Clinical evidence of sesame (Sesamum indicum L.) products and its bioactive compounds on anthropometric measures, blood pressure, glycemic control, inflammatory biomarkers, lipid profile, and oxidative stress parameters in humans: a GRADE-assessed systematic review and dose–response meta-analysis

Abstract

This comprehensive systematic review and meta-analysis aimed to assess the impact of sesame (Sesamum indicum L.) supplementation on cardiovascular disease risk factors. Relevant research was discovered via PubMed, Scopus, Web of Science, CENTRAL, and EMBASE up to June 2024. The assessment of study quality was conducted using the Cochrane risk-of-bias tool. Thirteen trials, with interventions ranging from 4 to 12 weeks and involving 521 participants, demonstrated significant reductions in glycated hemoglobin (HbA1c) (Standardized Mean Difference [SMD] = − 0.67; 95% Confidence Interval [CI] − 1.01, − 0.32; P < 0.001), C-reactive protein (CRP) (SMD = − 0.51; 95% CI − 0.96, − 0.05; P = 0.028), and interleukin-6 (IL-6) (SMD = − 0.74; 95% CI − 1.16, − 0.32; P < 0.001), and a marginally significant effect on fasting blood sugar (FBS) (SMD = − 0.57; 95% CI − 1.16, 0.02; P = 0.057). Subgroup analyses revealed that sesame supplementation significantly reduced CRP and malondialdehyde (MDA) in populations without chronic diseases, while total cholesterol (TC) and MDA were reduced in those with chronic diseases. MDA was significantly reduced in females, especially those aged 50 or older. At dosages of 10 g per day or less, CRP, high-density lipoprotein cholesterol (HDL), and TC showed significant improvements. Meta-regression highlighted a significant dose-dependent reduction in TC levels at 10 g/day, and a significant duration-dependent decrease in TG levels at 8 weeks of supplementation. Sesame supplementation demonstrates potential benefits in improving glycemic control, inflammatory markers, and lipid profiles, making it a promising adjunct therapy for reducing cardiovascular disease risk factors.

Graphical abstract

Supplementary Information

The online version contains supplementary material available at 10.1186/s12986-025-00910-7.

Introduction

Cardiovascular disease (CVD) encompasses a variety of conditions that impact the heart and blood vessels, such as hypertension, coronary heart disease, cerebrovascular disease, heart failure, and associated ailments [1]. CVD stands as a prominent cause of mortality on a global scale, representing a third of all worldwide deaths in 2021, totaling 20.5 million lives lost [2, 3]. Diet plays a crucial role in the prevention, management, and treatment of CVD [4, 5]. Research highlights the importance of dietary components such as polyunsaturated fatty acids (PUFAs), monounsaturated fatty acids (MUFAs), dietary fiber, antioxidants, and phytochemicals found in oils like sesame oil as potential contributors to reducing the risk of chronic diseases, including CVD and metabolic disorders [6, 7].

Sesame (Sesamum indicum L.), a member of the Pedaliaceae family [8], produces nutrient-dense seeds that are rich in protein and fat. Sesame seeds and their derivatives, including oil, flour, and supplements, contain valuable lignan compounds such as sesamin, sesamolin, sesamol, and episesamin [9]. In addition to their nutritional value, sesame seeds offer various health benefits, including antioxidant activity, cholesterol reduction, regulation of blood lipids, and protective effects on the liver and kidneys. They are also rich in oxalic acid, dietary fiber, antioxidants, minerals, unsaturated fatty acids, phenolics, vitamins, and phytosterols [10, 11].

Recent studies have examined the potential benefits of sesame supplementation in specific health contexts. For example, a meta-analysis from 2024 included 10 trials involving patients with type 2 diabetes. It found improvements in lipid profile indicators but no significant effects on body mass index (BMI), body weight, or high-density lipoprotein (HDL) levels [12]. Another review encompassed eight trials up to December 2022, which suggested that sesame supplementation led to reductions in fasting blood sugar (FBS) and hemoglobin A1c (HbA1c), indicating potential benefits for glycemic control in individuals with type 2 diabetes [13]. It is worth noting that these studies focused exclusively on individuals with type 2 diabetes and did not include a dose–response analysis.

In a meta-analysis conducted in 2022, Huang et al. examined the impact of sesame supplementation on cardiovascular risk factors. Their findings revealed potential benefits in improving blood lipids, reducing blood pressure, and managing body weight. Despite acknowledging study heterogeneity and potential biases, the analysis notably highlighted significant reductions in body weight and BMI [14]. Conversely, Moghtaderi et al.’s [15] findings suggest caution regarding sesame's efficacy as an adjunct therapy for controlling glycemic parameters in overweight adults.

To the best of our knowledge, despite numerous meta-analyses on sesame and various clinical factors, our review is the first meta-analysis that comprehensively examines all cardiovascular factors affected by sesame. We include a highly diverse and wide range of subgroups, enhancing the robustness and applicability of our findings. Uniquely, we have performed both meta-analysis and dose–response analysis in the field of sesame and cardiovascular health, providing a nuanced understanding of the intervention's impact. Furthermore, we have employed GRADE evaluation to ensure greater generalizability and reliability of our results, enabling health policymakers to have greater confidence in the conclusions drawn from our study. This comprehensive and rigorous approach not only fills existing research gaps but also offers valuable insights that can influence clinical guidelines and health policies, thereby significantly contributing to the field of cardiovascular health management.

Methods

Protocol and registration

The development of this extensive assessment has been enhanced through the utilization of a predetermined methodology in line with the instructions and recommended particulars outlined in the checklist of the 2015 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [16].

The comprehensive assessment and meta-analysis were formally recorded in International Prospective Register of Systematic Reviews (PROSPERO), a highly esteemed repository for thorough evaluations. The registration code CRD42024561721 was obtained to ensure openness and compliance with the evaluation process. Furthermore, the research conformed to the principles established in the Declaration of Helsinki. Ethical authorization for the investigation was acquired from the Ethics Committee of Golestan University of Medical Sciences (IR.GOUMS.REC.1403.209).

Search strategy and study selection

A thorough assessment was carried out to identify articles published up to June 2024. The assessment covered various electronic databases such as the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, Medline, SCOPUS, and EMBASE. To ensure inclusivity, additional sources including reputable journals and reference lists of relevant research articles, meta-analyses, and review publications on sesame were manually reviewed to uncover any further eligible studies.

The primary focus was on examining the impact of sesame supplementation, particularly on various biomarkers such as: body fat (BF), BMI, hip circumference (HC), waist circumference (WC), weight, waist-to-hip ratio (WHR), diastolic blood pressure (DBP), systolic blood pressure (SBP), FBS, HbA1c, homeostatic model assessment of insulin resistance (HOMA-IR), serum insulin, high-sensitivity c-reactive protein (hs-CRP), interleukin 6 (Il-6), tumour ncrosis factor alpha (TNF-α), HDL, low-density lipoprotein (LDL), total cholesterol (TC), triglycerides (TG), malondialdehyde (MDA), and total antioxidant capacity (TAC). These parameters were evaluated as the key outcomes post sesame supplementation.

The aim of the literature search was to identify all pertinent RCTs involving human participants using specific keywords like ‘sesame’ and ‘clinical trial’. The search terms were derived from EMTREE and Medical Subject Headings (MeSH) tags of the PubMed database, and a combination of these terms was used to devise an effective electronic search strategy. The search strategy was tailored for PubMed, Web of Science, EMBASE, Scopus, and CENTRAL databases by integrating (Supplementary Table S1).

Inclusion/exclusion criteria and data extraction

The meta-analysis conducted in this study involved the selection of studies that adhered to specific criteria. These criteria encompassed various factors, such as the inclusion of primary studies based on RCTs in the systematic review, the necessity for the RCTs to be single-blind and follow either parallel or crossover designs, the presence of concurrent control groups in the studies, and the publication of the research in English. The research question was structured using the PICO framework: Population (adults aged 18 years and older, regardless of health status), Intervention (sesame products including seeds, oil, powder, or extracts and their bioactive compounds, in any dosage form or administration method), Comparator (placebo, no intervention, standard care, or other dietary interventions), and Outcomes (anthropometric measurements, blood pressure, glycemic control markers, inflammatory biomarkers, lipid profile, and oxidative stress parameters).

Conversely, studies that did not meet certain criteria were excluded from the analysis. These excluded criteria consisted of the omission of non-RCT methods involving human subjects, as well as study types like review articles, case studies, observational studies (including cross-sectional, case–control, and cohort studies), and experimental studies with animals or in vitro. Moreover, proceedings, editorials/commentaries, letters, and reports were excluded if they lacked adequate data on baseline or follow-up cardiometabolic factors, such as anthropometric measures, blood pressure, glycemic profile, inflammatory markers, lipid profile and oxidative stress parameters in each group. Additionally, studies that combined sesame with other substances and articles in languages other than English were also excluded from consideration.

The initial investigation in this meta-analysis was conducted by two reviewers (B.P and A.A), who obtained and evaluated complete texts of studies meeting the inclusion criteria. The data management process utilized EndNote X7 software to merge search outcomes from various databases and eliminate any duplicates. Following the PRISMA guidelines, the systematic review selection process was carried out, with eligible articles comprehensively reviewed, and relevant information extracted using a standardized form developed by primary reviewers (A.J and A.R). Data extraction from the included studies was performed independently by two researchers (E.AD and N.R), covering various variables such as author details, study year, country, design, population characteristics, intervention specifics, and outcome measures. Any discrepancies were resolved through discussion, and if consensus was not reached, the project supervisor (A.J) was consulted to ensure a unified interpretation.

Methodological quality assessment and evaluation of the strength of evidence

Two reviewers (B.P and A.A) conducted a comprehensive assessment of the methodological quality of the trials included in the study by applying the Cochrane criteria. Any disagreements were resolved through discussion or with the involvement of a third reviewer (A.J). The criteria utilized to evaluate each individual trial included sequence generation adequacy, allocation concealment, blinding, management of dropouts (incomplete outcome data), selective outcome reporting, and identification of potential sources of bias.

