Effects of propolis supplementation on glycemic status, lipid profiles, inflammation and oxidative stress, liver enzymes, and body weight: a systematic review and meta-analysis of randomized controlled clinical trials

Abstract

The aim of meta-analysis was to assess the effects of propolis on markers of oxidative stress, lipid profiles, inflammation and glycemic control, liver enzymes, and weight control. The heterogeneity between the included studies was indicated using the Cochrane’s Q test and I-square (I²) statistic. 14 trials were included in this meta-analysis. Our meta-analysis indicated a significant reduction in fating glucose (WMD: -17.00; 95% CI: −30.88, −3.11), HbA1C (WMD: -0.42; 95% CI: −0.75, −0.10), and insulin (WMD: -1.75; 95% CI: −3.24, −0.26) and a marginally significant reduction in insulin resistance (WMD: -0.60; 95% CI: −1.20, 0.00) following propolis supplementation in 10, 8, 6, and 5 studies, respectively. Pooling 5 effect sizes, a significant reduction was seen in ALT (WMD: -5.63; 95% CI: −10.59, −0.67) and aspartate aminotransferase (AST) (WMD: -3.09; 95% CI: −5.15, −1.03) following propolis. A significant beneficial effect was observed for CRP (WMD: -1.11; 95% CI: −1.92, −0.29), TNF-α (WMD: -6.71; 95% CI: −9.44, −3.98) and interleukin-6 (IL-6) (WMD: -17.99; 95% CI: −35.56, −0.42) concentrations after propolis supplementation. This study demonstrated the beneficial effects of propolis on FPG, HbA1c, insulin, CRP, TNF-α and liver enzymes levels.

Supplementary Information

The online version contains supplementary material available at 10.1007/s40200-020-00696-w.

Introduction

Propolis is a natural material made with honey bees (workers) from gums, blossoms, and plants. After being made with saliva and enzymes secreted by the bee’s salivary glands, it produces a compound and a viscous substance used in the hive [1]. Because of the physical properties and waxy nature of this bee product, propolis is used as cementing substances in the manufacture and repair of beehives. It also acts as a protective barrier against animals and natural agents and antiseptic to preserve the larvae, honey stores, comb from microbial invaders, invaders corpse, hive temperature [2]. Propolis has been widely used by men in traditional medicine to treat wounds, injuries, cancer infection and maintenance of corpses [3]. In Persian Medicine propolis is described as a drug with efficacy against rheumatism, eczemas and myalgia [4].

Propolis has been reported to exhibit diverse roles including anti-inflammatory [5–7], antibacterial [8, 9], antioxidant [9–11], hepatoprotective [12, 13], anti-cancer [9, 14], neuroprotective [15], and immune activity [16, 17]. In limited studies, the effect of propolis on blood pressure has also been evaluated [18, 19]. Recently, Karimian et al. [20] conducted on six RCTs among diabetic patients and indicated that propolis supplementation improved the status of FPG and HbA1c, while did not affect insulin resistance, and insulin status.

Propolis compounds are highly affected by geographical area, environmental factors and beekeeper actions [1]. The main constituents of propolis responsible for biological activity are flavonoids (rutin, quercetin, galangin, CAPE, terpenes, phenols,β-steroids, sesquiterpenes and aromatic [21]. Recently, several human studies have investigated the effect of propolis from different geographical regions on metabolic parameters in different populations. However, existing studies have contradictory results. Discrepancies among evidence might related to difference in the duration of supplementation, source region and dosage of propolis, population characteristics and the sample size of trials. Therefore, with accumulating evidence, the present meta-analysis was conducted to determine the efficacy of propolis on inflammation, glycemic control, oxidative stress, and lipid profiles, liver enzymes, and weight control.

Methods

Current review was done according to the PRISMA directions, except the protocol has not already been registered in the PROSPERO. PRISMA checklist is provided in supplemental Table 1.

