Nutrition Research and Practice

The Korean Nutrition Society (한국영양학회)
권호 표지
DOI QR코드

DOI QR Code

Effect of soy isoflavones supplement on climacteric symptoms, bone biomarkers, and quality of life in Korean postmenopausal women: a randomized clinical trial

  • Lee, Hansongyi (Department of Medical Nutrition, Graduate School of East-West Medical Science, Kyung Hee University) ;
  • Choue, Ryowon (Department of Medical Nutrition, Graduate School of East-West Medical Science, Kyung Hee University) ;
  • Lim, Hyunjung (Department of Medical Nutrition, Graduate School of East-West Medical Science, Kyung Hee University)
  • Received : 2016.11.02
  • Accepted : 2017.02.27
  • Published : 2017.06.01
Download PDF
⟨ Previous Next ⟩

Abstract

BACKGROUND/OBJECTIVES: Soy isoflavones are expected to improve menopausal symptoms and osteoporosis in women. However, their efficacy is still inconclusive, and there was limited data for postmenopausal women in South Korea. We examined the effects of soy isoflavones on climacteric symptoms, bone biomarkers, and quality of life in Korean postmenopausal women. SUBJECTS/METHODS: A randomized, double-blind study design was used. Eighty-seven participants who had undergone natural menopause were randomly administered either 70 mg/day isoflavones (n = 43) or placebo (n = 41) for 12 weeks. We assessed the Kupperman index for climacteric symptoms and the menopause-specific quality of life (MENQOL) questionnaire for quality of the life. Biomarkers of bone metabolism were also measured in serum bone-specific alkaline phosphatase (BALP), osteocalcin (OC), N- and C-terminal cross-linking telopeptides of type Ι collagen (NTx, CTx), and urine-deoxypyridinolin (u-DPD). RESULTS: Scores of the Kupperman index were decreased in both the isoflavones group ($-7.0{\pm}15.8$, P = 0.0074) and placebo group ($-6.3{\pm}14.6$, P = 0.0064) during the intervention, but no significant difference was noted between the groups. Regarding the bone formation markers, the level of serum BALP increased by $6.3{\pm}4.1%$ (P = 0.004) and OC increased by $9.3{\pm}6.2%$ (P < 0.001), meanwhile those of the placebo were not changed. For the bone resorption markers, NTx, CTx, and u-DPD were not significantly different in either group. MENQOL was significant decreased in the isoflavone group ($-0.6{\pm}0.5$) and placebo group ($-0.6{\pm}0.4$), with a significant difference between groups (P = 0.0228). CONCLUSIONS: Our study suggests that 70 mg isoflavones supplement has beneficial effects on bone formation markers; however, it showed no benefit compared to the placebo on climacteric symptoms or quality of life.

