Journal of Traditional and Complementary Medicine xxx (2015) 1e5

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Journal of Traditional and Complementary Medicine

journal homepage: http://www.elsevier.com/locate/jtcme

Original article

Cinnamon extract lowers glucose, insulin and cholesterol in people

with elevated serum glucose
Richard A. Anderson a, *, Zhiwei Zhan b, Rencai Luo c, Xiuhua Guo d, Qingqing Guo d,
Jin Zhou e, Jiang Kong f, Paul A. Davis g, Barbara J. Stoecker h
a
PolyChrom Technology, LLC, Edgewater, MD 21037, USA
b
The General Hospital of 2nd Artillery, Beijing, China
c
Beijing CDC, Beijing, China
d
Beijing Capital Medical University, Beijing, China
e
Dalian Dakang Clinic, Dalian, China
f
Beijing Tang-An Clinic, Beijing, China
g
Department of Nutrition, University of Calif-Davis, Davis, CA, USA
h
Oklahoma State University, USA

a r t i c l e i n f o a b s t r a c t

Article history: Cinnamon (肉桂 ro  u guì) has in vitro insulin potentiating activity, and proanthocyanidins from cinnamon
Received 25 February 2015 prevent in vitro formation of advanced glycation end products. Some human studies were equivocal, but
Received in revised form several have shown beneficial effects of cinnamon supplementation on circulating glucose, lipids, and/or
12 March 2015
insulin. This placebo-controlled double-blind trial tested the effects of a dried water extract of cinnamon
Accepted 13 March 2015
Available online xxx
(Cinnamomum cassia) on circulating glucose, lipids, insulin, and insulin resistance. Men and women from
Beijing and Dalian, China, were invited to participate if they had fasting serum glucose >6.1 mmol/L or 2-
h glucose >7.8 mmol/L. Participants, (173 were enrolled and 137 completed the study) were randomly
Keywords:
Cinnamon
assigned to receive either a spray-dried, water extract of cinnamon (CinSulin®), 250 mg/capsule, or a
Type A procyanidin polyphenols placebo, twice a day for two months. Mean ± SEM age of participants was 61.3 ± 0.8 years, BMI was
Insulin sensitivity 25.3 ± 0.3 and M/F ratio was 65/72. After 2 mo, fasting glucose decreased (p < 0.001) in the cinnamon
Glucose extract-supplemented group (8.85 ± 0.36 to 8.19 ± 0.29 mmol/L) compared with the placebo group
Lipids (8.57 ± 0.32 to 8.44 ± 0.34 mmol/L, p ¼ 0.45). Glucose 2 h after a 75 g carbohydrate load, fasting insulin,
and HOMA-IR also decreased with cinnamon extract compared with placebo. Total and LDL-cholesterol
decreased with cinnamon extract and HDL-cholesterol decreased in both the cinnamon-extract and
placebo groups. In conclusion, supplementation with 500 mg of water-extract of cinnamon for two
months reduced fasting insulin, glucose, total cholesterol, and LDL cholesterol and enhanced insulin
sensitivity of subjects with elevated blood glucose.
Copyright © 2015, Center for Food and Biomolecules, National Taiwan University. Production and hosting
by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license (http://
creativecommons.org/licenses/by-nc-nd/4.0/).

1. Introduction Khan et al2 reported that subjects with type 2 diabetes given 1, 3 or
6 g of ground cinnamon per day for 40 days showed significant
Cinnamon (Cinnamomum verum, Cinnamomum zeylanicum; 錫蘭 reductions in fasting serum glucose (18e29%), triglycerides
肉桂 xı l
an rou guì) and cassia (Cinnamomum aromaticum; 中國肉桂 (23e30%), LDL cholesterol (7e27%), and total cholesterol (12e26%)
 ng guo
zho  ro
u guì) have a long history of uses as flavoring agents, with no significant changes in the placebo group. Several follow-up
preservatives, and pharmacological agents.1 In addition, in 2004, human studies have also reported beneficial effects of cinnamon on
people with varying degrees of glucose intolerance ranging from
normal to type 2 diabetes.313 Not all studies have reported bene-
ficial effects of cinnamon or cinnamon extracts in human supple-
* Corresponding author. Tel./fax: þ1 410 798 0846.
E-mail address: PolyChrom.Anderson@gmail.com (R.A. Anderson).
mentation trials. However, three of four recent meta-analyses
Peer review under responsibility of The Center for Food and Biomolecules, conclude that there are positive effects of supplemental cinnamon
National Taiwan University. or cinnamon extract and that further studies are needed.10,1416