This meta-analysis was performed to determine the effects of propolis supplementation on 1) anthropometric measurements: Weight and BMI. 2) Markers of glycemic control: FPG, HOMA-IR, HbA1c. 3) Lipid profiles: total-, HDL, TG, LDL-, and VLDL- levels. 4) Inflammatory profiles: CRP, TNF-a, and IL-6. 5) Oxidative stress markers: TAC, and MDA. 6) Liver enzymes: ALT, and AST. In this study, primary outcomes were FPG and TG.

Search strategy

Search strategy was done using the following text keywords, and MeSH; intervention (“propolis”), and outcomes markers (“FPG” OR “fasting glucose” OR “fasting blood sugar (FBS)” OR “insulin” OR “HOMA-IR” OR “HbA1c” OR “high-density lipoprotein (HDL-cholesterol)” OR “TG” OR “total cholesterol (TC)” OR “LDL-C” OR “low-density lipoprotein (LDL-cholesterol)” OR “HDL-C” OR “VLDL” OR “very low-density lipoprotein” OR “tumor necrosis factor-α (TNF-α)” OR “oxidative stress” OR “C-reactive protein (CRP)” OR “malondialdehyde (MDA)” OR “total antioxidant capacity (TAC)” OR “interleukin-6 (IL-6)” OR “alanine aminotransferase (ALT)” OR “aspartate aminotransferase (AST)” OR “BMI” OR “weight”). In addition, we searched international prospective register of systematic reviews (PROSPERO) database to identify similar records.

Inclusion criteria

RCTs which fulfilled the following criteria were included: 1) Intervention: propolis supplementation. 2) Comparisons: control, including placebo, usual diet/treatment or no intervention. 3) Outcomes: body weight, BMI, glycemic control factors, lipoproteins, liver enzymes, inflammatory biomarkers and markers of oxidative stress. 4) Study design: parallel or cross-over.

Exclusion criteria

Following studies were excluded: in vitro studies, animal experiments, case reports, observational studies, and trials without control group.

Data extraction

Two independent reviewers (JH and EA) screened included articles and extracted relevant information. Any disagreements were resolved by discussion and judgment of the third author (SMM). The following data were extracted: the first authors’ name, publication year, study sample size and location, propolis dosage, study design, type of disease, study duration, mean and SD of markers of glycemic status, inflammation, serum lipoproteins and oxidative stress, liver enzymes and weight control in each groups at baseline and final or mean and SDs of changes in these variables throughout the study.

Statistical analysis

Propolis supplementation on changes in outcomes of interest was calculated using random-effect model and weighted mean difference (WMD) with 95% CI were obtained. Mean/median with SDs of study outcomes were used in our analyses. Therefore, other reports including 95% confidence intervals or SE or interquartile range (IQR) were converted to SDs. Among-study heterogeneity was evaluated using Cochrane’s Q test (P value <0.1 considered as statistically significant) by the I-square statistic [22]. The funnel plot, also the Egger’s regression test were used to evaluate publication bias [23].

Results

Study characteristics

Fourteen studies were included in the current review. Flow-diagram of study selection is presented in Fig. 1. This evidence was published between 2003 and 2019. A total of 812 subjects were participated. General characteristics of included are summarized in Table 1. Evidence was done in Japan, Egypt, China, Iran, Chile, Brazil, and South Korea. Participants were healthy or had type 2 diabetes, chronic periodontitis, chronic kidney disease, athma, and asthenozoospermia. Study duration varied from 4 weeks to 24 months. Body weight, BMI, FPG, insulin,, HbA1C, TC, LDL,TG, HDL, HOMA-IR, CRP, IL-6, TNF-α, MDA, TAC, ALT, and AST were measured in the included studies.

Fig. 1.

Literature search and review flowchart for selection of studies

Table 1.

