Systematic literature retrieval was performed in the PubMed, SCOPUS, Cochrane Library, Embase, and ISI Web of Science databases from inception to July 2021 to determine a randomized controlled trial evaluating the effects of sesamin on obesity, blood pressure, and lipid profile. Medical subject heading terms (Mesh) were used: (“sesame” OR “sesamin” OR “sesamum”) AND (“Blood Pressure” OR “Hypertension” OR “High Blood Pressure”) AND(”HDL” OR “LDL” OR “Triglyceride” OR “Total cholesterol”) AND (“BMI” OR “Weight”) ( Supplementary Material , which illustrates the search strategies). Then, the retrieved manuscripts were imported into EndNote software (version X9) to remove the duplicates. The inclusion and exclusion criteria are listed in Table 1 . Two authors (YS and JR) independently and cooperatively determined suitable manuscripts for inclusion. Disagreements were discussed by the third author (SZ).

Based on the pre-designed table, the important report data are listed as the following: publication information (first author’s last name, the year published, study location), the details of the clinical trial (study design, intervention duration), the participants’ characteristics (sample size, age, gender, health status), and all reported outcomes of interest. Standard deviation (SD), belonging to the category of descriptive statistics, was the experimental index to be captured. When SE was reported, we use the formula between SD and SEM (SD = SEM × sqrt (n); n = number of participants) to convert.

Trials were assessed for bias risk using the Cochrane Bias Risk Tool (26) which includes sequence generation, allocation concealment, blinding, blinding of outcome assessment, incomplete outcome data, selective outcome reporting, and other bias. We ranked for “low”, “high”, or “unclear” risk of bias.

All the analyses were performed using STATA version 11. Weighted mean difference (WMD), SD, and 95% CI were used as the effective measures for SBP, DBP, HDL-c, LDL-c, TG, TC, and weight. The net changes in them were equal to the post-intervention values minus the baseline values. The SD of the mean difference was calculated by the following formula:

assuming a correlation coefficient (R) = 0.5 for both the pre-test/post-test (parallel groups) and the crossover designed studies. The heterogeneity index I² is used for quantitative analysis of heterogeneity, which ranges from 0% to 100%. There is no heterogeneity at 0%. The greater the I² value, the greater the heterogeneity. There was no statistical heterogeneity (I² < 50%) among the results of each study, and a fixed-effect model was used. If there was statistical heterogeneity (I² ≥ 50%) among the results, the random-effect model was used.

Meta-regression analysis was performed to calculate the duration–effect relationship between WMD and duration to explore potential explanations for heterogeneity.

We also conducted subgroup analysis studies including treatment duration (<42 days or ≥42 days), study design (crossover or parallel), and participants’ health status (healthy or unhealthy). To evaluate the influence of individual study on the pooled-effect size, sensitivity analysis (leave-one-out) was conducted and p < 0.05 was considered as statistically significant.

Begg’s rank correlation and Egger’s weighted regression statistics were used to evaluate potential publication bias (27, 28). p values less than 0.1 were considered statistically significant.

The initial search identified 527 papers for screening, of which 121 were removed because of duplication ( Figure 1 ). After title and abstract screening, 365 records were excluded due to irrelevance to the inclusion criteria. The full texts of the remaining 41 articles were further screened, after which 34 studies were excluded for the following reasons: lack of sufficient information on the outcomes of interest (n = 6); the dosage of sesamin was not specified (n = 17); study not designed as an RCT (n = 6); and article published as meta-analysis or review (n = 5). Finally, 7 articles (15, 21–24, 29, 30) with 212 arms were enrolled in the present meta-analysis. The PRISMA flowchart of the study is shown in the following.

Characteristics of the included studies are shown in Table 2 . Each of the included articles stated sesamin dosage, and four of the studies had dosages less than 200 mg/day. Four studies were on obesity, four studies were on BP, and five studies were on lipid profile. Included studies have been published between 1996 and 2016 and were conducted in 5 different areas: Japan, Taiwan, Australia, Thailand, and Iran. A total of 212 participants were enrolled in studies, and intervention duration ranged from 28 to 60 days. Four studies had a parallel design and three studies had a crossover design. Six trials were conducted in unhealthy individuals, and one trial was carried through healthy individuals.