http://dx.doi.org/10.1016/j.jtcme.2015.03.005
2225-4110/Copyright © 2015, Center for Food and Biomolecules, National Taiwan University. Production and hosting by Elsevier Taiwan LLC. This is an open access article
under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Please cite this article in press as: Anderson RA, et al., Cinnamon extract lowers glucose, insulin and cholesterol in people with elevated serum
glucose, Journal of Traditional and Complementary Medicine (2015), http://dx.doi.org/10.1016/j.jtcme.2015.03.005
2 R.A. Anderson et al. / Journal of Traditional and Complementary Medicine xxx (2015) 1e5

One region where further studies are needed is China with only Nutrition Society recommends BMI cutoffs of 28 for obesity and 24
a single positive study.13 The present study used a spray-dried for overweight.26
water-extract of cinnamon for supplementing adults with hyper- Blood pressure was measured after the participants had rested
glycemia in a placebo controlled double-blind two-month trial for 15 min and measurements were repeated two times. Post-
conducted in China. In China, it is estimated that there are 90 prandial glucose was obtained by measuring plasma glucose two
million people with diabetes and over 150 million people with pre- hours after each participant consumed 100 g of white steamed
diabetes who are likely to become diabetic due to the current bread (equivalent to 75 g of carbohydrate).
rapidly changing lifestyle in China.17 (替代醫療 tì da i yı lia
o) are
urgently needed to control the hyperglycemia which precedes the 2.5. Biochemical analyses
escalating incidence of type 2 diabetes and the resulting exploding
health care costs. Serum glucose and lipids were analyzed on a Hitachi 7071A
clinical analyzer. Insulin was analyzed by radioimmunoassay and
2. Research design and methods fructosamine with a kit from RANDOX Laboratories.

