Red clover isoflavones

Isoflavones/Drug Interactions:

  • Alzheimer's agentsAlzheimer's agents: Theoretically, soy (which contains isoflavones) may interact with neurological agents. Animal research suggests that soy may potentially play a role in Alzheimer's disease (13), although human research is conflicting. In postmenopausal women, soy isoflavone supplementation was found to improve cognitive performance (87). However, in human epidemiological research, cognitive impairment and atrophy of the brain were reported to be associated with greater tofu consumption (a source of soy isoflavones) during middle adult life (133).
  • AntibioticsAntibiotics: Consumption of soy-based foods (which contain isoflavones) by humans with tuberculosis may increase tolerance to antimicrobial agents (142). Theoretically, the effect of antibiotics on intestinal bacteria may reduce intestinal metabolism of isoflavones, thus reducing their beneficial effects.
  • Anticoagulants and antiplateletsAnticoagulants and antiplatelets: In human research, isoflavones resulted in a decline in platelet thromboxane A2 receptor density (44). Also, red clover is a source of coumarin, which may increase bleeding risk.
  • Antidiabetic agentsAntidiabetic agents: In epidemiological research, women with high genistein intake had lower fasting insulin levels compared with those that did not consume genistein daily (45). In humans, soy isoflavones lowered blood glucose and insulin levels in some (46), but not all (47), studies.
  • AntiestrogensAntiestrogens: In animal research, genistein bound to the estrogen receptor (48). In human research, consumption of soy, containing isoflavones, decreased estrone and estradiol levels (49). Other changes observed in premenopausal women include decreased 17beta-estradiol, estrone sulfate, estrone, and dehydroepiandrosterone sulfate, dependent on the phase of the menstrual cycle (50; 51; 52; 53), as well as an increased urinary 2/16alpha-(OH) estrone ratio and decreased excretion of 4-(OH) estrone (54). In premenopausal women, soy isoflavones affected menstrual cycle length in some, but not all, studies (143; 112), whereas menstruation was interfered with (increased, decreased, irregular) in a separate study (50).
  • AntihypertensivesAntihypertensives: In human research, isoflavone supplementation has been reported to decrease blood pressure in hypertensive patients (55). In human research, consumption of soy, containing isoflavones, did not have an effect on blood pressure, although the area-under-the-curve profiles of 24-hour blood pressure measurements were higher after soy vs. gluten (144). Isolated isoflavones increased blood pressure in further human research (56). Thus, isoflavones may have additive or antagonistic effects with hypotensive agents.
  • AntilipemicsAntilipemics: In human research, consumption of soy protein from various sources, containing isoflavones, resulted in a reduction of total and LDL cholesterol and triglycerides, in some, but not all, studies (57; 58; 59; 60; 61; 62; 63; 64). The ratios of total and LDL cholesterol to HDL cholesterol, as well as apoB to apo A-1, were also improved (95; 96; 63; 97). Purified isoflavones did not have a reducing effect on plasma lipids in some human studies (47; 61; 98), although increases in HDL (and HDL3) cholesterol and apolipoprotein A-1 have been noted (99; 90; 70; 100; 101; 4), as have reductions in total cholesterol (65), triglycerides (66; 67; 68), and LDL cholesterol (69; 70; 71; 72; 4), and changes in LDL size to be less atherogenic (72) in other studies.
  • AntineoplasticsAntineoplastics: Reduced prostate cancer risk is associated with increased blood levels of certain isoflavones in some epidemiological studies (145), and epidemiological research suggests that consumption of foods such as soy may reduce the risk of endometrial cancer (146). In postmenopausal women, isoflavone supplementation has been reported to decrease plasma concentrations of 8-hydroxy-2-deoxy-guanosine (147). Increased soy consumption, or supplementary isoflavones, did not have an effect on breast epithelial cell proliferation, breast density, or biochemical endpoints indicative of breast cancer risk (148; 118; 116). Purified red clover isoflavones did not have an antiproliferative effect on the endometrium (149). Genistein stimulated the growth of male pancreatic tumor cells in vitro (139).
  • Antiobesity agentsAntiobesity agents: In epidemiological research, women with high genistein intake had a lower body mass index and waist circumference compared with those that did not consume genistein daily (45).
  • Aromatase inhibitorsAromatase inhibitors: In theory, due to potential estrogen-like properties of soy, the effects of aromatase inhibitors may be reduced.
  • CalcitriolCalcitriol: In vitro, genistein has been reported to be a potent inhibitor of CYP24 (150).
  • Cardiovascular agentsCardiovascular agents: In human research, consumption of soy-containing isoflavones resulted in reduced postocclusion peak flow velocity of the brachial artery (151) and improved endothelium-dependent vasodilation (152). Animal research suggests that soy isoflavonoids reduce the extent of common carotid and internal carotid artery atherosclerosis (153; 154). Red clover isoflavones decreased levels of plasminogen activator inhibitor type 1 in human research (67).
