Soy
Soy/Drug Interactions:
Alzheimer's agentsAlzheimer's agents: Animal research suggests that soy may potentially play a role in Alzheimer's disease (12), although rigorous human research is lacking in this population. According to a systematic literature review, soy has demonstrated conflicting effects on human cognition (59). In clinical research on postmenopausal women, soy isoflavone supplementation was found to improve cognitive performance (257). In older men and women, isoflavones improved visual-spatial memory and construction, verbal fluency, and speeded dexterity (258). AntibioticsAntibiotics: In clinical research, consumption of soy-based foods by humans with tuberculosis increased the tolerance of antimicrobial agents (259). Antibiotics may inhibit intestinal bacteria from converting isoflavones to their active forms (260). Anticoagulants and antiplateletsAnticoagulants and antiplatelets: Soy protein may decrease platelet aggregation ex vivo (52; 53). Soymilk has reportedly reduced the international normalized ratio in a patient stabilized on warfarin (54). The exact mechanism is not well understood. Antidiabetic agentsAntidiabetic agents: Data from a meta-analysis suggest that a whole soy diet, but not supplementation with isolated soy protein, reduces fasting glucose (64). In clinical research, consumption of soy nuts reduced fasting plasma glucose in women with metabolic syndrome on the DASH diet (149). In other clinical research, compared with other sources of protein in a meal, soy protein decreased postprandial area under the curve for glucose, as well as the insulin:glucose and insulin:C peptide ratios (62). Also, use of a soy-based meal replacement compared with an individualized diet plan as recommended by the American Diabetes Association resulted in a greater number of patients reducing use of sulfonylureas and metformin (261). AntidiarrhealsAntidiarrheals: In clinical research, soy formula reduced the duration of diarrhea in children due to an enhancement of sodium and water absorption by digested soy glucose and amino acids in the gut (170). In other clinical research, the addition of soy polysaccharide to nonregular diets increased the moisture content of stool and decreased the number of liquid stools (122; 123). AntiestrogensAntiestrogens: Soy isoflavones, genistein and daidzein, have been shown to reduce the effectiveness of tamoxifen in animal research, possibly due to competition at alpha and beta estrogen receptor binding sites (262). In theory, soy may competitively inhibit conventional estrogen replacement therapy. Soy contains "phytoestrogens" (plant-based compounds with weak estrogen-like properties) such as isoflavones, which may stimulate or block the effects of estrogen. AntihypertensivesAntihypertensives: In clinical research, supplementation with 40g of soy protein daily in cereal increased the 24-hour area under curve for blood pressure, daytime systolic blood pressure, and daytime diastolic blood pressure (51). However, results from other clinical research suggests that soy protein decreases blood pressure (125; 124; 127). The effects of soy with antihypertensive agents are not well understood. Antilipemic agentsAntilipemic agents: In clinical research, use of soy protein has been shown to reduce plasma total cholesterol and low-density lipoprotein (LDL) cholesterol as well as triglycerides (7; 8; 263; 132; 76; 133; 77; 78). Increased high-density lipoprotein (HDL) levels have also been observed in human and animal research (227; 264; 7; 132; 76; 77; 78). According to limited human research, simvastatin in combination with a soy protein diet may further lower serum total cholesterol, LDL, and very-low-density lipoprotein (VLDL), and may increase HDL, compared to diet alone (265). Antineoplastic agentsAntineoplastic agents: According to case-control, epidemiological, and clinical research, soy may reduce the risk of various types of cancer (266; 267; 268; 71; 269; 270; 271; 272; 273; 274; 48; 91; 87; 88; 275; 276; 277; 278; 279; 280; 281; 282; 283; 284). The soy isoflavones genistein and daidzein have been shown to reduce the effectiveness of tamoxifen in animal research, possibly due to competition at alpha and beta estrogen receptor binding sites (262). According to limited animal research, soybean meal and soybean concentrate may be protective and/or alleviate methotrexate-induced anorexia and diarrhea (285). Antiobesity agentsAntiobesity agents: In clinical research, consumption of soy isoflavones as part of cereal bars increased levels of peptide YY, a satiety hormone (286). However, other human research has shown a lack of effect on weight, height, body mass index (BMI), and percentage body fat following the use of soy isolate, soy concentrate, a mixture of soy isolate and whey blend, or adjunct soy protein to a cholesterol-lowering diet (158; 287). The effects of soy with antiobesity agents are not well understood. Aromatase inhibitorsAromatase inhibitors: In theory, due to potential estrogen-like properties of soy, the effects of aromatase inhibitors may be reduced. Soy contains "phytoestrogens" (plant-based compounds with weak estrogen-like properties) such as isoflavones, which may stimulate or block the effects of estrogen.CalcitriolCalcitriol: In vitro, genistein, a major component of soy, is a potent inhibitor of the activity of CYP24, the enzyme that initiates the degradation of calcitriol (71). Cardiovascular agentsCardiovascular agents: Animal research suggests that soy isoflavonoids in soy protein reduce the extent of common carotid and internal carotid artery atherosclerosis (288; 289). In clinical research, use of soy protein has been shown to reduce plasma total and LDL cholesterol as well as triglycerides (7; 8; 263; 132; 76; 133; 77; 78). According to limited human research, simvastatin in combination with a soy protein diet may further lower serum total cholesterol, LDL, VLDL, and may increase HDL, compared to diet alone (265). Various adverse cardiovascular effects, including reduced endothelial function (93), impaired coronary microvascular function (61), and increased blood pressure (51) have been associated