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LE Magazine Special Edition, Winter 2004/2005
How Sesame Lignans Enhance the Effects of GLA

If you take gamma linolenic acid (GLA), new information indicates that sesame lignans could enable the GLA to work much better in the body.

When GLA is absorbed into the blood, it is first broken down to the biologically active di-homo gamma linolenic acid (DGLA). From there DGLA can go in two directions, one of them highly beneficial, the other possibly detrimental.

The beneficial route involves the DGLA being converted into an inflammatory-suppressing hormone-like substance called prostaglandin E1. The undesirable route involves DGLA being converted into arachidonic acid, which is a precursor to pro-inflammatory prostaglandin E2 and leukotriene B4.1-6

Sesame lignans suppress the enzyme (delta-5 desaturase) that converts DGLA into arachidonic acid. By blocking the undesirable enzyme (delta-5 desaturase), more DGLA is available for conversion into beneficial prostaglandin E1.7-12

Enlarge Chart

The chart shows that GLA can follow a pro-inflammatory or anti-inflammatory pathway in the body.

If you study the chart, it provides insight as to why certain people are more vulnerable to inflammatory-related problems. Those with high delta-5 desaturase levels convert a lot of their dietary fats into arachidonic acid, while those with low delta-5 desaturase should transform their dietary fat into beneficial prostaglandin E1.

What the chart does not reveal is what causes delta-5 desaturase to increase or decrease. Scientists have not identified all the factors yet, but we do know that insulin activates delta-5 desaturase while EPA (from fish and other omega-3 oils) limits it.3,13-21 Epidemiological data conclusively shows that excess insulin is very dangerous, while diets high in omega-3 oils are very beneficial.3,22

Obesity, excess insulin (hyper- insulinemia), chronic inflammation and its related diseases go hand in hand. Since insulin activates delta-5 desaturase, which then transforms DGLA into the pro-inflammatory precursor arachidonic acid, we can understand why obese people suffer from so many inflammatory disorders.23,24

It is important to note that gamma linolenic acid (GLA) can be naturally formed in the body from the ingestion of linoleic acid, an omega-6 fat that almost everyone consumes. Even those who do not take GLA can benefit from supplements that suppress excess delta-5 desaturase—for example, fish oil and insulin-suppressing agents such as PGX™ (soluble fiber blend). Sesame lignans, however, may be the most effective way of reducing the delta-5 desaturase enzyme.

It should be noted, however, that the first step in the natural conversion process that transforms linolenic acid to GLA is controlled by another enzyme called D6D (delta-6 desaturase). Unfortunately, D6D activity declines with age and other factors such as excess consumption of trans fats and alcohol.25,26 As highlighted in the chart, GLA supplementation can circumvent impaired D6D function by providing gamma linolenic acid directly to the body.27

References

1. Miles, EA, Banerjee, T, Calder, PC. The influence of different combinations of gamma-linolenic, stearidonic and eicosapentaenoic acids on the fatty acid composition of blood lipids and mononuclear cells in human volunteers. Prostaglandins Leukot. Essent. Fatty Acids. 2004 Jun;70(6):529-38.

2. Levin G, Duffin KL, Obukowicz MG, et al. Differential metabolism of dihomo-gamma-linolenic acid and arachidonic acid by cyclo-oxygenase-1 and cyclo-oxygenase-2: implications for cellular synthesis of prostaglandin E1 and prostaglandin E2. Biochem. J. 2002 Jul 15;365(Pt 2):489-96.

3. Barham, JB, Edens, MB, Fonteh, AN, et al. Addition of eicosapentaenoic acid to gamma-linolenic acid-supplemented diets prevents serum arachidonic acid accumulation in humans. J. Nutr. 2000 Aug;130(8):1925-31.

4. Johnson MM, Swan DD, Surette ME, et al. Dietary supplementation with gamma-linolenic acid alters fatty acid content and eicosanoid production in healthy humans. J Nutr. 1997 Aug;127(8):1435-44.

5. Ziboh VA, Fletcher MP. Dose-response effects of dietary gamma-linolenic acid-enriched oils on human polymorphonuclear-neutrophil biosynthesis of leukotriene B4. Am J Clin Nutr. 1992 Jan;55(1):39-45.

6. Chilton-Lopez, Surette ME, Swan DD, et al. Metabolism of gammalinolenic acid in human neutrophils. J Immunol. 1996 Apr 15;156(8):2941-7.