  • Cystic fibrosis transmembrane conductance regulator (CFTR) agentsCystic fibrosis transmembrane conductance regulator (CFTR) agents: According to a review, isoflavones may increase the activity of CFTR (155).
  • Cytochrome P450-metabolized agentsCytochrome P450-metabolized agents: In vitro, genistein has been reported to be a potent inhibitor of the activity of CYP24 (150). The effect of flavanoids, in general, including isoflavones, on cytochrome P450 has been reviewed (156). In human research, soy isoflavones did not have an effect on cytochrome P450 3A enzyme induction (157).
  • DiureticsDiuretics: Animal research suggests that the soy isoflavone genistein induced maximal salidiuretic action similar to that of furosemide in rat kidneys (158).
  • Drugs used for osteoporosisDrugs used for osteoporosis: Animal, human, and in vitro research suggests soy protein, containing isoflavones, may have positive effects on bone density (159; 160; 161; 162; 163; 164). Loss of bone mineral content at the hip over one year was reduced in Taiwanese women supplemented with isolated soy isoflavones; this was significant in women who were at least four years past menopause and had lower body weights or lower calcium intakes (165). In men, soy consumption also increased bone density (97).
  • EstrogensEstrogens: In animal research, genistein bound to the estrogen receptor (48). In human research, consumption of soy, containing isoflavones, decreased estrone and estradiol levels (49). Other changes observed in premenopausal women include decreased 17beta-estradiol, estrone sulfate, estrone, and dehydroepiandrosterone sulfate, dependent on the phase of the cycle (50; 51; 52; 53; 4), as well as increased urinary 2/16alpha-(OH) estrone ratio and decreased excretion of 4-(OH) estrone (54). In premenopausal women, soy isoflavones affected menstrual cycle length in some, but not all, studies (143; 112), whereas menstruation was interfered with (increased, decreased, irregular) in a separate study (50). Consumption of soy did not have an effect plasma hormone levels in patients using oral contraceptives (166).
  • Gastrointestinal agents, miscellaneousGastrointestinal agents, miscellaneous: In postmenopausal women, isoflavones have been reported to stimulate the dominant microorganisms of the Clostridium coccoides-Eubacterium rectale cluster, Lactobacillus-Enterococcus group, Faecalibacterium prausnitzii subgroup, and Bifidobacterium genus (167).
  • Hormonal agentsHormonal agents: Based on human research, soy and isoflavones may alter levels of various hormones including progesterone, estrone, estradiol, luteinizing hormone, testosterone, and follicle-stimulating hormone (108; 49; 110; 19; 105; 112). Other changes observed in premenopausal women include decreased 17beta-estradiol, estrone sulfate, estrone, and dehydroepiandrosterone sulfate; increased sex hormone-binding globulin; and altered androstenedione and testosterone levels, dependent on the phase of the menstrual cycle (50; 51; 52; 53), as well as increased urinary 2/16alpha-(OH) estrone ratio and decreased excretion of 4-(OH) estrone (54).
  • ImmunosuppressantsImmunosuppressants: In postmenopausal women, isoflavones alone and from soy milk increased B cell populations and lowered levels of 8-hydroxy-2-deoxy-guanosine, an oxidative marker of DNA damage (147). The potential for decreased immunity following isoflavone use has been suggested, based on animal models (131). In women, but not men, soy protein high in isoflavones increased levels of interleukin-6 (168).
  • IndomethacinIndomethacin: Based on limited animal research, indomethacin may reduce the salidiuretic effect of the soy isoflavone genistein in the kidney (158).
  • MethotrexateMethotrexate: Based on limited animal research, soybean meal and soybean concentrate, sources of isoflavones, may be protective or alleviate methotrexate-induced anorexia and diarrhea (169). Soybean concentrate and soybean isolate have been found to be protective against small intestine necrosis.
  • Neurologic agentsNeurologic agents: In postmenopausal women, soy isoflavone supplementation was found to improve cognitive performance (87).
  • P-glycoprotein-regulated agentsP-glycoprotein-regulated agents: The effect of flavanoids, including isoflavones, on ATB binding cassette efflux transporters has been reviewed (170).
  • ProgesteroneProgesterone: In human research, consumption of soy, containing isoflavones, increased plasma progesterone levels in females (108). In women with osteoporosis given the combination of transdermal progesterone with soy milk containing isoflavones, significant bone loss occurred (171). Bone loss did not occur in women taking soy milk or progesterone alone.
  • Selective estrogen receptor modifiers (SERMs)Selective estrogen receptor modifiers (SERMs): In theory, isoflavones may antagonize the antitumor effects of tamoxifen.
  • TestosteroneTestosterone: Dietary consumption of soy flour reduced levels of testosterone in males (19), and red clover isoflavones increased plasma testosterone in postmenopausal females (105). Testosterone levels were altered in premenopausal women, dependent on the phase of the menstrual cycle.
