Sesame and cardiovascular balance: a GRADE-assessed systematic review and meta-analysis of its role in modulating risk factors among individuals with prehypertension and hypertension

Abstract

Background

This systematic review aimed to evaluate the clinical effectiveness of sesame supplementation on cardiovascular health parameters in pre-hypertensive and hypertensive individuals.

Methods

A systematic search was conducted up to August 2024.Eligible studies evaluated the effects of sesame supplementation on blood pressure, anthropometric indices, lipid profiles, and oxidative stress markers. Study quality and evidence strength were assessed using the Cochrane Risk of Bias tool and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach, respectively.

Results

Six trials, with interventions ranging from 4 to 8 weeks and involving 465 participants, reported reductions in body mass index (weighted mean difference [WMD], −3.00 kg/m²; 95% confidence interval [CI], −3.43 to −2.57; P < 0.001), weight (WMD, −7.51 kg; 95% CI, −8.64 to −6.37; P < 0.001), diastolic blood pressure (WMD, −16.29 mmHg; 95% CI, −25.37 to −7.22; P < 0.001), systolic blood pressure (WMD, −20.78 mmHg; 95% CI, −32.26 to −9.31; P < 0.001), high-density lipoprotein cholesterol (WMD, 2.21 mg/dL; 95% CI, 0.09 to 4.33; P = 0.041), total cholesterol (WMD, −49.29 mg/dL; 95% CI, −96.71 to −1.86; P = 0.042), triglycerides (WMD, −55.05 mg/dL; 95% CI, −79.51, −30.59; P < 0.001), catalase (WMD, 3.38 U/mg of protein; 95% CI, 3.24 to 3.52; P < 0.001), erythrocyte glutathione peroxidase (WMD, 0.93 U/min/mg of hemoglobin [Hb]; 95% CI, 0.38 to 1.47; P = 0.001), erythrocyte superoxide dismutase (WMD, 3.11 U/ mg of Hb; 95% CI, 2.92 to 3.29; P < 0.001), and thiobarbituric acid reactive substances (WMD, −2.94 nmol/dL; 95% CI, −3.99 to −1.89; P < 0.001). In contrast, no significant effects were observed on low-density lipoprotein cholesterol or malondialdehyde). However, the GRADE assessment rated the evidence as very low across all outcomes due to high heterogeneity, small sample sizes, and methodological limitations, rendering the clinical plausibility of these findings uncertain.

Conclusions

While sesame supplementation showed apparent improvements in several cardiovascular risk factors, the very low certainty of evidence, driven by study limitations and implausible effect sizes, precludes definitive conclusions. High-quality, well-designed randomized controlled trials are needed to clarify sesame's therapeutic role in prehypertension and hypertension.

Trial Registration

PROSPERO Identifier: CRD42025634033

Graphical Abstract

BACKGROUND

Hypertension (HTN) remains one of the most prevalent yet preventable risk factors for cardiovascular diseases, affecting approximately 1.28 billion adults worldwide [1]. Despite advances in pharmacological treatments, the management of blood pressure continues to present significant challenges to global health systems, with nearly half of affected individuals failing to achieve adequate control [2]. This pressing health concern has led to increased exploration of complementary approaches, particularly through dietary interventions and functional foods that may offer natural alternatives or adjunct therapies for blood pressure management [3,4,5].

Sesame (Sesamum indicum L.), a traditional oilseed crop with millennia of cultivation history, has emerged as a promising candidate for cardiovascular health support [6]. This ancient crop contains an impressive array of bioactive compounds, including lignans (sesamin, sesamolin), tocopherols, phytosterols, and polyunsaturated fatty acids, which demonstrate potential antihypertensive properties [7,8]. Recent meta-analyses have highlighted sesame’s multiple mechanisms of action, including its ability to improve blood pressure [9], reduce oxidative stress [10], and modulate inflammatory pathways [11]. Preliminary studies have also suggested its role in improving lipid profiles and enhancing the efficacy of conventional antihypertensive medications [12].

While individual clinical trials have investigated sesame’s effects on blood pressure and related cardiovascular parameters, the findings have varied in terms of dosage, duration, and observed outcomes [13,14,15,16,17,18]. Some studies report significant reductions in both systolic and diastolic blood pressure [13,14], while others show more modest effects [15,16]. The heterogeneity in research methodologies and participant characteristics has created a need for a comprehensive analysis to establish evidence-based recommendations for clinical practice.

The present study represents the first systematic review and meta-analysis to evaluate the multifaceted effects of sesame supplementation in pre-hypertensive and hypertensive populations. Our investigation encompasses a broad spectrum of clinically relevant outcomes, including blood pressure parameters, anthropometric indices, lipid profiles, and oxidative stress markers. By employing rigorous statistical methodologies, including sensitivity analyses and publication bias assessments, we provide a thorough synthesis of existing randomized controlled trials (RCTs). This systematic evaluation is particularly timely given the growing global burden of HTN and the increasing interest in natural therapeutic approaches. Our analysis offers valuable insights into the potential role of sesame supplementation in cardiovascular health management, addressing a critical gap in the current literature and providing evidence-based guidance for healthcare practitioners. Through this comprehensive assessment, we aim to establish a foundation for future clinical recommendations regarding the use of sesame supplementation as a complementary approach in the management of pre-HTN and HTN.

METHODS

Protocol and registration

We conducted this systematic review and meta-analysis in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement guidelines [19]. Our review protocol was registered beforehand on PROSPERO (registration ID: CRD42025634033).

Search strategy and study selection

We performed a systematic search across five major databases: PubMed, ISI Web of Science, Scopus, Embase, and the Cochrane Library, covering publications through August 2024. Our search terms encompassed variations of sesame (including ‘Sesamum indicum,’ ‘sesamin,’ ‘sesamol,’ ‘sesamolin’) combined with methodology-related terms (‘randomized,’ ‘clinical trial,’ ‘RCT’). The detailed search syntax is available in Supplementary Data 1.

We supplemented our electronic search by examining reference lists of included papers and relevant review articles. Our inclusion criteria focused on clinical trials investigating sesame supplementation's effects on blood pressure, anthropometric measurements, lipid parameters, and oxidative stress indicators in adults with pre-HTN or HTN. We excluded non-interventional research, review articles, correspondence, animal experiments, and laboratory studies.

Title and abstract screening was performed independently by 2 team members (V.M. and H.M.) using predetermined eligibility criteria. Selected articles underwent full-text review, with any selection disagreements resolved through team discussion or arbitration by a third researcher (A.J.). We managed duplicate entries using EndNote X7 software.

Data extraction

Two independent reviewers extracted information using a custom data collection template. We documented: author information, publication date, study location, participant demographics (age, gender, health status), intervention specifications (sesame preparation, dose, treatment duration), control conditions, and key outcomes including:

• • Anthropometric measurements: body mass index (BMI), body weight

• • Cardiovascular parameters: systolic blood pressure (SBP), diastolic blood pressure (DBP)

• • Lipid markers: high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglycerides (TG)

• • Oxidative stress indicators: catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), malondialdehyde (MDA), thiobarbituric acid reactive substances (TBARS)

Quality assessment

We assessed methodological quality using the Cochrane Risk of Bias tool version 2.0 [20]. Two independent reviewers evaluated 7 key domains: randomization process, allocation concealment, participant/personnel blinding, outcome assessment blinding, data completeness, selective reporting, and other potential biases. Based on these criteria, we classified studies as good, fair, or poor quality.

Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) assessment

We evaluated the strength of evidence for each outcome using GRADE methodology [21]. This systematic approach considered 5 key factors: study limitations, effect consistency, precision, directness, and publication bias. Two team members independently conducted GRADE assessments, resolving disagreements through discussion or consultation with a third reviewer.

Statistical analysis

We conducted all analyses using Stata 15.0 software (StataCorp, College Station, TX, USA). Treatment effects were quantified using weighted mean differences (WMDs) with corresponding 95% confidence intervals (CIs). Given the expected variation between studies, we employed a random-effects model. We quantified heterogeneity using the I² statistic, interpreting values of 25%, 50%, and 75% as low, moderate, and high heterogeneity, respectively [22].

To test result robustness, we performed leave-one-out sensitivity analyses. We assessed publication bias through Egger’s regression test and funnel plot examination. For outcomes showing significant effects, we conducted additional analyses to validate our findings [23].

We set statistical significance at P < 0.05 throughout our analyses. Primary outcomes are presented as forest plots.

