Osteoporosis International

, Volume 18, Issue 5, pp 671–679

Modulation of soy isoflavones bioavailability and subsequent effects on bone health in ovariectomized rats: the case for equol

  • J. Mathey
  • J. Mardon
  • N. Fokialakis
  • C. Puel
  • S. Kati-Coulibaly
  • S. Mitakou
  • C. Bennetau-Pelissero
  • V. Lamothe
  • M. J. Davicco
  • P. Lebecque
  • M. N. Horcajada
  • V. Coxam
Original Article

Abstract

Introduction

Soy products are of particular interest because of their potential health benefits in a range of hormonal conditions, such as osteoporosis, due to their high content in phytoestrogens. Because equol, the main metabolite from soy isoflavones, is thought to be powerful, the present study was designated to evaluate the bone-sparing effects of equol by either providing the molecule through the diet or by eliciting its endogenous production by modulating intestinal microflora by short-chain fructooligosaccharides (sc-FOS) or live microbial (Lactobacillus casei) together with daidzein, its precursor.

Methods

A comparison with daidzein and genistein was also performed. Rats (3 months old) were ovariectomised (OVX) or sham-operated (SH). Ovariectomised rats were randomly assigned to six experimental diets for 3 months: a control diet (OVX), the control diet supplemented with either genistein (G), or daidzein (D), or equol (E) at the level of 10 μg/g body weight/d. The remaining OVX rats were given daidzein at the dose of 10 μg/g body weight/d, simultaneously with short-chain FOS (Actilight®, Beghin-Meiji) (D+FOS) or Lactobacillus casei (Actimel, Danone) (D+L). The SH rats were given the same control diet as OVX.

Results

Genistein, daidzein or equol exhibited a bone sparing effect. Indeed, total femoral bone mineral density (BMD) was significantly enhanced (compared to that of OVX rats), as was the metaphyseal compartment. Bone strength was improved by E consumption, but not by genistein or daidzein given alone. As far as the FOS diet is concerned, the addition of prebiotics significantly raised efficiency of the daidzein protective effect on both femoral BMD and mechanical properties. The effects of lactobacillus were similar, except that the increase in metaphyseal-BMD was not significant.

Conclusion

In conclusion, long-term equol consumption, like genistein and daidzein, in the ovariectomized rat, provides bone sparing effects. Adding indigestible sugars, such as FOS or live microbial as L. casei, in the diet significantly improves daidzein protective effects on the skeleton.

