Sesame: Potential Health Benefits : Nutrition Today

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Food Science

Sesame

Potential Health Benefits

Singletary, Keith W. PhD

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doi: 10.1097/NT.0000000000000562
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Abstract

Sesame (Sesamum indicum L., family Pedaliaceae), also known as sesamum, gingelly, til, goma, ajonjoli, and benniseed, is an annual plant (Figure 1). The seeds are purported to be one of the oldest oilseeds used by humans. The seed colors of this plant vary considerably including white, yellow, gray, brown, and black, depending on the variety and strain of S indicum. Black sesame seeds and white sesame seeds are the most available worldwide. Although the chemical differences among the various colored sesame seeds are not well characterized, it has been reported that the contents of indole-3-carboxylic acid, hesperidin, 2-methoxycinnamic acid, vitamin B2, and hyoscyamine are significantly higher in black seeds compared with white seeds. However, at least for sesame lignans, seed color and content of these bioactives are unrelated.1,2 Although apparently originating in Africa and India, this plant is currently cultivated in diverse regions worldwide from semiarid tropics to temperate areas, and India, China, Tanzania, Sudan, and Myanmar are considered the major producers. Because of the high content of oil, sesame seed is called the queen of oilseeds. Its major use is the production of a notably oxidative rancidity-resistant oil. This oil has numerous uses such as a solvent, a hydrophobic vehicle for drug delivery, and a skin softener, and in the preparation of soaps and margarines.2–7 In cosmetics, it can function as a binder, emulsifier, and viscosity-increasing agent.8 As an edible seed oil, it has many routine and diverse uses in food preparation. It has widespread use globally in salads, and in Asia, the seed and oil are routinely used in cooking. Some Europeans substitute it for olive oil in cooking. The dehulled seed is included in the preparation of numerous food products, condiments, and confectionaries, imparting a distinctive savory, nutty, roasted flavor. For example, besides being sprinkled on the surface of breads, sesame seeds are incorporated into pastries, cakes, and crackers. A sesame-based milk alternative is marketed as well. International culinary applications include, for example, mixing the seed with sugar or honey to make candies in Asia and in the Middle East. In India, sesame is also known as til. Til ke laddu, a traditional sweet enjoyed during the Sankranti spring festival, is a small, rounded product made with dry roasted til, clarified butter (ghee), roasted and crushed peanuts, unrefined cane sugar (jaggery), and cardamom. Shirini konjedi is a Persian sesame brittle. Also in the Middle East, tahini, a butter or paste, is made from ground roasted seeds. This tahini paste can enrich other regional dishes. For example, hummus bi tahini is made with tahini, lemons, and chickpeas and may be additionally flavored with such seasonings as garlic, onion, cumin, or paprika. Baba ghanoush is a dip traditionally prepared from eggplant, tahini, garlic, lemon juice, olive oil, salt, and pepper. The soft, fudgelike confection halva/halvah, popular in the Balkans and Middle East, is a combination of tahini, sugar, salt, and vanilla. Sfouf, also called yellow cake or curcuma cake, is a popular Lebanese snack made with semolina, tahini, aniseed, turmeric, sugar, and pine nuts or almonds. Sesame is a component of the spice mixture zahtar (oregano, thyme, sumac, toasted sesame seed) in the Middle East. The Chinese version of sesame paste, zhi ma jiang, uses heavily roasted hulled raw seeds often blended with peanut, to create a denser, strong-flavored product. Chinese black sesame buns are made from leavened, steamed dough filled with a mix of toasted black sesame seeds, toasted peanuts, lard or butter, sugar, and salt. Goma dofu is a sesame-containing Japanese custard. In Japan, sesame is part of the spice blend, shichimi togarashi (chili pepper flakes, orange peel, sesame seed, ginger, seaweed), and is in the sesame salt, gomasio. Sesame oilseed meal, the by-product from oil extraction, is an ingredient for poultry, fish, and livestock feed. Because of its high protein content, it has garnered increasing attention as a functional food ingredient for human consumption.9–12

F1
FIGURE 1.:
Sesamum indicum L. This figure is available in color online (www.nutritiontodayonline.com).

The approximate composition of sesame seeds is 20% to 25% protein, 45% to 60% fat, and 3% to 14% carbohydrates. γ-Tocopherol is the major tocopherol in seeds, and ß-sitosterol is the principal sterol in the oil. Besides the presence of antioxidant phytochemicals, the sesame seeds also contain lignans that are of interest for potential health benefits due in part to their conversion by intestinal bacteria to biologically active enterolignans, enterodiol, and enterolactone.13 In the Middle East, sesame consumption is higher than in North America. Studies evaluating the relationship of total lignan intake to disease risk in this region are inconsistent.14–18 The major lignans, unique to sesame, are sesamin and sesamolin (Figure 2). The amounts of sesame lignans depend on plant variety, strain, and geographical factors, and vary from 1500- to 4200-mg/kg seeds for sesamin and from 620 to 3590 mg/kg for sesamolin. Sesamol, sesaminol, sesamolinol, and pinoresinol are lignans present in lesser amounts. Sesamol is nearly undetectable in unroasted, raw seeds. However, during heat processing of sesame seeds and oils and the acidic decoloration (bleaching) of sesame oil, sesamolin is converted to sesamol and sesaminol. Bleaching also leads to the epimerization of sesamin to episesamin.

F2
FIGURE 2.:
Structures of sesame compounds.

Sesame has a long history of use in traditional medicines. Black sesame seeds can be more expensive than other seeds because of the belief in Chinese traditional medicine that they have more health benefits.1 Global applications of sesame-based folk medicines include treatment of hemorrhoids, wounds, asthma, blurred vision, abdominal pain and ulcers, alopecia, toothaches and gum disease, migraine, menstrual irregularities, and inadequate lactation, to name a few. More recently, experimental studies provide preliminary evidence of sesame's antioxidant and anti-inflammatory properties, as well as its potential benefits toward atherosclerosis, cancer, diabetes, hypertension, microbial infections, pain, and wound healing. Furthermore, sesame lignans are marketed in supplemental form for their antioxidant, nutritional, and other purported health benefits.2,3,5,6,9,12,19–22 The current narrative summarizes human studies evaluating sesame seeds, oil, and extracts for alleviating the signs and symptoms of diverse human disorders, and provides suggestions for future research.

METHODS

For evidence on the potential health benefits of foods and plant constituents, data were gathered from cell culture experiments, animal studies, and human clinical trials. Human studies are particularly important in determining public health recommendations, especially randomized controlled trials that test well-characterized treatments applying appropriate study designs and statistical analyses. With this in mind, a search of the PubMed and Science Direct databases was conducted using terms including S indicum, sesame, sesamin, sesamol, sesamolin, gingelly, arpeh, and benniseed. Full reports of English-language publications and English-language abstracts of foreign-language articles from peer-reviewed journals were the primary sources of information. Although the quality of identified studies varied considerably, all relevant, published investigations were included in this overview so that the totality and diversity of information can be described, and issues for future research can be identified. Additional studies were gleaned from these sources. Studies of sesame as a component in multi-ingredient preparations were not included in this overview.

Absorption, Metabolism, and Distribution of Sesame Constituents

International data on the intake of lignans from plants in general and from sesame in particular in different countries are limited. Individual lignan intakes in several Western countries and Middle East locations were reported.14–16,18,23 In South Korea, the total intake of sesame lignans by men was determined to be 18.4 mg/d and that by women was 13.3 mg/d. The contribution to total sesame lignan intake from sesame seeds was 23%, and that from sesame oil was 77%.24 In Lebanon, sfouf cake was determined to possess one of the highest concentrations of sesame protein with per-occasion consumption in children varying from 78 to 103 mg.25

Little is known about the metabolism and disposition of ingested sesame and its lignan constituents in humans. Such data are important, because any potential contributions of sesame in improving health are impacted by how much is consumed and the ultimate amount and form of its individual bioactive components in target tissues. This information also helps in discerning any negative effects of sesame constituents and their metabolites to various organs.

In a study26 in Finland, individuals (n = 4) were provided a single dose of sesame from whole, crushed, nonroasted seeds (50 g, 3.73-mg lignans/g) after consuming a low-lignan diet for 1 week. The main lignans present in the seeds were sesamin, pinoresinol, and lariciresinol, with the latter 2 at levels only 7.5% and 1.6%, respectively, of that for sesamin. These nonroasted seeds contained no sesamolin or sesamolinol. The time of peak plasma concentrations (tmax) for sesamin and pinoresinol were 1 and 1.1 hours, respectively, with maximum plasma concentrations (Cmax) of 105 and 209 nmol/L, respectively. The plasma elimination half-life values for the ingested lignans were short, less than 6 hours. The major plasma enterolignan metabolites were enterodiol and enterolactone, which were detected at mean concentrations of approximately 720 and 580 nmol/L, respectively, at 24 hours. This suggests that sesame seeds are an important source of sesamin that can efficiently be converted to these enterolignans. In a small Swedish human trial,27 urine metabolites were quantified after consumption of a single dose of a sesame oil–containing muffin (180-mg sesamin, 71-mg sesamolin) by healthy volunteers (n = 6) following a low-lignan diet for 1 week. After 48 hours, the major urine metabolite was a sesamin monocatechol at levels of 22% to 39% of the ingested sesamin amount. No sesamin or sesamolin was detected in the urine, and only small amounts of enterolactone were present. No sesamolin metabolite was found in the urine, which the authors suggested was due to decomposition of sesamolin under the acidic conditions of the stomach. For a Japanese trial with 24 volunteers,28 the plasma concentrations of sesame lignans were evaluated after oral intake of 50-mg sesamin and episesamin (sesamin/episesamin = 1/1). Both sesamin and episesamin were absorbed with Cmax at 5 hours of 2.7 and 19.0 ng/mL, respectively. After repeated oral dosing for 28 days, plasma concentrations of sesamin and episesamin reached steady state levels by 7 days, which were approximately 1.0 and 5.0 ng/mL, respectively. At 5 hours, the unidentified main metabolites of sesamin and episesamin reached a Cmax of 187 and 87.7 ng/mL, respectively. No adverse events were recorded after ingestion of this test sample.