In order to assess and summarize the evidence pertaining to each outcome analyzed in the meta-analysis, we utilized the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework. This framework classifies evidence derived from systematic reviews and meta-analyses into four categories: “high,” “moderate,” “low,” or “very low.” The quality of the reported effect size may be adjusted based on the study’s design, along with other methodological and statistical constraints. Two independent reviewers (A.J and N.R), with one author (A.R) as an adjudicator in case of discrepancies, considered various factors for each outcome to determine the certainty of the estimate. These factors encompassed study design, bias risk, consistency, precision, directness, presence of a significant effect, dose–response pattern, and publication bias.

Statistical analysis

The statistical analysis was conducted using Stata software, version 17.0, developed by Stata Corp located in College Station, Texas, to perform a Meta-analysis. The analysis encompassed the extraction of pre- and post-treatment means, standard deviations, and participant numbers from intervention and placebo groups for various clinical outcomes such as anthropometric measures, blood pressure, glycemic profile, inflammatory markers, lipid profile and oxidative stress parameters. The assessment of the impact of sesame supplementation involved the evaluation of standardized mean differences (SMDs) in changes between the intervention and placebo groups.

Owing to the diverse populations and settings in the included RCTs, a random effects model was utilized to determine the overall effect based on the SMDs, employing the DerSimonian-Laird weighting methodology. In cases where standard deviations (SDs) were not provided for changes but only for baseline and trial conclusion, the SD for net change was computed using the Follmann method with an assumed correlation coefficient (R) of 0.5. If the standard error (SE) was presented, the SD was derived using the formula SD: SE × sqrt(n), where n denoted the sample size in each group. The SDs of the change difference were calculated using the formula: SD = square root [(SD pre-treatment)² + (SD post-treatment)² − (2R × SD pre-treatment × SD post-treatment)], with an assumed correlation coefficient (R) of 0.5.

The I-square (I²) statistic was employed for the assessment of heterogeneity among studies. Moreover, the prediction interval was calculated to assess the clinical significance of the observed variations across studies. Subgroup analyses were carried out to explore the impact of sesame on clinical outcomes, considering pertinent study characteristics like study population, follow-up duration, and sesame dosage as potential contributors to heterogeneity. Meta-regression was utilized to investigate the potential effects of sesame dosage (in grams per day) and duration on risk factors linked to CVDs.

Furthermore, a nonlinear model was utilized to combine dose–response data from different studies to evaluate the impact of sesame supplementation on CVD risk factors [17]. To investigate the impact of individual studies on the results of the meta-analysis, a leave-one-out analysis was performed by recalculating the meta-analysis statistic after excluding one study at a time.

Results

Study selection

The selection process for the included studies is illustrated in Fig. 1. Our database search identified a total of 9,855 studies, distributed as follows: PubMed (n = 1043), ISI Web of Science (n = 2946), Scopus (n = 2279), Embase (n = 2949), and Cochrane Library (n = 638). After removing 1425 duplicate studies, we screened 192 studies based on their titles and abstracts. Subsequently, we excluded 55 studies for being irrelevant. The full text of 80 studies was then assessed for eligibility. Ultimately, 67 studies were excluded due to not reporting the desired outcomes. Supplementary Table S2 details the studies excluded during the full-text review and the reasons for their exclusion. Consequently, 13 studies, comprising a total of 521 participants, were included in the systematic review and meta-analysis [6, 18–29].

Fig. 1.

Flowchart of study selection for inclusion trials in the systematic review

Study characteristics

The characteristics of the included studies are presented in Table 1. The SMD and 95% confidence intervals (CI) for BF, BMI, HC, WC, weight, WHR, DBP, SBP, FBS, HbA1c, HOMA-IR, serum insulin, CRP, IL-6, TNF-α, HDL, LDL, TC, TG, MDA, and TAC and their changes are presented in Supplementary Figures S1–S6 respectively.

Table 1.

Characteristics of included studies in the meta-analysis

References	Country	Study design	Health condition	Sample size (Sex)	Sample size (INT/CON)	Trial duration (Week)	Means age (INT/CON)	Dose of supplement (mg/d)	Type of supplement (INT/CON)	Outcomes
Tobeiha et al. [18]	Iran	DB, RCT, PC	T2DM	39 (B)	21/18	8	50/55.38	15,000	Sesame oil/Placebo	MDA, TAC, CRP, FBS, Insulin, HOMA-IR, TG, Weight, BMI, BF, WHR, TC, LDL, HDL,
Mokhber et al. [19]	Iran	DB, RCT, PC	CVD Patients	36 (B)	19/17	10	60.78/51.35	500	Sesame Lignan capsule/Placebo	FBS, TG, LDL, HDL, TC, HC, BMI, Weight, WC, WHR
Helli et al. [20]	Iran	TB, RCT, PC	Rheumatoid Arthritis	44 (F)	22/22	6	55.49/55.49	200	Sesamin capsule/Placebo	hs‐CRP, IL-6, TNF‐α
Aslam et al. [6]	Pakistan	RCT, PC	T2DM	46 (B)	23/23	12	18–60/18–60	30 ml	Sesame oil/Placebo	Insulin, HbA1c
Mohammad Shahi et al. [21]	Iran	DB, RCT, PC	T2DM	48 (B)	24/24	8	50/51.72	200	Sesamin capsule/Placebo	Weight, BMI, WC, HC, WHR, BF, FBS, HbA1c, IL-6, Insulin, hs-CRP, HOMA-IR, TNF-α
Mohammad Shahi et al. [22]	Iran	DB, RCT, PC	T2DM	44 (B)	22/22	8	50/51.72	200	Sesamin capsule/Placebo	Weight, BMI, WC, WHR, FBS, HbA1c, Insulin Level, HOMA-IR, TG, TC, LDL, HDL, MDA
Helli et al. [23]	Iran	DB, RCT, PC	Rheumatoid Arthritis	44 (F)	22/22	6	49.6 /48	200	Sesamin capsule/Placebo	Weight, BMI, BF, WC, HC, WHR, SBP, DBP, TC, TG, HDL, LDL, MDA, TAC
Haghighian et al. [24]	Iran	RCT, PC	Knee Osteoarthritis	45 (B)	22/23	8	56.9/58.27	40,000	Sesame seed/ Placebo powder(glucosamine) + Acetaminophen	MDA, TAC, hs-CRP, IL-6
Wichitsranoi et al. [25]	Thailand	DB, RCT, PC	Pre-hypertensive	30 (B)	15/15	4	49.3/50.3	2520	Black sesame meal capsules/Placebo	SBP, DBP, MDA
Wu et al. [26]	Australia	RCT, PC, CR	Overweight or obese	66 (B)	33/33	5	54.7/54.7	25,000	Sesame bars/Iso-caloric placebo matched for macronutrient bars	Weight, TC, LDL, HDL, TG, SBP, DBP, IL-6, TNF-a, hs-CRP
Miyawaki et al. [27]	Japan	DB, RCT, PC, CR	Hypertensive	25 (B)	12/13	4	49.1/49.1	60	Sesamin capsul/Placebo	SBP, DBP
Wu et al. [28]	Taiwan	RCT, PC, CR	Healthy	24 (F)	12/12	5	59/59	50,000	Sesame seed powder/Placebo	Weight, BF, TC, TG, LDL, HDL
Khajehdehi et al. [29]	Iran	RCT, PC	Hemodialysis	30 (B)	15/15	8	32.3/31.1	4500	Sesame oil/Placebo	TG, TC, LDL, HDL

B, both sex; BF, body fat; BMI, body mass index; CON, control group; CVD, cardio vascular disease; DB, double-blinded; DBP, diastolic blood pressure; F, female; FBS, fasting blood sugar; HbA1c, hemoglobin A1C; HC, hip circumference; HDL, high-density lipoprotein; HOMA-IR, homeostatic model assessment of insulin resistance; hs-crp, high-sensitivity C-reactive protein; IL-6, interleukin 6; INT, intervention group; LDL, low-density lipoprotein; MDA, malondialdehyde; RCT, randomized controlled trial; SBP, systolic blood pressure; T2DM, type 2 diabetes mellitus; TAC, total antioxidant capacity; TC, total cholesterol; TG, triglycerides; TB, triple-blinded; TNF-a, tumor necrosis factor alpha; WC, waist circumference; WHR, waist-to-hip ratio

The studies were published between 2000 and 2024 and conducted in Iran, Australia, Japan, Pakistan, Taiwan, and Thailand. In the intervention groups, the mean age of participants ranged from 32.3 to 60.78 years. The sesame supplementation dose ranged from 60 to 50,000 g/day, and the duration of the intervention ranged from 4 to 12 weeks. The sample size in the intervention groups ranged from 24 to 66 participants. Three studies included only female participants [20, 23, 28], while the remaining studies included both genders. The included studies involved participants with cardiovascular disease [19], undergoing hemodialysis [29], pre-hypertensive and hypertensive [25, 27], knee osteoarthritis [24], overweight or obese [26], rheumatoid arthritis [20, 23], type 2 diabetes mellitus (T2DM) [6, 18, 21, 22] and healthy subjects [28]. The sample sizes for the intervention and control groups across various outcomes were as: BF: 194 (intervention: 100, control: 94), BMI: 211 (intervention: 108, control: 103), HC: 128 (intervention: 65, control: 63), WC: 172 (intervention: 87, control: 85), Weight: 301 (intervention: 153, control: 148), WHR: 211 (intervention: 108, control: 103), DBP: 165 (intervention: 82, control: 83), SBP: 165 (intervention: 82, control: 83), FBS: 167 (intervention: 86, control: 81), HbA1c: 138 (intervention: 69, control: 69), HOMA-IR: 131 (intervention: 67, control: 64), Serum insulin: 177 (intervention: 90, control: 87), CRP: 242 (intervention: 122, control: 120), IL-6: 203 (intervention: 101, control: 102), TNF-α: 158 (intervention: 79, control: 79), HDL: 283 (intervention: 144, control: 139), LDL: 283 (intervention: 144, control: 139), TC: 283 (intervention: 144, control: 139), TG: 283 (intervention: 144, control: 139), MDA: 202 (intervention: 102, control: 100), TAC: 128 (intervention: 65, control: 63).

