Impact of jujube fruit on serum lipid profile, glycemic index, and liver function: a systematic review and meta-analysis

Abstract

Jujube is a widely consumed fruit with a long history in traditional medicine. Numerous studies have explored its potential effects on various health parameters. However, the overall quality of this evidence and the specific impact of jujube on metabolic syndrome remain unclear. This meta-analysis investigates the effect of jujube on body mass index, serum lipid profile, blood sugar levels, and other metabolic factors and blood indicators. The databases Web of Science, Scopus, PubMed, Google Scholar, and SID were searched up to September 2023. Our review included various clinical studies written in English and Persian that focused on the effect of jujube on lipid profiles. In vivo, in vitro, review studies, book chapters, observational studies, and low-quality studies based on critical appraisal tools were excluded from the analysis. A total of seven studies involving 483 participants were included in this review. Jujube significantly reduced BMI and TG, and also markedly decreased FBS in subjects with type 2 diabetes. Furthermore, the results varied significantly based on subgroups defined by dosage, treatment duration, and disease type. Notably, LDL and total cholesterol levels showed a significant decrease within some of these subgroups. However, HDL, AST, and ALT did not have significant changes. The findings suggest that jujube may exert beneficial effects on metabolic diseases, particularly in patients with hyperlipidemia and type 2 diabetes. However, the overall quality of the evidence is limited, and further research is needed to confirm these findings and elucidate the mechanisms underlying jujube’s effects.

Impact of jujube fruit on serum lipid profile, glycemic index, and liver function: a systematic review and meta-analysis.

Introduction

Cardiovascular disease (CVD) is the leading cause of death among adults in the United States, people with hyperlipidemia are at higher risk of stroke and cardiovascular diseases. Therefore, early diagnosis and treatment are considered to be essential in order to reduce the risk of cardiovascular events and early death [1]. Blood lipids, including cholesterol, triglycerides, and lipoproteins, play a crucial role in the structure and function of cells and tissues throughout the human body [2]. These essential components are necessary for synthesizing cell membranes, hormones, vitamins, and other compounds. However, excessive increases in blood lipids can lead to blood clotting and arterial blockage, resulting in serious health issues such as cardiovascular diseases, including atherosclerosis [3].

Today, various drugs such as statins, fibrates, and nicotinic acid are used as effective methods to reduce blood lipid levels. Statins play a pivotal role in managing of blood cholesterol levels by primarily targeting the HMG-CoA enzyme, thereby diminishing cholesterol synthesis within the liver [4]. Studies have shown that intervention programs leading to reduced serum lipid levels decrease the risk of coronary artery problems and promote the analysis of atherosclerotic plaques in coronary arteries [5]. Statins are the primary treatment for hyperlipidemia. However, limitations of statins, including treatment resistance, intolerance due to side effects, and non-adherence, lead to poor outcomes. Therefore, many patients require adjunctive therapies such as niacin, bile acid sequestrants, fibric acids, and ezetimibe for proper hyperlipidemia control [6]. Treatment and management of hyperlipidemia mainly involves continuous lipid lowering using various therapeutic drugs such as statins, fibrates, bile acid sequestrants, and niacin. However, various reviews have shown that the efficacy of these drugs can be questioned and debated due to numerous adverse effects [7].

Ziziphus Jujuba (jujube), is an edible medicinal plant belonging to the Ramnaceae family. This plant is cultivated in various regions worldwide, including the Mediterranean region and Southern European countries such as Spain, Greece, and Cyprus. In Iran, jujube is abundant and widely used [8]. In addition to its favorable effects on the lipid profile, jujube has also been shown to be effective in reducing liver enzyme levels and blood glucose [9].

Numerous studies have investigated the presence of a diverse range of chemical compounds in jujube. It has been revealed that jujube fruit is rich in carbohydrates, fiber, protein, fats, essential vitamins, and minerals. Compared to its stems, roots, and leaves, jujube fruit contains higher levels of vitamins A and C and is rich in linoleic acid. Additionally, flavonoids, triterpenoids, alkaloids, saponins, sterols, and lactic acid have been identified in jujube fruit, which possess strong antioxidant properties that may have beneficial effects on human health [10].