Subgroup analyses were conducted based on health condition (HTN without diabetes, including HTN, pre-HTN, and mild HTN vs. HTN with diabetes), sesame dosage (≤ 3,000, > 3,000 mg/day), intervention duration (< 8, ≥ 8 weeks), control approach (placebo, usual care or usual treatment), intervention age (< 50, ≥ 50 years), geographic region (South Asia, including India; East and Southeast Asia, including Thailand and Japan), intervention type (capsule form, oil form), baseline BMI (healthy weight or overweight: ≤ 30 kg/m², obese: > 30 kg/m²), and sample size (< 100, ≥ 100 participants).

RESULTS

Study selection

The study selection process is illustrated in Fig. 1. A total of 337 studies were identified through database searches: PubMed (n = 29), ISI Web of Science (n = 69), Scopus (n = 92), Embase (n = 113), and the Cochrane Library (n = 34). After removing 100 duplicates, irrelevant studies (n = 69), and animal studies (n = 24), 244 studies were screened based on titles and abstracts. Of these, 204 were excluded, resulting in 44 full-text studies evaluated further. 38 studies were excluded for not reporting the desired outcomes, as detailed in Supplementary Table 1. Consequently, 6 studies comprising 465 participants were included in the systematic review and meta-analysis.

Fig. 1. Flowchart of study selection for inclusion trials in the systematic review.

Study characteristics

The characteristics of the included studies are summarized in Table 1. Table 2 and Supplementary Figs. 1, 2, 3, 4 show the WMDs and 95% CIs for changes in BMI, weight, DBP, SBP, HDL-C, LDL-C, TC, TG, CAT, erythrocyte GPx, erythrocyte SOD, MDA, and TBARS.

Table 1. Characteristic of included studies in the meta-analysis.

Studies	Country	Study design	Health condition	Sample size (INT/CON)	Baseline lipid profile status (INT/CON)	Means age (yr) (INT/CON)	BMI (kg/m2) (INT/CON)	Dose (mg/day)	Duration (week) of supplementation	Type of supplement (INT/CON)	Outcomes
Sankar et al., 2006 [13]	India	Cross over	Hypertensive diabetic	40/40 (B)	TC (mg/dL): 250.7/205.8	56.63 ± 7.3/56.63 ± 7.3	31.8 ± 1.8/29.9 ± 1.8	35,000	6	Oil: Sesame/Regular oil like palm or groundnut oils	SBP, DBP, weight, BMI, WC, HC, WHR, fasting glucose, HbA1c, TC, HDL-C, LDL-C, TG, TBARS, CAT, SOD, GPx, GSH
					HDL-C (mg/dL): 47.8/48.3					+
					LDL-C (mg/dL): 158.96/121.3					Beta blocker (atenolol, 50–100 mg/day) & sulfonylurea (glibenclamide, 10 mg/day)
					TG (mg/dL): 236/181.16
Sankar et al., 2006 [14]	India	Cross over	Hypertensive diabetic	50/50 (B)	TC (mg/dL): 220/217	35–60/35–60	29.4 ± 3/27.08 ± 3.30	35,000	6	Oil: Sesame/Whatever original oil they had been taking before (mostly sesame oil, grounnut oil or palm oil)	SBP, DBP, weight, BMI, TC, HDL-C, LDL-C, TG, TC/HDL-C, TBARS, erythrocyte SOD, erythrocyte GPx, plasma CAT, reduced GSH
					HDL-C (mg/dL): 46/47					+
					LDL-C (mg/dL): 136.0/138					Diuretics (hydrochlorothiazid) or beta blocker (atenolol)
					TG (mg/dL): 194.8/159.0
					TC/HDL-C ratio: 4.8/4.7
Miyawaki et al., 2009 [15]	Japan	PC, DB, cross over	Mild HTN	12/13 (B)	NA	49.07 ± 8.16/49.07 ± 8.16	24.56 ± 0.46/24.56 ± 0.46	60	4	Capsule: Sesame/Placebo	SBP, DBP
Wichitsranoi et al., 2011 [16]	Thailand	R, PC, DB	Pre-HTN	15/15 (B)	NA	49.3 ± 7.7/50.3 ± 5.6	26.6 ± 3.2/25.6 ± 2.4	2,520	4	Capsule: Black sesame meal/Placebo	SBP, DBP, MDA
Karatzi et al., 2012 [17]	Greece	Controlled trial	HTN	17/13 (M)	NA	49.8 ± 8.4/56.8 ± 12	27.7 ± 2.4/28.5 ± 2.9	35,000	8	Oil: Sesame/Placebo	CRP, TNF-α, MDA, TAC
Devarajan et al., 2016 [18]	India	R, open label	HTN	100/100 (B)	TC (mg/dL): 232.0/231.0	48.1 ± 10.2/50.1 ± 13.4	26.7 ± 3.9/25.8 ± 4.6	34,500	8	Oil: Sesame oil + rice bran oil + nifedipine/Nifedipine	SBP, DBP, MAP, TC, TG, HDL-C, LDL-C, non-HDL-C
					HDL-C (mg/dL): 43.8/43.8
					LDL-C (mg/dL): 151.0/150.0
					TG (mg/dL): 184.0/186.0
					Non-HDL-C (mg/dL): 188.0/187.0

INT, intervention group; CON, control group; BMI, body mass index; B, both sex; TC, total cholesterol; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; TG, triglycerides; SBP, systolic blood pressure; DBP, diastolic blood pressure; WC, waist circumference; HC, hip circumference; WHR, waist-to-hip ratio; HbA1c, hemoglobin A1c; TBARS, thiobarbituric acid reactive substances; CAT, catalase; SOD, superoxide dismutase; GPx, glutathione peroxidase; GSH, glutathione; PC, placebo-controlled; DB, double-blinded; M, male; HTN, hypertension; NA, not applicable; MDA, malondialdehyde; R, randomized; CRP, C-reactive protein; TNF-α, tumor necrosis factor-α; TAC, total antioxidant capacity; MAP, mean arterial pressure.

Table 2. Description of the analysis results of sesame supplementation on pre-hypertensive and hypertensive patients.

