Cinnamon Use in Type 2 Diabetes: An Updated Systematic Review and Meta-Analysis

Robert W. Allen; Emmanuelle Schwartzman; William L. Baker; Craig I. Coleman; Olivia J. Phung

doi:10.1370/afm.1517

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Cinnamon as an alternative antidiabetic: new evidence for an old therapy
Fawzi Mahomoodally

Published on: 19 November 2013
Cinnamon use in diabetes
Rajadurai Akilen

Published on: 23 October 2013
The jury is still out...
Paul F. Crawford

Published on: 22 October 2013
Cinnamon for type 2 diabetes - news is not so sweet for this spice
Matthew J Leach

Published on: 23 September 2013
Cinnamon and Diabetes
Mona Boaz

Published on: 17 September 2013

Published on: (19 November 2013)
Page navigation anchor for Cinnamon as an alternative antidiabetic: new evidence for an old therapy
Cinnamon as an alternative antidiabetic: new evidence for an old therapy
Fawzi Mahomoodally, Senior Lecturer
I read with much interest the recently published article by Allen et al.1 on the potential of cinnamon as an alternative therapy in the management of glycemia and lipid levels. They showed following an updated systematic review and meta-analysis that the consumption of cinnamon is associated with a statistically significant decrease in levels of fasting plasma glucose, total cholesterol, LDL-C, and triglyceride levels, a...
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I read with much interest the recently published article by Allen et al.1 on the potential of cinnamon as an alternative therapy in the management of glycemia and lipid levels. They showed following an updated systematic review and meta-analysis that the consumption of cinnamon is associated with a statistically significant decrease in levels of fasting plasma glucose, total cholesterol, LDL-C, and triglyceride levels, and an increase in HDL-C levels.
With the increasing drive for more stringent glucose control in diabetes coupled with new therapies which may carry different risks for hypoglycemia; and as current modalities of therapies fail to achieve the ideals of normoglycemia and the prevention of diabetic complications, there has been a plethora of research that has been geared during the last past few decades towards alternative therapies for the management of diabetes.2-3 Indeed, as the knowledge of heterogeneity of diabetes increases, there is a need to explore more efficacious agents with lesser side effects.
It is important to recall that prior to the introduction of insulin, the management of diabetes relied heavily on dietary measures, which included the use of traditional plant therapies. Interestingly, the discovery of the widely used hypoglycemic drug, metformin has been developed from the traditional medicinal plant Galega officinalis, and which subsequently led to the synthesis of biguanides. It would thus appear that traditionally used anti-diabetic herbs and spices might present a useful source of new oral hypoglycemic compounds for possible development as pharmaceutical entities, or as simple dietary adjuncts to existing therapies. Although an orally active botanical substitute endogenous to insulin seems unlikely, new phytochemicals to stimulate endogenous insulin biosynthesis and secretion and to promote insulin action are realistic possibilities.2-3
One such spice that has attracted much attention among both the scientific community and consumers is cinnamon. Cinnamon is among the earliest known spice used by humankind with frequent references available in both pre-biblical and post-biblical scripts. It is a famous spice obtained from the bark of several trees from the genus Cinnamomum which is used in panoply of recipes. Additionally, it is traditionally used for metabolic diseases (mainly diabetes) in India, China, Korea and Russia; and has been reported to reduce fasting plasma glucose concentrations.1,4 Cinnamon also has medicinal properties that may be beneficial in the prevention and/or treatment of several chronic diseases. Improvements in markers of oxidative stress, blood pressure, blood lipids glucose, and insulin sensitivity have been observed with ingestion of cinnamon, usually as a ground solid or an aqueous extract of cinnamon.
Nonetheless, it is only recently under the lens of modern scientific philosophy that the beneficial therapeutic antidiabetic properties of cinnamon is being probed for its potential to be developed as a phytopharmaceutical in an endeavor to curb down the health burden associated with diabetes and related complications. Indeed, global cinnamon consumption has increased nearly 60% during the past two decades and is projected to gain momentum for years to come in part because of its perceived health benefits amongst end users with regard to diabetes and insulin resistance.5