More information about sesame bioavailability and lignan metabolism is available from animal models. Collectively, the experiments in rats indicate that, after oral dosing, sesamin is converted by rapid first-pass metabolism in the liver to hydroxylated monocatechol and dicatechol metabolites by cytochromes (CYP) P450 and to their subsequent methylated forms by catechol-O-methyltransferase. These transformations occur in humans as well. Several CYPs can catalyze this conversion of sesamin and episesamin, with CYP2C9 being the main isoform in human liver microsomes.29,30 Sulfate conjugation (by sulfotransferases) and glucuronide conjugation (by uridine diphosphate-glucuronyl transferases) are the next steps in metabolism of these intermediates, which are then distributed in the plasma to numerous tissues in the body including the brain, with highest amounts detected in the liver and kidney. In humans, conjugation reactions occur in the intestinal epithelium and liver, with glucuronide conjugates predominating in the plasma.31 In a more recent pharmacokinetic study in rats,32 100–mg/kg body weight sesamin was orally administered. Blood was sampled up to 24 hours post dosing and liver was harvested 1 hour post dosing in a portion of the animals. In the liver, monocatechol and methylated monocatechol metabolites were detected, and sulfate conjugates were the major products of sesamin metabolism. The level of sesamin-catechol-3-sulfate was detected at 10-fold greater levels than that of sesamin. In addition, only sulfate conjugates were detected in the plasma, with the Cmax values of 2 sulfate conjugates registered at levels 5- to 10-fold higher than that of sesamin suggesting that, in rats, sesamin is rapidly metabolized to sulfate conjugates by the enzyme sulfotransferase. The apparent absorption of sesamin was 54%, with excretion in the urine and feces as metabolite forms. It should be emphasized that, in addition to the parent sesamin molecule, several metabolites of sesamin also possess appreciable biological activity.29,33–36 In light of reported plasma levels of metabolite conjugates, and on the basis of novel hypotheses for other sulfate and glucuronide conjugates,37,38 sesame metabolite conjugates may actually be an effective means of in vivo metabolite transport to target tissues where parent molecules are regenerated after cellular uptake. This warrants further substantiation.

Sesamolin and sesamol are also converted to catechol metabolites, and sulfate and glucuronide conjugates after ingestion.39–45 Absorption of sesamol was determined to be 35% to 46% via multiple sites of absorption.40,41

As far as formation of enterolignans in rats is concerned, sesamin can be converted to enterodiol and enterolactone by gut microbiota with subsequent metabolism to hydroxylated metabolites in the liver and intestinal epithelium. The levels of enterodiol and enterolactone in plasma of rats fed sesame are influenced not only by the amount of lignans ingested but also by the form of sesame-based diet consumed. For example, after rats were fed 1 dose of either sesame- or tahini-containing diets, enterodiol and enterolactone concentrations were higher in plasma from the tahini group, compared with levels in the sesame group.46 This differential effect of the 2 diets was lost after extended feeding. This underscores the need to further evaluate how diverse diets and food matrices may affect sesame disposition and modulate enterodiol and enterolactone formation.

Sesame Intake and Tocopherol Status

In 4 trials, the effect of sesame intake on the status of γ-tocopherol in humans was evaluated. In young women (n = 11) provided buns with 22.5-g sesame oil per day and 9.5-mg γ-tocopherol per day for 4 weeks, compared with baseline, serum γ-tocopherol levels increased but α-tocopherol did not.47 Similar outcomes were reported in an investigation48 in which γ-tocopherol– and sesame seed powder–containing muffins (10.8-g sesame seed) were fed to healthy volunteers (n = 9) for 3 days. Compared with baselines, consumption of sesame was associated with a significant increase in γ-tocopherol level, a decrease in plasma ß-tocopherol, and no changes in plasma α- and δ-tocopherols. In 2 studies,49,50 volunteers (n = 16) were fed 1 dose of sesame oil– and γ-tocopherol–containing muffins (136-mg sesamin and sesamolin). After 48 to 72 hours, compared with baseline, there was a significant decrease in urinary excretion of γ-carboxymethylhydroxychroman (γ-CEHC), which are metabolites of γ-tocopherol. Of interest from one of the studies,50 sesame oil consumption, compared with baseline, resulted in a decrease in plasma area under the curve and Cmax for γ-CEHC in men but not in women, although in both genders, urinary γ-CEHC decreased with sesame intake. The reason for this difference was not discussed.

In rats orally administered sesamin or sesame seed, significant increases were observed not only in plasma levels of γ-tocopherol but also in other tissues such as the liver and lung. Much smaller changes in plasma α-tocopherol levels were observed. Consistent with increased tissue levels of γ-tocopherol was a corresponding decrease in urinary excretion of γ-CEHC, a relationship that also was observed in humans.51–54 Elevation of plasma γ-tocopherol levels was considered to be due to inhibition of further CYP3A-based metabolism of γ-tocopherol by sesamin.55 Sesamin ingestion also affected the disposition of n-3 fatty acids. Specifically, in rats consuming sesamin along with oil containing eicosapentaenoic acid, there was a significant decrease in liver content of eicosapentaenoic acid without influencing lymphatic absorption. No similar effect of sesamin intake was observed for n-6 and n-9 fatty acids. The reason for this sesamin-associated drop in liver n-3 fatty acid content is not known, although the authors suggest that sesamin may be affecting ∆5-desaturase activity. Taken together, these findings suggest that sesame seed intake can potentially lead to elevated plasma γ-tocopherol concentrations likely resulting in greater circulating antioxidant activity, to changes in relative tissue levels of other tocopherols, and to altered n-3 fatty acid status.

Potential Health Benefits of Sesame in Human Trials

Relatively more information is available regarding the impact of plant lignans on health compared with sesame lignans. Consumption of plant lignans in general has the potential to decrease risk of cardiovascular disease.23 For other diseases, such as, for example, breast cancer, the relationship of dietary lignans to risk requires further clarification especially in light of the lower amounts of lignans typically consumed in many countries and the possibly different effects depending on the disease.56–59

Blood Glucose and Lipid Regulation

The effect of sesame seed extracts in particular on blood glucose and lipid regulation in several health disorders is summarized in Table 1. When all trials are considered together, considerable heterogeneity is apparent and several methodological shortcomings were noticeable. Most of the studies identified were small, with 81% evaluating 40 subjects or less. Duration of sesame administration was short with 78% of the trials continuing for 60 days or less. Furthermore, some studies lacked statistical comparisons between the separate outcomes of the control and treatment groups, and blinding in studies was inconsistent. Amounts of sesame given to participants also varied substantially. Moreover, sesame samples varied considerably in the form and manner that they were administered to participants. Specifically, sesame was provided as unground seeds,61,90 seed powder,48,60,66,68,74,86,88 oil incorporated into vegetable soup,70 oil dispensed to individuals for inclusion in foods,77 oil dispensed individually to patients for exclusive use as cooking oil,80 bulk quantities of oil provided to households for use as the only edible oil in food preparation and cooking,69,71,75,76,78,79 and sesame-containing food bars.61 These differences in treatment methods are important to acknowledge, because they may alter the bioavailability of bioactives present in sesame products.

