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● Research Article
Effects of bee propolis supplementation on
glycemic control, lipid profile and insulin
resistance indices in patients with type 2
diabetes: a randomized, double-blind clinical trial
Nazli Samadi1, Hassan Mozaffari-Khosravi1,2, Masoud Rahmanian2,3, Mohsen Askarishahi4
1. Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences,
Yazd, Iran
2. Yazd Diabetic Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
3. Department of Internal Medicine, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences,
Yazd, Iran
4. Department of Biostatistics and Epidemiology, Faculty of Health, Shahid Sadoughi University of Medical
Sciences, Yazd, Iran

ABSTRACT
BACKGROUND: Propolis, a natural resinous substance made by bees from material extracted from
plants, flowers and bee’s wax, has shown great therapeutic effects and been widely used in food and
drug industries. Recently, some researchers have studied the effect of this substance in the treatment of
diabetes.
OBJECTIVE: The purpose of this trial was to determine the effect of bee propolis on glycemic control,
serum lipid profile and insulin resistance indices in patients with type 2 diabetes (T2D).
DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: This randomized clinical trial involved 66
patients with T2D, which were randomly divided into two groups of intervention (IG) and placebo (PG).
IG received 300 mg three times a day for a total of 900 mg/d of propolis pills, while PG received similar
pills, lacking propolis, on the same schedule for 12 weeks.
MAIN OUTCOME MEASURES: Fasting blood glucose (FBG), hemoglobin A1c (HbA1c), total cholesterol
(TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride (TG), serum insulin and
insulin resistance indices were the main outcome measures.
RESULTS: The mean change in FBG between the IG ((17.76 ± 27.72) mg/dL decrease) and the PG
((6.48 ± 42.77) mg/dL increase) was significantly different (P = 0.01). Change in mean HbA1c had a
similar pattern to FBG. The mean change in TC between the IG ((5.16 ± 43.80) mg/dL increase) and the
PG ((28.9 ± 27.4) mg/dL increase) was also significantly different (P = 0.01), showing the protective role
of propolis against the increase in TC. The change in mean LDL was similar to mean TC. There was no
significant difference in other lipids or insulin resistance indices between the two groups.
CONCLUSION: Based on this study, the daily intake of 900 mg of bee propolis supplement for 12 weeks
results in improvement of glycemic and some serum lipid levels in patients with T2D.
TRIAL REGISTRATION: This study is registered on the website of Iranian Ministry of Health (www.irct.ir)

http://dx.doi.org/10.1016/S2095-4964(17)60315-7
Received August 15, 2016; accepted November 2, 2016.
Correspondence: Hassan Mozaffari-Khosravi, PhD; E-mail: mozaffari.kh@gmail.com

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with proprietary code of IRCT2014080218659N1.

Keywords: propolis; diabetes mellitus, type 2; blood glucose; insulin resistance
Citation: Samadi N, Mozaffari-Khosravi H, Rahmanian M, Askarishahi M. Effects of bee propolis
supplementation on glycemic control, lipid profile and insulin resistance indices in patients with type 2
diabetes: a randomized, double-blind clinical trial. J Integr Med. 2017; 15(2): 124–134.