Keywords

References

  1. Han KK, Soares JM Jr, Haidar MA, de Lima GR, Baracat EC. Benefits of soy isoflavone therapeutic regimen on menopausal symptoms. Obstet Gynecol 2002;99:389-94.
  2. Nahas EA, Nahas-Neto J, Orsatti FL, Carvalho EP, Oliveira ML, Dias R. Efficacy and safety of a soy isoflavone extract in postmenopausal women: a randomized, double-blind, and placebo-controlled study. Maturitas 2007;58:249-58. https://doi.org/10.1016/j.maturitas.2007.08.012
  3. Ferrari A. Soy extract phytoestrogens with high dose of isoflavones for menopausal symptoms. J Obstet Gynaecol Res 2009;35:1083-90. https://doi.org/10.1111/j.1447-0756.2009.01058.x
  4. Albertazzi P, Steel SA, Bottazzi M. Effect of pure genistein on bone markers and hot flushes. Climacteric 2005;8:371-9. https://doi.org/10.1080/13697130500345257
  5. Cancellieri F, De Leo V, Genazzani AD, Nappi C, Parenti GL, Polatti F, Ragni N, Savoca S, Teglio L, Finelli F, Nichelatti M. Efficacy on menopausal neurovegetative symptoms and some plasma lipids blood levels of an herbal product containing isoflavones and other plant extracts. Maturitas 2007;56:249-56. https://doi.org/10.1016/j.maturitas.2006.07.001
  6. Evans M, Elliott JG, Sharma P, Berman R, Guthrie N. The effect of synthetic genistein on menopause symptom management in healthy postmenopausal women: a multi-center, randomized, placebocontrolled study. Maturitas 2011;68:189-96. https://doi.org/10.1016/j.maturitas.2010.11.012
  7. Yamori Y, Moriguchi EH, Teramoto T, Miura A, Fukui Y, Honda KI, Fukui M, Nara Y, Taira K, Moriguchi Y. Soybean isoflavones reduce postmenopausal bone resorption in female Japanese immigrants in Brazil: a ten-week study. J Am Coll Nutr 2002;21:560-3. https://doi.org/10.1080/07315724.2002.10719255
  8. Murkies AL, Lombard C, Strauss BJ, Wilcox G, Burger HG, Morton MS. Dietary flour supplementation decreases post-menopausal hot flushes: effect of soy and wheat. Maturitas 1995;21:189-95. https://doi.org/10.1016/0378-5122(95)00899-V
  9. Washburn S, Burke GL, Morgan T, Anthony M. Effect of soy protein supplementation on serum lipoproteins, blood pressure, and menopausal symptoms in perimenopausal women. Menopause 1999;6:7-13.
  10. Alekel DL, Germain AS, Peterson CT, Hanson KB, Stewart JW, Toda T. Isoflavone-rich soy protein isolate attenuates bone loss in the lumbar spine of perimenopausal women. Am J Clin Nutr 2000;72: 844-52. https://doi.org/10.1093/ajcn/72.3.844
  11. Wangen KE, Duncan AM, Merz-Demlow BE, Xu X, Marcus R, Phipps WR, Kurzer MS. Effects of soy isoflavones on markers of bone turnover in premenopausal and postmenopausal women. J Clin Endocrinol Metab 2000;85:3043-8.
  12. Dennerstein L, Dudley EC, Hopper JL, Guthrie JR, Burger HG. A prospective population-based study of menopausal symptoms. Obstet Gynecol 2000;96:351-8.
  13. Levis S, Strickman-Stein N, Ganjei-Azar P, Xu P, Doerge DR, Krischer J. Soy isoflavones in the prevention of menopausal bone loss and menopausal symptoms: a randomized, double-blind trial. Arch Intern Med 2011;171:1363-9. https://doi.org/10.1001/archinternmed.2011.330
  14. Dodin S, Lemay A, Jacques H, Legare F, Forest JC, Masse B. The effects of flaxseed dietary supplement on lipid profile, bone mineral density, and symptoms in menopausal women: a randomized, double-blind, wheat germ placebo-controlled clinical trial. J Clin Endocrinol Metab 2005;90:1390-7. https://doi.org/10.1210/jc.2004-1148
  15. Khaodhiar L, Ricciotti HA, Li L, Pan W, Schickel M, Zhou J, Blackburn GL. Daidzein-rich isoflavone aglycones are potentially effective in reducing hot flashes in menopausal women. Menopause 2008;15: 125-32.
  16. Nelson HD, Vesco KK, Haney E, Fu R, Nedrow A, Miller J, Nicolaidis C, Walker M, Humphrey L. Nonhormonal therapies for menopausal hot flashes: systematic review and meta-analysis. JAMA 2006;295: 2057-71. https://doi.org/10.1001/jama.295.17.2057
  17. Lee MJ, Kim JH. Estimated dietary isoflavone intake among Korean adults. Nutr Res Pract 2007;1:206-11. https://doi.org/10.4162/nrp.2007.1.3.206
