Free Shipping on All Orders $75 Or More!

Your Trusted Brand for Over 35 Years

Life Extension Magazine

<< Back to February 2005

Do Your Antioxidants Suppress Enough Free Radicals?

February 2005

By Jim English

In 1991, researchers in Kyoto, Japan, demonstrated that sesamin lignans effectively inhibit delta-5 desaturase, the enzyme responsible for converting DGLA into highly inflammatory arachidonic acid.35

This anti-inflammatory effect was also noted in animals that were fed linseed oil and sesame lignans. Linseed oil is a source of DGLA. Linseed and sesame lowered blood levels of tumor necrosis factor-alpha and PGE-2, two inflammatory mediators. Feeding rats sesame led to significant accumulations of DGLA in the tissues and reduced inflammation caused by tumor necrosis factor-alpha and PGE-2.36

An undesirable side effect of supplementing with highly polyunsaturated fats is increased production of free radicals. The addition of sesame lignans to fish oil can help lower lipid peroxidation rates caused by the fish oil. Sesame suppresses the formation of lipid peroxides from docosahexaenoic acid (DHA), which is highly susceptible to oxidation but is also one of the primary omega-3 fatty acids in fish oil that block inflammation. The combination of sesame with fish oil thus helps to enhance the fish oil’s anti-inflammatory effects by protecting it from lipid peroxidation.37

Sesame Lignans May Support Weight Loss

Optimizing the liver’s oxidation of fatty acids has been proposed to help promote fat loss.38 Numerous studies suggest that sesame lignans may aid in weight loss by enhancing fatty acid oxidation in liver tissues. In a study of rats, the addition of sesamin, one of the most abundant sesame lignans, increased the activity of numerous fatty acid oxidation enzymes.39 While this effect was observed in all groups of rats given various dietary oils, it was especially pronounced in rats consuming fish oil.39 Fish oil appears to act synergistically with sesame lignans to promote fat burning.

Conjugated linoleic acid (CLA) is a fatty acid known to promote weight loss. In a study in rats, the addition of sesamin to CLA promoted even greater weight loss, as measured by a reduction in adipose tissue weight.40 Sesame lignans thus appear to have a synergistic effect, enhancing the benefits of fish oil and CLA in promoting optimal fat burning and healthy weight.

New Study Confirms Sesame’s Synergistic Effects

In response to these remarkable published studies on sesame, Life Extension conducted a clinical trial to see what would happen to people who took supplements containing gamma tocopherol and sesame lignans.

To establish a baseline, three markers of oxidative stress and inflammation—dityrosine, isoprostane, and PLGF-1—were measured in the blood of a group of human test subjects. The group was then divided into two subgroups, with one subgroup given gamma tocopherol plus tocotrienols and the other receiving the same amount of gamma tocopherol plus sesame lignans.

The dityrosine marker measures serum levels of deep-tissue protein oxidation caused by the peroxynitrite radical reacting with tyrosine, an amino acid found in all human proteins. Tyrosine is the amino acid most readily attacked by the pero-xynitrite radical, an extremely powerful free radical that has been implicated in a host of disorders. Gamma tocopherol is the only tocopherol that reacts with, or traps, the peroxynitrite radical to any appreciable degree. Compared to the gamma tocopherol-tocotrienol group, those taking gamma tocopherol plus sesame showed a 45% reduction in serum dityrosine oxidation levels after two weeks of supplementation.

A three-dimensional spiral CT scan of carotid atherosclerosis.

The isoprostane marker measures the amount of cell membrane damage caused by free radicals. Also called lipid peroxidation, cell membrane damage involves a free radical chain reaction of cell membrane fatty acids. Normally, lipid peroxidation results in one free radical destroying 8 to 10 normal molecules before being quenched. Supplementing with vitamin E products can limit this destruction to one or two molecules rather than the normal 8-10 molecules that occurs without supplementation. Compared to the gamma tocopherol-tocotrienol group, those taking gamma tocopherol plus sesame showed a 22% reduction in serum isoprostane levels after two weeks of supplementation.