TABLE 1 - Effect of Sesame on Cardiovascular Disease (CVD) and Diabetes (T2DM) Risk Factors
Subjects Sesame Form Dose/Duration Main CVD/T2DM Outcomes Other Outcomes Ref.
Healthy adults Seed powder 10.8 g/d (n = 9); 3 d *NE: TC, TG, HDL, LDL NE: MDA, plasma carotenoids 48
50 g/d (n = 24); 5 wk, postmenopausal ♀ *↓LDL, ↓TC, ↑BW, ↑% body fat
NE: HDL, TG
↓TBARS, ↑Vit E, ↑γ-tocopherol, ↓DHEAS, ↓SHBG, ↑U-2OH-E1
NE: estrone, estradiol, FSH
60
Unground seed 25 g/d (n = 16); 4 wk, postmenopausal ♀ *↑ApoA1
NE: TC, TG, LDL, HDL
↑γ-tocopherol, ↑n-6FA
NE: FRAP
61
Seed oil 30 g/d (n = 70); 9 wk *↓Muscle mass, ↓WC, ↓HC, ↑% body fat, ↓ICO, ↓BAI
NE: BW, BMI, % visceral fat
62
22.5 g/d (n = 11); 4 wk, ♀ *NE: TC, TG, LDL, HDL NE: MDA 47
Sesamin 64.8 mg/d (n = 6), placebo (n = 6); 4 wk, ♂ #↓TC, ↓LDL, ↓ApoB
NE: TG, HDL
63
Tahini 50 g (n = 20); 4 h postprandial, ♂ *↓FBG, ↓DBP, ↑TG, ↓pulse rate, ↑FMD,
NE: TC, LDL, HDL, SBP, PWV
↑Urinary 8-iso-PG-F
NE: ICAM-1, VCAM-1, E-sel, FRAP
64,65
Overweight Seed powder 25 g/d (n = 33), placebo (n = 33); 5 wk #NE: BW, TC, LDL, HDL, TG, BP, HR ↑Urinary excretion of mammalian lignans, enterolactone, enterodiol
NE: IL-6, TNF-α, CRP, F2-isoP
66
Seed oil 30 g/d (n = 68); 9 wk *↓SI, ↓HOMA-IR, ↑HOMA-%S, ↓HOMA-%B, ↑QUICKI
NE: TC, TG, LDL, HDL, ApoB, Apo-A1, L(p)a, VAI, SBP, DBP, FBG, stroke risk, MI risk, CVD risk
↓ALT
NE: creatinine, ALP, AST, GGT
67
Prehypertensive Seed powder 2.52 g/d (n = 15); 4 wk *↓SBP
NE: DBP
↓MDA, ↑Vit E 68
Hypertensive Seed oil 35 g/d (n = 17-50); 45-60 d *↓TG, ↓BW, ↓BMI, ↑↓SBP, ↑↓DBP
NE: TC, HDL, LDL
↓TBARS, ↑TAC, ↑SOD, ↑CAT, ↑GSH, ↑ß-carotene, ↓Na+, ↑K+
NE: TNF-α, CRP, MDA
69,70
35-40 g/d (n = 356), controls (n = 40); 60 d #↓TC, ↓TG, ↓LDL, ↑HDL, ↓SBP, ↓DBP ↓TBARS, ↑SOD, ↑GPx, ↑CAT, ↑GSH, ↑Vit C, ↑Vit E, ↑ß-carotene 71
35 g/d (n = 14);
2 h
*↑FMD
NE: SBP, DBP
NE: blood ICAM, blood ADMA 70
Hypertensive (mild) Sesamin 60 mg/d (n = 12), placebo (n = 13); 4 wk #↓SBP, ↓DBP 72
T2DM Seed powder 28 g/d (n = 20), controls (n = 16); 6 wk #↓TG, ↓AIP
↑↓HDL
NE: TC, LDL, WC, SBP, DBP, FBG
73,74
Seed oil 35 g/d (n = 40); 45 d *↓TC, ↓TG, ↓LDL, ↓FBG, ↓HbA1c, ↓BW, ↓BMI, ↓SBP, ↓DBP
NE: HDL
↑SOD, ↑CAT, ↑Vit E, ↑Vit C, ↑ß-carotene, ↑GSH
NE: GPx
75
36 g/d (n = 18), glibenclamide (n = 18); 60 d Sesame: *↓FBG, ↓HbA1c, ↓TC, ↓LDL, ↓TG, ↑HDL
Glibenclamide: *↓FBG, ↓HbA1c,
NE: TC, LDL, TG, HDL
Sesame: ↑SOD, ↑GPx, ↑CAT, ↑GSH, ↑Vit C, ↑Vit E, ↑ß-carotene
Glibenclamide: ↑SOD, ↑GPx, ↑CAT
NE: Vit C, Vit E, GSH, ß-carotene
76
30 mL/d (n = 23), soybean oil controls (n = 23); 90 d #↓FBG, ↓HbA1c, ↑SI
NE: BW, BMI, RBC, WBC, Hct, Hb, albumin, globulin
↑GPx, ↑SOD, ↑CAT, ↓TBARS, ↓ALP, ↓ALT, ↓AST, ↓CK, ↓Fe, ↓Zn, ↓Na+
NE: K+, Ca++
77
30 g/d (n = 93); 9 wk *↓SI, ↓HOMA-IR, ↓HOMA-%B, ↑HOMA-%S, ↑QUICKI, ↑BW, ↑BMI, ↓WHR, ↑visceral fat (%), ↓WC, ↓ICO
NE: FBG, % muscle mass, % body fat, BAI, HC
NE: GGT, AST, ALP 78,79
30 g/d (n = 25); 45 d *↓FBG, ↓TC, ↓LDL, ↓HbA1c
NE: TG, HDL
80
Sesamin 200 mg/d (n = 24), placebo (n = 24); 8 wk #↓FBG, ↓HbA1c
NE: BMI, WC, % body fat, SI, HOMA-IR, BAI
↓TNF-α
NE: IL-6, CRP, adiponectin
81,82
8.7 mg/d; 8 wk *↓TC, ↓LDL, ↑SI
NE: TG, HDL
83
Tahini 30 g/d (n = 20); 6 wk *NE: FBG, SI, HOMA-IR, anthropometric measures ↓CRP 84
Defatted seed flour 30 g/d (n = 14); 60 d, ♀ *↓BW
NE: FBG, HbA1c
85
MetS Seed powder 50 g/d (n = 24); 6wk *NE: BMI, BW, WC, TC, TG, LDL, HDL, AIP 86
Seed oil 30 mL/d (n = 24); 8 wk *↓FBG, ↓HOMA-IR, ↓TC, ↓TG, ↓BP
NE: HDL, SI
↓MDA
NE: CRP
87
Hypercholesterolemic Seed powder 40 g/d (n = 21); 4 wk *↓LDL, ↓TC, ↓LDLox, ↓LDLTBARS
NE: BW, BMI, TG, HDL
88
Seed oil 60 g/d (n = 24); 1 mo *↓TG, ↓LDL
NE: TC, HDL, BW
89
Hyperlipidemic Unground seeds 40 g/d (n = 19); 60 d *↓TC, ↓LDL,
NE: HDL, TG
↓TBARS, ↑SOD, ↑GPx 90
Hemodialysis patients Seed oil 4.5 g/d (n = 15); 2 mo *NE: TC, TG, LDL, HDL 91
Arthritic Sesamin 200 mg/d (n = 22), placebo (n = 22); 6 wk, ♀ #↑HDL
NE: TC, LDL, TG, SBP, DBP, WC, BAI
↑TAC
NE: MDA
92
Abbreviations: ADMA, asymmetric dimethylarginine; AIP, adiposity index of plasma; ALP, alkaline phosphatase; ALT, alanine aminotransferase; ApoA1, apolipoprotein A1; ApoB, apolipoprotein B; AST, aspartate aminotransferase; BAI, body adiposity index; BMI, body mass index; BP, blood pressure; BW, body weight; CAT, catalase; CK, creatine kinase; CRP, C-reactive protein; DBP, diastolic blood pressure; DHEAS, dehydroepiandrosterone sulfate; E-sel, E-selectin; F2-isoP, F2-isoprostane; FBG, fasting blood glucose; FMD, flow-mediated dilation; FRAP, ferric-reducing ability of plasma; FSH, follicle-stimulating hormone; GGT, gamma-glutamyl transferase; GPx, glutathione peroxidase; GSH, reduced glutathione; Hb, hemoglobin; HbA1c, glycated hemoglobin A1c; HC, hip circumference; Hct, hematocrit; HDL, high-density lipoprotein; HR, heart rate; HOMA-IR, homeostasis model assessment for insulin resistance; HOMA-%B, homeostasis model assessment for ß-cell function; HOMA-%S, homeostasis model assessment for insulin sensitivity; ICAM, intracellular adhesion molecules; ICO, index of central obesity; IL-6, interleukin 6; 8-iso-PG-F, urinary 8-iso-prostaglandin F; LDL, low-density lipoprotein; LDLTBARS, low-density lipoprotein–associated TBARS; LDLOX, oxidized low-density lipoprotein; L(p)a, L(p)a cholesterol; MDA, malondialdehyde; MetS, metabolic syndrome; MI, myocardial infarction; NE, no effect; n-6FA, n6-polyunsaturated fatty acids; PWV, carotid-femoral pulse wave velocity; QUICKI, quantitative insulin sensitivity check index; RBC, red blood cell; SBP, systolic blood pressure; SHBG, serum hormone-binding globulin; SI, serum insulin; SOD, superoxide dismutase; TAC, total antioxidant capacity; TBARS, thiobarbituric acid reactive substances; TC, total cholesterol; TG, serum triglycerides; TNF-α, tumor necrosis factor α; U-2OH-E1, urinary 2-hydroxy estrone; VAI, visceral adiposity index; VCAM, vascular cell adhesion molecule-1; Vit, vitamin; WBC, white blood cells; WC, waist circumference; WHR, waist-to-height ratio.
Symbols: ♀, only female participants; ♂, only male participants; *, treatment compared with baseline; #, treatment compared with placebo control; ↑, increase; ↓, decrease; ↑↓, inconsistent.

In healthy subjects, no consistent effects on blood glucose levels, lipid profiles, and anthropometric measures were observed among participants provided sesame seed, oil, flour, or sesamin.47,48,60,61,63,85 Similar inconsistencies in these outcomes were observed for hypercholesterolemic/hyperlipidemic, overweight, and hypertensive subjects.66–68,70–72,88–90 Furthermore, in hypertensive individuals, overall effects on blood pressure were inconsistent. Despite the methodological weaknesses noted, trials administering sesame oil showed evidence of a trend toward correcting aberrant blood glucose and hemoglobin A1c levels in subjects with diabetes and metabolic syndrome.76–79,87 When markers of inflammation were measured in 3 studies,69,70,87 there was no consistent influence of sesame oil consumption. In addition, in those trials that evaluated the impact of ingestion of sesame extracts on anthropometric measures, no consistent effect was reported. Furthermore, no adverse effects from consuming these diverse sesame products were reported.

Several meta-analyses were initiated to determine whether sesame consumption significantly affected blood glucose and lipid dysregulation, blood pressure, and body weight. Four meta-analyses were published analyzing the impact of sesame on cardiovascular disease and type 2 diabetes mellitus risk factors.93–96 The duration of interventions was noted to range from approximately 4 to 8 weeks; doses of sesame varied from 2.5 to 50 g/d, and those for sesamin varied from 3.6 to 200 mg/d.96 In meta-analyses by Sohouli et al94 and Yargholi et al,95 both reported that sesame consumption, compared with controls, was associated with a significant decrease in fasting blood glucose (weighted mean difference, −21.3 to −28.2 mg/dL) and in hemoglobin A1c values (weighted mean difference, −0.75% to −1.00%). However, no significant effect of sesame on serum insulin or homeostatic model assessment for insulin resistance was detected. In contrast, Huang et al96 found no significant effect of sesame intake on fasting blood sugars. The basis for this inconsistency is not known but may be due partly to participants' characteristics and the methodological qualities of specific trials selected for inclusion in the analysis. Specifically, the report by Huang et al96 included 16 trials in the analysis, whereas 8 trials were selected for each of the other 2 analyses.94,95 From 1 analysis, no specific source of sesame supplementation was identified as a main contributor to decreasing fasting blood glucose and hemoglobin A1c values.95 All sources of sesame were effective, although this should be confirmed in future studies. Taken together, these findings suggest that sesame seed products favorably influence blood glucose levels without influencing insulin resistance.

Two meta-analyses93,96 examined the influence of sesame feeding on blood lipid profiles. Both were in agreement that sesame intake significantly suppressed serum triglyceride levels, compared with controls. There was no agreement as to whether sesame intake significantly influenced total cholesterol, low-density lipoprotein, and high-density lipoprotein values. In contrast, a recent meta-analysis of randomized controlled trials determined that consumption of sesamin supplements significantly reduced serum total cholesterol and low-density lipoprotein levels but did not affect triglyceride and high-density lipoprotein.97

Two meta-analyses96,98 detected a significant decrease in systolic blood pressure associated with sesame intake, compared with controls, but found no consistent effect on diastolic blood pressure. A similar outcome was observed in the analysis of studies with supplemental sesamin.97 In addition, as reported in 3 meta-analyses,96,97,99 the effect of sesame and sesamin on body weight and body mass index was inconsistent.

