TABLE 1.
Trial characteristics for the studies included in the analyses of the effect of soy protein intake on circulating LDL cholesterol and TC concentrations in adults
| Study, year (reference) | Participants | Age (y)1 | Baseline plasma LDL-C (mg/dL)1 | Baseline plasma TC (mg/dL)1 | Design | Follow-up | Test soy food/product | Soy protein dose (g/d) | Control food/product | Funding sources |
|---|---|---|---|---|---|---|---|---|---|---|
| Bakhit et al., 1994 (15) | 21 (21 M) HC | 43 (14) | 157.8 (24.0) | 189.9 | Randomized crossover | 4 wk | Muffins with ISP ± cellulose | 25 | Muffins with casein ± cellulose | Industry |
| Blum et al., 2003 (16) | 24 (24 W) HC, PM | 55 (5) | 178.5 (28.5) | 270.5 (31.9) | Randomized crossover | 6 wk | Supplement packets with ISP + isoflavones | 25 | Supplement packets with milk protein | Industry |
| Bosello et al., 1988 (17) | 24 (12 M, 12 W) OB | 25–42 | 149 | 217 | Parallel | 60 d | Commercial textured preparation with soy protein + mineral salts and vitamins | ∼28 | Commercial textured preparation with casein + mineral salts and vitamins | N/A |
| Chen et al., 2006 (19) | 26 (19 M, 7 W) HC, CKD | 58.6 (11.4) | 162.4 | 269.3 | Randomized parallel | 12 wk | Packet of ISP | 30 | Packet of milk protein | Agency |
| Cuevas et al., 2003 (20) | 18 (18 W) HC, PM | 59 (47–70) | 194.8 (25.5) | 285.9 (28.8) | Randomized crossover | 4 wk | Powder with ISP + isoflavones mixed with water | 40 | Powder with caseinate mixed with water | AgencyIndustry |
| Evans et al., 2007 (21) | 22 (22 W) PM | 61.5 (8.2) | N/A | N/A | Randomized crossover | 4 wk | Powder packets and packets of granules with soy protein + isoflavones ± lecithin; powder was mixed with water | 25 | Powder packets and packets of granules with caseinate ± lecithin; powder was mixed with water | Industry |
| Gardner et al., 2001 (23) | 94 (94 W) HC, PM | 59.1 (6.9) | 152 | 230.6 | Randomized parallel | 12 wk | Powder packets with soy protein ± isoflavones mixed with juice, water, or soup | 42 | Powder packets with milk protein mixed with juice, water, or soup | AgencyIndustry |
| Gardner et al., 2007 (22) | 28 (6 M, 22 W) HC | 52 (9) | 183.0 (19.0) | 265.2 (51.4) | Randomized crossover | 4 wk | Whole bean soy milk or isolated soy protein milk | 25 | Dairy milk | AgencyIndustry |
| Goldberg et al., 1982 (24) | 4 (3 M, 1 W) NC, 12 (7 M, 5 W) HC | 36.8 (18.6)43.6 (12.7) | 191.0 (19.0)106.0 (31.0) | 260.0 (23.0)176.0 (17.0) | Randomized crossover | 6 wk | Soy milk and ISP meat analogues | ∼93 ∼98 | Nonfat milk and meat protein products (pork, sausage, hamburger, turkey roll, ham, and bologna) | AgencyIndustry |
| Greany et al., 2004 (26) | 12 (12 W) PM25 (25 W) HC, PM | 57.5 (2.2) | 136.5 (25.9) | 202.6 (5.0) | Randomized crossover | 6 wk | ISP powder ± probiotic capsules | ∼26 | Isolated milk protein powder ± probiotic capsules | Agency |
| Harrison et al., 2004 (27) | 213 (112 M, 101 W) HC or HTN | 52 (4) | 201.1 (42.5) | 263.0 (42.5) | Randomized parallel | 5 wk | Bread, cereal bars, and cracker biscuits fortified with soy protein ± DHA | 25 | Bread, cereal bars, and cracker biscuits fortified with placebo ± DHA | AgencyIndustry |