These antioxidant compounds protect body cells against oxidative damage and may help reduce the risk of heart diseases, cancer, and chronic inflammations. Jujube is also abundant in fiber, which can improve the digestive system, reduce blood sugar levels, and control weight [11].

Animal and human studies have indicated the effect of Z.Jujube on regulating blood lipid metabolism. Jujube increases adiponectin levels, which can have significant effects on lipid metabolism, appetite control, and reducing blood sugar levels [12]. Furthermore, in animal studies, a combination of jujube, dandelion, and silymarin on non-alcoholic fatty liver disease has led to reduced liver enzymes and lipid profiles and induced hepatic histological changes [13].

Jujube has been identified in previous studies as a promising natural remedy with wide availability, multiple therapeutic benefits, and a consistent safety profile. Consequently, due to the lack of a high-quality systematic review on the effect of jujube fruit consumption on reducing human blood lipids and other metabolic factors, we decided to design this study with the aim of investigating this issue in detail.

Methods

Literature eligibility

This study presents a systematic review of scientific studies on the effect of jujube on reducing lipid profiles conducted in 2023. Various clinical studies focusing on the effect of jujube on lipid profile, which were written in English and Persian, were included in our review. In-vivo, in-vitro, review studies, book chapters, observational studies (case reports, case-control, cohort, and cross-sectional studies), and studies with low quality (based on critical appraisal tools) were excluded from the study.

All experimental studies that included healthy individuals or those with metabolic diseases of different ages, genders, and ethnicities who used various jujube products with different doses were included in the study. In the experimental group, participants were administered jujube in different dosage forms, including powder, tablets, or decoctions, either singly or in combination with other botanicals, at varying dosages of jujube fruit. The control group comprised individuals undergoing standard therapy or receiving a placebo, as well as healthy individuals who did not receive any treatment, all of whom were included in the research study.

Literature search and study selection

The English databases Scopus, PubMed, Web of Science, and Google Scholar, as well as gray literature, and the Persian database SID, were evaluated up to September 2023. Keywords obtained from Mesh search were selected, and the search strategy was formulated based on these keywords. Two researchers independently conducted searches in the titles and abstracts using the following search strategy:

((“Ziziphus jujuba”) OR (“ziziphus jujube”)) OR (jujube)) OR (“ziziphus vulgaris”)) OR (ziziphus)) OR (jujubes)) OR (“jujube seed”)) OR (“jujube fruit”)) OR (“Ziziphus extract”)) AND (((((((((((((((((((((((“lipid profile”) OR (cholesterol)) OR (triglyceride)) OR (“high-density lipoprotein”)) OR (“low-density lipoprotein”)) OR (ldl-c)) OR (hdl-c)) OR (tg)) OR (tc)) OR (ldl)) OR (hdl)) OR (dyslipidemia)) OR (hyperlipidemia)) OR (lipids)) OR (“lipid level”)) OR (“cardiometabolic factors”)) OR (dyslipoproteinemias)) OR (dyslipoproteinemia)) OR (dyslipidemic)) OR (hyperlipidemic)) OR (hyperlipemias)) OR (lipidemia)) OR (lipidemias)).

After removing duplicates, the articles were initially screened by two independent reviewers based on title and abstract. Full texts of the remaining studies were then assessed against the eligibility criteria. Following that, the references of the included articles were examined to find potentially related studies.

Data extraction

In the review process, two independent reviewers (M.A. and M.R.) extracted relevant characteristics from the included studies using a standard extraction form. The reviewers were aware of the authors’ names, institutions, and publication journals. Any discrepancies in data extraction between the first two reviewers were resolved by a third reviewer (H.Sh.). Subsequently, the extracted information was entered into an Excel sheet. The extracted information from each study is as follows: Author’s last name, publication year, implementation area, study design, the sample size in intervention and control groups, the dosage and duration of medication, mean or median age of the studied population, and the mean and standard deviation of study outcomes.

The primary outcome, including changes in lipid profiles and weight changes, was assessed based on blood test results and BMI measurements. Other metabolic and blood indicators such as blood sugar and liver enzymes were considered as secondary outcomes.

