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

Abstract

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.

Keywords: coumarins; dietary phytoestrogens; epidemiology; isoflavones; lignans; mortality; public health.

Figure

Dose–response analyses between phytoestrogen intake and total mortality. Data were truncated at 2.5 and 97.5th percentiles of dietary phytoestrogen intake to limit the impact of extreme values. Dose–response relationships between phytoestrogens and total mortality were estimated by restricted cubic spline Cox proportional-hazards model among 118,618 participants. Multivariable model adjusted for age, ethnicity (Caucasians/other races), smoking status (never, former, current [1–14, 15–24, or ≥25 cigarettes/d], or missing), alcohol intake (0, 0.1–4.9, 5.0–14.9, and ≥15.0 g/d for females; 0, 0.1–4.9, 5.0–29.9, and ≥30.0 g/d for males; or missing), physical activity (metabolic equivalents of task-hour/week), multivitamin use (yes/no), aspirin use (yes/no), history of hypertension (yes/no) and hypercholesterolemia (yes/no), family history of myocardial infarction (yes/no), family history of cancer (yes/no), family history of diabetes (yes/no), menopausal status and postmenopausal hormone use (premenopause, postmenopause [never, former, or current hormone use], or missing; for females), body mass index (<23, 23–24.9, 25–29.9, 30–34.9, >35 kg/m², or missing), total energy intake (kcal/d), and modified alternative health eating index score. Solid line is point estimate, and dashed lines are 95% CIs. P values for nonlinearity of total phytoestrogens, isoflavones, lignans, and coumarins with total mortality were 0.10, 0.07, 0.04, and 0.003, respectively. P value for nonlinearity <0.05 was considered statistically significant.