Effects of Cinnamon Supplementation on Systolic and Diastolic Blood Pressure: a Systematic Review and Meta-analysis of Randomized Controlled Clinical Trials

Yazdanpanah, Zeinab; Amiri, Mandana; Najarzadeh, Azadeh; Hooshmandi, Hadis; Azadi-Yazdi, Maryam

doi:10.18502/CCB.V2I1.5871

Shahid Sadoughi University of Medical Sciences Journals

Number of Journals	8
Number of Issues	49
Number of Articles	355
Article View	88,477
PDF Download	56,528

Effects of Cinnamon Supplementation on Systolic and Diastolic Blood Pressure: a Systematic Review and Meta-analysis of Randomized Controlled Clinical Trials

Critical Comments in Biomedicine

Volume 2, Issue 1, March 2021, Pages 100-6 PDF (4.12 M)

Document Type: Article

DOI: 10.18502/CCB.V2I1.5871

Authors

Zeinab Yazdanpanah¹; Mandana Amiri²; Azadeh Najarzadeh^* ¹; Hadis Hooshmandi²; Maryam Azadi-Yazdi²

¹1. Nutrition and Food Security Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran 2. Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

²1 Nutrition and Food Security Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran 2 Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

Abstract

ABSTRACT
Background: Hypertension is a chronic condition that might lead to renal and cardiovascular diseases. Previous clinical trials examining the effect of cinnamon supplementation on blood pressure have led to conflicting results. The present study aimed to summarize the effect of cinnamon supplementation on blood pressure using a meta-analysis of published randomized controlled clinical trials.
Methods: To identify the eligible articles, MEDLINE, SCOPUS, ISI Web of Science, and Google Scholar were searched from inception until September 2019 for relevant articles. The risk of bias assessment was performed using the Cochrane collaboration’s tool. A Random-effects model was applied to calculate the summary effects.
Results: Totally, 11trials with 686 participants were included in this systematic review and meta-analysis. The dose of cinnamon supplement consumption varied from 500 to 10000 mg/d. The meta-analysis revealed that cinnamon supplementation significantly decreases systolic blood pressure (SBP) [WMD (weighted mean difference) = -5.72 mmHg, 95% confidence interval (CI): -8.63 to -2.80; p <0.001, I2= 81.1)] and diastolic blood pressure (DBP) (WMD= -4.06 mmHg, 95% CI: -6.68 to -1.44; P= 0.002, I2 = 88.6). Subgroup analysis suggested no significant reduction in DBP in subjects with diabetes (WMD= -2.015 mmHg, 95% CI: -4.55 to 0.52; P= 0.12, I2 = 72.3) and prediabetes or metabolic syndrome (WMD= -4.8 mmHg, 95% CI: -10.06 to 0.44; P= 0.073, I²= 92.5).
Conclusions: Cinnamon supplementation could be beneficial in lowering SBP and DBP in adults. Further studies with different doses are recommended to conﬁrm the present findings.

Keywords

Blood pressure; Cinnamon; Randomized controlled clinical trials; Systematic review; Meta-analysis

Full Text

Introduction

Hypertension is an important public health problem, leading to complications such as cardiovascular diseases, renal damage, and stroke; as it is considered as a substantial cause of death, worldwide [1]. It is proposed that approximately
35-45% of the world population and also 21.4% of Iranians suffer from hypertension [2, 3]. Common treatments consist of health behavior modification and then antihypertensive drugs; therefore, lifestyle and nutrition are considered as important steps for its prevention and control [4, 5]. Recently, there has been a focus on the role of functional foods such as garlic, dietary fiber, licorice and also cinnamon in the treatment of hypertension [6-9].

Cinnamon is one of herbal medicines that is used for the treatment of intestinal colic, common cold, and respiratory and gastrointestinal disorders [10]. Nowadays, studies have found that it has antioxidant, anti-inflammatory, antidiabetic, and antihyperlipidemic effects, and also might improve cardiovascular diseases [11-13]. Cinnamon consists of a variety of bioactive ingredients, including cinnamaldehyde, cinnamic acid, cinnamate [14], and numerous antioxidants, polyphenols, and flavonoids [15]. Animal studies have postulated that cinnamaldehyde might be able to regulate blood pressure by peripheral vasodilatation and also to dilate vascular smooth muscle via an endothelium-independent manner [16]. The vasodilatory effect of cinnamaldehyde maybe because of inhibiting both Ca²⁺ influx and release [17]. A study revealed that cinnamic aldehyde and cinnamic acid of cinnamon have cardioprotective effects against myocardial ischemia injury [13]. Cinnamon polyphenols could impact insulin activity and diabetes symptoms [18]. Cinnamaldehyde may also prevent the development of hypertension in type 1 and 2 diabetes through normalization of vascular contractility, as well as its insulinotropic effect in hypoinsulinemia [19].

Some clinical trials have suggested that cinnamon consumption reduces the elevated systolic blood pressure (SBP) [20-25]. However, other studies could not confirm this finding [26-30]. Besides, ﬁndings regarding the effect of cinnamon supplementation on diastolic blood pressure (DBP) are inconclusive, as several trials observed significant improvements [20-23, 27] and the others reported no effect on DBP [24-26, 28-30]. Due to the contradictions observed in the literature, the present systematic review and meta-analysis of randomized controlled trials (RCTs), was conducted to clarify the effect of cinnamon on SBP and DBP in adults. Moreover, this study aimed to assess the possible difference in the effect of cinnamon on blood pressure based on gender, supplementation dose, duration, and participants’ health status.

Materials and Methods

The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement was followed [31] for reporting this systematic review and meta-analysis. The protocol was registered in the international prospective register of systematic reviews (PROSPERO) in July 2019 (registration code: CRD42019137565).

Search strategy

A comprehensive literature search was done from inception up to September 15^th, 2019, in electronic databases including PubMed/Medline, ISI Web of Science, Scopus, and Google Scholar. The search was carried out without any language or time restriction. To find the relevant papers and the following Medical Subject Headings (MeSH) and non-MeSH keywords were used: 1) "cinnamomum aromaticum", cinnamon*, "cinnamomum cassia", "cinnamomum zeylanicum", rinnamomum*, cinnamaldehyde, "cinnamic aldehyde"; 2) "blood pressure", BP, "diastolic pressure", "systolic pressure", "pulse pressure", hypertension, "arterial tensions", "systolic blood pressure", "diastolic blood pressure", SBP, DBP, “systolic arterial pressure”; and 3) rats, mice, mouse, “in vitro”, “in vivo”, "animal experimentation", “animal Model”, “laboratory animals”. The searched studies were included the keywords group 1 and 2 in their titles/abstracts without keywords group 3. We also used keywords related to anthropometric indices, inflammatory and antioxidant factors, blood lipids, glucose, and CVD since BP might be regarded as a secondary outcome in some related studies. In addition, reference lists of related articles were checked manually to find the possibly missing papers.

Eligibility criteria

The following inclusion criteria were applied to select the related articles: (1) the design of the study should be randomized controlled trial (RCT); (2) performed in adults (aged 18 years or older); (3) reporting blood pressure as a primary or secondary outcome variable; (4) evaluating the effect of oral cinnamon supplementation (extract or powder) vs. either placebo, or no intervention. Trials were excluded if they (1) used a mixture of cinnamon supplementation and other herbs for intervention, and the difference between the intervention and control group was not only in cinnamon supplementation; (2) examined only the short-term or immediate post-consumption effect of cinnamon supplementation (less than 7 days of intervention); (3) reported duplicate data; (4) were letters, editorial articles, case reports or review article.

Data extraction

Three researchers (MAY, HH, ZY) conducted the initial screening of articles (title and abstract) and examined the full-text of relevant studies. Two investigators (ZY, MA) independently extracted data (the last name of the ﬁrst author, year of publication, country, study design, gender, sample size, age, subjects’ health status, type and dosage of supplementary cinnamon, duration (weeks), and mean [standard deviation (SD)] for SBP and DBP changes in the intervention and the placebo groups) from eligible studies. Means ± SDs for baseline and after intervention period were used to calculate mean change ± SD in SBP and DBP for each group. For studies that did not report the change values, P values or estimated correlation coefﬁcient (r = 0.63 for SBP and r = 0.75 for DBP) for baseline and endpoint values which were extracted from the other clinical trials were used to impute the SE for mean changes. All processes were checked by the other authors.