Study quality assessment

For critical review of the studies and the risk of bias, we used the Rob 2 tool published by Cochrane. This tool examines the studies from five aspects (randomization process, deviations from intended interventions, missing outcome data, measurement of the outcome, selection of the reported result), in each part the articles quality are scored with words (high, low, some concerns) to finally determine the degree of study bias.

Two independent researchers (M.A. and M.R.) used the Cochrane Collaboration’s Risk of Bias Assessment tool for critical appraisal of studies, and studies deemed low quality by consensus were excluded from the study. In case of disagreement between the two researchers, the study was reviewed by the third researcher (H.Sh.).

Data synthesis and statistical analysis

Data were pooled using the random-effects model of restricted maximum likelihood (REML) estimator for variance estimation. The variability among the studies was measured by I² value and assessed visually through forest plots and statistically via the chi-square-based Q statistic. Significant heterogeneity was defined as a p-value of <0.10 in the Q-test or I² > 50%. A meta-analysis was conducted to determine the impact of Jujube on serum lipid profile, glycemic index, and liver function. Subgroup analyses were conducted to assess the impact of Jujube Fruit on serum lipid profile, glycemic index, and liver function, taking into account relevant study characteristics such as type of disease, duration of medication, and Jujube dosage as potential sources of heterogeneity. Publication bias was statistically assessed by conducting Egger’s regression test to detect plot asymmetry. The results of publication bias were further validated by constructing a trim and fill counter-enhanced funnel plot. This method allowed for the identification and correction of any potential asymmetry in the funnel plot, providing a more accurate representation of the data and reducing the impact of publication bias on the overall results. Statistical analyses were performed using Stata software. (Version 17.0) (Stata Corp, College Station, Texas).

Results

Features of the included studies

During the database search, a total of 1015 articles were retrieved. After eliminating duplicates and non-trial articles, the titles and abstracts of 630 articles were screened. Ultimately, seven studies were included in the present review, as depicted in Fig. 1.

Fig. 1.

Flow chart of study selection for inclusion trials in the systematic review.

Based on Table 1, there has been an increased focus on the impact of jujube on controlling blood lipids and other blood metabolites in recent years. All studies were clinical trials, with one being a triple-masked study, three being double-blind, and three being other clinical trials (CT) without blinding. Three studies were conducted on diabetic patients, two studies on individuals with lipid disorders, one study on hypertensive individuals, and one on individuals with different BMI levels. The sample size of the studies ranged from 36 to 110 participants, which were conducted in different age groups. Out of the seven studies identified, five were carried out in Iran, one in Syria, and one in Pakistan. Various jujube species products, such as syrup, decoction, and powder, were used in the intervention groups, with six studies using the Zizphus jujuba species and one study using the Zizphus vulgaris species. In the control group, three studies used a placebo, one used routine treatment, one used standard treatment, and one used nutrition as the control. Among the studies, one study examined the effect of jujube on different groups with different body masses and doses, leading to six comparison scenarios based on different body masses and doses received. The duration of assessment and follow-up in the studies varied from a minimum of 4 weeks to 12 weeks, with jujube doses administered one to three times daily.

Table 1.

Systematic review of articles.

Author (Year)	Type of study	country	Age (Years)	Disease	Sample Size	Intervention(dose of medication) Times per day	Control(dose of medication) Times per day	Duration treatment	Study Outcomes
Mostafa, U. E. S(2013) [14]	CT	Syria	20 to 57	Healthy	83 people	zizphus jujube(5/15/30gr)	zizphus jujube(5/15/30gr)	2 months	BMI AST CHOL ALT TG LDL HDL
Ali Mohammad Sabzghabaee(2013) [15]	triple-masked placebo-controlled	Iran	12 to 18	Dyslipidemia	70 people	zizphus jujube(5gr) 3 times	placebo powder(5gr) 3 times	1month	BMI FBS CHOL TG LDL HDL
Zeinab Yazdanpanah(2017) [16]	parallel-group randomized controlled clinical trial	Iran	older than 30	diabetes type 2	110 people	Diet + zizphus jujube(10 g/100 mL) 3 times	Diet only -	12 weeks	CHOL FBS TG LDL HDL
KHALID NIAZ(2019) [17]	CT	Pakistan	20 to 60	Hyperlipidemia	60 people	zizphus jujuba	Rusvastatin (10 mg daily)	2 months	LDL HDL
Zahra Irannejad niri(2021) [8]	double-blind randomized placebo-controlled clinical trial	Iran	20 to 65	diabetes type 2	76 people	zizphus vulgaris(30gr) 2 times	placebo powder	12 weeks	BMI AST CHOL ALT TG FBS LDL HDL
Hossein Farhadnejad(2022) [18]	double-blind randomized controlled trial	Iran	30 to 65	diabetes type 2	48 people	zizphus jujube(15gr) 2 times	Routine treatment	12 weeks	BMI FBS CHOL TG LDL HDL
Davoud Hasani(2022) [19]	double-blind randomized placebo-controlled clinical trial	Iran	30 to 75	hypertension	36 people	zizphus jujube+ thymus(5 ml syrup) 2 times	Sucrose syrup	8 weeks	AST ALT CHOL LDL HDL

