For centuries cinnamon has been a culinary spice and folk remedy for various maladies. In traditional medicines, its uses include for relief of gastrointestinal distress, arthritis, high blood pressure (BP), dermatitis, toothache, and colds; for improving menstrual irregularities; and for wound healing. Depending on the cultural culinary context, cinnamon is added to beverages, desserts, liqueurs, teas, chicken and lamb dishes, breads and pastries, and fruit preparations.1–3 Four species of the genus Cinnamomum are main contributors to its commercial applications. These are Cinnamomum verum (also known as Cinnamomum zeylanicum, Sri Lankan/Ceylon cinnamon), Cinnamomum cassia (also called Cinnamomum aromaticum, Chinese cinnamon), Cinnamomum burmannii (Indonesian/Java cinnamon), and Cinnamomum loureiroi (Saigon/Vietnamese cinnamon). The chemical profiles of the oils and other extracts derived from the dried inner bark of these different species exhibit varying levels of main constituents, which include cinnamaldehyde, cinnamic acid, coumarin, linalool, eugenol, caryophyllene, and polyphenol polymers.4–6 Recently, cinnamon supplements received increased attention for their use as adjuncts in treating high blood glucose and lipid levels and other symptoms of the metabolic syndrome.7–9 In the past decade, in particular, more clinical studies evaluated the efficacy of cinnamon toward these conditions, as well as toward polycystic ovary syndrome (PCOS) and inflammatory disorders. The current article provides a brief summary of these human trials, highlights recommendations based on current scientific evidence, and addresses issues for future research.
METHODS
A search of the PubMed database was conducted using the search terms cinnamon, Cinnamomum, C verum, C zeylanicum, C cassia, C aromaticum, C burmannii, and C loureiroi to identify human studies evaluating health or medical benefits of cinnamon administration. Full reports of English-language publications and English-language abstracts of foreign-language articles from peer-reviewed journals were the primary sources of information. Although the quality of clinical studies varied considerably, all published human investigations identified were included in this discussion so that the totality and diversity of information can be evaluated, and issues for future research identified.
EFFECTS OF CINNAMON
Amelioration of Female Endocrine and Reproductive Disorders
Seven clinical studies evaluated cinnamon supplementation in nondiabetic women with PCOS or with primary dysmenorrhea (Table 1). Polycystic ovary syndrome is characterized by sonographic evidence of ovary cysts, anovulation, and hyperandrogenism frequently accompanied by hyperinsulinemia, insulin resistance (IR), and dyslipidemia. Women with primary dysmenorrhea experience cyclic, painful cramping and nausea accompanying menstrual bleeding.
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TABLE 1: Effect of Cinnamon in Nondiabetic Women With Dysmenorrhea and Polycystic Ovary Syndrome (PCOS)
In the 5 randomized controlled trials (RCTs) for PCOS, patients received cinnamon doses from 999 to 1500 mg/d for periods of 2 to 6 months.10,11,15,16 Patient populations were relatively small, consisting of 6 to 42 individuals. In the 4 trials in which IR was measured,10,11,14,16 3 showed improvements in insulin sensitivity, compared with controls. In 2 of 3 trials, fasting blood glucose (FBG) levels decreased for those provided cinnamon, compared with controls. Improvements in blood levels of low-density lipoprotein cholesterol were observed, although responses of other blood lipids to cinnamon were inconsistent among studies. No effects of cinnamon supplementation on androgen or adiponectin levels were detected.11,14,16 Only 1 PCOS trial measured postintervention ultrasonographic changes in ovaries11 and found no change in volume. It would be useful for future studies to provide this information because it would add important insights into the response of these structures to cinnamon treatment. Also, not all measured the effect of cinnamon on ovulation and menstrual regularity, and only 1 study14 provided a chemical analysis of the cinnamon administered.