Meta-analysis showed that sesamin supplementation caused a great reduction in TC (WMD: -10.893 mg/dl, 95% CI: −19.745 to −2.041, p = 0.016), LDL-c (WMD: -8.429 mg/dl, 95% CI: −16.086 to −0.771, p = 0.031), and SBP (WMD: −3.662 mmHg, 95% CI: −6.220 to −1.105, p = 0.005) ( Figure 2 ).

The quality of studies was evaluated by using the Cochrane collaboration’s risk-of-bias assessment tool. Random sequence generation, allocation concealment, and blinding of outcome assessment of participants were low risk of bias in all included studies. Only one trial had a high risk of bias due to the incomplete outcome. Details of the quality of studies are shown in Table 3 .

Results of meta-regression suggested no clear relationship between the duration and biomarkers we conducted (TC: coefficient = 0.377, p = 0.671; LDL-c: coefficient = 0.395, p = 0.686; HDL-c: coefficient = 1.043, p = 0.988; TG: coefficient = 2.039, p = 0.806; SBP: coefficient = 1.414, p = 0.921; DBP: coefficient = 1.575, p = 0.897; weight: coefficient = 0.987, p = 0.996; Figure 3 ).

Subgroup analyses showed no significant differences in the effect of sesamin on HDL-c, TG concentrations, and weight between subgroups, which are stratified by intervention duration (≥42 days vs.<42 days), study design (parallel vs. crossover), and health status (healthy vs. unhealthy) ( Table 4 ). It indicated that reduction was greater in trials conducted with longer duration, as for TC (WMD = -21.363 mg/dl, 95% CI: -34.090 to -8.636, p = 0.001; I² = 0.0%) and LDL-c (WMD = -14.434 mg/dl, 95% CI: -24.929 to -3.939, p = 0.007; I² = 55.2%). However, the reduction was more remarkable in participants with shorter duration (<42 days), as for SBP (WMD = -3.824 mmHg, 95% CI: -6.588 to -1.060, p = 0.007; I² = 45.9%). In addition, the trials conducted in unhealthy participants showed a remarkable reduction in TC (WMD = -21.363 mg/dl, 95% CI: -34.09 to -8.636, p = 0.001; I² = 0.0%), LDL-c (WMD = -14.434 mg/dl, 95% CI: -24.929 to -3.939, p = 0.007; I² = 55.2%), SBP (WMD = -4.490 mmHg, 95% CI: -7.315 to -1.666, p = 0.002; I² = 0.0%), and DBP (WMD = -3.542 mmHg, 95% CI: -6.873 to -0.210, p = 0.037; I² = 46.0%). Subgroup analysis also suggested that trials with a parallel design were correlated with its reduction of TC (WMD = -21.363 mg/dl, 95% CI: -34.090 to -8.636, p = 0.001; I² = 0.0%), LDL-c (WMD = -14.434 mg/dl, 95% CI: -24.929 to -3.939, p = 0.007; I² = 55.2%), and SBP (WMD = -5.778 mmHg, 95% CI: -10.197 to -1.360, p = 0.010; I² = 28.9%).

There was no significant impact for any individual trial on the pooled effect sizes of meta-analyses results, so the results are reliable.

The funnel plots were asymmetric ( Figure 4 ), indicating a possible publication bias in meta-analysis of the effects of sesamin on hemodynamics. However, the Begg’s rank correlation test and Egger’s linear regression test suggested no significant publication bias in this meta-analysis (all p>0.10) ( Table 5 ).

The rapid increase in obesity rates among adolescents and children around the world has shocked us (37). The status of obesity is not hopeful either, and the rise in adult obesity continues to rise (38). Since the outbreak of COVID-19, the interplay of obesity and COVID-19 has had devastating consequences with increased morbidity and mortality (39). Neidich et al. demonstrated that obese individuals were twice as likely to get the flu as healthy people who received the same vaccine (40). The health-related burden associated with obesity is estimated to have a substantial economic impact (41). Helli et al. have proved that intake of sesamin had a decrease in body weight (p = 0.001) (30). Sesamin increases lipolytic enzyme activity and decreases the activity of lipogenic enzymes, which also affects as an antagonist to liver X receptor (LXRα) and pregnane X receptor (PXR) ameliorating drug-induced hepatic lipogenesis (42, 43). However, our meta-analysis showed that the supplementation of sesamin had no association with reduction in body weight, so the effect of sesamin on weight could not be fully determined.

