Korean J Nutr.  2010 Apr;43(2):123-131. 10.4163/kjn.2010.43.2.123.

The Effect of Isoflavone and Gamma-linolenic Acid Supplementation on Serum Lipids and Menopausal Symptoms in Postmenopausal Women

• Gwak JH
• Kim JY
• Kim HJ
• Shin DH
• Lee JH

• KMID: 2267976
• DOI: http://doi.org/10.4163/kjn.2010.43.2.123

Abstract

This study was performed to examine the combined effects of gamma linolenic acid and isoflavone supplementation on menopausal symptoms and serum lipids in 73 postmenopausal women. A total subjects were randomly assigned to isoflavone (30 mg) + gamma-linolenic acid (110 mg) group or placebo group. We measured menopausal symptoms by modified Kupperman Index (KI) and oxidized LDL, lipid peroxides, blood components and anthropometric parameters before and after the 12 week intervention period. After the 12 weeks of supplementation, supplement group and placebo group showed a significant reduction of modified kupperman index (p < 0.001). Isoflavone (30 mg) + gamma-linolenic acid (110 mg) supplement group showed a significant reduction of oxidized LDL cholesterol concentration (p = 0.006) whereas placebo group did not show significant change. Isoflavone and gamma-linolenic acid consumption did not significantly affect plasma concentrations of total, LDL, HDL cholesterol, triglyceride, apo A1, B and blood components. The result of present study demonstrated the supplementation of 30 mg isoflavone and 110 mg gamma-linolenic acid per day for 12 weeks may protect LDL cholesterol from oxidative stress.

Keyword

isoflavone; gamma-linolenic acid; menopausal symptoms; serum lipids; postmenopausal women

MeSH Terms

Apolipoprotein A-I
Cholesterol, HDL
Cholesterol, LDL
Female
gamma-Linolenic Acid
Humans
Lipid Peroxides
Lipoproteins, LDL
Oxidative Stress
Plasma
Apolipoprotein A-I
Cholesterol, HDL
Cholesterol, LDL
Lipid Peroxides
Lipoproteins, LDL
gamma-Linolenic Acid

Reference

1. Yaffe K, Sawaya G, Lieberburg I, Grady D. Estrogen theraphy in postmenopausal women: effects on cognitive function and dementia. JAMA. 1998. 279:688–695.

2. Rosano GM, Vitale C, Marazzi G, Volterrani M. Menopause and cardiovascular disease: the evidence. Climacteric. 2007. 10:19–24.

3. Collins P, Rosano G, Casey C. Management of cardiovascular risk in the perimenopausal women: a consensus statement of European cardiologists and gynecologists. Climacteric. 2007. 10:508–526.

4. Barentsen R. The climacteric in the Netherlands: a review of Dutch studies on epidemiology, attiudes and use of hormone replacement therapy. Eur J Obstet Gynecol Reprod Biol. 1996. 64:suppl. S7–S11.

5. Beral V. Breast cancer and hormone-replacement theraphy in the Million Women Study. Lancet. 2003. 362:419–427.

6. Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial. JAMA. 2002. 288:321–333.

7. Boker LK, van der Schouw YT, de Kleijn MJ, Jasques PF, Grobbee DE, Peeters PH. Intake of dietary phytoestrogens by Dutch women. J Nutr. 2002. 132:1319–1328.

8. Morito K, Hirose T, Kinjo J. Interaction of phytoestrogens with estrogen receptors alpha and beta. Biol Pharm Bull. 2001. 24:351–356.

9. Petri Nahas E, Nahás Neto J, De Luca L, Traiman P, Pontes A, Dalben I. Benefits of soy germ isoflavones in postmenopausal women with contraindication for conventional hormone replacement therapy. Maturitas. 2004. 48(4):372–380.

10. Han KK, Soares JM Jr, Haidar MA, de Lima GR, Baracat EC. Benefits of soy isoflavone therapeutic regimen on menopausal symptoms. Obstet Gynecol. 2002. 99(3):389–394.

11. Kaari C, Haidar MA, Júnior JM, Nunes MG, Quadros LG, Kemp C, Stavale JN, Baracat EC. Randomized clinical trial comparing conjugated equine estrogens and isoflavones in postmenopausal women: a pilot study. Maturitas. 2006. 53(1):49–58.

12. Albertazzi P, Pansini F, Bonaccorsi G, Zanotti L, Forini E, De Aloysio D. The effect of dietary soy supplementation on hot flushes. Obstet Gynecol. 1997. 91(1):6–11.

13. Cheng G, Wilczek B, Warner M, Gustafsson JA, Landgren BM. Isoflavone treatment for acute menopausal symptoms. Menopause. 2007. 14:468–473.

