Cinnamon and Glycemic Control of Type 2 Diabetes

Jessica Livshits
The Sage Colleges

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Introduction:

Cinnamon is a versatile spice; it is commonly used as a flavoring agent and holds

medicinal properties (Medagama, 2015). Cinnamon is a genus of the Lauraceae family

(Medagama, 2015). Around 250 species of cinnamon have been discovered, 4 of which produce

cinnamon (Medagama, 2015). The most available type of cinnamon is cassia cinnamon. This

type can be found in stick form or ground powder. Ceylon cinnamon is said to be true

cinnamon (Medagama, 2015). Cinnamon is thought to have anti-diabetic effects, along with anti-

oxidant and anti-inflammatory effects as well (Medagama, 2015). The focus of this paper will be

on cinnamon and its potential to be used in treatment of type 2 diabetes.

Type 2 Diabetes Mellitus is a chronic disease that involves elevated blood glucose levels;

the body is unable to effectively use produced insulin (CDC, 2017). Diabetes mellitus is a major

contributor to worldwide morbidity and mortality. The prevalence of diabetes has nearly doubled

since 1980 (Talaei et al., 2017)) The World Health Organization estimated that in 2015, 347

million people had diabetes (Medagama, 2015). In the United States, diabetes was the seventh

leading cause of death in 2013 (CDC, 2017).

There has been a 30-57 percent increase in the use of complementary and alternative

medicines (CAMs) in the treatment or maintenance of diabetes (Bell, 2006). Around 2-3.6

million people in the United States rely on complementary and alternative medicines for the

treatment of their diabetes mellitus (Medagama, 2015). Integrative medicine combines

traditional medicine with evidence-based complementary options (Medagama, 2015). Currently,

the American Diabetes Association does not endorse natural supplement use in the treatment or

management of type 2 diabetes (Allen et al., 2013). This paper will examine the potential role

cinnamon may play in glycemic control of type 2 diabetes.

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Type 2 Diabetes:

Type 2 diabetes is characterized by high blood glucose levels and defects in insulin action

(Ota and Ulrih, 2017). Defects in insulin action lead to glucose staying in the bloodstream.

Insulin resistance is associated with impaired insulin signaling pathways (Medagama, 2015).

Prolonged periods of elevated blood glucose levels are associated with long-term damage and

organ failure (Ota and Ulrih, 2017). Extended hyperglycemia can lead to heart disease, vision

problems, kidney problems, and nerve damage (CDC, 2017). The development of type 2 diabetes

is correlated with obesity, family history, poor diet, sedentary lifestyle, age, ethnicity, high blood

pressure, and dyslipidemia (Ota and Ulrih, 2017). In 2012, 1.5 million deaths were caused by

diabetes while high blood glucose levels were associated with an additional 2.2 million deaths

(Ota and Ulrih, 2017). Type 2 diabetes is primarily diagnosed in the adult population, but recent

data shows an increase in childhood diagnosis. 95 percent of people with diabetes mellitus have

type 2 diabetes (CDC, 2017). Type 2 diabetes can be managed through medications, insulin, and

healthier lifestyle choices (CDC, 2017).

Cinnamon:

Cinnamon is thought to be capable of lowering serum lipids and blood glucose (Allen et

al., 2013). Cinnamon has been shown to reduce markers of oxidative stress (Kawatra, 2015). It is

also shown to contain anti-microbial actions and anti-oxidant properties (Kawatra, 2015).

Cinnamon can cause peripheral vasodilation, so research is being conducted in the role of

cinnamon in treating hypertension (Kawatra, 2015). Using hydro-distillation techniques, the

isolated compounds of cinnamon were eugenol, cinnamaldehyde, copane, cinnamyl acetate and

camphor, and others (Jayaprakasha et al., 2011). Cinnamaldehyde was one of the compounds

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shown to have hypoglycemic properties (Medagama, 2015). In one study, procyanidin oligomers

were identified as holding anti-diabetic properties (Chen et al., 2012). This study also showed

that different cinnamon species may have different hypoglycemic effects (Chen et al., 2012).

Various studies isolated active compounds to examine hypoglycemic properties, but the results

were inconclusive. Polyphenols are thought to lower the risk of type 2 diabetes (Kim et al.,

2015). Human studies have only utilized cassia cinnamon. Ceylon cinnamon has been used in

animal studies. (Medagama, 2015). In animal studies, Ceylon cinnamon was shown to have a

negative impact on renal function while liver impacts were short-term (Medagama, 2015). Cassia

cinnamon was not shown to have any significant negative effects; although, there were a few

cases of rashes, hives, and nausea (Medagama, 2015). The concern with cassia cinnamon is in its

high coumarin content (Medagama, 2015). High Performance Liquid Chromatography (HPLC)

showed that cassia cinnamon had a range of 2880-4820 mg/kg (Medagama, 2015). Coumarins

are said to contain carcinogenic and hepatoxic properties (Medagama, 2015).