2.1. Study participants 2.6. Quantitative glycemic measures

Men and women with fasting serum glucose >6.1 mmol/L or 2- The homeostasis model assessment for insulin resistance
h glucose >7.8 mmol/L from the clinic of the General Hospital of (HOMA-IR) was used as a proxy measurement of insulin sensitivity.
the 2nd Artillery, Beijing Tang-An Clinic and Dalian Dakang Clinic, HOMA-IR was calculated as (fasting serum glucose  fasting serum
in Beijing and Dalian, China, were invited to join this study. insulin) divided by 22.5.27
Exclusion factors were fasting glucose >20 mmol/L or 2-hr glucose
>25 mmol/L, serum insulin <5 IU, taking insulin therapy, or 2.7. Statistical analyses
serious complications such as cardiac/cerebral vascular diseases,
or renal dysfunction. The study was approved by the human use Descriptive statistics were summarized as means and standard
committee of both hospitals and all participants gave informed error of the mean using the SAS version 9.1 (SAS Institute, Cary, NC).
consent.18 Initially 173 persons were enrolled in the study, 89 in Parameters that were heavily right skewed (fasting insulin, HOMA-
the placebo group and 84 in the treatment group. A total of 137 IR, and triacylglycerols) were log transformed prior to statistical
completed the study with 73 in the placebo group and 64 in the analyses. Treatment effects were analyzed using analysis of vari-
treatment group. No complications were reported in either the ance with repeated measures (PROC MIXED) with an autore-
placebo or the treatment groups; the 36 subjects who did not gressive period 1 error structure. The simple effect of treatment
complete the study were dropped because of a change in medi- given time (SLICE option in an LSMEANS statement) was used to
cation or missing a blood draw. Participants were asked to return identify significant changes from baseline with supplementation
their capsule bottles to allow study personnel to confirm study with cinnamon extract.
compliance.
3. Results
2.2. Study design
3.1. Baseline characteristics of subjects
Study participants were assigned to groups using a random
number table in this double-blind placebo-controlled trial. The Mean ± SEM age of participants was 61.3 ± 0.8 y; 47% were men.
treatment group received a commercially available spray-dried Mean body mass index (BMI) was 25.3 ± 0.3 but 56% of the subjects
water extract of cinnamon (肉桂 ro u guì) (CinSulin®) containing had BMI between 24e28, which based on Chinese standards,26 is
more than 4% type A procyanidin polyphenols,19 in 250 mg cap- classified as overweight; nearly 14% were classified as obese with
sules, twice a day. (This product does not contain added chromium BMI >28. Participants were hyperglycemic with baseline fasting
or Vitamin D which is found in some commercial products using glucose values of 8.70 ± 0.24 mmol/L (Table 1). Baseline parameters
the same name). Type A procyanidin polyphenols are associated for the entire group for fasting insulin, postprandial glucose and
with insulin potentiating,1922 antioxidant5,23 and anti- insulin, lipids and blood pressure are also shown in Table 1.
inflammatory activities.24,25 The control group received placebo Fasting insulin and HOMA-IR were significantly higher in the
capsules which contained 250 mg of dark brown (baked) overweight and obese groups than in the normal weight group
wheat flour and were very similar in appearance to the cinnamon (Table 1). The insulin at 2 h after a glucose load was markedly and
extract. significantly higher in the obese group than in the groups with
lower BMIs. Glucose and fructosamine values were not different for
2.3. Outcomes the three BMI groups. Diastolic blood pressure was significantly
higher in the obese group. Total cholesterol and LDL-cholesterol
In the present study, the by-group differences in fasting and in were not significantly different by BMI, but HDL-cholesterol was
2-hr serum glucose and in insulin resistance estimated as HOMA-IR significantly lower in the overweight and obese groups and tri-
were the primary outcome variables. Additional measurements acyglycerols were higher in those two groups.
included systolic and diastolic blood pressure, serum lipids, and At baseline, homeostasis model assessment-estimated that in-
fructosamine. sulin resistance (HOMA-IR) was significantly correlated with dia-
stolic blood pressure (r ¼ 0.23) postprandial glucose (r ¼ 0.45),
2.4. Anthropometry and clinical procedures insulin (r ¼ 0.42), triacylglycerols (r ¼ 0.29), fructosamine
(r ¼ 0.23), and BMI (r ¼ 0.29) and negatively correlated with HDL-
Height and weight were measured initially and weight was cholesterol (r ¼ 0.37).
repeated at the end of the study. Subjects wore light clothing and Participants were assigned to placebo or treatment groups using
removed their shoes for these measurements. Body mass index was a random number table. There were no significant differences at
calculated as weight (kg) divided by height (m2). The Chinese baseline in any parameters between the two groups (Table 2). After

Please cite this article in press as: Anderson RA, et al., Cinnamon extract lowers glucose, insulin and cholesterol in people with elevated serum
glucose, Journal of Traditional and Complementary Medicine (2015), http://dx.doi.org/10.1016/j.jtcme.2015.03.005
 R.A. Anderson et al. / Journal of Traditional and Complementary Medicine xxx (2015) 1e5 3

Table 1
Baseline characteristics of subjects and classification by Chinese guidelines for body mass index (BMI) indicating normal, overweight, and obese.a