In the recent decade, hypertension is widely recognized to sharply increase the incidence of cardiovascular disease, which has dramatically increased the medical expenditure for patients around the world (44, 45). Through many in vitro and in vivo experiments, we now know that long-term effective antihypertensive therapy can avert hypertension-related mortality by nearly 50% (46). However, a systematic review written by Tadesse indicated that 45% of the subjects did not adhere to their antihypertensive medication, existing a low compliance (47). As dietary therapy becomes more and more accepted, sesamin has a good compliance prospect.

Our study revealed that a 4-week administration of 60 mg sesamin caused a decrease in BP with an average of 3.5 mmHg for SBP and 1.9 mmHg for DBP. Wu et al. proceeded a 4-week administration of sesamin and achieved a good antihypertensive effect that can greatly decrease SBP and DBP in mild-hypertensive participants (15). It was reported that patients with RA who consumed 200 mg/day sesamin showed a lower SBP level, but with no remarkable effect on DBP (30). According to Nakano (48), the mechanism of sesamin against high pressure is improving impaired endothelium-dependent vasodilatory responses. Our meta-analysis which covered both SBP and DBP levels indicated significant hypotensive effects of sesamin supplements, depending on study design, duration of treatment, and participants’ health status. Our subgroup analyses indicated the antihypertensive function of sesamin in the experimental design type was parallel. What is more, patients who received shorter than 42 days of sesamin and had an unhealthy status can show more obvious effects. Kong et al. showed that sesamin inhibited the progress of eNOS uncoupling, coupled with the effect on p-eNOS increases NO biosynthesis to relieve hypertension. Sesamin also inhibits NADPH oxidase contributing to the suppression of hypertension in hypertensive rats (49).

Hyperlipidemia, a life-threatening health condition endangering the life of most patients (50), represents as increasing TC/TG/LDL-c or decreasing HDL-c (51). With elevated LDL-c concentration as a risk factor, statins can effectively reduce the concentration to play an anti-hyperlipidemia role (52, 53). Although statins’ primary application is to lower cholesterol (54), drug toxicity to the human body is still unavoidable. “Pharmacograde nutrients” may be a potentially safe, healthy, and cheap way to optimize lipid levels (55). Hirata et al. suggested that sesamin together with vitamin E can reduce the LDL-c level effectively (p<0.05) (21). Another research conducted by Mohammadshahi (22) declared that by supplementing a daily dose of 200 mg sesamin to patients with Type II diabetes, the level of TG, TC, and LDL-c became reduced. There is a biological basis of lipid lowering; Tai et al. (43)showed that sesamin might improve blood lipid by reducing hepatic steatosis and absorption of cholesterol through the intestine. Majdalawieh et al. (36) revealed that sesamin mainly played anti-hyperlipidemic roles by aiming at Δ5 desaturase, HMGCR, ABCA1, and ABCG1 through PPARα, PPARγ, LXRα, and SREBP signaling pathways, which is important for the future supplement of sesamin.

Our meta-analysis showed that daily intake of sesamin was effective in improving LDL-c and TC levels but had no significant influence on TG and HDL-c. Long-term (≥42 days) sesamin intake is more effective than a short period of supplement. The reason may be that sesamin, as a food of nutrition, can make its accumulation in the body more obvious after long-term ingestion. The meta-regression showed LDL-c’s trend becoming flat over time. Perhaps this is because LDL-c fluctuates in a dynamic range for different individuals, flattening out as its concentration nears a critical level. In the experiment conducted by Wu et al. (23), the duration was so short that sesamin played no role. Therefore, no significant influence on the indexes of lipid profile was indicated. Probably due to one crossover RCT with short-term included, findings also indicated that TC and LDL-c levels were decreased when the RCT was designed to be parallel-controlled.

Integrated data from numerous selected studies are the major superiority of our study, so the reliability and accuracy of our analysis are robust. The seven indicators we included were carefully selected and of great clinical guiding significance. What is more, the studies we included from various geographic regions around the world, so our conclusion has a wide range of application value for people in different cultural backgrounds. Additionally, our review not only provides a new food therapy target for people who are in an unhealthy status but also facilitates guidance for the development of dietary intervention therapy in the future.

The limitations of our study were self-explanatory. Firstly, a relatively small sample size of the included studies may cause a higher risk for publication bias whereas Begg’s and Egger’s tests suggested no significant publication bias in our meta-analyses. Secondly, the heterogeneity of LDL-c was relatively high, but we found that this may be caused by long duration, unhealthy status, or parallel-design trials. Thirdly, the gender ratio in the studies we included was different, and the influence of hormone level on obesity, lipid profile, and blood pressure could not be ignored.