Variables			No. of studies	No. of participant	WMD (95% CI)	P-value	Heterogeneity
							P heterogeneity	I2	P between sub-groups
BMI (kg/m2)			2	180	−3.00 (−3.43 to −2.57)	< 0.001	0.870	0.0%
Weight (kg)			2	180	−7.51 (−8.64 to −6.37)	< 0.001	0.766	0.0%
DBP (mmHg)			5	435	−16.29 (−25.37 to −7.22)	< 0.001	< 0.001	98.7%
	Health condition								< 0.001
		HTN without diabetes	3	255	−8.38 (−15.36 to −1.40)	0.019	< 0.001	93.2%
		HTN with diabetes	2	180	−28.01 (−29.55 to −26.46)	< 0.001	0.822	0.0%
	Sesame dosage (mg/day)								0.012
		≤ 3,000	2	55	−5.73 (−12.82 to 1.36)	0.113	0.020	81.6%
		> 3,000	3	380	−23.03 (−34.47 to −11.58)	< 0.001	< 0.001	99.2%
	Intervention duration (weeks)								0.509
		< 8	4	235	−17.10 (−29.20 to −4.99)	0.006	< 0.001	98.4%
		≥ 8	1	200	−13.00 (−14.13 to −11.87)	< 0.001	-	-
	Control approach								0.012
		Placebo	2	55	−5.73 (−12.82 to 1.36)	0.113	0.020	81.6%
		Usual care or usual traetment	3	380	−23.03 (−34.47 to −11.58)	< 0.001	< 0.001	99.2%
	Intervention age (yr)								0.006
		< 50	4	355	−13.28 (−23.50 to −3.06)	0.011	< 0.001	98.8%
		≥ 50	1	80	−28.30 (−31.28 to −25.32)	< 0.001	-	-
	Geograohic region								0.012
		South Asia	3	380	−23.03 (−34.47 to −11.58)	< 0.001	< 0.001	99.2%
		East and Southeast Asia	2	55	−5.73 (−12.82 to 1.36)	0.113	0.020	81.6%
	Intervention type								0.012
		Capsule form	1	55	−5.73 (−12.82 to 1.36)	0.113	0.020	81.6%
		Oil form	2	380	−23.03 (−34.47 to −11.58)	< 0.001	< 0.001	99.2%
	Baseline BMI								0.006
		Healthy weight or overweight (≤ 30 kg/m2)	4	355	−13.28 (−23.50 to −3.06)	0.011	< 0.001	98.8%
		Obese (> 30 kg/m2)	1	80	−28.30 (−31.28 to −25.32)	< 0.001	-	-
	Sample size								0.540
		< 100	3	135	−13.40 (−30.49 to 3.70)	0.125	< 0.001	98.4%
		≥ 100	2	300	−20.43 (−35.03 to −5.83)	0.006	< 0.001	99.5%
SBP (mmHg)			5	435	−20.78 (−32.26 to −9.31)	< 0.001	< 0.001	98.5%
	Health condition								0.001
		HTN without diabetes	3	255	−11.17 (−22.17 to −0.16)	0.047	< 0.001	95.6%
		HTN with diabetes	2	180	−35.08 (−46.45 to −26.71)	< 0.001	< 0.001	95.3%
	Sesame dosage (mg/day)								< 0.001
		≤ 3,000	2	55	−6.41 (−10.66 to −2.15)	0.003	0.219	33.9%
		> 3,000	3	380	−30.39 (−40.89 to −19.89)	< 0.001	< 0.001	98.0%
	Intervention duration (weeks)								0.966
		< 8	4	235	−20.67 (−35.77 to −5.57)	0.007	< 0.001	98.8%
		≥ 8	1	200	−21.00 (−23.62 to −18.38)	< 0.001	-	-
	Control approach								< 0.001
		Placebo	2	55	−6.41 (−10.66 to −2.15)	0.003	0.219	33.9%
		Usual care or usual traetment	3	380	−30.39 (−40.89 to −19.89)	< 0.001	< 0.001	98.0%
	Intervention age (yr)								0.115
		< 50	4	355	−18.19 (−33.66 to −2.71)	0.021	< 0.001	98.8%
		≥ 50	1	80	−30.80 (−33.44 to −28.16)	< 0.001	-	-
	Geograohic region								< 0.001
		South Asia	3	380	−30.39 (−40.89 to −19.89)	< 0.001	< 0.001	98.0%
		East and Southeast Asia	2	55	−6.41 (−10.66 to −2.15)	0.003	0.219	33.9%
	Intervention type								< 0.001
		Capsule form	2	55	−6.41 (−10.66 to −2.15)	0.003	0.219	33.9%
		Oil form	3	380	−30.39 (−40.89 to −19.89)	< 0.001	< 0.001	98.0%
	Baseline BMI								0.115
		Healthy weight or overweight (≤ 30 kg/m2)	4	355	−18.19 (−33.61 to −2.71)	0.021	< 0.001	98.8%
		Obese (> 30 kg/m2)	1	80	−30.80 (−33.44 to −28.16)	< 0.001	-	-
	Sample size								0.226
		< 100	3	135	−14.35 (−32.59 to 3.91)	0.123	< 0.001	98.4%
		≥ 100	2	300	−30.18 (−48.15 to −12.20)	0.001	< 0.001	99.0%
HDL-C (mg/dL)			3	380	2.21 (0.09 to 4.33)	0.041	< 0.001	97.8%
	Health condition								< 0.001
		HTN without diabetes	1	200	5.00 (4.01 to 5.99)	< 0.001	-	-
		HTN with diabetes	2	180	0.87 (−0.30 to 2.05)	0.146	< 0.001	92.8%
	Sesame dosage (mg/day)
		≤ 3,000	0	0	-	-	-	-
		> 3,000	3	380	2.21 (0.09 to 4.33)	0.041	< 0.001	97.8%
	Intervention duration (weeks)								< 0.001
		< 8	2	180	0.87 (−0.30 to 2.05)	0.146	< 0.001	92.8%
		≥ 8	1	200	5.00 (4.01 to 5.99)	< 0.001	-	-
	Control approach
		Placebo	0	0	-	-	-	-
		Usual care or usual traetment	3	380	2.21 (0.09 to 4.33)	0.041	< 0.001	97.8%
	Intervention age (yr)								0.095
		< 50	2	300	3.23 (−0.20 to 6.66)	0.065	< 0.001	97.2%
		≥ 50	1	80	0.30 (0.05 to 0.55)	0.018	-	-
	Geograohic region
		South Asia	3	380	2.21 (0.09 to 4.33)	0.041	< 0.001	99.5%
		East and Southeast Asia	0	0	-	-	-	-
	Intervention type
		Capsule form	0	0	-	-	-	-
		Oil form	3	380	2.21 (0.09 to 4.33)	0.041	< 0.001	99.5%
	Baseline BMI								0.095
		Healthy weight or overweight (≤ 30 kg/m2)	2	300	3.23 (−0.20 to 6.66)	0.065	< 0.001	97.2%
		Obese (> 30 kg/m2)	1	80	0.30 (0.05 to 0.55)	0.018	-	-
	Sample size								0.095
		< 100	1	80	0.30 (0.05 to 0.55)	0.018	-	-
		≥ 100	2	300	3.23 (−0.20 to 6.66)	0.065	< 0.001	97.2%
LDL-C (mg/dL)			3	380	−41.11 (−92.19 to 9.97)	0.115	< 0.001	99.8%
	Health condition								0.790
		HTN without diabetes	1	200	−48.00 (−53.74 to −42.26)	< 0.001	-	-
		HTN with diabetes	2	180	−37.67 (−113.49 to 38.14)	0.330	< 0.001	99.9%
	Sesame dosage (mg/day)
		≤ 3,000	0	0	-	-	-	-
		> 3,000	3	380	−41.11 (−92.19 to 9.97)	0.115	< 0.001	99.8%
	Intervention duration (weeks)								0.790
		< 8	2	180	−37.67 (−113.49 to 38.14)	0.330	< 0.001	99.9%
		≥ 8	1	200	−48.00 (−53.74 to −42.26)	< 0.001	-	-
	Control approach
		Placebo	0	0	-	-	-	-
		Usual care or usual traetment	3	380	−41.11 (−92.19 to 9.97)	0.115	< 0.001	99.8%
	Intervention age (yr)								0.031
		< 50	2	300	−23.44 (−71.46 to 24.58)	0.339	< 0.001	99.5%
		≥ 50	1	80	−76.36 (−80.28 to −72.44)	< 0.001	-	-
	Geograohic region
		South Asia	3	380	−41.11 (−92.19 to 9.97)	0.115	< 0.001	99.8%
		East and Southeast Asia	0	0	-	-	-	-
	Intervention type
		Capsule form	0	0	-	-	-	-
		Oil form	3	380	−41.11 (−92.19 to 9.97)	0.115	< 0.001	99.8%
	Baseline BMI								0.031
		Healthy weight or overweight (≤ 30 kg/m2)	2	300	−23.44 (−71.46 to 24.58)	0.339	< 0.001	99.5%
		Overweight or obese (> 30 kg/m2)	1	80	−76.36 (−80.28 to −72.44)	< 0.001	-	-
	Sample size								0.031
		< 100	1	80	−76.36 (−80.28 to −72.44)	< 0.001	-	-
		≥ 100	2	300	−23.44 (−71.46 to 24.58)	0.339	< 0.001	99.5%
TC (mg/dL)			3	380	−49.29 (−96.71 to −1.86)	0.042	< 0.001	99.6%
	Health condition								0.979
		HTN without diabetes	1	200	−50.00 (−55.65 to −44.35)	< 0.001	-	-
		HTN with diabetes	2	180	−48.94 (−127.24 to 29.36)	0.221	< 0.001	99.8%
	Sesame dosage (mg/day)
		≤ 3,000	0	0	-	-	-	-
		> 3,000	3	380	−49.29 (−96.71 to −1.86)	0.042	< 0.001	99.6%
	Intervention duration (weeks)								0.979
		< 8	2	180	−48.94 (−127.24 to 29.36)	0.221	< 0.001	99.8%
		≥ 8	1	200	−50.00 (−55.65 to −44.35)	< 0.001	-	-
	Control approach
		Placebo	0	0	-	-	-	-
		Usual care or usual traetment	3	380	−49.29 (−96.71 to −1.86)	0.042	< 0.001	99.6%
	Intervention age (yr)								0.004
		< 50	2	280	−29.46 (−69.64 to 10.72)	0.151	< 0.001	99.2%
		≥ 50	1	100	−88.90 (−94.17 to −83.62)	< 0.001	-	-
	Geograohic region
		South Asia	3	380	−49.29 (−96.71 to −1.86)	0.042	< 0.001	99.6%
		East and Southeast Asia	0	0	-	-	-	-
	Intervention type
		Capsule form	0	0	0	-	-	-
		Oil form	3	380	−49.29 (−96.71 to −1.86)	0.042	< 0.001	99.6%
	Baseline BMI								0.004
		Healthy weight or overweight (≤ 30 kg/m2)	2	300	−29.46 (−69.64 to 10.72)	0.151	< 0.001	99.2%
		Obese (> 30 kg/m2)	1	80	−88.90 (−94.17 to −83.62)	< 0.001	-	-
	Sample size								0.004
		< 100	1	80	−88.90 (−94.17 to −83.62)	< 0.001	-	-
		≥ 100	2	300	−29.46 (−69.64 to 10.72)	0.151	< 0.001	99.2%
TG (mg/dL)			3	380	−55.05 (−79.51 to −30.59)	< 0.001	< 0.001	99.3%
	Health condition								0.001
		HTN without diabetes	1	200	−28.00 (−32.96 to −23.04)	< 0.001	-	-
		HTN with diabetes	2	180	−68.45 (−91.55 to −45.34)	< 0.001	< 0.001	99.1%
	Sesame dosage (mg/day)
		≤ 3,000	0	0	-	-	-	-
		> 3,000	3	380	−55.05 (−79.51 to −30.59)	< 0.001	< 0.001	99.3%
	Intervention duration (weeks)								0.001
		< 8	2	180	−68.45 (−91.55 to −45.34)	< 0.001	< 0.001	99.1%
		≥ 8	1	200	−28.00 (−32.96 to −23.04)	< 0.001	-	-
	Control approach
		Placebo	0	0	-	-	-	-
		Usual care or usual traetment	3	380	−55.05 (−79.51 to −30.59)	< 0.001	< 0.001	99.3%
	Intervention age (yr)								0.009
		< 50	2	300	−42.43 (−70.56 to −14.31)	0.003	< 0.001	99.0%
		≥ 50	1	80	−80.28 (−84.04 to −76.52)	< 0.001	-	-
	Geograohic region
		South Asia	3	380	−55.05 (−79.51 to −30.59)	< 0.001	< 0.001	99.3%
		East and Southeast Asia	0	0	-	-	-	-
	Intervention type
		Capsule form	0	0	-	-	-	-
		Oil form	3	380	−55.05 (−79.51 to −30.59)	< 0.001	< 0.001	99.3%
	Baseline BMI								0.009
		Healthy weight or overweight (≤ 30 kg/m2)	2	300	−42.43 (−70.56 to −14.31)	0.003	< 0.001	99.0%
		Obese (> 30 kg/m2)	1	80	−80.28 (−84.04 to −76.52)	< 0.001	-	-
	Sample size								0.009
		< 100	1	80	−80.28 (−84.04 to −76.52)	< 0.001	-	-
		≥ 100	2	300	−42.43 (−70.56 to −14.31)	0.003	< 0.001	99.0%
CAT (U/mg of protein)			2	180	3.38 (3.24 to 3.52)	< 0.001	0.559	0.0%
GPx (U/min/mg of Hb)			2	180	0.93 (0.38 to 1.47)	0.001	< 0.001	95.7%
SOD (U/ mg of Hb)			2	180	3.11 (2.92 to 3.29)	< 0.001	0.752	0.0%
MDA (µmol/L)			2	60	−0.27 (−1.01 to 0.47)	0.468	0.095	64.1%
TBARS (nmol/dL)			2	180	−2.94 (−3.99 to −1.89)	< 0.001	< 0.001	97.4%

