Table 1.
Characteristics of selected randomized controlled studies assessing the effects of soy isoflavones on biochemical bone turnover markers in postmenopausal women.
| First Author Year Country |
Study Design Follow-up |
Participants a Age, y (Range) Treated/Control |
Intervention form Therapy and Daily Dosage b vs. Control |
Indices c Formation Markers Resorption Markers |
|---|---|---|---|---|
| Knight [36] 2001 UK |
Double-blind, parallel group 3-months |
53.1 ± 4.6 (40–65) 3.6 ± 4.5 ysm 9/11 |
Beverage powder 60 g SP, 134.4 mg Isof (aglycones: 77.4 mg) vs. casein protein |
OC |
| Morabito [37] 2002 Italy |
Double-blind, parallel group 12-months |
51.5 ± 4.5 (47–57) 6.5 ± 2.5 ysm BMI 24 ± 3 T-score = 1 SD 30/30 |
Tablet 54 mg Isof (Gen, purity ~98%) vs. placebo |
OC, BAP YD, DPD |
| Arjmandi [38] 2003 USA |
Double-blind, parallel group 3-months |
62.1 ± 11.0 BMI 32.2 ± 8.0 20/22 |
Powder in drink mix 40 g SP, 88.4 mg Isof vs. 40 g milk protein |
BAP DPD |
| Dalais [39] 2003 Australia |
Double-blind, parallel group 3-months |
60.0 ± 6.2 (50–75) BMI 25.5 ± 4.6 38/40 |
Powder mixed with drinks or food 40 g SP, 118 mg Isof (aglycones: 69 mg) vs. 40 g casein protein |
PYD, DPD |
| Uesugi [40] 2003 Japan |
Double-blind, parallel group 3-months |
53.7 ± 6.9 (45–65) 6.0 ± 6.0 ysm BMI 22.6 ± 2.8 11/10 |
Capsule 61.8 mg Isof (glycosides: 31.2 mg Dai, 6.8 mg Gen, 21.6 Gly) vs. placebo (dextrin) |
PYD |
| Brooks [41] 2004 Canada |
Double-blind, parallel group 16-weeks |
53.4 ± 3.02 <5 ysm BMI 27.4 ± 5.3 13/15 |
Muffins 25 g SP, 41.9 mg Isof (15.5 mg Dai, 25.7 mg Gen, 0.7 mg Gly) vs. 25 g whole-wheat flour |
BAP DPD |
| Nikander [42] 2004 Finland |
Double-blind, cross-over trial 3-months |
55 ± 6 (35–69) ≥ 5 ysm BMI 26.3 ± 3.3 28/28 |
Tablet 114 mg Isof (aglycones: 58% Gly, 36% Dai,6% Gen) vs. placebo |
BAP, PINP, PICP PYD, DPD, NTX |
| Kreijkamp-Kaspers [43] 2004 Netherlands |
Double-blind, parallel group 12-months |
66.6 ± 4.8 (60–75) 18.0 ± 7.0 ysm BMI 26.2 ± 3.8 88/87 |
Powder mixed with drinks or food 25.6 g SP: 99 mg Isof (aglycones: 52 mg Gen, 41 mg Dai, 6 mg Gly) vs. 25.6 g milk protein |
BAP |
| Harkness [44] 2004 USA |
Double-blind, cross-over trial 6-months |
70.6 ± 6.3 19.1 ± 5.5 ysm BMI 26.1 ± 4.8 T = score ≥ −2.5 10/9 |
Pill 110 mg Isof (98% glycosides and 2% aglycones) vs. placebo |
OC, BAP |
| Arjmandi [45] 2005 USA |
Double-blind, parallel group 12-months |
54.5 ± 5.5 (<65) 5.5 ± 5.0 ysm BMI 27.9 ± 5.3 35/27 |
Snack, drink mix or cereal 25 g SP, 60 mg Isof vs. 20 g protein (devoid of soy and isof) |
OC, BAP DPD |
| Wu [46] 2006 Japan |
Double-blind, parallel group 6-months |
54.3 ± 2.9 (45–60) 3.2 ± 1.7 ysm BMI 21.1 ± 2.4 33/33 |
Capsule 75 mg Isof (47 mg aglycones) vs. placebo (dextrin) |
OC, BAP DPD |
| Ye [47] 2006 China |
Single-blind, parallel group, 3 arms trial 6-months |
52.3 ± 3.3 (45–60) 2.6 ± 1.5 ysm BMI 22.6 ± 2.3 25/26/27 |
Capsule (a) 126 mg Isof, (b) 84 mg isoflavones (aglycones: 52% Dai, 15% Gen, 33% Gly) vs. placebo (starch) |
OC, BAP DPD |
| Evans [48] 2007 USA |
Double-blind, parallel group 9-months |
