Decreased circulating levels of tumor necrosis factor-alpha in postmenopausal women during consumption of soy-containing isoflavones

CONTEXT: TNF-alpha is a key mediator of inflammatory responses and may play a pivotal role in the development of cancer and in bone resorption. OBJECTIVE: This study determined the effect of soy rich in isoflavones on levels of TNF-alpha. DESIGN: Twelve postmenopausal women ingested a 36-oz portion of soymilk containing isoflavones daily for 16 wk and provided fasting blood samples multiple times before, during, and after soy consumption for the analyses of cytokines and monocyte content. RESULTS: Compared with prediet levels (36.3 +/- 14.0 pg/ml), serum levels of TNF-alpha decreased by 25.1% (27.2 +/- 10.3 pg/ml; P < 0.01) as early as 2 wk after soy consumption and by 66.7% (11.6 +/- 5.3 pg/ml; P < 0.01) 10 wk after soy consumption and recovered to the prediet levels 4 wk after the termination of soy consumption (38.6 +/- 19.6 pg/ml; P = 0.66). A similar decrease of up to 56.6 and 14.4% was found for serum IL-1alpha and the mean percentage of blood monocytes during soy consumption, respectively, but not for IL-6. In cultures of monocytes or whole blood from postmenopausal women, soy isoflavones (genistein and daidzein, 10-1000 nm), tamoxifen (10-1000 nm), or 17beta-estradiol (0.1-10 nm) inhibited lipopolysaccharide (1 microg/ml)-induced TNF-alpha production by up to 55.8%. CONCLUSIONS: Isoflavones may be the active components in soy responsible for the decrease of TNF-alpha found in postmenopausal women during a soy diet. This antiinflammatory effect of the isoflavones may be important in immune modulation and the prevention of bone loss and cancer.