Bold values denote statistical significance at the P < 0.05 level.

WMD, weighted mean difference; CI, confidence interval; BMI, body mass index; DBP, diastolic blood pressure; HTN, hypertension; SBP, systolic blood pressure; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; TC, total cholesterol; TG, triglycerides; CAT, catalase; GPx, glutathione peroxidase; SOD, superoxide dismutase; MDA, malondialdehyde; TBARS, thiobarbituric acid reactive substances.

Studies were published between 2006 and 2016, and were conducted in Greece [17], India [13,14,18], Japan [15], and Thailand [16]. Participant ages in intervention groups ranged from 35 to 60 years, with sesame doses varying from 60 to 35,000 mg/day over intervention durations of 4 to 8 weeks. Sample sizes ranged from 25 to 200 participants. Participants were patients with HTN [17,18], hypertensive diabetic [13,14] mild HTN [15], and pre-HTN [16]. The following are the sample sizes for the intervention and control groups across various outcomes: BMI: n = 180 (intervention: 90, control: 90), weight: n = 180 (intervention: 90, control: 90), DBP: n = 435 (intervention: 217, control: 218), SBP: n = 435 (intervention: 217, control: 218), HDL-C: n = 380 (intervention: 190, control: 190), LDL-C: n = 380 (intervention:190, control: 190), TC: n = 380 (intervention: 190, control: 190), TG: n = 380 (intervention: 190, control: 190), CAT: n = 180 (intervention: 90, control: 90) erythrocyte GPx: n = 180 (intervention:90, control: 90), erythrocyte SOD: n = 180 (intervention: 90, control: 90), MDA: n = 60 (intervention: 32, control: 28), TBARS: n = 180 (intervention: 90, control: 90).

Qualitative data assessment

Using the Cochrane Risk of Bias Assessment tool, none of the studies were rated as good quality, one as fair [18], and the remaining studies as poor [13,14,15,16,17]. Details of quality of included studies in the meta-analysis are presented in Fig. 2.

Fig. 2. Quality of included studies in the meta-analysis.

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

Effects of sesame supplementation on anthropometric indices

Sesame supplementation demonstrated significant effects on BMI (WMD, −3.00 kg/m²; 95% CI, −3.43 to −2.57; P < 0.001; I² = 0.0%; P heterogeneity = 0.870) (Supplementary Fig. 1) and weight (WMD, −7.51 kg; 95% CI, −8.64 to −6.37; P < 0.001; I² = 0.0%; P heterogeneity = 0.766).

Effects of sesame supplementation on blood pressure

Based on our findings, the incorporation of sesame as a dietary supplement conferred significant beneficial effects on DBP (WMD, −16.29 mmHg; 95% CI, −25.37 to −7.22; P < 0.001; I² = 98.7%; P heterogeneity < 0.001) (Supplementary Fig. 2) and SBP (WMD, −20.78 mmHg; 95% CI, −32.26 to −9.31; P < 0.001; I² = 98.5%; P heterogeneity < 0.001).

Sensitivity analysis revealed that excluding any single study did not significantly alter the results for DBP and SBP. Additionally, Egger’s test indicated no significant publication bias for DBP (P = 0.919) or SBP (P = 0.105).

Effects of sesame supplementation on lipid profile

According to our results, sesame supplementation is not beneficial on LDL-C (WMD, −41.11 mg/dL; 95% CI, −92.19 to 9.97; P = 0.115; I² = 99.8%, P heterogeneity < 0.001) (Supplementary Fig. 3). However, sesame supplementation is beneficial on HDL-C (WMD, 2.21 mg/dL; 95% CI, 0.09 to 4.33; P = 0.041; I² = 97.8%; P heterogeneity < 0.001), TC (WMD, −49.29 mg/dL; 95% CI, −96.71 to −1.86; P = 0.042; I² = 99.6%; P heterogeneity < 0.001), and TG (WMD, −55.05 mg/dL; 95% CI, −79.51 to −30.59; P < 0.001; I² = 99.3%; P heterogeneity < 0.001).

Sensitivity analysis indicated that excluding Sankar et al. [14] (WMD, −62.26 mg/dL; 95% CI, −90.05 to −34.47) results in changes to the overall findings for LDL-C levels. Similarly, the exclusion of Devarajan et al. [18] (WMD, −48.94 mg/dL; 95% CI, −127.24 to 29.36) and Sankar et al. [14] (WMD, −29.46 mg/dL; 95% CI, −69.64 to 10.72) affects the overall outcomes for TC levels. Whereas, the analysis showed that removing any single study did not lead to significant changes in the results for HDL-C and TG. There is no publication bias based on Egger’s test for HDL-C (P = 0.160), LDL-C (P = 0.701), TC (P = 0.482), or TG (P = 0.829).

