Sesamon Dietary Supplement
Sesamon™ is a dietary supplement that is the latest product of my research on the insulin resistance and inflammation syndrome (IRIS). Sesamon™ is a formula of sesamin, cinnamon, and other supporting botanical extracts. The following studies support the benefits of the ingredients found in Sesamon™. These benefits include: improves insulin sensitivity, enhances fat metabolism, lowers serum triglycerides, prevents inflammation by correcting the polyunsaturated fatty PUFA metabolism, reduces high blood pressure, improves cholesterol profiles, fights cancer, prevents allergic reactions, and enhances the activity of Vitamin E.

Sesamin, the sensational lignan from sesame seeds


The main ingredient in Sesamon™ is an amazing discovery that was found in an unexpected place, the simple sesame seed. Sesame seeds contain a lignan called sesamin. What a treasure this lignan sesamin is! When I began my research I happened upon some studies of sesamin that caught my attention.

Briefly, here’s what sesamin does. First of all it enhances the ability to burn fat. Sesamin actually stimulates fatty acid oxidation and that helps to adapt our metabolism to use fat as an energy source instead of carbohydrates. Manipulating our metabolism to enhance its ability to burn fat is a very healthy thing. Sesamin enhances the benefits of a low-carb diet and exercise. In this way it helps stabilize blood sugar levels and improve insulin sensitivity. Probably the most important thing that sesamin does is to manipulate the PUFA metabolism so that it inhibits the inflammatory N-6 metabolic pathway and at the same time, enhance the anti-inflammatory N-3 pathway. I was very excited to see this! Sesamin also reduces high blood pressure, tryglycerides, cholesterol, fights cancer and allergies.

Below is a list of references that support the benefits of sesamin.

Studies show that sesamin improves the ability to metabolize fat and lower serum triglyceride levels in the blood

Metabolism 1999 Oct;48(10):1303-13
Sesamin, a sesame lignan, is a potent inducer of hepatic fatty acid oxidation in the rat.
Ashakumary L, Rouyer I, Takahashi Y, Ide T, Fukuda N, Aoyama T, Hashimoto T, Mizugaki M, Sugano M Laboratory of Nutrition Biochemistry, National Food Research Institute, Ministry of Agriculture, Forestry and Fisheries, Tsukuba, Japan.

….. Dietary sesamin dose-dependently increased both mitochondrial and peroxisomal palmitoyl-coenzyme A (CoA) oxidation rates. Mitochondrial activity almost doubled in rats on the 0.5% sesamin diet. Peroxisomal activity increased more than 10-fold in rats fed a 0.5% sesamin diet in relation to rats on the sesamin-free diet. Dietary sesamin greatly increased the hepatic activity of fatty acid oxidation enzymes, including carnitine palmitoyltransferase, acyl-CoA dehydrogenase, acyl-CoA oxidase, 3-hydroxyacyl-CoA dehydrogenase, enoyl-CoA hydratase, and 3-ketoacyl-CoA thiolase. Dietary sesamin also increased the activity of 2,4-dienoyl-CoA reductase and delta3,delta2-enoyl-CoA isomerase, enzymes involved in the auxiliary pathway for beta-oxidation of unsaturated fatty acids dose-dependently. Examination of hepatic mRNA levels using specific cDNA probes showed a sesamin-induced increase in the gene expression of mitochondrial and peroxisomal fatty acid oxidation enzymes. Among these various enzymes, peroxisomal acyl-CoA oxidase and bifunctional enzyme gene expression were affected most by dietary sesamin (15- and 50-fold increase by the 0.5% dietary level). Sesamin-induced alterations in the activity and gene expression of carnitine palmitoyltransferase I and acyl-CoA oxidase were in parallel with changes in the mitochondrial and peroxisomal palmitoyl-CoA oxidation rate, respectively. In contrast, dietary sesamin decreased the hepatic activity and mRNA abundance of fatty acid synthase and pyruvate kinase, the lipogenic enzymes. However, this lignan increased the activity and gene expression of malic enzyme, another lipogenic enzyme. An alteration in hepatic fatty acid metabolism may therefore account for the serum lipid-lowering effect of sesamin in the rat.

J Nutr Sci Vitaminol (Tokyo) 1999 Aug;45(4):437-48
Effect of dietary sesamin on metabolic fate of an exogenous linolelaidic acid in perfused rat liver. Fukuda N, Zhang L, Kodama M, Sakono M, Ide T, Yamamoto K, Sugano M Department of Biological Resource Sciences, Faculty of Agriculture, Miyazaki University, Japan.

To estimate the relative significance of exogenous and endogenous fatty acid substrates in decreasing hepatic triacylglycerol secretion after sesamin feeding, livers from rats fed diets supplemented with and without sesamin (sesamin: episesamin, 1:1, w/w) were perfused in the presence and absence of an exogenous di-trans isomer of linoleic acid (linolelaidic acid, trans,trans-9,12-octadecadienoic acid). Both exogenous trans fatty acid and dietary sesamin, as compared with respective controls, resulted in a marked increase in hepatic ketogenesis; however, the beta-hydroxybutyrate to acetoacetate ratio was elevated by exogenous fatty acid and decreased by dietary sesamin. On the other hand, hepatic secretions of triacylglycerol, phospholipid and cholesterol were markedly lowered in rats fed sesamin, especially when exogenous fatty acid substrate was provided. The relative significance of the exogenous fatty acid was observed in the dietary sesamin-induced decrease in hepatic secretion of triacylglycerol. These results suggest that increased fatty acid oxidation by dietary sesamin, as reflected by enhanced ketone body production, leads to decreased partition of fatty acid substrates to the esterification pathways, and this in turn reduces the synthesis and secretion of triacylglycerol. The altered metabolism of exogenous fatty acids in the liver was therefore a major determinant for the synthesis and secretion of triacylglycerol.