14. Kotsopoulos D, Dalais FS, Liang YL, McGrath BP, Teede HJ. The effects of soy protein containing phytoestrogens on menopausal symptoms in postmenopausal women. Climacteric. 2000. 3:161–167.

15. Wangen KE, Duncan AM, Xu X, Kurzer MS. Soy isoflavones improve plasma lipids in normocholesterolemic and mildly hypercholesterolemic postmenopausal women. Am J Clin Nutr. 2001. 73:225–231.

16. Jenkins DJ, Kendall CW, Garsetti M, Rosenberg-Zand RS, Jackson CJ, Agarwal S, Rao AV, Diamandis EP, Parker T, Faulkner D, Vuksan V, Vidgen E. Effect of soy protein foods on low-density lipoprotein oxidation and ex vivo sex hormone receptor activity-a controlled crossover trial. Metabolism. 2000. 49:537–543.

17. Lee JH, Kim EM, Chae JS, Jang YS, Lee JH, Lee G. The effect of isoflavone supplement on plasma lipid & antioxidant status in hypercholesterolemic postmenopausal women. Korean J Nutr. 2003. 36(6):603–612.

18. Ishikawa T, Fujiyama Y, Igarashi O, Morino M, Tada N, Kagami A, Sakamoto T, Nagano M, Nakamura H. Effects of gammalinolenic acid on plasma lipoproteins and apolipoproteins. Atherosclerosis. 1989. 75(2-3):95–104.

19. Abraham RD, Riemersma RA, Elton RA, Macintyre C, Oliver MF. Effects of safflower oil and evening primrose oil in men with a low dihomo-gamma-linolenic level. Atherosclerosis. 1990. 81(3):199–208.

20. Guivernau M, Meza N, Barja P, Roman O. Clinical and experimental study on the long-term effect of dietary gamma-linolenic acid on plasma lipids, platelet aggregation, thromboxane formation, and prostacyclin production. Prostaglandins Leukot Essent Fatty Acids. 1994. 51(5):311–316.

21. Hidalgo LA, Chedraui PA, Morocho N, Ross S, San Miguel G. The effect of red clover isoflavones on menopausal symptoms, lipids and vaginal cytology in menopausal women: a randomized, double-blind, placebo-controlled study. Gynecol Endocrinol. 2005. 21(5):257–264.

22. Sammartino A, Tommaselli GA, Gargano V, di Carlo C, Attianese W, Nappi C. Short-term effects of a combination of isoflavones, lignans and Cimicifuga racemosa on climacteric-related symptoms in postmenopausal women: a double-blind, randomized, placebo-controlled trial. Gynecol Endocrinol. 2006. 22(11):646–650.

23. Park HM. The efficacy of phytoestrogen in postmenopausal women. J Korean Soc Menopause. 2007. 50(3):389–415.

24. Lee SY, Lee MJ, Yoon S, Kwon DJ. Estimated Isoflavone intake from soy products in korean middle-aged women. J Korean Soc Food Sci Nutr. 2000. 29(5):948–956.

25. Hsieh CY, Santell RC, Haslam SZ, Heiferich WG. Estrogenic effects of genistein on the growth of estrogen recepter-positive human breast cancer (MCF-7) cells in vitro and in vivo. Cancer Res. 1998. 58:3833–3838.

26. Allered CA, Allred KF, Ju YH, Virant SM, Helferich WG. Soy diets containning varying amounts of genistein stimulate growth of estrogen-dependent (MCF-7) tumors in dose-dependent manner. Cancer Res. 2001. 61:5045–5050.

27. Hankinson SE, Eliassen AH. Endogenous estrogen, testosterone and progesterone levels in relation to breast cancer risk. J Steroid Biochem Mol Biol. 2007. 106:24–30.

28. Verhoeven MO, van der Mooren MJ, van de Weijer PH, Verdegem PJ, van der Burgt LM, Kenemans P. CuraTrial Research Group. Effect of a combination of isoflavones and Actaea racemosa Linnaeus on climacteric symptoms in healthy symptomatic perimenopausal women: a 12-week randomized, placebo-controlled, double-blind study. Menopause. 2005. 12(4):412–420.

29. Baber RJ, Templeman C, Morton T, Kelly GE, West L. Randomized placebo-controlled trial of an isoflavone supplement and menopausal symptoms in women. Climacteric. 1999. 2(2):85–92.

30. Knight DC, Howes JB, Eden JA, Howes LG. Effects on menopausal symptoms and acceptability of isoflavone-containing soy powder dietary supplementation. Climacteric. 2001. 4(1):13–18.

31. St Germain A, Peterson CT, Robinson JG, Alekel DL. Isoflavone-rich or isoflavone-poor soy protein does not reduce menopausal symptoms during 24 weeks of treatment. Menopause. 2001. 8(1):17–26.

