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Sesamin is a lignan compound that is named after the source it was found in, Sesame seeds. Most of its actions appear to be secondary to activating PPAR proteins (which underlie its effects on fat mass); this is a similar mechanism to Conjugated Linoleic Acid, and because of this and the lack of human studies on Sesamin it would be prudent to be cautious about its influences on fat mass. PPARα activation in rodents tends to be more promising than it is in humans due to species-related reasons.
Beyond that, Sesamin appears to act as a phytoestrogen and possible estrogen receptor modulator. It is possible that Sesamin can be metabolized into a molecule known as enterolactone (which is a biologically significant estrogenic compound), but the degree of enterolactone made from Sesamin and other Sesame seed lignans is relatively minor; metabolism into enterolactone is more of a concern with Flax Seeds.
Sesamin does appear to be effective in enhancing blood flow in persons with impaired circulation, but those studies are all confounded with inclusion of Schizandra Chinensis.
The more remarkable effects of Sesamin that make it relatively unique are neuroprotective effects that, although not inherently potent, occur at a very low concentration (1 picomole) and the ability of Sesamin to alter the omega-3:omega-6 fatty acid balance without ingesting either omega-3 or omega-6 fatty acids; this is by apparently inhibiting the Delta-5-Desaturase enzyme towards omega-6 enzymes only, and favorably influencing omega-3 metabolism.
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The only human study using Sesamin noted benefits with 60mg daily, and doses up to 215mg/kg in animals (35mg/kg human dose conversion) does not appear to be associated with toxicity.
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The Human Effect Matrix looks at human studies (excluding animal/petri-dish studies) to tell you what effect Sesamin has in your body, and how strong these effects are.
|Grade||Level of Evidence|
|A||Robust research conducted with repeated double blind clinical trials|
|B||Multiple studies where at least two are double-blind and placebo controlled|
|C||Single double blind study or multiple cohort studies|
|D||Uncontrolled or observational studies only|
|Level of Evidence ||Effect||Change||Magnitude of Effect Size ||Scientific Consensus||Comments|
A small decrease in blood pressure has been noted with sesamin supplementation
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Sesamin is the most abundant lignan in Sesame Seed Oil alongside the other lignan, Sesamolin, which were isolated in 1951.
Sources of Sesamin include:
Unlike other lignans in Sesame (Pinoresinol, Matairesinol, and Syringaresinol), the structure of Sesamin does not allow conjugation and it exists in its free form in food products. Below are the structures of Sesamin and two metabolic by-products produced in the human gut, thought to mediate some of the effects of Sesamin after oral consumption.
In rats, ingestion of 0.2% of the diet as Sesamin after 10 days resulted in serum levels of over 200ng/mL with slightly higher levels of Sesamin monocatechol and Sesamin Dicatechol; serum levels were not influenced by Vitamin E at 1% of the diet.
Following ingestion of 50g ground Sesame Seeds, Sesamin in serum (n=4) appears to have a Cmax of 105+/-11.7nmol/L at a Tmax of 1 hour, with an absorption half-life of 0.24+/-0.01 hours and an elimination half-life (in serum) of 2.08+/-0.58 hours; conferring an AUC of 362+/-92.0nmol/h/L.
In regards to the other Sesame lignans, one study indicated that episesamin and sesamolin may have longer half-lives than Sesamin; referencing unpublished research saying that one time administration of all three compounds led to a Tmax of 6-7 hours with half lives of 4.7+/-0.2, 6.1+/-0.3, and 7.1+/-0.4 respectively; dose unspecified.
In human liver microsomes, Sesamin is metabolized into Sesamin monocatechol via CYP2C9 and can be further metabolized into Sesamin dicatechol via the same enzyme. These Sesamin catechol structures have been detected in human urine following consumption of food products containing 508 μmol (180 mg) sesamin and 192 μmol (71 mg) sesamolin and monocatechol has been quantified at 22.2-38.6% the oral dose of Sesamin.
Sesamin monocatechol can metabolized into Sesamin Monocatechol Glucuronide (via UGT enzymes) or Sesamin Monocatechol Methylate (via Catechol-O-Methyltransferase; COMT).
