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. 2022 Dec 20;117(1):130–140. doi: 10.1016/j.ajcnut.2022.10.019

Table 3.

Pooled associations of dietary phytoestrogens and cause-specific mortality1

CVD mortality
Total phytoestrogens
Q1 (Low)
Q2
Q3
Q4
Q5 (High)
Ptrend
Number of case/person y 3144/681,423 2808/684,044 2461/685,743 2238/686,568 1841/689,379
Model 1 1 0.88 (0.84, 0.93) 0.82 (0.78, 0.86) 0.81 (0.77, 0.85) 0.98 (0.92, 1.04) <0.0001
Model 2 1 0.98 (0.93, 1.03) 0.95 (0.90, 1.00) 0.93 (0.88, 0.99) 0.86 (0.81, 0.92) <0.0001
Model 3 1 0.98 (0.93, 1.04) 0.95 (0.90, 1.01) 0.95 (0.90, 1.01) 0.90 (0.85, 0.96) 0.0006
Isoflavones
Q1
Q2
Q3
Q4
Q5
Ptrend
Numebr of case/person y 3211/681,594 2736/684,822 2403/686,157 2273/685,819 1869/688,763
Model 1 1 0.89 (0.84, 0.93) 0.82 (0.78, 0.87) 0.85 (0.81, 0.90) 0.74 (0.70, 0.79) <0.0001
Model 2 1 0.97 (0.92, 1.03) 0.94 (0.89, 0.99) 0.96 (0.91, 1.02) 0.87 (0.82, 0.92) <0.0001
Model 3 1 0.97 (0.92, 1.03) 0.94 (0.89, 0.99) 0.97 (0.91, 1.02) 0.90 (0.84, 0.95) 0.0008
Lignans
Q1
Q2
Q3
Q4
Q5
Ptrend
Number of case/person y 2883/682,662 2526/684,633 2475/685,908 2331/686,626 2277/687,326
Model 1 1 0.81 (0.77, 0.86) 0.79 (0.74, 0.83) 0.71 (0.68, 0.76) 0.67 (0.63, 0.71) <0.0001
Model 2 1 0.90 (0.86, 0.96) 0.93 (0.88, 0.98) 0.88 (0.83, 0.93) 0.84 (0.80, 0.89) <0.0001
Model 3 1 0.92 (0.87, 0.98) 0.96 (0.90, 1.01) 0.92 (0.87, 0.98) 0.91 (0.85, 0.97) 0.002
Coumarins
Q1
Q2
Q3
Q4
Q5
Ptrend
Number of case/person y 2848/681,517 2324/687,127 2259/686,496 2333/686,484 2728/685,531
Model 1 1 0.82 (0.78, 0.87) 0.76 (0.72, 0.80) 0.73 (0.69, 0.77) 0.74 (0.70, 0.78) <0.0001
Model 2 1 0.93 (0.88, 0.98) 0.89 (0.85, 0.95) 0.88 (0.83, 0.93) 0.88 (0.83, 0.93) <0.0001
Model 3 1 0.95 (0.89, 1.00) 0.92 (0.87, 0.97) 0.91 (0.86, 0.96) 0.91 (0.86, 0.96) 0.002
Cancer mortality
Total phytoestrogens
Q1 (Low)
Q2
Q3
Q4
Q5 (High)
Ptrend
Number of case/person y 2789/681,423 2881/684,044 2912/685,743 2829/686,568 2315/689,379
Model 1 1 0.99 (0.94, 1.04) 1.03 (0.97, 1.08) 1.04 (0.99, 1.10) 0.89 (0.84, 0.94) <0.0001
Model 2 1 1.04 (0.99, 1.10) 1.07 (1.01, 1.13) 1.06 (1.00, 1.12) 0.95 (0.90, 1.01) 0.003
Model 3 1 1.05 (0.99, 1.10) 1.08 (1.02, 1.13) 1.07 (1.01, 1.13) 0.97 (0.92, 1.03) 0.04
Isoflavones
Q1
Q2
Q3
Q4
Q5
Ptrend
Number of case/person y 2833/681,594 2826/684,822 2901/686,157 2854/685,819 2312/688,763
Model 1 1 0.99 (0.94, 1.05) 1.04 (0.99, 1.10) 1.08 (1.02, 1.14) 0.91 (0.86, 0.96) <0.0001
Model 2 1 1.04 (0.98, 1.09) 1.08 (1.02, 1.14) 1.07 (1.02, 1.13) 0.95 (0.89, 1.00) 0.001
Model 3 1 1.04 (0.98, 1.09) 1.08 (1.02, 1.14) 1.08 (1.02, 1.14) 0.96 (0.91, 1.02) 0.02
Lignans
Q1
Q2
Q3
Q4
Q5
Ptrend
Number of case/person y 2956/682,662 2820/684,633 2617/685,908 2567/686,626 2766/687,326
Model 1 1 0.91 (0.86, 0.95) 0.82 (0.78, 0.87) 0.79 (0.75, 0.83) 0.81 (0.77, 0.86) <0.0001
Model 2 1 0.98 (0.93, 1.03) 0.93 (0.88, 0.98) 0.91 (0.86, 0.96) 0.94 (0.89, 0.99) 0.003