1 Introduction Generally, raw propolis contains 50% resin, 30% wax,

10% essential oils, 5% pollen and 5% other organic
Diabetes mellitus (DM) is a disease characterized by compounds. [ 13,14] The main components of propolis
high blood glucose and resulting in defects in insulin responsible for its biological activities include flavonoids,
secretion, insulin action, or both. Insulin is a hormone phenols and aromatic compounds. [8,15] Propolis has
produced by β-cells in the pancreas and is necessary for shown great therapeutic effects, and is widely used in the
using or storing body fuels.[1] DM may be caused by low food and drug industries. Its biological effects include
levels of insulin, dysfunction of pancreas cells, or tissue anti-inflammatory,[16–19] antibacterial,[20] antifungal,[21,22]
resistance, especially in skeletal muscle and adipose antioxidant, [23,24] anticancer, [25–29] and immune system
tissue.[1–3] regulation.[30,31] Some studies have also been performed to
In 2013, it was reported that there were 382 million assess the effect of propolis on blood pressure.[32,33]
people with diabetes worldwide, accounting for 8.3% Flavonoids in propolis are powerful antioxidants that
of the global population; 90% of these patients were can eliminate free radicals and protect cell membranes
diagnosed with type 2 diabetes (T2D).[4–6] The prevalence from lipid peroxidation.[34] Propolis can reduce cellular
of this metabolic disorder is higher in men than women. levels of hydrogen perioxide and nitric oxide.[35] Another
The prevalence of DM varies by region around the important component of propolis’s antioxidant properties
world, especially in urban areas. The incidence of DM is caffeic acid phenyl ester (CAPE), which blocks the
is increasing rapidly and it is estimated that the total production of reactive oxygen species.[36] Propolis, in
number of people with DM will increase to 366 million vitro, is a low-density lipoprotein (LDL) peroxidation
by 2030.[7] inhibitor.[37] In vivo, it increases the antioxidant capacity
Propolis is a natural resinous substance made by bees of humans[38] and animals.[39] In vivo and in vitro studies
from material extracted from plants and bee’s wax, have shown the mechanisms of action for propolis’s
as well as saliva and enzymes secreted by the bee’s cardiac protective effects, including regulation of
salivary glands.[8–10] Propolis is a word of Greek origin; glucose and lipoprotein metabolisms, regulation of gene
in this case, the “pro” means before and “polis” means a expression, decreased activity of inflammatory cytokines,
community or town. In this sense, the term is defined as a improved endothelial function and inhibition of platelet
natural substance produced to protect the hive. Bee glue is aggregation.[40] In addition, polyphenols commonly found
another name of propolis.[11] From ancient times, propolis in propolis reduce the risk of cardiovascular disease and
has been used widely by man in traditional medicine to prevent the formation of atherogenic plaques.[41–43]
treat diseases. Ancient Egyptians used it for embalming The antimicrobial activity of propolis has been
the dead. Incas used the substance as febrifuge. Greek and investigated on Gram-positive bacteria (Staphylococcus
Roman physicians applied propolis to disinfect the mouth and Streptococcus) and Gram-negative bacteria
and also disinfect and heal wounds. The use of propolis (Escherichia coli). [44] It seems that its antimicrobial
has been approved in London pharmacies since the 17th activity is due to the flavonoids pinocembrin, galangin,
century, and has been a popular remedy throughout the and pinobanksin.[44,45] Many studies have identified anti-
17th–20th centuries due to its antibacterial properties. inflammatory effects of propolis against both acute and
Propolis is a lipophilic, bitter material that is hard at room chronic inflammation. Rossi et al.[46] and Lee et al.[47]
temperature; when heated, it becomes soft, flexible, and showed that propolis inhibits cyclooxygenase-dependent
sticky. It has a spicy flavor and the color can range from activity. Among the compounds in propolis, CAPE and
yellow and green to red and dark brown depending on the galangin have this effect, but CAPE is more effective
materials used by the bees during its formation. Because and has shown regenerative properties for tissues and
of its waxy nature and physical characteristics, bees use antineoplastic properties against most cancer cells.
this substance to build and repair the hive. It is also used Propolis was also suggested as a feed additive with
as a defense barrier against animals and microbiological promising effect on animal productivity, immunity and
factors.[12] health status.[48,49]