  18. de Kleijn MJ, van der Schouw YT, Wilson PW, Adlercreutz H, Mazur W, Grobbee DE, Jacques PF. Intake of dietary phytoestrogens is low in postmenopausal women in the United States: the Framingham study(1-4). J Nutr 2001;131:1826-32. https://doi.org/10.1093/jn/131.6.1826
  19. Keinan-Boker L, Peeters PH, Mulligan AA, Navarro C, Slimani N, Mattisson I, Lundin E, McTaggart A, Allen NE, Overvad K, Tjonneland A, Clavel-Chapelon F, Linseisen J, Haftenberger M, Lagiou P, Kalapothaki V, Evangelista A, Frasca G, Bueno-de-Mesquita HB, van der Schouw YT, Engeset D, Skeie G, Tormo MJ, Ardanaz E, Charrondiere UR, Riboli E. Soy product consumption in 10 European countries: the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Public Health Nutr 2002;5:1217-26. https://doi.org/10.1079/PHN2002400
  20. Chun OK, Chung SJ, Song WO. Estimated dietary flavonoid intake and major food sources of U.S. adults. J Nutr 2007;137:1244-52. https://doi.org/10.1093/jn/137.5.1244
  21. National Research Institute of Health (KR). Clinical Research Information Service [Internet]. Cheongju: National Research Institute of Health; [cited 2015 December 30]. Available from: https://cris.nih.go.kr/cris/index.jsp.
  22. Petri Nahas E, Nahas 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;48:372-80. https://doi.org/10.1016/j.maturitas.2003.09.026
  23. Association of Official Analytical Chemists (US). Official Methods of Analysis of AOAC International. 18th ed. Gaithersburg (MD): AOAC International; 2005.
  24. Food Safety Commission of Japan. Fundamental concepts in the safety assessment of foods containing soy isoflavones for the purpose of specified health use, in Japanese [Internet]. Tokyo: Food Safety Commission of Japan; 2006 [cited 2015 June 6]. Available from: http://www.fsc.go.jp/sonota/daizu_isoflavone.html.
  25. Lee SK, Lee MJ, Yoon S, Kwon DJ. Estimated isoflavone intake from soy products in Korean middle-aged women. J Korean Soc Food Sci Nutr 2000;29:948-56.
  26. Bhagwat S, Haytowitz DB, Holden JM. USDA database on the isoflavone content of selected food: release 2.0 [Internet]. Beltsville (MD): U.S. Department of Agriculture; 2008 [cited 2015 August 14]. Available from: https://www.ars.usda.gov/ARSUserFiles/80400525/Data/isoflav/Isoflav_R2.pdf.
  27. Wakai K, Egami I, Kato K, Kawamura T, Tamakoshi A, Lin Y, Nakayama T, Wada M, Ohno Y. Dietary intake and sources of isoflavones among Japanese. Nutr Cancer 1999;33:139-45. https://doi.org/10.1207/S15327914NC330204
  28. Kim MS, Lee YS. A study on the menopause management practice and the quality of life in climacteric women. J Korean Soc Matern Child Health 1999;3:75-87.
  29. Hilditch JR, Lewis J, Peter A, van Maris B, Ross A, Franssen E, Guyatt GH, Norton PG, Dunn E. A menopause-specific quality of life questionnaire: development and psychometric properties. Maturitas 1996;24:161-75. https://doi.org/10.1016/0378-5122(96)01038-9
  30. Moher D, Schulz KF, Altman DG. The CONSORT statement: revised recommendations for improving the quality of reports of parallel-group randomised trials. Lancet 2001;357:1191-4. https://doi.org/10.1016/S0140-6736(00)04337-3
  31. Ye YB, Wang ZL, Zhuo SY, Lu W, Liao HF, Verbruggen M, Fang S, Mai HY, Chen YM, Su YX. Soy germ isoflavones improve menopausal symptoms but have no effect on blood lipids in early postmenopausal Chinese women: a randomized placebo-controlled trial. Menopause 2012;19:791-8. https://doi.org/10.1097/gme.0b013e31823dbeda
  32. Taku K, Melby MK, Kronenberg F, Kurzer MS, Messina M. Extracted or synthesized soybean isoflavones reduce menopausal hot flash frequency and severity: systematic review and meta-analysis of randomized controlled trials. Menopause 2012;19:776-90. https://doi.org/10.1097/gme.0b013e3182410159
  33. Taku K, Melby MK, Kurzer MS, Mizuno S, Watanabe S, Ishimi Y. Effects of soy isoflavone supplements on bone turnover markers in menopausal women: systematic review and meta-analysis of randomized controlled trials. Bone 2010;47:413-23. https://doi.org/10.1016/j.bone.2010.05.001
