Table 7. Serum and plasma enterolactone (and enterodiol) and cardiovascular disease risk.

Outcome	Author, year, reference	Study	Population characteristics	Cases (N)	p ≤0.05	p >0.05 – 0.15	p > 0.15
Cardiovascular disease mortality	Vanharanta et al (2003)¹⁴⁹	Prospective, Kuopio, Finland	1889 M, age 42, 48, 54, or 60, 12.2 yr follow up	103	0.55 RR (0.29, 1.01) CI p=0.04 [23.9 vs 6.9 nmol/l]^a
Coronary heart disease mortality	Vanharanta et al (2003)¹⁴⁹	Prospective, Kuopio, Finland	M, age 42, 48, 54, or 60, 12.2 yr follow up	70	0.44 RR (0.20, 0.96) CI p=0.03 [23.9 vs 6.9 nmol/l]^a
	Kilkkinen et al (2006)¹⁵¹	Prospective case-cohort, ATBC, Finland	M, smokers, 11.1 yr follow up	340 cases (205 MI, 135 deaths) 420 controls			0.57 RR (0.26, 1.25) CI p for trend=0.18 [28.25 vs 5.02 nmol/l]^b
Coronary heart disease risk (acute events & mortality)	Kilkkinen et al (2006)¹⁵¹	Prospective case-cohort, ATBC, Finland	M, smokers, 11.1 yr follow up	340 cases (205 MI, 135 deaths) 420 controls		0.63 RR (0.33, 1.11) CI p for trend=0.07 [28.25 vs 5.02 nmol/l]^b
Coronary heart disease risk (acute events)	Kilkkinen et al (2006)¹⁵¹	Prospective case-cohort, ATBC, Finland	M, smokers, 11.1 yr follow up	340 cases (205 MI, 135 deaths) 420 controls		0.67 RR (0.37, 1.23) CI p for trend=0.10 [28.25 vs 5.02 nmol/l]^b
^c	Kuijsten et al (2009)¹⁵²	Prospective nested case control Netherlands	M, F, age 20-59, 11 yr follow up	236 cases, 283 controls		1.51 OR (0.87, 2.61) CI p for trend = 0.12 [17.5 vs 3.8 nmol/l]^a
^c	Kuijsten et al (2009)¹⁵²	Prospective nested case control Netherlands	F, premenopausal, age 20-59, 11 yr follow up	34 cases	0.16 OR (0.02, 1.03) CI p for trend = 0.05 [per 13.7 nmol/l, 17.5 vs 3.8 nmol/l]^a
^c	Kuijsten et al (2009)¹⁵²	Prospective nested case control Netherlands	F, postmenopausal, age 20-59, 11 yr follow up	30 cases	1.17 OR END (1.00, 1.36) CI p for trend = 0.05 [per 1.3 nmol/l, 1.7 vs 0.4 nmol/l]^a		2.27 OR (0.57, 8.95) CI p for trend = 0.24 [per 13.7 nmol/l, 17.5 vs 3.8 nmol/l]^a
	Vanharanta et al (1999)¹⁵⁰	Prospective nested case control, Kuopio, Finland	M, age 42, 48, 54, or 60, 7.7 yr follow up	167 cases, 167 controls	0.35 OR (0.14, 0.88) CI p=0.03 [30.1 vs 7.2 nmol/l]^a
Hypertension	Vanharanta et al (2003)¹⁴⁹	Prospective, Kuopio, Finland	M, age 42, 48, 54, or 60, 12.2 yr follow up	1889 at baseline	-12 % p for heterogeneity <001 [23.9 vs 6.9 nmol/l]^a
Blood pressure, diastolic	Vanharanta et al (1999)¹⁵⁰	Prospective nested case control, Kuopio, Finland	M, age 42, 48, 54, or 60, 7.7 yr follow up	167 cases, 167 controls at baseline	-3 mm Hg p for heterogeneity =0.017 [30.1 vs 7.2 nmol/l]^a
	Vanharanta et al (2003)¹⁴⁹	Prospective, Kuopio, Finland	M, age 42, 48, 54, or 60, 12.2 yr follow up	1889 at baseline	-3 mm Hg p for heterogeneity <001 [23.9 vs 6.9 nmol/l]^a
^c	Kuijsten et al (2009)¹⁵²	Prospective nested case control Netherlands	M, F, age 20-59, 11 yr follow up	283 controls at baseline		-3 mm Hg p for trend = 0.08 [17.5 vs 3.8 nmol/l]^a
	Kilkkinen et al (2006)¹⁵¹	Prospective case-cohort, ATBC, Finland	M, smokers, 11.1 yr follow up	420 controls at baseline			-6 mm Hg p for heterogeneity = 0.21 [28.25 vs 5.02 nmol/l]^b
Blood pressure, systolic	Vanharanta et al (2003)¹⁴⁹	Prospective, Kuopio, Finland	M, age 42, 48, 54, or 60, 12.2 yr follow up	1889 at baseline	-5 mm Hg p for heterogeneity <001 [23.9 vs 6.9 nmol/l]^a
	Vanharanta et al (1999)¹⁵⁰	Prospective nested case control, Kuopio, Finland	M, age 42, 48, 54, or 60, 7.7 yr follow up	167 cases, 167 controls at baseline	-5 mm Hg p for heterogeneity =0.026 [30.1 vs 7.2 nmol/l]^a