Characteristics of included studies

Authors (Ref)	Publication year	Sample size (control/intervention)	Country/Population	Intervention (name and daily dose)	Duration	Age (y) (control, intervention)	Presented data
Khayyal et al. [48]	2003	23/22	Egypt/ Mild to moderate asthma	2 mL/d of 13% aqueous extract of propolis solution (260 mg/d)	8 weeks	19–52	IL-6, TNF-α
Fukuda et al. [49]	2015	39/41	Japan/T2DM	226.8 mg/d Brazilian green propolis	8 weeks	62.9 ± 7.8, 63.7 ± 9.3	FPG, Ins, HOMA-IR, HbA1c, TC, HDL-C, LDL-C, IL-6, TNF-α
El-Sharkawy et al. [50]	2016	26/24	Egypt/T2DM + chronic periodontitis	400 mg/d propolis + scaling and root planning	6 months	51.2 ± 6.5, 48.9 ± 8.3	FPG, HbA1c
Zhao et al. [31]	2016	32/33	China/T2DM	900 mg/d Brazilian green propolis	18 weeks	60.8 ± 8.6 59.5 ± 8.0	FPG, Ins, HbA1c, TAC, MDA
Afsharpour et al. [51]	2017	30/30	Iran/T2DM	1500 mg/d Iranian propolis	8 weeks	49.05 ± 8.2, 51.81 ± 6.35	Weight, BMI, FPG, Ins, HOMA-IR, HbA1c, CRP, TNF-α, AST, ALT
Mujica et al. [44]	2017	32/35	Chile/Healthy individuals	13 drops/d propolis	90 days	44.5 ± 13.7, 48 ± 12.1	Weight, BMI, FPG, HOMA-IR, HbA1c, TG, TC, HDL-C, LDL-C, CRP, AST, ALT
Samadi et al. [29]	2017	27/30	Iran/T2DM	900 mg/d propolis	12 weeks	56.07 ± 9.02 51.30 ± 6.57	Weight, BMI, FPG, Ins, HOMA-IR, HbA1c, TG, TC, HDL-C, LDL-C
Zhu et al. [42]	2018	30/30	China/Elderly people living at high altitude	830 mg/d Brazilian green propolis	24 months	73.23 ± 7.32, 72.28 ± 7.23	IL-6, TNF-α, AST, ALT
Gao et al. [32]	2018	30/25	China/T2DM	900 mg/d Chinese propolis	18 weeks	60.6 ± 8.4, 57.7 ± 7.5	FPG, Ins, HbA1c, TAC, MDA
Afsharpour et al. [45]	2019	30/30	Iran/T2DM	1500 mg/d Iranian propolis	8 weeks	49.05 ± 8.2, 51.81 ± 6.35	TAC
Zakerkish et al. [52]	2019	44/50	Iran/T2DM	1000 mg/d Iranian propolis	90 days	54.86 ± 8.89, 55.40 ± 9.09	Weight, BMI, FPG, Ins, HOMA-IR, HbA1c, TG, TC, HDL-C, LDL-C, CRP, IL-6, TNF-α, AST, ALT
Silveira et al. [43]	2019	14/18	Brazil/Chronic kidney disease	500 mg/d Brazilian green propolis	12 months	61.50 ± 10.77, 61.39 ± 10.47	AST, ALT
Gholaminejad et al. [28]	2019	28/29	Iran/Infertile Men with Asthenozoospermia	1500 mg/d Iranian propolis	10 weeks	30 ± 3.96 31.61 ± 4.18	Weight, BMI, CRP, TNF-α, TAC, MDA
Koo et al. [53] (a)	2019	5/10	South Korea/Smokers	600 mg/d propolis	4 weeks	20–28	FPG
Koo et al. [53] (b)	2019	5/10	South Korea/Smokers	180 mg/d propolis +420 mg/d aloe polysaccharide	4 weeks	20–28	FPG

BMI, Body Mass Index; FPG, Fasting Plasma Glucose; HbA1C, Hemoglobin A1C; IR, Insulin Resistance; TC, Total Cholesterol; TG, Triglyceride; LDL, Low Density Lipoprotein; HDL, High Density Lipoprotein; ALT, Alanine Aminotransferase; AST, Aspartate Aminotransferase; CRP, C - reactive protein; IL-6, Interleukin-6; TNF-α, Tumor Necrosis Factor-α; MDA, Malondialdehyde; TAC, Total Antioxidant Capacity

Findings for the effects of propolis on anthropometric measures

Combining 5 effect sizes, we shown no significant effect of propolis on WMD: -0.76; 95% Confidence Interval (CI): −1.90, 0.38] and BMI (WMD: -0.16; 95% CI: −0.54, 0.21) (Fig. 2). Subgroup analyses did not change overall findings (Table 3).