J Nutr Sci Vitaminol (Tokyo) 1998 Oct;44(5):715-22
Reciprocal effects of dietary sesamin on ketogenesis and triacylglycerol secretion by the rat liver.
Fukuda N, Miyagi C, Zhang L, Jayasooriya AP, Sakono M, Yamamoto K, Ide T, Sugano M Department of Biological Resource Sciences, Faculty of Agriculture, Miyazaki University, Japan.

The effects of dietary sesamin (a mixture of sesamin and episesamin, 1:1, w/w) on ketone body production and lipid secretion were studied in isolated perfused liver from rats given sesamin. Feeding sesamin at the dietary level of 0.2% from 14 to 16 d resulted in an enlargement of liver weight. Ketone body production was significantly elevated in the livers perfused with oleic acid in comparison with those perfused without an exogenous-free fatty acid, and sesamin feeding caused a stimulation of ketone body production, especially when exogenous oleic acid was provided. On the other hand, the ratio of beta-hydroxybutyrate to acetoacetate, an index of mitochondrial redox potential, tended to increase in the livers perfused with oleic acid compared with those without fatty acid, thought it was consistently lowered by dietary sesamin. The cumulative secretion of triacylglycerol, but not of cholesterol, by the livers from sesamin-fed rats was decreased markedly, especially when exogenous oleic acid was provided, suggesting an inverse relationship between the rates of ketogenesis and triacylglycerol secretion. These results suggest that dietary sesamin exerts its hypotriglyceridemic effect at least in part through an enhanced metabolism of exogenous-free fatty acid to oxidation at the expense of esterification in rat liver.

The following studies show how sesamin improves the PUFA pathways so that they produce less inflammatory mediators

Prostaglandins Leukot Essent Fatty Acids 1999 Dec;61(6):347-52
Decreased production of interleukin-6 and prostaglandin E2 associated with inhibition of delta-5 desaturation of omega6 fatty acids in mice fed safflower oil diets supplemented with sesamol.
Chavali SR, Forse RA Harvard Institutes of Medicine, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.

The differences in the immune responses in mice fed sesame oil diets and those fed sesamin may be attributed to the presence of other lignans in the non-fat portion of the oil. The fatty acid composition (mean +/- SD mol. %) of liver membrane phospholipids and the levels of endotoxin-induced prostaglandin (PG) E2, interleukin (IL)-6, IL-10, IL-12 and tumor necrosis factor (TNF)-alpha were determined in mice fed diets supplemented with 5% safflower oil (SO) in the absence or presence of 1% sesamol. The levels of dihomo-gamma-linolenic acid (20:3omega6) were markedly higher (P<0.025) in the livers from mice fed sesamol supplemented SO diets (1.6 +/- 0.1) compared to the controls (1.4 +/- 0.1). These data suggest that sesamol or its metabolite could inhibit the in vivo delta-5 desaturation of omega6 fatty acids. Further, in animals fed sesamol supplemented SO diets, the levels of PGE2 (228 +/- 41 pg/ml) were markedly lower (P<0.01) compared to those fed SO diet alone (1355 +/- 188 pg/ml). Concomitantly, the concentrations of IL-6 were also lower (P<0.01) in mice fed sesamol diet (63 +/- 11 ng/ml) compared to the controls (143 +/- 22 ng/ml). A marked reduction in the levels of PGE2 in animals fed sesamol diets suggests that sesamol or its metabolite could inhibit the activity of cyclooxygenase enzyme.

Prostaglandins Leukot Essent Fatty Acids 1998 Mar;58(3):185-91
Dietary alpha-linolenic acid increases TNF-alpha, and decreases IL-6, IL-10 in response to LPS: effects of sesamin on the delta-5 desaturation of omega6 and omega3 fatty acids in mice.
Chavali SR, Zhong WW, Forse RA
Department of Surgery, Harvard Institute of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.

Sesamin (a non-fat portion of sesame seed oil) inhibits delta-5 desaturase activity resulting in an accumulation of dihomo-gamma-linolenic acid (DGLA) which can displace arachidonic acid (AA) and decrease the formation of pro-inflammatory mediators. We investigated the effects of consumption of diets containing 0.25wt% sesamin and 15 wt% safflower oil (SO) (providing 12% of the added fat as linoleic acid) or a 15 wt% 2:1 mixture of linseed oil and SO (LOSO) (providing 6% alpha-linolenic acid and 6% linoleic acid) for 3 weeks on the liver membrane fatty acid composition and on the production of prostaglandin (PG) E2, TNF-alpha, IL-6 and IL10 in mice. Consumption of sesamin-supplemented SO and LOSO diets resulted in a significant increase in the levels of 20:3omega6 (DGLA), suggesting that sesamin inhibited delta-5 desaturation of omega6 fatty acids. In animals fed LOSO diets, the levels of alpha-linolenic acid, eicosapentaenoic acid (EPA) and of docosahexaenoic acid (DHA) were elevated with a concomitant decrease of arachidonic acid (AA) in the liver membrane phospholipids. Further, in animals fed LOSO diets with or without sesamin, an increase in the circulating levels of TNF-alpha was associated with a concomitant decrease in PGE2. Despite a lack of differences in the levels of AA, the PGE2 levels were significantly lower in mice fed sesamin-supplemented SO compared to those fed SO alone. Thus, these data suggest that irrespective of the availability of a specific fatty acid as a substrate, through regulating the PGE2 synthesis, the production of TNF-alpha could be modulated.