Risk of bias assessment

The quality of included publications were evaluated using Cochrane Collaboration’s Risk of Bias tool (16) based on the following criteria: (1) random sequence generation (selection bias), (2) allocation concealment, (3) blinding of participants and personnel, (4) blinding outcome data, (5) incomplete outcome data, and (6) selective reporting. These studies were classiﬁed as “high risk” of bias, “low risk” of bias and” unclear risk” based on each domain. Two authors (ZY and MA) independently assessed the methodological quality of the eligible studies against the six criteria. Any discrepancy was resolved by discussing a third author (AN).

Statistical analysis

The difference in mean change values and its standard error between the intervention (cinnamon supplementation) and control groups was calculated for each trial and used as effect size for meta-analyses. A DerSimonian and Laird random-effects model was applied to calculate the weighted mean difference (WMD) and the corresponding 95% confidence interval (CI) [32].

Cochran’s Q test and the I² statistic (I²) were used to evaluate the inter-study heterogeneity [33]. Different subgroup analyses were performed to detect the possible sources of between-study heterogeneity by considering the following variables: gender (both, female, and male), health status (T2DM, prediabetes/ metabolic syndrome, and others), duration of intervention ([34]. Publication bias was investigated for each outcome through visual inspection of funnel plots and conducting statistical asymmetry tests (Begg's and Egger's tests) [35]. STATA software (version 11.2; Stata Corp, College Station, TX) was used for all statistical analyses. P values lower than 0.05 were considered as statistically signiﬁcant.

Results

Study selection

The initial database search resulted in 4337 potentially relevant studies of which 3497 records remained after removing duplicate references. Based on the screening of the titles/abstracts, 99 studies were identified to be carefully checked by reading their full-texts; of these, 88 articles were excluded for the following reasons: (1) did not assess the effect of cinnamon supplementation on BP (n = 82), (2) had no control group (n = 1), (3) data were already reported in another included publication (n = 2), (4) examined the immediate post-consumption effect of cinnamon (n = 1), and (5) study participants were younger than 18 years (n = 2). The references for excluded studies and the reason for their exclusion are available in Table 1. Finally, 11 eligible RCTs were included in the current systematic review and meta-analysis [20-30]. The study selection ﬂow diagram is illustrated in Figure 1.

Table 1. Excluded studies with reasons (n = 88)

Reason for exclusion	References
Not systolic and diastolic blood pressure as outcome (n= 82)	[36-117]
Evaluation of immediate post-consumption effect (n=1)	[118]
Duplicate data of other studies (n=2)	[119, 120]
Had no control group (n= 1)	[121]
Studies conducted in children (n= 2)	[122, 123]

Figure 1. Study selection flow diagram

Characteristics of included articles

The characteristics of the eleven clinical trials which were eligible to be included in the current systematic review and meta-analysis are presented in Table 2. All studies had a parallel design, and their duration varied from 6 to 16 weeks. The studies were published between 2006 and 2018 in the United Kingdom [20, 21], Iran [27, 28, 30], India [22, 24], USA [25, 26], and other countries [23, 29]. Eight studies included both genders [20, 22, 23, 25, 26, 28-30], two were conducted only in females [21, 27] and one only included male participants [24], with the age ranging from 44 to 64.5 years. One study used cinnamon supplementation in the form of dried water extract [26], and other studies administered cinnamon powder with a dose of 500 to 10000 mg/d [20-25, 27-30]. Moreover, of the 11 included studies, five presented dietary intakes of participants during the study [20, 21, 25, 27, 30]. Two studies mentioned that they instructed their participants to maintain their previous food habits [24, 28] and also in two studies, participants continued the diet that was recommended during the run-in period [22, 23]. The remaining studies did not report information about dietary intake [26, 29]. Four included trials reported a reduction in both SBP and DBP [20-23], and some found a significant decline only in SBP [24, 25] or DBP [27]. However, four trials did not observe a significant difference between intervention and control groups [26, 28-30]. The effects of cinnamon supplementation were evaluated in different health status, as six studies focused on T2DM patients [20, 23, 24, 28-30], and the other studies included subjects with metabolic syndrome (MetS) and prediabetes [22, 25, 26], rheumatoid arthritis [27], and overweight [21].

Table 2. Characteristics of eligible studies evaluating the effect of cinnamon supplementation on SBP and DBP

Author (Ref)	Publication year	Participants	Gender	Sample size (control / intervention)	Age (years)	Study design	Duration (wk)	Intervention/control (name and daily dose)	Result	Diet	Notes about glycemic indicators (cinnamon vs. placebo group)	The time of consumption
Akilen et al. [20]	2010	T2DM	Both	30/28	54.9 ± 9.8	RCT double blind	12	2000 mg of cinnamon powder (Cinnamomum cassia)/starch	↓ DBP ↓ SBP	Follow their normal routine diet	Signiﬁcant decrease	With meals
Azimi et al. [30]	2014	T2DM	Both	40/39	54.33 ± 0.5	RCT single blind	8	3000 mg of cinnamon powder (Cinnamomum verum) + three glasses of tea/three glasses of tea	↔ DBP ↔ SBP	Follow their normal routine diet	No change	Three times throughout the day
Aldayel et al. [124]	2016	Overweight	F	8/7	Control= 53 ± 2.7 Intervention= 56 ± 1.3	RCT single blind	8	5000 mg of cinnamon powder (Cinnamomum cassia)/corn flour	↓ DBP ↓ SBP	Follow their normal routine diet	No change	Immediately after meals
Gupta et al. [22]	2017	MetS	Both	58/58	44.8 ± 7.8	RCT double blind	16	3000 mg of cinnamon powder/ wheat flour	↓ DBP ↓ SBP	Macronutrients equal to placebo group	Signiﬁcant decrease	Immediately after meals
Vafa et al. [28]	2012	T2DM	Both	19/18	Control= 55.67 ± 7.98 Intervention= 54.11 ± 10.37	RCT double blind	8	3000 mg of cinnamon powder (Cinnamomumzeylanicum)/wheat flour	↔ DBP ↔ SBP	Follow their normal routine diet	Signiﬁcant decrease	With meals
Shishehbor et al. [125]	2018	RA	F	18/18	Control= 49.11 ± 7.45 Intervention= 44.66 ± 11.22	RCT double blind	8	2000 mg of cinnamon powder (Cinnamomum burmannii)/starch	↓ DBP ↔ SBP	Follow their normal routine diet	No change	Immediately after meals
Soni et al. [24]	2015	T2DM	M	15/15	52 (40-60)	RCT, parallel	6	2000 mg of cinnamon powder (Cinnamomum cassia)/ no receiving supplementation	↔ DBP ↓ SBP	Follow their normal routine diet	Signiﬁcant decrease	Immediately after meals
Wainstein et al. [29]	2011	T2DM	Both	29/30	63.05 ± 10.85	RCT, parallel	12	1200 mg of cinnamon powder (Cinnamomum cassia)/ microcrystalline cellulose	↔ DBP ↔ SBP	NA	No change	With meals
Anderson et al. [26]	2015	Prediabetic	Both	63/72	61.3 ± 6.36	RCT double blind	8	500 dried water extract of cinnamon (Cinnamomum cassia)/ wheat flour	↔ DBP ↔ SBP	NA	Signiﬁcant decrease	Twice a day
Sengsuk et al. [23]	2016	T2DM	Both	49/50	control= 56.9 ± 1.2 Intervention= 57.2 ± 1.1	RCT double blind	8	1500 mg of cinnamon powder/ placebo	↓ DBP ↓ SBP	Macronutrients equal to placebo group	Signiﬁcant decrease	Immediately after meals
Zeigenfuss et al. [126]	2006	Prediabetes & MetS	Both	12/10	46.0 ± 9.7	RCT double blind	12	500 mg of water soluble extract (equivalent to 10000 mg of whole cinnamon powder)/ microcrystalline cellulose	↔ DBP ↓ SBP	Follow their normal routine diet	Signiﬁcant decrease	With meals

SBP, systolic blood pressure; DBP, diastolic blood pressure; Ref, reference; F, females; M, males; T2DM, type 2 diabetes mellitus; MetS, metabolic syndrome; RA, rheumatoid arthritis; RCT, randomized clinical trial; NA, not available; ↓, reduction; ↔, no change

Risk of Bias Assessment

Results of the quality assessment based on the Cochrane Collaboration’s tool are summarized in Table 3. In brief, five trials had a low risk of bias for all items of methodological quality assessment [20, 22, 23, 27, 29]. The method used to generate the random sequence and allocation concealment were unclear in four studies [21, 24, 25, 28]. Also, two included studies were high risk regarding blinding of personnel and outcome assessment [21, 30]. All of the studies were “low risk” regarding the incomplete outcome data and selective reporting.