Fig. 2.

Meta-analysis markers of glycemic control, lipid profiles, inflammation and oxidative stress, liver enzymes, and weight control weighted mean difference estimates in the Propolis and control groups (CI = 95%)

Table 3.

Subgroup analyses for the effects of propolis supplementation on study variables

Variables		Subgroups	Number of effect sizes	Pooled WMD	95% CI	I2 (%)	Between-study I2 (%)
Weight	Participants’ age	<50 year	2	−1.10	−2.96, 0.77	00.0	0.65
		≥50 year	3	−0.56	−2.00, 0.88	00.0
	Chronic disease	Yes	3	−0.56	−2.00, 0.88	00.0	0.65
		No	2	−1.10	−2.96, 0.77	00.0
	Study duration	<12 weeks	2	−0.98	−2.70, 0.74	00.0	0.73
		≥12 weeks	3	−0.59	−2.11, 0.94	00.0
	Study sample size	<60	2	−0.90	−2.76, 0.96	00.0	0.85
		≥60	3	−0.68	−2.12, 0.77	00.0
BMI	Participants’ age	<50 year	2	−0.07	−0.66, 0.52	00.0	0.69
		≥50 year	3	−0.22	−0.71, 0.26	00.0
	Chronic disease	Yes	3	−0.22	−0.71, 0.26	00.0	0.69
		No	2	−0.07	−0.66, 0.52	00.0
	Study duration	<12 weeks	2	−0.17	−0.69, 0.36	00.0	0.96
		≥12 weeks	3	−0.15	−0.69, 0.38	00.0
	Study sample size	<60	2	−0.10	−0.67, 0.48	00.0	0.77
		≥60	3	−0.21	−0.70, 0.29	00.0
FPG	Participants’ age	<50 year	4	−18.07	−19.54, −16.60	99.6	<0.001
		≥50 year	6	−5.71	−9.70, −1.73	73.6
	Chronic disease	Yes	7	−16.00	−18.52, −13.47	90.3	0.58
		No	3	−16.85	−18.49, −15.20	99.7
	Study duration	<12 weeks	4	−36.21	−38.60, −33.83	98.4	<0.001
		≥12 weeks	6	−6.74	−8.43, −5.05	96.6
	Study sample size	<60	6	−32.92	−34.90, −30.94	97.5	<0.001
		≥60	4	−1.16	−3.09, 0.76	81.9
HbA1C	Participants’ age	<50 year	2	−0.12	−0.19, −0.05	98.9	0.06
		≥50 year	6	−0.25	−0.36, −0.14	82.0
	Study duration	<12 weeks	2	−0.07	−0.23, 0.09	85.4	0.27
		≥12 weeks	6	−0.17	−0.24, −0.11	95.7
	Study sample size	<60	4	−0.65	−0.80, −0.51	90.7	<0.001
		≥60	4	−0.05	−0.11, 0.02	91.5
Insulin	Study duration	<12 weeks	2	−0.60	−1.37, 0.17	16.0	0.23
		≥12 weeks	4	−0.12	−0.20, −0.05	95.5
	Study sample size	<60	3	−0.12	−0.20, −0.05	95.9	0.03
		≥60	3	−0.95	−1.70, −0.20	87.5
IR	Chronic disease	Yes	2	−0.61	−0.82, −0.40	95.6	<0.01
		No	3	−0.10	−0.34, 0.14	88.5
ALT	Chronic disease	Yes	3	−2.91	−5.76, −0.06	75.3	0.99
		No	2	−2.91	−4.52, −1.29	96.0
AST	Chronic disease	Yes	3	−3.82	−5.84, −1.80	9.9	0.04
		No	2	−1.67	−2.30, −1.04	91.9
CRP	Participants’ age	<50 year	2	−0.64	−0.87, −0.41	95.9	<0.001
		≥50 year	2	−0.002	−0.001, −0.003	98.1
	Chronic disease	Yes	2	−0.002	−0.001, −0.003	98.1	<0.001
		No	2	−0.64	−0.87, −0.41	95.9
	Study duration	<12 weeks	2	−0.002	−0.001, −0.003	97.9	<0.001
		≥12 weeks	2	−0.60	−0.84, −0.35	97.2
TNF-α	Chronic disease	Yes	4	−0.16	−0.39, 0.06	95.6	<0.001
		No	2	−2.32	−2.75, −1.89	97.8
	Study duration	<12 weeks	4	−0.62	−0.82, −0.42	97.8	<0.001
		≥12 weeks	2	−63.05	−75.82, −50.27	00.0
TAC	Study duration	<12 weeks	2	0.71	0.69, 0.73	95.4	<0.001
		≥12 weeks	2	−0.01	−0.03, 0.02	00.0

