. 2016 Jul 19;5:e30. doi: 10.1017/jns.2016.18

Table 1.

Demographic and clinical characteristics of the participants in the randomised controlled trials (RCT) employing soya interventions and examining the effect of equol producer (EP) status on risk factors for CHD

First author, year	Country	Sex (no. M/no. F)	Mean age (years)	No. of EP (no. EP/no. NEP)	Guidelines for determining EP status	Subjects’ characteristics	Study design	Quality rating^*
Acharjee et al. (2015)⁽²⁷⁾^†	USA	60 F	MetS: 54·1 (sd 6·5), without MetS: 54·6 (sd 5·8)	35 EP/25 NEP	Urinary equol concentration >1000 nmol/l	Postmenopausal, with and without MetS	CO	Fair
Badeau et al. (2007)⁽²⁸⁾^‡	Finland	30 F	54	15 EP/15 NEP	Equol concentration > five times baseline	Postmenopausal breast cancer survivors	CO, DB	Fair
Campbell et al. (2004)⁽²⁹⁾	UK	23 F	Premenopausal: 34, postmenopausal: 57	7 EP/9 NEP in premenopausal group, 1 EP/6 NEP in postmenopausal group	Urinary equol concentrations >1 mg/ml	Healthy	CO, DB	Fair
Clerici et al. (2007)⁽⁵⁶⁾	Italy	25 M/37 F	Control: 52·0 (sem 2·4), intervention: 58·1 (sem 2·2)	20 EP/9 NEP (of intervention group)	Plasma equol concentrations >83 nmol/l are EP, <40 nnmol/l are NEP, 24 h urinary log₁₀ S-equol:daidzein ratio > −1·75 after daidzein challenge	Hypercholesterolaemic, adhering to Italian Heart Association Step II diet	CO, P, B	Fair
Curtis et al. (2013)⁽³⁰⁾	UK	118 F	Control: 63·0 (sem 0·8), intervention: 62·1 (sem 0·7)	17 EP/30 NEP (of intervention group)	Not reported	Postmenopausal, type 2 diabetic, using statins	DB	Poor
Gallagher et al. (2004)⁽³¹⁾	USA	65 F	55	36 EP/29 NEP	Serum equol >10 ng/ml	Postmenopausal	DB	Poor
Gardner et al. (2007)⁽⁵⁷⁾	USA	6 M/22 F	52 (sd 9)	9 EP/19 NEP	Plasma equol >50 nM	Hypercholesterolaemic	CO, SB	Poor
Greany et al. (2004)⁽³²⁾^§	USA	37 F	57·5 (sem 2·2)	8 EP/29 NEP	Plasma equol concentrations >15 nmol/l and urinary excretion >1500 nmol/24 h	Postmenopausal, history of breast cancer not treated with chemotherapy or no family history of breast cancer, no history of reproductive cancer	CO	Poor
Greany et al. (2008)⁽³³⁾^§	USA	34 F	57·7 (sd 6·0)	6 EP/28 NEP	Plasma equol concentration >15 nmol/l and urinary equol excretion >1500 nmol/d	Postmenopausal, with and without a history of breast cancer	CO	Poor
Hall et al. (2005)⁽³⁴⁾^‖	UK, Germany, Denmark, Italy	117 F	57·7 (sd 5·4)	33 EP/84 NEP	24 h urinary equol concentration during the isoflavone intervention >936 nmol/l	Postmenopausal	CO, DB	Fair
Hall et al. (2006)⁽³⁵⁾^‖	UK, Germany, Denmark, Italy	117 F	57·7 (sd 5·4)	33 EP/84 NEP	24 h urinary equol concentration during the isoflavone intervention >936 nmol/l	Postmenopausal	CO, DB	Fair
Hallund et al. (2006)⁽³⁶⁾^‖	Denmark, UK, Germany, Italy	28 F	57 (sd 5)	6 EP/22 NEP	24 h urinary equol concentration during the isoflavone intervention >936 nmol/l	Postmenopausal	CO, DB	Fair
Hodis et al. (2011)⁽¹⁴⁾	USA	350 F	60·9	39 consistent EP/35 intermittent EP/76 NEP	Consistent EP: plasma equol >20 nmol/l at all visits, intermittent EP: plasma equol >20 nmol/l at some visits, NEP: plasma equol never >20 nmol/l	Postmenopausal	DB	Good