Table 3. Study quality and risk of bias assessment

Author, year (reference)	Random sequence generation	Allocation concealment	Blinding of participants and personnel	Blinding of outcome assessment	Incomplete outcome data	Selective reporting
Akilen, 2010 [20]	L	L	L	L	L	L
Azimi, 2014 [30]	L	L	H	H	L	L
Aldayel, 2016 [124]	U	U	H	H	L	L
Gupta, 2017 [22]	L	L	L	L	L	L
Vafa, 2012 [28]	U	U	L	L	L	L
Shishehbor, 2018 [125]	L	L	L	L	L	L
Soni, 2015 [24]	U	U	U	U	L	L
Wainstein, 2011[29]	L	L	L	L	L	L
Anderson, 2015 [26]	L	L	L	U	L	L
Sengsuk, 2016 [23]	L	L	L	L	L	L
Zeigenfuss, 2006 [126]	U	U	L	U	L	L

Ref, reference; L, low risk; H, high risk; U, unclear

Meta-analysis results

Effect of cinnamon supplementation on systolic blood presssure

The pooled analysis of eleven trials with 686 participants, demonstrated an overall significant reduction in SBP by -5.72 mmHg (95% CI: -8.64, -2.80; P < 0.001), and the between-study heterogeneity was signiﬁcant (Cochran’s Q statistic = 23.38, P < 0.001, I²= 81.1%) (Figure 2). The subgroup analysis according to the administered dose, revealed a significant decrease 2000-3000 mg/d (WMD = -6.04 mmHg; 95% CI: -9.81, -2.27 mmHg; P= 0.002); however, the supplementation was not significant at the dose of ≥3000 mg/d (WMD = -5.52; 95% CI: -11.44, 0.39 mmHg; P = 0.067). The subgroup analysis based on participants’ health status showed that SBP was significantly declined by cinnamon supplementation in subgroups (T2DM, prediabetes/Mets and others). Moreover, significant decrease in SBP following cinnamon consumption was observed in both subgroups of duration, and the effect was considerable in studies with more than 12 weeks of follow-up (WMD = -6.62 mmHg; 95% CI: -9.23, -4.02 mmHg; P <0.001; I² = 53%). Subgroup analysis revealed that cinnamon supplementation with or immediately after meals could decrease systolic blood pressure; however, the reducing effect was greater when the supplementation was done after meals (WMD = --9.5 mmHg; 95% CI: -8.63, -2.80 mmHg; P <0.001; I² = 36.8%). The results of subgroup analyses, as well as overall analyse are illustrated in Table 4.

Figure 2. Forest plot summarizing the effects of cinnamon supplementation on systolic blood pressure

Effect of cinnamon supplementation on diastolic blood pressure

The meta-analysis of 11 trials suggested that cinnamon supplementation considerably decreased DBP (WMD = -4.06 mmHg, 95% CI: -6.68, -1.44, P = 0.002) and the heterogeneity among studies was signiﬁcant (Cochran’s Q statistic = 88.08, P < 0.001, I² = 88.6%) (Figure 3). The subgroup analysis based on the health status of participants revealed that cinnamon could not signiﬁcantly lower DBP in patients with T2DM (WMD = -2.01, 95% CI: -4.55, 0.52, P = 0.12). It appears that the consumption of cinnamon supplement immediately after meals can lead to a greater reduction in DBP (WMD = -7.32; 95% CI: -11.50, -3.15 mmHg; P = 0.001). The results of subgroup analyses indicated that trials with a significant decrease in glycemic indicators (fasting blood glucose or hemoglobin A1c) were associated with further DBP reduction. The subgroup analyses based on gender, health status, duration, and dose as well as overall analysis are provided in Table 4.

Figure 3. Forest plot summarizing the effects of cinnamon supplementation on diastolic blood pressure

Table 4. Results of overall and subgroup analysis of relevant randomized controlled trials in meta-analysis of the effect of cinnamon supplement on systolic and diastolic bllod pressure¹

Systolic blood pressure								Diastolic blood pressure
Study group	No. of trials	Meta-analysis		Heterogeneity				Meta-analysis		Heterogeneity
Study group	No. of trials	WMD² (95%CI)	P effect	Q statistic	P within group	I² (%)	P between subgroups	WMD (95%CI)	P effect	Q statistic	P within group	I² (%)	P between subgroups
Overall	11	-5.72 (-8.63, -2.80)	<0.001	53.04	<0.001	81.1	-	-4.06 (-6.68, -1.44)	0.002	88.08	<0.001	88.6	-
Gender
Both	8	-4.87 (-8.15, -1.60)	0.004	46.29	<0.001	84.9	0.034	-3.641 (-6.66, -.61)	0.0018	64.29	<0.001	89.1	<0.001
Females	2	-12.41 (-18.5, -6.33)	<0.001	0.00	0.97	0.00		-8.89 (-11.29, -6.49)	<0.001	0.23	0.63	0
Males	1	-3.87 (-10.42. 2.68)	0.24	0.00	-	-		0.4 (-2.5, 3.42)	0.72	0.00	-	-
Health status
T2DM	6	-4.06 (-7.84, -.27)	0.035	31.07	<0.001	83.9	0.004	-2.015 (-4.55, 0.52)	0.12	18.08	0.003	72.3	<0.001
Prediabetes & MetS	3	-6.57 (-13.05, -0.098)	0.047	10.69	0.005	81.3		-4.8 (-10.06, 0.44)	0.073	26.68	<0.001	92.5
Others (Overweight & RA)	2	-12.41 (-18.5, -6.33)	<0.001	0.00	0.97	0		-8.89 (-11.29, -6.49)	<0.001	0.23	0.63	0
Duration
	7	-5.19 (-9.90, -0.47)	0.03	33.97	<0.001	82.3	<0.001	-4.03 (-7.31, -0.75)	0.016	46.02	<0.001	87.0	<0.001
≥12 wk	4	-6.62 (-9.23, -4.02)	<0.001	6.39	0.094	53	<0.001	-4.11 (-8.48, 0.24)	0.064	26.2	<0.001	88.6	<0.001
Dose
	3	-6.63 (-13.79, 1.07)	0.094	12/19	0.002	83.6	0.22	-4.88 (-10.44, 0.66)	0.085	10.58	0.005	81.1	<0.001
2000-3000 mg/d	3	-6.04 (-9.81, -2.27)	0.002	3.56	0.16	43.8		-2.58 (-6.09, 0.92)	0.14	6.41	0.04	68.8
≥ 3000 mg/d	5	-5.52 (-11.44, 0.39)	0.067	34.34	<0.001	88.4		-4.27 (-8.67, 0.13)	0.057	52.40	<0.001	92.4
The time of consumption
With meals	5	-4.67 (-8.20, -1.13)	0.01	6.62	0.085	54.7	<0.001	-1.65 (-3.43, 0.11)	0.067	3.32	0.34	9.7	<0.001
Immediately after meals	4	-9.5 (-8.63, -2.80)	<0.001	6.33	0.17	36.8		-7.32 (-11.50, -3.15)	0.001	35.36	<0.001	88.7
Others	2	0.77 (-1.39, 2.41)	0.48	0.63	0.42	0.00		-1.87 (-3.48, -0.27)	0.022	1.02	0.31	1.7
The results of glycemic indicators
Signiﬁcant decreased	7	-5.72 (-8.81, -2.64)	<0.001	23.82	0.001	74.8	0.001	-3.81 (-7.21, -0.42)	0.027	65.30	<0.001	90.8	0.92
No change	4	-6.35 (-13.56, 0.85)	0.084	18.92	<0.001	84.1	0.001	-4.54 (-9.54, 0.44)	0.074	22.78	<0.001	86.8	0.92

¹ All analyses were performed using random effects model

WMD, weighted mean difference. T2DM, type 2 diabetes mellitus; MetS, metabolic syndrome; wk, week; RA, rheumatoid arthritis

Sensitivity analysis and publication bias

The results of the sensitivity analysis indicated that excluding each study from the whole sample or subgroups did not change the overall effect of the cinnamon supplementation on SBP and DBP. Egger's and Begg’s tests showed no presence of publication bias for meta-analyses assessing the effect of cinnamon supplementation on SBP (Begg’s test, P = 0.21; Egger’s test, P = 0.37) and DBP (Begg’s test, P = 1; Egger’s test, P = 0.49).

Discussion

The results of the present study showed that cinnamon consumption can be beneficial in reducing SBP and DBP (-5.72, -4.06 mmHg, respectively). This supplement significantly reduced SBP in patients with T2DM, whereas failed to find any significant effect on DBP in these subjects. These findings might be of clinical importance. A meta-analysis of controlled trials reported that each 5 mmHg SBP or 2 mmHg reduction in DBP could lead to lower risk of cardiovascular morbidity and mortality [127]. On the other hand, it is proposed that cinnamon and its components may be important in the prevention and alleviation of all factors associated with metabolic syndrome including insulin sensitivity, body weight, inﬂammation and blood pressure [128].