BMI, Body Mass Index; FPG, Fasting Plasma Glucose; HbA1C, Hemoglobin A1C; IR, Insulin Resistance; ALT, Alanine Aminotransferase; AST, Aspartate Aminotransferase; CRP, C - reactive protein; TNF-α, Tumor Necrosis Factor-α; TAC, Total Antioxidant Capacity

Findings for the effects of propolis on glycemic control

We showed a significant reduction in serum FPG (WMD: -17.00; 95% CI: −30.88, −3.11), HbA1C (WMD: -0.42; 95% CI: −0.75, −0.10), and insulin (WMD: -1.75; 95% CI: −3.24, −0.26) and a marginally significant reduction in HOMA-IR (WMD: -0.60; 95% CI: −1.20, 0.00) following propolis supplementation in 10, 8, 6, and 5 studies, respectively (Fig. 2). These findings remained significant after subgroup analysis in most cases. However, it disappeared in studies with a sample size of ≥60 for FPG, evidence with a duration of <12 weeks or a sample size of ≥60 for HbA1C, evidence with a duration of <12 weeks for insulin, and studies done on individuals without chronic diseases for HOMA-IR (Table 3).

Findings for the effects of propolis on lipid profiles

Our indicated no significant effects of propolis on serum TC (WMD: 4.69; 95% CI: −13.09, 22.48), TG (WMD: 0.05; 95% CI: −11.48, 11.57), LDL (WMD: -0.25; 95% CI: −5.72, 5.23), and HDL (WMD: 3.33; 95% CI: −1.41, 8.07) concentrations (Fig. 2).

Findings for the effects of propolis on liver enzymes

Pooling 5 effect sizes, a significant reduction was seen in ALT (WMD: -5.63; 95% CI: −10.59, −0.67) and AST (WMD: -3.09; 95% CI: −5.15, −1.03) following propolis supplementation (Fig. 2). These findings remained unchanged after subgroup analysis (Table 2).

Table 2.

The effects of propolis supplementation on study variables

Variables	Number of effect sizes	Weighted mean difference	CI 95%	Heterogeneity
				I2 (%)	P- value heterogeneity
Weight	5	-0.76	−1.90, 0.38	00.0	0.97
BMI	5	−0.16	−0.54, 0.21	00.0	0.96
FPG	10	−17.00	−30.88, −3.11	98.8	<0.001
HbA1C	8	−0.42	−0.75, −0.10	94.4	<0.001
Insulin	6	−1.75	−3.24, −0.26	92.7	<0.001
IR	5	−0.60	−1.20, 0.00	92.1	<0.001
TC	4	4.69	−13.09, 22.48	94.8	<0.001
TG	3	0.05	−11.48, 11.57	17.5	0.29
LDL	4	−0.25	−5.72, 5.23	55.9	0.07
HDL	4	3.33	−1.41, 8.07	92.6	<0.001
ALT	5	−5.63	−10.59, −0.67	87.9	<0.001
AST	5	−3.09	−5.15, −1.03	77.1	<0.01
CRP	4	−1.11	−1.92, −0.29	97.2	<0.001
IL-6	4	−17.99	−35.56, −0.42	98.7	<0.001
TNF-α	6	−6.71	−9.44, −3.98	97.8	<0.001
MDA	3	0.15	−1.51, 1.82	54.4	0.11
TAC	4	0.23	−0.25, 0.71	99.8	<0.001