Pain Management

Sesame seed powder, oil, and sesamin were evaluated as treatments for diverse conditions and found to have analgesic properties (Table 2). Doses and methods of delivery differed considerably, and numbers of subjects varied from 17 to 60. For arthritic conditions, ingestion of seed powder100,101 or sesamin103 resulted in significant decreases in reported joint pain and tenderness, and improved joint flexibility and mobility of participants. In fact, topical seed oil was associated with similar magnitudes of improvement as those observed for topical administration of the nonsteroidal anti-inflammatory drug diclofenac.102 Three trials measured markers of inflammation.100,101,103 Blood levels of tumor necrosis factor α and cyclooxygenase-2 decreased after treatment with sesamin, whereas C-reactive protein and interleukin-6 levels responded inconsistently for subjects provided seed powder or sesamin. In those trials evaluating the topical administration of sesame oil for subjects with trauma to the extremities or for phlebitis,104–110 a significant suppression of pain was observed, compared with controls. Collectively, these studies suggest that further examination of sesame dose, manner of administration, and treatment duration for the alleviation of different sources of pain is warranted.

TABLE 2 - Human Studies of Sesame for Pain Management
Condition Sesame Form Dose/Duration Outcomes Ref.
Osteoarthritis Seed powder Standard treatment + 40 g/d (n = 22); 2 mo Versus control (standard treatment, n = 23):
↓knee pain, ↑mobility, ↓IL-6
NE: MDA, TAC, CRP
100,101
Seed oil Topical oil 5 drops 3×/d (n = 47), topical 1% diclofenac gel 3×/d (n = 47); 4 wk Sesame vs baseline:
↓knee joint pain, ↑knee flexion angle, ↓time for 8-m walk
NE: analgesic consumption
Sesame vs diclofenac: similar magnitude of benefits, less use of analgesics compared with sesame oil
102
Rheumatoid arthritis ♀ Sesamin 200 mg/d (n = 22); 6 wk Versus placebo (n = 22):
↓swollen joints, ↓joint tenderness, ↓pain severity, ↑physical activity, ↓CRP, ↓COX-2, ↓TNF-α, ↓serum hyaluronidase
NE: serum aggrecanase, IL-1ß, IL-6
103
Trauma: upper/lower extremity Seed oil Topical oil 10 drops 2×/d (n = 17); 9 d Versus control (topical paraffin oil, n = 18):
↓pain severity
NE: frequency of NSAID use
104
Standard treatment + 10 drops topical oil 1×/d (n = 60); 10 d Versus control (standard treatment, n = 66):
↓pain severity, ↓use of NSAIDs
105
Topical oil 10 drops + massage 3×/d (n = 41); 2 d Versus control (topical cooking oil + massage, n = 41):
↓pain severity
106
Phlebitis (chemotherapy induced) Seed oil Topical oil, 10 drops + massage 2×/d (n = 28); 7 d Versus control (massage, n = 30):
↓pain severity
107
Topical oil, 10 drops 2×/d (n = 30); 2 wk Versus control (n = 30):
↓pain + erythema + swelling, ↓incidence of phlebitis, delayed occurrence of phlebitis
108
Topical oil, 5 drops every 6 h (n = 18); 30 h Versus control (topical liquid paraffin, n = 18):
↓onset phlebitis
109
Topical oil, 10 drops 2×/d (n = 30); 30 d Versus control (topical liquid paraffin, n = 30):
↓pain + erythema + swelling, ↓incidence of phlebitis, ↑vein survival time, delayed phlebitis development
110
Abbreviations: COX-2, cyclooxygenase-2; CRP, C-reactive protein; IL-1ß, interleukin 1ß; IL-6, interleukin 6; MDA, malondialdehyde; NE, no effect; NSAID(s), nonsteroidal anti-inflammatory drug(s); TAC, total antioxidant capacity; TNF-α, tumor necrosis factor α.

Sesame extracts were tested in small trials or pilot studies to treat other diverse disorders (Table 3). These preliminary findings may provide a basis for further pursuit of preclinical and additional clinical studies of sesame extracts to treat these diverse conditions.

TABLE 3 - Human Studies of Sesame for Relief of Diverse Conditions
Condition Sesame Form Dose/Duration Outcomes Ref.
Nasal dryness Seed oil 1 spray of Nozoil/nostril, 3×/d (n = 40); 20 d
1-3 sprays of Nozoil/nostril, 3×/d (n = 79); 14 d
Versus baseline:
↓nasal mucus dryness, ↓crust formation, ↓nasal blockage vs control (isotonic NaCl, n = 79):
↓nasal mucus dryness, ↓nasal stuffiness, ↓nasal crustiness
111
112
Functional dyspepsia Seed oil Soft oil capsule, 3×/d (n = 35); 6 wk Versus baseline:
↓total dyspepsia symptom score
113
Cough in children Seed oil 5 mL at bedtime (n = 53); 3 d Versus placebo (starch syrup, n = 54):
NE: cough frequency, cough strength
114
Multiple sclerosis Seed oil 0.5 mL/d + 30 μg/wk IFN-ß-1α (n = 54); 6 mo Versus control = 30 μg/wk IFN-ß-1α (n = 39):
↑serum IL-10, ↓NO, ↓IFN-γ, ↓TNF-α, ↓lymphocyte proliferation
NE: clinical relapse of disease
115
Adhesive small bowel obstruction (SBO) Seed oil 150 mL/d adjunct to nasogastric intubation + conventional treatment (n = 31); 6-10 d Versus control (conventional treatment, n = 33):
↓time for spontaneous stool passage, ↓length hospitalization, ↓need for corrective relaparotomy
NE: complications and recurrence of SBO after surgery
116
Sleep disturbance Seed oil 30 min/d Ayurvedic forehead oil-dripping treatment (n = 20); 2 wk Versus control (warm H2O forehead drip, n = 20):
↑self-reported sleep quality
NE: perception of sleepiness, specific sleep measurements, quality of life, postintervention sleep quality
117
Male infertility Seed powder 0.5 mg/kg bw/d (n = 25); 3 mo Versus baseline:
↑sperm count, ↑sperm motility
NE: sperm morphology
118
Sport training improvement Seed powder 40-g/d powder paste (n = 10); 28 d Versus control paste (n = 10):
↓CK, ↓MDA, ↑Vit A, ↑Vit E
NE: LDH, CRP, max aerobic capacity, peak aerobic capacity speed
119
Oligomenorrhea Alcohol/water extract from 60-g seed powder 400-mL tea per day (n = 21); 7 d Versus baseline:
↑frequency menstrual bleeding, ↓menstrual delay, ↓use menstrual drugs
NE: blood flow, pain
120
Management of early pregnancy loss Water extract from 30-g seed powder 200 mL tea per day (n = 44); 5 d Versus control (expectant management, n = 43):
↑ in complete resolution of retained product of conception, ↓vaginal blooding, ↓vaginal pain
121
Mild cognitive impairment Alcohol/water extract from sesame seed cake 1.5 g/d (n = 28); 12 wk Versus control (n = 30):
↑verbal learning, ↓plasma amyloidß(1-40), ↓plasma amyloidß(1-42)
NE: visual learning, 8-OHdG
122
Abbreviations: CK, creatine kinase; CRP, C-reactive protein; IFN-ß-1α, interferon-ß1α; IFN-γ, interferon-γ; IL-10, interleukin 10; LDH, lactate dehydrogenase; max, maximum; MDA, malondialdehyde; NaCl, sodium chloride; NE, no effect; NO, nitric oxide; TNF-α, tumor necrosis factor α; Vit, vitamin; 8-OHdG, 8-hydroxy-2'-deoxyguanosine.

Of interest are reports that sesame oil can improve oral health by its use in a traditional Ayurvedic treatment, oil pulling,123–130 and other oral hygiene approaches.131–133 The practice of oil pulling involves swishing an oil around the mouth for a specified time and then spitting out the oil. Its purpose is to remove bacteria and improve oral health.

Potential Mechanisms

There is limited information from human trials supporting specific mechanisms of action of sesame in mediating physiological responses. A meta-analysis evaluating the influence of sesame intake on inflammatory biomarkers134 concluded that sesame consumption was associated with a significant decrease in serum levels of interleukin 6, but not for C-reactive protein and tumor necrosis factor α. There is evidence in humans that sesame oil may suppress oxidative stress (thiobarbituric acid reactive substances, malondialdehyde), elevate antioxidant defense markers (total antioxidant capacity, superoxide dismutase, catalase, reduced glutathione, glutathione peroxidase), and enhance levels of the nutrients vitamin E, vitamin C, and beta carotene.69–71,75,77,87 Other potential mechanisms observed from animal trials have been reviewed2,3,12,135–142 and include exhibiting estrogenic and antiestrogenic properties, inhibiting neurological damage and neurodegeneration, lowering levels of proinflammatory markers and cytokines, suppressing fatty acid synthesis and cholesterol synthesis and absorption, maintaining cholesterol homeostasis, promoting fatty acid oxidation, altering immunomodulatory and anti-inflammation signaling networks, and modifying endothelium-dependent vasodilatory and vasorelaxation responses.

Safety

Sesame is considered generally recognized as safe for human consumption by the US Food and Drug Administration for inclusion in food consistent with its intended use as a natural seasoning or flavoring (21 CFR 182.0). Furthermore, sesame oil, as an indirect additive, is approved for incorporation into coatings that interface with food during manufacturing, packaging, and transporting (21 CFR 175.300). A toxicological and clinical assessment of sesame determined it to be safe for numerous cosmetic applications.8

Some limited adverse events after use of sesame131,143,144 were reported. However, a significant issue regarding sesame is its allergenicity in children and adults, with varying prevalence worldwide. There is some evidence, although limited, that sesame allergy is more prevalent in the Middle East than in Western countries.25,145–147 Several sesame constituents were identified as potential human allergens.148 The forms of sesame eaten, for example, as whole seeds or in tahini, may affect the magnitude of the allergic response.149,150 Nonetheless, one report suggested that an oral dose of 1-g sesame protein (approximately 4-g tahini paste, 1 teaspoon) will cause objective symptoms in more than 90% of sesame-allergic individuals.150 Although its prevalence in North America is low,151 it can produce serious immediate and delayed hypersensitivity in sensitive individuals. Precautionary allergen avoidance is recommended to minimize this.2,8,145,151–153 Labeling of sesame presence in food products is mandatory in the European Union. Although food labeling regulations in the United States currently do not recognize sesame as a priority allergen to be routinely included in food labels, there are efforts to change this.154,155