The PLGF-1 marker is an extremely sensitive new test for atherosclerotic risk in humans. PLGF-1 stands for “placental growth factor” because it was originally identified in the placenta. For adults, however, high levels of PLGF-1 are indicative of atherosclerotic lesions. PLGF-1 stimulates vascular smooth muscle cell growth, recruits macrophages into atherosclerotic lesions, up-regulates production of tumor necrosis factor-alpha and stimulates undesirable angiogenesis. In the animal model, inhibition of PLGF-1 suppressed both atherosclerotic plaque growth and arterial wall inflammatory reactions. PLGF-1 may be considered a marker for the presence of unstable arterial wall plaque. Compared to the gamma tocopherol-tocotrienol group, those taking gamma tocopherol plus sesame showed an 11.5% reduction in serum PLGF-1 levels after two weeks of supplementation.

Considering that the subjects in this experiment were a healthy group to begin with—with baseline PLGF-1 levels that were already in the lowest percentage quartile—the 11.5% reduction recorded in the gamma tocopherol plus sesame group was impressive. Presumably, those with arterial wall dysfunction, who normally have high PLGF-1 levels, would derive even greater benefit from supplements that lowered this very sensitive inflammatory marker. The same would hold true for aging adults whose baseline oxidative stress levels are very high compared to this healthy group of test subjects.

Based on these three advanced measurements of free radical and inflammatory damage, gamma tocopherol plus sesame lignans is on average 25% more effective in reducing three biomarkers of oxidative stress and inflammation than the more expensive gamma tocopherol plus tocotrienols.

Spiral CT scan showing atherosclerosis of left carotid artery.

What is so impressive about this recent trial is that unlike previous studies, the effects of sesame were not compared to a placebo or control group. Instead, this human study compared the effects of supplementing with low-cost sesame to those of taking very expensive tocotrienols. The tocotrienols are considered nature’s most potent natural antioxidants. Yet in this study, sesame was found to work 25% better than the tocotrienols.


Sesame and its lignans have been shown to possess multiple health benefits, both alone and in synergistic combination with other compounds, including gamma tocopherol and fish oil. Sesame lignans help to increase tissue and serum levels of biological antioxidants that have been strongly correlated with improved health in mammals and humans.

Sesame lignans have also demonstrated anti-inflammatory benefits and block free radical lipid peroxidation in fish oil supplements to suppress inflammation. Lignans are powerful inhibitors of LDL oxidation, effectively reducing atherogenic processes. Lastly, lignans are potent stimulators of fatty acid oxidation, one of the key processes involved in weight control.

By influencing biochemical processes in the body, sesame and its lignans promise to help reduce risk for many of today’s most common diseases, including heart disease, obesity, and inflammatory disorders.


1. Qidwai W, Alim SR, Dhanani RH, et al. Use of folk remedies among patients in Karachi Pakistan. J Ayub Med Coll Abbottabad. 2003 Apr;15(2):31-3.

2. Minamiyama Y, Takemura S, Yoshikawa T, Okada S. Fermented grain products, production, properties and benefits to health. Pathophysiology. 2003 Oct;9(4):221-7.

3. Yamashita K, Nohara Y, Katayama K, Nami ki M. Sesame seed lignans and gamma-tocopherol act synergistically to produce vitamin E activity in rats. J Nutr. 1992;122(12):2440-6.

4. Kontush A, Spranger T, Reich A, Baum K, Beisiegel U. Lipophilic antioxidants in blood plasma as markers of atherosclerosis: the role of alpha-carotene and gamma-tocopherol. Atherosclerosis. 1999 Jun;144(1):117-22.

5. Boje KM. Nitric oxide neurotoxicity in neurodegenerative diseases. Front Biosci. 2004 Feb 1;9:763-76.

6. Jiang Q, Elson-Schwab I, Courtemanche C, Ames BN. gamma-tocopherol and its major metabolite, in contrast to alpha-tocopherol, inhibit cyclooxygenase activity in macrophages and epithelial cells. Proc Natl Acad Sci USA. 2000 Nov 10;97(21):11494-9.