Effects of sesame supplementation on oxidative stress parameters

Sesame supplementation demonstrated significant effects on CAT (WMD, 3.38 U/mg of protein; 95% CI, 3.24 to 3.52; P < 0.001; I² = 0.0%; P heterogeneity = 0.559) (Supplementary Fig. 4), erythrocyte GPx (WMD, 0.93 U/min/mg of Hb; 95% CI, 0.38 to 1.47; P = 0.001; I² = 95.7%; P heterogeneity < 0.001), erythrocyte SOD (WMD, 3.11 U/mg of Hb; 95% CI, 2.92 to 3.29; P < 0.001; I² = 0.0%; P heterogeneity = 0.752), and TBARS (WMD, −2.94 nmol/dL; 95% CI, −3.99 to −1.89; P < 0.001; I² = 97.4%; P heterogeneity < 0.001). However, sesame supplementation did not demonstrate significant effects on MDA (WMD, −0.27 µmol/L; 95% CI, −1.01 to 0.47; P = 0.468; I² = 64.1%; P heterogeneity = 0.095).

Subgroup analysis

Sesame supplementation significantly influenced DBP, SBP, and TG levels in both hypertensive participants with and without diabetes. However, significant changes in HDL-C, LDL-C, and TC levels were observed only in hypertensive participants without diabetes.

Administration of sesame at both dosage levels (≤ 3,000 and > 3,000 mg/day) significantly altered SBP. Additionally, doses exceeding 3,000 mg/day significantly influenced DBP, HDL-C, TC, and TG levels. In contrast, LDL-C showed no significant changes at either dosage level.

Sesame supplementation over intervention durations of both < 8 and ≥ 8 weeks significantly impacted DBP, SBP and TG levels. However, significant changes in HDL-C, LDL-C, and TC levels were observed only in interventions lasting ≥ 8 weeks.

In the evaluation of control approaches, sesame supplementation significantly affected SBP in both the placebo and usual care or usual treatment groups. Conversely, significant effects on TC, TG, DBP, and HDL-C levels were observed exclusively in the usual care or usual treatment group, while LDL-C showed no significant changes in either group.

Analysis by age group revealed that sesame supplementation significantly influenced DBP, SBP, and TG levels across both age categories (< 50 and ≥ 50 years). However, significant changes in HDL-C, LDL-C, and TC levels were observed only in participants aged ≥ 50 years.

Examination of geographic regions showed that sesame supplementation significantly impacted SBP in both South Asia and East and Southeast Asia. In contrast, DBP, HDL-C, TC, and TG levels exhibited significant changes only in the South Asia region, while LDL-C showed no significant effects in either region.

Assessment of intervention types demonstrated that sesame supplementation in both capsule and oil forms significantly affected SBP. However, significant effects on DBP, HDL-C, TC, and TG levels were observed exclusively in the oil form group, while LDL-C showed no significant changes in either group.

Evaluation by baseline BMI revealed that sesame supplementation significantly influenced DBP, SBP, and TG levels in both the healthy weight or overweight (≤ 30 kg/m²) and obese (> 30 kg/m²) groups. In contrast, significant changes in HDL-C, LDL-C, and TC levels were observed only in the obese group.

Analysis based on sample size indicated that sesame supplementation significantly affected TG levels in both groups with < 100 and ≥ 100 participants. However, significant changes in HDL-C, LDL-C, and TC levels were observed only in studies with < 100 participants, while DBP and SBP showed significant effects exclusively in studies with ≥ 100 participants (Table 2).

Meta-regression and non-linear dose-response analysis

Meta-regression analysis revealed a significant linear relationship between sesame dosage and SBP (P = 0.036), indicating that higher doses may enhance metabolic health in individuals with HTN (Supplementary Figs. 5 and 6). Additionally, non-linear dose-response analysis demonstrated a significant association between the duration of sesame supplementation and DBP (P = 0.041), with an estimated optimal supplementation duration of approximately 6 weeks (Supplementary Figs. 7 and 8).

GRADE assessment

The GRADE profile of sesame supplementation, indicating the certainty of outcomes is presented in Table 3. The evidence quality was rated as very low for all outcomes.

Table 3. GRADE profile of sesame supplementation on pre-hypertensive and hypertensive patients.

Outcomes	Risk of bias	Inconsistency	Indirectness	Imprecision	Publication bias	Number (INT/CON)	WMD (95% CI)	Quality of evidence
BMI	Very seriousa	Not seriousf	Seriousb	Seriousc	Noneg	90/90	−3.00 (−3.43 to −2.57)	⨁◯◯◯ Very low
Weight	Very seriousa	Not seriousf	Seriousb	Seriousc	Noneg	90/90	−7.51 (−8.64 to −6.37)	⨁◯◯◯ Very low
DBP	Seriousd	Very seriouse	Seriousb	Not serious	Noneg	217/218	−16.29 (−25.37 to −7.22)	⨁◯◯◯ Very low
SBP	Seriousd	Very seriouse	Seriousb	Not serious	Noneg	217/218	−20.78 (−32.26 to −9.31)	⨁◯◯◯ Very low
HDL-C	Seriousd	Very seriouse	Seriousb	Seriousc	Noneg	190/190	2.21 (0.09 to 4.33)	⨁◯◯◯ Very low
LDL-C	Seriousd	Very seriouse	Seriousb	Very seriousc,h	Noneg	190/190	−41.11 (−92.19 to 9.97)	⨁◯◯◯ Very low
TC	Seriousd	Very seriouse	Seriousb	Seriousc	Noneg	190/190	−49.29 (−96.71 to −1.86)	⨁◯◯◯ Very low
TG	Seriousd	Very seriouse	Seriousb	Seriousc	Noneg	190/190	−55.05 (−79.51 to −30.59)	⨁◯◯◯ Very low
CAT	Very seriousa	Not seriousf	Seriousb	Seriousc	Noneg	90/90	3.38 (3.24 to 3.52)	⨁◯◯◯ Very low
Erythrocyte GPx	Very seriousa	Very seriouse	Seriousb	Seriousc	Noneg	90/90	0.93 (0.38 to 1.47)	⨁◯◯◯ Very low
Erythrocyte SOD	Very seriousa	Not seriousf	Seriousb	Seriousc	Noneg	90/90	3.11 (2.92 to 3.29)	⨁◯◯◯ Very low
MDA	Very seriousa	Seriousi	Seriousb	Very seriousc,h	Noneg	32/28	−0.27 (−1.01 to 0.47)	⨁◯◯◯ Very low
TBARS	Very seriousa	Very seriouse	Seriousb	Seriousc	Noneg	90/90	−2.94 (−3.99 to −1.89)	⨁◯◯◯ Very low

GRADE, Grading of Recommendations, Assessment, Development, and Evaluation; INT, intervention group; CON, control group; WMD, weighted mean difference; CI, confidence interval; BMI, body mass index; DBP, diastolic blood pressure; SBP, systolic blood pressure; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; TC, total cholesterol; TG, triglycerides; CAT, catalase; GPx, glutathione peroxidase; SOD, superoxide dismutase; MDA, malondialdehyde; TBARS, thiobarbituric acid reactive substances.

^aDowngraded two levels for very serious risk of bias, as more than 50% of participants were from studies with high risk of bias (e.g., unclear randomization, lack of blinding, or incomplete outcome reporting).

^bDowngraded one level for indirectness, as studies were primarily conducted in Asian populations (India, Japan, Thailand) with one in Greece, limiting generalizability to other populations.

^cDowngraded one level for imprecision, as the total number of participants was less than 400, reducing confidence in the precision of the effect estimate.

^dDowngraded one level for serious risk of bias, as less than 50% but more than 25% of participants were from studies with high risk of bias, primarily due to unclear randomization or lack of blinding.

^eDowngraded two levels for very serious inconsistency, as heterogeneity was high (I² > 75%), indicating substantial variability in effect sizes across studies.

^fNot downgraded for inconsistency, as heterogeneity was low (I² < 25%), suggesting consistent effect sizes across studies.

^gNot downgraded for publication bias, as Egger’s test showed no significant evidence of bias (P > 0.05 for all outcomes).

^hDowngraded one additional level for very serious imprecision, as the 95% confidence interval crosses the threshold of no effect, reducing confidence in the direction and magnitude of the effect.

ⁱDowngraded one level for serious inconsistency, as heterogeneity was moderate (I² = 64.1%), indicating some variability in effect sizes.