Int Arch Allergy Immunol 1997 Oct;114(2):153-60
Decreased production of interleukin-1-beta, prostaglandin-E2 and thromboxane-B2, and elevated levels of interleukin-6 and -10 are associated with increased survival during endotoxic shock in mice consuming diets enriched with sesame seed oil supplemented with Quil-A saponin.
Chavali SR, Zhong WW, Utsunomiya T, Forse RA Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Mass. 02215, USA.

Sesamin, present in sesame seed oil (SSO), can inhibit delta-5-desaturase activity and cause accumulation of dihomo-gamma-linolenic acid (DGLA), which displaces arachidonic acid, and subsequently decrease production of dienoic eicosanoids. The effects of diets containing both SSO and Quil A, a saponin that emulsifies fats and potentiates the immune responses, were also studied. A mixture of oils having a fatty-acid composition similar to that of SSO served as a control diet. The levels of docosapentaenoic acid in mice fed Quil-A-supplemented diets and of DGLA in those fed SSO diets were markedly higher in the liver. These changes were associated with a significant reduction in the plasma prostaglandin-E(1+2) and thromboxane-B2 levels in response to an intraperitoneal injection of a lethal dose of lipopolysaccharide (LPS) endotoxin (LD50 20 mg/kg). The levels of interleukin (IL-)6 were elevated and those of IL-1beta were decreased in mice consuming Quil-A-supplemented diets. The IL-10 levels that were elevated in all mice after LPS exposure, remained higher (even at 9 h) only in those fed Quil-A-supplemented diets, but declined rapidly in others. During a 48-hour observation period following LPS injection, all control animals died, and survival was 40% in the SSO group, and 27 and 50%, respectively, in those fed Quil-A-supplemented control and SSO diets. These data suggest that SSO and Quil A when present in the diet exerted cumulative effects that resulted in a decrease in the levels of dienoic eicosanoids with a reduction in IL-1beta and a concomitant elevation in the levels of IL-10 that were associated with a marked increase in survival in mice.

Biosci Biotechnol Biochem 1995 Dec;59(12):2268-73
Interaction of sesamin and eicosapentaenoic acid against delta 5 desaturation and n-6/n-3 ratio of essential fatty acids in rat.
Umeda-Sawada R, Takahashi N, Igarashi O Institute of Environmental Science for Human Life, Ochanomizu University, Tokyo, Japan.

Sesamin is a specific inhibitor of delta 5 desaturation, the conversion from dihomo-gamma-linolenic acid (20:3, n-6) to arachidonic acid (AA, 20:4, n-6). Previously, we reported that sesamin inhibited delta 5 desaturation of n-6 fatty acids in rat hepatocytes but not that of n-3 fatty acids, from 20:4 (n-3) to eicosapentaenoic acid (EPA, 20:5, n-3). In this study, we investigated the interaction of sesamin and EPA on delta 5 desaturation of both series and the n-6/n-3 fatty acids ratio by measuring actual fatty acid contents in vivo. Rats were fed three types of dietary oils; 1) linoleic acid (LA, 18:2, n-6): linolenic acid (LLA, 18:3, n-3) = 3:1, n-6/n-3 ratio of 3:1 (LA group), 2) LA:LLA = 1:3, n-6/n-3 ratio of 1:3 (LLA group), 3) LA:LLA:EPA = 1:0.5:3, n-6/n-3 ratio of 1:3.5 (EPA group) with or without sesamin (0.5% w/w) for 4 weeks. In all groups, sesamin administration increased the content of dihomo-gamma-linolenic acid (20:3, n-6) in the liver and decreased the delta 5 desaturation index of n-6 fatty acid, the ratio of 20:4/20:3 (n-6). On the contrary, the delta 5 desaturation index of n-3 fatty acid, the ratio of 20:5 + 22:5 + 22:6/20:4 (n-3), was increased by the administration of sesamin. These results suggest that sesamin inhibits the delta 5 desaturation of n-6 fatty acid, but not that of n-3 fatty acid in rat livers. Sesamin administration decreased incorporation of EPA (n-3) and simultaneously increased the AA (n-6) content in the liver. The n-6/n-3 ratio in the liver was increased by administering sesamin under n-3 rich conditions, i.e., the LLA and EPA groups.