BMI, Body Mass Index; FPG, Fasting Plasma Glucose; HbA1C, Hemoglobin A1C; IR, Insulin Resistance; TC, Total Cholesterol; TG, Triglyceride; LDL, Low Density Lipoprotein; HDL, High Density Lipoprotein; ALT, Alanine Aminotransferase; AST, Aspartate Aminotransferase; CRP, C - reactive protein; IL-6, Interleukin-6; TNF-α, Tumor Necrosis Factor-α; MDA, Malondialdehyde; TAC, Total Antioxidant Capacity

Findings for the effects of propolis on oxidative stress, and inflammation

A significant reduction was found in CRP (WMD: -1.11; 95% CI: −1.92, −0.29), TNF-α (WMD: -6.71; 95% CI: −9.44, −3.98) and IL-6 (WMD: -17.99; 95% CI: −35.56, −0.42) concentrations after propolis supplementation, whereas, we failed to find significant changes in serum status of MDA (WMD: 0.15; 95% CI: −1.51, 1.82) as well as in TAC levels (WMD: 0.23; 95% CI: −0.25, 0.71) by the propolis supplementation (Fig. 2). Subgroup analysis did not change overall findings in most cases, however, propolis had no significant effect on TNF-α concentrations among evidence done on individuals with chronic diseases and it increased TAC levels among studies with a duration of <12 weeks (Table 3).

Discussion

This study was conducted to summarize the results of previous RCTs evaluated the effects of propolis consumption on glycemic and lipid control, inflammatory indicators, parameters of oxidative stress, liver enzymes and some anthropometric variables. This meta-analysis demonstrated the beneficial effects of propolis on FPG, HbA1c, insulin, CRP, TNF-α and liver enzymes levels.

Effects of propolis on weight control

In the present study, after pooling data for propolis administration, no significant effect was found on weight and BMI. Also, in subgroup analyses based on participants’ age, disease, duration and sample size the results did not differ. In accordance with the results of our study, Salehi-Sahlabadimet al. [24] conducted a meta-analysis on five studies and reported that propolis supplementation was not linked to a significant improvement in anthropometric indices. To date, several human RCT studies have indicated that propolis had no effect on weight and BMI [25–29]. However, an experimental investigations has proposed that the administration of propolis could reduce body weight gain in part through the inhibition of repository of visceral adipose tissue via controlling transcription factors like SREBP- 1, and SREBP-2 which are involved in fatty acid [30].

Effects of propolis on glycemic parameters and lipid control

This meta-analysis revealed that the consumption of propolis supplements decreased indices of glycemic control including FPG, HbA1c and insulin levels while did not improve HOMA-IR and parameters of lipid control. Also in subgroup analysis based on the presence of chronic diseases, direction and significance of results did not differ for FPG, while a significant reduction of HOMA-IR was found in individuals with chronic diseases. Similar with our findings, a previous Meta by Karimian et al. [20] conducted on six RCTs among diabetic patients demonstrated that propolis supplementation improved FPG and HbA1c. Another meta-analysis which conducted on five clinical trials revealed that propolis administration led to decreased TG and increased HDL-cholesterol while had no significant effect on other lipid profiles [24]. On the other hand, a trial by Samadi et al. [29], reported that the intake of 900 mg/d propolis during 12 weeks in patients with T2DM significantly decreased FPG, HbA1c, TG, total and LDL-cholesterol, but did not change HDL-cholesterol and insulin resistance indices. However, supplementation with 900 mg/day Brazilian green propolis during 18 weeks significantly did not change insulin, FPG, HbA1C [31]. Also, an 18-week supplementation with 900 mg/day Chinese propolis did not improve glycemic status [32]. It is suggested that possesses the potential to exert glucose-lowering effects due to the excitation of pancreatic β-cells for production of more insulin and increased sensitivity of cells to insulin via increasing insulin receptor number and phosphorylation [25, 33], increased glucose uptake and increased translocation of insulin-sensitive GLUT 4 [34], and down-regulation of genes involved in gluconeogenesis pathway [35]. One of the possible mechanisms for the blood lipid-lowering effect of propolis is the up-regulation of the ATP-binding cassette transporters (ABC) A1 and G1 expression in the liver’s cells that can lead to increase cholesterol efflux, and HDL [36]. On the other hand, propolis could increase the up-regulation of the ABCA1 pathway via stimulation of PPAR gamma, and liver X receptor expression that can lead to reduced cholesterol accumulation in macrophage foam cells [37]. Also, propolis can lower blood TG levels through the improvement of insulin sensitivity and insulin-mediated lipoprotein lipase activity [38].