Primarily metabolized into one of two catechol structures (which circulate and can be excreted via the urine) or the first monocatechol metabolite can be further metabolized into two other urinary byproducts
Other known metabolite of Sesamin are enterolactone and enterodiol, which have been produced ex vivo by human intestinal microflora with pure Sesamin. These two metabolites are common metabolic by-products of dietary lignans. The conversion rate of Sesamin to these endogenous lignans are fairly low (1.1% in rats), while the minor lignan in sesame and major lignan in flax known as secoisolariciresinol (conjugated as diglucoside) showed a much higher conversion rate (57.2%). Sesamin converts into both enterolactone and enterodiol fairly evenly, and despite higher levels of total lignans in serum relative to flax it produces less enterolactone and enterodiol in women ingesting the food products. Tahini also appears to produce significantly more serum enterodiol and enterolactone than does Sesame in rats fed equal amounts of each.
Like many other lignan compounds, can be metabolized into Enterolactone and Enterodiol, although at a lower rate than flax seed
In regards to episesamin, an isomer commonly found alongside Sesamin in supplements at a 1:1 ratio, it can be methylated in a similar manner to the catechol metabolites as does Sesamin (yielding three metabolites depending on whether either one or both methylendioxyphenyl (pentagon) groups get demethylated) and these metabolites are subject to the COMT enzyme.
Episesamin goes through similar metabolism as does Sesamin
Sesamin has been found to attenuate the induction of CYP3A4 by interfering with the coregulators of PXR and the CYP3A4 promoter, and thereby preventing PXR from inducing CYP3A4.
Basal CYP3A4 activity was inhibited at 10, 20, 30, and 40uM by Sesamin 15.6%, 23.4%, 37.1%, and 55.8% respectively while coincubation with a CYP3A4 inducer was able to (relative to induced control) reduce CYP3A4 activity by 21.3%, 25.7%, 41%, and 77.3% at the same concentrations.
May prevent CYP3A4 induction, and exert some inhibitory effects on this enzyme
In regards to P-glycoprotein, Sesamin was tested in concentrations of 1-100uM in a test of Rhodamine 123 accumulation in LS-180V Cells noted 2.2-fold higher concentrations under the influence of 100uM (of similar potency to 300uM Piperine) although 1-10uM was ineffective. 10uM Sesamin was able to increase MDR1 mRNA expression as well as that of MDR2 and MDR3 (MDR2 being statistically insignificant) and after incubation of the cell for 48 hours Sesamin at 100uM failed to increase Rhodamine 123 uptake..
Technically inhibits P-Glycoprotein, but cells may adapt over time to make it irrelevant
Sesamin has been found to inhibit the delta-5-desaturase enzyme without influencing Delta 6, 9, or 12 desaturases, and this specificity extends to Sesamin-like lignans. This enzyme is the rate limiting step of EPA and subsequently DHA (the fatty acids of Fish Oil) but also that of Arachidonic Acid (AA; a pro-inflammatory fatty acid) and following consumption of 50g Sesame Seed powder (not isolated Sesamin) a decrease in serum EPA and AA has been found at the magnitude of 12% and 8%, respectively, when compared to baseline values.
May reduce circulating levels of bioactive fatty acids involved in inflammation and antiinflammation
In PC12 cells and N9 microglia, sesamin at 1pM was able to attenuate the increase in cytokine mRNA induced by 1-methyl-4-phenylpyridinium (MPP+ at 500uM) without influencing baseline cytokine mRNA. The potency on suppressing mRNA induction of IL-6, IL-1β, and TNFα was lesser than 0.1uM Quercetin. A reduction of iNOS and oxygen radicals were also noted, which resulted in less neuronal cell death secondary to inflammation, with sesamin nonsignificantly more effective than quercetin. This concentration of sesamin (1pM) has been noted effective elsewhere in protecting neurons from MPP+ mediated oxidative cell death, yet much higher concentrations (0.1-2uM) are associated with protection from cell death induced by kainate, and in these concentrations reduced ERK1/2 and COX-2 expression (relative to kainate-induced controls) and the subsequent PGE2 induction.
An attenuation of oxidative stress has also been noted following oral intake of 30mg/kg Sesamin extract (90% Sesamin, 10% Sesamolin) for 3 days prior to kainate injection, where lipid peroxidation (TBARS) was reduced from 142% of control with kainate to 117% with kainate with Sesamin; an increase in serum alpha-tocopherol (Vitamin E) was noted to 50-55.8% of baseline levels. There was no apparent effect noted with 15mg/kg, and 30mg/kg was able to reduce mortality from 22% to 0% in response to kainate. In vitro using PC12 cells, it appears that preventing Sesamin's anti-oxidative effects abolishes protective effects on the neuronal cell.
Prevention of an induction of NO in response to LPS (typical anti-inflammatory agent) has been noted with Sesamin in Microglia cells in vitro.