with the use of soy in human research. Cytochrome P450 metabolized agentsCytochrome P450 metabolized agents: In vitro, genistein, a major component of soy, was a potent inhibitor of the activity of CYP24 (71). Dermatologic agentsDermatologic agents: In human research, oral fermented soy extract reduced skin wrinkling, and topical coadministration of soy, milk thistle, and gotu kola extract improved skin elasticity and firmness (290). DiureticsDiuretics: In animal research, the soy isoflavone genistein induced maximal salidiuretic action similarly to that of furosemide in the kidney (291). Drugs used for osteoporosisDrugs used for osteoporosis: Animal, human, and in vitro research suggest that soy protein may have positive effects on bone density (292; 293; 294; 295; 296; 297), although findings in this area have been inconsistent (161; 80). The effects of soy with other drugs used for osteoporosis are not well understood. EstrogensEstrogens: In theory, soy may competitively inhibit conventional estrogen replacement therapy. Soy contains phytoestrogens (plant-based compounds with weak estrogen-like properties) such as isoflavones, which may stimulate or block the effects of estrogen.Gastrointestinal agentsGastrointestinal agents: In human in vivo research, soy protein has been reported to reduce gastric acid secretion by 30-40% compared to beef protein (298). In clinical research, the addition of soy polysaccharide to nonregular diets increased the moisture content of stool and decreased the number of liquid stools (122; 123). In infants with colic, soymilk formula (e.g., ProSobee?, Soy Enfamil?, and Isomil?) reduced symptoms of colic and the duration of crying vs. both placebo and cow's milk formula, but not vs. dicyclomine (182; 183). Various adverse gastrointestinal effects, including constipation, diarrhea, bloating, and nausea, have been associated with the use of soy in human research (58; 59). Hormonal agentsHormonal agents: Soy may interact with hormonal agents, particularly estrogens, although some human research has demonstrated a lack of effect on total testosterone, free testosterone, circulating estrogen, luteinizing hormone (LH), follicle-stimulating hormone (FSH), sex hormone-binding globulin (SHBG), estradiol, and estrone (26; 27; 299), In theory, soy may competitively inhibit conventional estrogen replacement therapy. In theory, soy may also affect thyroid function, although a literature review suggests there is little evidence that soy foods or isoflavones adversely affect thyroid function in euthyroid, iodine-replete individuals (217). Soy isoflavones, genistein and daidzein, have been shown to reduce the effectiveness of tamoxifen in animal research, possibly due to competition at alpha and beta estrogen receptor binding sites (262). ImmunosuppressantsImmunosuppressants: In clinical research on postmenopausal women, isoflavones alone and from soymilk increased B cell populations and lowered levels of 8-hydroxy-2-deoxy-guanosine, an oxidative marker of DNA damage (65). The potential for decreased immunity following isoflavone use has been suggested, based on animal models (66). The effects of soy with immunosuppressant agents are not well understood. IndomethacinIndomethacin: According to animal research, indomethacin may reduce the salidiuretic effect of the soy isoflavone, genistein, in the kidney (291). Insect repellantsInsect repellants: In human research, a soybean oil-based repellent was shown to protect against mosquito bites, although it was less effective than DEET-based products (30). Iron saltsIron salts: Soy protein has been shown to modify iron status in various human research. Changes include a reduction in the percentage of nonheme iron absorption (69; 70). Other research suggests enhanced iron absorption with increased soy food intake in humans (67) or no effect (300). Phytic acid and a protein-related moiety in the conglycinin fraction of soybean-protein isolates may be responsible for the potential inhibition of iron absorption (301). A study of 242 Indian women found iron absorption to be enhanced by silken tofu, natto, tempeh, rice miso, barley miso, and soybean miso (67). Iron-fortified soy sauce has been investigated as a source of iron fortification in China (302). Another study found the iron status of 69 perimenopausal women to be unaffected by a soy protein isolate diet (300). A clinical study of 10 infants found that the removal of phytic acid or increasing ascorbic acid in soy-based infant formulas improved the bioavailability of iron in the formulas (168). Neurologic agentsNeurologic agents: Animal research suggests that soy may potentially play a role in Alzheimer's disease (12), although rigorous human research is lacking in this population. According to a systematic literature review, soy has demonstrated conflicting effects on human cognition (59). In clinical research on postmenopausal women, soy isoflavone supplementation was found to improve cognitive performance (257). In older men and women, isoflavones improved visual-spatial memory and construction, verbal fluency, and speeded dexterity (258). ProgestinsProgestins: In clinical research, significant bone loss occurred in women with osteoporosis who received a combination of transdermal progesterone with soymilk containing isoflavones (160). Bone loss was lacking in women taking soymilk or progesterone alone. Selective estrogen receptor modifiers (SERMs)Selective estrogen receptor modifiers (SERMs): Soy isoflavones, genistein and daidzein, have been shown to reduce the effectiveness of tamoxifen in animal research, possibly due to competition at alpha and beta estrogen receptor binding sites (262). Soy contains phytoestrogens (plant-based compounds with weak estrogen-like properties) such as isoflavones, which may stimulate or block the effects of estrogen. Thyroid hormonesThyroid hormones: A literature review suggests that there is little evidence that soy foods or isoflavones adversely affect thyroid function in euthyroid, iodine-replete individuals (217). Soy foods and formulas may increase the dose of thyroid hormone (e.g., levothyroxine) required by hypothyroid patients by impairing absorption of levothyroxine (303). Also, in theory, soy protein foods may increase the risk of developing hypothyroidism in individuals with compromised thyroid function or in those whose iodine intake is marginal. TiboloneTibolone: The potential for soy supplementation for interaction with tibolone has been investigated in various human studies. Soy supplementation lacked an effect on arterial stiffness, endothelial function, or blood pressure in women on tibolone (304; 305). In women and monkeys, soy protein use reduced tibolone-induced increases in LDL cholesterol (306). In long-term tibolone users, soy decreased levels of testosterone and estrone in some patients (307). Soy/Herb/Supplement Interactions:
Alzheimer's agentsAlzheimer's agents: Animal research suggests that soy may potentially play a role in Alzheimer's disease (12), although rigorous human research is lacking in this population. According to a systematic literature review, soy has demonstrated conflicting effects on human cognition (59). In clinical research on postmenopausal women, soy isoflavone supplementation was found to improve cognitive performance (257). In older men and women, isoflavones improved visual-spatial memory and construction, verbal fluency, and speeded dexterity (258). AntibacterialsAntibacterials: In clinical research, consumption of soy-based foods by humans with tuberculosis increased the tolerance of antimicrobial agents (259). Antibiotics may inhibit intestinal bacteria to convert isoflavones to their active forms (260). Anticoagulants and antiplateletsAnticoagulants and antiplatelets: Soy protein may decrease platelet aggregation ex vivo (52; 53). Soymilk has reportedly reduced the international normalized ratio in a patient stabilized on warfarin (54). The exact mechanism is not well understood. AntidiarrhealsAntidiarrheals: In clinical research, soy formula reduced the duration of diarrhea in children due to an enhancement of sodium and water absorption by digested soy glucose and amino acids in the gut (170). In other clinical research, the addition of soy polysaccharide to nonregular diets increased the moisture content of stool and decreased the number of liquid stools (122; 123). AntiestrogensAntiestrogens: Soy isoflavones, genistein and daidzein, have been shown to reduce the effectiveness of tamoxifen in animal research, possibly due to competition at alpha and beta estrogen receptor binding sites (262). Soy contains phytoestrogens (plant-based compounds with weak estrogen-like properties) such as isoflavones, which may stimulate or block the effects of estrogen. AntilipemicsAntilipemics: In clinical research, use of soy protein has been shown to reduce plasma total cholesterol and LDL cholesterol as well as triglycerides (7; 8; 263; 132; 76; 133; 77; 78). Increased HDL levels have also been observed in human and animal research (227; 264; 7; 132; 76; 77; 78). According to clinical research, soy protein and beta-sitosterol may have additive effects in humans (308; 309; 310). AntineoplasticsAntineoplastics: According to case control, epidemiological, and clinical research, soy may reduce the risk of various types of cancer (266; 267; 268; 71; 269; 270; 271; 272; 273; 274; 48; 91; 87; 88; 275; 276; 277; 278; 279; 280; 281; 282; 283; 284). The soy isoflavones genistein and daidzein have been shown to reduce the effectiveness of tamoxifen in animal research, possibly due to competition at alpha and beta estrogen receptor binding sites (262). According to limited animal research, soybean meal and soybean concentrate may be protective and/or alleviate methotrexate-induced anorexia and diarrhea (285). Antiobesity herbs and supplementsAntiobesity herbs and supplements: In clinical research, consumption of soy isoflavones as part of cereal bars increased levels of peptide YY, a satiety hormone (286). However, other human research has shown a lack of effect on weight, height, BMI, and percentage body fat following the use of soy isolate, soy concentrate, a mixture of soy isolate and whey blend, or adjunct soy protein to a cholesterol-lowering diet (158; 287). The effects of soy with antiobesity agents are not well understood. AntioxidantsAntioxidants: According to human research, soy may have antioxidant effects (83; 49). The effects of soy with other antioxidants are not well understood. AvocadoAvocado: In clinical research, a combination of avocado and soybean unsaponifiables improved symptoms of knee or hip osteoarthritis (311; 312; 313). Beta-sitosterolBeta-sitosterol: According to clinical research, soy protein and beta-sitosterol may have additive effects in humans (308; 309; 310). Black cohosh (Actaea racemosa)Black cohosh (Actaea racemosa): A supplement containing soy isoflavones and Actaea racemosa L. did not modify lipid and nonlipid cardiovascular disease risk factors in menopausal women (314). Dietary soy counseling in women using a multibotanical containing black cohosh lacked an effect on vaginal epithelium, endometrium, or reproductive hormones (315). The combined effects of soy protein and Actaea racemosa are unclear. Branched-chain amino acidsBranched-chain amino acids: In clinical research, the addition of branched-chain amino acids to a soy protein meal in humans with chronic obstructive pulmonary disease increased whole-body protein synthesis and decreased breakdown over soy protein alone (316). CalciumCalcium: Theoretically, soy protein may inhibit calcium absorption. In humans, urinary calcium excretion was significantly less with consumption of a soy diet vs. a control diet, and fractional calcium absorption was unaffected (317). In a study in women, urinary calcium did not differ with the type of protein (animal vs. soy) (318). However, in a subset of subjects, intestinal calcium absorption was slightly lower when the soy diet was consumed. In clinical research, a combination of soy isoflavones, lactobacilli, calcium, vitamin D3, magnolia bark extract, and magnesium decreased menopausal symptoms and increased well-being (319). Cardiovascular herbs and supplementsCardiovascular herbs and supplements: Animal research suggests that soy isoflavonoids