There are likely wide arrays of cinnamon constituents responsible for these positive health effects. One well-described group of compounds is cinnamon polyphenols which have been reported to improve glucose, insulin, lipid metabolism and improve inflammation in cell culture, animal, and human studies. Interestingly, Qin et al.6 reported that cinnamon extracts regulate genes associated with insulin sensitivity, inflammation, and cholesterol/lipogenesis metabolism and the activity of the mitogen activated protein kinase signal pathway in intestinal lipoprotein metabolism which tend to support the conclusion of Allen et al.1 Additionally, cinnamon consumption has been reported to reduce postprandial intestinal glucose absorption, inhibits gluconeogenesis and stimulates glucose metabolism, glycogen synthesis and insulin release in vitro. In diabetic animal models, cinnamon shows multiple beneficial effects including attenuation of diabetes-associated weight loss, reduction of fasting blood glucose and HbA1c, and up-regulation of circulating insulin levels.6 Magistrelli and Chezem,7 has recently aimed at comparing any decline in postprandial glycemic response in normal- weight and obese subjects with ingestion of 6 g ground cinnamon. They found that cinnamon may be effective in moderating postprandial glucose response in normal weight and obese adults.7
As a concluding remark, irrespective of the complexity of the statistical analysis with any inherent limitation(s) and the robustness of RCT which Allen et al1 and previous authors referred; it is becoming increasing evident from in vitro, in vivo, ex vivo and clinical studies that cinnamon holds promising potential which has a strong traditional ancient root but with immense potential for modern medicines which might offer a natural alternative and complementary key to unlock the diabetologist's pharmacy. Thus, I strongly believe that cinnamon extracts could be a potential source of anti-diabetic pharmacophores and template molecules geared towards alleviating chronic complications of diabetes. Nonetheless, patients should be cautious in relation to dosage and any potential drug-herb interaction(s) while opting for cinnamon as a complementary and alternative therapy for the management of diabetes as there is still a paucity of data on the molecular characterization of cinnamon extracts. Last but not least, unlocking the therapeutic secrets hidden within cinnamon will require the application of all of our modern tools of medical sciences including nutrigenomics, proteomics, metabolomics and detailed studies of sub-cellular signaling pathways in normal and diseased systems.
References
1. Allen RW, Schwartzman E, Baker W, Coleman CI, Phung OJ. Cinnamon use in type 2 diabetes: an updated ad meta analysis. Ann Fam Med. 2013; 11(5):452-459.
2. Ravindran PN, Nirmal Babu K, Shylaja M. Cinnamon and cassia- The genus Cinnamomum- medicinal and aromatic plants - industrial profiles. CRC Press. 2007.
3. Mahomoodally MF. Recent advances to evaluate anti-diabetic medicinal plants. In: advances in the study of medicinal plants; Eds; Rai M, Rastrelli L, Marinoff M, Martinez J, Cordell G. CRC Press 2012.
4. Mahomoodally MF. Phytochemicals as potential pharmacophores to target diabetes. In: Phytochemicals: occurrence in nature, health effects and antioxidant properties. Nova science publisher, Inc, USA.
5. Ranasinghe P, Jayawardana R, Galappaththy P, de Vas Gunawardana N, Katulanda P. Efficacy and safety of 'true' cinnamon (Cinnamomum zeylanicum) as a pharmaceutical agent in diabetes: a systematic review and meta-analysis. Diabetic Med. 2012;29:1480-1492.
6. Qin B, Dawson H, Schoene N, Polansky M, Anderson R. Cinnamon polyphenols regulate multiple metabolic pathways involved in insulin signaling and intestinal lipoprotein metabolism of small intestinal enterocytes. Nutr. 2012;28(12):1172-1179.
7. Magistrelli A, Chezem JC. Effect of ground cinnamon on postprandial blood glucose concentration in normal-weight and obese adults. J Acad Nutr Diet. 2012; 112(11):1806-1809.
Competing interests: ?? None declared
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Competing Interests: None declared.
Published on: (23 October 2013)
Page navigation anchor for Cinnamon use in diabetes
Cinnamon use in diabetes
Rajadurai Akilen, Research Fellow.
Other Contributors:
With inquisitiveness, we read the original article by Allen et al.1 In their systematic review and meta-analysis on cinnamon use in type 2 diabetes mellitus, they concluded that the consumption of cinnamon is associated with statistically significant reductions in fasting plasma glucose, total and LDL cholesterols, triglycerides and an increase in HDL cholesterol levels. Although this is a well conducted meta-analysis, t...