Lipids 1998 Jun;33(6):567-72
The metabolism and n-6/n-3 ratio of essential fatty acids in rats: effect of dietary arachidonic acid and a mixture of sesame lignans (sesamin and episesamin).
Umeda-Sawada R, Ogawa M, Igarashi O Institute of Environmental Science for Human Life, Ochanomizu University, Tokyo, Japan. sawada@cc.ocha.ac.jp

In this study, we examined the effect of dietary arachidonic acid (AA) and sesame lignans on the content and n-6/n-3 ratio of polyunsaturated fatty acid (PUFA) in rat liver and the concentrations of triglyceride (TG) and ketone bodies in serum. For 4 wk, rats were fed two types of dietary oils: (i) the control oil diet groups (CO and COS): soybean oil/perilla oil = 5:1, and (ii) the AA-rich oil group (AO and AOS): AA ethyl esters/palm oil/perilla oil = 2:2:1, with (COS and AOS) or without (CO and AO) 0.5% (w/w) of sesame lignans. Dietary AA and sesame lignans significantly affected hepatic PUFA metabolism. AA content and n-6/n-3 ratio in the liver were significantly increased in the AO group, despite the dietary total of n-6 PUFA being the same in all groups, while AOS diet reduced AA content and n-6/n-3 ratio to a level similar to the CO and COS groups. These results suggest that (i) dietary AA considerably affects the hepatic profile and n-6/n-3 ratio of PUFA, and (ii) dietary sesame lignans reduce AA content and n-6/n-3 ratio in the liver. In the AO group, the concentration of acetoacetate was significantly increased, but the ratio of beta-hydroxybutyrate/acetoacetate was decreased. On the other hand, the AO diet increased the concentration of TG in serum by almost twofold as compared to other groups. However, the AOS diet significantly reduced serum TG level as compared to the AO group. In addition, the AOS diet significantly increased the acetoacetate level, but reduced the beta-hydroxybutyrate/acetoacetate ratio. These results suggest that dietary sesame lignans promote ketogenesis and reduce PUFA esterification into TG. This study resulted in two findings: (i) sesame lignans inhibited extreme changes of the n-6/n-3 ratio by reducing hepatic PUFA content, and (ii) the reduction of hepatic PUFA content may have occurred because of the effects of sesame lignans on PUFA degradation (oxidation) and esterification.

Lipids 1991 Jul;26(7):512-6
Sesamin is a potent and specific inhibitor of delta 5 desaturase in polyunsaturated fatty acid biosynthesis.
Shimizu S, Akimoto K, Shinmen Y, Kawashima H, Sugano M, Yamada H Department of Agricultural Chemistry, Kyoto University, Japan.

Incubation with sesame oil increases the mycelial dihomo-gamma-linolenic acid content of an arachidonic acid-producing fungus, Mortierella alpina, but decreases its arachidonic acid content [Shimizu, S., K. Akimoto, H. Kawashima, Y. Shinmen and H. Yamada (1989) J. Am. Oil Chem. Soc. 66, 237-241]. The factor causing these effects was isolated and identified to be (+)-sesamin. The results obtained in experiments with both a cell-free extract of the fungus and with rat liver microsomes demonstrated that (+)-sesamin specifically inhibits delta 5 desaturase at low concentrations, but does not inhibit delta 6, delta 9 and delta 12 desaturases. Kinetic analysis showed that (+)-sesamin is a noncompetitive inhibitor (Ki for rat liver delta 5 desaturase, 155 microM). (+)-Sesamolin, (+)-sesaminol and (+)-episesamin also inhibited only delta 5 desaturases of the fungus and liver. These results demonstrate that (+)-sesamin and related lignan compounds present in sesame seeds or its oil are specific inhibitors of delta 5 desaturase in polyunsaturated fatty acid biosynthesis in both microorganisms and animals.

The next group of studies indicate that sesamin is able to reduce blood pressure

Biol Pharm Bull 1998 May;21(5):469-73
Antihypertensive effect of sesamin. III. Protection against development and maintenance of hypertension in stroke-prone spontaneously hypertensive rats.
Matsumura Y, Kita S, Tanida Y, Taguchi Y, Morimoto S, Akimoto K, Tanaka T Department of Pharmacology, Osaka University of Pharmaceutical Sciences, Takatsuki, Japan.

The antihypertensive effect of sesamin, a lignan from sesame oil, was examined using salt-loaded and unloaded stroke-prone spontaneously hypertensive rats (SHRSP). The animals at 6 weeks of age were separated into a salt-loaded group and an unloaded group. Salt-loaded animals were maintained on 1% NaCl drinking water. Each group was further divided into two groups: normal-diet group and sesamin-diet group. Systolic blood pressure of all animals was monitored once weekly. At the end of the feeding periods, cardiovascular hypertrophy and renal damage were evaluated. In the salt-loaded group, sesamin feeding significantly suppressed the development of hypertension, and efficient suppression was maintained from 9 to 26 weeks (e.g., 215+/-4 vs. 180+/-4 mmHg, at 17 weeks old). The left ventricle plus septum weight-to-body weight ratio was slightly but significantly lowered by sesamin feeding. When the degree of vascular hypertrophy of the aorta and superior mesenteric artery was histochemically evaluated, wall thickness and wall area of these vessels were significantly decreased by the sesamin feeding. Histological renal damage such as thickening of the tunica intima and fibrinoid degeneration of the arterial wall were often observed in the normal-diet group, but this damage was efficiently reduced in the sesamin-fed animals. On the other hand, in the salt-unloaded group, only a slight and nonsignificant suppressive effect of sesamin on the development of hypertension was observed. Although the wall area of the aorta was significantly decreased by the sesamin feeding, other vascular parameters were not ameliorated. The incidence of histological renal damage tended to decrease in sesamin-fed animals, but these alterations were not statistically significant. Thus, sesamin feeding was much more effective as an antihypertensive regimen in salt-loaded SHRSP than in unloaded SHRSP, thereby suggesting that sesamin is more useful as a prophylactic treatment in the malignant status of hypertension and/or hypertension followed by water and salt retention.