Qualitative data assessment

Using the Cochrane Risk of Bias Assessment tool, we evaluated the risk of bias in the included studies. Five studies were assessed as having a high risk of bias [6, 22, 24, 28, 29]. Three studies were determined to have a moderate risk of bias [18, 19, 27], and five studies were found to have a low risk of bias [20, 21, 23, 25, 26] (Table 2).

Table 2.

Quality of included studies in the meta-analysis

References	Random sequence generation	Allocation concealment	Blinding of participants and personnel	Blinding of outcome assessment	Incomplete outcome data	Selective outcome reporting	Other sources of bias	Overall quality
Tobeiha et al. [18]	L	L	L	U	H	L	L	Fair
Mokhber et al. [19]	U	U	L	L	L	L	L	Fair
Helli et al. [20]	L	L	L	L	L	L	L	Good
Aslam et al. [6]	U	H	U	H	H	L	L	Poor
Mohammad Shahi et al. [21]	U	U	L	L	L	L	L	Good
Mohammad Shahi et al. [22]	U	H	U	H	L	L	L	Poor
Helli et al. [23]	L	L	L	L	L	L	L	Good
Haghighian et al. [24]	U	U	L	U	H	L	L	Poor
Wichitsranoi et al. [25]	U	U	L	L	L	L	L	Good
Wu et al. [26]	U	L	L	L	L	L	L	Good
Miyawaki et al. [27]	U	U	L	L	L	L	L	Fair
Wu et al. [28]	U	H	U	L	L	L	L	Poor
Khajehdehi (29)	U	H	L	H	L	L	L	Poor

H, high risk of bias; L, low risk of bias; U, unclear risk of bias

Effects of sesame supplementation on anthropometric measures

Supplementary Figure S1 delineates the impact of sesame supplements on anthropometric measures. The analysis of five studies examining the effect of sesame supplements on BF concluded that there was no significant effect (SMD = − 0.12; 95% CI − 0.40, 0.16; P = 0.390). Furthermore, no heterogeneity was detected among these studies (I² = 0.00%, P = 0.881).

Five studies evaluated the effect of sesame supplements on BMI. The meta-analysis indicated no substantial impact on BMI (SMD = − 0.03; 95% CI − 0.30, 0.24; P = 0.832), with no observed heterogeneity (I² = 0.00%, P = 0.915).

Three studies investigated the effects of sesame supplements on HC. The analysis did not demonstrate a significant effect of sesame supplements on HC (SMD = − 0.17; 95% CI − 0.52, 0.17; P = 0.323), and no significant heterogeneity was observed (I² = 0.00%, P = 0.842).

In the case of four studies exploring the impact of sesame supplements on WC, the meta-analysis revealed no significant effect (SMD = − 0.16; 95% CI − 0.46, 0.13; P = 0.280), with no observed heterogeneity (I² = 0.00%, P = 0.941).

Seven studies examined the effect of sesame supplements on weight. The meta-analysis showed no substantial impact on weight (SMD = − 0.02; 95% CI − 0.24, 0.21; P = 0.887), with no observed heterogeneity (I² = 0.00%, P = 0.997).

Additionally, five studies assessed the effect of sesame supplements on WHR. The meta-analysis revealed no significant impact on WHR (SMD = − 0.05; 95% CI − 0.32 to 0.22; P = 0.735), with no significant heterogeneity observed (I² = 0.00%, P = 0.990).

Sensitivity analysis conducted for BF, BMI, HC, WC, weight, and WHR indicated that excluding any of the studies did not alter the overall findings. Moreover, there was no evidence of publication bias for BF (Egger’s P = 0.62), BMI (Egger’s P = 0.89), HC (Egger’s P = 0.13), WC (Egger’s P = 0.22), weight (Egger’s P = 0.49), and WHR (Egger’s P = 0.96).

Effects of sesame supplementation on blood pressure

Supplementary Figure S2 delineates the impact of sesame supplements on blood pressure. The analysis of four studies examining the effect of sesame supplements on DBP concluded that there was no significant effect (SMD = − 0.23; 95% CI − 1.41, 0.95; P = 0.703). However, there was significant heterogeneity among these studies (I² = 91.5%, P < 0.001).

Similarly, four trials examined the effect of sesame supplements on SBP. The meta-analysis showed no substantial impact on SBP (SMD = − 0.32; 95% CI − 1.47, 0.83; P = 0.587), with significant heterogeneity observed among these studies (I² = 91.1%, P < 0.001).

Sensitivity analysis conducted for DBP and SBP indicated that excluding any of the studies did not alter the overall findings. Moreover, there was no evidence of publication bias for DBP (Egger's P = 0.57) and SBP (Egger's P = 0.64).

Effects of sesame supplementation on glycemic profile

Supplementary Figure S3 delineates the impact of sesame supplements on the glycemic profile. The analysis of four studies examining the effect of sesame supplements on FBS concluded that there was a marginally significant effect (SMD = − 0.57; 95% CI − 1.16, 0.02; P = 0.057). Moreover, a substantial heterogeneity was detected among these studies (I² = 71.1%, P = 0.016).

Three trials examined the effect of sesame supplements on HbA1c. The meta-analysis showed a substantial impact on HbA1c (SMD = − 0.67; 95% CI − 1.01, − 0.32; P < 0.001), with no heterogeneity observed among these studies (I² = 0.00%, P = 0.575).

Three trials investigated the effects of sesame supplements on HOMA-IR. The analysis did not indicate a significant effect of sesame supplements on HOMA-IR (SMD = − 0.08; 95% CI − 0.42, 0.26; P = 0.642), with no significant heterogeneity observed (I² = 0.00%, P = 0.747).

In the case of four trials exploring the impact of sesame supplements on serum insulin, the meta-analysis revealed no significant effect (SMD = 1.25; 95% CI − 0.27, 2.77; P = 0.108). However, there was significant heterogeneity among these studies (I² = 94.9%, P < 0.001).

Sensitivity analysis conducted for HbA1c, HOMA-IR, and serum insulin revealed that excluding any of the studies did not alter the overall findings. However, upon the exclusion of Mokhber et al. [19] (SMD: − 0.76, 95% CI − 1.39, − 0.14) and Tobeiha et al. [18] (SMD: − 0.72, 95% CI − 1.43, − 0.01), the overall effect of sesame on FBS notably changed. Additionally, there was no evidence of publication bias for FBS (Egger’s P = 0.62), HbA1c (Egger’s P = 0.58), HOMA-IR (Egger’s P = 0.25), and serum insulin (Egger’s P = 0.10).

Effects of sesame supplementation on inflammatory markers

Supplementary Figure S4 delineates the impact of sesame supplements on inflammatory markers. The analysis of five studies examining the effect of sesame supplements on CRP concluded that a significant effect was observed (SMD = − 0.51; 95% CI − 0.96, − 0.05; P = 0.028). However, there was significant heterogeneity among these studies (I² = 66.5%, P = 0.018).

Four trials examined the effect of sesame supplements on IL-6. The meta-analysis showed a substantial impact on IL-6 (SMD = − 0.74; 95% CI − 1.16, − 0.32; P < 0.001), with moderate heterogeneity among these studies (I² = 52.1%, P = 0.100).

Additionally, three trials assessed the effect of sesame supplements on TNF-a. The meta-analysis revealed no significant impact on TNF-a (SMD = − 0.73; 95% CI − 1.84, 0.38; P = 0.198), and there was high heterogeneity observed among these studies (I² = 90.8%, P < 0.001).

Sensitivity analysis conducted for IL-6 revealed that excluding any of the studies did not alter the overall findings. However, excluding Mohammad Shahi et al. [21] (SMD: − 0.51; 95% CI − 1.10, 0.07) and Wu et al. [26] (SMD: − 0.50; 95% CI − 1.11, 0.11) notably changed the overall effect of sesame on CRP. Additionally, excluding Wu et al. [26] (SMD: − 1.26; 95% CI − 1.71, − 0.81) changed the overall effect of sesame on TNF-a. Moreover, there was no evidence of publication bias for CRP (Egger’s P = 0.71), IL-6 (Egger’s P = 0.13), and TNF-a (Egger’s P = 0.10).

Effects of sesame supplementation on lipid profile

Supplementary Figure S5 delineates the impact of sesame supplements on the lipid profile. The analysis of seven studies examining the effect of sesame supplements on HDL concluded that no significant effect was observed (SMD = 0.21; 95% CI − 0.06, 0.48; P = 0.121). Moreover, low heterogeneity was detected among these studies (I² = 20.7%, P = 0.272).

Seven trials were found to examine the effect of sesame supplements on LDL. The meta-analysis showed no substantial impact on LDL (SMD = − 0.16; 95% CI − 0.50, 0.18; P = 0.347), with moderate heterogeneity observed among these studies (I² = 50%, P = 0.062).

Seven trials investigated the effects of sesame supplements on TC. The analysis did not indicate a significant effect of sesame supplements on TC (SMD = − 0.22; 95% CI − 0.49, 0.05; P = 0.108), with low heterogeneity observed among these studies (I² = 22.2%, P = 0.260).

In the case of seven trials exploring the impact of sesame supplements on TG, the meta-analysis revealed no significant effect on TG (SMD = 0.44; 95% CI − 0.19, 0.28; P = 0.711). Similarly, no heterogeneity was observed among these studies (I² = 0.00%, P = 0.593).