Appears to exert protective effects in brain tissue (antioxidative and antiinflammatory), both at very low concentrations in vitro and in some oral studies with rats; suggesting these results are relevant to human supplementation
Sesamin metabolites (sesamin and episesamin monocatechols) are able to enhance NGF-induced neuronal differentiation in vitro in PC12 cells independent of the TrkA receptor (affinity for NGF) but appeared to be mediated via activation of ERK1/2, downstream of TrkA.
Sesamin appears to inhibit cholesterol absorption from the intestines when fed to rats at 0.5% of the diet, but failed to influence fatty acid and bile acid absorption/resorption. This may underlie hypocholesterolemic effects of Sesamin after consumption in humans.
When looking at oxidized LDL (oLDL) induced endothelial dysfunction, Sesamin was able to reduce the oxidative effects of oLDL (and indirectly preserve the Superoxide dismutase (SOD) enzyme) which was thought to be secondary to an attenuation of nF-kB activation; a pro-inflammatory response.
Dietary sesamin at 63.7+/-0.4mg/kg in both wild type and ApoE-/- mice (prone to artherosclerosis) trended (40%) but failed to significantly reduced aortic/thoracic lesion size after 26 weeks (whereas Quercetin and Theaflavin were effective) while the induction of eNOS was lesser than that of the aforementioned two molecules.
A possible mechanism tying in Sesamin with cardioprotection may be the antioxidant effects of Sesamin, inhibiting Superoxide radical production. 0.1-1% of the diet as Sesamin in spontaneously hypertensive rats was effectively able to normalize deoxycorticosterone acetate (DOCA) induced oxidation (although it only attenuated the increase in systolic blood pressure by 29-55%) while not significantly influencing oxygen radical levels in control.
One intervention in middle-aged women with mild hypertension following 60mg Sesamin over 4 weeks in a double-blind crossover manner noted significant reductions in systolic blood pressure (137.6+/-2.2 to 134.1+/-1.7mmHg; 2.6% reduction) and diastolic blood pressure (87.7+/-1.3 to 85.8+/-1.0mmHg; 2.2% reduction). Sesamin has once been implicated in improving blood flow in otherwise healthy humans with under average blood flow, but this study was confounded with the inclusion of Schizandra Chinensis.
A very small but statistically significant reduction in blood pressure may exist following low dose Sesamin consumption
Sesamin has been found to increase activity of peroxisomal fatty acid oxidation in the liver, which occurs per se after oral administration of 2% Sesamin in the diet of rats and may be enhanced with co-ingestion of Arachidonic Acid.
Appears to mediate its benefits through increasing fatty acid oxidation in the liver via peroxisomes and acting as a PPARα agonist
When looking at the isomers, 0.2% of the diet containing either Sesamin, Episesamin, or Sesamolin was able to modify gene expression of various fatty acid regulatory genes in the range of 1.5 to 2-fold that of the control diet. Notable changes were that increases in enzymes of fatty acid oxidation (n=22) increased 10-280% with Sesamin, 60-1200% with Episesamin, and 50-1100% with Sesamolin (relative to control diet). Similar changes were seen with mitochondrial biogenesis genes (n=3) while no significant differences existed with lipogenesis or lipid transport gene suppression.
This study noted that Episesamin and Sesamolin were able to increase hepatic weight (22-27%) while reducing the weight of epididymal white adipose tissue (19-20%), with Sesamin not affecting either parameter. In vitro, Sesamin appears to be weaker than both Episesamin and Sesamolin at inducing genetic expression
Sesamin and related sesame lignans appear to influence a variety of genomic responses that suggest it may be a fat burning compound
50g of Sesame seeds, when compared to either a control of rice powder at the same weight or their own baseline when caloric intake was controlled, failed to influence body mass over 4 weeks in post-menopausal women.
Insufficient evidence to support Sesamin as a fat burning supplement
In vitro, Sesamin has been shown to suppress proliferation of various cell lines. The cell lines suppressed and their respective IC50 values (umol/L) are leukemic KBM-5(42.7), leukemic K562(48.3), myeloma U266(51.7), prostatic DU145(60.2), colon HCT116(57.2), Pancreatic MiaPaCa-2(58.3), Lung adenocarcinoma H1299(40.1), and BreastMDA-MB-231(51.1). An augmented TNF-a mediated apoptosis was noted in KBM-5 and U266 cell (no others tested) ranging from 4.7 to 7.2-fold increased apoptosis, thought to be from Sesamin preventing TNF-a induction of Bcl-2 and Survivin which can preserve cancer cells.