^c	Kuijsten et al (2009)¹⁵²	Prospective nested case control Netherlands	M, F, age 20-59, 11 yr follow up	283 controls at baseline		-4 mm Hg p for trend = 0.09 [17.5 vs 3.8 nmol/l]^a
	Kilkkinen et al (2006)¹⁵¹	Prospective case-cohort, ATBC, Finland	M, smokers, 11.1 yr follow up	420 controls at baseline			-6 mm Hg p for heterogeneity = 0.84 [28.25 vs 5.02 nmol/l]^b
Cholesterol, HDL	Kuijsten^c et al (2009)¹⁵²	Prospective nested case control Netherlands	M, F, age 20-59, 11 yr follow up	283 controls at baseline		3.86 mg/dl p for trend = 0.07 [17.5 vs 3.8 nmol/l]^a
	Vanharanta et al (1999)¹⁵⁰	Prospective nested case control, Kuopio, Finland	M, age 42, 48, 54, or 60, 7.7 yr follow up	167 cases, 167 controls at baseline			1.54 mg/dl p for heterogeneity = 0.74 [30.1 vs 7.2 nmol/l]^a
	Vanharanta et al (2003)¹⁴⁹	Prospective, Kuopio, Finland	M, age 42, 48, 54, or 60, 12.2 yr follow up	1889 at baseline			1 mg/dl p for heterogeneity = 0.66 [23.9 vs 6.9 nmol/l]^a
	Kilkkinen et al (2006)¹⁵¹	Prospective case-cohort, ATBC, Finland	M, smokers, 11.1 yr follow up	420 controls at baseline			1.16 mg/dl p for heterogeneity = 0.47 [28.25 vs 5.02 nmol/l]^b
Cholesterol, LDL	Vanharanta et al (1999)¹⁵⁰	Prospective nested case control, Kuopio, Finland	M, age 42, 48, 54, or 60, 7.7 yr follow up	167 cases, 167 controls at baseline			-2.32 mg/dl p for heterogeneity = 0.52 [30.1 vs 7.2 nmol/l]^a
	Vanharanta et al (2003)¹⁴⁹	Prospective, Kuopio, Finland	M, age 42, 48, 54, or 60, 12.2 yr follow up	1889 at baseline			0.0 mg/dl p for heterogeneity = 0.91 [23.9 vs 6.9 nmol/l]^a
Cholesterol, total	Kuijsten ^c et al (2009)¹⁵²	Prospective nested case control Netherlands	M, F, age 20-59, 11 yr follow up	283 controls at baseline			5.80 mg/dl p for trend = 0.22 [17.5 vs 3.8 nmol/l]^a
	Vanharanta et al (1999)¹⁵⁰	Prospective nested case control, Kuopio, Finland	M, age 42, 48, 54, or 60, 7.7 yr follow up	167 cases, 167 controls at baseline			3.47 mg/dl p for heterogeneity = 0.82 [30.1 vs 7.2 nmol/l]^a
	Kilkkinen et al (2006)¹⁵¹	Prospective case-cohort, ATBC, Finland	M, smokers, 11.1 yr follow up	420 controls at baseline			3.86 mg/dl p for heterogeneity = 0.22 [28.25 vs 5.02 nmol/l]^b
Apolipoprotein B	Vanharanta et al (1999)¹⁵⁰	Prospective nested case control, Kuopio, Finland	M, age 42, 48, 54, or 60, 7.7 yr follow up	167 cases, 167 controls at baseline			41 mg/l p for heterogeneity = 0.22 [30.1 vs 7.2 nmol/l]^a
Reduced F2-isoprostanes	Vanharanta et al (2002)¹⁵³	Cross-sectional, ASAP, Finland	M, age 58.6 ± 6.5	100	-37.4% p for trend = 0.008 [25.6 vs 3.9 nmol/l]^b

Highest versus lowest quartile of serum (or plasma) enterolactone (or enterodiol

Highest versus lowest quintile of serum (or plasma) enterolactone

In Kuijsten et al (2009)¹⁵² (the only study using plasma), diastolic and systolic blood pressure, HDL, total cholesterol and coronary heart disease risk (acute events) were not significant for enterodiol

Abbreviations: M – males, F – females, CI – 95% Confidence Interval, OR – Odds ratio, RR – Rate ratio, [ ] – definition of comparison groups or per SD (standard deviation) unit, END – enterodiol, MI – myocardial infarction

Underlying causes of death coded according to the International Classification of Diseases, 9^th and 10^th revisions (ICD-9 and ICD-10). Cardiovascular disease deaths defined as ICD-9 codes 390-459 and ICD-10 codes I20-I99, coronary heart disease deaths as ICD-9 codes 410-414 (ischemic heart disease) and 492.2 (atherosclerotic heart disease) and ICD-10 codes I20-I25, and stroke as ICD-9 codes 430-438 (ischemic and hemorrhagic cerebrovascular disease) and ICD-10 codes I60-I69 (cerebrovascular diseases).