Gut Microbiota Metabolites of Dietary Lignans and Risk of All-Cause and Cause-Specific Mortality in Adults

OBJECTIVES: Lignans are bioactive compounds exhibiting various biological properties, including anti-inflammatory, antioxidant and antitumor activities. Epidemiological studies regarding long-term health effects of lignans are sparse. In humans, most lignans in plant-based foods are converted by the intestinal microbiota to enterolactone and enterodiol after ingestion. We examined the association of urinary levels of enterolactone and enterodiol with the risk of mortality among adults in the United States. METHODS: This is a prospective cohort study including 6262 adults aged 40 years or older who participated in the National Health and Nutrition Examination Survey 1999–2010. These participants were linked to mortality data through December 31, 2015. We used Cox proportional hazards regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of urinary enterolactone and enterodiol levels with mortality from all causes, cardiovascular disease (CVD), and cancer. RESULTS: During on average 9.3 years (maximum 16.8 years) of observation, 1456 death occurred including 329 death from CVD, and 330 death from cancer. After adjustment for age, sex, race/ethnicity, socioeconomic status, dietary and lifestyle factors, and urinary creatinine levels, the HRs (95% CIs) of all-cause mortality across increasing quartiles of urinary enterolactone levels were 1.00 (reference), 0.90 (0.77–1.05), 0.83 (0.71–0.97), and 0.81 (0.66–0.99), respectively (P for trend 0.02). We did not observe significant associations of urinary enterolactone levels with CVD mortality (HR for the highest vs. lowest quartiles 1.17, 95% CI 0.71–1.91) or cancer mortality (HR 0.82, 95% CI 0.55–1.21). For enterodiol, the HRs (95% CIs) of all-cause mortality, CVD mortality, and cancer mortality comparing the highest with lowest quartile of urinary enterodiol levels were 1.17 (0.94–1.45), 1.23 (0.83–1.81), and 1.05 (0.69–1.58), respectively. There was no significant interaction effects by sex and race/ethnicity for the observed associations. CONCLUSIONS: In this nationally representative sample of US adults, urinary enterolactone levels was inversely associated with all-cause mortality. Further studies are needed to replicate the findings and determine the underlying mechanisms. FUNDING SOURCES: N/A.