TNF-a induced expression of cell-proliferative (cyclin D1, COX-2) and invasive (ICAM-1, MMP-9, VEGF) gene products was prevented with Sesamin, all of which was thought to be from preventing nF-kB translocation at 100umol/L. An attenuation of TNF-a induced ICAM-1 expression has been noted elsewhere in human endothelial cells.
Appears to augment TNF-a induced chemotherapy in vitro, and prevent TNF-a from enhancing cell survival
Sesamin has been found to inhibit nF-kB activation in a dose and time dependent manner by a variety of inflammatory agents, affecting constitutive and inductive nF-kB. Sesamin also prevented TNF-a induced degradation of the inhibitory subunit IκBα, and both inhibited TNF-a induced activation of IKK and IKK-induced nF-kB activation.
Sesamin appears to directly possess anti-oxidative effects when it is converted to its main CYP2C9 metabolites, Sesamin monocatechol or Sesamin dicatechol. These anti-oxidative effects have been found to exert a Vitamin E sparing effect in vitro, and increase serum levels of Vitamin E after consumption of Sesamin in isolation at 30mg/kg in rats has reached 50% higher levels than baseline.
Catechol derivatives of Sesamin have anti-oxidant properties directly
Sesamin and episesamin metabolites (monocatechols) appear to be able to induce Nrf2/ARE genomic signaling and the subsequent induction of Heme-Oxygenase 1 (HO-1), which is thought to be secondary to a small pro-oxidative effect via activating p38 MAPK; incubation of a PC12 cell with N-AcetylCystine to prevent this pro-oxidative effect abolishes the induction of HO-1 and subsequent anti-oxidation. These anti-oxidative effects may underlie neuroprotective effects of Sesamin.
Catechol derivatives may also induce a small hormetic (pro-oxidative) effect in vitro, inducing anti-oxidant gene expression
When incubated in Ishikawa cells as a test for estrogenicity, Sesamin per se at 0.5-4uM failed to induce estrogenic effects and failed to inhibit the estrogenicity of 1nM estradiol.
When tested in T47D Breast cancer cells via Luciferase transcript, Sesamin appeared to possess weak estrogenic activities on the receptor that were abolished with an estrogen receptor antagonist. At 10uM, the estrogenic response to 1nM estradiol was attenuated while the response to a lower concentration of 1pM estradiol was enhanced additively, suggesting that Sesame lignans (Sesamin, Sesamol, and enterolactone but not enterodiol) could act as Estrogen Receptor Modulators. Ingestion of 1% isolated Sesamin in the diet of mice with high circulating estrogen levels reduced the size of their (estrogen-responsive) breast cancer tumors, suggesting that these anti-estrogenic effects could be relevant in vivo.
One study conducted in post-menopausal women following consumption of Sesame Seeds at 50g for 4 weeks failed to find any influence on urinary estrone or estradiol (two estrogen compounds) while serum sulfates DHEA declined by 22%. A nonsignificant (P=0.065) increase in SHBG was noted at 15%. These effects could not be attributed to Sesamin per se.
Sesamin may act as an Estrogen Receptor modulator, normalizing the effects of estrogen by activating the receptor at low circulating estrogen and attenuating its effects at high estrogen concentrations. At least one study in humans suggests that it does not influence circulating estrogen per se
In regards to enterolactone and enterodiol (minor lignan metabolites of Sesamin), these metabolites appear to activate estrogen receptors and are classified as phytoestrogens. Due to low conversion rates from Sesame seed exclusive lignans, the practical significance of enterolactone estrogenicity is not known.
Enterolactones are known to be estrogenic, but the effects of these after oral consumption are not known
Mechanistically, Sesamin has been found to inhibit the Delta-5-Desaturase enzyme in vitro and does not alter lymphatic absorption of either fatty acid (excluding its influence on the following). The inhibition on Delta-5-Desaturase only seems to apply to Omega-6 fatty acids, preventing DihydroGamma-Linoleic acid (DGLA) from converting into Arachidonic Acid (AA), and an increase in hepatic DGLA appears to reliably occur in rats fed 0.5% Sesamin. These effects are associated with a hepatic Sesamin concentration of 1.32mcg/g, which follows 0.5% of the diet in rats.