Keywords

Bone prevention Equol Isoflavones Pre- or probiotics Rat 

References

  1. 1.
    Kanis JA, Melton LJ 3rd, Christiansen C, Johnston CC, Khaltaev N (1994) The diagnosis of osteoporosis. J Bone Miner Res 9:1137–1141PubMedCrossRefGoogle Scholar
  2. 2.
    Katz A (2003) Observations and advertising: controversies in the prescribing of hormone replacement therapy. Health Care Women Int 24:927–939PubMedCrossRefGoogle Scholar
  3. 3.
    Cushman M (2003) Hormone therapies and vascular outcomes: who is at risk? J Thromb Thrombolysis 16:87–90PubMedCrossRefGoogle Scholar
  4. 4.
    Welnicka-Jaskiewicz M, Jassem J (2003) The risks and benefits of hormonal replacement therapy in healthy women and in breast cancer survivors. Cancer Treat Rev 29:355–361PubMedCrossRefGoogle Scholar
  5. 5.
    WHI (2002) Risks and benefits of estrogen plus progestin in healthy post menopausal women. JAMA 288:321–333CrossRefGoogle Scholar
  6. 6.
    Cauley JA, Zmuda JM, Ensrud KE, Bauer DC, Ettinger B (2001) Timing of estrogen replacement therapy for optimal osteoporosis prevention. J Clin Endocrinol Metab 86:5700–5705PubMedCrossRefGoogle Scholar
  7. 7.
    Setchell KD (1998) Phytoestrogens: the biochemistry, physiology, and implications for human health of soy isoflavones. Am J Clin Nutr 68:1333S–1346SPubMedGoogle Scholar
  8. 8.
    Murkies AL, Wilcox G, Davis SR (1998) Clinical review 92: phytoestrogens. J Clin Endocrinol Metab 83:297–303PubMedCrossRefGoogle Scholar
  9. 9.
    Adlercreutz H, Mazur W (1997) Phyto-oestrogens and Western diseases. Ann Med 29:95–120PubMedGoogle Scholar
  10. 10.
    Potter SM, Baum JA, Teng H, Stillman RJ, Shay NF, Erdman JW Jr (1998) Soy protein and isoflavones: their effects on blood lipids and bone density in postmenopausal women. Am J Clin Nutr 68:1375S–1379SPubMedGoogle Scholar
  11. 11.
    Alekel DL, Germain AS, Peterson CT, Hanson KB, Stewart JW, Toda T (2000) Isoflavone-rich soy protein isolate attenuates bone loss in the lumbar spine of perimenopausal women. Am J Clin Nutr 72:844–852PubMedGoogle Scholar
  12. 12.
    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 (2002) 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 17:1904–1912PubMedCrossRefGoogle Scholar
  13. 13.
    Wang H-J, Murphy PA (1994b) Isoflavone content in commercial soybean foods. J Agric Food Chem 42:1666–1673CrossRefGoogle Scholar
  14. 14.
    Setchell KD, Borriello SP, Hulme P, Kirk DN, Axelson M (1984) Nonsteroidal estrogens of dietary origin: possible roles in hormone-dependent disease. Am J Clin Nutr 40:569–578PubMedGoogle Scholar
  15. 15.
    Day AJ, DuPont MS, Ridley S, Rhodes M, Rhodes MJ, Morgan MR, Williamson G (1998) Deglycosylation of flavonoid and isoflavonoid glycosides by human small intestine and liver beta-glucosidase activity. FEBS Lett 436:71–75PubMedCrossRefGoogle Scholar
  16. 16.
    Setchell KD, Brown NM, Zimmer-Nechemias L, Brashear WT, Wolfe BE, Kirschner AS, Heubi JE (2002) Evidence for lack of absorption of soy isoflavone glycosides in humans, supporting the crucial role of intestinal metabolism for bioavailability. Am J Clin Nutr 76:447–453PubMedGoogle Scholar
  17. 17.
    Xu X, Harris KS, Wang HJ, Murphy PA, Hendrich S (1995) Bioavailability of soybean isoflavones depends upon gut microflora in women. J Nutr 125:2307–2315PubMedGoogle Scholar
  18. 18.
    Joannou GE, Kelly GE, Reeder AY, Waring M, Nelson C (1995) A urinary profile study of dietary phytoestrogens. The identification and mode of metabolism of new isoflavonoids. J Steroid Biochem Mol Biol 54:167–184PubMedCrossRefGoogle Scholar
  19. 19.
    Lampe JW, Karr SC, Hutchins AM, Slavin JL (1998) Urinary equol excretion with a soy challenge: influence of habitual diet. Proc Soc Exp Biol Med 217:335–339PubMedGoogle Scholar
  20. 20.
    Setchell KD, Brown NM, Lydeking-Olsen E (2002) The clinical importance of the metabolite equol-a clue to the effectiveness of soy and its isoflavones. J Nutr 132:3577–3584PubMedGoogle Scholar