Cinnamon: Mechanisms of Action

There is extensive research on the mechanisms by which cinnamon is capable of

producing anti-diabetic effects (Medagama, 2015). Changes within the insulin receptor may be

one mechanism. Increased phosphorylation and decreased dephosphorylation of the receptor

increases the insulin sensitivity (Medagama, 2015). Under normal conditions, binding to the

alpha-subunit leads to activation of the beta-subunit and this process results in

autophosphorylation (Medagama, 2015). GLUT-4 is a glucose transporter that is induced by

insulin (Medagama, 2015). Insulin promotes the shift from GLUT-4 inside the cell to the cell

membrane. GLUT-4 is decreased in diabetes (Medagama, 2015). Cinnamon may increase the

number of GLUT-4 receptors. Current research suggests that facilitating translocation through

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GLUT-4 will increase glucose uptake and utilization, benefiting hyperglycemic control (Allen

et al., 2013). Another study looked at the gastric emptying rate when 6 grams of cinnamon was

added to rice pudding (Medagama, 2015). Inhibition of gluconeogenesis was examined. In

diabetic rats, pyruvate kinase activity was reduced while Phosphenol Pyruvate Carboxi-kinase

(PEPCK) activity was increased (Megadama, 2015). Cinnamon causes an increase in the

expression of PPAR (and PPAR (, which increases insulin sensitivity (Medagama, 2015).

PPAR agonists are currently utilized in conventional medicine (Medagama, 2015).

Research

In a meta-analysis of 10 RCTs, cinnamon doses of 120 mg/day to 6 g/day for 4 to 18

weeks reduced levels of fasting plasma glucose (-24.59 mg/dL; 95% CI, -40.52 to -8.67 mg/dL)

(Allen et al., 2013). This meta-analysis also characterized total cholesterol (-15.6 mg/dL; 95%

CI, -29.76 to -1.44 mg/dL), LDL (-9.42 mg/dL; 95% CI, -17.21 to -1.63 mg/dL), and

triglycerides (-29.59 mg/dL; 95% CI, -48.27 to -10.91 mg/dL) (Allen et al., 2013). In this meta-

analysis, there was not a significant impact on hemoglobin A1c numbers (-.16%; 95% CI, -.39%

to .02%) (Allen et al., 2013). There was also an increase in HDL levels (1.66 mg/dL; 95% CI,

1.09 to 2.24 mg/dL) (Allen et al., 2013). Contradictions are seen in various data from these

studies. Cinnamon consumption of 1 to 1.2 g/day was associated with an increase in fasting

glucose levels in one study; although, this study was only published as a research brief and the

number of withdrawn patients was not reported (Allen et al., 2013). In another study, glucose

levels were shown to decrease with doses between 1 to 6 g/day and in hemoglobin A1c (Allen et

al., 2013). Two trials examined the benefits of cinnamon (1 to 2 g/day) on patients with

hemoglobin A1c values greater than 8% while also taking diabetes medications. These trials

were statistically significant (Akilen et al., 2010). The reductions in fasting plasma glucose

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levels (-24.59 mg/dL) are less than those achieved by metformin monotherapy (-58 mg/dL)

(Allen et al., 2013).

A randomized, placebo-controlled, double-blind clinical trial found that intake of 2

grams/day of cinnamon for 12 weeks significantly reduced hemoglobin A1c (-,36%; p<.005)

(Kim et al., 2015). A randomized, controlled trial (no placebo used with the concern that the

strong taste of cinnamon capsules would preclude any blinding), investigating whether daily

cinnamon plus usual care versus usual care alone lowers hemoglobin A1c in 109 patients with a

HbA1c>7, showed that supplementation with 1 gram of daily cassia cinnamon did not

significantly lower HbA1c over 90 days (Kim et al., 2015). A double-blind study found that

intake of 3 gram daily cinnamon powder for 120 days significantly decreased fasting glucose but

not HbA1c in 65 patients with type 2 diabetes treated with oral anti-diabetics or diet alone (Kim

et al., 2015). In this trial, fasting glucose was decreased by 10.3% +/- 13.2% in the experimental

group and 3.37% +/- 14.2% in the placebo group (p= .046) (Kim et al., 2015).

In Paul Crawfords randomized, controlled trial, the effect of cinnamon on hemoglobin

A1c was examined. This study was done to evaluate whether an intake of daily cinnamon plus

conventional care lowers hemoglobin A1c (Crawford, 2009). In this study, participants were

reviewed after 90 days. They were randomized to take two tablets of 500 mg cassia cinnamon

daily, in addition to their usual medications (Crawford, 2009). Cinnamon lowered HbA1c .83%

(95% CI, .46-1.2) compared with usual care alone lowering HbA1c .37% (95% CI, .15-.59)

(Crawford, 2009). The lack of placebo made it difficult to prove beyond any doubt that the

cinnamon itself versus the daily reminder to take the cinnamon provided was the cause of the

lowered hemoglobin A1c (Crawford, 2009). In this study, recruitment was halted because of the

relocation of the investigator. The cinnamon used was not tested for purity since there is limited

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regulation on cinnamon as a supplement (Crawford, 2009). The benefits are this trial could be

attributed to the size of the sample and looking at patients with poorly controlled diabetes. Also,

this study included patients who used insulin, which could have impacted the effect of cinnamon

(Crawford, 2009).