Among the seven articles, all studies examined lipid profiles including cholesterol, triglycerides, HDL, and LDL except for one article that only focused on HDL and LDL. In addition to lipid profile assessment, four studies also investigated body mass index.

Alongside the primary outcomes of the project, we explored into examining liver enzymes and blood glucose as secondary outcomes of the project, which were investigated in three studies related to blood glucose and three studies related to liver enzymes.

Risk of bias assessment

Overall, in six studies, the risk of bias was low, and in one study, the risk of bias was unclear. Four studies reported randomization, two studies had unclear randomization, and one study did not have randomization. Among the seven studies, only one study did not report deviation from the intended intervention and adherence to the intervention. In evaluating other aspects of bias risk, all were clear and without bias (Figs. 2, 3).

Fig. 2.

Article risk of bias assessment with RoB2.

Fig. 3.

Risk of bias analysis.

Effect of intervention on primary outcome

Primary outcome

BMI

In three studies [9, 14, 15], the effect of jujube consumption on body mass index (BMI) was investigated, with the analysis results (Fig. 4) indicating a significant effect of jujube consumption on reducing BMI (MD-1.18, 95% CI −1.63 to −0.74). In one study [14], patients with hyperlipidemia were followed up for one month, receiving 5 grams of jujube every 12 hours. However, in two other studies [9, 15], patient follow-up continued for up to three months, and these patients had diabetes. In one study, they received 15 grams of jujube, and in another study, they received 30 grams of jujube.

Fig. 4.

BMI meta-analysis.

It is shown in the funnel diagram that despite the fact that the studies were found with low accuracy, but the symmetry in the diagram indicates that the studies with positive and negative results were reported (Fig. 5).

Fig. 5.

Funnel plot of BMI studies.

CHOL

Among the studies found, one study [16] was examined in a systematic review due to the lack of comparison and report of the results of the control group, but was not included in the meta-analysis. In this study, jujube consumption was not effective in reducing blood lipid factors. Five studies examined and analyzed cholesterol results, including one study [17] that involved three different groups compared under different doses. For ease of analysis, this study was divided into six sections and analyzed accordingly. Overall, jujube consumption did not show a significant effect on reducing cholesterol (MD-2.44, 95% CI-5.49 to 0.61) (Fig. 6). However, upon further analysis after excluding one of the articles [17] from the analysis, significant reductions in cholesterol levels were observed in subgroup analyses focusing on the specific diseases for which jujube was employed as a treatment. Jujube consumption has been successful in reducing cholesterol in patients with hyperlipidemia [14] and diabetes (MD-1.30, 95% CI-2.55 to -0.05) [9, 15, 18]. Treatment in diabetic patients lasted for three months, while the treatment duration in hyperlipidemic patients was one month, and in these subgroups, the analysis results showed the effectiveness of jujube. After examining the dosage in studies, the effectiveness of jujube in reducing cholesterol was shown to be dose-dependent, with doses higher than 30 grams being effective (Fig. 7).

Fig. 6.

Cholesterol meta-analysis.

Fig. 7.

Cholesterol meta-analysis in subgroups.

The funnel plot for cholesterol shows that there is a publication bias because the plot is not symmetrical. Studies are also outside the confidence interval of funnel (Fig. 8).

Fig. 8.

Funnel plot of cholesterol studies.