7. Gysin R, Azzi A, Visarius T. Gamma-tocopherol inhibits human cancer cell cycle progression and cell proliferation by down-regulation of cyclins. FASEB J. 2002;16(14):1952-4.

8. Campbell S, Stone W, Whaley S, Krishnan K. Development of gamma (gamma)-tocopherol as a colorectal cancer chemopreventive agent. Crit Rev Oncol Hematol. 2003 Oct;47(3):249-59.

9. Galli F, Stabile AM, Betti M, et al. The effect of alpha- and gamma-tocopherol and their carboxyethyl hydroxychroman metabolites on prostate cancer cell proliferation. Arch Biochem Biophys. 2004 Apr 1;423(1):97-102.

10. Kushi LH, Folsom AR, Prineas RJ, et al. Dietary antioxidant vitamins and death from coronary heart disease in postmenopausal women. N Engl J Med. 1996 Jun 2;334(18):1156-62.

11. Kayden HJ and Traber MG. Absorption, lipoprotein transport, and regulation of plasma concentrations of vitamin E in humans. J Lipid Res. 1993 Apr;34(3):343-58.

12. Handelman GJ, Epstein WL, Peerson J, et al. Human adipose alpha-tocopherol and gamma-tocopherol kinetics during and after 1 y of alpha-tocopherol supplementation. Am J Clin Nutr. 1994 Jun;59(5):1025-32.

13. Handelman GJ, Machlin LJ, Fitch K, Weiter JJ, Dratz EA. Oral alpha-tocopherol supplements decrease plasma gamma-tocopherol levels in humans. J Nutr. 1985 Jul;115(6):807- 13.

14. 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 Jun;132(5):961-6.

15. Sontag TJ, Parker RS. Cytochrome P450 omega-hydroxylase pathway of tocopherol catabolism. Novel mechanism of regulation of vitamin E status. J Biol Chem. 2002 Aug 12;277(28):25290-6.

16. Clement M, Bourre JM. Graded dietary lev- els of RRR-gamma-tocopherol induce a marked increase in the concentrations of alpha- and gamma-tocopherol in nervous tissues, heart, liver and muscle of vitamin-E-deficient rats. Biochim Biophys Acta. 1997 Apr 15;1334(2-3):173-81.

17. 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 Dec;30(11):1019-28.

18. Cooney RV, Custer LJ, Okinaka L, Franke AA. Effects of dietary sesame seeds on plasma tocopherol levels. Nutr Cancer. 2001;39(1):66-71.

19. Lemcke-Norojarvi M, Kamal-Eldin A, Appelqvist LA, Dimberg LH, Ohrvall M, Vessby B. Corn and sesame oil increase serum gamma-tocopherol concentrations in healthy Swedish women. J Nutr. 2001 Apr;131(4):1195-201.

20. Jessup W, Kritharides L, Stocker R. Lipid oxidation in atherogenesis: an overview. Biochem Soc Trans. 2004 Mar;32(Pt 1):134-8.

21. Esterbauer H, Gebicki J, Puhl H, Jurgens G. The role of lipid peroxidation and antioxidants in oxidative modification of LDL. Free Radic Biol Med. 1992 Nov;13(4):341-90.

22. Miura S, Watanabe J, Sano M, et al. Effects of various natural antioxidants on the Cu(2+)-mediated oxidative modification of low density lipoprotein. Biol Pharm Bull. 1995 Feb;18(1):1-4.

23. Hirose N, Inoue T, Nishihara K, et al. Inhibition of cholesterol absorption and synthesis in rats by sesamin. J Lipid Res. 1991 May;32(4):629-38.

24. Kang MH, Kawai Y, Naito M, Osawa T. Dietary defatted sesame flour decreases susceptibility to oxidative stress in hypercholesterolemic rabbits. J Nutr. 1999 Nov;129(10):1885-90.