Two reports by Jaafarpour et al12,13 evaluated cinnamon administered (1260 mg/d for 72 hours) to women (38/group) with primary dysmenorrhea. Compared with controls, cinnamon decreased severity of pain and nausea for women consuming cinnamon. Except for a rash and itchiness reported by 1 woman,14,17 no adverse effects of cinnamon were observed in these 7 studies.
Improved Regulation of Blood Glucose, Insulin, and Lipid Levels
Nondiabetic Subjects
More than a dozen trials from 10 countries examined the influence of cinnamon intake on blood glucose, insulin, and lipid responses in nondiabetic subjects (Table 2). Compared with controls, postprandial glycemic responses to cinnamon administration were inconsistent. For example, only 6 trials showed a significant decrease in postprandial blood glucose area under the curve (PBGAUC) for those given cinnamon.18–20,27,28,31 Improvements in serum insulin response or sensitivity in response to cinnamon also were inconsistent, with 3 of 6 studies showing a benefit.20,23,24 Compared with controls, measurements of gastric-emptying rates for those given cinnamon did not change in 2 of 3 studies. Also, cinnamon dosing did not significantly affect blood lipid levels and satiety when measured in 5 trials. In other related studies, a phase I trial provided escalating doses (85-500 mg/d) of C zeylanicum over a 3-month period.32 In this study, there was no effect on FBG; nor were there improvements in specific blood lipid fractions. In another study, nondiabetic patients with nonalcoholic fatty liver disease were administered 1.5 g/d cinnamon powder for 12 weeks, which resulted in significant reductions in serum levels of 3 liver enzymes and significant improvement in abnormal lipid profiles and glycemic responses (FBG and Homeostatic Model Assessment of Insulin Resistance or HOMA-IR), compared with controls.33
TABLE 2: Effect of Cinnamon on Glucose/Lipid Regulation and Satiety in Nondiabetic Individuals
Of interest, a recent crossover trial31 treated nondiabetic males with a constituent of cinnamon, cinnamyl isobutyrate. This phytochemical is a food and flavoring ingredient approved by the US Food and Drug Administration for human consumption. Compared with controls, significant decreases were observed for ad lib energy intake and PBGAUC, without affecting insulin levels or several metabolic factors regulating appetite. The impact of this one cinnamon constituent underscores the need to characterize several components for their influence on metabolic responses.
Individuals With Impaired Glucose and Lipid Regulation
More than 2 dozen trials in the past 15 years have evaluated cinnamon supplementation for the treatment of hyperglycemia and dyslipidemia (Table 3). For trials listed in Table 3 (as well as Table 1), it should be noted that studies varied in the statistical analyses performed. Some trials determined statistical significance by comparing outcomes between treatment and placebo groups, whereas other trials determined statistical significance separately within treatment and placebo groups by comparing baseline and final values. Some reported both manners of comparison. The specific statistical approach used is noted for each reference in Tables 1 to 4.
TABLE 3: Effect of Cinnamon in Subjects With Glucose/Lipid Dysregulation in Randomized Controlled Trials
Both powder samples and proprietary aqueous extracts from several cinnamon species were used for oral supplementation. The specific species chosen for evaluation were not routinely identified. Study populations included those with type 2 diabetes mellitus (T2DM), both stable and poorly controlled, those with symptoms of impaired glucose tolerance, and those classified as presenting with the metabolic syndrome. Only 1 evaluated efficacy of cinnamon in T1DM. Trials were conducted with diverse populations of patients with diabetes from both western and Asian cultures (locations noted in Table 3). Treatment groups included both men and women, with ages generally 40 years or older. Concurrent use of hypoglycemic and hypolipidemic medicines was not consistently described.