Effects of propolis on liver enzymes, inflammation and oxidative stress

For control of oxidative stress, inflammation and liver enzymes, diverse approaches have been suggested including the use of various supplements [39, 40].

In this meta, it was indicated that propolis resulted in reduced the status of inflammatory indicators and liver enzymes, but it did not change oxidative stress indices. In line with our findings, a recent study by Shang et al. [41] indicated that propolis supplementation decreased TNF-a, and CRP concentrations. The effects of propolis on parameters of oxidative stress and liver functions have been investigated in several trials. Zhu et al. [42] reported that two years supplementation with 830 mg/d Brazilian green propolis to elderly individuals living at high altitude decreased the levels of liver enzymes. In another study, it was indicated that 12 months supplementation with 500 mg/d Brazilian green propolis prevented the increase in ALT concentrations in CKD patients [43]. In contrast, Mujica et al. [44] found that the administration of 13 drops/d propolis to healthy individuals did not reduce liver enzymes values. On the other hand, two 18-week clinical trials have reported that after the supplementation with 900 mg/d Brazilian [31] and Chines [45] propolis there were no significant changes in TAC, and MDA in diabetic patients. Although, a significant improvement was indicated in the status of oxidative stress indicators in infertile men with asthenozoospermia who received 1500 mg/d Iranian propolis for 10 weeks [28]. Evidence have proposed that propolis administration could alleviate inflammation through the downregulation of NF-κB, and c-Jun-N-terminal kinase and cyclooxygenase 2 expression [21]. In addition, hepatoprotective effects of propolis mainly could be mediated by CAPE which is one of its active components [46]. Although we did not observe any significant effects on TAC and MDA concentrations, propolis is proposed to act antioxidant roles due to high polyphenols content which are capable to inhibiting the formation of ROS, scavenging free radicals, chelating metal ions and exerting synergistic roles with other antioxidants [47].

Strength and limitations

One of the strength of present study is that all included trials were designed as RCTs. In addition, in the present study we conducted certain subgroup analyses to achieve more complete results. First limitations, in this study some of the included trials were conducted on healthy individuals and some others were performed among patients with chronic diseases like diabetes mellitus, which could be a source of heterogeneity. In addition, the number of participants and included studies were middle and intervention period was limited in most of the included studies. Also, due to the other possible sources of heterogeneity including difference in propolis composition in different regions and various doses the results of present study should be interpreted with cautious.

Conclusions

In conclusion, propolis supplementation lowered serum FPG, insulin, HbA1C and also decreased TNF-α, AST, IL-6, CRP and ALT, but did not changed HOMA-IR, stress oxidative biomarkers(MDA,TAC), lipid profiles (TG,HDL-C,LDL-C,TC) and weight parameters (weight, BMI).

Abbreviations

LDL

Low Density Lipoprotein

AST

Aspartate Aminotransferase

FPG

Fasting Plasma Glucose

BMI

Body Mass Index

HbA1C

Hemoglobin A1C

IR

Insulin Resistance

TG

Triglyceride

TC

Total Cholesterol

ALT

Alanine Aminotransferase

HDL

High Density Lipoprotein

IL-6

Interleukin-6

CRP

C-reactive protein

TAC

Total Antioxidant Capacity

MDA

Malondialdehyde

TNF-α

Tumor Necrosis Factor-α

Author contributions

JH and SMM contributed in design, statistical analysis, conception and drafting of the manuscript. AM, VEA, EA and HM contributed in manuscript drafting and data collection.

Funding

IR.QUMS.REC.1398.306.

Data availability

Not applicable.

Compliance with ethical standards

Ethics approval and consent to participate

Not applicable.

Competing interests

No.