There is some evidence from preclinical experiments that sesame constituents may have the potential to interact with drugs by affecting the activity of several CYP enzymes involved in their metabolism. Specifically, sesamin is an inhibitor of CYP2C9, which is a CYP isoform that metabolizes anticlotting, diabetic, and nonsteroidal anti-inflammatory drugs.29,30 Preclinical studies by Yasuda et al156 suggest that no serious effect on CYP2C9-dependent drug metabolism would be expected at doses of sesamin typically ingested by humans. Similarly, the clinical investigation of Tomimori et al28 concluded that no clinically significant effect on CYP2C9 was apparent after repeated ingestion of 50-mg sesamin per day for 28 days and that sesamin would be safe and tolerable in healthy subjects at typical levels encountered in supplements. However, 2 recent preclinical reports evaluating the CYP2C9-dependent 7-hydroxylation of warfarin157,158 provide conflicting conclusions as to whether likely blood levels resulting from oral intake of sesamin have the potential to affect warfarin metabolism by human liver enzymes. The potential for interactions of sesamin with drugs metabolized by CYP2C9 in humans is not well characterized and warrants additional monitoring. Furthermore, there is evidence that sesamin can inhibit the activities of cytochrome P450 3A4 and cytochrome P450 4F2.12,55,159–161 Inhibition of CYP3A4 is associated with increased plasma concentrations of γ-tocopherol. CYP3A4 also participates in the metabolism of a wide variety of substrates including retinoic acid, bile acid, testosterone, estrogen, cholesterol, dietary chemicals, and environmental toxins, as well as drugs such as acetaminophen, codeine, and cyclosporin A and the novel heart rate-lowering agent, ivabradine. CYP4F2 catalyzes the ω-oxidation of the n-6 fatty acid arachidonic acid and the proinflammatory agent leukotriene B as well as the metabolism of vitamins E and K1. The potential interactions of sesamin with CYP3A4- and CYP4F2-dependent substrate metabolism as well as with drug conjugation reactions in humans are not well characterized and deserve further evaluation. This issue is important to clarify because commercial sesamin supplements are currently readily available with recommended daily doses of up to 200 to 250 mg/d, whereas other sesame seed products for human consumption provide little information on the amounts of bioactives present.

CONCLUSION

There is initial evidence that sesame intake may improve blood glucose regulation, but less consistent is the evidence for its capacity to improve lipid dysregulation and hypertension. Additional larger, well-designed randomized controlled trials are needed that evaluate multiple doses and intervention durations for different sources of sesame (eg, whole seeds, powdered seeds, oil, specific constituents) and that also address potential mechanisms of action. In addition, on the basis of preliminary results, human studies are warranted that examine sesame's possible analgesic effects for participants with different sources of pain. The inadequate standardization of doses among trials needs to be improved by more consistent reporting of sample composition. Measuring blood levels of select metabolites can provide more insights into sesame bioavailability and participants' compliance. Routinely reporting analyses of diets is important so that the effect of subjects' diets on treatment outcomes can be better characterized. Furthermore, whether the administration of sesame at typical culinary doses can provide consistent benefits deserves clarification. Although the results of some studies seem promising, they are too preliminary to recommend the use of sesame products and supplements for customary use in improving health or treating disorders.