Biol Pharm Bull 1995 Sep;18(9):1283-5
Antihypertensive effect of sesamin. II. Protection against two-kidney, one-clip renal hypertension and cardiovascular hypertrophy.
Kita S, Matsumura Y, Morimoto S, Akimoto K, Furuya M, Oka N, Tanaka T Department of Pharmacology, Osaka University of Pharmaceutical Sciences, Japan.

We investigated the antihypertensive effect of sesamin, a lignan from sesame oil, using two-kidney, one-clip (2K,1C) renal hypertensive rats. After clipping the left renal artery, animals were assigned to either a normal diet group (control group) or a sesamin-containing (1% (w/w)) diet group (sesamin group). The sham-operated rats (sham group) were fed a normal diet and tap water. The systolic blood pressure of the control group increased progressively in comparison with the sham group. This 2K,1C-induced hypertension was markedly reduced by feeding the sesamin-containing diet. The systolic blood pressure after 4 weeks was 123.60 +/- 4.01 mmHg in the sham group, 187.43 +/- 5.69 mmHg in the control group and 145.57 +/- 6.78 mmHg in the sesamin group, respectively. There were significant increases in left ventricle plus septum weight-body weight ratio in the control group compared with the sham group. This rise was also significantly reduced in the sesamin group. When the thoracic aorta was histochemically evaluated, the wall thickness and wall-to-lumen ratio in the control group were significantly increased, compared with the sham group, indicating that vascular hypertrophy had occurred in the control group. The sesamin diet tended to ameliorate this vascular hypertrophy, although its effect was not statistically significant. These findings suggest that sesamin is useful as prophylactic treatment to combat the development of renal hypertension and cardiac hypertrophy.

Biol Pharm Bull 1995 Jul;18(7):1016-9
Antihypertensive effect of sesamin. I. Protection against deoxycorticosterone acetate-salt-induced hypertension and cardiovascular hypertrophy.
Matsumura Y, Kita S, Morimoto S, Akimoto K, Furuya M, Oka N, Tanaka T Department of Pharmacology, Osaka University of Pharmaceutical Sciences, Osaka, Japan.

We investigated the antihypertensive effect of sesamin, a lignan from sesame oil, using deoxycorticosterone acetate (DOCA)-salt hypertensive rats. The animals were unilaterally nephrectomized, and then separated into a sham-operated group (sham group) and a DOCA-salt-treated group. The latter was further separated into a normal diet group (control group) and a sesamin-containing diet group (sesamin group). The systolic blood pressure of control group progressively increased in comparison with that of sham group. This DOCA-salt-induced hypertension was markedly suppressed by feeding a sesamin-containing diet. Systolic blood pressure after 5 weeks was 130.6 +/- 1.9 mmHg in the sham group, 198.1 +/- 7.3 mmHg in the control group and 152.5 +/- 8.4 mmHg in the sesamin group, respectively. The treatment with DOCA and salt for 5 weeks significantly increased the weight of the left ventricle plus the septum. However, this increase was significantly suppressed in the sesamin group. When the degree of vascular hypertrophy of the aorta and superior mesenteric artery was histochemically evaluated, there were significant increases in wall thickness, wall area and the wall-to-lumen ratio in the control group, compared with the sham. Sesamin feeding ameliorated the development of DOCA-salt-induced vascular hypertrophy in both the aorta and mesenteric artery. These findings strongly suggest that sesamin is useful as a prophylactic treatment in the development of hypertension and cardiovascular hypertrophy.

The following studies show how sesamin improves cholesterol profiles

Clin Exp Pharmacol Physiol 1995 Dec;22 Suppl 1:S310-2
Sesame lignans modulate cholesterol metabolism in the stroke-prone spontaneously hypertensive rat. Ogawa H, Sasagawa S, Murakami T, Yoshizumi H
Department of Hygiene, Kinki University School of Medicine, Japan.

1. Effects of sesamin and episesamin (an epimer of sesamin) on lipid metabolism, in particular cholesterol metabolism, were examined in normocholesterolaemic and hypercholesterolaemic stroke-prone spontaneously hypertensive rats (SHRSP). 2. In normocholesterolaemic SHRSP fed a regular diet, both sesamin and episesamin significantly increased the concentration of serum total cholesterol, which was due to an increase of high density lipoprotein (HDL) subfraction rich in apoE (apoE-HDL). In addition, both substances effectively decreased serum very low density lipoprotein (VLDL). In the liver, only episesamin significantly decrease the activity of microsomal acyl-CoA: cholesterol acyltransferase. 3. In hypercholesterolaemic SHRSP fed a high-fat and high-cholesterol diet (HFC diet), only episesamin improved serum lipoprotein metabolism with an increase in apoA-I and a decrease in apoB. In the liver, both sesamin and episesamin significantly suppressed cholesterol accumulation. Interestingly, only episesamin significantly increased the activity of microsomal cholesterol 7 alpha-hydroxylase. 4.These results indicate that sesamin may be effective in preventing cholesterol accumulation in the liver. In comparison with sesamin, episesamin may be effective in the regulation of cholesterol metabolism in the serum and liver.