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Recently, some researchers have studied the effect tracked to control and prevent attrition, and participants’
of this substance in the treatment of diabetes. [23,50–60] commitment to the study protocol was verified once a week
However, the effect of propolis on insulin resistance and by phone and once every 3 weeks in person. Supplement
lipid profiles in these studies has rarely been investigated. tablets were distributed to patients every 3 weeks during
Accordingly, the present study aimed to investigate the office visits to reinforce the participants’ adherence to
effects of short-term use of bee propolis supplement on the study protocol; a reminder calendar was given to
fasting blood glucose (FBG), lipid profile and indicators each patient, which they were asked to mark after taking
of insulin resistance in T2D. each pill. Patients were also asked to bring their checked
calendar and empty cans in their next visit. Patients were
2 Materials and methods advised to avoid changing their diet and physical activities
during the intervention period.
2.1 Study design 2.5 Outcome measurements
This was a double-blind, placebo-controlled clinical trial In interviews, we collected participants’ demographic
which lasted one year, from December 2014 to December characteristic, anthropometric measurement and 24-
2015. Both the participants and researchers were unaware hour dietary intake data before and after the intervention.
about the type of consumed supplements. The participants Laboratory analyses of blood characteristics were
were randomly divided into intervention (IG) and placebo performed on fasting samples taken the day after these
groups (PG) using a table of random numbers. interviews marking the beginning and end of the study.
2.2 Inclusion and exclusion criteria To measure the blood variables, 5 mL venous blood was
Included patients had five to ten years history of taken from each individual. The lipid profiles and FBG
T2D and were using the conventional therapy of oral were performed on the day of blood sampling; samples
medications for blood glucose control. Screened patients for serum insulin (SI) levels were stored at –80 °C and
were excluded for any of the following criteria: lack of analyzed at the end of the trial.
desire to continue participating in the study; pregnancy FBG was measured by enzymatic assay and HbA1c
or lactation; insulin injection; underlying diseases was measured following a turbidimetry protocol.
(autoimmune, gastrointestinal, liver, thyroid and unstable Lipid profile data, including total cholesterol (TC) and
heart diseases, etc.); severe respiratory diseases (asthma, triglycerides (TG), were measured using an enzymatic
chronic bronchitis, etc.); taking any vitamin, minerals, or method. LDL was measured using the sedimentation
other nutritional supplements; and allergies to propolis, method. Friedewald formula[61] was used to measure high-
honey or any bee products. density lipoprotein (HDL). Fasting SI was measured with
2.3 Participants enzyme-linked immunosorbent assay kits (PadginTeb Co,
To determine the sample size of the study, we presumed Tehran, Iran). Other insulin resistance indices, including
a significance level (α) of 0.05 and test power of 80% homeostasis model assessment (HOMA-IR), insulin
in order for our analysis to detect a difference of 2 units sensitivity (%S) and β-cell function (%β) and quantitative
of the hemoglobin A1c (HbA1c); according to Murata insulin sensitivity check index (QUICKI) were calculated
et al.,[59] in two groups of previous studies, a sample of using HOMA calculator software (version 2.2.2 by
30 individuals was determined to be necessary. When an Diabetes Trials Unit, University of Oxford, UK) and
attrition rate of 10% was considered, the minimum group standard formulae.[62,63]
size for this study was determined to be 33. Therefore, 2.6 Data analysis
66 patients with T2D were chosen from the Imam Ali and SPSS software (Version 19.0, IBM Corp., USA) was
Yazd Diabetes Research Center, affiliated to the Shahid used for data analysis. The Kolmogrov-Smirnov test
Sadoughi University of Medical Sciences in Yazd. was used at the outset to examine the normality of data.
2.4 Intervention Normally distributed data were tested with paired t-test
Patients in the IG received 300 mg propolis pills, three and Student’s t-test to compare means within and between
times a day, one hour after each meal with a glass of water. groups, respectively. For data that were not normally
Patients in the PG received a daily dose of 3 placebo distributed, the Wilcoxon test and Mann-Whitney test
pills with the same shape, color and size, following the were applied to compare within and between group means,
same protocol as the IG. It should be noted that placebo respectively. The Nutritionist IV (Bruno, CA, USA) was
pills were produced by the same company (Soren Tech used to examine the 24-hour dietary recall data. P-value
Toos, Mashhad, Iran) that manufactured the propolis pills, less than 0.05 was set as the threshold for significance.
containing all the ingredients except the active ingredient 2.7 Ethical considerations
of propolis. Both pills also had very similar packaging. The subject, objectives and methodology of this
The study lasted 12 weeks. Patients were closely study were explained to all patients, and all participants

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taking part in this study signed a consent form. Patients difference.