BMI

The evidence for BMI was rated as very low due to multiple downgrades. It was downgraded 2 levels for very serious risk of bias because both included studies were rated as poor quality using the Cochrane Risk of Bias tool, primarily due to unclear randomization processes, lack of blinding, and potential selective reporting. It was also downgraded one level for serious indirectness, as the studies were conducted in India, limiting generalizability to other populations with different dietary habits or genetic profiles. Additionally, it was downgraded one level for imprecision, as the total sample size was less than 400, reducing confidence in the precision of the effect estimate. Despite low heterogeneity, no downgrade was applied for inconsistency, and Egger’s test showed no publication bias.

Weight

The evidence for weight was rated very low due to similar concerns. It was downgraded two levels for very serious risk of bias, as both studies were of poor quality, with issues such as unclear allocation concealment and lack of blinding. Indirectness was downgraded one level due to the studies’ focus on Indian populations, which may not reflect outcomes in other regions. Imprecision was downgraded one level because the sample size was below 400, limiting confidence in the effect estimate’s precision. No downgrade was applied for inconsistency, and no publication bias was detected, resulting in a very low-quality rating.

DBP

The evidence for DBP was rated very low. It was downgraded one level for serious risk of bias, as less than 50% but more than 25% of participants were from studies with high risk of bias, primarily due to unclear randomization and lack of blinding in some trials. Inconsistency was downgraded two levels due to very high heterogeneity, reflecting substantial variability in effect sizes, possibly due to differences in sesame doses (60–35,000 mg/day) and intervention durations (4–8 weeks). Indirectness was downgraded one level because most studies were conducted in Asian countries, limiting generalizability. Imprecision was not downgraded, as the sample size was sufficiently large, and no publication bias was detected.

SBP

The evidence for SBP was rated very low. It was downgraded one level for serious risk of bias, with issues similar to DBP, including unclear randomization and lack of blinding in some studies. Very serious inconsistency was noted (downgraded 2 levels) due to high heterogeneity, likely driven by diverse intervention protocols and populations. Indirectness was downgraded one level due to the predominance of Asian studies. Imprecision was not downgraded, as the sample size was adequate, and no publication bias was found, resulting in a very low-quality rating.

HDL-C

The evidence for HDL-C was rated very low. It was downgraded one level for serious risk of bias, as some studies had issues with blinding and randomization. Inconsistency was downgraded 2 levels due to very high heterogeneity, reflecting variability in effect sizes, possibly due to differences in sesame forms (oil vs. capsules). Indirectness was downgraded one level due to the Asian-centric study populations. Imprecision was downgraded one level, as the sample size was less than 400, and the confidence interval was wide. No publication bias was detected.

LDL-C

The evidence for LDL-C was rated very low. It was downgraded one level for serious risk of bias due to methodological flaws in some studies. Inconsistency was downgraded 2 levels due to very high heterogeneity, driven by diverse intervention protocols. Indirectness was downgraded one level due to limited generalizability from Asian and Greek studies. Imprecision was downgraded two levels because the sample size was less than 400 and the confidence interval crossed the threshold of no effect, reducing confidence in the result. No publication bias was found.

TC

The evidence for TC was rated very low. It was downgraded one level for serious risk of bias due to issues like lack of blinding in some studies. Inconsistency was downgraded 2 levels due to very high heterogeneity, reflecting variability in sesame interventions. Indirectness was downgraded one level due to the Asian-centric study populations. Imprecision was downgraded one level, as the sample size was less than 400 and the confidence interval was wide. No publication bias was detected.

TG

The evidence for TG was rated very low. It was downgraded one level for serious risk of bias due to methodological limitations in some studies. Inconsistency was downgraded 2 levels due to very high heterogeneity, likely due to diverse sesame doses and forms. Indirectness was downgraded one level due to limited generalizability. Imprecision was downgraded one level, as the sample size was less than 400. No publication bias was found.

CAT

The evidence for CAT was rated very low. It was downgraded 2 levels for very serious risk of bias, as both studies were rated poor due to unclear randomization and lack of blinding. Indirectness was downgraded one level due to the Indian study population, limiting generalizability. Imprecision was downgraded one level, as the sample size was less than 400. Inconsistency was not downgraded, as heterogeneity was low, and no publication bias was detected.

Erythrocyte GPx

The evidence for erythrocyte GPx was rated very low. It was downgraded 2 levels for very serious risk of bias, as both studies were of poor quality. Inconsistency was downgraded 2 levels due to very high heterogeneity, indicating variability in effect sizes. Indirectness was downgraded one level due to the Indian study population. Imprecision was downgraded one level, as the sample size was less than 400. No publication bias was detected.

Erythrocyte SOD

The evidence for erythrocyte SOD was rated very low. It was downgraded 2 levels for very serious risk of bias, as both studies were poor quality. Indirectness was downgraded one level due to the Indian study population. Imprecision was downgraded one level, as the sample size was less than 400. Inconsistency was not downgraded, as heterogeneity was low, and no publication bias was found.

MDA

The evidence for MDA was rated very low. It was downgraded 2 levels for very serious risk of bias, as both studies were of poor quality. Inconsistency was downgraded one level due to moderate heterogeneity, suggesting some variability. Indirectness was downgraded one level due to limited generalizability from Asian and Greek studies. Imprecision was downgraded 2 levels, as the sample size was very small and the confidence interval crossed the threshold of no effect. No publication bias was detected.

TBARS

The evidence for TBARS was rated very low. It was downgraded 2 levels for very serious risk of bias, as both studies were poor quality. Inconsistency was downgraded 2 levels due to very high heterogeneity. Indirectness was downgraded one level due to the Indian study population. Imprecision was downgraded one level, as the sample size was less than 400. No publication bias was found.

DISCUSSION

This GRADE-assessed systematic review and meta-analysis synthesized findings from six trials examining the effects of sesame (Sesamum indicum L.) supplementation in individuals with prehypertension and hypertension. The results suggest potential improvements in BMI, weight, DBP, SBP, HDL-C, TC, TG, CAT, erythrocyte GPx, erythrocyte SOD, and TBARS, though no effects were observed on LDL-C and MDA levels (Fig. 3). However, the very low certainty of evidence, due to high heterogeneity, small sample sizes, and methodological limitations, warrants cautious interpretation, as these findings may not reliably reflect sesame’s true clinical impact.

Fig. 3. Overall effects of sesame supplementation on cardiovascular outcomes in individuals with prehypertension and hypertension.

BMI, body mass index; CI, confidence interval; SBP, systolic blood pressure; DBP, diastolic blood pressure; TC, total cholesterol; TG, triglycerides; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; CAT, catalase; SOD, superoxide dismutase; GPx, glutathione peroxidase; TBARS, thiobarbituric acid reactive substances; MDA, malondialdehyde.

Experimental and molecular studies favor the direct and indirect effectiveness of administrating sesame oil on arterial blood pressure, via improving the equilibrium among factors affecting the contraction of the blood vessel endothelium, modulating lipid profile, inflammatory and antioxidant status [17]. These properties are related to the high content of unsaturated fatty acids, antioxidants such as lignans, sesamin, sesamol, episesamin and sesamolin, and vitamin E (alpha-tocopherol and gamma-tocopherol) of sesame oil [18]. The efficacy of sesame in reducing blood pressure, since sesamin employs blood pressure declining actions via intruding with renin-angiotensin system, since lignin mainly effects the renin-independent deoxycorticosterone acetate-salt HTN model [13]. Moreover, sesamin posseses Ca⁺ antagonistic vasorelaxing activities [24]. Sesamin also inhibits enzymes involved in CYP450 and 20-hydroxyeicosatetraenoic acid production [25].

Vitamin E as a highly efficient antioxidant is responsible for detoxifying free radicals, declining lipid peroxidation and production of massive tissue aldehydes. Interestingly, the vitamin E content of sesame oil is highly bioavailable [14]. The antioxidant effect, is also contributed to vasorelaxing factors such as enhancing nitric oxide (NO) and inhibiting endothelin-1 production [16]. Furthermore, gamma-tocopherol enhances the expression of NO synthase, which stimulates vasorelaxation [26]. An in-vitro study showed that in oxidized LDL cells, vitamin E is efficient in preserving endothelial cell migration and restore the endothelial monolayer caused from injury [27]. The anti-inflammatory effects of sesame via declining tumor necrosis factor α and interleukin 1 and 6 levels, have been previously confirmed in experimental studies [28].

Sesame supplementation had a significant effect on BMI and weight in pre-hypertensive and hypertensive patients. In numerous studies, the relationship between BMI and blood pressure has been detected [29]. Subsequently, individuals whom are overweight or obese, are at high risk for HTN. Studies suggest that polyunsaturated fatty acid (PUFA) enhances leptin plasma level, which, subsequently, helps reduce weight. In fact, the high PUFA content of sesame oil not only modulates the endothelial functions, declines fat storage and efficiently boosts weight loss [30].