in soy protein reduce the extent of common carotid and internal carotid artery atherosclerosis (288; 289). In clinical research, use of soy protein has been shown to reduce plasma total and LDL cholesterol as well as triglycerides (7; 8; 263; 132; 76; 133; 77; 78). Various adverse cardiovascular effects, including reduced endothelial function (93), impaired coronary microvascular function (61), and increased blood pressure (51) have been associated with the use of soy in human research. Cytochrome P450 metabolized herbs and supplementsCytochrome P450 metabolized herbs and supplements: In vitro, genistein, a major component of soy, was a potent inhibitor of the activity of CYP24 (71). Dermatologic agentsDermatologic agents: In human research, oral fermented soy extract reduced skin wrinkling, and topical coadministration of soy, milk thistle, and gotu kola extract improved skin elasticity and firmness (290). DiureticsDiuretics: In animal research, the soy isoflavone genistein induced maximal salidiuretic action similar to that of furosemide in the kidney (291). FlaxseedFlaxseed: According to clinical research, a combination of soy and flax may have additive effects on menopausal symptoms (320; 321). Gastrointestinal herbs and supplementsGastrointestinal herbs and supplements: In human in vivo research, soy protein was reported to reduce gastric acid secretion by 30-40% compared to beef protein (298). In clinical research, the addition of soy polysaccharide to nonregular diets increased the moisture content of stool and decreased the number of liquid stools (122; 123). In infants with colic, soymilk formula (e.g., ProSobee?, Soy Enfamil?, and Isomil?) reduced symptoms of colic and the duration of crying vs. both placebo and cow's milk formula, but not vs. dicyclomine (182; 183). Various adverse gastrointestinal effects, including constipation, diarrhea, bloating, and nausea, have been associated with the use of soy in human research (58; 59). GinsengGinseng: Theoretically, there is a potential for interaction between soy extract and Panax ginseng. The potential for interaction with soy protein is unclear.Green teaGreen tea: In human research, a combination of soy and green tea reduced cholesterol levels over either of these compounds alone (86). Hormonal herbs and supplementsHormonal herbs and supplements: Soy may interact with hormonal agents, particularly estrogens, although some human research has demonstrated a lack of effect on total testosterone, free testosterone, circulating estrogen, LH, FSH, SHBG, estradiol, and estrone (26; 27; 299). In theory, soy may competitively inhibit conventional estrogen replacement therapy. Soy contains phytoestrogens (plant-based compounds with weak estrogen-like properties) such as isoflavones, which may stimulate or block the effects of estrogen. In theory, soy may also affect thyroid function, although a literature review suggests that there is little evidence that soy foods or isoflavones adversely affect thyroid function in euthyroid, iodine-replete individuals (217). Soy isoflavones, genistein and daidzein, have been shown to reduce the effectiveness of tamoxifen in animal research, possibly due to competition at alpha and beta estrogen receptor binding sites (262). Hormone replacement therapyHormone replacement therapy: In theory, soy may competitively inhibit conventional estrogen replacement therapy. Soy contains phytoestrogens (plant-based compounds with weak estrogen-like properties) such as isoflavones, which may stimulate or block the effects of estrogen.HypoglycemicsHypoglycemics: Data from a meta-analysis suggest that a whole soy diet, but not supplementation with isolated soy protein, reduces fasting glucose (64). In clinical research, consumption of soy nuts reduced fasting plasma glucose in women with metabolic syndrome on the DASH diet (149). In other clinical research, compared with other sources of protein in a meal, soy protein decreased postprandial area under the curve for glucose, as well as the insulin:glucose and insulin:C peptide ratios (62). Also, use of a soy-based meal replacement compared with an individualized diet plan as recommended by the American Diabetes Association resulted in a greater number of patients reducing use of sulfonylureas and metformin (261). HypotensivesHypotensives: In clinical research, supplementation with 40g of soy protein daily in cereal increased the 24-hour area under curve for blood pressure, daytime systolic blood pressure, and daytime diastolic blood pressure (51). However, results from other clinical research suggests that soy protein decreases blood pressure (125; 124; 127). The effects of soy with antihypertensive agents are not well understood. ImmunosuppressantsImmunosuppressants: In clinical research on postmenopausal women, isoflavones alone and from soymilk increased B cell populations and lowered levels of 8-hydroxy-2-deoxy-guanosine, an oxidative marker of DNA damage (65). The potential for decreased immunity following isoflavone use has been suggested, based on animal models (66). The effects of soy with immunosuppressant agents are not well understood. Insect repellantsInsect repellants: In human research, a soybean-oil-based repellent was shown to protect against mosquito bites, although it was less effective than DEET-based products (30). IronIron: Soy protein has been shown to modify iron status in various human research. Changes include a reduction in the percentage of nonheme iron absorption (69; 70). Other research suggests enhanced iron absorption with increased soy food intake in humans (67) or no effect (300). Phytic acid and a protein-related moiety in the conglycinin fraction of soybean-protein isolates may be responsible for the potential inhibition of iron absorption (301). A study of 242 Indian women found iron absorption to be enhanced by silken tofu, natto, tempeh, rice miso, barley miso, and soybean miso (67). Iron-fortified soy sauce has been investigated as a source of iron fortification in China (302). Another study found the iron status of 69 perimenopausal women to be unaffected by a soy protein isolate diet (300). A clinical study of 10 