were assured that they were free to participate in the 3.2 FBG, HbA1c and lipid profiles
study and that their withdrawal would be permitted at Means of the FBG, HbA1c and lipid profile
any time, and not affect their treatment at the Imam Ali characteristics are reported in Table 3. There were no
and Yazd Diabetes Research Center. Supplements had significant differences in these variables between groups at
no side effects and were licensed by the Ministry of the beginning of the study. At the end of the intervention,
Health. Patients’ information was coded, and protected the means of FBG and HbA1c had significantly decreased
from the public eye. The proposal was approved by the in the IG, and there was a significant difference in mean
Ethics Commission of the Department of Research and FBG changes (P = 0.010) between the two groups: the
Technology at Shahid Sadoughi University of Medical mean decrease in FBG of the IG was 17.76 mg/dL, while
Sciences and Health Services of Yazd and archived on the the PG had a mean increase of 6.48 mg/dL. Change in
website of Iranian Ministry of Health (www.irct.ir) with HbA1c was similar to that of FBG.
the proprietary code of IRCT2014080218659N1. The mean TC before and after the intervention
showed no significant difference in the IG, but there
3 Results was a significant increase in the PG (P < 0.001); thus,
the amount of change in TC was significantly different
3.1 Demographic characteristics and dietary intake between the two groups (P = 0.010). The pattern of
Of the 66 patients initially enrolled in the study, 9 change in LDL levels was similar to that found in TC.
withdrew from the study (3 from the IG and 6 from the The mean of HDL in the IG did not change significantly
PG) due to their lack of desire to continue the trial and during the intervention, but it significantly increased post-
initiation of insulin. At the end of the study, 30 patients treatment in the PG (P = 0.020). This change did not result
remained in the IG and 27 patients in the PG. Data from in significant difference between the two groups. There
these 57 patients were analyzed at the end of the twelfth were not significant differences in serum TG or very low-
week (Figure 1). density lipoprotein (VLDL) either between groups or over
Demographic characteristics of both groups at the the course of the study.
beginning of the study are shown in Table 1. As can be 3.3 Insulin resistance indices
seen, qualitative and quantitative characteristics between Kolmogrov-Smirnov test results showed that the
the two groups had no significant differences. Average insulin indices data did not follow a normal distribution.
daily dietary intake and anthropometric indices before Therefore, the medians and percentiles of these variables
and after the intervention are shown in Table 2. As can are reported in Table 4. As it can be seen, the median of
be seen, means between two groups had no significant SI significantly increased in both groups (P < 0.001,

Figure 1 Participant flowchart

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P = 0.003), but there was no significant difference effect on insulin resistance indices.
between groups or their changes in SI over the course of Several studies have been conducted to evaluate the
the study. Insulin resistance data were quite similar to SI. effect of propolis on FBG, and they mostly pointed the
The median of both %S and %β decreased significantly in effectiveness of this substance, findings which were
both over the course of the study; however, there were no consistent with the current study. For example, several
significant differences in those variables between groups researchers have reported that supplementation for different
or their changes. QUICKI mean is reported in Table 5, periods of time as well as with different doses of propolis
with between and within group comparison statistics. The had the same decreasing effect on rats’ FBG.[23,50,54–56,58]
changes of this variable are similar to insulin sensitivity Furthermore, a human study conducted on this subject also
and β-cells performance. reported that supplementation with a mixture of propolis
and mulberry leaf extract reduced FBG significantly.[59]
4 Discussion One mechanism that has been proposed in the
literature suggests that this substance might reduce the
Based on the results of this study, the addition of 3 expression and activity of the glucose-6 phosphatase
propolis pills to the daily medication regimen of T2D enzyme.[52] On the other hand, with the increased activity
patients for 12 weeks can lead to better glycemic control, of glucose transporter 4 in skeletal muscle, glucose
reduction of FBG and HbA1c, and also limit TC and LDL uptake is increased.[53] The 8-week study conducted by
cholesterol increases; however, there was no significant Zhu et al.[55] on diabetic rats showed a 4.8% decrease in

Table 1 Baseline demographic characteristics of the two groups

Variables Propolis group (n = 30) Placebo group (n = 27) P-value

Quantitative variables
　Height (mean ± standard deviation, cm) 164.01 ± 9.42 166.19 ± 7.35 0.32*
　Weight (mean ± standard deviation, kg) 76.00 ± 12.39 75.98 ± 12.37 0.99*
2
　Body mass index (mean ± standard deviation, kg/m ) 28.18 ± 3.64 27.53 ± 4.28 0.53*
　Waist circumference (mean ± standard deviation, cm) 99.11 ± 11.31 99.89 ± 11.11 0.79*
　Age (mean ± standard deviation, years) 51.30 ± 6.57 56.07 ± 9.02 0.02*
　History of disease (mean ± standard deviation, years) 6.06 ± 1.81 6.70 ± 2.58 0.28*
Qualitative variables (n (%))
　Gender
　　Female 17 (56.7) 11 (40.7)
0.230**
　　Male 13 (43.3) 16 (59.3)
　Marital status
　　Single 0 (0.0) 1 (3.8)
0.288**
　　Married 30 (100.0) 26 (96.2)
　Education
　　Elementary 3 (10.0) 5 (18.5)
　　Under high school diploma 12 (40.0) 11 (40.7)
0.516**
　　High school diploma 4 (13.3) 3 (11.1)
　　Academic 8 (26.7) 5 (18.5)
　Occupation
　　Homemaker 15 (5.0) 11 (40.7)
　　Self-employed 9 (30.0) 7 (25.9)
0.685**
　　Employee 2 (6.7) 4 (14.8)
　　Retired 4 (13.5) 5 (18.5)
*: compare propolis group to placebo group’s quantitative variables (P-value, Student’s t-test); **: compare propolis group to placebo
group’s qualitative variables (P-value, Chi-squared test).