  21. 21.
    Kalu DN (1991) The ovariectomized rat model of postmenopausal bone loss. Bone Miner 15:175–191PubMedCrossRefGoogle Scholar
  22. 22.
    Omi N, Aoi S, Murata K, Ezawa I (1994) Evaluation of the effect of soybean milk and soybean milk peptide on bone metabolism in the rat model with ovariectomized osteoporosis. J Nutr Sci Vitaminol (Tokyo) 40:201–211Google Scholar
  23. 23.
    Arjmandi BH, Getlinger MJ, Goyal NV, Alekel L, Hasler CM, Juma S, Drum ML, Hollis BW, Kukreja SC (1998) Role of soy protein with normal or reduced isoflavone content in reversing bone loss induced by ovarian hormone deficiency in rats. Am J Clin Nutr 68:1358S–1363SPubMedGoogle Scholar
  24. 24.
    Arjmandi BH, Birnbaum R, Goyal NV, Getlinger MJ, Juma S, Alekel L, Hasler CM, Drum ML, Hollis BW, Kukreja SC (1998) Bone-sparing effect of soy protein in ovarian hormone-deficient rats is related to its isoflavone content. Am J Clin Nutr 68:1364S–1368SPubMedGoogle Scholar
  25. 25.
    Anderson JJ, Garner SC (1998) Phytoestrogens and bone. Baillieres Clin Endocrinol Metab 12:543–557PubMedCrossRefGoogle Scholar
  26. 26.
    Arjmandi BH, Alekel L, Hollis BW, Amin D, Stacewicz-Sapuntzakis M, Guo P, Kukreja SC (1996) Dietary soybean protein prevents bone loss in an ovariectomized rat model of osteoporosis. J Nutr 126:161–167PubMedGoogle Scholar
  27. 27.
    WHI (2002) WHI (Writing group for the Women’s Health Initiative investigators). Risks and benefits of estrogen plus progestin in healthy post menopausal women. JAMA 288:321–333CrossRefGoogle Scholar
  28. 28.
    Picherit C, Coxam V, Bennetau-Pelissero C, Kati-Coulibaly S, Davicco MJ, Lebecque P, Barlet JP (2000) Daidzein is more efficient than genistein in preventing ovariectomy-induced bone loss in rats. J Nutr 130:1675–1681PubMedGoogle Scholar
  29. 29.
    Molis C, Flourie B, Ouarne F, Gailing MF, Lartigue S, Guibert A, Bornet F, Galmiche JP (1996) Digestion, excretion, and energy value of fructooligosaccharides in healthy humans. Am J Clin Nutr 64:324–328PubMedGoogle Scholar
  30. 30.
    Ohta A, Uehara M, Sakai K, Takasaki M, Adlercreutz H, Morohashi T, Ishimi Y (2002) A combination of dietary fructooligosaccharides and isoflavone conjugates increases femoral bone mineral density and equol production in ovariectomized mice. J Nutr 132:2048–2054PubMedGoogle Scholar
  31. 31.
    Mathey J, Puel C, Kati-Coulibaly S, Bennetau-Pelissero C, Davicco MJ, Lebecque P, Horcajada MN, Coxam V (2004) Fructooligosaccharides maximize bone-sparing effects of soy isoflavone-enriched diet in the ovariectomized rat. Calcif Tissue Int 28:28Google Scholar
  32. 32.
    Robins SP (1994) Biochemical markers for assessing skeletal growth. Eur J Clin Nutr 48:S199–S209PubMedGoogle Scholar
  33. 33.
    Garnero P, Delmas PD (1999) Biochemical markers of bone turnover: clinical usefulness in osteoporosis. Ann Biol Clin (Paris) 57:137–148Google Scholar
  34. 34.
    Bennetau-Pelissero C, Le Houerou C, Lamothe V, Le Menn F, Babin P, Bennetau B (2000) Synthesis of haptens and conjugates for ELISAs of phytoestrogens. Development of the immunological tests. J Agric Food Chem 48:305–311PubMedCrossRefGoogle Scholar
  35. 35.
    Pastoureau P, Chomel A, Bonnet J (1995) Specific evaluation of localized bone mass and bone loss in the rat using dual-energy X-ray absorptiometry subregional analysis. Osteoporos Int 5:143–149PubMedCrossRefGoogle Scholar
  36. 36.
    Rose N, Constantin P, Leterrier C (1996) Sex differences in bone growth of broiler chickens. Growth Dev Aging 60:49–59PubMedGoogle Scholar
  37. 37.
    Cook JGH (1975) Factors influencing the assay of creatinine. Ann Clin Biochem 12:219–232PubMedGoogle Scholar
  38. 38.
    Gallagher JC (1990) The pathogenesis of osteoporosis. Bone Miner 9:215–227PubMedCrossRefGoogle Scholar
  39. 39.
    Stepan JJ, Pospichal J, Presl J, Pacovsky V (1987) Bone loss and biochemical indices of bone remodeling in surgically induced postmenopausal women. Bone 8:279–284PubMedCrossRefGoogle Scholar