25. Nakabayashi A, Kitagawa Y, Suwa Y, et al. Alpha-tocopherol enhances the hypocholesterolemic action of sesamin in rats. Int J Vitam Nutr Res. 1995;65(3):162-8.

26. Hirata F, Fujita K, Ishikura Y, et al. Hypocholesterolemic effect of sesame lignan in humans. Atherosclerosis. 1996 May 26;122(1):135-6.

27. Noguchi T, Ikeda K, Sasaki Y, et al. Effects of vitamin E and sesamin on hypertension and cerebral thrombogenesis in stroke-prone spontaneously hypertensive rats. Hypertens Res. 2001 Dec;24(6):735-42.

28. Kita S, Matsumura Y, Morimoto S, et al. Antihypertensive effect of sesamin. II. Protection against two-kidney, one-clip renal hypertension and cardiovascular hypertrophy. Biol Pharm Bull. 1995 Oct;18(9):1283-5.

29. Matsumura Y, Kita S, Morimoto S, et al. Antihypertensive effect of sesamin. I. Protection against deoxycorticosterone acetate- salt-induced hypertension and cardiovascular hypertrophy. Biol Pharm Bull. 1995 Aug;18(7):1016-9.

30. Matsumura Y, Kita S, Tanida Y, et al. Anti- hypertensive effect of sesamin. III. Protection against development and maintenance of hypertension in stroke-prone spontaneously hypertensive rats. Biol Pharm Bull. 1998 Jun;21(5):469-73.

31. Matsumura Y, Kita S, Ohgushi R, Okui T. Effects of sesamin on altered vascular reactivity in aortic rings of deoxycorticosterone acetate-salt-induced hypertensive rat. Biol Pharm Bull. 2000 Oct;23(9):1041-5.

32. Nakano D, Itoh C, Takaoka M, et al. Antihypertensive effect of sesamin. IV. Inhibition of vascular superoxide production by sesamin. Biol Pharm Bull. 2002 Oct;25(9):1247-9.

33. Nakano D, Itoh C, Ishii F, et al. Effects of sesamin on aortic oxidative stress and endothelial dysfunction in deoxycorticosterone acetate-salt hypertensive rats. Biol Pharm Bull. 2003;26(12):1701-5.

34. Sankar D, Sambandam G, Rao MR, Pugal- endi KV. Impact of sesame oil on nifedipine in modulating oxidative stress and elec- trolytes in hypertensive patients. Asia Pac J Clin Nutr. 2004;13(Suppl):S107.

35. Shimizu S, Akimoto K, Shinmen Y, et al. Sesamin is a potent and specific inhibitor of delta 5 desaturase in polyunsaturated fatty acid biosynthesis. Lipids. 1991 Aug;26(7):512-6.

36. Utsunomiya T, Chavali SR, Zhong WW, Forse RA. Effects of sesamin-supplemented dietary fat emulsions on the ex vivo production of lipopolysaccharide-induced prostanoids and tumor necrosis factor alpha in rats. Am J Clin Nutr. 2000 Oct;72(3):804-8.

37. Ikeda S, Kagaya M, Kobayashi K, et al. Dietary sesame lignans decrease lipid peroxidation in rats fed docosahexaenoic acid. J Nut Sci Vitaminol (Tokyo). 2003 Sep;49(4):270-6.

38. McCarty MF. Hepatothermic therapy of obesity: rationale and an inventory of resources. Med Hypotheses. 2001 Oct;57(3):324-36.

39. Ide T, Hong DD, Ranasinghe P, et al. Interaction of dietary fat types and sesamin on hepatic fatty acid oxidation in rats. Biochim Biophys Acta. 2004 Jul 1;1682(1-3):80-91.

40. Sugano M, Akahoshi A, Koba K, et al. Dietary manipulations of body fat-reducing potential of conjugated linoleic acid in rats. Biosci Biotechnol Biochem. 2001 Dec;65(11):2535-41.