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Table 2 Comparison of daily intake mean at the beginning and end of the study in the two groups
Variables Propolis group (n = 30) Placebo group (n = 27) P-value**
Energy (kcal)
　Before 1 671.40 ± 437.02 1 555.40 ± 322.69 0.26
　After 1 686.30 ± 414.89 1 584.18 ± 295.01 0.29
　P-value* 0.53 0.17
Carbohydrate (g)
　Before 248.83 ± 67.84 220.00 ± 61.43 0.10
　After 239.18 ± 66.68 227.84 ± 51.74 0.48
　P-value* 0.13 0.24
Protein (g)
　Before 73.54 ± 26.04 76.72 ± 19.71 0.60
　After 76.48 ± 27.60 79.67 ± 22.19 0.63
　P-value* 0.59 0.45
Fat (g)
　Before 45.83 ± 19.26 45.06 ± 12.05 0.85
　After 47.63 ± 16.77 43.02 ± 12.32 0.24
　P-value* 0.55 0.44
Weight (kg)
　Before 76.00 ± 12.39 75.98 ± 12.37 0.99
　After 75.27 ± 12.19 75.98 ± 12.37 0.83
　P-value* 0.009 0.87
Body mass index (kg/m2)
　Before 28.18 ± 3.64 27.53 ± 4.28 0.54
　After 27.91 ± 3.51 27.52 ± 4.39 0.71
　P-value* 0.01 0.96
Waist circumference (cm)
　Before 99.11 ± 11.31 99.89 ± 11.11 0.79
　After 98.47 ± 11.04 99.80 ± 11.19 0.65
　P-value* 0.15 0.78
Data are expressed as mean ± standard deviation. *: P-value in the same group comparing before to after intervention (paired t-test);
**: P-value between propolis group and placebo group at the beginning or end of the study, respectively (Student’s t-test).

blood glucose among rats receiving bee propolis for 3 HDL. But in study of Li et al.,[50] the administration of
months. In addition to this, using a combination of bee propolis to rats for 10 weeks had no significant effect on
propolis with mulberry leaf extract for 30 d considerably HDL. The propolis used in this study also had no effect on
reduced this index; this reduction was comparable to the triglycerides. In the studies of Fuliang et al.[23] and Tang
effect of acarbose.[59] et al.,[58] both of which were performed on rats, propolis
In fact, it can be concluded that in the current study, the significantly decreased triglycerides, while the results
use of propolis has prevented a significant increase in TC. of Li et al. [50] pointed to a significant increase in this
Other studies have found that propolis supplementation substance.
can actually reduce TC.[23,48,54,55,58] In the case of LDL, no In the present study, prescribed propolis had no effect on
significant increase was observed in IG, while PG showed insulin resistance indices. However, Tang et al.[58] found
significant increase in this variable. The mean difference that propolis supplementation significantly decreased
between the two groups was significant. Hence, it can be the level of serum insulin. Al-Hariri et al. [56] showed
said that taking supplements of this substance can prevent that insulin levels in diabetic rats receiving propolis and
an increase in LDL. Fuliang et al.[23] showed that the use insulin combination therapy, were higher than those
of bee propolis can significantly reduce LDL and increase of rats that just received insulin. Based on the results