  40. 40.
    Picherit C, Chanteranne B, Bennetau-Pelissero C, Davicco MJ, Lebecque P, Barlet JP, Coxam V (2001) Dose-dependent bone-sparing effects of dietary isoflavones in the ovariectomised rat. Br J Nutr 85:307–316PubMedGoogle Scholar
  41. 41.
    Xu X, Wang HJ, Murphy PA, Cook L, Hendrich S (1994) Daidzein is a more bioavailable soymilk isoflavone than is genistein in adult women. J Nutr 124:825–832PubMedGoogle Scholar
  42. 42.
    King RA (1998) Daidzein conjugates are more bioavailable than genistein conjugates in rats. Am J Clin Nutr 68:1496S–1499SPubMedGoogle Scholar
  43. 43.
    Axelson M, Setchell KD (1981) The excretion of lignans in rats-evidence for an intestinal bacterial source for this new group of compounds. FEBS Lett 123:337–342PubMedCrossRefGoogle Scholar
  44. 44.
    Uehara M, Ohta A, Sakai K, Suzuki K, Watanabe S, Adlercreutz H (2001) Dietary fructooligosaccharides modify intestinal bioavailability of a single dose of genistein and daidzein and affect their urinary excretion and kinetics in blood of rats. J Nutr 131:787–795PubMedGoogle Scholar
  45. 45.
    Raffi F, Davis C, Park M, Heinze TM, Beger RD (2003) Variations in metabolism of the soy isoflavonoid daidzein by human intestinal microfloras from different individuals. Arch Microbiol 180:11–16CrossRefGoogle Scholar
  46. 46.
    Miller SC, Bowman BM, Miller MA, Bagi CM (1991) Calcium absorption and osseous organ-, tissue-, and envelope-specific changes following ovariectomy in rats. Bone 12:439–446PubMedCrossRefGoogle Scholar
  47. 47.
    Uebelhart D, Schlemmer A, Johansen JS, Gineyts E, Christiansen C, Delmas PD (1991) Effect of menopause and hormone replacement therapy on the urinary excretion of pyridinium cross-links. J Clin Endocrinol Metab 72:367–373PubMedCrossRefGoogle Scholar
  48. 48.
    Ishida H, Uesugi T, Hirai K, Toda T, Nukaya H, Yokotsuka K, Tsuji K (1998) Preventive effects of the plant isoflavones, daidzin and genistin, on bone loss in ovariectomized rats fed a calcium-deficient diet. Biol Pharm Bull 21:62–66PubMedGoogle Scholar
  49. 49.
    Setchell KD, Brown NM, Desai P, Zimmer-Nechemias L, Wolfe BE, Brashear WT, Kirschner AS, Cassidy A, Heubi JE (2001) Bioavailability of pure isoflavones in healthy humans and analysis of commercial soy isoflavone supplements. J Nutr 131:1362S–1375SPubMedGoogle Scholar
  50. 50.
    Brown NM, Setchell KD (2001) Animal models impacted by phytoestrogens in commercial chow: implications for pathways influenced by hormones. Lab Invest 81:735–747PubMedCrossRefGoogle Scholar
  51. 51.
    Ohta A, Motohashi Y, Ohtsuki M, Hirayama M, Adachi T, Sakuma K (1998) Dietary fructooligosaccharides change the concentration of calbindin-D9k differently in the mucosa of the small and large intestine of rats. J Nutr 128:934–939PubMedGoogle Scholar
  52. 52.
    Takahara S, Morohashi T, Sano T, Ohta A, Yamada S, Sasa R (2000) Fructooligosaccharide consumption enhances femoral bone volume and mineral concentrations in rats. J Nutr 130:1792–1795PubMedGoogle Scholar
  53. 53.
    Scholz-Ahrens KE, Schaafsma G, van den Heuvel EG, Schrezenmeir J (2001) Effects of prebiotics on mineral metabolism. Am J Clin Nutr 73:459S–464SPubMedGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2007

Authors and Affiliations

  • J. Mathey
    • 1
  • J. Mardon
    • 1
  • N. Fokialakis
    • 2
  • C. Puel
    • 1
  • S. Kati-Coulibaly
    • 3
  • S. Mitakou
    • 2
  • C. Bennetau-Pelissero
    • 4
  • V. Lamothe
    • 4
  • M. J. Davicco
    • 1
  • P. Lebecque
    • 1
  • M. N. Horcajada
    • 1
  • V. Coxam
    • 1
  1. 1.Groupe Ostéoporose, U3MINRA TheixSaint Genès-ChampanelleFrance
  2. 2.Division of Pharmacognosy, Panapistimioupolis, ZografouUniversity of AthensAthensGreece
  3. 3.Laboratoire de Nutrition et PharmacologieUFR BiosciencesAbidjan 22Ivory Coast
  4. 4.Unité Micronutriments, Reproduction, SantéENITA BordeauxGradignan CedexFrance

Personalised recommendations