In 20 trials administering cinnamon powder, glycemic responses exhibited substantial inconsistencies. Although 55% of the studies demonstrated some degree of improvement related to blood glucose control, no specific dose of cinnamon or feeding period was consistently associated with these changes, which were generally modest. Specifically, from an analysis of studies of T2DM, Santos and DaSilva65 determined that FBG concentrations decreased by 12.9 to 52.2 mg/dL, and glycated hemoglobin A1c (HbA1c) values by 0.27% to 0.83%. In only a few studies did these modest benefits meet the American Diabetes Association goals (FBG <130 mg/dL, HbA1c <7.0%) for these measures.9
In 7 of 11 trials evaluating intake of cinnamon powder on blood lipid levels, at least 1 individual blood lipid measurement improved for those given cinnamon, compared with controls, although other blood lipid values in the same profile often showed no change. Despite the recent suggestion that cinnamon supplementation is effective in decreasing total blood cholesterol and blood triglycerides concentrations,66 the collective lipid profile data from cinnamon studies are nonetheless inconsistent and preclude generalizations.
Similarly, in trials where BP was measured, limited data suggest that short-term cinnamon intake can suppress systolic BP and diastolic BP in those with prediabetes and T2DM.67 However, additional studies are warranted because any therapeutic effect of cinnamon on BP may likely depend on subjects’ baseline BP.45,46,67 Moreover, human trials have not provided direct insights into mechanisms responsible for cinnamon’s effects on BP, although it has been suggested that the mechanisms mediating these effects are interrelated with cinnamon’s biological activities improving IR and lipid regulation.36,44,45
Suppression of Inflammation and Oxidative-Associated Conditions
Responses to cinnamon interventions for diverse inflammation-associated conditions are presented in Table 4. Cinnamon was given to female athletes (15/group) in 2 studies,61,62 but the findings do not support a clear benefit. In a recent trial, 18 women with rheumatoid arthritis were given 2 g/d cinnamon for 8 weeks along with antirheumatic drugs. Significant improvements in arthritic symptoms and in blood markers of inflammation were detected for women receiving cinnamon, compared with controls.64 There were no changes in blood glucose and lipid levels in these women. In a dental study, 30-day administration of a cinnamon-containing mouth rinse decreased the amount of sticky, bacteria-containing biofilm (plaque) on the teeth and reduced the magnitude of inflammatory gingivitis in adults,63 compared with controls. The cinnamon rinse had similar strength to chlorhexidine.
TABLE 4: Effect of Cinnamon on Inflammation- and Oxidative-Associated Conditions
POTENTIAL SOURCES OF INCONSISTENCIES AMONG TRIALS
When considering the human studies in Tables 1 to 4, considerable heterogeneity in outcomes hampers crafting recommendations regarding cinnamon’s role in treatment strategies for these conditions. When these diverse cinnamon trials are considered together, there are a number of common shortcomings, many associated with the methods of cinnamon treatment and characteristics of the participants, which may contribute to conflicting trial outcomes.
Methodological issues have been reviewed1,9,68–70 and include inadequate numbers of subjects, incomplete statistical analyses, and inadequate blinding, to name a few. No feeding period was longer than 4 months. Longer testing periods evaluating multiple doses of cinnamon in larger patient populations are needed, especially to detect modest dose-dependent changes in HbA1c, glycemic indicators, lipid profiles, and insulin sensitivity/resistance, as well as to identify any adverse effects from chronic cinnamon intakes. It is worth noting that the HOMA-IR and quantitative insulin Sensitivity Check Index (QUICKI) tests were used to monitor IR/sensitivity in 12 studies listed in Tables 1, 2, and 3.10,11,14,16,20,30,38,54,56,57,59,60 Seven reported improvements in insulin sensitivity or decreases in IR for those groups receiving cinnamon treatment. The 5 trials reporting no effect of cinnamon on HOMA-IR are consistent with the 1 trial in Table 3 using the euglycemic-hyperinsulinemic clamp method, considered the criterion standard for measuring IR in smaller studies.52 HOMA-IR and QUICKI are considered valid estimates of clamp-derived insulin sensitivity in patients with hypertension and T2DM.71 These mixed results for cinnamon’s effects in these smaller trials utilizing the HOMA-IR test underscore the challenge to uncover the true effect of this spice on the insulin response. In all future, large-scale RCTs evaluating cinnamon, it could be beneficial to incorporate this indirect and relatively simple method of assessing IR along with measurements of FBG and PBG in order to improve comparisons of cinnamon’s effects among trials and enhance uniformity of methods used to characterize insulin responses.