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With inquisitiveness, we read the original article by Allen et al.1 In their systematic review and meta-analysis on cinnamon use in type 2 diabetes mellitus, they concluded that the consumption of cinnamon is associated with statistically significant reductions in fasting plasma glucose, total and LDL cholesterols, triglycerides and an increase in HDL cholesterol levels. Although this is a well conducted meta-analysis, there are several limitations in this study and thus we do not perfectly agree with the approach followed to validate the methodology of this meta- analysis. We are focusing on a few points in an attempt to criticize the results of this systematic review. In order to appraise the methodological excellence of this meta-analysis, we would like the authors to elucidate some of the following key points.
One of our main concerns is that, this systematic review did not rely substantially on the assessment of the methodological quality of the individual trials. Although the authors stated that the validity assessment was performed by using Cochrane risk of bias tool, they failed to report the results of the validity appraisal. We suggest the authors' could perform a Delphi critical appraisal tool2 to evaluate the methodological quality and/or scoring of the selected studies, which could avoid the potential prejudice in this review.
Moreover, we would like the authors to clarify the following statistics. In figure 2, the authors compared studies reporting SEM and SD [for e.g. Vanschoonbeek et al 3 and Lu et al 4 studies]. Furthermore, there is no evidence in this study on how they calculated the differences in SD or SEM from studies reported pre and post intervention SD or SEM values only. Besides, the heterogeneity (I2) between studies in figure 2 was found to be higher for most of the variables. This showed significantly higher variations between studies and cannot be comparable. We are eager to know the authors' opinion concerning this.
Most importantly, this is the first meta-analysis reporting a significant blood cholesterol lowering effect of cinnamon. However, we do not agree with this due to the following reasons. Firstly, only 3 studies 4-6 in this meta-analysis showed a statistically significant reduction in cholesterol compared to all other studies, and thus we would like to know whether these 3 studies pull the data more than the rest and favours cinnamon? Furthermore, the Delphi critical appraisal score for Khan et al 5 study was very poor, and as a result, this study is not comparable with other studies. Additionally, we do not understand why the authors' presented Khan et al 6 study as 3 different experiments, instead of using the pooled data of this study. Secondly, Lu et al 4 used three arms (control, low and high dose groups) in their experiment to compare the cholesterol lowering effect of cinnamon. Though, the authors' divide this study into two experiments and presented the results in figure 2. We strongly disagree with this comparison as there was no comparable control group for low (120mg/d) and high dose (360mg/d) cinnamon separately in this study. Due to these reasons the pooled effect of the above mentioned 3 experiments 4-6 might show a positive effect on blood cholesterol, and this is unacceptable. We strongly believe that if we exclude these 3 studies 4-6 from the forest plot in figure 2, the cholesterol lowering effect of cinnamon might favours the control group. Consequently, we would like the authors to clarify this matter for us. Further, it is not clear what percentage of participants were treated with cholesterol lowering medications in these studies?
In summary, we prefer to pay more attention on some specific studies in this meta-analysis particularly on blood cholesterol lowering potential of cinnamon. Although blood glucose lowering potential of cinnamon is well acknowledged in previous meta-analysis 7, we need to elucidate the methodological rigour of the studies reporting a definite association between cinnamon and blood cholesterol. Therefore, the therapeutic and/or clinical benefits of cinnamon on cholesterol lowering effects needs to be confirmed by placebo controlled studies of large cohort of patients.
Competing interests: Nothing to Declare
Akilen R,1 and Tsiami A,2
1Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Canada. 2 School of Psychology, Social Work and Human Sciences, University of West London, London, UK.
References:
1. Allen RW, Schwartzman E, Baker W, Coleman CI, Phung OJ. Cinnamon use in type 2 diabetes: an updated systematic review and meta analysis. Annals of Family Medicine. 2013; 11(5):452-459.
2. Verhagen AP, Vet HCW, Bie RA, Kessels AGH, Boers M, Bouter LM, Knipschild PG. The Delphi List: A Criteria List for Quality Assessment of Randomized Clinical Trials for Conducting Systematic Reviews Developed by Delphi Consensus. J Clin Epidemiol. 1998; 51(12):1235-1241.
3. Vanschoonbeek K, Thomassen BJ, Senden JM, Wodzig WK, vanLoon LJ. Cinnamon supplementation does not improve glycemic control in postmenopausal type 2 diabetes patients. J Nutr. 2006; 136(4):977-980.
4. Lu T, Sheng H, Wu J, Cheng Y, Zhu J, Chen Y. Cinnamon extract improves fasting blood glucose and glycosylated hemoglobin level in Chinese patients with type 2 diabetes. Nutr Res. 2012; 32(6):408-412.