Model 3 1 0.99 (0.94, 1.04) 0.94 (0.89, 1.00) 0.94 (0.88, 0.99) 0.98 (0.92, 1.04) 0.23
Coumarins
Q1
Q2
Q3
Q4
Q5
Ptrend
Number of case/person y 3164/681,517 2626/687,127 2607/686,496 2490/686,484 2839/685,531
Model 1 1 0.84 (0.80, 0.88) 0.81 (0.77, 0.85) 0.74 (0.70, 0.78) 0.77 (0.73, 0.81) <0.0001
Model 2 1 0.95 (0.90, 1.00) 0.95 (0.90, 1.00) 0.87 (0.83, 0.92) 0.90 (0.85, 0.95) 0.0001
Model 3 1 0.95 (0.90, 1.00) 0.95 (0.90, 1.01) 0.88 (0.84, 0.93) 0.91 (0.86, 0.96) 0.001
Other mortality
Total phytoestrogens
Q1 (Low)
Q2
Q3
Q4
Q5 (High)
Ptrend
Number of case/person y 6350/681,423 5469/684,044 4806/685,743 4348/686,568 3543/689,379
Model 1 1 0.85 (0.82, 0.88) 0.78 (0.75, 0.81) 0.76 (0.73, 0.79) 0.66 (0.63, 0.69) <0.0001
Model 2 1 0.97 (0.93, 1.01) 0.93 (0.89, 0.96) 0.90 (0.86, 0.93) 0.81 (0.78, 0.85) <0.0001
Model 3 1 0.98 (0.94, 1.02) 0.94 (0.90, 0.97) 0.92 (0.88, 0.96) 0.86 (0.82, 0.90) <0.0001
Isoflavones
Q1
Q2
Q3
Q4
Q5
Ptrend
Number of case/person y 6360/681,594 5349/684,822 4740/686,157 4402/685,819 3665/688,763
Model 1 1 0.87 (0.84, 0.90) 0.81 (0.78, 0.84) 0.80 (0.77, 0.83) 0.71 (0.68, 0.74) <0.0001
Model 2 1 0.98 (0.94, 1.01) 0.94 (0.91, 0.98) 0.93 (0.89, 0.97) 0.84 (0.81, 0.88) <0.0001
Model 3 1 0.97 (0.94, 1.01) 0.94 (0.91, 0.98) 0.94 (0.90, 0.98) 0.88 (0.84, 0.92) <0.0001
Lignans
Q1
Q2
Q3
Q4
Q5
Ptrend
Number of case/person y 5616/682,622 5157/684,633 4785/685,908 4647/686,626 4311/687,326
Model 1 1 0.86 (0.82, 0.89) 0.78 (0.75, 0.81) 0.73 (0.70, 0.76) 0.66 (0.64, 0.69) <0.0001
Model 2 1 0.95 (0.92, 0.99) 0.92 (0.89, 0.96) 0.90 (0.87, 0.94) 0.83 (0.79, 0.86) <0.0001
Model 3 1 0.98 (0.94, 1.02) 0.97 (0.93, 1.01) 0.97 (0.93, 1.01) 0.92 (0.87, 0.96) 0.03
Coumarins
Q1
Q2
Q3
Q4
Q5
Ptrend
Number of case/person y 5634/681,517 4652/687,127 4488/686,496 4612/686,484 5130/685,531
Model 1 1 0.82 (0.79, 0.85) 0.76 (0.73, 0.79) 0.73 (0.71, 0.76) 0.73 (0.71, 0.76) <0.0001
Model 2 1 0.97 (0.93, 1.01) 0.93 (0.89, 0.97) 0.91 (0.88, 0.95) 0.90 (0.86, 0.93) <0.0001
Model 3 1 0.99 (0.95, 1.03) 0.97 (0.93, 1.01) 0.96 (0.92, 1.00) 0.95 (0.91, 0.99) 0.004

Values are hazard ratios (95% CIs).

Model 1: adjustment for age and race (Caucasians/other races).

Model 2: model 1 + 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), and total energy intake (kcal/d).

Model 3: model 2 + modified alternative health eating index score.

Results from Nurses’ Health Study and Health Professionals Follow-Up Study were calculated using the fixed-effects model. Ptrend < 0.05 was considered statistically significant.

2The number of case/person-years was pooled from Nurses’ Health Study and Health Professionals Follow-Up Study.

1

The median values of total phytoestrogen, isoflavones, lignans, and coumarins within each quintile in Nurses’ Health Study and Health Professionals Follow-Up Study were the same with those in Table 1.