Other potential contributors to these inconsistencies within and among trials are disparate glycemic and blood lipid baseline values of subjects. Variable responses of diabetic subjects to cinnamon administration also may be due to diverse types and doses of hypoglycemic medications used concurrently by patients. This information was not routinely provided. In light of these issues, some have suggested that cinnamon supplementation might have greater benefit for those with poorly controlled diabetes and presenting with higher baseline blood glucose levels compared with those receiving adequate care in maintaining blood glucose levels.23,37,47,48 The relationship between response to cinnamon intake and baseline glycemic levels of subjects needs to be clarified.45
Differences in ethnicity or in characteristics of patients with diabetes among these diverse global regions were suggested as another potential source of variability among trial outcomes.40,45,57 Based on data provided in Table 3, no clear association is readily apparent between cinnamon efficacy and locations of patients with diabetes. Specific metabolic traits or treatment strategies that could possibly cause ethnicity-based differences among patients with diabetes in response to cinnamon dosing need to be examined. Nonetheless, culturally based dietary and lifestyle differences among participants deserve closer scrutiny.72
Differences in anthropometric characteristics and sex of participants may be a source of variability. Roussel et al42 observed benefits of cinnamon in a small group of obese or overweight individuals specifically recruited for study. A larger cohort specifically addressed the effect of body mass index (BMI) differences on cinnamon-associated outcomes.60 In this trial, improvements in glycemic control and lipid regulation were significantly more prominent for those patients with diabetes with BMI of 27 kg/m2 or greater compared with those with BMI of less than 27 kg/m2. In contrast, no effect of BMI was reported when cinnamon and BMI were evaluated in patients with no diabetes.26,30 The influence of body mass on cinnamon efficacy deserves further characterization, especially in light of global increases in obesity prevalence. It is unclear whether sex differences may be an influence because mixed populations of male and female subjects were often evaluated without distinguishing between sex-associated responses. Insulin sensitivity is known to vary within phases of the menstrual cycle,73–76 suggesting that contributions of life stage or hormonal status to cinnamon-related responses are worth further scrutiny.
Among studies in patients with no diabetes (Table 2), the type, dose, and mode of administration of carbohydrate as part of oral glucose tolerance test (OGTT) protocols were dissimilar. It was suggested that differences in standardization of pre-OGTT diets among trials can substantially affect glucose and insulin outcomes.20,77 For example, carbohydrate amounts in tests varied from 48 g to 75 g and were given in varied contexts, such as in a bolus20,24,29,30 or in meals characterized by different carbohydrate sources and amounts of fat. Rice milk or pudding,19,22,23 white bread,18,27 farina cereal,26 or a high-fat meal composed of breads, meats, cheeses, vegetables, yogurt, and added fats25 exemplified the variety of sources. It is known that the type of food, method of preparation, and other factors may affect PBG levels.78 In this regard, it was suggested22 that OGTT feeding protocols with lower carbohydrate/cinnamon ratios were those showing better blood glucose-lowering actions of cinnamon.