Our result regarding the effect of cinnamon supplementation on DBP is consistent with a meta-analysis by Akilen et al. [9], which evaluated the effects of short-term administration of cinnamon on blood pressure in T2DM and prediabetes and found a significant benefit in terms of DBP decline in these patients. However, the mentioned meta-analysis included three studies with 139 subjects.

Advanced glycation end products (AGEs) have a substantial role in the pathophysiology of coronary heart disease [129]. Increased AGEs result in endothelial dysfunction, oxidative stress and inﬂammation, which can cause hypertension and atherosclerosis. It is proposed that therapies that reduce insulin resistance and/or AGEs levels are effective in attenuating blood pressure, oxidative stress, and atherosclerotic vascular changes [130]. Recent studies demonstrated that cinnamon compounds, such as catechin, epicatechin, procyanidin B2, proanthocyanidin oligomers, and phenol polymers could scavenge reactive carbonyl species and thus effectively prevent the formation of AGEs [131, 132]. The other main ingredient of cinnamon is cinnamaldehyde, which is a potent agonist of epithelial transient receptor potential ankyrin 1 (TRPA1) [133], and stimulates the release of calcitonin gene-related peptide and causes vasodilation in peripheral arteries [134]. The results of published studies have shown that cinnamaldehyde relaxes blood vessels by the inhibition of endogenous vasoconstrictors such as angiotensin II, and also dilates the smooth muscle by interfering with both Ca²⁺ influx and release [17, 19, 135]. The other possible antihypertensive mechanism of cinnamon might be its ability to increase the endothelial nitric oxide and activate the ATP-sensitive potassium (KATP) channels in vascular smooth muscle [13, 17, 19, 135]. Moreover, improvement of insulin resistance is one of the presumptive mechanisms for the effect of cinnamon on blood pressure [136-138]. Nevertheless, it is expressed that more research is necessary to be done to exactly understand the underlying mechanism of how cinnamon supplementation could help to prevent and treat hypertension [139].

The ﬁndings of the current meta-analysis suggested that daily consumption of cinnamon with a dose of 2000-3000 mg is the most beneﬁcial dose for lowering SBP. A recent systematic review of RCTs that investigated the association between cinnamon supplementation and obesity, reported a non-significant dose-response trend of cinnamon supplementation with body mass index, and fat mass [140]. Furthermore, several human and animal studies have mentioned that there is no evidence of a dose-response relationship between cinnamon supplementation and several markers including blood pressure and response to all dosages of cinnamon was similar [135, 138, 141]. It seems that the detailed mechanism of cinnamon on BP is not well understood and needs to be further investigated. Moreover, it was shown that the consumption of cinnamon supplements immediately after meals can signiﬁcantly reduce DBP. Cinnamon can delay gastric emptying and thereby acts as a factor in blood glucose homeostasis [142, 143]. Since a close association exists between glycemic indicators and blood pressure levels [9, 20, 25], cinnamon consumption might reduce BP more effectively if ingested after meals. The subgroup analyses also demonstrated that there is a relationship between glycemic indicators and SBP or DBP values, which is consistent with the proposed mechanism in this context and the results of meta‐analyses done by Akilen et al. [9] in patients with prediabetes and type 2 diabetes.

The present study was undertaken based on a comprehensive and systematic search to identify all relevant literature and no evidence for publication bias was detected. Furthermore, to minimize bias, the study was restricted to RCTs. In addition, this review included all related published research and even those assessed BP as a secondary outcome in adults. Another strength of the current study is that the overall results were not sensitive to any single study. Even though, the present review has some limitations which need to be addressed. It should be considered that heterogeneity remained even after subgroup analyses. The heterogeneity might be explained by other variables not reported in the included studies. For instance, some studies did not report the species and composition of cinnamon used for supplementation and the dietary intake evaluation of participants. Moreover, the low number of studies included in some subgroup analyses restricted the interpretation of findings.

Conclusion

In summary, the present systematic review and meta-analysis suggest that cinnamon supplementation reduces SBP and DBP in adults, but has not signiﬁcant effect on DBP in subjects with T2DM. Furthermore, cinnamon has a DBP lowering effect when ingested immediately after meals. Albeit, the mechanism of its effect is not fully clear and requires subsequent investigation. Further studies with different doses are recommended to conﬁrm the present findings and to give a definitive answer to the question about the best effective dose of cinnamon that might decline blood pressure.

Acknowledgments

The authors would like to thank the research council of Nutrition and Food Security Research Center, Shahid Sadoughi University of Medical Sciences for comprehensive support of the present study.

Authors’ contribution

ZY designed the search strategy, conducted data extraction, analyzed the data, interpreted the results and wrote the first draft of the manuscript; MA conducted data extraction and quality of the eligible studies; HH conducted the study selection; MAY conducted the study selection; AN conceived the study, interpreted the results and critically revised the manuscript. All authors read and approved the final version of the manuscript.

Funding Source

The present systematic review was ﬁnancially supported by Nutrition and Food Security research center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.

Conflict of interest

The authors declare that there is no conflict of interest.

References

[1] Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, Boehm M, et al. 2013 ESH/ESC guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Blood pressure. 2013;22:193-278

[2] Chow CK, Teo KK, Rangarajan S, Islam S, Gupta R, Avezum A, et al. Prevalence, awareness, treatment, and control of hypertension in rural and urban communities in high-, middle-, and low-income countries. Jama. 2013;310:959-68

[3] Kazemi T, Tavakoli T, Hajihosseini M, Yari E. Prevalence of Pre-hypertension and Risk Factors in an Iranian Population: East of Iran. International Cardiovascular Research Journal. 2018;12:34-7

[4] Daskalopoulou SS, Rabi DM, Zarnke KB, Dasgupta K, Nerenberg K, Cloutier L, et al. The 2015 Canadian Hypertension Education Program recommendations for blood pressure measurement, diagnosis, assessment of risk, prevention, and treatment of hypertension. Canadian Journal of Cardiology. 2015;31:549-68

[5] Mancia G, De Backer G, Dominiczak A, Cifkova R, Fagard R, Germano G, et al. 2007 Guidelines for the Management of Arterial Hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Journal of hypertension. 2007;25:1105-8710.1097/HJH. 0b013e3281fc975a.

[6] Wang HP, Yang J, Qin LQ, Yang XJ. Effect of garlic on blood pressure: A meta‐analysis. The Journal of Clinical Hypertension. 2015;17:223-31

[7] Aleixandre A, Miguel M. Dietary fiber and blood pressure control. Food & function. 2016;7:1864-71

[8] Luís Â, Domingues F, Pereira L. Metabolic changes after licorice consumption: a systematic review with meta-analysis and trial sequential analysis of clinical trials. Phytomedicine. 2018;39:17-24

[9] Akilen R, Pimlott Z, Tsiami A, Robinson N. Effect of short-term administration of cinnamon on blood pressure in patients with prediabetes and type 2 diabetes. Nutrition. 2013;29:1192-6

[10] Ebadi M. Pharmacodynamic basis of herbal medicine: CRC press; 2010

[11] Maierean SM, Serban M-C, Sahebkar A, Ursoniu S, Serban A, Penson P, et al. The effects of cinnamon supplementation on blood lipid concentrations: A systematic review and meta-analysis. Journal of clinical lipidology. 2017;11:1393-406

[12] Allen RW, Schwartzman E, Baker WL, Coleman CI, Phung OJ. Cinnamon use in type 2 diabetes: an updated systematic review and meta-analysis. The Annals of Family Medicine. 2013;11:452-9

[13] Song F, Li H, Sun J, Wang S. Protective effects of cinnamic acid and cinnamic aldehyde on isoproterenol-induced acute myocardial ischemia in rats. Journal of ethnopharmacology. 2013;150:125-30

[14] Rao PV, Gan SH. Cinnamon: a multifaceted medicinal plant. Evidence-Based Complementary and Alternative Medicine. 2014;2014:12 pagesdoi.org/10.1155/2014/642942.