All BMI <24.0b BMI 24.0e<28.0c BMI 28.0d

Age, years 61.3 ± 0.8 59.0 ± 1.4 62.2 ± 1.0 62.4 ± 2.2
Fasting glucose, mmol/L 8.70 ± 0.24 8.99 ± 0.48 8.52 ± 0.28 8.82 ± 0.83
2-hr glucose, mmol/L 14.60 ± 0.42 14.61 ± 0.85 14.41 ± 0.51 15.37 ± 1.21
Fasting insulin, mU/L 22.9 ± 1.3 16.0 ± 1.3B 24.4 ± 1.8A 32.4 ± 4.2A
2-hr insulin, mU/L 89.4 ± 3.9 76.2 ± 6.9B 89.9 ± 5.0B 114.8 ± 9.8A
HOMA-IR 9.0 ± 0.6 6.6 ± 0.7B 9.4 ± 0.8A 13.2 ± 2.4A
Fructosamine, mmol/L 343 ± 6 338 ± 11 344 ± 8 350 ± 13
Systolic blood pressure, mm Hg 125.3 ± 1.2 122.9 ± 2.6 125.1 ± 1.5 131.4 ± 3.4
Diastolic blood pressure, mm Hg 77.0 ± 0.7 75.4 ± 1.4B 76.7 ± 0.8B 81.3 ± 2.2A
Total cholesterol, mmol/L 5.16 ± 0.09 5.19 ± 0.17 5.10 ± 0.11 5.35 ± 0.17
LDL cholesterol, mmol/L 3.46 ± 0.08 3.56 ± 0.15 3.38 ± 0.11 3.59 ± 0.20
HDL cholesterol, mmol/L 1.27 ± 0.03 1.41 ± 0.07A 1.23 ± 0.03B 1.16 ± 0.04B
Triacylglycerols, mmol/L 2.12 ± 0.13 1.54 ± 0.15B 2.32 ± 0.16A 2.54 ± 0.59A
a
Mean ± SEM; Means (by BMI classification) in a row with superscripts (uppercase alphabets) are significantly different if they do not share a common letter. BMI clas-
sifications are based on recommendations from the Chinese Diabetes Association.
b
n ¼ 37e41 for glucose, insulin, HOMA-IR and blood pressure and 32 for lipids and fructosamine.
c
n ¼ 77 for glucose, insulin, HOMA-IR and blood pressure and 63 for lipids and fructosamine.
d
n ¼ 17e19 for glucose, insulin, HOMA-IR and blood pressure and 14e15 for lipids & fructosamine.

two months of supplementation with placebo or water-extract of 4. Discussion

cinnamon (肉桂 ro u guì), the only significant changes in the placebo
group were an increase in triacylglyerols (p < 0.0001), an increase The incidence of type 2 diabetes (T2D) in China and worldwide
in systolic blood pressure (p < 0.05) and a decrease in HDL- is exploding and the associated morbidity, mortality and costs have
cholesterol (p < 0.005). Cinnamon extract supplementation, low- energized the search for ways to reduce type 2 diabetes.28 Impaired
ered fasting serum glucose (p < 0.001) in the cinnamon- glucose tolerance (IGT) is a recognized intermediary condition be-
supplemented group, 8.85 ± 0.36 to 8.19 ± 0.29 mmol/L tween normal glucose regulation and T2DM and is associated with
(p < 0.005), compared with 8.57 ± 0.32 to 8.44 ± 0.34 mmol/L in the a substantially elevated risk of disease progression.29 A recent
placebo control group (p ¼ 0.45). Serum glucose 2 h after a 75 g meta-analysis, looking at rates of natural progression to diabetes in
carbohydrate load also decreased significantly (p < 0.0001) in the high-risk individuals, found that progression rates to diabetes in
cinnamon extract-supplemented group, 15.09 ± 0.57 to subjects exhibiting elevated fasting glucose, IGT, or both are
13.3 ± 0.55 mmol/L, compared with non-significant differences in roughly double those for normal glucose tolerance progressing to
the placebo group, 14.18 ± 0.60 to 13.74 ± 0.58 mmol/L. Fasting diabetes.30,31 These results point to plasma glucose levels as a po-
insulin concentrations decreased significantly and postprandial tential target to reduce progression to and hence prevalence of type
insulin tended (p < 0.06) to be reduced by cinnamon extract sup- 2 diabetes. Studies of pharmaceutical agents such as metformin,32
plementation. Insulin sensitivity, assessed by HOMA-IR, was acarbose,33 and pioglitazone,34 that all lower glucose levels, were
significantly improved by cinnamon extract as were fructosamine found to lower diabetes mellitus onset in high-risk populations.
concentrations. However the high costs, side effects and difficult compliance issues
Total cholesterol decreased with cinnamon extract supple- of these interventions have slowed or blocked widespread
mentation as did LDL-cholesterol. HDL-cholesterol was decreased implementation.
in both the placebo and cinnamon extract-supplemented groups Cinnamon (肉桂 ro u guì) extract may offer a low cost, readily
and triacylglycerols increased in both groups (Table 2). Responses available and relatively easily implemented means of reducing
to cinnamon extract were independent of BMI. plasma glucose levels and thereby reducing T2D. The present study