Sensitivity analysis conducted for LDL and TG revealed that excluding any of the studies did not alter the overall findings. However, excluding Tobeiha et al. [18] (SMD: 0.28; 95% CI − 1.11, 0.11) notably changed the overall effect of sesame on HDL. Sensitivity analysis for TC showed that excluding Wu et al. [26] (SMD: − 0.34; 95% CI − 0.61, − 0.07) altered the overall findings. Additionally, there was no evidence of publication bias for HDL (Egger’s P = 0.63), LDL (Egger’s P = 0.44), TC (Egger’s P = 0.23), and TG (Egger’s P = 0.74).

Effects of sesame supplementation on oxidative stress parameters

Supplementary Figure S6 delineates the impact of sesame supplements on oxidative stress parameters. The analysis of five studies examining the effect of sesame supplements on MDA concluded that no significant effect was observed (SMD = − 1.35; 95% CI − 2.90, 0.20; P = 0.088). However, there was significant heterogeneity among these studies (I² = 95.4%, P < 0.001).

Three trials examined the effect of sesame supplements on TAC. The meta-analysis showed no substantial impact on TAC (SMD = 0.16; 95% CI − 0.39, 0.72; P = 0.564), with substantial heterogeneity among these studies (I² = 60.5%, P = 0.079).

Sensitivity analysis conducted for TAC revealed that excluding any of the studies did not alter the overall findings. However, excluding Wichitsranoi et al. [25] (SMD: − 2.02; 95% CI − 3.66, − 0.38) notably changed the overall effect of sesame on MDA. Additionally, there was no evidence of publication bias for MDA (Egger's P = 0.25) and TAC (Egger's P = 0.94).

Subgroup analysis

Table 3 presents the results of a subgroup analysis based on various factors: country (Iran vs. other countries, including Australia, Japan, Pakistan, Taiwan, and Thailand), health status (chronic diseases such as T2D, hypertension, rheumatoid arthritis, hemodialysis, knee osteoarthritis, and cardiovascular disease patients vs. healthy/at-risk but without a chronic disease, such as being overweight or obese and pre-hypertensive), sex (female vs. both sexes), intervention duration (≥ 6 weeks vs. < 6 weeks), intervention age (≥ 50 years vs. < 50 years), intervention type (supplements/capsules vs. food products, including black sesame meal capsules, sesame bars, sesame oil, sesame seeds, and sesame seed powder), dosage of the sesame supplement (< 10 g vs. ≥ 10 g), and sample size (≤ 40 vs. > 40).

Table 3.

Description of the analysis and subgroup results of sesame supplementation on cardiovascular disease risk factors