| Higashi et al., 2001 (28) | 14 (14 M) | 31 (4) | 125.5 | 196.0 | Randomized crossover | 4 wk | ISP mixed with milk or yogurt | 20 | Milk or yogurt | Industry |
| Høie et al., 2005 (29) | 116 (54 M, 62 W) HC | 55.2 (9.5) | 168.0 | 268.8 | Randomized parallel | 8 wk | Powder sachets of soy protein mixed with cold water | 25 | Powder sachets of milk protein mixed with cold water | N/A |
| Høie et al., 2005 (30) | 117 (63 M, 54 W) HC | 53.6 (9.6) | 162.3 | 260.4 | Randomized Parallel | 8 wk | Powder sachets of soy protein mixed with cold water | 15, 25 | Powder sachets of milk protein mixed with cold water | N/A |
| Høie et al., 2006 (31) | 80 (29 M, 51 W) HC | 53.5 | 143.3 | 252.2 | Randomized parallel | 4 wk | ISP + chocolate-flavored milk + ultra-heat-treated | 12.5, 25 | Casein + chocolate-flavored milk + ultra-heat-treated | N/A |
| Høie et al., 2007 (32) | 88 (34 M, 54 W) HC | 54.6 (9.6) | 164.2 | 253.4 | Randomized parallel | 8 wk | ISP powder dissolved in 150 mL of cold water | 25 | Placebo preparation made out of milk protein | Industry |
| Hori et al., 2001 (33) | 21 (21 M) HC | 44.9 | 166.2 | 265.0 | Randomized parallel | 3 mo | Powder drink made with soy protein hydrolysate and bound phospholipids | 4.5 | Powder drink made with casein hydrolyzate | N/A |
| Jayagopal et al., 2002 (34) | 31 (31 W) PM, DM2 | 62.5 (6.77)2 | 137.3 | 220.4 | Randomized crossover | 12 wk | Sachets of ISP ± isoflavones | 30 | Sachets with microcrystalline cellulose | N/A |
| Jenkins et al., 2000 (36) | 25 (15 M, 10 W) PM, HLP | 60.0 (2) | 184.1 | 268.9 | Randomized crossover | 3 wk | Cereal made with soy flour + isoflavones | 36 | Wheat protein + soy oil (7.9 g/d) | AgencyIndustry |
| Jenkins et al., 2002 (35) | 41 (23 M, 18 W) PM, HLP | 62 (12.8) | 176.5 | 261.4 | Randomized crossover | 4 wk | Soy products (low-fat soy milk, soy hot dogs, breakfast links, soy burgers, cold cuts, and tofu burgers) + isoflavones | 51 | Dairy products (skim milk, yogurt, cottage cheese, very low-fat Hoop cheese, cheese made with skim milk) and egg substitute | AgencyIndustry |
| Jenkins et al., 1989 (37) | 11 (11 W) OB | 38 (13.3) | 125.7 (43.6) | 197.6 (55.1) | Randomized crossover | 4 wk | Soy formula with ISP and full-fat soy flour | 17.4 | Milk formula with milk protein isolate and nonfat dry milk | AgencyIndustry |
| Kohno et al., 2006 (38) | 126 (88 M, 38 W)3 95 (47 M, 48 W)3 | 44.8 | 141.4 | 220.9 | Randomized parallel | 12 wk20 wk | Candy containing soybean β-conglycinin | 5 | Candy containing casein | Agency |
| Lichtenstein et al., 2002 (39) | 42 (18 M, 24 W) HC | 62.7 (8.8) | 160.1 (25.1) | 238.6 (18.6) | Randomized crossover | 6 wk | ISP ± powder isoflavones | 63 | Dairy, meat ± powder isoflavones | AgencyIndustry |
| Liu et al., 2012 (40) | 180 (180 W) PM, PD, or DM2 | 56.2 (4.4) | 145.7 | 217.1 | Randomized parallel | 6 mo | Powder with soy protein + isoflavones | 15 | Powder with milk protein ± isoflavones | AgencyIndustry |
| Ma et al., 2005 (41) | 159 (70 M, 89 W) HC | 56.6 (8.4) | 181.6 | 252.6 | Randomized parallel | 5 wk | Powder packets with soy protein + isoflavones in vanilla or chocolate flavors mixed with water | 31.5 | Powder packets with milk protein in vanilla or chocolate flavors mixed with water | Industry |
