Impact of equol-producing capacity and soy-isoflavone profiles of supplements on bone calcium retention in postmenopausal women: a randomized crossover trial

Am J Clin Nutr. 2015 Sep;102(3):695-703. doi: 10.3945/ajcn.114.093906. Epub 2015 Aug 5.


Background: Postmenopausal estrogen depletion is a major contributing factor to bone loss. Soy isoflavones have variable effects on the prevention of postmenopausal bone loss, which is possibly related to the specific isoflavone content or the variable equol-producing capacity of individuals.

Objective: We aimed to determine the effects of the content of isoflavones in a soy supplement and the equol-producing ability of the individual on postmenopausal bone calcium retention.

Design: The study was a blinded, randomized, crossover intervention trial in 24 postmenopausal women who were prescreened for their ability to convert daidzein to equol. Women were equilibrated with (41)Ca before the intervention. Interventions were 5 soy isoflavone oral supplements (2 doses of a genistein-rich soy supplement and 3 doses of mixed isoflavones in various proportions) and a bisphosphonate (risedronate). Each intervention was given sequentially for 50 d followed by a 50-d washout period. The percentage of bone calcium retention was determined from the change in urinary (41)Ca:calcium.

Results: Interventions that ranged from 52 to 220 mg total isoflavones/d increased bone calcium retention between 3.4% and 7.6% (P < 0.05), which was a moderate effect compared with that of risedronate at 15.3% (95% CI: 7.1%, 22.7%; P = 0.0014). The most-effective soy intervention delivered 105.23 mg total isoflavones/d as genistein, daidzein, and glycitein in their natural ratios and increased bone calcium retention by 7.6% (95% CI: 4.9%, 10.2%; P < 0.0001). Genistein, at 52.85 mg/d, increased bone calcium retention by 3.4% (95% CI: 0.5%, 6.2%; P = 0.029); but there was no benefit at higher amounts (113.52 mg/d). There was no difference (P = 0.5) in bone calcium retention between equol producers and nonproducers.

Conclusion: Soy isoflavones, although not as potent as risedronate, are effective bone-preserving agents in postmenopausal women regardless of their equol-producing status, and mixed isoflavones in their natural ratios are more effective than enriched genistein. This trial was registered at as NCT00244907.

Keywords: 41Ca; bone resorption; equol; genistein; postmenopausal women; soy isoflavones.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Administration, Oral
  • Aged
  • Bone and Bones / drug effects*
  • Calcium / metabolism*
  • Cross-Over Studies
  • Dietary Supplements
  • Dose-Response Relationship, Drug
  • Equol / administration & dosage*
  • Female
  • Genistein / administration & dosage
  • Humans
  • Isoflavones / administration & dosage
  • Middle Aged
  • Osteoporosis, Postmenopausal / prevention & control
  • Phytoestrogens / administration & dosage
  • Postmenopause*
  • Risedronic Acid / pharmacology
  • Soybeans / chemistry*


  • Isoflavones
  • Phytoestrogens
  • Equol
  • daidzein
  • glycitein
  • Genistein
  • Risedronic Acid
  • Calcium

Associated data