63.1 ± 5.1 (50–65) 8.2 ± 5.1 ysm BMI 26.8 ± 2.8 21/22 |
Protein beverage products 25.6 g SP, 91.5 mg Isof (aglycones) vs. 25.6 g milk protein |
BAP CTX |
| Brink [49] 2008 Netherlands, Italy, France |
Double-blind, parallel group, international, multicenter trial 12-months |
53 ± 3 2.7 ± 1.3 ysm BMI 24.5 ± 2.1 118 (NL 45; I, 39; F, 34)/119 (NL, 46; I, 39; F, 34) |
Biscuits or bars 110 mg Isof (aglycones: 60–75% Gen, 25–35% Dai, 1–5% Gly) vs. control |
BAP, PINP PYD, DPD |
| Marini [50] 2008 Italy |
Double-blind, parallel group 24-months |
53.7 ± 2.5 3.6 ± 2.6 ysm BMI 24.9 ± 3.7 71/67 |
Tablet 54 mg Isof (Gen, purity ~98% vs. placebo |
BAP PYD, DPD, CTX |
| Turhan [51] 2008 Turkey |
Single-blind, parallel group 6-months |
51.5 ± 5.2 (42–59) 3.7 ± 1.8 ysm BMI 27.0 ± 3.1 45/45 |
Tablet 80 mg isof (aglycones: 59.6 mg Gen, 15.6 mg Dai, 4.8 Gly) vs. placebo (starch) |
OC CTX |
| Kenny [52] 2009 United States |
Double-blind, parallel group 12-months |
72.9 ± 5.9 (60–93) 23.1 ± 9.0 ysm BMI 28.9 ± 5.9 25/22 |
Dietary protein + pill 8 g SP + 105 mg Isof (aglycones) vs. 18 g mix of protein (whey, caseinate, egg white) + placebo (maltodextrin) |
BAP NTX |
| Vupadhyayula [53] 2009 USA |
Double-blind, parallel group 24-monts |
66.5 ± 4.5 (>55) 14.3 ± 5.4 ysm BMI 26.3 ± 3.8 T-score > −2.5 30/35 |
Powder 25 g SP, 90 mg Isof vs. 25 g milk protein |
NTX |
| Levis [54] 2011 USA |
Double-blind, parallel group 24-months |
52.5 ± 3.3 (45–60) BMI 26.3 ± 3.3 T-score > −2.0 99/83 |
Tablet 200 mg Isof (aglycones: 91 mg Gen, 103 mg Dai) vs. placebo |
NTX |
| Tai [55] 2012 Taiwan |
Double-blind, parallel group 24-months |
55.9 ± 3.8 (45–65) 5.1 ± 2.7 ysm BMI 22.9 ± 2.6 200/199 |
Capsule 300 mg Isof (aglycones: 57.5% Gen, 42.5% Dai) vs. placebo (cellulose) |
BAP NTX |
| Lee [56] 2017 Korea |
Double-blind, parallel group 3-months |
53.6 ± 3.4 (45–60) 3.6 ± 2.3 ysm BMI 19.0–30.0 41/43 |
Tablet 70 mg Isof (glycosides: 38 mg Gly, 20 mg Dai, 12.4 mg Gen)vs. placebo (dextrin) |
OC, BAP DPD, NTX, CTX |
| Sathyapalan [57] 2017 UK |
Double-blind, parallel group 6-months |
50 y≤ 2 ysm, BMI, 26.9 ± 5.8 60/60 |
Snack bar 15 g SP, 66 mg Isof (90% glycosides, 10% aglycones) vs. 15 g soy protein alone |
PINP CTX |
| Zhang [58] 2020 China |
Double-blind, parallel group 6-months |
58 ± 3.1 (40–55) 4.0 ± 3.2 ysm BMI 23.3 ± 3.2 38/37 |
Tablet 60 mg Isof vs. placebo (microcrystalline cellulose, dextrin) |
OC |
Data are presented as mean ± standard deviation. Here: a BMI, body mass index (kg/m2); n, number of women; T-score, the standard deviation from peak bone mass in healthy people 30-year-old; ysm, years since menopause; NL, the Netherlands; I, Italy; F, France; b Agly, aglycones; Dai, daidz(in)ein; Gen, genist(in)ein; Gly, glycit(in)ein; Glyco, glycosides; Isof, isoflavones; SP, soy protein; c BAP, bone alkaline phosphatase; CTX, C-terminal telopeptide of type I collagen; u-DPD, urine deoxypyridinoline; OC, osteocalcin; PINP, procollagen I amino-terminal propeptide; u-PYD, urine pyridinoline; u-NTX, urine N-terminal telopeptide of type I collagen.