| Maesta et al., 2007 (42) | 46 (46 W) PM | 59.4 | 146.3 | 233.3 | Randomized parallel | 16 wk | Chocolate-flavored powder with soy protein ± resistance exercise + 200 mL of skim milk | 25 | Chocolate-flavored powder with maltodextrin ± resistance exercise + 200 mL of skim milk | AgencyIndustry |
| Mangano et al., 2013 (43) | 97 (97 W) PM | 73.14 | 132.3 | 207.8 | Randomized parallel | 1 y | Powder packets with ISP ± isoflavones incorporated into commonly consumed beverages or foods | 18 | Powder packets with sodium caseinate + whey + egg white protein ± isoflavones incorporated into commonly consumed beverages or foods | Agency |
| Matthan et al., 2007 (44) | 28 (2 M, 26 W) HC | 65 (6) | 154.3 (20.1) | 237.4 (20.9) | Randomized crossover | 6 wk | Whole soybean (whole organic soybeans, soynuts, defatted soyflakes, soya granules, and soynut butter), soy flour (soy nutlettes, whole-grain soy flour, and textured soy protein products such as Chicken-Not, Beef-Not, and Turkey-Not), or soy milk (tofu, plain soy yogurt, and plain soy milk) products | 37.5 | Animal protein (meats, chicken, eggs, and dairy products) | Agency |
| McVeigh et al., 2006 (45) | 35 (35 M) | 27.9 (5.7) | 106.0 (41.0) | 174.0 (48.3) | Randomized crossover | 57 d | Powder with ISP + isoflavones | 32 | Powder with IMP | AgencyIndustry |
| Mitchell and Collins, 1999 (46) | 10 (10 M) | 20–50 | N/A | 186.1 | Randomized parallel | 4 wk | Soy milk | 1 litter = ∼375 | Rice milk or semi-skim cow's milk | Agency |
| Murkies et al., 1995 (47) | 47 (47 W) PM | 54.9 | 148.3 | 232.3 | Randomized parallel | 12 wk | Raw soy flour, added to a drink or mixed with cereal (or cooked in a muffin) | 45 | Raw wheat flour, added to a drink or mixed with cereal (or cooked in a muffin) | N/A |
| Murray et al., 2003 (48) | 30 (30 W) PM | 54.9 | 133.8 | 224.3 | Randomized parallel | 6 mo | Powder packets with ISP + isoflavones mixed into a morning beverage + estradiol | 25 | Powder packets with placebo mixed into a morning beverage + estradiol | Industry |
| Sagara et al., 2004 (49) | 50 (50 M) HR for CVD | 52.2 | N/A | 235.5 | Randomized parallel | 5 wk | Soy powder mixed in cereals, biscuits, and bread rolls + isoflavones | 20 | Cereals, biscuits, and bread rolls | AgencyIndustry |
| Santo et al., 2008 (50) | 30 (30 M) | 24.2 (2.3) | 116.5 | 179.9 | Randomized parallel | 28 d | Powder packets with ISP ± isoflavones mixed with a beverage of participants’ choice (including milk) | 25 | Powder packets with IMP mixed with a beverage of participants’ choice (including milk) | Industry |
| Steinberg et al., 2003 (51) | 24 (24 W) PM | 54.9 (5.3) | 111.8 (18.9) | 189 (18.9) | Randomized crossover | 6 wk | Powder packets with ISP ± isoflavones mixed with a beverage of participants’ choice | 25 | Powder packets with total milk protein mixed with a beverage of participants’ choice | Industry |
| Takatsuka et al., 2000 (52) | 52 (52 W) PM | 26.1 | 92.7 | 176.6 | Randomized parallel | 2 mo | Usual diet + soy milk (400 mL) | 17.2 | Usual diet | Agency |
| Teede et al., 2001 (53) | 179 (96 M, 83 W) PM | 60.5 (9.6) | 148.8 | 228.2 | Randomized parallel | 3 mo | Powder sachets with ISP + isoflavones mixed into a beverage | 40 | Powder sachets with casein mixed into a beverage | Agency |