  34. Morabito N, Crisafulli A, Vergara C, Gaudio A, Lasco A, Frisina N, D'Anna R, Corrado F, Pizzoleo MA, Cincotta M, Altavilla D, Ientile R, Squadrito F. Effects of genistein and hormone-replacement therapy on bone loss in early postmenopausal women: a randomized double-blind placebo-controlled study. J Bone Miner Res 2002;17:1904-12. https://doi.org/10.1359/jbmr.2002.17.10.1904
  35. Choi EM, Suh KS, Kim YS, Choue RW, Koo SJ. Soybean ethanol extract increases the function of osteoblastic MC3T3-E1 cells. Phytochemistry 2001;56:733-9. https://doi.org/10.1016/S0031-9422(00)00484-2
  36. Kanno S, Hirano S, Kayama F. Effects of phytoestrogens and environmental estrogens on osteoblastic differentiation in MC3T3-E1 cells. Toxicology 2004;196:137-45. https://doi.org/10.1016/j.tox.2003.12.002
  37. Sugimoto T, Nishiyama K, Kuribayashi F, Chihara K. Serum levels of insulin-like growth factor (IGF) I, IGF-binding protein (IGFBP)-2, and IGFBP-3 in osteoporotic patients with and without spinal fractures. J Bone Miner Res 1997;12:1272-9. https://doi.org/10.1359/jbmr.1997.12.8.1272
  38. Dalais FS, Ebeling PR, Kotsopoulos D, McGrath BP, Teede HJ. The effects of soy protein containing isoflavones on lipids and indices of bone resorption in postmenopausal women. Clin Endocrinol (Oxf) 2003;58:704-9. https://doi.org/10.1046/j.1365-2265.2003.01771.x
  39. Vedrine N, Mathey J, Morand C, Brandolini M, Davicco MJ, Guy L, Remesy C, Coxam V, Manach C. One-month exposure to soy isoflavones did not induce the ability to produce equol in postmenopausal women. Eur J Clin Nutr 2006;60:1039-45. https://doi.org/10.1038/sj.ejcn.1602415
  40. Thomas AJ, Ismail R, Taylor-Swanson L, Cray L, Schnall JG, Mitchell ES, Woods NF. Effects of isoflavones and amino acid therapies for hot flashes and co-occurring symptoms during the menopausal transition and early postmenopause: a systematic review. Maturitas 2014;78:263-76. https://doi.org/10.1016/j.maturitas.2014.05.007
  41. Wu J, Oka J, Higuchi M, Tabata I, Toda T, Fujioka M, Fuku N, Teramoto T, Okuhira T, Ueno T, Uchiyama S, Urata K, Yamada K, Ishimi Y. Cooperative effects of isoflavones and exercise on bone and lipid metabolism in postmenopausal Japanese women: a randomized placebo-controlled trial. Metabolism 2006;55:423-33. https://doi.org/10.1016/j.metabol.2005.10.002
  42. Hall WL, Vafeiadou K, Hallund J, Bugel S, Koebnick C, Reimann M, Ferrari M, Branca F, Talbot D, Dadd T, Nilsson M, Dahlman-Wright K, Gustafsson JA, Minihane AM, Williams CM. Soy-isoflavoneenriched foods and inflammatory biomarkers of cardiovascular disease risk in postmenopausal women: interactions with genotype and equol production. Am J Clin Nutr 2005;82:1260-8. https://doi.org/10.1093/ajcn/82.6.1260
  43. Tousen Y, Ezaki J, Fujii Y, Ueno T, Nishimuta M, Ishimi Y. Natural S-equol decreases bone resorption in postmenopausal, non-equolproducing Japanese women: a pilot randomized, placebo-controlled trial. Menopause 2011;18:563-74. https://doi.org/10.1097/gme.0b013e3181f85aa7
  44. Loprinzi CL, Sloan J, Stearns V, Slack R, Iyengar M, Diekmann B, Kimmick G, Lovato J, Gordon P, Pandya K, Guttuso T Jr, Barton D, Novotny P. Newer antidepressants and gabapentin for hot flashes: an individual patient pooled analysis. J Clin Oncol 2009;27:2831-7. https://doi.org/10.1200/JCO.2008.19.6253
  45. U.S. Food and Drug Administration. Guidance for industry estrogen and estrogen/progestin drug products to treat vasomotor symptoms and vulvar and vaginal atrophy symptoms: recommendations for clinical evaluation [Internet]. Rockville (MD): U.S. Food and Drug Administration; 2003 [cited 2014 July 20]. Available from: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulat oryInformation/Guidances/ucm071643.pdf.
  46. Enck P, Klosterhalfen S, Zipfel S. Novel study designs to investigate the placebo response. BMC Med Res Methodol 2011;11:90. https://doi.org/10.1186/1471-2288-11-90