[15] Jakhetia V, Patel R, Khatri P, Pahuja N, Garg S, Pandey A, et al. Cinnamon: a pharmacological review. Journal of advanced scientific research. 2010;1:19-23

[16] HARADA M, YANO S. Pharmacological studies on Chinese cinnamon. II. Effects of cinnamaldehyde on the cardiovascular and digestive systems. Chemical and pharmaceutical bulletin. 1975;23:941-7

[17] Xue Y-L, Shi H-X, Murad F, Bian K. Vasodilatory effects of cinnamaldehyde and its mechanism of action in the rat aorta. Vascular health and risk management. 2011;7:273-80

[18] Anderson RA, Broadhurst CL, Polansky MM, Schmidt WF, Khan A, Flanagan VP, et al. Isolation and characterization of polyphenol type-A polymers from cinnamon with insulin-like biological activity. Journal of agricultural and food chemistry. 2004;52:65-70

[19] El-Bassossy HM, Fahmy A, Badawy D. Cinnamaldehyde protects from the hypertension associated with diabetes. Food and Chemical Toxicology. 2011;49:3007-12

[20] 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. Diabetic medicine : a journal of the British Diabetic Association. 2010;27:1159-6710.1111/j.1464-5491. 2010.03079.x.

[21] Aldayel TS. Health benefits of cinnamon supplement : in vitro and in vivo [Doctoral]: University of Surrey; 2016

[22] Gupta Jain S, Puri S, Misra A, Gulati S, Mani K. Effect of oral cinnamon intervention on metabolic profile and body composition of Asian Indians with metabolic syndrome: a randomized double -blind control trial. Journal of the science of food and agriculture. 2017;16:113-2310.1002/jsfa.8490

10.1186/s12944-017-0504-8.

[23] Sengsuk C, Sanguanwong S, Tangvarasittichai O, Tangvarasittichai S. Effect of cinnamon supplementation on glucose, lipids levels, glomerular filtration rate, and blood pressure of subjects with type 2 diabetes mellitus. Diabetology International. 2016;7:124-3210.1007/s13340-015-0218-y.

[24] Soni R, Bhatnagar V. Effect Of CinnamoN (Cinnamomum Cassia) Intervention On Metabolic Features Of Adult Male With Type 2 Diabetes. International Journal of Pharma and Bio Sciences. 2015;6:P772-P6

[25] Ziegenfuss TN, Hofheins JE, Mendel RW, Landis J, Anderson RA. Effects of a water-soluble cinnamon extract on body composition and features of the metabolic syndrome in pre-diabetic men and women. Journal of the International Society of Sports Nutrition. 2006;3:45-5310.1186/1550-2783-3-2-45.

[26] Anderson RA, Zhan Z, Luo R, Guo X, Guo Q, Zhou J, et al. Cinnamon extract lowers glucose, insulin and cholesterol in people with elevated serum glucose. Journal of traditional and complementary medicine. 2016;6:332-610.1016/j.jtcme.2015.03.005.

[27] Shishehbor F, Rezaeyan Safar M, Rajaei E, Haghighizadeh MH. Cinnamon Consumption Improves Clinical Symptoms and Inflammatory Markers in Women With Rheumatoid Arthritis. Journal of the American College of Nutrition. 2018;37:685-9010.1080/07315724.2018.1460733.

[28] Vafa M, Mohammadi F, Shidfar F, Sormaghi MS, Heidari I, Golestan B, et al. Effects of cinnamon consumption on glycemic status, lipid profile and body composition in type 2 diabetic patients. International journal of preventive medicine. 2012;3:531-6

[29] Wainstein J, Stern N, Heller S, Boaz M. Dietary cinnamon supplementation and changes in systolic blood pressure in subjects with type 2 diabetes. Journal of medicinal food. 2011;14:1505-1010.1089/jmf.2010.0300.

[30] Azimi P, Ghiasvand R, Feizi A, Hosseinzadeh J, Bahreynian M, Hariri M, et al. Effect of cinnamon, cardamom, saffron and ginger consumption on blood pressure and a marker of endothelial function in patients with type 2 diabetes mellitus: A randomized controlled clinical trial. Blood pressure. 2016;25:133-40

[31] Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JP, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS medicine. 2009;6:e1000100

[32] DerSimonian R, Laird N. Meta-analysis in clinical trials. Controlled clinical trials. 1986;7:177-88

[33] Higgins JP, Thompson SG. Quantifying heterogeneity in a meta‐analysis. Statistics in medicine. 2002;21:1539-58

[34] Egger M, Davey-Smith G, Altman D. Systematic reviews in health care: meta-analysis in context: John Wiley & Sons; 2008

[35] Egger M, Smith GD, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. Bmj. 1997;315:629-34

[36] Anderson RA. Chromium and polyphenols from cinnamon improve insulin sensitivity. The Proceedings of the Nutrition Society. 2008;67:48-5310.1017/s0029665108006010.

[37] Azzeh FS. Synergistic effect of green tea, cinnamon and ginger combination on enhancing postprandial blood glucose. Pakistan journal of biological sciences : PJBS. 2013;16:74-9

[38] Cao Van H, Guinand N, Damis E, Mansbach AL, Poncet A, Hummel T, et al. Olfactory stimulation may promote oral feeding in immature newborn: a randomized controlled trial. European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery. 2018;275:125-910.1007/s00405-017-4796-0.

[39] Crawford P. Effectiveness of cinnamon for lowering hemoglobin A1C in patients with type 2 diabetes: a randomized, controlled trial. Journal of the American Board of Family Medicine : JABFM. 2009;22:507-1210.3122/jabfm.2009.05.080093.

[40] Crawford P, Thai C, Obholz J, Schievenin J, True M, Shah SA, et al. Assessment of the effeCt of lIfestyle iNtervention plus water-soluble ciNnAMon extract On loweriNg blood glucose in pre-diabetics, a randomized, double-blind, multicenter, placebo controlled trial: study protocol for a randomized controlled trial. Trials. 2016;17:910.1186/s13063-015-1138-7.

[41] Gharaiy NR, Shahnazi M, Kia PY, Javadzadeh Y. The effect of cinnamon on cyclical breast pain. Iranian Red Crescent Medical Journal. 2017;1910.5812/ ircmj.26442.

[42] Graham G, Johnson EB, Johnson A, Anderson R, Devine P. Cinnamon for glycemic control in gestational diabetes: A randomized double-blind placebo controlled pilot study. American Journal of Obstetrics and Gynecology. 2005;193:S91-S10.1016/j.ajog.2005.10.306.

[43] Gupta D, Jain A. Effect of Cinnamon Extract and Chlorhexidine Gluconate (0.2%) on the Clinical Level of Dental Plaque and Gingival Health: A 4-Week, Triple-Blind Randomized Controlled Trial. Journal of the International Academy of Periodontology. 2015;17:91-8

[44] Hasanzade F, Toliat M, Emami SA, Emamimoghaadam Z. The Effect of Cinnamon on Glucose of Type II Diabetes Patients. Journal of traditional and complementary medicine. 2013;3:171-410.4103/2225-4110.114900.

[45] Hoehn AN, Stockert AL. The Effects of Cinnamomum Cassia on Blood Glucose Values are Greater than those of Dietary Changes Alone. Nutrition and metabolic insights. 2012;5:77-8310.4137/nmi.s10498.

[46] Islam H, Yorgason NJ, Hazell TJ. Creatine co-ingestion with carbohydrate or cinnamon extract provides no added benefit to anaerobic performance. European journal of sport science. 2016;16:685-9310.1080/17461391.2015.1071877.

[47] Jaafarpour M, Hatefi M, Khani A, Khajavikhan J. Comparative effect of cinnamon and Ibuprofen for treatment of primary dysmenorrhea: a randomized double-blind clinical trial. Journal of clinical and diagnostic research : JCDR. 2015;9:Qc04-710.7860/jcdr/2015/12084.5783.

[48] Jaafarpour M, Hatefi M, Najafi F, Khajavikhan J, Khani A. The effect of cinnamon on menstrual bleeding and systemic symptoms with primary dysmenorrhea. Iranian Red Crescent medical journal. 2015;17:e2703210.5812/ircmj.17(4)2015.27032.

[49] Jensen TK, Andersen MV, Nielsen KA, Arendt-Nielsen L, Boudreau SA. Interaction between intra-oral cinnamaldehyde and nicotine assessed by psychophysical and physiological responses. European journal of oral sciences. 2016;124:349-5710.1111/eos.12279.

[50] 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;26:3215-8

[51] Khan R, Khan Z, Shah SH. Cinnamon may reduce glucose, lipid and cholesterol Level in Type 2 diabetic individuals. Pakistan Journal of Nutrition. 2010;9:430-310.3923/pjn.2010.430.433.

[52] Kleefstra N, Logtenberg SJ, Groenier KH, Bilo HJ. Reply to Akilen et al. Effect of cinnamon on glycated haemoglobin and blood pressure. Diabetic medicine : a journal of the British Diabetic Association. 2011;28:38010.1111/j.1464-5491.2010.03225.x.