infants found that the removal of phytic acid or increasing ascorbic acid in soy-based infant formulas improved the bioavailability of iron in the formulas (168). IsoflavonesIsoflavones: Theoretically, use of soy protein with purified isoflavone supplements may have additive effects. According to clinical research, plasma and urinary isoflavones (including genistein, daidzein, equol) may increase with increased intake of isoflavones from soy protein (322; 129; 323; 324; 325; 326; 63; 327). LecithinLecithin: According to human research, a combination of soy lecithin and soy protein may have additive effects on cholesterol levels (328). LycopeneLycopene: In human research, an additive effect was lacking between lycopene supplementation and soy isoflavones with respect to prostate-specific antigen levels and prostate cancer (329). MagnesiumMagnesium: In clinical research, a combination of soy isoflavones, lactobacilli, calcium, vitamin D3, magnolia bark extract, and magnesium decreased menopausal symptoms and increased well-being (319). Magnolia bark extractMagnolia bark extract: In clinical research, a combination of soy isoflavones, lactobacilli, calcium, vitamin D3, magnolia bark extract, and magnesium decreased menopausal symptoms and increased well-being (319). ManganeseManganese: A study of 16 healthy volunteers found that the dephytinization of soy formula approximately doubled the absorption rate of fractional manganese (330). Neurologic agentsNeurologic agents: Animal research suggests that soy may potentially play a role in Alzheimer's disease (12), although rigorous human research is lacking in this population. According to a systematic literature review, soy has demonstrated conflicting effects on human cognition (59). In clinical research on postmenopausal women, soy isoflavone supplementation was found to improve cognitive performance (257). In older men and women, isoflavones improved visual-spatial memory and construction, verbal fluency, and speeded dexterity (258). OatsOats: In clinical research, a soy- and oat-supplemented American Heart Association Step I diet has been shown to be effective in reducing total and LDL cholesterol levels in postmenopausal women with moderate hypercholesterolemia (331). Osteoporosis herbs/supplementsOsteoporosis herbs/supplements: Animal, human, and in vitro research suggest that soy protein may have positive effects on bone density (292; 293; 294; 295; 296; 297), although findings in this area have been inconsistent (161; 80). The effects of soy with other agents used for osteoporosis are not well understood. Plant sterolsPlant sterols: A diet containing soy protein and plant sterols resulted in cholesterol reduction in human subjects (332; 333). A soy and plant sterol-enriched drink has also been shown to reduce LDL cholesterol vs. soy drink alone, although effects were lacking for HDL cholesterol and triglycerides (334). PhosphorusPhosphorus: Theoretically, soy protein may inhibit phosphate absorption.PhytoestrogensPhytoestrogens: In theory, soy may competitively inhibit conventional estrogen replacement therapy. Soy contains phytoestrogens (plant-based compounds with weak estrogen-like properties) such as isoflavones. These isoflavones may stimulate or block the effects of estrogen.PhytoprogestinsPhytoprogestins: In clinical research, significant bone loss occurred in women with osteoporosis who received a combination of transdermal progesterone with soymilk containing isoflavones (160). Bone loss was lacking in women taking soymilk or progesterone alone. ProbioticsProbiotics: In human research, increased probiotic yogurt lacked an effect on isoflavone bioavailability in subjects consuming a high-soy diet (335; 336). In one study, probiotics reduced excretion of soy isoflavones following use of soy (337). In clinical research, a combination of soy isoflavones, lactobacilli, calcium, vitamin D3, magnolia bark extract, and magnesium decreased menopausal symptoms and increased well-being (319). ResveratrolResveratrol: According to in vitro and animal research, resveratrol and genistein may have additive anticancer effects (266). SeaweedSeaweed: Soy supplementation lacked an effect on thyroid endpoints in women supplemented with seaweed (338). SeleniumSelenium: In clinical research, infants fed soy formula were found to have lower plasma, red blood cell, and urine selenium concentrations than infants fed soy formula with added selenium (339). SpirulinaSpirulina: In human research, both spirulina and soy protein increased blood levels of superoxide dismutase following exercise (340). Thyroid agentsThyroid agents: A literature review suggests that there is little evidence that soy foods or isoflavones adversely affect thyroid function in euthyroid, iodine-replete individuals (217). Soy foods and formulas may increase the dose of thyroid hormone (e.g., levothyroxine) required by hypothyroid patients by impairing absorption of levothyroxine (303). Also, in theory, soy protein foods may increase the risk of developing hypothyroidism in individuals with compromised thyroid function or in those whose iodine intake is marginal. Vitamin CVitamin C: A clinical study of 10 infants found that increasing ascorbic acid in soy-based infant formulas improved the bioavailability of iron in the formulas (168). Vitamin DVitamin D: In vitro, genistein, a major component of soy, is a potent inhibitor of the activity of CYP24, the enzyme that initiates the degradation of calcitriol (71). In clinical research, a combination of soy isoflavones, lactobacilli, calcium, vitamin D3, magnolia bark extract, and magnesium decreased menopausal symptoms and increased well-being (319). ZincZinc: In human research, infants four months of age fed a soy-based formula had lower plasma zinc levels than breastfed infants (244). Soy/Food Interactions:
AvocadoAvocado: In clinical research, a combination of avocado and soybean unsaponifiables improved symptoms of knee or hip osteoarthritis (311; 312; 313). Branched-chain amino acidsBranched-chain amino acids: In clinical research, the addition of branched-chain amino acids to a soy protein meal in humans with chronic obstructive pulmonary disease increased whole body protein synthesis and decreased breakdown over soy protein alone (316). Calcium-containing foodsCalcium-containing foods
