J Korean Med Sci.  2009 Oct;24(5):867-873. 10.3346/jkms.2009.24.5.867.

Marked Individual Variation in Isoflavone Metabolism After a Soy Challenge Can Modulate the Skeletal Effect of Isoflavones in Premenopausal Women

• Kwak HS
• Park SY
• Kim MG
• Yim CH
• Yoon HK
• Han KO

• KMID: 1782008
• DOI: http://doi.org/10.3346/jkms.2009.24.5.867

Abstract

Soy-isoflavones may act as estrogenic agonists or antagonists depending on the endogenous hormone status. These clinical effects can be exerted variably in individuals by the metabolic ability to produce a more potent metabolite than precursors. The objective of this randomized, double-blind, placebo-controlled study was to investigate the skeletal effect of isoflavones according to their metabolic variability in premenopausal women. Volunteers were randomly assigned to receive either soy-extract isoflavones (n=32) or lactose (n=21) once a day for three menstrual cycles. After intervention, the urinary excretions of isoflavones and their metabolites were significantly higher in the soy group than in the placebo group and showed a large inter-individual variation. Women in the soy group were divided into subgroups according to their ability to excrete more potent metabolites. Serum osteocalcin and urine deoxypyridinoline showed a tendency to increase after a challenge in equol high-excretors. Serum osteocalcin concentration in the genistein high-excretors increased significantly after a challenge (P=0.04) but did not increase in either the placebo or genistein low-excretors. An estrogenic antagonistic effect of isoflavones on bone turnover was observed in premenopausal women who are able to produce more potent metabolites.

Keyword

Premenopausal Women; Isoflavones; Equol; Genistein; Bone Turnover; Estrogen Antagonists

MeSH Terms

Adult
Amino Acids/urine
Bone and Bones/*drug effects/metabolism
Double-Blind Method
Estrogen Antagonists/*pharmacokinetics/pharmacology/urine
Female
Humans
Isoflavones/*pharmacokinetics/pharmacology/urine
Middle Aged
Osteocalcin/blood
*Premenopause

Figure

• 

  Fig. 1 Metabolic pathway of the major soy isoflavones daidzin and genistin. They are cleaved by intestinal glucosidases to the aglycones, daidzein (DZ) and genistein (GTN). DZ and GTN are further metabolized by intestinal microflora into several metabolites: dihydrogenistein (DGTN), dihydrodaidzein (DDZ), tetrahydrodaidzein (TDZ), o-desmethylangolensin (O-DMA), and equol (EQL).

• 

  Fig. 2 Mean (±SEM) urinary excretion of isoflavones and their metabolites before and after a soy challenge in the placebo (left) and soy group (right). *, †, ‡Significantly different from baseline: *P<0.05; †P<0.01; ‡P<0.001 (paired two-tailed t test).

• 

  Fig. 3 Urinary equol (EQL), o-desmethangiolensin (O-DMA), dihydrodaidzein (DDZ), dihydrogenistein (DGTN), genistein (GTN), and daidzein (DZ) excretion in 32 subjects in the soy group after a soy challenge.

• 

  Fig. 4 Changes of serum osteocalcin (OC), a bone-formation marker, and urine deoxypyridinoline (DPD), a bone-resorption marker, before and after a soy challenge in the placebo and the soy group (paired two-tailed t test).

• 

  Fig. 5 Scatter plots between urinary concentrations of isoflavonoid metabolites. Daidzein (DZ) was significantly correlated with its metabolites, except for equol (EQL) (upper three and lower first plots). EQL was not correlated with any other metabolites (lower panel) (r=Pearson correlation, P=significance by two-tailed Z test).

• 

  Fig. 6 Changes of serum osteocalcin (OC) before and after the challenge in subgroups divided by several metabolic phenotypes. Eight women (25%) were categorized as EQL excretors (>1,000 nM/day). The GTN high-excretors were defined arbitrarily as women whose urinary excretion of GTN was greater than 2,000 nM/day.

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