HDL

Six studies [9, 14, 15, 17–19] were reviewed to assess the impact of jujube on high-density lipoprotein (HDL) levels. The overall analysis (Fig. 9) demonstrated that jujube supplementation did not significantly increase HDL levels (MD-1.66, 95% CI −2.99 to −0.41). However, subgroup analyses (Figs. 10, 11) stratified by treatment duration and underlying medical conditions suggested a notable increase in HDL levels with jujube consumption exceeding three months and in participants with diabetes (MD-0.32, 95% CI 0.07 to 0.58).

Fig. 9.

HDL meta-analysis.

Fig. 10.

HDL meta-analysis in treatment duration subgroups.

Fig. 11.

HDL meta-analysis in disease type subgroups.

A HDL funnel plot shows non-normality and publication bias, which, according to the shape of the plot, identifies publication bias and studies with small sample sizes (Fig. 12).

Fig. 12.

Funnel plot of HDL studies.

LDL

Six studies [9, 14, 15, 17–19] examined the effect of jujube on low-density lipoprotein (LDL). In the overall analysis (Fig. 13), it was determined that jujube does not affect on reducing LDL (MD3.99, 95% CI-2.53 to 10.51). However, upon further analysis of subgroups (Figs. 14, 15) related to treatment duration and diseases for which jujube was used in treatment, it was found that jujube reduces LDL levels when used for three months and in diabetic patients (MD-1.59, 95% CI-2.99 to -0.28).

Fig. 13.

LDL meta-analysis.

Fig. 14.

LDL meta-analysis in treatment duration subgroups.

Fig. 15.

LDL meta-analysis in disease type subgroups.

In examining the funnel plot of LDL, we observed that the funnel is narrow, indicating that most studies have similar sample sizes. Additionally, the funnel is asymmetric, suggesting the presence of publication bias (Fig. 16).

Fig. 16.

Funnel plot of LDL studies.

TG

Five studies [9, 14, 15, 17, 18] examined the effect of jujube on triglycerides (TG) (Fig. 17). Among them, one study [17], which was divided into six parts, provided conflicting information about the effect of jujube. However, four other studies indicated that jujube consumption can be effective in reducing triglyceride levels. Ultimately, the meta-analysis showed that jujube consumption is effective in reducing triglyceride levels (MD-1.87, 95% CI-3.22 to −0.53).

Fig. 17.

TG meta-analysis.

The effect of jujube on triglyceride reduction in different subgroups was investigated, as shown in the following Figs. 18 and 19.

Fig. 18.

TG meta-analysis in disease type subgroups.

Fig. 19.

TG meta-analysis in treatment dosage subgroups.

The funnel plot of TG indicates the presence of publication bias, as well as includes studies with small sample sizes (Fig. 20).

Fig. 20.

Funnel plot of TG studies.

Secondary outcome

AST

Three studies [9, 16, 17] examined Aspartate transaminase (AST) levels, among which two studies had complete data for analysis. Therefore, one study [16] was excluded. Additionally, one study had zero values for AST, and parts of it were removed from the analysis. In the remaining studies, the investigation of jujube’s effectiveness in reducing AST levels showed a reduction in one study, while conflicting information was observed in another study. Overall, meta-analysis showed (Fig. 21) that jujube does not significantly affect AST reduction (MD-0.26, 95% CI-1.95 to 1.44).

Fig. 21.

AST meta-analysis.

In one study, a daily dose of 60 grams of jujube showed significant effects, while another study found no significant effects at lower doses (Fig. 22).

Fig. 22.

AST meta-analysis in treatment dosage subgroups.

The AST funnel plot exhibits asymmetry and indicates publication bias, which may make cloud conclusions (Fig. 23).

Fig. 23.

Funnel plot of AST studies.

ALT

In one study [16], the effect of jujube on ALT was investigated, which did not show a significant effect, and this study was not included in the meta-analysis. One study [17] presented conflicting information regarding the effect of jujube on Alanine transaminase (ALT) reduction, while another study [9] demonstrated a significant effect of jujube on reducing ALT. Meta-analysis (Fig. 24) indicated that jujube consumption is not effective in reducing ALT (MD-0.13, 95% CI-1.41 to 1.14).

Fig. 24.