[53] Magistrelli A, Chezem JC. Effect of ground cinnamon on postprandial blood glucose concentration in normal-weight and obese adults. Journal of the Academy of Nutrition and Dietetics. 2012;112:1806-910.1016/j.jand.2012.07.037.

[54] Mang B, Wolters M, Schmitt B, Kelb K, Lichtinghagen R, Stichtenoth DO, et al. Effects of a cinnamon extract on plasma glucose, HbA1c, and serum lipids in diabetes mellitus type 2. European Journal of Clinical Investigation. 2006;36:340-410.1111/j.1365-2362.2006.01629.x.

[55] Marzouk TMF, El-Nemer AMR, Baraka HN. The effect of aromatherapy abdominal massage on alleviating menstrual pain in nursing students: A prospective randomized cross-over study. Evidence-based Complementary and Alternative Medicine. 2013;201310.1155/2013/742421.

[56] Metugriachuk Y, Marotta F, Kuroi O, Tsuchiya J, Goh KL, Minelli E, et al. Effect of a phyto-compound on delayed gastric emptying in functional dyspepsia: A randomized-controlled study. Journal of Digestive Diseases. 2008;9:204-710.1111/j.1751-2980.2008. 00347.x.

[57] Molania T, Saeedi M, Ehsani H, Azizi M, Moosazadeh M, Rostamkalaei S, et al. Evaluation of Anti-inflammatory Effect of Cinnamaldehyde Mouthwash in Comparison with Chlorhexidine in Patients with Gingivitis. Journal of Research in Medical and Dental Science. 2018;6:76-8410. 24896/jrmds.20186113.

[58] Moncada MM, Bernardo MA, Silva ML, Jorge A, Pereira P, Brito J, et al. Effect of cinnamon powder addition to a Portuguese custard tart (Pastel de Nata) on healthy adults’ postprandial glycemia. World Heart Journal. 2017;9:135-44

[59] Moraveji M, Sahebalzamani M, Safaee M. Effects of cinnamon on glucose control in glucose intolerant patients. Life Science Journal. 2013;10:438-40

[60] Niinimäki A. Double‐blind placebo‐controlled peroral challenges in patients with delayed‐type allergy to balsam of Peru. Contact Dermatitis. 1995;33:78-8310.1111/j.1600-0536.1995.tb00505.x.

[61] Nir Y, Potasman I, Stermer E, Tabak M, Neeman I. Controlled trial of the effect of cinnamon extract on Helicobacter pylori. Helicobacter. 2000;5:94-7

[62] Singh TN, Upadhyay BN, Tewari CM, Tripathi SN. Management of diabetes mellitus (prameha) with inula racemosa and cinnamomum tamala. Ancient science of life. 1985;5:9-16

[63] Soni R, Bhatnagar V. Effect of cinnamon (Cinnamomum cassia) intervention on blood glucose of middle aged adult male with non insulin dependent diabetes mellitus (NIDDM). Studies on Ethno-Medicine. 2009;3:141-410.1080/09735070.2009.11886352.

[64] Tang MH, Larson-Meyer DE, Liebman M. Effect of cinnamon and turmeric on urinary oxalate excretion, plasma lipids, and plasma glucose in healthy subjects. American Journal of Clinical Nutrition. 2008;87:1262-7

[65] Ullah A, Abbasi NA, Shafique M, Qureshi AA. Influence of Edible Coatings on Biochemical Fruit Quality and Storage Life of Bell Pepper cv. "Yolo Wonder". Journal of Food Quality. 2017;201710.1155/2017/2142409.

[66] White JML, White IR, Kimber I, Basketter DA, Buckley DA, McFadden JP. Atopic dermatitis and allergic reactions to individual fragrance chemicals. Allergy: European Journal of Allergy and Clinical Immunology. 2009;64:312-610.1111/j.1398-9995. 2008.01904.x.

[67] Wilborn C, Hayward S, Taylor L, Urbina S, Foster C, Deshpande P, et al. Effects of a proprietary blend rich in glycoside based standardized fenugreek seed extract (IBPR) on inflammatory markers during acute eccentric resistance exercise in young subjects. Asian Journal of Pharmaceutical and Clinical Research. 2017;10:99-10410.22159/ajpcr.2017.v10i10.18811.

[68] Wiweko B, Susanto CA. The Effect of Metformin and Cinnamon on Serum Anti-Mullerian Hormone in Women Having PCOS: A Double-Blind, Randomized, Controlled Trial. Evidence-based complementary and alternative medicine : eCAM. 2017;10:31-610.1155/2017/2687173

10.4103/jhrs.JHRS_90_16.

[69] Yiannias JA, Winkelmann RK, Connolly SM. Contact sensitivities in palmar plantar pustulosis (acropustulosis). Contact Dermatitis. 1998;39:108-1110.1111/j.1600-0536.1998.tb05857.x.

[70] Zahedifar A, Khodashenas M, Bijari B, Zahedifar F. Effects of cinnamon on fasting blood sugar and hemoglobin A1C in patients with type II diabetes mellitus: A randomized clinical trial. Journal of Mazandaran University of Medical Sciences. 2018;27:80-8

[71] Zahmatkash M, Vafaeenasab MR. Comparing analgesic effects of a topical herbal mixed medicine with salicylate in patients with knee osteoarthritis. Pakistan journal of biological sciences : PJBS. 2011;14:715-9

[72] Zahmatkesh M, Fallah Huseini H, Hajiaghaee R, Heidari M, Mehrafarin A, Tavakoli-far B. The effects of Cinnamomum zeylanicum J. Presl on blood glucose level in patients with type 2 diabetes, a double-blind clinical trial. Journal of Medicinal Plants. 2012;11:258-63

[73] Zeng Y, Bi D, Yi Z, Lu J, Zhong F, Jiang B. [Clinical study of medicinal-cake-separated moxibustion for senile osteoporosis]. Evidence-based complementary and alternative medicine : eCAM. 2017;37:473-610.1155/ 2017/ 4730878 10.13703/j.0255-2930. 2017. 05. 005.

[74] Lee MS, Wahlqvist ML, Chou YC, Fang WH, Lee JT, Kuan JC, et al. Turmeric improves post-prandial working memory in pre-diabetes independent of insulin. Asia Pacific journal of clinical nutrition. 2014;23:581-9110.6133/apjcn.2014.23.4.24.

[75] Wang JG, Anderson RA, Graham Iii GM, Chu MC, Sauer MV, Guarnaccia MM, et al. The effect of cinnamon extract on insulin resistance parameters in polycystic ovary syndrome: a pilot study. Fertility and Sterility. 2007;88:240-310.1016/j.fertnstert. 2006.11.082.

[76] Mina Wassef Girgiss WGN, Dawoud Fakhry Habib, EmanRefaat Youness, Nadia Mohamed Ahmed and Mohamed Elsayed Elnemr. Potential role of cinnamon in the prevention and management of diabetic vascular complications in humans. Bioscience Research. 2018;15:348-56

[77] Bernardo MA, Silva ML, Santos E, Moncada MM, Brito J, Proenca L, et al. Effect of Cinnamon Tea on Postprandial Glucose Concentration. Journal of diabetes research. 2015;2015:91365110.1155/ 2015/913651.

[78] Kadhim HM. Antiinflmmatory and antihyperlipidemic effect of adjuvant cinnamon in type 2 diabetic patients. International Journal of Pharmaceutical Sciences Review and Research. 2016;41:88-93

[79] Otto AD. Cinnamon as a supplemental treatment for impaired glucose tolerance and type 2 diabetes. Current diabetes reports. 2010;10:170-210.1007/ s11892-010-0106-6.

[80] Ranjbar A, Ghaseminejhad S, Takalu H, Baiaty A, Rahimi F, Abdollahi M. Anti oxidative stress potential of Cinnamon (Cinnamomum zeylanicum) in operating room personnel; a before/after cross sectional clinical trial. International Journal of Pharmacology. 2007;3:482-610.3923/ijp.2007.482. 486.

[81] Ranjbar A, Ghasmeinezhad S, Zamani H, Malekirad AA, Baiaty A, Mohammadirad A, et al. Antioxidative stress potential of Cinnamomum zeylanicum in humans: A comparative cross-sectional clinical study. Therapy. 2006;3:113-710.1586/14750708.3. 1.113.

[82] Roussel AM, Hininger I, Benaraba R, Ziegenfuss TN, Anderson RA. Antioxidant effects of a cinnamon extract in people with impaired fasting glucose that are overweight or obese. Journal of the American College of Nutrition. 2009;28:16-21

[83] Sahib AS. Anti-diabetic and antioxidant effect of cinnamon in poorly controlled type-2 diabetic Iraqi patients: A randomized, placebo-controlled clinical trial. Journal of intercultural ethnopharmacology. 2016;5:108-1310.5455/jice.20160217044511.