: Theoretically, soy protein may inhibit calcium absorption. In humans, urinary calcium excretion was significantly less with consumption of a soy diet vs. a control diet, and fractional calcium absorption was unaffected (317). In a study in women, urinary calcium did not differ with the type of protein (animal vs. soy) (318). However, in a subset of subjects, intestinal calcium absorption was slightly lower when they consumed the soy diet. In clinical research, a combination of soy isoflavones, lactobacilli, calcium, vitamin D3, magnolia bark extract, and magnesium decreased menopausal symptoms and increased well-being (319). DASH diet (Dietary Approaches to Stop Hypertension)DASH diet (Dietary Approaches to Stop Hypertension): In clinical research, substituting soy protein or soy nuts for red meat in the DASH diet has been investigated (149). Consumption of soy nuts decreased the homeostasis model of assessment-insulin resistance (HOMA-IR) score and reduced fasting plasma glucose and LDL cholesterol. According to review data, soy consumption may have additive effects with the DASH diet for increasing HDL cholesterol levels (341). FiberFiber: In clinical research, when soy fiber was added to soy formula for infants with diarrhea, the duration of illness, percent of stools with watery consistency, or duration of diarrhea was reduced (342; 343; 344). In other clinical research, seven healthy women consuming a single dose of 0.9mg of isoflavones/kg were found to have reduced absorption of genistein when combined with wheat fiber (345). FlaxseedFlaxseed: According to clinical evidence and reviews, a combination of soy and flax may have additive effects on menopausal symptoms (320; 321; 346). Green teaGreen tea: In human research, a combination of soy and green tea reduced cholesterol levels over either of these compounds alone (86). Infant formulasInfant formulas: A clinical study of 10 infants found that removal of phytate or increasing ascorbic acid in soy-based infant formulas improved the bioavailability of iron in the formulas (168). Ironcontaining foodsIron-containing foods
: Soy protein has been shown to modify iron status in various human research. Changes include a reduction in the percentage of nonheme iron absorption (69; 70). Other research suggests enhanced iron absorption with increased soy food intake in humans (67) or no effect (300). Phytic acid and a protein-related moiety in the conglycinin fraction of soybean-protein isolates may be responsible for the potential inhibition of iron absorption (301). A study of 242 Indian women found iron absorption to be enhanced by silken tofu, natto, tempeh, rice miso, barley miso, and soybean miso (67). Iron-fortified soy sauce has been investigated as a source of iron fortification in China (302). Another study found the iron status of 69 perimenopausal women to be unaffected by a soy protein isolate diet (300). A clinical study of 10 infants found that the removal of phytic acid or increasing ascorbic acid in soy-based infant formulas improved the bioavailability of iron in the formulas (168). LactoseLactose: In clinical research, stool output, stool sodium content, and diarrhea symptoms significantly improved in infants receiving a soy-lactose formula vs. soy-based formulas containing sucrose or maltose (347). Low-carbohydrate dietLow-carbohydrate diet: According to review data, soy consumption may have additive effects with a diet low in carbohydrates for increasing HDL cholesterol levels (341). Low-cholesterol dietLow-cholesterol diet: According to review data, a cholesterol-lowering diet with adjunct soy protein lacked an effect on total cholesterol, LDL, HDL, triglycerides, and apolipoproteins A1 and B compared to the diet alone (287). OatsOats: In clinical research, a soy- and oat-supplemented American Heart Association Step I diet has been shown to be effective in reducing total and LDL cholesterol levels in postmenopausal women with moderate hypercholesterolemia (331). Phosphatecontaining foodsPhosphate-containing foods
: Theoretically, soy protein may inhibit phosphate absorption.Probiotic-containing yogurtProbiotic-containing yogurt: In human research, increased probiotic yogurt lacked an effect on isoflavone bioavailability in subjects consuming a high-soy diet (335; 336). ProteinProtein: According to clinical research, compared with other sources of protein in a meal, soy protein may decrease the postprandial area under the curve for glucose, as well as the insulin:glucose and insulin:C peptide ratios (62). Seleniumcontaining foodsSelenium-containing foods
: In clinical research, infants fed soy formula were found to have lower plasma, red blood cell, and urine selenium concentrations than infants fed soy formula with added selenium (339). Soy flourSoy flour: According to clinical research, soy flour may lack inhibition of absorption or elimination of isoflavones from supplements, but may reduce bioavailability of daidzein (324). SucroseSucrose: In clinical research, infants fed a soy-based formula with sucrose, as opposed to lactose, had a lower stool output during the first 24 hours and during illness, and a reduced likelihood of vomiting (179). TomatoesTomatoes: Increased consumption of tomatoes and soy products by prostate cancer patients resulted in good compliance and bioavailability of soy isoflavones (348). Vegetarian dietVegetarian diet: According to clinical research, soy as part of a diet high in fiber, vegetables, and nuts may reduce C-reactive protein (CRP) (349; 350; 351; 352) and LDL cholesterol (353; 264; 354; 355; 349; 350; 351; 352) to the same extent as statins (349; 350; 351; 352). WheatWheat: In clinical research, seven healthy women consuming a single dose of 0.9mg of isoflavones/kg were found to have reduced absorption of genistein when combined with wheat fiber (345). Zinc-containing foodsZinc-containing foods
: In human research, infants four months of age fed a soy-based formula had lower plasma zinc levels than breastfed infants (244). Soy/Lab Interactions:
8-Hydroxy-2-deoxy-guanosine8-Hydroxy-2-deoxy-guanosine: In clinical research on postmenopausal women, soymilk containing isoflavones, as well as isoflavones alone, lowered levels of 8-hydroxy-2-deoxy-guanosine, an oxidative marker of DNA damage (65). AlbuminAlbumin: In clinical research, soy consumption decreased urinary albumin excretion by 9.5% (p<0.0001) in male patients with type 2 diabetes and nephropathy (356). ApolipoproteinApolipoprotein: In clinical research, the ratio of apo B to apo A1 was reduced following a soy protein diet (322). In other clinical research, apo A1 increased following a soy protein diet (357). B cellsB cells: In clinical research on postmenopausal women, soymilk containing isoflavones, as well as isoflavones alone, increased B cell populations (65). Blood glucoseBlood glucose: Data from a meta-analysis suggest that a whole soy diet, but not supplementation with isolated soy protein, reduces fasting glucose (64). In clinical research, consumption of soy nuts reduced fasting plasma glucose in women with metabolic syndrome on the DASH diet (149). In other clinical research, compared with other sources of protein in a meal, soy protein decreased postprandial area under the curve for glucose, as well as the insulin:glucose and insulin:C peptide ratios (62). In clinical research, use of isoflavone supplements in women decreased fasting glucose (63). Also, use of a soy-based meal replacement compared with an individualized diet plan as recommended by the American Diabetes Association resulted in a greater number of patients reducing use of sulfonylureas and metformin (261). Blood pressureBlood pressure: In clinical research, soy protein increased and decreased blood pressure (51; 125; 124; 127). Soy isoflavones lacked an effect on blood pressure in postmenopausal women with endothelial dysfunction (358). Bone markersBone markers: In clinical research, use of soy protein or soy-containing products lacked an effect (359) or reduced (360) urinary pyridinoline or deoxypyridinoline, and increased serum deoxypyridinoline in the early follicular phase of premenopausal women (293). Due to soy intake, other bone marker changes have included reduced serum insulin-like growth factor (IGF)-1 and bone-specific alkaline phosphatase (293), increased bone specific alkaline phosphatase (361), an increased ratio of C-telopeptide to osteocalcin (362), increased serum osteocalcin (363), and decreased levels of undercarboxylated osteocalcin (361). In humans, supplementation with isoflavones (0, 84, or 126mg daily for six months) increased bone mineral density of the spine and femoral neck in a dose-dependent manner (296), and urinary total deoxypyridinoline increased. C-reactive protein (CRP)C-reactive protein (CRP): In clinical research, consumption of soy nuts in place of meat as part of the DASH diet has been shown to reduce CRP (149). In clinical research, soy as part of a diet high in fiber, vegetables, and nuts has been shown to reduce CRP to the same extent as statins (349). In humans, a trend toward decreased CRP was observed after soy protein use (129). A reduction in CRP has been shown by others (110). CalcitriolCalcitriol: In clinical research, the serum concentration of calcitriol was higher during a soy food period compared with a meat protein period (318). CalciumCalcium: Preliminary research suggests that soy may possess estrogen-like effects that affect calcium levels (317; 318). CholecystokininCholecystokinin: In clinical research, consuming soy prolonged the postprandial elevation of cholecystokinin (364). Coagulation panelCoagulation panel: Soy protein may decrease platelet aggregation ex vivo (52; 53). Soymilk has reportedly reduced the international normalized ratio in a patient stabilized on warfarin (54). The exact mechanism is not well understood. Fatty acidsFatty acids: Use of a soy-based infant formula enriched in docosahexaenoic acid and arachidonic acid increases blood levels of these fatty acids (365). FerritinFerritin: In clinical research on postmenopausal women, soy protein reduced ferritin (366). GhrelinGhrelin: In clinical research, consuming soy prolonged the postprandial suppression of ghrelin (364). Also, ghrelin levels were shown to be reduced in individuals who naturally produce equol (286). Glucagon-like peptideGlucagon-like peptide: In clinical research, consuming soy prolonged the postprandial elevation of glucagon-like peptide (GLP)-1 (364). Growth hormoneGrowth hormone: In humans, soy protein stimulated release of growth hormone (367). Heart rateHeart rate: In clinical research, soy protein increased resting heart rate (51). Hemoglobin A1cHemoglobin A1c: In clinical research, use of a soy-based meal replacement compared with an individualized diet plan as recommended by the American Diabetes Association decreased glycosylated hemoglobin Alc (HbA1c) (261). Hemoglobin/hematocritHemoglobin/hematocrit: In women, shoyu soy sauce polysaccharides increased serum levels of hemoglobin and hematocrit (68) Hemostatic factorsHemostatic factors: In clinical research, intake of soy protein lacked an effect on fibrinogen concentration or factor VII or plasminogen activator inhibitor-1 activities (357). HomocysteineHomocysteine: In humans, 50g of soy protein for six weeks decreased homocysteine levels (98). Soy protein also reduced homocysteine in postmenopausal women (366). This has not been observed in all studies (368). HormonesHormones: In clinical research, supplementation with soy protein increased concentrations of estrone and decreased concentrations of dehydroepiandrosterone (DHEA) (369). In healthy men, consumption of soymilk decreased serum estrone and 17? estradiol (370; 371). In healthy females consuming soymilk containing isoflavones, salivary estradiol increased in 24 subjects and decreased in 12 subjects (323). In premenopausal women supplemented with soy isoflavones, serum hormone-binding globulin levels increased, free estradiol decreased, and estrone increased, in more women than in the placebo group (372). In men with prostate cancer, use of soy protein isolate increased urinary estrogens and