REFERENCES

1. Wang D, Zhang L, Huang X, et al. Identification of nutritional components in black sesame determined by widely targeted metabolomics and traditional Chinese medicines. Molecules. 2018;23:1180. doi:10.3390/molecules23051180.
2. Andargie M, Vinas M, Rathgeb A, et al. Lignans of sesame (Sesamum indicum L.): A comprehensive review. Molecules. 2021;26:883. doi.org/10.3390/molecules26040883.
3. Mili A, Das S, Nandakumar K, Lobo R. A comprehensive review on Sesamum indicum L.: botanical, ethnopharmacological, phytochemical, and pharmacological aspects. J Ethnopharmacol. 2021;281:114503. doi.org/10.1016/j.jep.2021.114503.
4. Elleuch M, Besbes S, Roiseux O, Blecker C, Hamadi Attia. Quality characteristics of sesame seeds and by-products. Food Chem. 2007;103:641–650.
5. Mushtaq A, Hanif M, Ayub M, Bhatti I, Jilani M. Sesame. In: Hanif M, Nawaz H, Byrne J, eds. Medicinal Plants of South Asia. Chap. 44. Amsterdam, the Netherlands: Elsevier Press; 2020:601–615.
6. Yaseen G, Ahmad M, Zafar M, et al. Sesame (Sesamum indicum L.). In: Inamuddin G, Boddula R, Asiri A, eds. Green Sustainable Process for Chemical and Engineering and Science. Amsterdam, the Netherlands: Elsevier Press; 2021:253–269.
7. Hegde D Sesame. In: Peter K, ed. Handbook of Herbs and Spices. Vol. 2, Chap. 23. Woodhead Publishing Ltd, Sawston, UK, 2012:449–486.
8. Johnson W Jr., Bergfeld WF, Belsito DV, et al. Amended safety assessment of Sesamum indicum (sesame) seed oil, hydrogenated sesame seed oil, Sesamum indicum (sesame) oil unsaponifiables, and sodium sesameseedate. Int J Toxicol. 2011;30(3, suppl):40S–53S.
9. Anilakumar K, Pal J, Khanum F, Bawa A. Nutritional, medicinal and industrial uses of sesame (Sesamum indicum L.) seeds—an overview. Agric Conspec Sci. 2020;75:159–168.
10. Elleuch M, Bedigian D, Zitoun A. Sesame (Sesamum indicum L.) seeds in food, nutrition, and health. In: Nuts & Seeds in Health and Disease Prevention. Chap. 122. Elsevier Press, Amsterdam, the Netherlands, 2011:1029–1036. doi: 10.1016/B978-0-12-375688-6.10122-7.
11. Nevara GA, Giwa Ibrahim S, Syed Muhammad SK, et al. Oilseed meals into foods: an approach for the valorization of oilseed by-products. Crit Rev Food Sci Nutr. 2022;1–14. doi:https://doi.org/10.1080/10408398.2022.2031092.
12. Kamal-Eldin A, Moazzami A, Washi S. Sesame seed lignans: potent physiological modulators and possible ingredients in functional foods & nutraceuticals. Recent Pat Food Nutr Agric. 2011;3:17–29.
13. Li Y, Wang F, Li J, et al. Dietary lignans, plasma enterolactone levels, and metabolic risk in men: exploring the role of the gut microbiome. BMC Microbiol. 2022;22:82. doi.org/10.1186/s12866-022-02495-0.
14. Mirmiran P, Yuzbashian E, Rahbarinejad P, et al. Dietary intakes of total polyphenol and its subclasses in association with the incidence of chronic kidney diseases: a prospective population-based cohort study. BMC Nephrol. 2021;22:84. doi.org/10.1186/s12882-021-02286-1.
15. Sohrab G, Hosseinpour-Niazi S, Hejazi J, et al. Dietary polyphenols and metabolic syndrome among Iranian adults. Int J Food Sci Nutr. 2013;64:661–667.
16. Sohrab G, Ebrahimof S, Hosseinpour-Niazi S, et al. Association of dietary intakes of total polyphenol and its subclasses with the risk of metabolic syndrome: Tehran lipid and glucose study. Metab Syndr Relat Disord. 2018;16:274–281.
17. Aali Y, Ebrahimi S, Shiraseb F, Mirzaei K. The association between dietary polyphenol intake and cardiometabolic factors in overweight and obese women: a cross-sectional study. BMC Endocr Disord. 2022;22:120. doi.org/10.1186/s12902-022-01025-3.
18. Bahrami A, Makiabadi E, Jalali S, et al. Dietary intake of polyphenols and the risk of breast cancer: a case-control study. Clin Nutr Res. 2021;10:330–340.
19. Amoo S, Okorogbona A, DuPlooy C, Venter S. Sesamum indicum. In: Kuete Victor, ed. Medicinal Spices and Vegetables from Africa. Vol. Chap. 26. Amsterdam, the Netherlands: Elsevier Press; 2017:549–579.
20. Ahmed IAM, AlJuhaimi F, Özcan MM, et al. Evaluation of chemical properties, amino acid contents and fatty acid compositions of sesame seed provided from different locations. J Oleo Sci. 2020;69:795–800.
21. Shasmitha R. Health benefits of Sesamum indicum: a short review. Asian J Pharmaceut Clin Res. 2015;8:1–3.
22. Pathak N, Rai AK, Kumari R, Bhat KV. Value addition in sesame: a perspective on bioactive components for enhancing utility and profitability. Pharmacogn Rev. 2014;8:147–155.
23. Peterson J, Dwyer J, Adlercreutz H, et al. Dietary lignans: physiology and potential for cardiovascular disease risk reduction. Nutr Rev. 2010;68:571–603.
24. Kim AY, Yun CI, Lee JG, Kim YJ. Determination and daily intake estimation of lignans in sesame seeds and sesame oil products in Korea. Foods. 2020;9:394. doi:10.3390/foods9040394.
25. Touma J, Dominguez S, La Vieille S, et al. Sesame as an allergen in Lebanese food products: occurrence, consumption and quantitative risk assessment. Food Chem Toxicol. 2021;156:112511. doi.org/10.1016/j.fct.2021.112511.
26. Peñalvo J, Heinonen S, Aura A, Adlerkreutz H. Dietary sesamin is converted to enterolactone in humans. J Nutr. 2005;135:1056–1062.
27. Moazzami AA, Andersson RE, Kamal-Eldin A. Quantitative NMR analysis of a sesamin catechol metabolite in human urine. J Nutr. 2007;137:940–944.
28. Tomimori N, Tanaka Y, Kitagawa Y, et al. Pharmacokinetics and safety of the sesame lignans, sesamin and episesamin, in healthy subjects. Biopharm Drug Dispos. 2013;34:462–473.
29. Yasuda K, Sakaki T. How is sesamin metabolised in the human liver to show its biological effects?Expert Opin Drug Metab Toxicol. 2012;8:93–102.
30. Yasuda K, Ikushiro S, Kamakura M, Ohta M, Sakaki T. Metabolism of sesamin by cytochrome P450 in human liver microsomes. Drug Metab Dispos. 2010;38:2117–2123. doi:10.1124/dmd.110.035659.
31. Lampe JW, Atkinson C, Hullar MA. Assessing exposure to lignans and their metabolites in humans. J AOAC Int. 2006;89:1174–1181.
32. Yasuda K, Okamoto K, Ueno S, et al. Sulfate conjugates are the major metabolites in rats administrated with sesamin. Drug Metab Pharmacokinet. 2019;34:134–140.
33. Tomimori N, Rogi T, Shibata H. Absorption, distribution, metabolism, and excretion of [14 C]sesamin in rats. Mol Nutr Food Res. 2017;61(8). doi:10.1002/mnfr.201600844.
34. Liu Z, Saarinen NM, Thompson LU. Sesamin is one of the major precursors of mammalian lignans in sesame seed (Sesamum indicum) as observed in vitro and in rats. J Nutr. 2006;136:906–912.
35. Umeda-Sawada R, Ogawa M, Igarashi O. The metabolism and distribution of sesame lignans (sesamin and episesamin) in rats. Lipids. 1999;34:633–637.
36. Nakai M, Harada M, Nakahara K, et al. Novel antioxidative metabolites in rat liver with ingested sesamin. J Agric Food Chem. 2003;51:1666–1670.
37. Patel KR, Andreadi C, Britton RG, et al. Sulfate metabolites provide an intracellular pool for resveratrol generation and induce autophagy with senescence. Sci Transl Med. 2013;5:205ra133.
38. Kawai Y, Nishikawa T, Shiba Y, et al. Macrophage as a target of quercetin glucuronides in human atherosclerotic arteries: implication in the anti-atherosclerotic mechanism of dietary flavonoids. J Biol Chem. 2008;283:9424–9434.
39. Kang MH, Naito M, Tsujihara N, Osawa T. Sesamolin inhibits lipid peroxidation in rat liver and kidney. J Nutr. 1998;128:1018–1022.
40. Hou YC, Tsai SY, Liu IL, et al. Metabolic transformation of sesamol and ex vivo effect on 2,2'-azo-bis(2-amidoinopropane)dihydrochloride-induced hemolysis. J Agric Food Chem. 2008;56:9636–9640.
41. Jan KC, Ho CT, Hwang LS. Bioavailability and tissue distribution of sesamol in rat. J Agric Food Chem. 2008;56:7032–7037.
42. Jan KC, Ho CT, Hwang LS. Elimination and metabolism of sesamol, a bioactive compound in sesame oil, in rats. Mol Nutr Food Res. 2009;53:S36–S43.
43. Mochizuki M, Tsuchie Y, Nakamura Y, Osawa T. Identification and characterization of sesaminol metabolites in the liver. J Agric Food Chem. 2009;57:10429–10434.
44. Jan KC, Ku KL, Chu YH, et al. Tissue distribution and elimination of estrogenic and anti-inflammatory catechol metabolites from sesaminol triglucoside in rats. J Agric Food Chem. 2010;58:7693–7700.
45. Jan KC, Ku KL, Chu YH, et al. Intestinal distribution and excretion of sesaminol and its tetrahydrofuranoid metabolites in rats. J Agric Food Chem. 2011;59:3078–3086.
46. Papadakis EN, Lazarou D, Grougnet R, et al. Effect of the form of the sesame-based diet on the absorption of lignans. Br J Nutr. 2008;100:1213–1219.
47. Lemcke-Norojärvi M, Kamal-Eldin A, Appelqvist LA, et al. Corn and sesame oils increase serum gamma-tocopherol concentrations in healthy Swedish women. J Nutr. 2001;131:1195–1201.
48. Cooney RV, Custer LJ, Okinaka L, Franke AA. Effects of dietary sesame seeds on plasma tocopherol levels. Nutr Cancer. 2001;39:66–71.
49. Frank J, Kamal-Eldin A, Traber MG. Consumption of sesame oil muffins decreases the urinary excretion of gamma-tocopherol metabolites in humans. Ann N Y Acad Sci. 2004;1031:365–367.
50. Frank J, Lee S, Leonard SW, et al. Sex differences in the inhibition of gamma-tocopherol metabolism by a single dose of dietary sesame oil in healthy subjects. Am J Clin Nutr. 2008;87:1723–1729.
51. Kamal-Eldin A, Pettersson D, Appelqvist L. Sesamin (a compound from sesame oil) increases tocopherol levels in rats fed ad libitum. Lipids. 1995;30:499–505.
52. Yamashita K, Iizuka Y, Imai T, Namiki M. Sesame seed and its lignans produce marked enhancement of vitamin E activity in rats fed a low alpha-tocopherol diet. Lipids. 1995;30:1019–1028.
53. Ikeda S, Tohyama T, Yamashita K. Dietary sesame seed and its lignans inhibit 2,7,8-trimethyl- 2(2'-carboxyethyl)-6-hydroxychroman excretion into urine of rats fed gamma-tocopherol. J Nutr. 2002;132:961–966.
54. Yamashita K, Takeda N, Ikeda S. Effects of various tocopherol-containing diets on tocopherol secretion into bile. Lipids. 2000;35:163–170.
55. Parker RS, Sontag TJ, Swanson JE. Cytochrome P4503A-dependent metabolism of tocopherols and inhibition by sesamin. Biochem Biophys Res Commun. 2000;277:531–534.
56. Jaskulski S, Jung AY, Huebner M, et al. Prognostic associations of circulating phytoestrogens and biomarker changes in long-term survivors of postmenopausal breast cancer. Nutr Cancer. 2020;72:1155–1169.
57. Liu Z, Fei YJ, Cao XH, et al. Lignans intake and enterolactone concentration and prognosis of breast cancer: a systematic review and meta-analysis. J Cancer. 2021;12:2787–2796.
58. Park SH, Hoang T, Kim J. Dietary factors and breast cancer prognosis among breast cancer survivors: a systematic review and meta-analysis of cohort studies. Cancers (Basel). 2021;13:5329. doi.org/10.3390/cancers13215329.
59. Velentzis LS, Cantwell MM, Cardwell C, et al. Lignans and breast cancer risk in pre- and post-menopausal women: meta-analyses of observational studies. Br J Cancer. 2009;100:1492–1498.
60. Wu WH, Kang YP, Wang NH, Jou HJ, Wang TA. Sesame ingestion affects sex hormones, antioxidant status, and blood lipids in postmenopausal women. J Nutr. 2006;136:1270–1275.
61. Coulman KD, Liu Z, Michaelides J, Quan Hum W, Thompson LU. Fatty acids and lignans in unground whole flaxseed and sesame seed are bioavailable but have minimal antioxidant and lipid-lowering effects in postmenopausal women. Mol Nutr Food Res. 2009;53:1366–1375.
62. Moghtaderi F, Amiri M, Zimorovat A, et al. The effect of canola, sesame and sesame-canola oils on body fat and composition in adults: a triple-blind, three-way randomised cross-over clinical trial. Int J Food Sci Nutr. 2021;72:226–235.