	Studies N	Participant N	SMD (95% CI)	P value	Heterogeneity
					P heterogeneity	I2	P between sub-groups
Analysis and subgroup results of Sesame supplementation on BF
Overall effect	5	194	− 0.12 (− 0.40, 0.16)	0.390	0.881	0
Country
Iran	4	170	− 0.13 (− 0.43, 0.17)	0.389	0.764	0	0.864
Other countries	1	24	− 0.06 (− 0.86, 0.74)	0.887	–	–
Health status
Chronic diseases	4	170	− 0.13 (− 0.43, 0.17)	0.389	0.764	0	0.864
Healthy/at-risk	1	24	− 0.06 (− 0.86, 0.74)	0.887	–	–
Sex
Female	2	68	− 0.28 (− 0.76, 0.20)	0.256	0.503	0	0.434
Both sex	3	126	− 0.04 (− 0.39, 0.31)	0.819	0.941	0
Age (year)
50 ≥	4	170	− 0.13 (− 0.43, 0.17)	0.389	0.764	0	0.864
50 <	1	24	− 0.06 (− 0.86, 0.74)	0.887	–	–
Duration (weeks)
6 ≥	2	68	− 0.28 (− 0.76, 0.20)	0.256	0.503	0	0.434
6 <	3	126	− 0.04 (− 0.39, 0.31)	0.819	0.941	0
Type
Supplements/capsules	2	92	− 0.25 (− 0.66, 0.16)	0.229	0.505	0	0.397
Food products	3	102	− 0.01 (− 0.40, 0.38)	0.969	0.990	0
Dose (gr/d)
10 ≥	2	92	− 0.25 (− 0.66, 0.16)	0.229	0.505	0	0.397
10 <	3	102	− 0.01 (− 0.40, 0.38)	0.969	0.990	0
Sample size
40 ≥	3	102	− 0.01 (− 0.40, 0.38)	0.969	0.990	0	0.397
40 <	2	92	− 0.25 (− 0.66, 0.16)	0.229	0.505	0
Analysis and subgroup results of Sesame supplementation on BMI
Overall effect	5	211	− 0.03 (− 0.30, 0.24)	0.832	0.915	0
Sex
Female	1	44	− 0.28 (− 0.87, 0.31)	0.357	–	–	0.354
Both sex	4	167	0.04 (− 0.27, 0.34)	0.815	0.991	0
Age (year)
50 ≥	4	175	− 0.34 (− 0.33, 0.26)	0.821	0.812	0	0.935
50 <	1	36	− 0.004 (− 0.66, 0.65)	0.989	–	–
Duration (weeks)
6 ≥	1	44	− 0.28 (− 0.87, 0.31)	0.357	–	–	0.354
6 <	4	167	0.04 (− 0.27, 0.34)	0.815	0.991	0
Type
Supplements/capsules	4	172	− 0.03 (− 0.33, 0.27)	0.845	0.810	0	0.991
Food products	1	39	− 0.03 (− 0.66, 0.60)	0.935	–	–
Dose (gr/d)
10 ≥	4	172	− 0.03 (− 0.33, 0.27)	0.845	0.810	0	0.991
10 <	1	39	− 0.03 (− 0.66, 0.60)	0.935	–	–
Sample size
40 ≥	2	75	− 0.02 (− 0.47, 0.44)	0.946	0.963	0	0.942
40 <	3	136	− 0.04 (− 0.37, 0.30)	0.831	0.620	0
Analysis and subgroup results of Sesame supplementation on HC
Overall effect	3	128	− 0.17 (− 0.52, 0.17)	0.323	0.842	0
Analysis and subgroup results of Sesame supplementation on WC
Overall effect	4	127	− 0.16 (− 0.46, 0.13)	0.280	0.941	0
Analysis and subgroup results of Sesame supplementation on Weight
Overall effect	7	301	− 0.02 (− 0.24, 0.21)	0.887	0.997	0
Country
Iran	5	211	− 0.04 (− 0.31, 0.23)	0.783	0.975	0	0.774
Other countries	2	90	0.03 (− 0.38, 0.45)	0.871	0.883	0
Health status
Chronic diseases	5	211	− 0.04 (− 0.31, 0.23)	0.783	0.975	0	0.774
Healthy/at-risk	2	90	0.03 (− 0.38, 0.45)	0.871	0.883	0
Sex
Female	2	68	− 0.14 (− 0.62, 0.33)	0.561	0.705	0	0.599
Both sex	5	233	0.02 (− 0.24, 0.28)	0.879	0.999	0
Age (year)
50 ≥	4	175	− 0.03 (− 0.33, 0.26)	0.817	0.922	0	0.849
50 <	3	126	0.01 (− 0.34, 0.36)	0.958	0.965	0
Duration (weeks)
6 ≥	3	134	− 0.04 (− 0.38, 0.30)	0.793	0.795	0	0.822
6 <	4	167	0.01 (− 0.30, 0.31)	0.964	0.994	0
Type
Supplements/capsules	4	99	− 0.04 (− 0.34, 0.26)	0.796	0.921	0	0.818
Food products	3	202	0.01 (− 0.33, 0.36)	0.935	0.975	0
Dose (gr/d)
10 ≥	4	99	− 0.04 (− 0.34, 0.26)	0.796	0.921	0	0.818
10 <	3	202	0.01 (− 0.33, 0.36)	0.935	0.975	0
Sample size
40 ≥	3	102	− 0.04 (− 0.43, 0.36)	0.858	0.998	0	0.905
40 <	4	92	− 0.01 (− 0.28, 0.27)	0.962	0.902	0
Analysis and subgroup results of Sesame supplementation on WHR
Overall effect	5	211	− 0.05 (− 0.32, 0.22)	0.735	0.990	0
Sex
Female	1	44	− 0.19 (− 0.78, 0.40)	0.530	–	–	0.594
Both sex	4	167	−0.01 (−0.31, 0.29)	0.954	1.00	0
Age (year)
50 ≥	4	175	−0.05 (−0.34, 0.25)	0.753	0.961	0	0.987
50 <	1	36	−0.04 (−0.70, 0.61)	0.901	–	–
Duration (weeks)
6 ≥	1	44	−0.19 (−0.78, 0.40)	0.530	–	–	0.594
6 <	4	167	−0.01 (−0.31, 0.29)	0.954	1.00	0
Type
Supplements/capsules	4	172	−0.06 (−0.36, 0.24)	0.708	0.965	0	0.872
Food products	1	39	0.00 (−0.63, 0.63)	1.000	–	–
Dose (gr/d)
10 ≥	4	172	−0.06 (−0.36, 0.24)	0.708	0.965	0	0.872
10 <	1	39	0.00 (−0.63, 0.63)	1.000	–	–
Sample size
40 ≥	2	75	−0.02 (−0.47, 0.43)	0.931	0.928	0	0.886
40 <	3	136	−0.06 (−0.40, 0.27)	0.721	0.875	0
Analysis and subgroup results of Sesame supplementation on DBP
Overall effect	4	165	−0.23 (−1.41, 0.95)	0.703	< 0.001	91.5
Analysis and subgroup results of Sesame supplementation on SBP
Overall effect	4	165	−0.32 (−1.47, 0.83)	0.587	< 0.001	91.1
Analysis and subgroup results of Sesame supplementation on FBS
Overall effect	4	167	−0.57 (−1.16, 0.02)	0.057	0.016	71.1
Analysis and subgroup results of Sesame supplementation on HbA1c
Overall effect	3	138	−0.67 (−1.01, −0.32)	< 0.001	0.575	0
Analysis and subgroup results of Sesame supplementation on HOMA-IR
Overall effect	3	131	−0.08 (−0.42, 0.26)	0.642	0.747	0
Analysis and subgroup results of Sesame supplementation on Insulin
Overall effect	4	177	1.25 (−0.27, 2.77)	0.108	< 0.001	94.9
Analysis and subgroup results of Sesame supplementation on CRP
Overall effect	5	242	−0.51 (−0.96, −0.05)	0.028	0.018	66.5
Country
Iran	4	176	−0.50 (−1.10, 0.11)	0.109	0.008	74.7	0.882
Other countries	1	66	−0.56 (−1.05, −0.06)	0.027	–	–
Health status
Chronic diseases	4	176	− 0.50 (− 1.10, 0.11)	0.109	0.008	74.7	0.882
Healthy/At-risk	1	66	− 0.56 (− 1.05, − 0.06)	0.027	–	–
Sex
Female	1	44	− 1.44(− 2.11, − 0.77)	< 0.001	–	–	0.002
Both sex	4	167	− 0.32 (− 0.60, − 0.42)	0.024	0.425	0
Age (year)
50 ≥	2	87	− 0.27 (− 0.75, 0.21)	0.274	0.260	21.3	0.347
50 <	3	155	− 0.68 (− 1.39, 0.03)	0.061	0.011	77.8
Duration (weeks)
6 ≥	2	110	− 0.97 (− 1.83, − 0.10)	0.028	0.036	77.2	0.110
6 <	3	132	− 0.21 (− 0.55, 0.13)	0.230	0.470	0
Type
Supplements/capsules	2	92	− 0.95 (− 1.88, − 0.03)	0.044	0.035	77.5	0.172
Food products	3	150	− 0.26 (− 0.61, 0.09)	0.144	0.311	14.5
Dose (gr/d)
10 ≥	2	92	− 0.95 (− 1.88, − 0.03)	0.044	0.035	77.5	0.172
10 <	3	150	− 0.26 (− 0.61, 0.09)	0.144	0.311	14.5
Sample size
40 ≥	1	39	− 0.005 (− 0.63, 0.62)	0.988	–	–	0.131
40 <	4	203	− 0.63 (− 1.13, − 0.12)	0.015	0.027	67.3
Analysis and subgroup results of Sesame supplementation on IL-6
Overall effect	4	203	− 0.74 (− 1.16, − 0.32)	0.001	0.100	52.1
Analysis and subgroup results of Sesame supplementation on TNF-α
Overall effect	3	158	− 0.73 (− 1.84, 0.38)	0.198	< 0.001	90.8
Analysis and subgroup results of Sesame supplementation on HDL
Overall effect	7	283	0.21 (− 0.06, 0.48)	0.121	0.272	20.7
Country
Iran	5	193	0.30 (− 0.07, 0.66)	0.115	0.162	38.8	0.347
Other countries	2	90	0.03 (− 0.38, 0.44)	0.885	0.931	0
Health status
Chronic diseases	5	193	0.30 (− 0.07, 0.66)	0.115	0.162	38.8	0.347
Healthy/at-risk	2	90	0.03 (− 0.38, 0.44)	0.885	0.931	0
Sex
Female	2	68	0.43 (− 0.32, 1.17)	0.261	0.136	54.9	0.448
Both sex	5	215	0.12 (− 0.15, 0.39)	0.379	0.445	0
Age (year)
50 ≥	4	157	0.26 (− 0.20, 0.72)	0.271	0.101	51.8	0.716
50 <	3	126	0.15 (− 0.20, 0.50)	0.398	0.554	0
Duration (weeks)
6 ≥	3	134	0.27 (− 0.22, 0.77)	0.274	0.149	47.5	0.716
6 <	4	149	0.16 (− 0.19, 0.52)	0.371	0.312	16.0
Type
Supplements/capsules	3	124	0.41 (− 0.04, 0.85)	0.073	0.218	34.3	0.207
Food products	4	159	0.06 (− 0.26, 0.37)	0.723	0.475	0
Dose (gr/d)
10 ≥	4	154	0.43 (0.10, 0.76)	0.011	0.370	4.7	0.05
10 <	3	129	− 0.05 (− 0.40, 0.29)	0.775	0.779	0
Sample size
40 ≥	4	129	0.18 (− 0.20, 0.56)	0.352	0.323	13.8	0.809
40 <	3	154	0.25 (− 0.21, 0.71)	0.281	0.133	50.5
Analysis and subgroup results of Sesame supplementation on LDL
Overall effect	7	283	− 0.16 (− 0.50, 0.18)	0.347	0.062	50
Country
Iran	5	193	− 0.20 (− 0.63, 0.23)	0.355	0.060	55.7	0.742
Other countries	2	90	− 0.07 (− 0.74, 0.60)	0.840	0.144	53.1
Health status
Chronic diseases	5	193	− 0.20 (− 0.63, 0.23)	0.355	0.060	55.7	0.742
Healthy/at-risk	2	90	− 0.07 (− 0.74, 0.60)	0.840	0.144	53.1
Sex
Female	2	68	− 0.21 (− 0.69, 0.27)	0.393	0.384	0	0.837
Both sex	5	215	− 0.14 (− 0.60, 0.32)	0.556	0.025	64.1
Age (year)
50 ≥	4	157	− 0.22 (− 0.78, 0.33)	0.426	0.030	66.4	0.569
50 <	3	126	− 0.03 (− 0.41, 0.35)	0.875	0.326	10.7
Duration (weeks)
6 ≥	3	134	− 0.01 (− 0.37, 0.34)	0.947	0.337	7.9	0.495
6 <	4	149	− 0.24 (− 0.80, 0.32)	0.397	0.034	65.4
Type
Supplements/capsules	3	124	− 0.40 (− 1.02, 0.23)	0.212	0.051	66.5	0.207
Food products	4	159	0.05 (− 0.26, 0.37)	0.747	0.436	0
Dose (gr/d)
10 ≥	4	154	− 0.24 (− 0.79, 0.32)	0.401	0.033	65.8	0.510
10 <	3	129	− 0.01 (− 0.38, 0.35)	0.939	0.336	8.2
Sample size
40 ≥	4	129	− 0.07 (− 0.42, 0.27)	0.682	0.556	0	0.620
40 <	3	154	− 0.27 (− 0.99, 0.44)	0.454	0.008	79.3
Analysis and subgroup results of Sesame supplementation on TC
Overall effect	7	283	− 0.22 (− 0.49, 0.05)	0.108	0.260	22.2
Country
Iran	5	193	− 0.33 (− 0.62, − 0.04)	0.023	0.499	0	0.420
Other Countries	2	90	− 0.03 (− 0.70, 0.63)	0.926	0.147	52.4
Health status
Chronic diseases	5	193	− 0.33 (− 0.62, − 0.04)	0.023	0.499	0	0.420
Healthy/at-risk	2	90	− 0.03 (− 0.70, 0.63)	0.926	0.147	52.4
Sex
Female	2	68	− 0.48 (− 0.96, 0.00)	0.052	0.954	0	0.262
Both sex	5	215	− 0.14 (− 0.48, 0.19)	0.409	0.192	34.4
Age (year)
50 ≥	4	157	− 0.37 (− 0.69, − 0.05)	0.024	0.381	2.3	0.193
50 <	3	126	− 0.03 (− 0.42, 0.36)	0.880	0.299	17.1
Duration (weeks)
6 ≥	3	134	− 0.18 (− 0.70, 0.33)	0.485	0.120	52.8	0.752
6 <	4	149	− 0.28 (− 0.61, 0.04)	0.088	0.389	0.5
Type
Supplements/capsules	3	124	− 0.47 (− 0.83, − 0.12)	0.010	0.474	0	0.053
Food products	4	159	− 0.00 (− 0.31, 0.31)	0.980	0.482	0
Dose (gr/d)
10 ≥	4	154	− 0.42 (− 0.74, − 0.10)	0.010	0.585	0	0.064
10 <	3	129	0.04 (− 0.32, 0.39)	0.844	0.348	5.3
Sample size
40 ≥	4	129	− 0.17 (− 0.52, 0.17)	0.325	0.846	0	0.720
40 <	3	154	− 0.30 (− 0.90, 0.30)	0.326	0.033	70.7
Analysis and subgroup results of Sesame supplementation on TG
Overall effect	7	283	0.44 (− 0.19, 0.28)	0.711	0.593	0
Country
Iran	5	193	0.18 (− 0.10, 0.47)	0.208	0.800	0	0.091
Other countries	2	90	− 0.25 (− 0.66, 0.16)	0.236	0.736	0
Health status
Chronic diseases	5	193	0.18 (− 0.10, 0.47)	0.208	0.800	0	0.091
Healthy/at-risk	2	90	− 0.25 (− 0.66, 0.16)	0.236	0.736	0
Sex
Female	2	68	− 0.14 (− 0.62, 0.33)	0.557	0.495	0	0.377
Both sex	5	215	0.10 (− 0.16, 0.37)	0.449	0.498	0
Age (year)
50 ≥	4	157	0.23 (− 0.08, 0.55)	0.148	0.768	0	0.080
50 <	3	126	− 0.19 (− 0.54, 0.16)	0.292	0.812	0
Duration (weeks)
6 ≥	3	134	− 0.17 (− 0.51, 0.16)	0.312	0.778	0	0.080
6 <	4	149	0.24 (− 0.08, 0.57)	0.140	0.787	0
Type
Supplements/capsules	3	124	0.09 (− 0.27, 0.44)	0.634	0.699	0	0.804
Food products	4	159	0.02 (− 0.34, 0.38)	0.905	0.283	21.2
Dose (gr/d)
10 ≥	4	154	0.12 (− 0.20, 0.44)	0.457	0.824	0	0.578
10 <	3	129	− 0.04 (− 0.50, 0.42)	0.870	0.199	38
Sample size
40 ≥	4	129	0.11 (− 0.23, 0.46)	0.525	0.439	0	0.602
40 <	3	154	− 0.01 (− 0.33, 0.30)	0.939	0.440	0
Analysis and subgroup results of Sesame supplementation on MDA
Overall effect	5	202	− 1.35 (− 2.90, 0.20)	0.088	< 0.001	95.4
Country
Iran	4	172	− 2.02 (− 3.66, − 0.38)	0.016	< 0.001	94.9	< 0.001
Other countries	1	30	1.35 (0.55, 2.15)	0.001	–	–
Health status
Chronic diseases	4	172	− 2.02 (− 3.66, − 0.38)	0.016	< 0.001	94.9	< 0.001
Healthy/at-risk	1	30	1.35 (0.55, 2.15)	0.001	–	–
Sex
Female	1	44	− 1.56 (− 2.24, − 0.88)	< 0.001	–	–	0.829
Both sex	4	158	− 1.33 (− 3.28, 0.62)	0.181	< 0.001	96.1
Age (year)
50 ≥	4	157	− 1.57 (− 3.72, 0.57)	0.150	< 0.001	96.5	0.452
50 <	1	45	− 0.72 (− 1.32, − 0.12)	0.019	–	–
Duration (weeks)
6 ≥	2	74	− 0.11 (− 2.97, 2.74)	0.938	< 0.001	96.6	0.255
6 <	3	128	− 2.27 (− 4.64, 0.10)	0.061	< 0.001	96.4
Type
Supplements/capsules	3	118	− 0.10 (− 1.63, 1.44)	0.902	< 0.001	93.4	0.248
Food products	2	84	− 3.60 (− 9.33, 2.14)	0.219	< 0.001	97.7
Dose (gr/d)
10 ≥	3	118	− 0.10 (− 1.63, 1.44)	0.902	< 0.001	93.4	0.248
10 <	2	84	− 3.60 (− 9.33, 2.14)	0.219	< 0.001	97.7
Sample size
40 ≥	2	69	− 2.58 (− 10.34, 5.19)	0.515	< 0.001	98.6	0.649
40 <	3	133	− 0.76 (− 1.60, 0.08)	0.075	0.004	81.6
Analysis and subgroup results of Sesame supplementation on TAC
Overall effect	3	128	0.16 (− 0.39, 0.72)	0.564	0.079	60.5