Talaei et al. examined the impact of 3 grams/day of cinnamon intake over eight weeks on

glycemic indicators (Talaei et al., 2017). This was a double-blind, randomized, placebo

controlled clinical trial. Fasting blood glucose, insulin, and hemoglobin A1c were some of the

measured markers (Talaei et al., 2017). 39 patients completed the study. The results for fasting

blood glucose (mg/dL) in the case group were -11.65+/- 29.34 (p=.09). (Talaei et al., 2017) The

results for the control group were 8.57+/- 35.10 (p=.3) (Talaei et al., 2017). The results in the

case group for hemoglobin A1c was .075+/- 1.51 (p=.83) while the results for the control group

were -.15+/- 1.93 (p=.97) (Talaei et al., 2017). This study revealed that cinnamon

supplementation had no significant effects on glycemic and inflammatory indicators in patients

with type 2 diabetes (Talaei et al., 2017).

Discussion

With a dramatic increase in the prevalence of worldwide diabetes mellitus, it is a crucial

time for research in affordable and accessible management of this metabolic disease. There have

been conflicting results regarding the efficiency of cinnamon to manage or treat type 2 diabetes.

Current research shows that cinnamon may have a beneficial effect on fasting glucose,

cholesterol, and triglyceride values in patients with type 2 diabetes (Allen et al., 2013).

Improvements on hemoglobin A1c values have not been shown to be significant (Medagama,

2015). Consumption of cinnamon may have glycemic-lowering effects, but more intervention

studies covering different types and amounts of cinnamon and types of subjects, are required as

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not all studies have shown positive effects of cinnamon on insulin resistance and many have

been poorly analyzed (Kim et al., 2015). Meta-analysis of these trials has shown intriguing

information, but the heterogeneity of these studies makes it complicated to gather conclusions

(Crawford, 2009). Caution should be exercised in applying the results of this analysis to patient

care because of the certainty of the dose and duration of cinnamon use and uncertainty of the

ideal patient population (Allen et al., 2013). A major limitation of the meta-analysis is the

diversity of populations. The populations included postmenopausal women, adults with

comorbidities, healthy adults, and use of anti-diabetic medications (Allen et al., 2013). Different

studies examined different dosages as well. These studies ranged from 4 to 18 weeks, which

limits the ability to observe changes in HbA1c (Allen et al., 2013). Hemoglobin A1c levels are

indicative of a 3-month average of blood glucose levels (Allen et al., 2013).

Variations in manufacturing processes may affect the quantity of active ingredient found

in a specific formulation (Allen et al., 2013). Furthermore, herbal products do not undergo the

same regulations as pharmaceuticals (Allen et al., 2013). Side effects of cinnamon have been

poorly documented in humans, because most research focusing on safety and efficacy has been

conducted either in vitro or in animals (Allen et al., 2013). The high coumarin content of cassia

cinnamon is of concern because of its hepatotoxic and carcinogenic effects (Medagama, 2015).

Ceylon cinnamon has low coumarin content, but it is not as available as cassia cinnamon and it is

more expensive (Kawatra, 2015). Ceylon cinnamon has only been studied in animal models

(Medagama, 2015).

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Further Research:

Cinnamon consumption has the potential to be a beneficial complementary therapy in

integrative medicine, but further research is needed (Medagama, 2015). At present the evidence

is inconclusive and long-term trials aiming to establish the efficacy and safety of cinnamon is

needed (Medgama, 2015). In Talaei et al.s trial, a longer intervention period may have

produced different results (Talaei et al., 2017). These studies have not addressed cinnamon usage

in food preparation and the potential benefits of this addition. Furthermore, these studies did not

address the potential variations in metabolic pathways of cinnamon supplementation versus

consuming cinnamon in food. The studies looked at supplemental cinnamon, mostly in powder

form. Future research could strongly benefit in addressing the role cinnamon could have on pre-

diabetes versus poorly controlled diabetes. Patients may benefit in consuming cinnamon, along

with conventional treatment, in the management of their diabetes, but further research needs to

be done on the proper dosing and methods of consumption for cinnamon. Further studies are

needed to better evaluate the impact of cinnamon intake on glycemic markers and indicators of

oxidative stress or inflammation in diabetic patients (Talaei et al., 2017). Limited data, short-

term interventions, and toxicity concerns have led to inconclusive data on this topic. In

conclusion, cinnamon has been found to contain anti-diabetic properties and further research

needs to be done in evaluating the role cinnamon plays in glycemic control of type 2 diabetes.

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