Atherosclerosis 1996 Apr 26;122(1):135-36
Hypocholesterolemic effect of sesame lignan in humans. Hirata F, Fujita K, Ishikura Y, Hosoda K, Ishikawa T, Nakamura H

No abstract available for this reference.

Int J Vitam Nutr Res 1995;65(3):162-8
alpha-Tocopherol enhances the hypocholesterolemic action of sesamin in rats.
Nakabayashi A, Kitagawa Y, Suwa Y, Akimoto K, Asami S, Shimizu S, Hirose N, Sugano M, Yamada H Institute for Biomedical Research, Suntory Ltd., Osaka, Japan.

The effect of alpha-tocopherol on the hypocholesterolemic action of sesamin was examined in rats given a cholesterol-enriched diet. When different levels (0.05 and 0.2%) of sesamin were fed, the supplementation of 1% alpha-tocopherol significantly accentuated the hypocholesterolemic action of sesamin, particularly with the higher sesamin level, although alpha-tocopherol alone did not affect the concentration of serum cholesterol. The dose-dependent promoting effect of alpha-tocopherol on the hypocholesterolemic action of sesamin was confirmed by supplementing different levels (0.2 and 1%) of alpha-tocopherol to a fixed level of sesamin (0.2%). alpha-Tocopherol was still effective at the 0.2% level. The metabolism of sesamin in the liver S9 fraction appeared to be interfered with alpha-tocopherol in vitro, suggesting a possible role of alpha-tocopherol in maintenance of the availability of sesamin.

J Lipid Res 1991 Apr;32(4):629-38
Inhibition of cholesterol absorption and synthesis in rats by sesamin.
Hirose N, Inoue T, Nishihara K, Sugano M, Akimoto K, Shimizu S, Yamada H Laboratory of Nutrition Chemistry, Kyushu University School of Agriculture, Fukuoka, Japan.

The effects of sesamin, a lignan from sesame oil, on various aspects of cholesterol metabolism were examined in rats maintained on various dietary regimens. When given at a dietary level of 0.5% for 4 weeks, sesamin reduced the concentration of serum and liver cholesterol significantly irrespective of the presence or absence of cholesterol in the diet, except for one experiment in which the purified diet free of cholesterol was given. On feeding sesamin, there was a decrease in lymphatic absorption of cholesterol accompanying an increase in fecal excretion of neutral, but not acidic, steroids, particularly when the cholesterol-enriched diet was given. Sesamin inhibited micellar solubility of cholesterol, but not bile acids, whereas it neither bound taurocholate nor affected the absorption of fatty acids. Only a marginal proportion (ca. 0.15%) of sesamin administered intragastrically was recovered in the lymph. There was a significant reduction in the activity of liver microsomal 3-hydroxy-3-methylglutaryl coenzyme A reductase after feeding sesamin, although the activity of hepatic cholesterol 7 alpha-hydroxylase, drug metabolizing enzymes, and alcohol dehydrogenase remained uninfluenced. Although the weight and phospholipid concentration of the liver increased unequivocally on feeding sesamin, the histological examination by microscopy showed no abnormality, and the activity of serum GOT and GPT remained unchanged. Since sesamin lowered both serum and liver cholesterol levels by inhibiting absorption and synthesis of cholesterol simultaneously, it deserves further study as a possible hypocholesterolemic agent of natural origin.

Studies show that sesamin enhances vitamin E activity

Lipids 1995 Nov;30(11):1019-28
Sesame seed and its lignans produce marked enhancement of vitamin E activity in rats fed a low alpha-tocopherol diet.
Yamashita K, Iizuka Y, Imai T, Namiki M
Department of Food and Nutrition, School of Life Studies, Sugiyama Jogakuen University, Nagoya, Japan.

Three series of experiments demonstrated that sesame seed and its lignans cause significant elevation of alpha-tocopherol content in rats. In Experiment 1, 20% sesame seed (with a negligible amount of alpha-tocopherol) supplementing 10 (low), 50 (normal), or 250 (high) mg/kg alpha-tocopherol diets (protein and fat concentrations in diets were adjusted to 200 and 110 g/kg, respectively) all caused a significant increase of alpha-tocopherol in the blood and tissue of rats. In Experiment 2, groups of rats were fed five different diets: a vitamin E-free control diet, a low alpha-tocopherol diet, and three low alpha-tocopherol diets supplemented with 5, 10, and 15% sesame seed. Changes in lipid peroxides in liver, red blood cell hemolysis, and pyruvate kinase activity, as indices of vitamin E deficiency, were examined. These indices were high in the low alpha-tocopherol diet, whereas supplementation with even 5% sesame seed suppressed these indices completely and caused a significant increase of alpha-tocopherol content in the plasma and liver. In Experiment 3, two diets containing sesame lignan (sesaminol or sesamin) and low alpha-tocopherol were tested. Results in both of the sesame lignan-fed groups were comparable to those observed in the sesame seed-fed groups as shown in Experiment 2. These experiments indicate that sesame seed lignans enhance vitamin E activity in rats fed a low alpha-tocopherol diet and cause a marked increase in alpha-tocopherol concentration in the blood and tissue of rats fed an alpha-tocopherol-containing diet with sesame seed or its lignans.