the ratio of 2:16alpha-hydroxyestrone (373). According to the NTP-CERHR expert panel report on the reproductive and developmental toxicity of soy formula, soy has lacked consistent effects on circulating endogenous estrogens (44). Inflammatory markersInflammatory markers: In human research, soy protein lacked an effect on sE-selectin, soluble vascular cell adhesion molecule-1 (sVCAM-1), and soluble intercellular cell adhesion molecule-1 (sICAM-1) levels (368). Inflammatory markers were reduced in hypertensive women (374). InsulinInsulin: According to review, soy protein decreased the insulin:glucagon ratio (375). In human research, compared with other sources of protein in a meal, soy protein decreased postprandial insulin:glucose and insulin:C peptide ratios (62). Use of isoflavone supplements in women decreased fasting insulin (63). Insulin-like growth factor-1 (IGF-1)Insulin-like growth factor-1 (IGF-1): In clinical research, addition of soy to a low fat diet in men with prostate cancer increased levels of IGF-1 (376). Dewell suggested that consumption of soy protein in the context of comprehensive lifestyle changes has little effect on IGF-1, but exceeding dietary recommendations is not suggested (377). InterleukinInterleukin: In women, a diet high in soy protein increased levels of interleukin-6 (IL-6) (378). IronIron: In women, shoyu soy sauce polysaccharides increased serum levels of iron (68). IsoflavonesIsoflavones: According to clinical research, plasma and urinary isoflavones (including genistein, daidzein, equol) may increase with increased intake of isoflavones from soy protein (322; 129; 323; 324; 325; 326; 63; 327; 379). IsoprostanesIsoprostanes: In clinical research, consumption of dark soy sauce decreased plasma total, free, and esterified F(2)-isoprostanes (380). LDL oxidationLDL oxidation: In humans, tofu increased LDL oxidation lag phase compared with lean meat (381). In humans consuming a diet high in soy protein, oxidized LDL (conjugated dienes in the LDL fraction and the ratio of conjugated dienes to LDL cholesterol) decreased (382). Lipid panelLipid panel: In human research, total and LDL cholesterol and triglyceride levels were reduced, and HDL levels increased, with soy products (7; 381; 149; 383; 132; 76; 133; 77; 78; 227; 264). In one study, cholesterol absorption from the human small bowel was reduced from 56% to 38% when patients ingested soy sterol ester for a period of three weeks (384). In postmenopausal women, soy isoflavones increased HDL levels in a particular subgroup of estrogen receptor-beta(cx) Tsp509I (genotype AA) (385). Liver enzymesLiver enzymes: Liver enzymes (alanine aminotransferase and aspartate aminotransferase) increased following a low-calorie diet with a soy-based meal replacement (386). It is unclear if this was due to the soy or the calorie reduction. Lp(a)Lp(a): In human research, increased Lp(a) has been shown with soy intake (387; 388; 93). It has also been noted that Lp(a) increased and then decreased to baseline following initiation of a diet high in soy protein (388). Parathyroid hormoneParathyroid hormone: In humans, the serum concentration of parathyroid hormone was higher during a soy food period compared with a meat protein period (318). Peptide YY (PYY)Peptide YY (PYY): In humans, isoflavone supplementation increased levels of PYY in serum (286). PhosphatePhosphate: Soy possesses estrogen-like effects that may theoretically affect phosphate levels.Prostate-specific antigen (PSA)Prostate-specific antigen (PSA): In humans, isoflavones from supplements or soy protein (average of 60-900mg daily) lacked an effect on PSA levels in healthy subjects, but PSA levels may decrease in individuals with prostate cancer (389). SeleniumSelenium: In clinical research, infants fed soy formula were found to have lower plasma, red blood cell, and urine selenium concentrations than infants fed soy formula with added selenium (339). Superoxide dismutaseSuperoxide dismutase: In clinical research, soy protein increased blood levels of superoxide dismutase following exercise (340). Thyroid function testsThyroid function tests: In infants with congenital hypothyroidism on replacement therapy with L-thyroxine, thyroxine levels increased when soy formula was discontinued (303). An infant with an elevated thyroid-stimulating hormone (TSH) level since one week of birth, regardless of L-thyroxine dose, had normalized TSH levels within three weeks of discontinuing soy formula. In another case, a 10-month-old infant was found to have rapid uptake of carrier-free sodium iodide131 after ingesting Mull-Soy? formula since birth (215). Serum T(4) significantly increased in female rats on a diet of 20% defatted soybean (390). There is a case report of an infant receiving soy formula with persistent hypothyroidism (55). In infants with congenital hypothyroidism fed soy formula, prolonged increase of TSH occurred when compared to infants fed nonsoy formula (391); the methods of this study were criticized by Karadag (392). A literature review suggested that there is little evidence that soy foods or isoflavones adversely affect thyroid function in euthyroid, iodine-replete individuals (217). In vitro, soy isoflavones were found to have antithyroid potential (393). Transferrin saturationTransferrin saturation: In postmenopausal women, soy protein reduced transferrin saturation (366). Uric acidUric acid: Infants fed a standard purine soy formula for 11 days were found to have an increase in urinary uric acid (394). 80g of soybean isolate increased serum uric acid and urate clearance three hours after administration in healthy patients (395). Urinary creatinineUrinary creatinine: In patients with diabetes, soy protein improved urinary creatinine levels (110). Urinary nephrogenous cAMPUrinary nephrogenous cAMP: In humans, the concentration of urinary nephrogenous cAMP was higher during a soy food period compared with a meat protein period (318). Urine protein testUrine protein test: In patients with diabetes, soy protein improved proteinuria (110). According to secondary sources, soymilk may induce hypoproteinuria in pediatrics diagnosed with cystic fibrosis.