5. Khan R, Khan Z, Shah S. Cinnamon may reduce glucose, lipid and cholesterol level in type 2 diabetic individuals. Pakistan J Nutr. 2010; 9(5):430-433.
6. Khan A, Safdar M, Ali Khan MM, Khattak KN, Anderson RA. Cinnamon improves glucose and lipids of people with type 2 diabetes. Diabetes Care. 2003; 26(12):3215-3218.
7. Akilen R, Tsiami A, Devendra D, Robinson N. Glycated haemoglobin and blood pressure-lowering effect of cinnamon in multi-ethnic Type 2 diabetic patients in the UK: a randomized, placebo-controlled, double-blind clinical trial. Diabet Med. 2010; 27(10):1159-1167.
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Competing Interests: None declared.
Published on: (22 October 2013)
Page navigation anchor for The jury is still out...
The jury is still out...
Paul F. Crawford, Program Director
This meta-analysis continues to point out that we do not yet know everything about cinnamon and its effects on diabetes.
It is rather clear, though, that performing research on individuals with type 1 diabetes is probably useless and perhaps harmful. Basic science research conducted to date indicates that it DOES not act like insulin, but does have characteristics similar to metformin and the "glitazones"....
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This meta-analysis continues to point out that we do not yet know everything about cinnamon and its effects on diabetes.
It is rather clear, though, that performing research on individuals with type 1 diabetes is probably useless and perhaps harmful. Basic science research conducted to date indicates that it DOES not act like insulin, but does have characteristics similar to metformin and the "glitazones".
The authors of the Cochrane Review point out that the results of this study are different than theirs. I wonder if they re-analyzed their data without Type 1 patients, would they have a different result.
Regardless, there are multiple trials of cinnamon underway, and they strive to have less of the methodological flaws in prior studies.
Competing interests: ?? None declared
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Competing Interests: None declared.
Published on: (23 September 2013)
Page navigation anchor for Cinnamon for type 2 diabetes - news is not so sweet for this spice
Cinnamon for type 2 diabetes - news is not so sweet for this spice
Matthew J Leach, Senior Lecturer & Researcher
Allen and colleagues recently reported the findings of a systematic review and meta-analysis of cinnamon for type 2 diabetes mellitus [1]. The authors concluded that cinnamon significantly reduces fasting plasma glucose, total cholesterol, LDL-C and triglycerides, and significantly increases HDL-C. While these findings corroborate the results of another recent review [2], these findings are not consistent with the conclus...
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Allen and colleagues recently reported the findings of a systematic review and meta-analysis of cinnamon for type 2 diabetes mellitus [1]. The authors concluded that cinnamon significantly reduces fasting plasma glucose, total cholesterol, LDL-C and triglycerides, and significantly increases HDL-C. While these findings corroborate the results of another recent review [2], these findings are not consistent with the conclusions drawn from other reviews of cinnamon [3], including a 2012 Cochrane systematic review [4]. Appraisal of Allen and colleagues' meta-analysis suggests that the conclusions drawn might have in fact been misinterpreted and thus, may be incorrect. The evidence for this assertion now follows.
High statistical heterogeneity was observed across all outcomes analysed in this review, yet there was no attempt to explain or address the heterogeneity. Analysis of FBGL data in the previously mentioned Cochrane review indicated that two of the studies (i.e. Khan et al 2003, 2010) were extreme outliers as they reported markedly different intervention effect estimates; possibly due to small study effects and high risk of bias [4]. When these outliers were removed from the analysis, the measure of heterogeneity (i.e. I2 statistic) dropped to 0%. It would be useful to know if this also applies to Allen and colleagues' analysis, not just for FBGL, but for all outcomes assessed; and further, whether the removal of these outliers alters the conclusions of their review.
Across almost all meta-analyses, and for at least two included studies, Allen et al represented data from the same study as multiple separate comparisons. Given that these 'duplicated' studies were relatively small, and findings were much in favour of cinnamon, this is likely to have overestimated the effects of the herbal extract [5]. This may have been compounded further by the use of a random-effects model, which gives more weight to these smaller studies [5].