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Table 3 Within and between groups comparison of FBG, HbA1c and lipid profile
Variables Propolis group (n = 30) Placebo group (n = 27) P-value**
FBG (mg/dL)
Before 152.20 ± 35.79 159.62 ± 48.20 0.510
After 134.43 ± 33.96 166.11 ± 65.77 0.240
Changes –17.76 ± 27.72 6.48 ± 42.77 0.010
P-value* 0.001 0.430
HbA1c (%)
Before 8.20 ± 1.89 7.95 ± 1.42 0.560
After 7.43 ± 1.29 8.14 ± 1.46 0.050
Changes –0.77 ± 1.34 0.19 ± 1.0 0.004
P-value* 0.004 0.320
Total cholesterol (mg/dL)
Before 164.83 ± 37.40 161.50 ± 35.06 0.730
After 170.00 ± 34.85 190.46 ± 36.38 0.350
Changes 5.16 ± 43.80 28.96 ± 27.41 0.010
P-value* 0.520 < 0.001
LDL (mg/dL)
Before 89.46 ± 30.84 88.71 ± 31.98 0.920
After 97.00 ± 31.41 113.43 ± 35.46 0.070
Changes 7.54 ± 36.87 24.71 ± 25.07 0.040
P-value* 0.270 < 0.001
HDL (mg/dL)
Before 44.26 ± 8.20 41.05 ± 6.54 0.100
After 45.18 ± 10.17 43.38 ± 5.84 0.420
Changes 0.91 ± 5.71 2.33 ± 3.56 0.270
P-value* 0.380 0.020
Triglycerides (mg/dL)
Before 155.38 ± 66.66 158.64 ± 68.85 0.850
After 144.21 ± 44.75 168.20 ± 93.97 0.230
Changes –11.166 ± 65.49 9.55 ± 48.58 0.170
P-value* 0.350 0.310
VLDL (mg/dL)
Before 31.07 ± 13.33 31.72 ± 12.77 0.800
After 28.84 ± 8.95 33.64 ± 18.79 0.210
Changes –2.2 ± 1.30 1.90 ± 9.71 0.180
P-value* 0.350 0.310
Data are expressed as mean ± standard deviation. *: P-value in the same group comparing before to after intervention (paired t-test);
**: P-value between propolis group and placebo group at the beginning or end of the study, respectively (Student’s t-test).
FBG: fasting blood glucose; HbA1c: glycosylated hemoglobin A1c; LDL: low-density lipoprotein; HDL: high-density lipoprotein;
VLDL: very low-density lipoprotein.

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Table 4 Comparison of the median of serum insulin, insulin resistance, insulin sensitivity and β-cell function before and after
intervention in the two groups

Variables Propolis group (n = 30) Placebo group (n = 27) P-value*

Fasting insulin (mU/L)
Before 2.95 (2.90, 4.35) 3.70 (3.00, 4.70) 0.09
After 6.43 (3.56, 10.00) 7.61 (3.10, 10.90) 0.93
P-value** < 0.001 0.003
Changes 1.73 (0.30, 6.66) 1.68 (0.00, 6.20) 0.47
Insulin resistance (%)
Before 0.45 (0.43, 0.62) 0.59 (0.45, 0.66) 0.12
After 0.89 (0.52, 1.45) 1.05 (0.59, 1.47) 0.80
P-value** < 0.001 0.002
Changes 0.22 (0.02, 0.93) 0.18 (0.00, 0.76) 0.68
Insulin sensitivity (%)
Before 220.10 (160.00, 234.70) 170.20 (151.00, 220.40) 0.08
After 112.20 (68.70, 190.50) 95.30 (61.60, 168.40) 0.66
P-value** < 0.001 0.001
Changes –69.55 (–155.22, –12.20) –58.20 (–103.90, 0.40) 0.43
β-cell function (%)
Before 20.80 (14.60, 28.30) 22.10 (13.80, 37.10) 0.82
After 6.43 (3.50, 10.00) 7.61 (3.10, 10.90) 0.32
P-value** < 0.001 < 0.005
Changes 19.00 (5.52, 30.90) 13.00 (–0.10, 24.20) 0.16
Data are expressed as mean (Q25, Q75). *: P-values between propolis group and placebo group before and after intervention,
respectively (Mann-Whitney test); **: P-value in the same group comparing before to after the intervention (Wilcoxon test).

Table 5 Within and between groups comparison of QUICKI

QUICKI
Group
Before After P-value* Changes
Propolis group (n = 30) 0.37 ± 0.03 0.34 ± 0.03 < 0.001 –0.03 ± 0.03
Placebo group (n = 27) 0.36 ± 0.03 0.03 ± 0.33 0.003 –0.02 ± 0.03
P-value** 0.10 0.48 0.29
QUICKI: quantitative insulin sensitivity check index. *: P-value in the same group comparing before to after intervention (paired
t-test); **: P-value between propolis group and placebo group at the beginning and end of the study, respectively (Student’s t-test).

