Association between urinary phytoestrogens and C-reactive protein in the continuous National Health and Nutrition Examination Survey
Serum C-reactive protein (CRP) is an inflammatory biomarker, with levels routinely measured to detect and monitor many human diseases. In past studies, elevated CRP levels have been associated with both cancer and cardiovascular disease. Where CRP has been linked to an increase in the risk of chronic conditions, phytoestrogens, a group of compounds found in plants with a structural similarity to estrogen, have been associated with a decreased risk. The potential protective effect of phytoestrogen intake on cancer risk may be mediated in part through its influence on serum CRP levels. This study is among the first to examine the associations between urinary concentrations of total and individual phytoestrogens and serum concentrations of CRP among 6,009 subjects aged ≥40 years in the continuous National Health and Nutrition Examination Survey (1999-2010). Phytoestrogen concentrations in spot urine (ng/mL) were measured using high performance liquid chromatography (HPLC) with tandem mass spectrometric (MS/MS) detection. Serum CRP levels (mg/L) were quantified by latex-enhanced nephelometry. After adjustment for urinary creatinine and other confounders, both linear and logistic regression analyses showed a significant inverse association between urinary excretion of total and all individual phytoestrogens and serum levels of CRP. Total phytoestrogens (β: -0.11; 95% CI: -0.13, -0.09) were associated with the largest reduction in CRP levels, followed by total lignan (β: -0.08; 95% CI: -0.10, -0.06) and enterolactone (β: -0.07; 95% CI: -0.08, -0.05). A reduced risk of developing high concentrations of CRP (≥ 3.0 mg/L) was most pronounced for enterolactone (OR for quartile 4 vs. quartile 1: 0.59; 95% CI: 0.51, 0.69), followed by total phytoestrogens (OR for quartile 4 vs. quartile 1: 0.63; 95% CI: 0.53, 0.73) and lignan (OR for quartile 4 vs. quartile 1: 0.64; 95% CI: 0.54, 0.75). In summary, dietary intake of total and individual phytoestrogens, assessed by measuring their urinary biomarkers, reduced the concentrations of CRP in a large, nationally representative sample of the US population.