ALT meat-analysis.

FBS

Four studies [9, 14, 15, 18] evaluated the effect of jujube on reducing fasting blood sugar (FBS) levels. One study [14] demonstrated an inverse and elevating effect of jujube on controlling FBS, while three studies [9, 15, 18] showed a significant reduction in FBS (MD-0.94, 95% CI-3.04 to 1.16). Due to jujube. However, meta-analysis (Fig. 25) did not reveal a significant effect on reducing FBS. In subgroup analysis (Fig. 26), one study investigated the impact of jujube on hyperlipidemic patients, which did not show a significant reduction in FBS. Three studies examined the effect of jujube on diabetic patients, all of which demonstrated a significant reduction in FBS. This effect may be attributed to the longer follow-up periods in these studies.

Fig. 25.

FBS meta-analysis.

Fig. 26.

FBS meta-analysis in treatment duration subgroups.

The funnel of FBS shows the asymmetry and publication bias. Most of the points are on the left side of the graph, which can be concluded that the sample size is small and also shows studies are also outside the confidence interval of funnel (Fig. 27).

Fig. 27.

Funnel plot of FBS studies.

Discussion

This meta-analysis included a diverse group of clinical trials (n = 7) investigating jujube’s impact on blood lipids and other metabolites. Blinding methods varied across studies, with some employing triple-masking or double-blinding for more robust results and other studies had no blindness. Among the unblinded studies, two studies by Mustafa and Khalid, which lacked blinding, influenced the overall results of the meta-analysis and affected the findings of other studies.

Participant conditions ranged from diabetes and lipid disorders to hypertension and varying BMIs, potentially influencing outcomes. One study investigated the effect of jujube on individuals with different BMIs. Two studies were conducted on hyperlipidemic patients, one on hypertensive patients, and three on diabetic patients. In all analyses performed, the effect of jujube on diabetic patients was significant, but this was not the case in other studies. This could be due to the number of studies conducted or the specific effect of jujube on diabetic patients.

Assessment durations varied from 4 to 12 weeks, with jujube administered one to three times daily. Studies in which jujube was administered for three months showed significant results for all parameters, indicating the impact of treatment duration on the effectiveness of this therapeutic model.

Out of the seven studies identified, five were carried out in Iran, one in Syria, and one in Pakistan. It is noteworthy that all included studies were conducted within the Middle Eastern region, specifically in Iran, Syria, and Pakistan. Given the well-documented influence of cultivation region on the chemical composition of Ziziphus jujuba plants, this geographical clustering of studies could potentially impact the quality of the plant material used [20].

While all studies examined lipid profiles (except one focusing solely on HDL/LDL), some additionally explored other outcomes like body mass index, blood glucose, and liver enzymes.

Meta-analysis indicated that jujube was not effective in reducing cholesterol overall. However, subgroup analysis excluding the study by Mustafa, which included individuals with different BMIs, showed significant effects in subgroups of diabetic and dyslipidemic patients. In the diabetic patient group, which included three studies, the effect of jujube was significant. The two other subgroups each included one study, which emphasizes the importance of analyzing the effect of jujube in the diabetic patient group. Moreover, it was revealed that the effect of this plant on cholesterol reduction is dose-dependent, with a significant impact observed at a daily intake of over 30 grams of jujube. Previous animal studies have reported the efficacy of jujube extract in reducing blood cholesterol in rats [21, 22].

The overall analysis demonstrated that jujube supplementation did not significantly increase HDL levels. Interestingly, a decrease in HDL levels was observed. However, subgroup analyses revealed potential moderating factors. Specifically, analyses stratified by treatment duration and underlying medical conditions suggested a notable increase in HDL levels with jujube consumption exceeding three months and in participants with diabetes. In a study on diabetic mice, the effects of jujube, barberry, and saffron extracts were separately evaluated on blood sugar and lipid reduction. In this study, only jujube extract at doses of 25 and 100 mg/kg caused a significant increase in HDL but did not affect on reducing cholesterol and LDL [12].

Based on the analysis of the findings, jujube does not reduce LDL. Some animal studies also reported no effect of jujube on LDL reduction in rats [12, 23]. However, subgroup analysis showed that increasing the treatment duration to three months in diabetic patients resulted in the effectiveness of jujube in reducing LDL. Another animal study has shown the efficacy of an aqueous extract of jujube in reducing blood cholesterol and LDL in hyperlipidemic rats [22].

