 2 diabetics, Akilen et al found that patients treated with 2 g of cassia cinnamon daily for 12 weeks showed a statistically significant decrease in mean HbA1c (−0.36%,
A study by Mang et al found that daily cassia cinnamon extract administration significantly reduced FPG but not HbA1c in 65 type 2 diabetics.
17
Fasting plasma glucose was reduced in the treatment group 10.3% versus 3.4% in those receiving placebo (
Interestingly, several of the studies that yielded insignificant effects from cinnamon supplementation looked at patients with lower baseline HbA1c levels. The studies by Lu, Crawford, and Akilen all showed favorable effects of cinnamon in study populations with baseline HbA1c levels >8%. The Khan study showed favorable results, but did not report baseline HbA1c levels. The studies with insignificant results are described below, each with baseline HbA1c levels <8%.
Blevins et al conducted a randomized trial of cinnamon in American type 2 diabetics. 20 The study found that taking cassia cinnamon did not yield a significant change in HbA1c after 3 months versus placebo. Baseline HbA1c levels in the Blevins study were relatively low and near HbA1c goal, with means of 7.2 ± 0.3% and 7.1 ± 0.2% in the treatment and control groups, respectively. Vanschoonbeek et al conducted a placebo controlled trial of postmenopausal women, which concluded that cinnamon did not improve whole body insulin sensitivity, oral glucose tolerance, or the blood lipid profile after 30 days. 21 Again, the baseline characteristics of the women showed blood glucose levels near goal, with mean HbA1c levels of less than 7.5%. Additionally, 30 days of treatment may not be enough time for changes in HbA1c to be realized. In the Mang study, despite statistically significant decreases in fasting plasma glucose, changes in HbA1c were insignificant. Baseline HbA1c values for participants in the Mang study were below 7%.
Cinnamon Dosing, Side Effects, and Precautions
Between 1 g and 6 g of cassia cinnamon daily for up to 4 months has been studied in the treatment of type 2 diabetes.4,5 According to the Natural Medicines Comprehensive Database (NMCD), 1 teaspoon of cinnamon spice is equal to 4.75 g. 4 Caution must be used when recommending cinnamon purchased as a spice, as this formulation is often a mixture of several species. Only cassia cinnamon has been shown to have a significant effect on glycemic control. Capsules of several strengths of cassia cinnamon are available over the counter. When recommending cinnamon for medicinal benefit, it is likely best for cassia cinnamon capsules to be used.
The side effect profile for cinnamon is relatively mild. The NMCD rates cinnamon as likely safe when used orally within the dosage range suggested (1-6 g daily). 4 High-dose, long-term use has been classified as possibly unsafe. There is some concern about ingesting large amounts of cassia cinnamon due to its coumarin content. High daily doses of coumarin (50-700 mg) have been known to cause reversible hepatotoxicity. It is unlikely that such doses would result from cinnamon supplementation; however, caution should be used in those at risk for liver disease. 4 Although cases of hypoglycemia have not been documented with cinnamon use, caution should be used when recommending cinnamon to patients already taking insulin or sulfonylureas due to the potential for hypoglycemic effects with these agents.
Discussion
The study of cinnamon supplementation for the treatment of type 2 diabetes has mixed results. There are several hypotheses as to why some studies have produced statistically significant results while others have not. The first is based on the baseline blood glucose levels of those being studied. It is likely that the most significant effect of cinnamon is seen in patients whose baseline blood glucose levels are highest. Second, varied types and extracts of cinnamon have been used, and in a wide range of doses. As only cassia cinnamon has demonstrated clinical efficacy, it is possible that use of other species or combinations of species have contributed to nonsignificant results. Third, studies varied in duration and some may not have had long enough follow-up periods to see significant results.
The use of cinnamon in uncontrolled type 2 diabetic patients has potential for glucose lowering as well as cost savings. The HbA1c reductions seen with cinnamon rival those of commonly prescribed oral antidiabetic agents, whose average A1c lowering range from 0.5% to 1.25%. 23 Although some generic oral antidiabetic agents may cost only $12 for a 3-month supply, costs for brand-name DPP-4 inhibitors can exceed $600 for 3 months of treatment. 24 In contrast, capsules containing 1 g of cinnamon daily may cost less than $20 for 3 months. 25 Because of this, the use of cinnamon in place of or in combination with other antidiabetic agents may result in significantly lower costs to patients.
Conclusion and Clinical Recommendations
Despite the mixed results coming from studies of cinnamon in type 2 diabetic patients, there is promise in its potential effects. Large, randomized, placebo-controlled studies of cinnamon need to be completed in order to fully evaluate its efficacy. However, due to the significant amount of favorable studies in patients with uncontrolled type 2 diabetes, cinnamon is a reasonable treatment option in this population. Cinnamon’s low cost, over-the-counter availability, and safety profile make it a relatively low-risk alternative to traditional glucose-lowering medications. When recommending cinnamon for medicinal benefit, it is likely best for cassia cinnamon capsules to be used rather than use of the spice. Cinnamon spice is generally a mixture of several species of cinnamon, some of which may not be effective at glucose lowering.