The sources and characteristics of cinnamon samples used in trials were not adequately identified.4,5 Several major species of cinnamon were used in clinical trials, each possessing distinctly different chemical profiles and thus having potentially different actions.4,47 Plant portion, quality of grade, species/varieties of cinnamon, and processing and extraction of cinnamon powder can impact sample composition and subsequent biological efficacy.4,5 Few studies reported chemical composition of samples fed to participants, information that could assist in identifying sources of disparities in response to cinnamon intake among trials, in determining relative effectiveness of types of cinnamon, and in providing clues about specific constituents contributing to beneficial biological activities. In this regard, trials listed in Table 3 administering aqueous extracts36,37,42,48,52,56 exhibited more consistent improvements in FBG levels than in those trials feeding cinnamon powder, underscoring the need for the specific chemical compositions of such extracts to be more thoroughly evaluated. Furthermore, use of aqueous extracts of cinnamon may be safer for human consumption than whole C cassia powder. These aqueous extracts of the powder do not contain the lipophilic, deleterious coumarins and flavor components present in the bark.37
Mechanisms of Action
Cinnamon’s purported health benefits have been investigated mainly in animal and in vitro studies.1,7 Cinnamon’s impact on numerous processes affecting the metabolic syndrome has been proposed and includes enhancing insulin signaling and glucose transport, altering carbohydrate metabolism and glucose absorption, stimulating satiety, delaying gastric emptying, inhibiting inflammation-associated enzyme activities, reducing expression of proinflammatory cytokines, and suppressing oxidative stress, to name a few.6,8,56,79–82 The specific constituents of cinnamon producing these bioactivities in humans are not known. From in vivo and in vitro studies, candidate components include A type polyphenols, a methylhydroxychalcone polymer, and cinnamaldehyde.56,83
Safety
The tolerability of specific doses of cinnamon powder and any adverse effects were not routinely reported. Cinnamon use as a spice or flavoring agent is considered generally recognized as safe by the US Food and Drug Administration (21CFR182.10, 21CFR182.20). Cinnamon species vary considerably in the content of the hepatoxic chemical coumarin, which is present from less than 0.01 g/kg in C zeylanicum to 3.6 g/kg in C cassia.14,84,85 The amount of coumarin in specific foods is regulated by the European Union,86 and practical recommendations for maintaining appropriate levels in food products have been offered.84 A recent review of adverse events associated with cinnamon use determined that cinnamon is generally safe for use in controlled clinical investigations.17 The authors of this report concluded that, although adverse events were not always noted, those events described in clinical trials and case reports were mostly allergic responses and gastrointestinal distress and were generally minor and self-limiting. Goncalves et al87 concluded there was no human health risk from 7 toxic elements for those who consume up to 6 g cinnamon. Nonetheless, administration of cinnamon in large amounts (>3 g/d) for long time periods needs to be carefully monitored for potential adverse effects, including interactions with prescription drugs.1,17,68,88 Of note is a recent case report of an adult man with diabetes in which chronic cinnamon consumption (1 g/d) was associated with fluid retention symptoms similar to those of thiazolidinedione medications.89
SUMMARY
Limited and conflicting data from human trials evaluating cinnamon supplementation for alleviation of inflammation, for controlling symptoms of dysmenorrhea and PCOS, and for improving glycemic responses and lipid profiles in patients with no diabetes prevent development of recommendations of cinnamon use for these conditions. Likewise, although some studies do show a benefit for T2DM when cinnamon is used as an adjunct to changes in diet/lifestyle and to hypoglycemic medications, any improvements are only modest, and the inconsistency of outcomes and weaknesses of trials hinder providing general recommendations for cinnamon’s routine use in improving the glycemic response.9 Similarly, no generalizations can be made for routine use of supplemental cinnamon in moderating abnormal BP and blood lipid levels.
Beyond the need for larger and longer RCTs, a number of other issues, as previously discussed, could be addressed in future investigations. The impact of patients’ baseline metabolic status and anthropometric characteristics on efficacy of cinnamon treatment needs to be clarified, as do the influences of concurrent diet, physical activity, and prescription medications. Sex-dependent and intercultural disparities in responses of patients with diabetes to cinnamon intake warrant clarification. Providing the identity and chemical composition of cinnamon samples, both as a powder or extract, will strengthen future trials. Human bioavailability studies of putative bioactive cinnamon constituents could contribute to discovering mechanisms of action and also to understanding any tissue-specific differences in responses. Evaluation of cinnamon’s effects on other metabolic indicators influencing glucose disposition, such as glucagon and adiponectin, and on intramuscular signaling pathways, to name a few, would provide additional valuable insights into cinnamon’s actions.20,23,24,58
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