A study was conducted in healthy individuals, one study in individuals with high triglycerides, and three studies in individuals with diabetes. Subgroup analysis showed that jujube is effective in lowering triglycerides in individuals with diabetes. The results also showed that the significant effect of jujube occurs at doses of 30 and 60 grams per day, and lower doses are not effective in reducing TG. The effects of Zizyphus jujube and Zizyphus spina christi on lipid profiles in diabetic and non-diabetic rats were investigated separately in a study. In this study, both jujube and Christ’s thorn jujube extracts led to a reduction in total cholesterol and triglycerides [24]. Other animal studies have also confirmed the effect of jujube on reducing triglycerides [22].

In a study investigating the effect of jujube on liver enzymes, no significant effect was found on the reduction of ALT and AST levels. However, in animal studies, jujube has led to a significant reduction in these enzymes [21, 24].

Overall analysis did not show a significant effect of jujube on blood sugar reduction, but subgroup analysis showed that jujube is effective in reducing fasting blood sugar in diabetic individuals [12, 25].

In the present meta-analysis, we assessed the presence of publication bias using funnel plots for various outcomes, including CHOL, TG, LDL, HDL, FBS, and BMI. The visual inspection of the funnel plots revealed a noticeable asymmetry in all examined parameters, indicating a potential issue with publication bias. This bias can lead to a misestimation of the true effect size and compromise the validity of the meta-analysis findings. The asymmetry observed in the funnel plots may be due to several reasons: 1) Small study effects: smaller studies tend to show larger effect sizes, potentially due to methodological limitations or random variability. 2) Heterogeneity: differences in study populations, intervention protocols, so the presence of asymmetry and publication bias should be considered when interpreting the findings of this meta-analysis. 3) Studies with significant or positive results are more likely to be published than those with non-significant or negative results. Therefore, we need future research to gain a broader perspective on this issue.

Advances in the prior systematic review

At the time of the commencement of the search for this study, no systematic review article was available. However, during the final stages of writing this article, a systematic review-meta-analysis article was found. This article included four RCT studies, and its search date was up to October 2022. The parameters they investigated only included lipid profile and blood glucose measurements. They also searched only English databases [26]. While our systematic review and meta-analysis included seven CT studies with a search date up to September 2023, the parameters investigated in our study included BMI, TG, Chol, LDL, HDL, FBS, AST, and ALT. We also only searched English and Persian databases. Our study encompasses an examination of various subgroups, including an analysis of the administered dosages, the duration of treatment, and the underlying medical conditions of the participants.

Limitations of this review

First, the small number of studies included in this review was our largest limitation. Due to the small number of included studies, the studies that could be included in the meta-analysis are highly restricted. Second, the risk of bias assessment was unclear in some of the included studies. Third, lack of access to all scientific databases for a more comprehensive search. Fourth lack of diversity in jujube harvest geographic regions hinders the provision of more comprehensive information.

Future prospective

Further RCTs are needed to investigate the effects of jujube on blood factors. It is recommended to conduct clinical trials using jujube samples from different geographical locations. Moreover, the duration of clinical studies should be extended.

Conclusions

Although a moderate volume of evidence is available investigating the efficacy of jujube use for blood metabolic factors, these findings should be interpreted with caution, given the low quality of the evidence base due to clinical and methodological heterogeneity, high risks of publication bias, poor reporting, and statistical issues. However, jujube appears to be useful for metabolic syndrome; it therefore could be used as a nutraceutical option or add-on therapy in the treatment of metabolic disorders.

Author contributions

Mostafa Ahmadi: Data curation; investigation; methodology; writing – original draft; writing – review and editing. Seyyed Ali Mozaffarpur: Data curation; investigation; writing – review and editing. Hoda Shirafkan: Formal analysis; methodology; writing – review and editing. Maedeh Rezghi: Data curation; investigation; supervision; writing – original draft; writing – review and editing.

Data availability

Data sharing is not applicable to this article as no datasets were generated during the current study.

Competing interests

The authors declare no competing interests.