When measuring liver tissue itself, there appears to be a reduced hepatic content of omega-3 fatty acids with no influence on omega-6 or omega-9 (and thus a relative increase). Another study measuring fatty acid content of the liver noted relative increases in omega-6 and decreases in omega-3 content of liver cells independent of dietary fatty acid composition, and an increase in fat liver phosphatidylcholine associated with omega-6 fatty acids (suggesting deposition into cell membranes). This may underlie an 8% reduction of circulating Arachidonic Acid seen in serum of postmenopausal women given 50g Sesame seed powder for 4 weeks.
An increase of Dihydrogamma-linoleic acid appears to result in the rat liver after supplementation with 0.5% Sesamin, and reduced conversion into arachidonic acid; Arachidonic appears to be sequestered in the liver, and a reduction in circulating levels results
In rats fed 0.2% sesamin in the diet alongside 1.5% and 3% Fish Oil found that the increase in hepatic enzymes involved in fatty acid oxidation was synergistically enhanced relative to the groups fed 1.5% and 3% in isolation; the results were synergistic rather than additive, and appeared to rival a diet of 8% fish oil. Adding in low doses of Fish Oil (both EPA and DHA appear effective) can preserve the efficacy of Sesamin when the dose of Sesamin is halved despite this dose of omega-3 being inactive; fish oil tends to need much higher doses (up to 10% of the diet) to exert similar effects.
Oddly, the sole human study measuring serum omega-3 status (50g sesame seeds for 4 weeks) noted a decrease in circulating EPA levels; this study also failed to notice any fat loss but did not design itself to measure fat loss.
In rats, Sesamin and omega-3 fatty acid such as Fish Oil are synergistic in increasing fat oxidation in the liver. Due to species differences on this PPARa system (using Conjugated Linoleic Acid as a case study), relevance to humans is unknown
Sesamin at 0.2% of the diet alongside 1% alpha-tocopherol (main form of Vitamin E) over 10 days noted synergistic reductions in total cholesterol and LDL-C when both are combined rather than either agent in isolation (although both outperformed control rats). Although all treatment groups had increases in cholesterol efflux transporters, the combination enhanced ABCG5 and ABCG8 while decreasing ABCA1 and ApoA4 without influencing ApoB or the LDL receptor.
Sesamin in isolation may increase serum Vitamin E levels due to preserving it, and coadministration of Sesamin with Vitamin E synergistically enhances serum alpha and delta-tocopherol (two Vitamin E molecules) more than Vitamin E treatment alone. This increase of serum Vitamin E has also been noted with Sesaminol, although another Sesame lignan (Hydroxymatairesinol) had no effect.
Synergistic with Vitamin E, specifically the alpha-tocopherol component
Sesamin at 2% of the diet in rats and Alpha-Lipoic Acid at 2.5% of the diet for 22 days exerts additive effects in reducing serum Triglycerides, despite inducing relatively similar gene expression.
There was no benefit to combining the compounds on liver triglyceride concentrations. Although the combination decreased lipogenesis in an additive fashion ALA partially negated the effects of Sesamin on increasing fatty acid oxidation.
One study suggests additive effects on reducing triglyceride synthesis, and antagonistic effects on fatty acid synthesis
One bioactive of Schisandra, known as Schisandrin B, has been tested alongside Sesamin at either 43mg/kg or 215mg/kg and had hepatoprotective effects against CCL4-induced toxicity with similar efficacy to 7.5mg/kg Silymarin (from Milk Thistle).
Schizandra Chinensis has been tested (65mg of the extract) with Sesamin (2.5mg) with a small amount of Vitamin E (3.75IU) in regards to blood viscosity, and in a small sample of 10 persons with subaverage blood flow noted that two of the above tablets daily for 2 weeks was associated with 9% faster blood flow at week 1 and 9.7% increased blood flow relative to baseline at week 2.
Schisandra and Sesamin has also been tested in a proper double-blind trial in persons with borderline liver enzymes, and combination therapy at double the dose in the above blood flow study decreased elevated ALT and AST without influencing Bilirubin levels; anti-oxidative parameters were increased after 5 months.
Has been tested in conjunction with Sesamin, no synergism has been tested
Conjugated Linoleic Acid (CLA) is a fatty acid mixture that is touted to increase fat loss via acting to similar mechanisms as Sesamin. One study has been conducted in rats where one group fed 1% CLA was compared to another group fed 1% CLA with 0.2% Sesamin (some Episesamin in the mixture) in addition to CLA for 8 weeks failed to find any additive or synergistic benefits. A lack of synergistic effects have been found with CLA and Sesamin at the same doses in a previous rat study, although both trended towards additive effects being statistically significant.
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