Dietary phytoestrogens and total and cause-specific mortality: results from 2 prospective cohort studies

Zhangling Chen, Frank Qian, Yang Hu, Trudy Voortman, Yanping Li, Eric B Rimm, Qi Sun*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

6 Citations (Scopus)


BACKGROUND: Evidence regarding dietary phytoestrogens in relation to mortality remains limited.

OBJECTIVES: The objective of the study is to examine the associations of intake of isoflavones, lignans, and coumarins with total and cause-specific mortality in US males and females.

METHODS: We followed 75,981 females in the Nurses' Health Study (1984-2018) and 44,001 males in the Health Professionals Follow-up Study (1986-2018), who were free of cardiovascular disease (CVD), diabetes, or cancer at baseline. Their diet was repeatedly assessed using validated food frequency questionnaires every 2-4 y. Associations with mortality were assessed using time-dependent Cox models with adjustments for demographics, dietary and lifestyle factors, and medical history.

RESULTS: During 3,427,156 person-years of follow-up, we documented 50,734 deaths, including 12,492 CVD deaths, 13,726 cancer deaths, and 24,516 other non-CVD and noncancer deaths. After multivariable adjustment, the higher total phytoestrogen intake was associated with lower risk of total CVD and other non-CVD and noncancer mortality: comparing extreme quintiles, the pooled HRs (95% CIs) were 0.89 (0.87, 0.92), 0.90 (0.85, 0.96), and 0.86 (0.82, 0.90), respectively. We did not find a significant association with cancer mortality [0.97 (0.92, 1.03)]. For individual phytoestrogens in relation to total mortality, the pooled HRs (95% CIs) comparing extreme quintiles were 0.90 (0.87, 0.92) for isoflavones, 0.93 (0.90, 0.96) for lignans, and 0.93 (0.90, 0.95) for coumarins. Individual phytoestrogens were also significantly associated with lower risk of CVD mortality and other types of mortality. Primary food sources of phytoestrogens, including tofu, soy milk, whole grains, tea, and flaxseed, were also inversely associated with total mortality.

CONCLUSIONS: A higher intake of total phytoestrogens, including isoflavones, lignans, and coumarins, and foods rich in these compounds was associated with lower risk of total and certain cause-specific mortality in generally healthy US adults. These data suggest that these phytochemicals and their dietary sources may be integrated into an overall healthy diet to achieve a longer life span.

Original languageEnglish
Pages (from-to)130-140
Number of pages11
JournalThe American journal of clinical nutrition
Issue number1
Publication statusPublished - Jan 2023

Bibliographical note

Funding Information:
The NHS and HPFS studies and the current analysis were supported by the National Institutes of Health grants (UM1 CA186107, P01 CA87969, R01 CA49449, R01 HL034594, R01 HL088521, U01 CA176726, R01 CA67262, U01 CA167552, R01 HL035464, R01 HL060712, and R01 DK120870). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Publisher Copyright:
© 2022 American Society for Nutrition


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