Kreijkamp-Kaspers et al. (2005)⁽³⁷⁾^¶	Netherlands	175 F	Control: 66·8 (sd 4·7), intervention: 66·6	26 EP/62 NEP (of intervention group)	Plasma equol concentration >83 nmol/l	Postmenopausal	DB	Fair
Kreijkamp-Kaspers et al. (2004)⁽³⁸⁾^¶	Netherlands	175 F	Control: 66·7 (sd 4·8), intervention: 66·5 (sd 4·7)	26 EP/62 NEP (of intervention group)	Plasma equol concentration >83 nmol/l	Postmenopausal	DB	Fair
Liu et al. (2014)⁽³⁹⁾^**	China	287 F	Control: 58·5 (sd 4·7), whole soya: 57·6 (sd 5·3), daidzein: 57·7 (sd 5·0)	287 EP/0 NEP	24 h urinary log₁₀ S-equol:daidzein ratio > −1·75 after daidzein challenge	Postmenopausal, prehypertensive	DB	Good
Liu et al. (2015)⁽⁴⁰⁾^**	China	265 F	Control: 58·5 (sd 4·7), whole soya: 57·6 (sd 5·3), daidzein: 57·7 (sd 5·0)	265 EP/0 NEP	24 h urinary log₁₀ S-equol:daidzein ratio > −1·75 after daidzein challenge	Postmenopausal, prehypertensive or untreated hypertensive	P, DB	Good
Liu et al. (2013)⁽⁴¹⁾^**	China	253 F	Control: 58·5 (sd 4·7), whole soya: 57·6 (sd 5·3), daidzein: 57·7 (sd 5·0)	253 EP/0 NEP	24 h urinary log₁₀ S-equol:daidzein ratio > −1·75 after daidzein challenge	Postmenopausal, prehypertensive	DB	Good
Ma et al. (2005)⁽⁵⁸⁾	USA	70 M/89 F	56 (sd 8·46)	21 EP/59 NEP (of intervention group)	Serum equol concentration >20 ng/ml	Hyperlipidaemic	DB	Fair
Mangano et al. (2013)⁽⁴²⁾	USA	97 F	Control: 72·9 (sd 6·1), soya protein: 74·0 (sd 6·2), isoflavone: 72·3 (sd 5·7), soya protein and isoflavone: 73·0 (sd 5·7)	25 EP/26 NEP	12-month serum concentration of S-equol 20 nmol/l (5 µg/l)	Postmenopausal	DB	Poor
McVeigh et al. (2006)⁽⁶⁷⁾	Canada	35 M	27·9 (sd 5·7)	12 EP/23 NEP	Urinary equol >1000 nmol/24 h	Healthy	CO, B	Poor
Meyer et al. (2004)⁽⁵⁹⁾	Australia	13 M/10 F	54·0 (sem 1·8)	8 EP/15 NEP	Equol detected in the plasma or urine	Postmenopausal, hypercholesterolaemic and/or hypertensive	CO	Poor
Nestel et al. (2004⁽⁶⁰⁾	Australia	46 M/34 F	Males: 58 (sd 7), Females: 58 (sd 6)	15 EP/65 NEP	Excretion of equol >1000 nmol/24 h	Postmenopausal	CO, P, DB	Fair
Nikander et al. (2004)⁽⁴³⁾^‡	Finland	56 F	54 (sd 6)	8 EP/40 NEP	EP: equol concentration >83 nmol/l, NEP: equol concentration <40 nmol/l	Postmenopausal	CO, DB	Fair
Pipe et al. (2009)⁽⁶¹⁾	Canada	16 M/13 F	60·1 (sd 9·64)	6 EP/23 NEP	Urinary equol > 1000 nmol/24 h	Postmenopausal, diet-controlled type 2 diabetic	CO, DB	Poor
Pop et al. (2008)⁽⁴⁴⁾	USA	30 F	Placebo: 53·50 (se 1·06), intervention: 56·78 (se 1·25)	6 EP/23 NEP/1 intermediate EP	EP: plasma equol concentrations >20 µg/l; intermediate EP: (≥10 to ≤20 µg/l; NEP: plasma equol concentration <10 µg/l	Postmenopausal	DB	Poor
Pusparini & Hidayat (2015)⁽⁴⁵⁾	Indonesia	182 F	Control EP: 54·3 (sd 3·42), control NEP: 52·2 (sd 3·24), intervention EP: 53·3 (sd 34·6), intervention NEP: 53·7 (sd 3·65)	110 EP/72 NEP	Baseline blood equol concentration >5 ng/ml	Postmenopausal	DB	Fair
Qin et al. (2014)⁽⁶²⁾	China	91 M/86 F	Control: 52·9 (sd 6·0), low daidzein: 54·5 (sd 6·6), high daidzein: 53·4 (sd 6·4)	106 EP/71 NEP	Urinary equol concentration >1000 nmol/l, log₁₀-transformed urinary S-equol:daidzein ratio > −1·75 after daidzein intervention	Hypercholesterolaemic	DB	Fair