[84] Tangvarasittichai S, Sanguanwong S, Sengsuk C, Tangvarasittichai O. Effect of cinnamon supplementation on oxidative stress, inflammation and insulin resistance in patients with type 2 diabetes mellitus. International Journal of Toxicological and Pharmacological Research. 2015;7

[85] Markey O, McClean CM, Medlow P, Davison GW, Trinick TR, Duly E, et al. Effect of cinnamon on gastric emptying, arterial stiffness, postprandial lipemia, glycemia, and appetite responses to high-fat breakfast. Cardiovascular diabetology. 2011;10:7810.1186/1475-2840-10-78.

[86] Walanj S, Walanj A, Mohan V, Thakurdesai PA. Efficacy and safety of the topical use of intranasal cinnamon bark extract in seasonal allergic rhinitis patients: A double-blind placebo-controlled pilot study. Journal of Herbal Medicine. 2014;4:37-4710.1016/j.hermed.2013.12.002.

[87] Hlebowicz J, Hlebowicz A, Lindstedt S, Bjorgell O, Hoeglund P, Holst JJ, et al. Effects of 1 and 3 g cinnamon on gastric emptying, satiety, and postprandial blood glucose, insulin, glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1, and ghrelin concentrations in healthy subjects. American Journal of Clinical Nutrition. 2009;89:815-2110.3945/ajcn.2008.26807.

[88] Hochkogler CM, Hoi JK, Lieder B, Muller N, Hans J, Widder S, et al. Cinnamyl Isobutyrate Decreases Plasma Glucose Levels and Total Energy Intake from a Standardized Breakfast: A Randomized, Crossover Intervention. Molecular nutrition & food research. 2018;62:e170103810.1002/mnfr.201701038.

[89] Siedentopp U. Effects of 1 and 3 g cinnamom on gastric emptying, satiety and postprandial blood glucose, insulin, glucose-dependent insulinotropic polypeptide, glucagons-like peptide 1, and ghrelin concentrations in healthy subjects. Deutsche Zeitschrift fur Akupunktur. 2009;52:40-110.1016/j. dza.2009.07.006.

[90] Siedentopp U. Effects of 1 g and 3 g cinnamon on gastric emptying, satiety and postprandial blood glucose, insulin, glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1, and ghrelin concentrations in healthy subjects. Revista Internacional de Acupuntura. 2010;4:39-4010.1016/ S1887-8369(10)70010-7.

[91] Zanzer YC, Plaza M, Dougkas A, Turner C, Björck I, Östman E. Polyphenol-rich spice-based beverages modulated postprandial early glycaemia, appetite and PYY after breakfast challenge in healthy subjects: A randomized, single blind, crossover study. Journal of Functional Foods. 2017;35:574-8310.1016/j.jff.2017.06.016.

[92] Gutierrez JL, Cooke M, Lutz R, Rodney B, Kane R, Willoughby D. Cassia cinnamon supplementation before an oral glucose tolerance test in overweight or obese young women. Faseb Journal. 2010;24

[93] Shirvani H, Taherichadorneshin H, Kimiyagar F. The effect of intense endurance exercise training and consumption of cinnamon powder on sex hormones in trained male cyclists. Journal of Military Medicine. 2017;19:245-52

[94] Solomon TPJ, Blannin AK. Changes in glucose tolerance and insulin sensitivity following 2 weeks of daily cinnamon ingestion in healthy humans. European Journal of Applied Physiology. 2009; 105:969-7610.1007/s00421-009-0986-9.

[95] Vanschoonbeek K, Thomassen BJ, Senden JM, Wodzig WK, van Loon LJ. Cinnamon supplementation does not improve glycemic control in postmenopausal type 2 diabetes patients. The Journal of nutrition. 2006;136:977-8010.1093/jn/ 136.4.977.

[96] Wickenbere J, Lindstedt S, Berntorp K, Nilsson J, Hlebowicz J. Ceylon cinnamon does not affect postprandial plasma glucose or insulin in
subjects with impaired glucose tolerance. British Journal of Nutrition. 2012;107:1845-910.1017/ s0007114511005113.

[97] Wickenberg J, Lindstedt S, Nilsson J, Hlebowicz J. Cassia cinnamon does not change the insulin sensitivity or the liver enzymes in subjects with impaired glucose tolerance. Nutrition journal. 2014;13:9610.1186/1475-2891-13-96.

[98] Lu T, Sheng HG, Wu J, Cheng Y, Zhu JM, Chen Y. Cinnamon extract improves fasting blood glucose and glycosylated hemoglobin level in Chinese patients with type 2 diabetes. Nutrition Research. 2012;32:408-1210.1016/j.nutres.2012.05.003.

[99] Kort DH, Lobo RA. Preliminary evidence that cinnamon improves menstrual cyclicity in women with polycystic ovary syndrome: A randomized controlled trial. Obstetrical and Gynecological Survey. 2015;70:94-510.1097/01.ogx. 0000461902. 16853.84.

[100] Faqih AM, Al-Nawaiseh FY. The immediate glycemic response to four herbal teas in healthy adults. Jordan Medical Journal. 2006;40:266-75

[101] Hlebowicz J, Darwiche G, Bjorgell O, Almer LO. Effect of cinnamon on postprandial blood glucose, gastric emptying, and satiety in healthy subjects. The American journal of clinical nutrition. 2007;85:1552-610.1093/ajcn/85.6.1552.

[102] Mettler S, Schwarz I, Colombani PC. Additive postprandial blood glucose-attenuating and satiety-enhancing effect of cinnamon and acetic acid. Nutrition research (New York, NY). 2009;29:723-710.1016/j.nutres.2009.10.002.

[103] Abraham K, Pfister M, Wöhrlin F, Lampen A. Relative bioavailability of coumarin from cinnamon and cinnamon-containing foods compared to isolated coumarin: A four-way crossover study in human volunteers. Molecular Nutrition and Food Research. 2011;55:644-5310.1002/mnfr.201000394.

[104] Girgiss MW, Nicola WG, Habib DF, Youness ER, Ahmed NM, Elnemr ME. Potential role of cinnamon in the prevention and management of diabetic vascular complications in humans. Bioscience Research. 2018;15:348-56

[105] Sharma P, Sharma S, Agrawal RP, Agrawal V, Singhal S. A randomised double blind placebo control trial of cinnamon supplementation on glycemic control and lipid profile in type 2 diabetes mellitus. Australian Journal of Herbal Medicine. 2012;24:52-7

[106] Al Jamal AR, Bayoumy HMM. Effects of cinnamon on blood glucose among type 1 and type 2 diabetic individuals: A comparative study. Jordan Medical Journal. 2009;43:299-307

[107] Askari F, Rashidkhani B, Hekmatdoost A. Cinnamon may have therapeutic benefits on lipid profile, liver enzymes, insulin resistance, and high-sensitivity C-reactive protein in nonalcoholic fatty liver disease patients. Nutrition research (New York, NY). 2014;34:143-810.1016/j.nutres.2013.11.005.

[108] Blevins SM, Leyva MJ, Brown J, Wright J, Scofield RH, Aston CE. Effect of cinnamon on glucose and lipid levels in non-insulin-dependent type 2 diabetes. Diabetes Care. 2007;30:2236-710.2337/ dc07-0098.

[109] Borzoei A, Rafraf M, Niromanesh S, Farzadi L, Narimani F, Doostan F. Effects of cinnamon supplementation on antioxidant status and serum lipids in women with polycystic ovary syndrome. Journal of traditional and complementary medicine. 2018;8:128-3310.1016/j.jtcme.2017.04.008.

[110] Hajimonfarednejad M, Nimrouzi M, Heydari M, Zarshenas MM, Raee MJ, Jahromi BN. Insulin resistance improvement by cinnamon powder in polycystic ovary syndrome: A randomized double-blind placebo controlled clinical trial. Phytotherapy Research. 2018;32:276-8310.1002/ptr.5970.

[111] Mirfeizi M, Mehdizadeh Tourzani Z, Mirfeizi SZ, Asghari Jafarabadi M, Rezvani HR, Afzali M. Controlling type 2 diabetes mellitus with herbal medicines: A triple-blind randomized clinical trial of efficacy and safety. Journal of diabetes. 2016;8:647-5610.1111/1753-0407.12342.

