Soy-isoflavone-enriched foods and inflammatory biomarkers of cardiovascular disease risk in postmenopausal women: interactions with genotype and equol production.
BACKGROUND
Dietary isoflavones are thought to be cardioprotective because of their structural similarity to estrogen. The reduction of concentrations of circulating inflammatory markers by estrogen may be one of the mechanisms by which premenopausal women are protected against cardiovascular disease.


OBJECTIVE
Our aim was to investigate the effects of isolated soy isoflavones on inflammatory biomarkers [von Willebrand factor, intracellular adhesion molecule 1, vascular cell adhesion molecule 1 (VCAM-1), E-selectin, monocyte chemoattractant protein 1, C-reactive protein (CRP), and endothelin 1 concentrations]. Differences with respect to single-nucleotide polymorphisms in selected genes [estrogen receptor alpha (XbaI and PvuII), estrogen receptor beta [ERbeta (AluI) and ERbeta[cx] (Tsp509I), endothelial nitric oxide synthase (Glu298Asp), apolipoprotein E (Apo E2, E3, and E4), and cholesteryl ester transfer protein (TaqIB)] and equol production were investigated.


METHODS
One hundred seventeen healthy European postmenopausal women participated in this randomized, double-blind, placebo-controlled, crossover dietary intervention trial. Isoflavone-enriched (genistein-to-daidzein ratio of 2:1; 50 mg/d) or placebo cereal bars were consumed for 8 wk, with a washout period of 8 wk between the crossover. Plasma inflammatory factors were measured at 0 and 8 wk of each study arm.


RESULTS
Isoflavones improved CRP concentrations [odds ratio (95% CI) for CRP values >1 mg/L for isoflavone compared with placebo: 0.43 (0.27, 0.69)]; no significant effects of isoflavone treatment on other plasma inflammatory markers were observed. No significant differences in the response to isoflavones were observed according to subgroups of equol production. Differences in the VCAM-1 response to isoflavones and to placebo were found with ERbeta AluI genotypes.


CONCLUSIONS
Isoflavones have beneficial effects on CRP concentrations, but not on other inflammatory biomarkers of cardiovascular disease risk in postmenopausal women, and may improve VCAM-1 in an ERbeta gene polymorphic subgroup.
Hall
Wendy L
WL
Hugh Sinclair Unit of Human Nutrition, School of Food Biosciences, University of Reading, Reading, United Kingdom. w.l.hall@reading.ac.uk
Vafeiadou
Katerina
K
Hallund
Jesper
J
Bügel
Susanne
S
Koebnick
Corinna
C
Reimann
Manja
M
Ferrari
Marika
M
Branca
Francesco
F
Talbot
Duncan
D
Dadd
Tony
T
Nilsson
Maria
M
Dahlman-Wright
Karin
K
Gustafsson
Jan-Ake
JA
Minihane
Anne-Marie
AM
Williams
Christine M
CM
D000368:Aged; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis*; D002318:Cardiovascular Diseases / Q000097:blood* / Q000453:epidemiology / Q000235:genetics; D018592:Cross-Over Studies; D004311:Double-Blind Method; D060754:Equol; D047629:Estrogen Receptor beta / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005527:Food, Fortified; D005838:Genotype; D006801:Humans; D007529:Isoflavones / Q000096:biosynthesis / Q000494:pharmacology* / Q000652:urine; D008875:Middle Aged; D048789:Phytoestrogens / Q000378:metabolism / Q000652:urine; D020641:Polymorphism, Single Nucleotide; D017698:Postmenopause; D012307:Risk Factors; D045730:Soy Foods; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood / Q000187:drug effects
C007610:4',7-dihydroxy-3,4-dihydroisoflavone; D015415:Biomarkers; D047629:Estrogen Receptor beta; D007529:Isoflavones; D048789:Phytoestrogens; D019010:Vascular Cell Adhesion Molecule-1; D060754:Equol; D002097:C-Reactive Protein