In light of the above-mentioned issues, and the high-risk of bias of most included studies [4], the authors should have concluded with greater restraint. The conclusion as it currently stands is likely to perpetuate misconceptions about the efficacy of cinnamon for diabetes and dyslipidaemia, which will inevitably mislead clinicians and consumers.
Dr Matthew J Leach RN, BN(Hons), ND, DipClinNut, PhD School of Nursing & Midwifery University of South Australia North Terrace Adelaide, SA 5000 Australia
References
1. Allen RW, Schwartzman E, Baker WL, Coleman CI, Phung OJ. (2013) Cinnamon use in type 2 diabetes: an updated systematic review and meta- analysis. Ann Fam Med; 11(5): 452-459.
2. Akilen R, Tsiami A, Devendra D, Robinson N. (2012) Cinnamon in glycaemic control: Systematic review and meta analysis. Clin Nutr; 31(5): 609-15
3. Baker WL, Gutierrez-Williams G, White CM, Kluger J, Coleman CI. (2008) Effect of cinnamon on glucose control and lipid parameters. Diab Care; 31(1): 41-3.
4. Leach MJ, Kumar S. (2012) Cinnamon for diabetes mellitus. Cochrane Database Syst Rev; 9: CD007170.
5. Higgins JPT, Green S. (eds.). Cochrane handbook for systematic reviews of interventions, version 5.1.0. The Cochrane Collaboration, 2011. www.cochrane-handbook.org. (accessed 20th April 2012)
Competing interests: ?? None declared
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Competing Interests: None declared.
Published on: (17 September 2013)
Page navigation anchor for Cinnamon and Diabetes
Cinnamon and Diabetes
Mona Boaz, Director
Other Contributors:
In their article, Cinnamon use in type 2 diabetes: an updated systematic review and meta-analysis (1), authors Allen et al. find that cinnamon has a significant therapeutic effect on a host of metabolic measures, including glucose and serum lipids. These findings are not consistent with those of a meta-analysis published last year in which the data for 577 participants were analyzed (2). In that meta-analysis, cinnamo...
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In their article, Cinnamon use in type 2 diabetes: an updated systematic review and meta-analysis (1), authors Allen et al. find that cinnamon has a significant therapeutic effect on a host of metabolic measures, including glucose and serum lipids. These findings are not consistent with those of a meta-analysis published last year in which the data for 577 participants were analyzed (2). In that meta-analysis, cinnamon was not found to confer any beneficial treatment effect on glucose levels in diabetic individuals.
Both meta-analyses included 10 randomized clinical trials, both included findings for more than 500 participants, both used rigorous statistical analyses. And yet they arrived at very different conclusions.
Reconciling these divergent conclusions may lie in understanding how studies were selected for inclusion. Allen et al.(1) included a single study three times to represent the three cinnamon doses used in the study, increasing included studies by 20% (3). Though the authors discussed the problematic nature of this practice, they do not calculate its possible impact on findings. In fact, this method may have artificially increased likelihood of positive findings, since in that study, all three doses were associated with reduced glucose levels and improved lipid profile. It is extremely important to consider sources of error in meta-analyses including selection bias and publication bias. Dividing a single study into three is not typical methodology.
Care is always required in re-interpreting data. For example, our study on cinnamon (4) was cited in the Allen's meta-analysis (1) and an increase in glucose was reported in the cinnamon group. In fact, the change-from-baseline glucose values did not differ between the cinnamon and placebo groups, and no within-group analysis of change was performed. Finally, does it truly seem likely that cinnamon can produce glucose reductions no less than those produced by sitigliptin? One might ask why physicians don't discontinue such medicaions and just treat patients with type 2 diabetes with cinnamon.
Sincerely,
Prof. Mona Boaz Dr. Julio Wainstein
1. Allen RW, Schwartzman E, Baker WL, Coleman CI, Phung OJ. Cinnamon Use in Type 2 Diabetes: An Updated Systematic Review and Meta- Analysis. Ann Fam Med 2013 11:452-459.
2. Leach MJ, Kumar S. Cinnamon for diabetes mellitus. Cochrane Database of Systematic Reviews 2012, Issue 9. Art. No.: CD007170. DOI: 10.1002/14651858.CD007170.pub2.
3. Khan A, Safdar M, Ali Khan MM, Khattak KN, Anderson RA. Cinnamon improves glucose and lipids of people with type 2 diabetes. Diabetes Care 2003;26:3215-3218.
4. Wainstein J, Stern N, Heller S, Boaz M. Dietary cinnamon supplementation and changes in systolic blood pressure in subjects with type 2 diabetes. J Med Food 2011;14:1505-1510.
Competing interests: ?? None declared
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Competing Interests: None declared.