    63. Hirata F, Fujita K, Ishikura Y, et al. Hypocholesterolemic effect of sesame lignan in humans. Atherosclerosis. 1996;122:135–136.
    64. Sakketou EI, Baxevanis GK, Tentolouris NK, et al. Tahini consumption affects blood pressure and endothelial function in healthy males. J Hum Hypertens. 2021 Oct 27. doi.org/10.1038/s41371-021-00624-2.
      65. Baxevanis G, Sakketou E, Tentolouris N, et al. Tahini consumption improves metabolic and antioxidant status biomarkers in the postprandial state in healthy males. Eur Food Res Technol. 2021;247:2721–2728.
        66. Wu JH, Hodgson JM, Puddey IB, et al. Sesame supplementation does not improve cardiovascular disease risk markers in overweight men and women. Nutr Metab Cardiovasc Dis. 2009;19:774–780.
        67. Moghtaderi F, Amiri M, Raeisi-Dehkordi H, et al. The effect of sesame, canola, and sesame-canola oils on cardiometabolic risk factors in overweight adults: a three-way randomized triple-blind crossover clinical trial. Phytother Res. 2022;36:1043–1057. doi:10.1002/ptr.7381.
        68. Wichitsranoi J, Weerapreeyakul N, Boonsiri P, et al. Antihypertensive and antioxidant effects of dietary black sesame meal in pre-hypertensive humans. Nutr J. 2011;10:82. http://www.nutritionj.com/content/10/1/82.
        69. Sankar D, Rao MR, Sambandam G, Pugalendi KV. Effect of sesame oil on diuretics or beta-blockers in the modulation of blood pressure, anthropometry, lipid profile, and redox status. Yale J Biol Med. 2006;79:19–26.
        70. Karatzi K, Stamatelopoulos K, Lykka M, et al. Sesame oil consumption exerts a beneficial effect on endothelial function in hypertensive men. Eur J Prev Cardiol. 2013;20:202–208.
        71. Sankar D, Sambandam G, Rao M, Pugalendi KV. Modulation of blood pressure, lipid profiles and redox status in hypertensive patients taking different edible oils. Clin Chim Acta. 2005;355:97–104.
        72. Miyawaki T, Aono H, Toyoda-Ono Y, et al. Antihypertensive effects of sesamin in humans. J Nutr Sci Vitaminol (Tokyo). 2009;55:87–91.
        73. Mirmiran P, Bahadoran Z, Golzarand M, Rajab A, Azizi F. Ardeh (Sesamum indicum) could improve serum triglycerides and atherogenic lipid parameters in type 2 diabetics: a randomized clinical trial. Arch Iran Med. 2012;16:652–656.
          74. Bahadoran G, Hosseinpoor-Niazi S, Mirzaee S, Azizi F, Mirmiran P. Effect of Ardeh on components of metabolic syndrome in type 2 diabetic patients: a randomized clinical trial. Iran J Endocrinol Metabol. 2013;15:1.
          75. Sankar D, Rao MR, Sambandam G, Pugalendi KV. A pilot study of open label sesame oil in hypertensive diabetics. J Med Food. 2006;9:408–412.
          76. Sankar D, Ali A, Sambandam G, Rao R. Sesame oil exhibits synergistic effect with anti-diabetic medication in patients with type 2 diabetes mellitus. Clin Nutr. 2011;30:351–358.
          77. Aslam F, Iqbal S, Nasir M, Anjum AA. White sesame seed oil mitigates blood glucose level, reduces oxidative stress, and improves biomarkers of hepatic and renal function in participants with type 2 diabetes mellitus. J Am Coll Nutr. 2019;38:235–246.
          78. Raeisi-Dehkordi H, Amiri M, Moghtaderi F, et al. Effects of sesame, canola and sesame-canola oils on body weight and composition in adults with type 2 diabetes mellitus: a randomized, triple-blind, cross-over clinical trial. J Sci Food Agric. 2021;101:6083–6092.
          79. Raeisi-Dehkordi H, Amiri M, Zimorovat A, et al. Canola oil compared with sesame and sesame-canola oil on glycaemic control and liver function in patients with type 2 diabetes: a three-way randomized triple-blind cross-over trial. Diabetes Metab Res Rev. 2021;37:e3399. doi:10.1002/dmrr.3399.
          80. Yazdi M, Eghtesadi S, Kaseb F, et al. Effects of sesame oil on blood glucose and lipid profile in type II diabetic patients referring to the Yazdi Diabetes Research Center. J Shahid Sadoughi Univ Med Sci Health Serv. 2008;16:15–23.
          81. Mohammad Shahi M, Zakerzadeh M, Zakerkish M, et al. Effect of sesamin supplementation on glycemic status, inflammatory markers, and adiponectin levels in patients with type 2 diabetes mellitus. J Diet Suppl. 2017;14:65–75.
            82. Mohammadshahi M, Zakerzadeh M, Zakerkish M, Zarei M, Saki A. Effects of sesamin on the glycemic index, lipid profile, and serum malondialdehyde level of patients with type II diabetes. J Babol Univ Med Sci. 2016;18:7–14.
              83. Ryu S, Park K, Kang M, et al. Hypocholesterolemic effect of sesamin on hyperlipidemia patients with NIDDM. J Korean Soc Inter Agricul. 1999;11:312–324.
                84. Bahadoran Z, Mirmiran P, Hosseinpoor-Niazi S, Azizi F. A sesame seeds-based breakfast could attenuate sub-clinical inflammation in type 2 diabetic patients: a randomized controlled trial. Int J Nutr Food Sci. 2015;4:1–5.
                  85. Figueiredo A, Modesto-Filho J. Effect of defatted sesame (Sesamum indicum L.) flour on blood glucose level in type 2 diabetic women. Rev Bras Farmacogn. 2008;18:77–83.
                  86. Shishehbor F, Hojati N, Jahanshahi A, Haghighizadeh M. Effects of sesame seed consumption on anthropometric indices, lipid profile and atherogenic index of plasma in women with metabolic syndrome. Iran J Endocrinol Metabol. 2015;17:329–338.
                  87. Farajbakhsh A, Mazloomi SM, Mazidi M, et al. Sesame oil and vitamin E co-administration may improve cardiometabolic risk factors in patients with metabolic syndrome: a randomized clinical trial. Eur J Clin Nutr. 2019;73:1403–1411.
                  88. Chen P, Chien K, Su T, et al. Dietary sesame reduces serum cholesterol and enhances antioxidant capacity in hypercholesterolemia. Nutr Res. 2005;25:559–567.
                  89. Namayandeh S, Kaseb F, Lesan S. Olive and sesame oil effect on lipid profile in hypercholesterolemic patients, which better?Int J Prev Med. 2013;4:1059–1062.
                  90. Alipoor B, Haghighian MK, Sadat BE, Asghari M. Effect of sesame seed on lipid profile and redox status in hyperlipidemic patients. Int J Food Sci Nutr. 2012;63:674–678.
                  91. Khajehdehi P. Lipid-lowering effect of polyunsaturated fatty acids in hemodialysis patients. J Ren Nutr. 2000;10:191–195.
                  92. Helli B, Mowla K, Mohammadshahi M, Jalali MT. Effect of sesamin supplementation on cardiovascular risk factors in women with rheumatoid arthritis. J Am Coll Nutr. 2016;35:300–307.
                  93. Khalesi S, Paukste E, Nikbakht E, Khosravi-Boroujeni H. Sesame fractions and lipid profiles: a systematic review and meta-analysis of controlled trials. Br J Nutr. 2016;115:764–773.
                  94. Sohouli MH, Haghshenas N, Hernández-Ruiz Á, Shidfar F. Consumption of sesame seeds and sesame products has favorable effects on blood glucose levels but not on insulin resistance: a systematic review and meta-analysis of controlled clinical trials. Phytother Res. 2022;36:1126–1134. doi:10.1002/ptr.7379.
                  95. Yargholi A, Najafi MH, Zareian MA, et al. The effects of sesame consumption on glycemic control in adults: a systematic review and meta-analysis of randomized clinical trial. Evid Based Complement Alternat Med. 2021;2021:2873534. doi:doi.org/10.1155/2021/2873534.
                  96. Huang H, Zhou G, Pu R, Cui Y, Liao D. Clinical evidence of dietary supplementation with sesame on cardiovascular risk factors: an updated meta-analysis of randomized controlled trials. Crit Rev Food Sci Nutr. 2022;62:5592–5602. doi.org/10.1080/10408398.2021.1888689.
                  97. Sun Y, Ren J, Zhu S, et al. The effects of sesamin supplementation on obesity, blood pressure, and lipid profile: a systematic review and meta-analysis of randomized controlled trials. Front Endocrinol (Lausanne). 2022;13:842152. doi.org/10.3389/fendo.2022.842152.
                  98. Khosravi-Boroujeni H, Nikbakht E, Natanelov E, Khalesi S. Can sesame consumption improve blood pressure? A systematic review and meta-analysis of controlled trials. J Sci Food Agric. 2017;97:3087–3094.
                  99. Raeisi-Dehkordi H, Mohammadi M, Moghtaderi F, Salehi-Abargouei A. Do sesame seed and its products affect body weight and composition? A systematic review and meta-analysis of controlled clinical trials. J Func Foods. 2018;49:324–332.
                  100. Eftekhar Sadat B, Khadem Haghighian M, Alipoor B, et al. Effects of sesame seed supplementation on clinical signs and symptoms in patients with knee osteoarthritis. Int J Rheum Dis. 2013;16:578–582.
                  101. Khadem Haghighian M, Alipoor B, Malek Mahdavi A, et al. Effects of sesame seed supplementation on inflammatory factors and oxidative stress biomarkers in patients with knee osteoarthritis. Acta Med Iran. 2015;53:207–213.
                  102. Askari A, Ravansalar SA, Naghizadeh MM, et al. The efficacy of topical sesame oil in patients with knee osteoarthritis: a randomized double-blinded active-controlled non-inferiority clinical trial. Complement Ther Med. 2019;47:102183. doi:https://doi.org/10.1016/j.ctim.2019.08.017.
                  103. Helli B, Shahi MM, Mowla K, et al. A randomized, triple-blind, placebo-controlled clinical trial, evaluating the sesamin supplement effects on proteolytic enzymes, inflammatory markers, and clinical indices in women with rheumatoid arthritis. Phytother Res. 2019;33:2421–2428.
                  104. Nasiri M, Farsi Z. Effect of light pressure stroking massage with sesame (Sesamum indicum L.) oil on alleviating acute traumatic limbs pain: a triple-blind controlled trial in emergency department. Complement Ther Med. 2017;32:41–48.
                  105. Bigdeli Shamloo MB, Nasiri M, Dabirian A, et al. The effects of topical sesame (Sesamum indicum) oil on pain severity and amount of received non-steroid anti-inflammatory drugs in patients with upper or lower extremities trauma. Anesth Pain Med. 2015;5:e25085. doi:10.5812/aapm.25085v2.
                  106. Gholami M, Torabi Davan S, Gholami M, et al. Effects of topical sesame oil extracted from tahini (Ardeh) on pain severity in trauma patients: a randomized double-blinded placebo-controlled clinical trial. Bull Emerg Trauma. 2020;8:179–185.
                  107. Shamloo M, Nasiri M, Maneiy M, et al. Effects of topical sesame (Sesamum indicum) oil on the pain severity of chemotherapy-induced phlebitis in patients with colorectal cancer: a randomized controlled trial. Complement Ther Med. 2019;35:78–85.
                  108. Nekuzad N, Ashke Torab T, Mojab F, et al. Effect of external use of sesame oil in the prevention of chemotherapy-induced phlebitis. Iran J Pharm Res. 2012;11:1065–1071.
                  109. Bagheri-Nesami M, Shorofi SA, Hashemi-Karoie SZ, Khalilian A. The effects of sesame oil on the prevention of amiodarone-induced phlebitis. Iran J Nurs Midwifery Res. 2015;20:365–370.
                  110. Mosayebi N, Shafipour S, Asgari F, et al. The efficacy and safety of sesame oil in prevention of chemo-therapy-induced phlebitis in children with acute lymphoblastic leukemia. Iran J Ped Hematol Oncol. 2017;7:198–206.
                  111. Björk-Eriksson T, Gunnarsson M, Holmström M, et al. Fewer problems with dry nasal mucous membranes following local use of sesame oil. Rhinology. 2000;38:200–203.
                  112. Johnsen J, Bratt BM, Michel-Barron O, et al. Pure sesame oil vs isotonic sodium chloride solution as treatment for dry nasal mucosa. Arch Otolaryngol Head Neck Surg. 2001;127:1353–1356.