7. Umeda-Sawada R, Ogawa M, Igarashi O. 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). Lipids. 1998 Jun;33(6):567-72.

8. 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 Jul;26(7):512-6.

9. Fujiyama-Fujiwara, Y. Umeda-Sawada R, Kuzuyama M, Igarashi O. Effects of sesamin on the fatty acid composition of the liver of rats fed N-6 and N-3 fatty acid rich diet. J. Nutr. Sci. Vitaminol. (Tokyo) 1995 Apr;41(2):217-25.

10. Gu, JY, Wakizono Y, Tsujita A, et al. 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. Biosci. Biotechnol. Biochem. 1995 Dec; 59(12):2198-202.

11. Chavali SR, Zhong WW, Forse RA. 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. Prostaglandins Leukot Essent Fatty Acids. 1998 Mar;58(3):185-91.

12. Akimoto K, Kitagawa Y, Akamatsu T, et al. Protective effects of sesamin against liver damage caused by alcohol or carbon tetrachloride in rodents. Ann Nutr Metab. 1993;37(4):218-24.

13. el Boustani S, Causse JE, Descomps B, et al. Direct in vivo characterization of delta 5 desaturase activity in humans by deuterium labeling: effect of insulin. Metabolism. 1989 Apr;38(4):315-21.

14. Pelikanova T, Kohout M, Base J, et al. Effect of acute hyperinsulinemia on fatty acid composition of serum lipids in non-insulin-dependent diabetics and healthy men. Clin Chim Acta. 1991 Dec 16;203(2-3):329-37.

15. van Doormaal JJ, Muskiet FA, van Ballegooie E, et al. The plasma and erythrocyte fatty acid composition of poorly controlled, insulin-dependent (type I) diabetic patients and the effect of improved metabolic control. Clin Chim Acta. 1984 Dec 29;144(2-3):203-12.

16. Medeiros LC, Liu YW, Park S, et al. Insulin, but not estrogen, correlated with indexes of desaturase function in obese women. Horm Metab Res. 1995 May;27(5):235-8.

17. Faas FH, Carter WJ. Altered microsomal phospholipid composition in the streptozotocin diabetic rat. Lipids. 1983 Apr;18(4):339-42.

18. Holman RT, Johnson SB, Gerrard JM, et al. Arachidonic acid deficiency in streptozotocin-induced diabetes. Proc Natl Acad Sci U S A. 1983 Apr;80(8):2375-9.

19. Huang YS, Horrobin DF, Manku MS, et al. Tissue phospholipid fatty acid composition in the diabetic rat. Lipids. 1984 May;19(5):367-70.

20. Dias VC, Parsons HG. Modulation in delta 9, delta 6, and delta 5 fatty acid desaturase activity in the human intestinal CaCo-2 cell line. J Lipid Res. 1995 Mar;36(3):552-63.

21. Gronn M, Christensen E, Hagve TA, et al. Effects of dietary purified eicosapentaenoic acid (20:5 (n-3)) and docosahexaenoic acid (22:6(n-3)) on fatty acid desaturation and oxidation in isolated rat liver cells. Biochim Biophys Acta. 1992 Apr 8;1125(1):35-43.

22. Christensen, J.H. N-3 fatty acids and the risk of sudden cardiac death. Emphasis on heart rate variability. Dan. Med. Bull. 2003 Nov;50(4): 347-67.

23. Browning LM. n-3 Polyunsaturated fatty acids, inflammation and obesity-related disease. Proc Nutr Soc. 2003 May;62(2):447-53.

24. Heller A, Koch T, Schmeck J, et al. Lipid mediators in inflammatory disorders. Drugs. 1998 Apr;55(4):487-96.

25. Horrobin DF. Loss of delta-6-desaturase activity as a key factor in aging. Med Hypotheses. 1981 Sep;7(9):1211-20.

26. Bolton-Smith C, Woodward M, Tavendale R. Evidence for age-related differences in the fatty acid composition of human adipose tissue, independent of diet. Eur J Clin Nutr. 1997 Sep;51(9):619-24.

27. Biagi PL, Bordoni A, Hrelia S, et al. Gamma-linolenic acid dietary supplementation can reverse the aging influence on rat liver microsome delta 6-desaturase activity. Biochim Biophys Acta. 1991 May 8;1083(2):187-92.