Lipids 1995 Jun;30(6):499-505
Sesamin (a compound from sesame oil) increases tocopherol levels in rats fed ad libitum.
Kamal-Eldin A, Pettersson D, Appelqvist LA
Department of Food Science, Swedish University of Agricultural Sciences, Uppsala.

Six groups of rats were fed diets low, but adequate, in alpha-tocopherol but high in gamma-tocopherol. The six diets differed only in their contents (0, 0.25, 0.5, 1.0, 2.0, and 4.0 g/kg, respectively) of sesamin, a lignan from sesame oil. After four weeks of ad libitum feeding, the rats were sacrificed and the concentrations of alpha- and gamma-tocopherols were measured in the plasma, livers, and lungs. Sesamin-feeding increased gamma-tocopherol and gamma-/alpha-tocopherol ratios in the plasma (P < 0.05), liver (P < 0.001), and lungs (P < 0.001). The increase was non-significant for alpha-tocopherol. Thus, sesamin appears to spare gamma-tocopherol in rat plasma and tissues, and this effect persists in the presence of alpha-tocopherol, a known competitor to gamma-tocopherol. This suggests that the bioavailability of gamma-tocopherol is enhanced in phenol-containing diets as compared with purified diets.

Biofactors 2000;11(1-2):11-3
Sesamin and alpha-tocopherol synergistically suppress lipid-peroxide in rats fed a high docosahexaenoic acid diet.
Yamashita K, Kagaya M, Higuti N, Kiso Y Department of Food and Nutrition, Sugiyama Jogakuen University, Nagoya, Japan.

Docosahexaenoic acid (DHA) is an essential nutrient for human health, but has extremely high oxidative susceptibility. We examined the suppressing effect of sesamin, a sesame seed lignan, on lipidperoxides in rats fed a low alpha-tocopherol and high DHA containing diet. Groups of rats were fed four experimental diets: low alpha-tocopherol (10 mg/kg diet) control diet, low alpha-tocopherol + 0.2% sesamin diet, low alpha-tocopherol + 0.5% DHA diet and low alpha-tocopherol + 0.5% DHA + 0.2% sesamin diet. TBARS concentrations in plasma and liver were significantly increased by DHA, but were completely suppressed by sesamin. Alpha-tocopherol concentrations in plasma and liver decreased by addition of DHA, but with sesamin recovered to the control level. The addition of DHA into the diets caused remarkable increases of DHA concentrations in plasma and liver lipids. Sesamin caused a significant increase of DHA concentrations in the triacylglycerol of plasma.

An important report shows the cancer fighting effect of sesamin.

Anticancer Res 1992 Jul-Aug;12(4):1259-65
Suppressive effect of sesamin against 7,12-dimethylbenz[a]-anthracene induced rat mammary carcinogenesis.
Hirose N, Doi F, Ueki T, Akazawa K, Chijiiwa K, Sugano M, Akimoto K, Shimizu S, Yamada H Laboratory of Nutrition Chemistry, Kyushu University School of Agriculture, Fukuoka, Japan.

The effects of dietary supplementation of sesamin on 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary carcinogenesis in female Sprague-Dawley rats were studied. Experimental diets containing 0.2% sesamin (an equiweight mixture of sesamin and episesamin) or 0.2% alpha-tocopheryl acetate were given to rats starting 1 week before intragastric administration of DMBA (10 mg/rat). Sesamin significantly (p less than 0.05) reduced the cumulative number of palpable mammary cancers by 36% at 12 weeks post-DMBA administration compared with animals on a control diet. Alpha-tocopheryl acetate inhibited both the incidence and the cumulative number of mammary tumors by 20% and 45%, respectively. Concentrations of lipid peroxides in plasma, liver and tumors were all decreased in both sesamin and alpha-tocopheryl acetate groups. The activity of peripheral blood mononuclear cells (PBMC) increased in rats fed sesamin (140 to 150% of the control and alpha-tocopheryl acetate groups). Fatty acid compositions of plasma, liver and tumor phosphatidylcholine showed a decreased tendency of the metabolism of linoleic acid to arachidonic acid and hence of the plasma concentration of prostaglandin E2 in the sesamin group. The inhibitory effect of sesamin on DMBA-induced mammary carcinogenesis may be ascribed, at least in part, to immunopotentiation and increased antioxidative activity.

Studies suggesting that sesamin is able to prevent allergies

Biosci Biotechnol Biochem 1995 Dec;59(12):2198-202
Effects of sesamin and alpha-tocopherol, individually or in combination, on the polyunsaturated fatty acid metabolism, chemical mediator production, and immunoglobulin levels in Sprague-Dawley rats.
Gu JY, Wakizono Y, Tsujita A, Lim BO, Nonaka M, Yamada K, Sugano M Department of Food Science and Technology, School of Agriculture, Kyushu University, Fukuoka, Japan.