| Teixeira et al., 2004 (55) | 14 (14 M) DM2, CKD | 53–73 | 98.8 | 182.7 | Randomized crossover | 8 wk | Vanilla-flavored powder with ISP incorporated into several dishes or drinks | ∼476 | Vanilla-flavored powder with casein incorporated into several dishes or drinks | AgencyIndustry |
| Van Horn et al., 2001 (56) | 127 (127 W) PM, HC | 66.6 (10.3) | 159.3 (29.4) | 251.4 (33.3) | Randomized parallel | 6 wk | Powder with soy protein + isoflavones + oats (cooked oatmeal or ready-to-eat oat bran cereal) Powder with soy protein + isoflavones + wheat cereal (cream of wheat or non-oat ready-to-eat cereal) | 29 | Powder with nonfat milk protein + oats (cooked oatmeal or ready-to-eat oat bran cereal) Powder with nonfat milk protein + wheat cereal (cream of wheat or non-oat ready-to-eat cereal) | Industry |
| van Raaij et al., 1981 (57) | 69 (∼41 M, ∼28 W)7 | 18–28 | 83.6 | 152.4 | Randomized parallel | 4 wk | Specially developed products (milk-like beverages and milk-like beverages fermented to yogurts, brown breads, cookies, and sandwich spreads) with ISP, and gelated product with ISP | 54ŧŧ8 | Specially developed products (milk beverages and milk beverages fermented to yogurts, brown breads, cookies, and sandwich spreads) with caseinate | AgencyIndustry |
| Washburn et al., 1999 (58) | 42 (42 W) PM | 51 (4.8) | 126.9 (38.5) | 208.0 (40.5) | Randomized crossover | 6 wk | Powder packets with soy protein + phytoestrogens mixed with milk, orange juice, yogurt, cereal, or different beverages | 20 | Powder packets with complex carbohydrate supplement mixed with milk, orange juice, yogurt, cereal, or different beverages | Industry |
| West et al., 2005 (59) | 32 (14 M, 18 W) PM, HC | 58 (5.2) | 142.6 (27.0) | 214.3 (24.4) | Randomized crossover | 6 wk | ISP + isoflavones powder, 15 g/d baked into a muffin and 10 g/d integrated into meals provided | 25 | IMP powder, 15 g/d baked into a muffin and 10 g/d integrated into meals provided | Industry |
| Wong et al., 1998 (60) | 13 (13 M) HC13 (13 M) NC | 35.5 (7.2)41.4 (7.8) | 193.0 (24.0)110.2 (18.2) | 273.0 (20.1)167.1 (18.9) | Randomized crossover | 5 wk | ISP incorporated into soy products (beverages, ground meat, and block meat substitutes) | ∼759 | Animal protein (meat) | AgencyIndustry |
1Values are means, means ± SDs, or ranges. CKD, chronic kidney disease; DM2, diabetes mellitus type 2; HC, hypercholesterolemic; HLP, hyperlipidemic; HR for CVD, high risk of cardiovascular disease; HTN, hypertension; IMP, isolated milk protein; ISP, isolated soy protein; M, men; N/A, not available; NC, normocholesterolemic; OB, obese; PD, prediabetes; PM, post-menopausal/perimenopausal; W, women.
2Mean age ± SD from 33 eligible participants.
3126 subjects were included in test 1 and 95 in test 2; however for data analysis, 12 and 7 subjects from test 1 and test 2, respectively, were excluded.
4Mean age for 131 randomized participants.
5Soy dose taken from Soya Unsweetened Drink (Provamel) as 3.7 g/100 mL.
6ISP = 0.5 g/d.
7Men and women taken from the percentage of selected subjects (60% men and 40% women).
865% of protein, 8.4% of energy (∼54 g protein based on 2565 kcal).
9Based on 2000 kcal/d, ∼75% soy protein from 20% total protein intake.