Role of phytoestrogens in prevention and management of type 2 diabetes

Table 1 Epidemiological studies on the relation between phytoestrogens (lignans or isoflavones) and risk of diabetes or diabetes biomarkers

Ref.	Ethnicity	Population	Sample size, total (outcome)	Mean follow-up years	Main exposures	Outcome	Exposure level (mean or median)	Maximum effect (highest vs ref.)
Cross-sectional study
Goodman-Gruen et al[39]	Mix1	Postmenopausal women, aged 45-74 yr	208	-	Dietary isoflavones	Diabetes biomarkers	4.4 mg/d genistein (mean)	Inverse with 2-h insulin (β = -0.2); not significant for FG and insulin
Yang et al[38]	Chinese	Women aged 40-70 yr	39385 (323)	-	Tofu and other soy products	Glycosuria	9 g/d soy protein	Inverse association in postmenopausal women
van der Schouw et al[42]	Caucasian	Men aged 47-83 yr	468	-	Dietary lignans and isoflavones	Diabetes biomarkers	Approximately 1 mg/d total phytoestrogens	Inverse association of lignans with fasting insulin and C-peptide; no significant association with isoflavones
Pan et al[11]	Chinese	Men and women aged 50-70 yr	2811	-	Dietary soy protein	Hyperglycemia (FG ≥ 5.6 mmol/L)	7.8 g/d soy protein	Increased odds in men, but not in women
Shi et al[41]	Mix1	Pregnant women aged 28 yr	299	-	Urinary isoflavones	Diabetes biomarkers	502 mg/g creatinine	Inverse association with FG, insulin, and HOMA-IR
Longitudinal study
Villegas et al[44]	Chinese	Women aged 40-70 yr	64191 (896)	4.6	Soy protein, soybeans, soy products	T2D	7.7 g/d soy protein	Inverse association with soybeans; inverse but not significant relation with soy protein or other products
Nanri et al[46]	Japanese	Men and women aged 45-75 yr	59791 (1114)	5	Soy products, daidzein, genistein	T2D	Approximately 73 g/d soy products, approximately 23 mg/d genistein, and 14.5 mg/d daidzein	No significant association
Morimoto et al[47]	Mix2	Men and women aged 45-75 yr	75344 (8564)	14	Soy products	T2D	Approximately 14.5 g/d in Japanese, approximately 8 g/d in Hawaiians, and 0 g/d in Caucasians	A modest increased risk in men and women
Mueller et al[45]	Chinese	Men and women aged 45-74 yr	43176 (2252)	5.7	Isoflavones, unsweetened and sweetened soy products	T2D	Approximately 5.2 g/d for soy protein, 15.8 mg/d for soy isoflavones	Inverse association for soy isoflavones and unsweetened soy products, while increased risk for sweetened soybean drinks
Zamora-Ros et al[48]	European whites	Men and women with mean age 52.4 yr	11559 cases and 15258 subcohort, case-cohort design	Approximately 12	Dietary isoflavones and lignans	T2D	0.9 mg/d isoflavones, 1.4 mg/d lignans	No significant association for isoflavones and lignans
Sun et al[49]	Caucasian	Women aged 65.6 yr from NHS and 45.4 from NHS II	1107 cases and 1107 controls, nested case-control design	Approximately 6	Urinary lignin metabolites (enterodiol and enterolactone)	T2D	2.2 μmol/g creatinine for NHS women, and 1.9 μmol/g creatinine for NHS II women	Inverse association and odds ratio 0.64 (95%CI: 0.45-0.91) comparing extreme quartiles

¹Mostly non-Hispanic whites;

²Caucasian, Japanese American, and Native Hawaiian. FG: Fasting glucose level; NHS: Nurses’ Health Study; T2D: Type 2 diabetes; HOMA-IR: Homeostatic model assessment of insulin resistance.