of Zamani et al.,[57] treating diabetic rats with propolis Similar to many pilot projects, our study also had
decreased their serum insulin significantly. As it can be some limitations. For instance, a larger sample size could
seen, results of these studies have been contradictory and demonstrate stronger relationships among response
non-conclusive. In the study carried out by Tang et al.,[58] variables. Similarly, the short intervention period is
insulin resistance was significantly reduced which is in another limitation, as 12 weeks may be enough for
line with the results observed by Kitamura et al.[54] Also, measuring changes in HbA1c. One of the main limitations
in the study of Zamani et al.,[57] the intervention improved may have been the small propolis dose. The doses of
insulin function.[58] In the 8-week study of Fukada et al.,[60] propolis were prescribed based on safe dose of propolis;
which included 80 diabetic patients, supplementation with however, the chosen dose may have been inadequate
propolis reduced insulin resistance. The contradictory to inspire changes in some variables, such as insulin
results of this study and the study carried out by Fukada resistance indices. Finally, more powerful study designs,
et al.[60] could be due to small sample sizes. such as crossover design, could be implemented in future

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This trial showed that, compared with placebo, the 7 Wild S, Roglic G, Green A, Sicree R, King H. Global
daily intake of 900 mg of bee propolis supplement for prevalence of diabetes estimates for the year 2000 and
12 weeks can result in the control of blood glucose projections for 2030. Diabetes Care. 2004; 27(5): 1047–
and some lipid levels in T2D; however, no significant 1053.
effects were observed on parameters related to insulin 8 Toreti VC, Sato HH, Pastore GM, Park YK. Recent progress
of propolis for its biological and chemical compositions and
resistance. Thus, propolis supplements can be useful for
its botanical origin. Evid Based Complement Alternat Med.
treatment of T2D and its complications. 2013; 2013: 697390.
9 Búfalo MC, Candeias JM, Sforcin JM. In vitro cytotoxic
6 Funding effect of Brazilian green propolis on human laryngeal
epidermoid carcinoma (HEp-2) cells. Evid Based
Shahid Sadoughi University of Medical Sciences funded Complement Alternat Med. 2009; 6(4): 483–487.
this work. 10 Castaldo S, Capasso F. Propolis, an old remedy used in
modern medicine. Fitoterapia. 2002; 73(Suppl 1): S1–S6.
11 Mizrahi A, Lensky Y. Bee products: properties, applications,
7 Acknowledgments
and apitherapy. New York: Springer Science & Business
Media. 1997.
The authors would like to thank the Shahid Sadoughi 12 Ghisalberti EL. Propolis: a review. Bee World. 1979; 60(2):
University of Medical Sciences (SSUMS), Yazd for its 59–84.
financial support. All patients who participated in this 13 Burdock GA. Review of the biological properties and
study and also staffs of Yazd Diabetes Research Center toxicity of bee propolis (propolis). Food Chem Toxicol.
are also appreciated. The SSUMS has fully funded this 1998; 36(4): 347–363.
research. Dr Hassan Mozaffari-Khosravi who is a senior 14 Pietta PG, Gardana C, Pietta AM. Analytical methods for
lecturer in Human Nutrition Department at SSUMS quality control of propolis. Fitoterapia. 2002; 73(Suppl 1):
designed and supervised this study. Nazli samadi and S7–S20.
15 Walker P, Crane E. Constituents of propolis. Apidologie.
Masoud Rahmanian participated in case selection and
1987; 18(4): 327–334.
writing the draft of manuscript. Mohsen Askarishahi 16 Bueno-Silva B, Alencar SM, Koo H, Ikegaki M, Silva
facilitated with data analysis and writing the manuscript. GV, Napimoga MH, Rosalen PL. Anti-inflammatory and
Hassan Mozaffari-Khosravi, Masoud Rahmanian and antimicrobial evaluation of neovestitol and vestitol isolated
Mohsen Askarishahi are employed by the SSUMS, but from Brazilian red propolis. J Agric Food Chem. 2013;
Nazli Samadi is MSc student. 61(19): 4546–4550.
17 Lopes AA, Ferreira TS, Nesi RT, Lanzetti M, Pires KMP,
8 Competing interests Silva AM, Borges RM, Silva AJR, Valença SS, Porto LC.
Antioxidant action of propolis on mouse lungs exposed
to short-term cigarette smoke. Bioorg Med Chem. 2013;
None declared.
21(24): 7570–7577.
18 Martin LFT, Rocha EM, Garcia SB, Paula JS. Topical
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