[112] Nakhaei K, Ghofrani M, Bakhsheshi MF, Nakhaei H. Effect of circuit resistance training and cinnamon supplement on body composition and omentin-1 in overweight women. Iranian Journal of Obstetrics, Gynecology and Infertility. 2018;20:74-8210.22038/IJOGI.2018.10230.

[113] Talaat B, Ammar IMM. The added value of cinnamon to metformin in controlling symptoms of polycystic ovary syndrome, a randomized controlled trial. Middle East Fertility Society Journal. 201810.1016/j.mefs.2018.03.005.

[114] Weitgasser R, Pfutzner A, Kerschgens B, Drexel H, Prager R, Ludvik B, et al. Impact of cinnamon vs. placebo on surrogate markers of metabolic control in patients with type 2 diabetes mellitus. Diabetologia. 2007;50:S378-S9

[115] Zare R, Nadjarzadeh A, Zarshenas MM, Shams M, Heydari M. Efficacy of cinnamon in patients with type II diabetes mellitus: A randomized controlled clinical trial. Clinical nutrition (Edinburgh, Scotland). 201810.1016/j.clnu.2018.03.003.

[116] Haghighian HK, Naimi AF, Gargari BP, Ali-Asgharzadeh A, Nemati A. Effect of cinnamon supplementation on blood glucose and lipid levels in type2 diabetic patients. JPS. 2011;2:2008-4978

[117] Suppapitiporn S, Kanpaksi N, Suppapitiporn S. The effect of cinnamon cassia powder in type 2 diabetes mellitus. Journal of the Medical Association of Thailand = Chotmaihet thangphaet. 2006;89 Suppl 3:S200-5

[118] Chezem JC, Tickle S, Fernandes N, Bolin JH. Effect of cinnamon on blood glucose, satiety and caloric intake in middle-aged obese adults. Faseb Journal. 2013;27

[119] Azimi P, Ghiasvand R, Feizi A, Hariri M, Abbasi B. Effects of Cinnamon, Cardamom, Saffron, and Ginger Consumption on Markers of Glycemic Control, Lipid Profile, Oxidative Stress, and Inflammation in Type 2 Diabetes Patients. The Review of Diabetic Studies. 2014;11:258-6610.1900/rds.2014.11.258.

[120] Nasri H, Madihi Y, Marikhi A. Commentary on: Effects of Cinnamon Consumption on Glycemic Status, Lipid Profile and Body Composition in Type 2 Diabetic Patients. International journal of preventive medicine. 2013;4:618-9

[121] Ranasinghe P, Jayawardena R, Pigera S, Wathurapatha WS, Weeratunga HD, Premakumara GAS, et al. Evaluation of pharmacodynamic properties and safety of Cinnamomum zeylanicum (Ceylon cinnamon) in healthy adults: A phase I clinical trial. BMC Complementary and Alternative Medicine. 2017;1710.1186/s12906-017-2067-7.

[122] Mashhadi NS, Ghiasvand R, Hariri M, Askari G, Feizi A, Darvishi L, et al. Effect of ginger and cinnamon intake on oxidative stress and exercise performance and body composition in Iranian female athletes. International journal of preventive medicine. 2013;4:S31-5

[123] Altschuler JA, Casella SJ, MacKenzie TA, Curtis KM. The effect of cinnamon on A1C among adolescents with type 1 diabetes. Diabetes Care. 2007;30:813-610.2337/dc06-1871.

[124] Aldayel TS. Health benefits of cinnamon supplement : in vitro and in vivo [Doctoral]: University of Surrey; 2016

[125] Shishehbor F, Rezaeyan Safar M, Rajaei E, Haghighizadeh MH. Cinnamon Consumption Improves Clinical Symptoms and Inflammatory Markers in Women With Rheumatoid Arthritis. Journal of the American College of Nutrition. 2018:1-610.1080/07315724.2018.1460733.

[126] Ziegenfuss TN, Hofheins JE, Mendel RW, Landis J, Anderson RA. Effects of a water-soluble cinnamon extract on body composition and features of the metabolic syndrome in pre-diabetic men and women. Journal of the International Society of Sports Nutrition. 2006;3:45-5310.1186/1550-2783-3-2-45.

[127] Verdecchia P, Gentile G, Angeli F, Mazzotta G, Mancia G, Reboldi G. Influence of blood pressure reduction on composite cardiovascular endpoints
in clinical trials. Journal of hypertension. 2010;28:1356-65

[128] Qin B, Panickar KS, Anderson RA. Cinnamon: potential role in the prevention of insulin
resistance, metabolic syndrome, and type 2 diabetes. Journal of diabetes science and technology. 2010;4:685-93

[129] Kosmopoulos M, Drekolias D, Zavras PD, Piperi C, Papavassiliou AG. Impact of advanced glycation end products (AGEs) signaling in coronary artery disease. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease. 2019;1865:611-9

[130] Vasdev S, Gill V, Singal P. Role of advanced glycation end products in hypertension and atherosclerosis: therapeutic implications. Cell biochemistry and biophysics. 2007;49:48-6310.1007/s12013-007-0039-0.

[131] Peng X, Ma J, Chao J, Sun Z, Chang RC-C, Tse I,
et al. Beneficial effects of cinnamon proanthocyanidins on the formation of specific advanced glycation endproducts and methylglyoxal-induced impairment on glucose consumption. Journal of agricultural and food chemistry. 2010;58:6692-6

[132] Peng X, Cheng K-W, Ma J, Chen B, Ho C-T, Lo C, et al. Cinnamon bark proanthocyanidins as reactive carbonyl scavengers to prevent the formation of advanced glycation endproducts. Journal of agricultural and food chemistry. 2008;56:1907-11

[133] Bandell M, Story GM, Hwang SW, Viswanath V, Eid SR, Petrus MJ, et al. Noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin. Neuron. 2004;41:849-57

[134] Kee Z, Kodji X, Brain SD. The role of calcitonin gene related peptide (CGRP) in neurogenic vasodilation and its cardioprotective effects. Frontiers in physiology. 2018;9:1-1310.3389/ fphys.2018.01249.

[135] Nyadjeu P, Nguelefack-Mbuyo EP, Atsamo AD, Nguelefack TB, Dongmo AB, Kamanyi A. Acute and chronic antihypertensive effects of Cinnamomum zeylanicum stem bark methanol extract in L-NAME-induced hypertensive rats. BMC complementary and alternative medicine. 2013;13:27-36

[136] Manaf A, Tjandrawinata RR, Malinda D. Insulin sensitizer in prediabetes: a clinical study with DLBS3233, a combined bioactive fraction of Cinnamomum burmanii and Lagerstroemia speciosa. Drug design, development and therapy. 2016;10:1279-89

[137] Ranilla LG, Kwon Y-I, Apostolidis E, Shetty K. Phenolic compounds, antioxidant activity and in vitro inhibitory potential against key enzymes relevant for hyperglycemia and hypertension of commonly used medicinal plants, herbs and spices in Latin America. Bioresource technology. 2010;101:4676-89

[138] Preuss HG, Echard B, Polansky MM, Anderson R. Whole cinnamon and aqueous extracts ameliorate sucrose-induced blood pressure elevations in spontaneously hypertensive rats. Journal of the American College of Nutrition. 2006;25:144-50

[139] Chezem J, Tickle S, Fernandes N, Bolin J. Short-term effect of cinnamon on blood pressure in middle-aged obese adults. Journal of the Academy of Nutrition and Dietetics. 2013;113:A32

[140] Mousavi SM, Rahmani J, Kord-Varkaneh H, Sheikhi A, Larijani B, Esmaillzadeh A. Cinnamon supplementation positively affects obesity: A systematic review and dose-response meta-analysis of randomized controlled trials. Clinical Nutrition. 2019;39:123-33

[141] Khan A, Safdar M, Khan MMA, Khattak KN, Anderson RA. Cinnamon improves glucose and lipids of people with type 2 diabetes. Diabetes care. 2003;26:3215-8

[142] Moncada MM, Bernardo M, Silva ML, Jorge A, Pereira P, Brito J, et al. Effect of cinnamon powder addition to a Portuguese custard tart (Pastel de Nata) on healthy adults' postprandial glycemia. World Heart Journal. 2017;9:1-10

[143] Hlebowicz J, Darwiche G, Björgell O, Almér L-O. Effect of cinnamon on postprandial blood glucose, gastric emptying, and satiety in healthy subjects. The American journal of clinical nutrition. 2007;85:1552-6

Statistics

Article View: 854

PDF Download: 337

Related Links

Statistics

Effects of Cinnamon Supplementation on Systolic and Diastolic Blood Pressure: a Systematic Review and Meta-analysis of Randomized Controlled Clinical Trials