32. Dalais FS, Rice GE, Wahlqvist ML, Grehan M, Murkies AL, Medley G, Ayton R, Strauss BJ. Effects of dietary phytoestrogens in postmenopausal women. Climacteric. 1998. 1(2):124–129.

33. Nagata C, Takasuka N, Kurisu Y, Shimizu H. Decreased serum total cholesterol concertration is associated with high intake of soy products in Japanese men and women. J Nutr. 1998. 128:209–213.

34. Potter SM. Overview of proposed mechanisms for the hypocholesterolemic effec soy. J Nutr. 1995. 125:606S–611S.

35. Hodgson JM, Puddey IB, Croft KD, Mori TA, Rivera J, Beilin LJ. Isoflavonoids do not inhibit in vivo lipid peroxidation in subjects with high-normal blood pressure. Atherosclerosis. 1999. 145(1):167–172.

36. Chio IS, Bea YJ, Jang S, Lee DH, Yun ME, Lee HS, Kim MH, Lee SH, Sung CJ. Effect of soy isoflavone supplementation and exercise on serum lipids in postmenopausal women. Korean J Nutr. 2005. 38(6):411–418.

37. Dewell A, Hollenbeck CB, Bruce B. The effects of soy-derived phytoestrogens on serum lipids and lipoproteins in moderately hypercholesterolemic postmenopausal women. J Chin Endocriol Metab. 2002. 87:118–121.

38. Simons LA, von Konigsmark M, Simons J, Celermajer DS. Phytoestrogens do not influence lipoprotein levels or endothelial function in healthy postmenopausal women. Am J Cardiol. 2000. 85:1297–1301.

39. Howes JB, Sulllivan D, Lai N, Nestel P, Pomeroy S, Wesf L, Eden JA, Howes LG. The effects of dietary supplementation with isoflavones from red clover on the lipoprotein profiles of post menopausal women with mild to moderate hypercholesterolaemia. Atherosclerosis. 2000. 152:143–147.

40. Park BS, Zammit AV. Effect of dietary oil containg r-linolenic acid on the plasma lipid levels and thrombotic activity in rats. Korean J Nutr. 2003. 36(9):889–897.

41. Jenkins DJ, Kendall CW, Jackson CJ, Connelly PW, Parker T, Faulkner D, Vidgen E, Cunnane SC, Leiter LA, Josse RG. Effects of high- and low-isoflavone soyfoods on blood lipids, oxidized LDL, homocysteine, and blood pressure in hyperlipidemic men and women. Am J Clin Nutr. 2002. 76:365–372.

42. Tikkanen MJ, Wahala K, Ojala S, Vihma V, Adlercreutz H. Effect of soybean phytoestrogen intake on low density lipoprotein oxidation resistance. Proc Natl Acad Sci. 1998. 95:3106–3110.

43. Wei H, Bowen R, Cai Q, Barnes S, Wang Y. Antioxidant and antipromotional effects of the soybean isoflavone genistein. Proc Soc Biol Med. 1995. 208:124–130.

44. Jenkins DJ, Kendall CW, Garsetti M, Rosenberg-Zand RS, Jackson CJ, Agarwal S, Rao AV, Diamandis EP, Parker T, Faulkner D, Vuksan V, Vidgen E. Effect of soy protein foods on low density lipoprotein oxidation and ex vivo sex hormone receptor activity-a controlled crossover trial. Metabolism. 2000. 49:537–543.

45. Ruiz-Larrea MB, Mohan AR, Paganga G, Miller NJ, Bolwell GP, Rice-Evans CA. Antioxidant activity of phytoestrogenic isoflavones. Free Radic Res. 1997. 26(1):63–70.

46. Arora A, Nair MG, Strasburg GM. Antioxidant activities of isoflavones and their biological metabolites in a liposomal system. Arch Biochem Biophys. 1998. 356(2):133–141.

47. Giles D, Wei H. Effect of structurally related flavones/isoflavones on hydrogen peroxide production and oxidative DNA damage in phorbol ester-stimulated HL-60 cells. Nutr Cancer. 1997. 29(1):77–82.

48. Cai Q, Wei H. Effect of dietary genistein on antioxidant enzyme activities in SENCAR mice. Nutr Cancer. 1996. 25(1):1–7.

49. Jenkins DJ, Kendall CW, Vidgen E, Vuksan V, Jackson CJ, Augustin LS, Lee B, Garsetti M, Agarwal S, Rao AV, Cagampang GB, Fulgoni V. Effect of soy-based breakfast cereal on blood lipids and oxidized low-density lipoprotein. Metabolism. 2000. 49(11):1496–1500.