Reimann et al. (2006)⁽⁴⁶⁾^‖	Denmark, UK, Germany	89 F	59 (sd 5)	29 EP/59 NEP	Urinary equol concentration >936 nmol/l urine	Postmenopausal	CO, DB	Poor
Reverri et al. (2015)⁽⁶³⁾	USA	5 M/12 F	56 (sd 5)	8 EP/9 NEP	Equol/daidzein ≥0·018 with a daidzein threshold of ≥2 nmol/mg creatinine	Postmenopausal, MetS	CO	Poor
Sen et al. (2012)⁽⁴⁷⁾	USA	82 F	39·2 (sd 6·1)	43 EP/39 NEP	Urinary daidzein excretion ≥2 nmol/mg creatinine, urinary equol:daidzein ≥0·018; participants who meet both criteria at least once during the study considered EP	Premenopausal	CO	Poor
Steinberg et al. (2003)⁽⁴⁸⁾	USA	28 F	54·9 (sem 1·0)	10 EP/18 NEP	Not reported	Postmenopausal	CO, DB	Poor
Thorp et al. (2008)⁽⁶⁴⁾	Australia	33 M/58 F	52·7 (sd 1·0)	30 EP/61 NEP	Urinary log₁₀ S-equol:daidzein value > −1·75 after soya or daidzein intervention	Hypercholesterolaemic	CO, DB	Poor
Törmälä et al. (2008)⁽⁴⁹⁾^††	Finland	36 F	57·7 (sem 0·8)	16 EP/20 NEP	>4-fold rise in serum equol concentration	Postmenopausal, using tibolone	CO	Fair
Törmälä et al. (2008)⁽⁵⁰⁾^††	Finland	36 F	57·7 (sem 0·8)	16 EP/20 NEP	>4-fold rise in serum equol concentration	Postmenopausal, using tibolone	CO	Fair
Törmälä et al. (2007)⁽⁵¹⁾^††	Finland	33 F	57·7 (sem 0·8)	14 EP/19 NEP	>4-fold rise in serum equol concentration	Postmenopausal, using tibolone	CO, DB	Fair
Törmälä et al. (2006)⁽⁵²⁾^‡	Finland	30 F	56 (sd 6)	15 EP/15 NEP	Equol concentration > five times baseline after soya isoflavone challenge	Postmenopausal, history of breast cancer	CO, DB	Fair
van der Velpen et al. (2014)⁽⁵³⁾	Netherlands	Low genistein group (LG): 24 F; high genistein group (HG): 31 F	LG: 63·2 (sd 5·5); HG: 63·0 (sd 5·5)	LG: 7 EP/17 NEP; HG: 8 EP/23 NEP	Log₁₀-transformed urinary S-equol:daidzein ratio > 1·75	Postmenopausal	CO, DB	Good
van der Velpen et al. (2013)⁽⁵⁴⁾	Netherlands	30 F	61·1 (sd 5·8)	30 EP/0 NEP	Log₁₀-transformed urinary S-equol:daidzein ratio > −1·75 post-isoflavone or daidzein challenge	Postmenopausal	CO, DB	Good
Welty et al. (2007)⁽⁵⁵⁾^†	USA	60 F	Normotensive: 53·5 (sd 5·3), hypertensive: 58·3 (sd 6·5)	35 EP/25 NEP	Urinary equol concentration greater than 1000 nmol/l	Postmenopausal; hypertensive, prehypertensive, or normotensive	CO	Fair
West et al. (2005)⁽⁶⁵⁾	USA	14 M/18 F	Males: 57·36 (se 1·43), females using HRT: 57·17 (se 2·18), females not using HRT: 59·08 (se 1·54)	11 EP/21 NEP	High concentrations of equol in urine	Postmenopausal, hypercholesterolaemic, adhering to National Cholesterol Education Program Step I diet	CO, DB	Fair
Wong et al. (2012)⁽⁶⁶⁾	Canada	42 M/43 F	59·9 (sd 8·9)	30 EP/55 NEP	Urinary equol >1000 nmol/24 h and log₁₀-transformed urinary equol:daidzein ratio > −1·75	Postmenopausal, hypercholesterolaemic, hyperlipidaemic	Studies 1 and 2: CO; study 3: P	Poor

M, male; F, female; NEP, non-equol producer; MetS, metabolic syndrome; CO, crossover; DB, double-blind; P, parallel; B, blinded; SB, single-blinded; HRT, hormone replacement therapy.

The quality of the RCT were evaluated based on the main outcomes reported. RCT were given a score of ‘good’, ‘fair’ or ‘poor’ after appraising the degree to which flaws in the study designs could affect the validity of the results.

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