Cited by

  1. Effects of Phytoestrogen Supplement on Quality of Life of Postmenopausal Women: A Systematic Review and Meta-Analysis of Randomized Controlled Trials vol.2019, pp.None, 2017, https://doi.org/10.1155/2019/3261280
  2. Biological Effect of Soy Isoflavones in the Prevention of Civilization Diseases vol.11, pp.7, 2017, https://doi.org/10.3390/nu11071660
  3. Isoflavones improve collagen I and glycosaminoglycans and prevent bone loss in type 1 diabetic rats vol.23, pp.1, 2020, https://doi.org/10.1080/13697137.2019.1627314
  4. Is soy protein effective in reducing cholesterol and improving bone health? vol.11, pp.1, 2017, https://doi.org/10.1039/c9fo01081e
  5. Soy isoflavones prevent bone resorption and loss, a systematic review and meta-analysis of randomized controlled trials vol.60, pp.14, 2020, https://doi.org/10.1080/10408398.2019.1635078
  6. Animal, Plant, Collagen and Blended Dietary Proteins: Effects on Musculoskeletal Outcomes vol.12, pp.9, 2017, https://doi.org/10.3390/nu12092670
  7. Therapeutic Potential of Isoflavones with an Emphasis on Daidzein vol.2021, pp.None, 2021, https://doi.org/10.1155/2021/6331630
  8. Effects of Soy Isoflavones on Biochemical Markers of Bone Metabolism in Postmenopausal Women: A Systematic Review and Meta-Analysis of Randomized Controlled Trials vol.18, pp.10, 2017, https://doi.org/10.3390/ijerph18105346
  9. Botanicals in Postmenopausal Osteoporosis vol.13, pp.5, 2017, https://doi.org/10.3390/nu13051609
  10. Current Perspectives on the Beneficial Effects of Soybean Isoflavones and Their Metabolites for Humans vol.10, pp.7, 2021, https://doi.org/10.3390/antiox10071064
  11. The effect of Cornus mas extract consumption on bone biomarkers and inflammation in postmenopausal women: A randomized clinical trial vol.35, pp.8, 2017, https://doi.org/10.1002/ptr.7143
  12. Efficacy and Safety of a Standardized Soy and Hop Extract on Menopausal Symptoms: A 12-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Trial vol.27, pp.11, 2017, https://doi.org/10.1089/acm.2021.0027