                  113. Zobeiri M, Parvizi F, Shahpiri Z, et al. Evaluation of the effectiveness of cinnamon oil soft capsule in patients with functional dyspepsia: a randomized double-blind placebo-controlled clinical trial. Evid Based Complement Alternat Med. 2021;2021:6634115. https://doi.org/10.1155/2021/6634115.
                    114. Saab BR, Pashayan N, El-Chemaly S, Sabra R. Sesame oil use in ameliorating cough in children: a randomised controlled trial. Complement Ther Med. 2006;14:92–99.
                      115. Faraji F, Hashemi M, Ghiasabadi A, et al. Combination therapy with interferon beta-1a and sesame oil in multiple sclerosis. Complement Ther Med. 2019;45:275–279.
                        116. Ji ZL, Li JS, Yuan CW, et al. Therapeutic value of sesame oil in the treatment of adhesive small bowel obstruction. Am J Surg. 2010;199:160–165.
                        117. Tokinobu A, Yorifuji T, Tsuda T, Doi H. Effects of Ayurvedic oil-dripping treatment with sesame oil vs. with warm water on sleep: a randomized single-blinded crossover pilot study. J Altern Complement Med. 2016;22:52–58.
                          118. Khani B, Bidgoli SR, Moattar F, Hassani H. Effect of sesame on sperm quality of infertile men. J Res Med Sci. 2013;18:184–187.
                          119. Barbosa CV, Silva AS, de Oliveira CV, et al. Effects of sesame (Sesamum indicum L.) supplementation on creatine kinase, lactate dehydrogenase, oxidative stress markers, and aerobic capacity in semi-professional soccer players. Front Physiol. 2017;8:196. doi:10.3389/fphys.2017.00196.
                            120. Yavari M, Rouholamin S, Tansaz M, et al. Sesame a treatment of menstrual bleeding cessation in Iranian traditional medicine: results from a pilot study. Shiraz E-Med J. 2014;15:e21893.
                              121. Aghababaei Z, Nejatbakhsh F, Mazaheri M, et al. Efficacy of sesame (Sesamum indicum L.) in the management of incomplete abortion: an open-label randomized controlled clinical trial. Complement Med Res. 2021;28:501–507. doi:10.1159/000510901.
                                122. Jung SJ, Jung ES, Ha KC, et al. Efficacy and safety of sesame oil cake extract on memory function improvement: a 12-week, randomized, double-blind, placebo-controlled pilot study. Nutrients. 2021;13:2606. doi.org/10.3390/nu13082606.
                                  123. Shanbhag VK. Oil pulling for maintaining oral hygiene—a review. J Tradit Complement Med. 2016;7:106–109.
                                  124. Asokan S, Emmadi P, Chamundeswari R. Effect of oil pulling on plaque induced gingivitis: a randomized, controlled, triple-blind study. Indian J Dent Res. 2009;20:47–51.
                                  125. Asokan S, Kumar RS, Emmadi P, Raghuraman R, Sivakumar N. Effect of oil pulling on halitosis and microorganisms causing halitosis: a randomized controlled pilot trial. J Indian Soc Pedod Prev Dent. 2011;29:90–94.
                                  126. Asokan S, Rathan J, Muthu MS, et al. Effect of oil pulling on Streptococcus mutans count in plaque and saliva using Dentocult SM Strip mutans test: a randomized, controlled, triple-blind study. J Indian Soc Pedod Prev Dent. 2008;26:12–17.
                                  127. Sood P, Devi MA, Narang R, V S, Makkar DK. Comparative efficacy of oil pulling and chlorhexidine on oral malodor: a randomized controlled trial. J Clin Diagn Res. 2014;8:ZC18–ZC21.
                                  128. Kandaswamy SK, Sharath A, Priya PG. Comparison of the effectiveness of probiotic, chlorhexidine-based mouthwashes, and oil pulling therapy on plaque accumulation and gingival inflammation in 10- to 12-year-old schoolchildren: a randomized controlled trial. Int J Clin Pediatr Dent. 2018;11:66–70.
                                  129. Vadhana VC, Sharath A, Geethapriya PR, Vijayasankari V. Effect of sesame oil, ozonated sesame oil, and chlorhexidine mouthwash on oral health status of adolescents: a randomized controlled pilot trial. J Indian Soc Pedod Prev Dent. 2019;37:365–371.
                                  130. Sezgin Y, Memis Ozgul B, Maraş ME, Alptekin NO. Comparison of the plaque regrowth inhibition effects of oil pulling therapy with sesame oil or coconut oil using 4-day plaque regrowth study model: a randomized crossover clinical trial. Int J Dent Hyg. 2021 June 14. doi:10.1111/idh.12532.
                                  131. Gupta S, Gupta S, Chaudhary C, et al. Novel treatment approach of oral submucous fibrosis in a 6-year-old girl: a case report. Int J Clin Pediatr Dent. 2021;14:575–579.
                                  132. Abdullah Al Qahtani W, Sandeepa NC, Khalid Abdullah E, et al. A clinical study comparing the efficacy of sesame oil with desensitizing tooth paste in reducing dentinal hypersensitivity: a randomized controlled trial. Int J Dent. 2020;2020:6410102. doi.org/10.1155/2020/6410102.
                                  133. Sultan S, Telgi C, Chaudhary S, et al. Effect of ACP-CPP chewing gum and natural chewable products on plaque pH, calcium and phosphate concentration. J Clin Diag Res. 2016;10:ZC13–ZC17.
                                  134. Rafiee S, Faryabi R, Yargholi A, et al. Effects of sesame consumption on inflammatory biomarkers in humans: a systematic review and meta-analysis of randomized controlled trials. Evid Based Complement Alternat Med. 2021;2021:6622981. doi.org/10.1155/2021/6622981.
                                  135. Oh E, Petersen K, Kris-Etherton P, Rogers C. Role of dietary spices in modulating inflammation and oxidative stress. In: Hernandez-Ledesma B, Martinez-Villaluenga C, eds. Current Advances for Development of Functional Foods Modulating Inflammation and Oxidative Stress. Amsterdam, the Netherlands: Elsevier Press; 2021:545–580.
                                  136. Gouveia Lde A, Cardoso CA, de Oliveira GM, et al. Effects of the intake of sesame seeds (Sesamum indicum L.) and derivatives on oxidative stress: a systematic review. J Med Food. 2016;19:337–345.
                                  137. Cardoso CA, Oliveira GMM, Gouveia LAV, Moreira ASB, Rosa G. The effect of dietary intake of sesame (Sesamumindicum L.) derivatives related to the lipid profile and blood pressure: a systematic review. Crit Rev Food Sci Nutr. 2018;58:116–125. doi.org/10.1080/10408398.2015.1137858.
                                  138. Hsu E, Parthasarathy S. Anti-inflammatory and antioxidant effects of sesame oil on atherosclerosis: a descriptive literature review. Cureus. 2017;9:e1438. doi:10.7759/cureus.1438.
                                  139. Afroz M, Zihad SMNK, Uddin SJ, et al. A systematic review on antioxidant and antiinflammatory activity of sesame (Sesamum indicum L.) oil and further confirmation of antiinflammatory activity by chemical profiling and molecular docking. Phytother Res. 2019;33:2585–2608.
                                  140. Dalibalta S, Majdalawieh AF, Manjikian H. Health benefits of sesamin on cardiovascular disease and its associated risk factors. Saudi Pharm J. 2020;28:1276–1289.
                                  141. Majdalawieh AF, Dalibalta S, Yousef SM. Effects of sesamin on fatty acid and cholesterol metabolism, macrophage cholesterol homeostasis and serum lipid profile: a comprehensive review. Eur J Pharmacol. 2020;885:173417. doi.org/10.1016/j.ejphar.2020.173417.
                                  142. Majdalawieh AF, Yousef SM, Abu-Yousef IA, Nasrallah GK. Immunomodulatory and anti-inflammatory effects of sesamin: mechanisms of action and future directions. Crit Rev Food Sci Nutr. 2022;62:5081–5112. doi.org/10.1080/10408398.2021.1881438.
                                  143. Darsow U, Bruckbauer H, Worret WI, et al. Subcutaneous oleomas induced by self-injection of sesame seed oil for muscle augmentation. J Am Acad Dermatol. 2000;42:292–294.
                                  144. Arnold J, Ouwehand WH, Smith GA, Cohen H. A young woman with petechiae. Lancet. 1998;352:618.
                                  145. Adatia A, Clarke AE, Yanishevsky Y, Ben-Shoshan M. Sesame allergy: current perspectives. J Asthma Allergy. 2017;10:141–151.
                                  146. Kahveci M, Koken G, Sahiner ÜM, et al. Immunoglobulin E-mediated food allergies differ in East Mediterranean children aged 0-2 years. Int Arch Allergy Immunol. 2020;181:365–374.
                                  147. Dalal I, Binson I, Reifen R, et al. Food allergy is a matter of geography after all: sesame as a major cause of severe IgE-mediated food allergic reactions among infants and young children in Israel. Allergy. 2002;57:362–365.
                                  148. Wolff N, Cogan U, Admon A, et al. Allergy to sesame in humans is associated primarily with IgE antibody to a 14 kDa 2S albumin precursor. Food Chem Toxicol. 2003;41:1165–1174.
                                  149. Ovadia A, Yoffe S, Orr YB, et al. Sesame-allergic patients can tolerate intact sesame seeds food challenge. J Allergy Clin Immunol Pract. 2022;10:336–338.
                                  150. Turner PJ, Gretzinger M, Patel N, et al. Updated threshold dose-distribution data for sesame. Allergy. 2022. doi:10.1111/all.15364.
                                  151. Warren CM, Chadha AS, Sicherer SH, Jiang J, Gupta RS. Prevalence and severity of sesame allergy in the United States. JAMA Netw Open. 2019;2(8):e199144. doi.10.1001/jamanetworkopen.2019.9144.
                                  152. Gangur V, Kelly C, Navuluri L. Sesame allergy: a growing food allergy of global proportions?Ann Allergy Asthma Immunol. 2005;95:4–11.
                                  153. Protudjer JLP, Abrams EM. Sesame: the new priority allergen?JAMA Netw Open. 2019;2:e199149. doi:10.1001/jamanetworkopen.2019.9149.
                                  154. Jaklevic MC. Sesame should be on food labels to warn consumers with allergy. JAMA. 2020;324:2357.
                                  155. Nguyen K, Greenthal E, Sorscher S, et al. Adverse events and labeling issues related to suspected sesame allergy reported in an online survey. Ann Allergy Asthma Immunol. 2022;128:279–282.
                                  156. Yasuda K, Ueno S, Ueda E, et al. Influence of sesamin on CYP2C-mediated diclofenac metabolism: in vitro and in vivo analysis. Pharmacol Res Perspect. 2015;3:e00174. doi.1002/prp2.174.
                                  157. Pilipenko N, Rasmussen MK, Doran O, Zamaratskaia G. 7-hydroxylation of warfarin is strongly inhibited by sesamin, but not by episesamin, caffeic and ferulic acids in human hepatic microsomes. Food Chem Toxicol. 2018;113:14–18.
                                  158. Fujii M, Yasuda K, Sakaki T. Inhibitory effects of sesamin on CYP2C9-dependent 7-hydroxylation of S-warfarin. Drug Metab Pharmacokinet. 2020;35:368–373.
                                  159. Lim YP, Ma CY, Liu CL, et al. Sesamin: a naturally occurring lignan inhibits CYP3A4 by antagonizing the pregnane X receptor activation. Evid Based Complement Alternat Med. 2012;2012:242810. doi.10.1155/2012/242810.
                                  160. Watanabe H, Yamaori S, Kamijo S, et al. In vitro inhibitory effects of sesamin on CYP4F2 activity. Biol Pharm Bull. 2020;43:688–692.
                                  161. Xu RA, Sun W, Chen R, et al. Inhibitory effect of sesamin on ivabradine metabolism in rats. Pak J Pharm Sci. 2020;33:2543–2546. doi.org/10.36721/PJPS.2020.33.6.REG.2543-2546.1.
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