Table 2
Effects of placebo or supplementation with 250 mg water extract of cinnamon twice per day for two months in hyperglycemic adults.a,b,c

Placebo  u guì)
Cinnamon (肉桂 ro

n Baseline Final n Baseline Final

d
BMI 70 25.8 ± 0.3 25.6 ± 0.3 63 24.8 ± 0.4 24.6 ± 0.4
Fasting glucose, mmol/L 73 8.57 ± 0.32 8.44 ± 0.34 64 8.85 ± 0.36 8.19 ± 0.29**
2-hr glucose, mmol/L 73 14.18 ± 0.60 13.74 ± 0.58 64 15.09 ± 0.57 13.30 ± 0.55***
Fasting insulin, mU/L 72 21.64 ± 1.66 23.65 ± 3.02 63 24.25 ± 2.01 22.26 ± 2.08*
2-hr insulin, mU/L 73 86.43 ± 5.19 82.58 ± 4.84 59 93.13 ± 5.78 83.17 ± 4.53
HOMA-IR 72 8.51 ± 0.80 9.12 ± 1.32 63 9.67 ± 0.90 8.32 ± 0.84**
Fructosamine, mmol/L 57 348 ± 9 338 ± 8 51 336 ± 8 319 ± 7*
Systolic blood pressure, mmHg 72 122.7 ± 1.5 126.2 ± 1.8¤ 63 128.3 ± 1.9 131.1 ± 1.9
Diastolic blood pressure, mmHg 72 75.9 ± 0.9 77.4 ± 1.0 63 78.2 ± 1.1 77.2 ± 1.1
Total cholesterol, mmol/L 57 5.12 ± 0.12 5.05 ± 0.14 53 5.20 ± 0.14 4.96 ± 0.16*
LDL cholesterol, mmol/L 57 3.45 ± 0.09 3.35 ± 0.11 53 3.48 ± 0.14 3.25 ± 0.14**
HDL cholesterol, mmol/L 57 1.28 ± 0.04 1.21 ± 0.04¤¤ 53 1.26 ± 0.04 1.17 ± 0.04**
Triacylglycerols, mmol/L 57 2.05 ± 0.17 2.48 ± 0.19¤¤¤ 53 2.20 ± 0.21 2.58 ± 0.28*
a
Mean ± SEM.
b
Placebo group e significantly different from baseline ¤p < 0.05; ¤¤p < 0.005; ¤¤¤p < 0.0001.
c
Cinnamon group e significantly different from baseline *p < 0.05;**p < 0.005;***p < 0.0001.
d
BMI ¼ Body Mass Index.

Please cite this article in press as: Anderson RA, et al., Cinnamon extract lowers glucose, insulin and cholesterol in people with elevated serum
glucose, Journal of Traditional and Complementary Medicine (2015), http://dx.doi.org/10.1016/j.jtcme.2015.03.005
4 R.A. Anderson et al. / Journal of Traditional and Complementary Medicine xxx (2015) 1e5