The findings of the current meta-analyses indicated that sesame concentration significantly declined SBP and DBP. Wichitsranoi et al. [16] revealed significant reduction in SBP; whilst, changes in DBP between groups were not significantly different after supplementation. In fact, DBP changes were negatively related to changes in vitamin E concentration [16]. Another study declared that although SBP and DBP were obviously reduced, only diastolic pressures reached statistical significance [17]. Sankar et al. [13] claimed that replacing sesame oil as the main cooking oil has a significant effect in declining BP in diabetics hypertensive individuals.

The significant blood pressure reductions were driven primarily by three studies: Sankar et al. [13,14] and Devarajan et al. [18]. These studies reported mean SBP and DBP reductions exceeding 20 mmHg, which are exceptional for a nutritional intervention. Several factors may explain these findings. First, all three studies involved participants concurrently using antihypertensive medications (e.g., beta-blockers [atenolol], diuretics [hydrochlorothiazide], or calcium channel blockers [nifedipine]), which likely produced synergistic effects with sesame supplementation. For example, Sankar et al. [13] combined sesame oil with atenolol and glibenclamide, while Devarajan et al. [18] used a blend of sesame and rice bran oil alongside nifedipine. These medications target complementary pathways (e.g., beta-adrenergic blockade, calcium channel inhibition), potentially amplifying sesame’s vasodilatory and antioxidant effects. Second, the single-arm crossover designs in Sankar et al. [13,14], where participants served as their own controls, may have inflated effect sizes due to reduced variability and potential carryover effects. Third, Devarajan et al. [18] used an open-label design and included rice bran oil, which contains additional bioactive compounds (e.g., γ-oryzanol, tocotrienols) that may have contributed to the observed effects. These co-interventions and design factors likely overestimate sesame’s independent effect on blood pressure.

The studies reporting the largest blood pressure reductions used mega doses of sesame oil (34,500–35,000 mg/day) over 6–8 weeks, far exceeding typical dietary intakes of sesame (e.g., 5–10 g/day in culinary use) [13,14,18]. Such high doses may enhance the bioavailability of bioactive compounds like sesamin and vitamin E, potentially amplifying their effects on vascular function and oxidative stress. However, the clinical relevance of these doses is questionable, as they are impractical for routine dietary incorporation and may not reflect real-world applicability.

According to findings, sesame oil was significantly efficient on HDL-C, TC, TG levels, but not LDL-C. In Devarajan et al.’s study [18], a combination of sesame oil and rice bran oil was administered, which are both rich in antioxidants and unsaturated fatty acids and exhibit a synergistic effect on cardiovascular health. Rice bran oil mainly consists of γ-oryzanol, tocopherols, and tocotrienols. Tocotrienols declines cholesterol level via possessing 3-hydroxy-3-methylglutaryl-coenzyme A reductase properties. Moreover, lignans and γ-oryzanol as significant antioxidants, display significant effects on blood pressure [18]. Experimental studies have also mentioned that sesamin and episesamin regulate cholesterol metabolism via limiting cholesterol production and absorption of hypertensive rats. Other researches have indicated that the high monounsaturated fatty acid content of sesame oil is responsible for declining TC, TG level and enhancing HDL-C [13]. One study mentioned that in hypertensive patients, using diuretics and beta-blockers, sesame oil was not efficient in providing cholesterol lowering effects [14]. Consuming sesame oil as the sole edible oil, magnifies the effects of blood glucose lowering treatments, declines cholesterol, as well as blood sugar and glycated hemoglobin in diabetic hypertensive patients [31].

Sesame oil mainly consists of vitamin E, sesamin, episesamin, and sesaminol, which are significant antioxidants in detoxifying hydroxy and peroxy radicals, and ultimately reducing lipid peroxidation. Based on results, TBARS, significantly declined after administrating sesame oil. In one study, TBARS plasma levels was not significantly changed after discontinuing sesame oil administration. This may be due to the lignans preserved in the tissue [14]. Sankar et al. [13] indicated that the enhance in SOD and CAT levels after substituting sesame oil could be because of decline in lipid peroxidation. The antioxidants available in sesame oil control lipid peroxidation and detoxify hydroxy and peroxy radicals. The significant decline in TBARS level could also be because of the massive amount of antioxidants present in sesame oil [13]. Furthermore, the excessive content of vitamin E available in sesame oil is responsible for elevating glutathione [32].

The reductions in SBP and DBP observed with sesame supplementation are notably larger than those typically achieved with first-line antihypertensive medications, such as angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) [33,34]. For instance, a meta-analysis by Law et al. reported that ACE inhibitors and ARBs typically reduce SBP by 5–10 mmHg and DBP by 3–6 mmHg in hypertensive patients, with greater reductions in those with higher baseline blood pressure [33]. Similarly, a recent systematic review and meta-analysis confirmed that thiazide diuretics and beta-blockers achieve comparable effect sizes, typically in the range of 8–12 mmHg for SBP and 4–7 mmHg for DBP [34]. The large effect sizes in our study may be attributed to methodological limitations, including high heterogeneity, small sample sizes, and poor-quality studies, which may inflate estimates due to bias or confounding. These findings suggest that while sesame supplementation shows promise, the observed blood pressure reductions are unlikely to be reproducible in well-controlled settings and should be interpreted cautiously until validated by higher-quality trials.

GRADE assessment indicated very low quality of evidence based on included studies. The assessed quality of the trials is affected by the limited number of the studies included, specially focused on Asian regions. Also, the small sample size and date of trials affect the quality of results. Devarajan et al.’s study [18] was open-labeled, not single or double blinded or controlled via placebo, also the actual fat intake and at the beginning or throughout the sesame oil intervention was not recorded, making the interpretation of findings difficult.

An important consideration in evaluating any therapeutic intervention is its safety profile and tolerability. Across the clinical trials included in our meta-analysis, sesame supplementation demonstrated a remarkably favorable safety profile with minimal reported adverse events. This finding aligns with existing literature demonstrating that sesame-based interventions are generally well-tolerated in diverse populations [35,36]. A recent clinical trial investigating sesame paste supplementation in semi-professional soccer players reported no adverse symptoms such as bloating, cramping, nausea, vomiting, or diarrhea during the 8-week intervention period, suggesting excellent gastrointestinal tolerability [37]. Similarly, multiple trials examining sesame oil and sesame lignans have consistently reported good tolerability profiles without significant treatment-related adverse events, supporting the clinical applicability of sesame supplementation in cardiovascular health management [13,38].

The excellent safety profile observed in our included studies is particularly noteworthy given the wide range of dosages examined (60 to 35,000 mg/day) and varying intervention durations (4 to 8 weeks). However, it is important to acknowledge that sesame allergy represents a significant concern in certain populations, with prevalence rates estimated at approximately 0.1–0.2% in Western countries [39]. While none of the included studies in our meta-analysis reported allergic reactions, this may reflect appropriate screening and exclusion of allergic individuals during participant recruitment. Future clinical trials should systematically document and report safety outcomes, including minor gastrointestinal effects, allergic reactions, and any potential interactions with concurrent medications, particularly antihypertensive drugs, to provide comprehensive safety data for clinical decision-making.

The present systematic review and meta-analysis exhibits several notable strengths that enhance its contribution to the field of cardiovascular health research. As the first comprehensive assessment of sesame supplementation specifically focused on pre-hypertensive and hypertensive populations, our study employed rigorous methodological approaches aligned with PRISMA guidelines and PROSPERO registration. The implementation of extensive search strategies across 5 major databases, coupled with manual reference screening, ensured comprehensive coverage of available evidence. Our analysis is particularly robust in its evaluation of multiple clinically relevant outcomes, extending beyond blood pressure to include anthropometric indices, lipid profiles, and oxidative stress markers. The application of standardized quality assessment tools, including the Cochrane Risk of Bias Assessment and GRADE framework, along with independent review processes, further strengthens the reliability of our findings.