BF, body fat; BMI, body mass index; DBP, diastolic blood pressure; FBS, fasting blood sugar; HbA1c, hemoglobin A1C; HC, hip circumference; HDL, high-density lipoprotein; HOMA-IR, homeostatic model assessment of insulin resistance; hs-CRP, high-sensitivity C-reactive protein; IL-6, interleukin 6; LDL, Low-density lipoprotein; MDA, malondialdehyde; SBP, systolic blood pressure; SMD, standardised mean difference; TAC, total antioxidant capacity; TC, total cholesterol; TG, triglycerides; TNF-a, tumor necrosis factor alpha; WC, waist circumference; WHR, waist-to-hip ratio

The results revealed that sesame supplementation had a more beneficial impact on TC in Iran. However, in other countries, sesame supplementation significantly affected CRP, although this was primarily based on one study by Wu et al. [26] from Australia. A substantial effect on MDA levels was observed in both categories based on country. In Iran, the supplementation demonstrated a protective effect against oxidative stress. However, the single study conducted in Thailand, classified under the ‘other countries’ category, indicates that supplementation may act as a risk factor for elevated MDA levels.

Regarding health status, sesame supplementation showed a more beneficial impact on TC in chronic diseases. In other conditions, sesame supplementation significantly affected CRP, although this was primarily based on one study by Wu et al. [26] on overweight or obese subjects. A significant effect on MDA was observed across all health conditions. In individuals with chronic diseases, supplementation demonstrated a protective effect, suggesting a potential benefit in reducing MDA levels. In contrast, the single study conducted in Thailand by Wichitsranoi et al. [25] classified under the ‘Healthy/At-risk without chronic diseases’ category, indicates that supplementation may act as a risk factor for elevated MDA levels.

Sesame supplementation had a notable impact on MDA in females, derived from a single study by Helli et al. [23]. However, the effect on CRP was significant in both sexes.

In subjects older than 50 years, a notable impact was observed in MDA, derived from a single study by Helli et al. [23]. In subjects under the age of 50 years sesame can have an impact on TC.

Regarding supplementation type, supplements or capsules had a significant effect on CRP and TC. However, no significant effect was observed when supplementing with sesame food products across the studied variables.

In dosages equal to or below 10 g per day, a notable impact was observed on CRP, HDL, and TC. No significant effect was observed in supplementation greater than 10 g per day across the studied variables.

A significant effect was observed on CRP in both durations shorter than 6 weeks and in studies with sample sizes larger than 40 subjects.

Meta-regression and non-linear dose–response analysis

Supplementary Figures S7–S10 present a detailed meta-regression analysis that rigorously assessed the impact of sesame doses and intervention duration on cardiovascular risk variables. Additionally, we employed a non-linear dose–response regression model to elucidate the complex relationship between sesame supplementation and cardiovascular outcomes.

A significant association was observed between the dose of sesame supplementation and an increase in TC levels (Coefficient = 0.15, p value = 0.019). According to the dose–response curve, the optimal dose of sesame supplementation for reducing TC levels is approximately 10,000 mg. This dose corresponds to the point where the reduction in TC is most pronounced, as indicated by the most negative effect size on the graph (Supplementary Figure S9).

Furthermore, a significant association was found between the duration of sesame supplementation and a decrease in TG levels (Coefficient = 0.02, p value = 0.002). The dose–response curve for TG levels shows an optimal effect at around 8 weeks of supplementation (Supplementary Figure S10).

GRADE assessment

The GRADE profile of sesame supplementation on the outcomes with the certainty in outcomes is shown in Table 4. The quality of evidence was reported very low for DBP, SBP, FBS, Insulin, TNF-a, HDL, LDL, TC, TG, MDA, and TAC and was reported low for BF, BMI, Weight, WHR, and HOMA-IR except for HC, WC, HbA1c, CRP, and IL-6 that was moderate.

Table 4.

GRADE profile of sesame supplementation on cardiovascular disease risk factors

Outcomes	Risk of bias	Inconsistency	Indirectness	Imprecision	Publication bias	Number (INT/CON)	SMD (95% CI)	Quality of evidence
BF	Serious a	Not serious	Not serious	Very seriousb,c	None	100/94	− 0.12 (− 0.40, 0.16)	⨁⨁◯◯ Low
BMI	Serious a	Not serious	Not serious	Very seriousb,c	None	108/103	− 0.03 (− 0.30, 0.24)	⨁⨁◯◯ Low
HC	Not serious	Not serious	Not serious	Very seriousb,c	None	65/63	− 0.17 (− 0.52, 0.17)	⨁⨁⨁◯ Moderate
WC	Not serious	Not serious	Not serious	Very seriousb,c	None	87/85	− 0.16 (− 0.46, 0.13)	⨁⨁⨁◯ Moderate
Weight	Serious a	Not serious	Not serious	Very seriousb,c	None	153/148	− 0.02 (− 0.24, 0.21)	⨁⨁◯◯ Low
WHR	Serious a	Not serious	Not serious	Very seriousb,c	None	108/103	− 0.05 (− 0.32, 0.22)	⨁⨁◯◯ Low
DBP	Not serious	Very serious d	Not serious	Very seriousb,c	None	82/83	− 0.23 (− 1.41, 0.95)	⨁⨁◯◯ Low
SBP	Not serious	Very serious d	Not serious	Very seriousb,c	None	82/83	− 0.32 (− 1.47, 0.83)	⨁◯◯◯ Very low
FBS	Serious a	Very serious d	Not serious	Very seriousb,c	None	86/81	− 0.57 (− 1.16, 0.02)	⨁◯◯◯ Very low
HbA1c	Serious a	Not serious	Not serious	Seriousc	None	69/69	− 0.67 (− 1.01, − 0.32)	⨁⨁⨁◯ Moderate
HOMA-IR	Serious a	Not serious	Not serious	Very seriousb,c	None	67/64	− 0.08 (− 0.42, 0.26)	⨁⨁◯◯ Low
Insulin	Very serious a	Very serious d	Not serious	Very seriousb,c	None	90/87	1.25 (− 0.27, 2.77)	⨁◯◯◯ Very low
Hs-CRP	Not serious	Serious d	Not serious	Seriousb	None	122/120	− 0.51 (− 0.96, − 0.05)	⨁⨁⨁◯ Moderate
IL-6	Not serious	Very serious d	Not serious	Seriousc	None	101/102	− 0.74 (− 1.16, − 0.32)	⨁⨁⨁◯ Moderate
TNF-a	Not serious	Very serious d	Not serious	Very seriousb,c	None	79/79	− 0.73 (− 1.84, 0.38)	⨁◯◯◯ Very low
HDL	Very serious a	Not serious	Not serious	Very seriousb,c	None	144/129	0.21 (− 0.06, 0.48)	⨁◯◯◯ Very low
LDL	Very serious a	Serious d	Not serious	Very seriousb,c	None	144/129	− 0.16 (− 0.50, 0.18)	⨁◯◯◯ Very low
TC	Very serious a	Not serious	Not serious	Very seriousb,c	None	144/129	− 0.22 (− 0.49, 0.05)	⨁◯◯◯ Very low
TG	Very serious a	Serious d	Not serious	Very seriousb,c	None	144/129	0.44 (− 0.19, 0.28)	⨁◯◯◯ Very low
MDA	Serious a	Very serious d	Not serious	Very seriousb,c	None	102/100	− 1.35 (− 2.90, 0.20)	⨁◯◯◯ Very low
TAC	Very serious a	Serious d	Not serious	Very seriousb,c	None	65/63	0.16 (− 0.39, 0.72)	⨁◯◯◯ Very low