used a well-controlled and defined parallel study design to care- Considerable effort has been focused on drugs that would serve as
fully characterize the response of plasma glucose metabolism in ligands for this receptor.42 Mueller and Jungbauer noted that cin-
Chinese adults with hyperglycemia to daily consumption of a well- namon extracts bound PPARg in competitive ligand binding as-
defined, spray-dried water-extract of cinnamon. Study participants says.43 Kim and Choung suggest that cinnamon regulates insulin
were hyperglycemic and 70% were overweight or obese based on sensitivity by regulating PPAR-mediated glucose metabolism.44
the Chinese standards for BMI.26 Recent research suggests that Qin et al45 reported a significantly higher glucose utilization rate
adipose tissue is an active endocrine organ that releases cytokines in animals fed a cinnamon extract compared to the rate in control
and contributes to inflammation and ultimately to insulin rats. They suggested that cinnamon extract may improve insulin
resistance.3537 In our study, fasting insulin was twice as high in the action via increasing glucose uptake, perhaps through enhancing
group with BMI above 28 compared to the group with BMI less than the insulin-signaling pathway in skeletal muscle.
24. Likewise, insulin resistance estimated by HOMA-IR and tri- More investigation is needed of dietary factors involved in
acylglycerols were significantly elevated in the overweight and control of glucose homeostasis. Insulin resistance seems to be a
obese BMI groups and BMI was correlated with diastolic blood common factor in virtually all markers for metabolic syndrome.
pressure, fasting insulin and triacylglycerols. Obesity is associated with low-grade inflammation, but cinnamon
Meeting the criteria for metabolic syndrome was not required extract may have a role in reducing pro-inflammatory factors that
for participation in this study; thus, no measure of central obesity promote insulin resistance. Moreover, cinnamon and cinnamon
was taken. However, many of the men and women had lipid and extract are rich sources of proanthocyanins that may be particularly
blood pressure values consistent with metabolic syndrome in effective in quelling inflammatory compounds and stimulating in-
addition to their elevated fasting glucose. Specifically, 40% of the sulin signaling pathways.25,46
men and women had inappropriately low HDL-cholesterol, 53% had The unexpected increase in triacylglycerols is not consistent
triglycerides above 1.7 mmol and 46% had systolic or diastolic blood with any of the previous studies and is likely due to unidentified
pressure above 130/85.38 dietary changes since it was present in both the treatment and
Mechanisms by which cinnamon or cinnamon extract supple- placebo groups.
ments lower glucose, insulin and estimates of insulin resistance are
not yet completely clear, but food composition analyses, in vitro, 5. Conclusion
animal, and human studies suggest possibilities. Proanthocyani-
dins, which are high in cinnamon, are plant metabolites with This study documents the beneficial effects of 500 mg of a cin-
antioxidant activity.39 Cinnamon has a particularly high hydrophilic namon (肉桂 ro  u guì) extract per day on Chinese adults with
oxygen radical absorbance capacity (ORAC)/total phenolics ratio.23 elevated blood glucose. The cinnamon extract used in this study
Furthermore, cinnamon bark extracts inhibited the formation was a commercially available spray-dried water extract of cinna-
in vitro of advanced glycation end products (AGEs) which mon (CinSulin®) containing more than 4% of type A procyanidin
contribute to diabetic complications. This inhibition has been polyphenols which are associated with improvements in insulin
attributed to the ability of phenolic compounds in the extracts to potentiating, antioxidant and anti-inflammatory activities. As
trap reactive carbonyl species.40 Antioxidant variables, ferric demonstrated by this and related studies, cinnamon extract should
reducing antioxidant potential and plasma thiols, increased while be considered for the prevention and alleviation of elevated blood
plasma malondyaldehyde (MDA) levels decreased in subjects glucose thereby likely reducing progression to type 2 diabetes and
receiving a cinnamon extract similar to the one used in this study.5 its associated morbidity and mortality.
In tests of insulin activity using the rat epididymal fat cell assay,
cinnamon extracts produced the greatest enhancement of glucose Conflicts of interest
utilization of all the forty-nine herb, spice, and medicinal plant
extracts tested.20 Subsequently, water-soluble polyphenolic poly- None.
mers from cinnamon were found to increase insulin activity by
approximately twenty-fold in the same assay.19 Acknowledgments
Several steps in insulin signaling pathways are affected by cin-
namon extracts. Various cinnamon compounds effect protein Authors contributed to the study and manuscript in the
phosphorylation-dephosphorylation reactions in adipocytes.21,22 following ways: Patient recruitment and sample collection and
Another study suggested that a cinnamon extract affects a tyro- management (ZZ, RL, XG, QG, JZ, JK); laboratory analyses (ZZ, RL,
sine phosphatase that would otherwise inactivate the insulin re- XM); statistical analyses (XG, QG, BJS); drafting and revision of
ceptor21 and Cao and coworkers reported that a water extract of manuscript (BJS, PAD, RAA); review of manuscript (All).
cinnamon increased insulin-dependent glucose transporter 4
(GLUT4). Cheng et al41 reported that water soluble cinnamon References
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Please cite this article in press as: Anderson RA, et al., Cinnamon extract lowers glucose, insulin and cholesterol in people with elevated serum
glucose, Journal of Traditional and Complementary Medicine (2015), http://dx.doi.org/10.1016/j.jtcme.2015.03.005