However, several important limitations must be considered when interpreting our results. The relatively small number of included studies (n = 6) restricted our ability to conduct meaningful subgroup analyses and explore potential effect modifiers. Due to the limited number of outcomes and high heterogeneity across studies, subgroup analyses were conducted; however, certain subgroups lacked sufficient studies for inclusion, which may have constrained the robustness of the findings. This limitation reduces the precision of our findings and limits the ability to identify variations in treatment effects across different population subsets. In our aim to synthesize all available evidence regarding sesame supplementation and blood pressure, we adopted relatively inclusive eligibility criteria, which resulted in the incorporation of studies where intervention groups received additional active substances beyond sesame, and some control groups utilized active comparators rather than placebos. While we employed advanced analytical techniques, including sensitivity analyses and publication bias assessments, to mitigate these methodological challenges, our findings may still be influenced by potential confounding variables. Substantial heterogeneity was observed across studies in terms of intervention protocols, with sesame doses ranging from 60 to 35,000 mg/day and treatment durations varying from 4 to 8 weeks. The methodological quality of included studies was predominantly poor, with five out of six studies rated as low quality and all outcomes receiving very low GRADE evidence ratings. Additionally, the variation in study populations, including differences in baseline characteristics and concurrent medical conditions, along with the diversity of intervention forms (oils, capsules, meals) and control group treatments, introduces potential confounding factors that may influence the interpretation of our findings.

The unusually large reductions in SBP (WMD, −20.78 mmHg) and DBP (WMD, −16.29 mmHg) reported in this meta-analysis, which surpass effect sizes typically observed with first-line antihypertensive medications, may be influenced by significant methodological limitations. These include high risks of bias in the included studies, substantial heterogeneity in intervention protocols (e.g., sesame doses ranging from 60 to 35,000 mg/day and durations from 4 to 8 weeks), and potential confounding due to the inclusion of active comparators or co-interventions in some studies. Such large effect sizes are likely not generalizable or reproducible in broader populations, necessitating cautious interpretation and further validation through high-quality, standardized clinical trials.

To address concerns regarding the methodological quality of the included studies, we acknowledge that the predominantly poor quality of the trials, with 5 out of 6 rated as poor using the Cochrane Risk of Bias tool and all outcomes graded as very low by the GRADE framework, significantly limits the reliability and generalizability of our pooled estimates. This low quality introduces a high risk of bias, which may overestimate or underestimate the true effects of sesame supplementation. Consequently, the findings should be interpreted with considerable caution, as the evidence base does not support definitive conclusions about the efficacy of sesame supplementation in pre-hypertensive and hypertensive populations. This underscores the critical need for future high-quality RCTs to provide more robust evidence.

The findings of our systematic review and meta-analysis underscore the potential of sesame supplementation as a complementary intervention for managing pre-HTN and HTN. However, the unusually large blood pressure reductions and significant gaps in the current body of evidence highlight the need for well-designed, high-quality RCTs to further elucidate the therapeutic benefits of sesame. Future studies should focus on isolating the effects of sesame by employing rigorous experimental designs with placebo-controlled interventions that exclude additional active substances. Standardizing intervention protocols, including dosage, form (e.g., oil, capsules, meals), and duration, will be critical to reducing heterogeneity and enabling more precise evaluations of the dose-response relationship. Furthermore, studies should include larger and more diverse populations with well-characterized baseline health profiles to explore subgroup-specific effects and enhance the generalizability of findings.

To address methodological shortcomings identified in existing studies, future research must prioritize adherence to robust quality assessment frameworks such as the Cochrane Risk of Bias tool and ensure transparency through detailed reporting of trial designs, randomization, and blinding procedures. Future studies should use placebo-controlled designs, exclude co-interventions, and standardize sesame doses and forms. Researchers should also aim to investigate the mechanisms underlying sesame’s antihypertensive effects, including its potential impact on lipid metabolism, oxidative stress, and inflammatory pathways. Long-term studies are warranted to assess sustained efficacy and safety, as well as potential benefits on clinical endpoints such as cardiovascular events. Incorporating advanced analytical approaches, such as network meta-analyses and individual patient data meta-analyses, can also provide deeper insights into the comparative effectiveness of sesame supplementation versus other dietary interventions. Ultimately, collaborative efforts between researchers, funding bodies, and stakeholders will be essential to advancing the evidence base and optimizing the role of sesame in managing HTN.

CONCLUSIONS

This GRADE-assessed systematic review and meta-analysis investigated the effects of sesame (Sesamum indicum L.) supplementation in individuals with prehypertension and hypertension. The analysis suggested potential reductions in BMI, weight, DBP, SBP, HDL-C, TC, TG, CAT, erythrocyte GPx, erythrocyte SOD, and TBARS. However, the very low certainty of evidence, attributed to high heterogeneity, small sample sizes, and implausible effect magnitudes, significantly limits the reliability of these findings. These results should be interpreted with caution, as the observed effects may not reflect true clinical benefits. Further rigorous, large-scale, and well-designed RCTs are essential to establish the efficacy and optimal use of sesame supplementation in managing cardiovascular risk factors.

Abbreviations

ACE

angiotensin-converting enzyme

ARB

angiotensin receptor blocker

BMI

body mass index

CAT

catalase

CI

confidence interval

CON

control group

CRP

C-reactive protein

DB

double-blinded

DBP

diastolic blood pressure

GPx

glutathione peroxidase

GRADE

Grading of Recommendations, Assessment, Development, and Evaluation

GSH

glutathione

Hb

hemoglobin

HbA1c

hemoglobin A1C

HC

hip circumference

HDL-C

high-density lipoprotein cholesterol

HTN

hypertension

INT

intervention group

LDL-C

low-density lipoprotein cholesterol

MAP

mean arterial pressure

MDA

malondialdehyde

NA

not applicable

NO

nitric oxide

PC

placebo-controlled

PRISMA

Preferred Reporting Items for Systematic reviews and Meta-Analyses

PUFA

polyunsaturated fatty acid

R

randomized

RCT

randomized controlled trial

SBP

systolic blood pressure

SOD

superoxide dismutase

TAC

total antioxidant capacity

TBARS

thiobarbituric acid reactive substances

TC

total cholesterol

TG

triglycerides

TNF-α

tumor necrosis factor-α

WC

waist circumference

WHR

waist-to-hip ratio

WMD

weighted mean difference

SUPPLEMENTARY MATERIALS

Supplementary Data 1

Search strategy to find potential eligible randomised controlled trials (August 2024)

Supplementary Table 1

A summary of excluded articles after full text review

Supplementary Fig. 1

Forest plot of the effects of okra supplement on anthropometric measures. (A) Body mass index and (B) weight.

Supplementary Fig. 2

Forest plot of the effects of sesame supplement on blood pressure. (A) Diastolic blood pressure and (B) systolic blood pressure.

Supplementary Fig. 3

Forest plot of the effects of sesame supplement on lipid profile. (A) High-density lipoprotein cholesterol, (B) low-density lipoprotein cholesterol, (C) total cholesterol, and (D) triglycerides.

Supplementary Fig. 4

Forest plot of the effects of sesame supplement on oxidative stress parameters. (A) Catalase, (B) erythrocyte glutathione peroxidase, (C) erythrocyte superoxide dismutase activity, (D) malondialdehyde, and (E) thiobarbituric acid reactive substance.

Supplementary Fig. 5

Random-effects meta-regression plots of the association between sesame dosage (mg/day) and cardiovascular disease outcomes in individuals with prehypertension and hypertension. (A) Diastolic blood pressure, (B) systolic blood pressure, (C) high-density lipoprotein cholesterol, (D) low-density lipoprotein cholesterol, (E) total cholesterol, and (F) triglycerides.

Supplementary Fig. 6

Random-effects meta-regression plots of the association between duration of intervention and cardiovascular disease outcomes in individuals with prehypertension and hypertension. (A) Diastolic blood pressure, (B) systolic blood pressure, (C) high-density lipoprotein cholesterol, (D) low-density lipoprotein cholesterol, (E) total cholesterol, (F) triglycerides.

Supplementary Fig. 7

Non-linear dose-response relations between sesame dosage (mg/d) and cardiovascular disease outcomes in individuals with prehypertension and hypertension. (A) Diastolic blood pressure, (B) systolic blood pressure, (C) high-density lipoprotein cholesterol, (D) low-density lipoprotein cholesterol, (E) total cholesterol, and (F) triglycerides.

Supplementary Fig. 8

Non-linear dose-response relations between duration of intervention and cardiovascular disease outcomes in individuals with prehypertension and hypertension. (A) Diastolic blood pressure, (B) systolic blood pressure, (C) high-density lipoprotein cholesterol, (D) low-density lipoprotein cholesterol, (E) total cholesterol, and (F) triglycerides.