BF, body fat; BMI, body mass index; CI, confidence interval; CON, control group; DBP, diastolic blood pressure; FBS, fasting blood sugar; HbA1c, hemoglobin A1C; HC, hip circumference; HDL, high-density lipoprotein; HOMA-IR, homeostatic model assessment of insulin resistance; hs-CRP, high-sensitivity C-reactive protein; IL-6, interleukin 6; INT, intervention group; LDL, low-density lipoprotein; MDA, malondialdehyde; SBP, systolic blood pressure; SMD, standardised mean difference; TAC, total antioxidant capacity; TC, total cholesterol; TG, triglycerides; TNF-a, tumor necrosis factor alpha; WC, waist circumference; WHR, waist-to-hip ratio

^aMore than 20% of RCTs for this outcome had a high risk of bias for at least one component of the Cochrane risk of bias tool. Those biases had a significant effect on the results of RCTs

^bDowngraded since the 95% CI crosses the threshold of interest

^cDowngraded since the participants included were less than 400 people

^dThe I² value was > 50% (or Heterogeneity among the studies was high)

Discussion

To our knowledge, this is the first systematic review and dose–response meta-analysis to evaluate the effects of sesame consumption on cardiovascular outcomes in adults. We identified 13 RCTs with 521 participants. These studies suggest that sesame supplementation had significant beneficial effects on some cardiovascular disease risk factors including HbA1c, CRP, and IL6. Also, there was a significant decline in serum levels of TC among participants living in Iran, aged less than 50 years, with chronic diseases, who received a dose of less than 10 gr/day of supplements based on subgroup analysis. Moreover, the serum levels of HDL increased with a dose of less than 10 gr/day. The results of the subgroup analysis showed that the sesame supplement reduces MDA in women older than 50 years, with chronic diseases among participants living in Iran. However, sesame consumption had no effect on other cardiovascular risk factors including anthropometric measurements and blood pressure.

Cardiovascular diseases encompass a broad spectrum of conditions related to the heart and blood vessels [30]. In recent investigations, the substantial promise of medicinal plants and their compounds has been emphasized as valuable assents for preventing and addressing a variety of health concerns [31–33]. Sesame is acknowledged as a medicinal spice with diverse properties such as numerous anti-cardiovascular and metabolic risk factors [11, 18, 34–36].

The study found that sesame supplementation significantly reduced IL-6. Also, the result showed that consuming 10 g or less of sesame significantly reduced CRP levels in healthy subjects regardless of sex or those at risk but without chronic disease, in a duration of less than 6 weeks, in a sample size of more than 40 subjects, compared to baseline measurements. The findings of this study are consistent with previous clinical research, indicating that sesame supplementation significantly reduces inflammatory markers [18, 20, 21]. Narasimhulu et al. [37] found that feeding female mice without LDL receptors a sesame oil rich diet for 3 months significantly lowered IL-1α and IL-6. As well as Helli et al. reported that a 6-week sesamin supplement significantly lowered serum levels of inflammatory biomarkers in rheumatoid arthritis patients [20]. The study suggested that sesame oil reduces the expression of genes for proinflammatory cytokines [38]. In terms of inflammation in another study, 15 gr/day of sesame oil supplementation for eight weeks did not significantly alter CRP levels, but it did notably reduce MDA levels [18]. Mohammad Shahi et al. [21] reported that the supplementation of sesame capsules at a dosage of 200 mg/day over an 8-week period was associated with a decline in inflammatory biomarkers including TNF-alpha, IL-6, and hs-CRP. In contrast, Wu et al. reported that a daily intake of 25 gr/day of sesame for 5 weeks did not impact inflammatory markers in obese or overweight individuals. This inconsistency with other studies may be attributed to the participants being healthy, with their baseline inflammatory levels already within normal limits [26]. Various mechanisms contribute to the effects of bioactive compounds in reducing oxidative stress [10, 11, 34]. While sesame oil and its lignans have shown anti-inflammatory benefits in animal models, human studies are scarce [39]. Sesame's anti-inflammatory effects may stem from preserving the antioxidants of serum, decreasing LDL oxidation, inhibiting delta-5 desaturase, reducing arachidonic acid and prostaglandin synthesis, boosting gamma tocopherol levels, and decreasing IL-1β, IL-6, and thromboxane B2 production and inhibiting free radicals [21, 38, 40]. Moreover, sesame, with its anti-inflammatory fatty acids, helps reduce inflammation by blocking prostaglandin E2 production [40]. Sesame also works by inhibiting the p38 mitogen-activated protein kinase pathway and blocking nuclear factor-κB pathways activation [40]. Sesame administration lowers serum lipid levels in rodents and boosts fatty acid oxidation. This effect may be due to sesame’s impact on peroxisome proliferator-activated receptor (PPAR)-mediated transcription, which influences on inflammation in both animal and human studies [40, 41].

In this meta-analysis, sesame supplementation improved the glycemic profile and decreased HbA1c without any significant effect on FBS, insulin, and HOMA-IR. Previously, Aslam et al. [6] showed that intake of 30 ml/day of sesame oil for 3 months could decrease the serum FBS, and HbA1c and increase insulin in type 2 diabetes patients. Our findings are consistent with the mentioned results, supporting the notion that sesame has the potential to reduce oxidative stress and subsequently improve HbA1c levels. Mohammad Shahi et al. [21] reported that the supplementation of sesame at a dosage of 200 mg/day for 2 months was associated with a decline in FBS and HbA1c in participants with type 2 diabetes mellitus. Moreover, Tobeiha et al. [18] showed that oral consumption of sesame oil (15 gr/daily) for 8 weeks may improve some glycemic markers of patients with type 2 diabetes. Intake of sesame resulted in better HbA1c levels, though the underlying mechanism remains uncertain; one possible explanation is the antioxidant activity of sesame. Additionally, monounsaturated oils contributed to glycation improvement, likely due to their blood sugar-lowering properties [42]. As well as sesame is a popular spice rich in bioactive compounds like flavonoids and phenolic acid. These compounds have various biological effects, including anti-hyperglycemic activities that help protect pancreatic beta cells [11, 43, 44]. Moreover, Nomura et al. reported that plant-extract phenolic compounds boost insulin levels in RIN-5F clonal beta cells [45].

The diverse therapeutic effects observed in our systematic review can be attributed to the synergistic actions of multiple bioactive components in sesame. Sesame lignans, particularly sesamin and sesamolin, serve as the primary bioactive compounds that modulate multiple physiological pathways [46]. These lignans enhance lipid metabolism by activating PPARα, while simultaneously inhibiting HMG-CoA reductase, the rate-limiting enzyme in cholesterol synthesis [9]. The unsaturated fatty acids in sesame oil, particularly oleic and linoleic acids, contribute to improved lipid profiles and reduced inflammation through modulation of membrane fluidity and cellular signaling pathways [47]. Sesame’s rich fiber content plays a crucial role in glycemic control by slowing glucose absorption and improving insulin sensitivity through enhanced incretin secretion [48]. The presence of both γ-tocopherol and sesamin creates a unique antioxidant system where sesamin inhibits γ-tocopherol metabolism, leading to sustained antioxidant activity and reduced oxidative stress [49]. Additionally, the protein content of sesame, with its high concentration of arginine and methionine, supports nitric oxide production and cellular antioxidant systems [11]. The minerals present in sesame, particularly magnesium and calcium, further complement these effects by supporting proper glucose metabolism and blood pressure regulation through their roles in cellular signaling and vascular function [11, 50].

A subgroup study demonstrated that taking sesame supplements or capsules in a dose of ≤ 10 gr/day and in patients with chronic diseases ≤ 50 years in Iran led to a substantial decrease in TC serum levels. Also, sesame supplementation in a dose of ≤ 10 gr/day caused an increase in the HDL-C serum levels, according to the findings of this systematic review and meta-analyses. Mokhber et al. [34] showed that intake of 500 mg/day of sesame lignans in patients with cardiovascular diseases who were candidates for angiography caused a significant decrease in serum lipid profile. Additionally, Shivaprasad et al. demonstrated that consuming 500 mg of sesame extract daily for six weeks reduced LDL-C and TC in individuals with hyperlipidemia [51]. The unsaturated fatty acids in sesame oil improve lipid profiles by lowering LDL-C and lipid oxidation while increasing HDL-C [6, 52]. Sesame administration in rodents has been associated with lower serum lipid levels and increased fatty acid oxidation, likely due to its impact on PPAR which regulates lipoprotein metabolism in vitro, as well as in animal and human studies [21, 41].

In this meta-analysis, sesame consumption improved antioxidant parameters such as MDA in women older than 50 years, with any health status, and in any country, based on subgroup analysis. The current findings align with prior investigations involving both human and animal subjects. Tobeiha et al. [18] in a double‑blind, randomized controlled trial showed that consumption of 15 g/day of sesame oil for 2 months can reduce MDA levels but not TAC in patients with type 2 diabetes. MDA levels in the body elevate during prolonged oxidative stress [53]. Sesame oil might possess antioxidant qualities and help lower the production of harmful metabolites from fatty acid oxidation. The antioxidative properties of sesame oil might be attributed to lignans like sesamin and sesamol. The antioxidant benefits of sesame could be connected to its role in reducing the production of free radicals and in preserving the concentration of antioxidants within the serum [38]. However, the precise active compounds responsible for its strong antioxidant effects have yet to be definitively identified [18]. Aslam et al. [6] conducted a randomized controlled trial with the aim of investigating the effect of white sesame seed oil supplementation oxidative stress biomarkers in participants with type 2 diabetes mellitus, in which the consumption of white sesame seed oil caused a decrease in thiobarbituric acid reactive substance and an increased in endogenous antioxidant enzymes in these participants. This phenomenon might result from improvements in the body's antioxidant defense mechanisms or a rise in the activity that neutralizes free radicals [6].