Feeding sesamin and alpha-tocopherol in combination, both at the 0.5% dietary level, to Sprague-Dawley rats for 3 weeks resulted in a trend toward decreasing the proportion of 20:4n-6 and 22:5n-6 and increasing that of 18:2n-6 in phosphatidylcholine from various tissues, suggesting interference with the metabolism of linoleic acid. This dietary manipulation significantly reduced the production of leukotriene C4 in the lung, the splenic production of leukotriene B4, and reduction of the plasma histamine level. Simultaneous administration of sesamin and alpha-tocopherol significantly increased the production of IgA, IgG, and IgM by mesenteric lymph node lymphocytes, while the IgE level tended to be reduced. These effects were not necessarily apparent by feeding these compounds separately. Thus, sesamin and alpha-tocopherol in combination would be effective for regulating the eicosanoid production and modifying the immune function.

Cinnamon Extracts
Enhance Insulin Sensitivity

Studies show that compounds extracted from cinnamon make cells much more sensitive to insulin.

As we know, insulin resistance is characterized by the failure of body cells to recognize and respond to insulin as well as they should or once did. This leads to elevated blood sugar because insulin's job is to prompt cells to take in glucose.

Studies have found that a few spices—especially cinnamon—made cells much more responsive to insulin, the hormone that regulates sugar metabolism and thus controls the level of glucose in the blood.

Researchers have identified the compounds in cinnamon responsible for its activity. They found that cinnamons most active compound—methylhydroxy chalcone polymer (MHCP)—increased glucose metabolism roughly 20-fold in a test tube assay of fat cells.

Horm Res 1998 Sep;50(3):177-82
Regulation of PTP-1 and insulin receptor kinase by fractions from cinnamon: implications for cinnamon regulation of insulin signalling.
Imparl-Radosevich J, Deas S, Polansky MM, Baedke DA, Ingebritsen TS, Anderson RA, Graves DJ
Department of Biochemistry and Biophysics, Iowa State University, Ames, Iowa, USA.

Bioactive compound(s) extracted from cinnamon potentiate insulin activity, as measured by glucose oxidation in the rat epididymal fat cell assay. Wortmannin, a potent PI 3'-kinase inhibitor, decreases the biological response to insulin and bioactive compound(s) from cinnamon similarly, indicating that cinnamon is affecting an element(s) upstream of PI 3'-kinase. Enzyme studies done in vitro show that the bioactive compound(s) can stimulate autophosphorylation of a truncated form of the insulin receptor and can inhibit PTP-1, a rat homolog of a tyrosine phosphatase (PTP-1B) that inactivates the insulin receptor. No inhibition was found with alkaline phosphate or calcineurin suggesting that the active material is not a general phosphatase inhibitor. It is suggested, then, that a cinnamon compound(s), like insulin, affects protein phosphorylation-dephosphorylation reactions in the intact adipocyte. Bioactive cinnamon compounds may find further use in studies of insulin resistance in adult-onset diabetes.

Prostaglandins Leukot Essent Fatty Acids 2000 Feb;62(2):107-10
Antioxidant activity of selected Indian spices.
Shobana S, Naidu KA Department of Biochemistry and Nutrition, Central Food Technological Research Institute, Mysore, India.

Spices and vegetables possess antioxidant activity that can be applied for preservation of lipids and reduce lipid peroxidation in biological systems. The potential antioxidant activities of selected spices extracts (water and alcohol 1:1) were investigated on enzymatic lipid peroxidation. Water and alcoholic extract (1:1) of commonly used spices (garlic, ginger, onion, mint, cloves, cinnamon and pepper) dose-dependently inhibited oxidation of fatty acid, linoleic acid in presence of soybean lipoxygenase. Among the spices tested, cloves exhibited highest while onion showed least antioxidant activity. The relative antioxidant activities decreased in the order of cloves, cinnamon, pepper, ginger, garlic, mint and onion. Spice mix namely ginger, onion and garlic; onion and ginger; ginger and garlic showed cumulative inhibition of lipid peroxidation thus exhibiting their synergistic antioxidant activity. The antioxidant activity of spice extracts were retained even after boiling for 30 min at 100 degrees C, indicating that the spice constituents were resistant to thermal denaturation. The antioxidant activity of these dietary spices suggest that in addition to imparting flavor to the food, they possess potential health benefits by inhibiting the lipid peroxidation.

J Pharm Pharmacol 1999 Nov;51(11):1305-12
The evaluation of long-term effects of cinnamon bark and olive leaf on toxicity induced by streptozotocin administration to rats.
Onderoglu S, Sozer S, Erbil KM, Ortac R, Lermioglu F
Hacettepe University, Faculty of Medicine, Department of Anatomy, Turkey.

The effects of cinnamon bark and olive leaf have been investigated on streptozotocin-induced tissue injury, and some biochemical and haematological changes in rats. The effects on glycaemia were also evaluated. Long-term administration of olive leaf caused significant improvement in tissue injury induced by streptozotocin treatment; the effect of cinnamon bark was less extent. No effects on blood glucose levels were detected. However, significant decreases in some increased biochemical and haematological parameters of streptozotocin-treated rats were observed. Aspartate aminotransferase, urea and cholesterol levels were significantly decreased by treatment with both plant materials, and alanine aminotransferase by treatment with olive leaf. Cinnamon bark also caused a significant decrease in platelet counts. In addition, any visible toxicity, except decrease in body weight gain, attributable to the long-term use of plant materials was not established in normal rats. The data indicate that long-term use of olive leaf and cinnamon bark may provide benefit against diabetic conditions. Determination of underlying mechanism(s) of beneficial effects, toxicity to other systems and clinical assessments of related plant materials are major topics requiring further studies.