In the present meta-analysis, it was shown that consumption of sesame had no effect on anthropometric measurements and blood pressure. After the intervention with sesame, there were no noticeable changes in most anthropometric measures, including weight, BMI, BF, WC, HC, and WHR. This result aligns with the findings of Tobeiha et al. [18] who also did not observe any effect of 15 gr/day of sesame oil intake for 2 months on anthropometric items. Research on the impact of sesame seeds and oil on body composition is relatively sparse, with only a few studies exploring their potential effects. Sankar et al. reported notable decreases in WHR, BMI, and weight in diabetics after 45 days of sesame oil use, but these changes largely reversed after the intervention ended. The study attributed the effects to the oil’s polyunsaturated fatty acids (PUFAs) [54]. In contrast, one study found no significant differences in anthropometric parameters between the sesame supplementation group and the placebo group [21]. As well as, in another study, consuming 25 g/day of sesame seeds for 5 weeks did not improve blood pressure in overweight or obese individuals which may be related to the small duration or health status of participants [26].

The clinical outcomes observed in our systematic review can be attributed to the complex interplay of sesame's bioactive compounds within key metabolic and physiological pathways. Specifically, sesame lignans (sesamin and sesamolin) act as potent modulators of lipid metabolism through the activation of peroxisome proliferator-activated receptor alpha (PPARα), leading to enhanced fatty acid oxidation and reduced lipogenesis, which explains the observed improvements in lipid profiles [55, 56]. The antihypertensive effects documented in our analysis align with sesame lignans' ability to inhibit angiotensin-converting enzyme (ACE) and enhance endothelial nitric oxide synthase (eNOS) activity, promoting vasodilation and blood pressure regulation [57]. On the glycemic control front, sesamin has been shown to enhance insulin sensitivity through activation of AMPK signaling pathways and increased glucose transporter type 4 (GLUT4) translocation in skeletal muscle cells, supporting our findings of improved glycemic parameters [36]. The reduction in inflammatory biomarkers observed in our meta-analysis can be mechanistically explained by sesame's ability to suppress nuclear factor-kappa B (NF-κB) signaling and subsequently decrease pro-inflammatory cytokine production [58]. Furthermore, the improvements in oxidative stress parameters align with sesame lignans' demonstrated capacity to upregulate antioxidant enzymes through the Nrf2/ARE pathway, while simultaneously inhibiting NADPH oxidase activity, thereby reducing reactive oxygen species generation [59].

The mechanisms underlying sesame's health benefits extend beyond cardiovascular parameters through interconnected biochemical pathways. Sesame lignans, particularly sesamin and sesamolin, exhibit pleiotropic effects by activating peroxisome proliferator-activated receptors (PPARs), which regulate lipid metabolism, glucose homeostasis, and inflammatory responses [60]. Recent evidence suggests that sesamin enhances mitochondrial biogenesis through PGC-1α activation, potentially improving cellular energy metabolism across multiple tissues [61]. Additionally, the antioxidant properties of sesame's bioactive compounds, including γ-tocopherol and sesaminol, contribute to neuroprotection by reducing oxidative stress and inflammatory mediators in the central nervous system [62]. For instance, sesamin has been shown to cross the blood–brain barrier and activate the Nrf2/HO-1 pathway, which enhances endogenous antioxidant defenses and suppresses neuroinflammation [63, 64]. Furthermore, sesame's immunomodulatory effects are mediated through the inhibition of NF-κB signaling and subsequent reduction in pro-inflammatory cytokine production, suggesting potential applications in immune-related disorders [49, 65]. These molecular mechanisms highlight how sesame's cardiovascular benefits may be part of a broader spectrum of physiological effects, including neuroprotection, metabolic regulation, and immune system modulation.

The effect of sesame on anthropometric measurements and blood pressure appears inconsistent, likely due to variations in types and doses of intervention, study populations, and durations. Overall, the impact of sesame supplementation on these indices is not well-established, and further research is needed to clarify its effects.

Strengths and limitations

This systematic review and dose–response meta-analysis represents the first comprehensive effort to evaluate the effects of sesame (Sesamum indicum L.) products and their bioactive compounds on a range of cardiovascular and metabolic health parameters in humans. By adhering to PRISMA guidelines and employing the GRADE framework, the study offers a robust synthesis of evidence, emphasizing methodological rigor and transparency. Random-effects models and sensitivity analyses were used to address heterogeneity, while subgroup and dose–response analyses provided nuanced insights into the effects of intervention duration, dosages, and forms of supplementation. Additionally, this analysis stands out for its inclusion of various sesame-based products, such as seeds, oil, and lignans, thereby capturing a broad spectrum of bioactive properties and their potential health benefits. Moreover, plausible biological mechanisms, such as sesame's antioxidant, anti-inflammatory, and lipid-modulating effects, were explored to strengthen the clinical relevance of the findings.

Despite its strengths, the study has certain limitations that should be acknowledged. The small number of included studies and participants (13 studies with 521 individuals) reduces statistical power, particularly for subgroup analyses and meta-regressions. Significant heterogeneity in study designs—such as variations in intervention duration (4–12 weeks), dosages (< 10 g/day to > 50 g/day), and forms of supplementation—complicated direct comparisons. Additionally, most of the included studies were conducted in Iran, which may limit the generalizability of findings to populations with different dietary habits, genetic profiles, and environmental conditions. Variability in measurement methodologies, such as the use of differing laboratory kits, introduces potential biases, while the exclusion of non-English studies may have omitted relevant evidence. Furthermore, the short-term nature of the included trials restricts insights into the long-term effects of sesame supplementation. Lastly, the GRADE assessment revealed low or very low-quality evidence for several outcomes, underscoring the need for future research to address gaps such as confounding factors, standardized protocols, and mechanistic investigations.

Future research directions

To build upon the findings of this systematic review and dose–response meta-analysis, future research should prioritize addressing the identified limitations to strengthen the evidence base for sesame (Sesamum indicum L.) supplementation. First, larger, multi-center RCTs are needed to enhance the statistical power and generalizability of findings. These trials should include diverse populations across different geographic regions, dietary habits, and genetic profiles to mitigate the potential biases introduced by the predominance of studies conducted in Iran. Additionally, extending the follow-up duration in future studies will help evaluate the long-term sustainability of sesame supplementation's effects on cardiovascular and metabolic health outcomes, offering valuable insights into its potential role in chronic disease prevention.

Further, future research should adopt standardized methodologies to improve the comparability and reproducibility of findings. This includes harmonizing measurement protocols for key outcomes such as inflammatory biomarkers, lipid profiles, and oxidative stress parameters. Mechanistic studies are also essential to elucidate the biological pathways through which sesame's bioactive compounds exert their effects, with a particular focus on antioxidants, anti-inflammatory agents, and lipid-modulating compounds like sesamin and sesamol. Moreover, trials should incorporate detailed assessments of participants' dietary intake, physical activity, and medication use to better account for potential confounders.

This study provides valuable insights into sesame supplementation's potential benefits but highlights critical areas for future exploration. Larger, multi-center trials with diverse populations, extended follow-up periods, and detailed mechanistic studies are needed to validate and expand on the findings. By addressing these gaps, future research can build a stronger evidence base and further clarify sesame's role in promoting cardiovascular and metabolic health.

Conclusion

The systematic review and meta-analysis of thirteen studies suggest that sesame supplementation exerts a beneficial effect on some cardiovascular disease risk factors in adults. However, further long-term and well-designed RCTs with better quality in different regions are needed to assess and confirm these results further.

Abbreviations

ACE

Angiotensin-converting enzyme

BF

Body fat

BMI

Body mass index

CVD

Cardiovascular disease

CI

Confidence intervals

DBP

Diastolic blood pressure

eNOS

Enhance endothelial nitric oxide synthase

FBS

Fasting blood sugar

GLUT4

Glucose transporter type 4

HbA1c

Hemoglobin A1c

HbA1c

Hemoglobin A1C

HDL

High-density lipoprotein

hs-CRP

High-sensitivity c-reactive protein

HC

Hip circumference

HOMA-IR

Homeostatic model assessment of insulin resistance

PROSPERO

International Prospective Register of Systematic Reviews

Il-6

Interleukin 6

LDL

Low-density lipoprotein

MDA

Malondialdehyde

MUFAs

Monounsaturated fatty acids

NF-κB

Nuclear factor-kappa B

PUFAs

Polyunsaturated fatty acids

PPARα

Peroxisome proliferator-activated receptor alpha

PRISMA

Preferred Reporting Items for Systematic Reviews and Meta-Analyses

RCTs

Randomized controlled trials

SDs

Serum insulin, standard deviations

SDs

Standard deviations

SE

Standard error

SMDs

Standardized mean differences

SBP

Systolic blood pressure

TAC

Total antioxidant capacity

TC

Total cholesterol

TG

Triglycerides

TNF-α

Tumour necrosis factor alpha

T2DM

Type 2 diabetes mellitus

WC

Waist circumference

WHR

Waist-to-hip ratio

Author contributions

Conceptualization: Ali Jafari. Data curation: Ali Jafari, Bahare Parsi Nezhad, Niloufar Rasaei, Elahe Aleebrahim-Dehkordi, Alireza Alaghi. Formal analysis: Ali Jafari, Abdolhalim Rajabi. Investigation: Ali Jafari, Bahare Parsi Nezhad, Alireza Alaghi. Methodology: Ali Jafari, Elahe Aleebrahim-Dehkordi, Alireza Alaghi. Project administration: Ali Jafari, Alireza Alaghi. Software: Ali Jafari, Bahare Parsi Nezhad. Visualization: Ali Jafari Supervision: Ali Jafari. Validation: Ali Jafari, Niloufar Rasaei, Abdolhalim Rajabi. Writing—original draft: Ali Jafari, Bahare Parsi Nezhad, Niloufar Rasaei, Alireza Alaghi. Writing—review and editing: Ali Jafari, Bahare Parsi Nezhad, Elahe Aleebrahim-Dehkordi, Abdolhalim Rajabi.

Funding

This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

Availability of data and materials

All relevant data are provided within the manuscript and supplementary file. Additionally, data analyzed for this study are available upon request from the corresponding author.

Declarations

Competing interests

The authors whose names are listed in this article certify that they have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.