  • Thyroid hormonesThyroid hormones: Soy isoflavones did not have an effect on thyroid hormone levels in postmenopausal women (113); however, ingestion of soy protein containing isoflavones altered thyroxine, thyroid-stimulating hormone, and triiodothyronine levels in other human studies (73; 50; 53). In a review, collective findings suggested that there is little evidence that, in euthyroid, iodine-replete individuals, soy foods or isoflavones adversely affected thyroid function (10). The review also suggested that soy foods may increase the dose of thyroid hormone required by hypothyroid patients and, in theory, soy protein foods may increase the risk of developing hypothyroidism in individuals with compromised thyroid function or those whose iodine intake is marginal.
  • Tyrosine kinase inhibitorsTyrosine kinase inhibitors: Based on in vitro research, genistein has been shown to be an inhibitor of tyrosine kinase (172; 103).
  • VasodilatorsVasodilators: In human research, isoflavones have been reported to improve endothelium-dependent vasodilatation without an effect on endothelial-independent arterial diameter or flow (80). In human research, infused dehydroequol, a metabolite of diadzein, had vasodilatory properties in human forearm arteries (173).
  • WarfarinWarfarin: In human research, isoflavones resulted in a decline in platelet thromboxane A2 receptor density (44). Also, red clover is a source of coumarin, which may increase bleeding risk. Red clover isoflavones decreased levels of plasminogen activator inhibitor type 1 in human research (67).
  • Isoflavones/Herb/Supplement Interactions:

  • Alzheimer's herbsAlzheimer's herbs: Theoretically, soy (which contains isoflavones) may interact with neurological agents. Animal research suggests that soy may potentially play a role in Alzheimer's disease (13), although human research is conflicting. In postmenopausal women, soy isoflavone supplementation was found to improve cognitive performance (87). However, in human epidemiological research, cognitive impairment and atrophy of the brain late in life were reported to be associated with greater tofu consumption (a source of soy isoflavones) during middle adult life (133).
  • AntibacterialsAntibacterials: Consumption of soy-based foods (which contain isoflavones) by humans with tuberculosis may increase the tolerance of antimicrobial agents (142). In theory, the effect of antibiotics on intestinal bacteria may reduce intestinal metabolism of isoflavones, thus reducing their beneficial effects.
  • Anticoagulants and antiplateletsAnticoagulants and antiplatelets: In human research, isoflavones resulted in a decline in platelet thromboxane A2 receptor density (44). Also, red clover is a source of coumarin, which may increase bleeding risk.
  • AntiestrogensAntiestrogens: In animal research, genistein bound to the estrogen receptor (48). In human research, consumption of soy, containing isoflavones, decreased estrone and estradiol levels (49). Other changes observed in premenopausal women include decreased 17beta-estradiol, estrone sulfate, estrone, and dehydroepiandrosterone sulfate, dependent on the phase of the menstrual cycle (50; 51; 52; 53), as well as increased urinary 2/16alpha-(OH) estrone ratio and decreased excretion of 4-(OH) estrone (54). In premenopausal women, soy isoflavones affected menstrual cycle length in some, but not all, studies (143; 112), whereas menstruation was interfered with (increased, decreased, irregular) in a separate study (50).
  • AntilipemicsAntilipemics: In humans, consumption of soy protein from various sources, containing isoflavones, resulted in a reduction in total and LDL cholesterol and triglycerides in some, but not all, studies (57; 58; 59; 60; 61; 62; 63; 64). The ratios of total and LDL cholesterol to HDL cholesterol, as well as apoB to apo A-1, were improved (95; 96; 63; 97). Purified isoflavones did not reduce plasma lipids in some human studies (47; 61; 98), although increases in HDL (and HDL3) cholesterol and apolipoprotein A-1 have been noted (99; 90; 70; 100; 101; 4), as have reductions in total cholesterol (65), triglycerides (66; 67; 68), and LDL cholesterol (69; 70; 71; 72; 4), and changes in LDL size to be less atherogenic (72) in other studies.
  • AntineoplasticsAntineoplastics: Reduced prostate cancer risk is associated with increased blood levels of certain isoflavones in some epidemiological research (145). Epidemiological research suggests that consumption of foods such as soy may reduce the risk of endometrial cancer (146). In postmenopausal women, isoflavone supplementation has been reported to decrease plasma concentrations of 8-hydroxy-2-deoxy-guanosine (147). Increased soy consumption, or supplementary isoflavones, did not have an effect on breast epithelial cell proliferation, breast density, or biochemical endpoints indicative of breast cancer risk (148; 118; 116). Purified red clover isoflavones did not have an antiproliferative effect on the endometrium (149). Genistein stimulated the growth of male pancreatic tumor cells in vitro (139).
  • Antiobesity herbs and supplementsAntiobesity herbs and supplements: In epidemiological research, women with high genistein intake had a lower body mass index and waist circumference compared with those that did not consume genistein daily (45).
  • AntioxidantsAntioxidants: Dietary consumption of soy flour had antioxidant effects in some, but not all, human studies (19; 174; 56; 14). Also, soy high in isoflavones reduced lipid peroxidation and increased the resistance of LDL to oxidation (175). In postmenopausal women, isoflavone supplementation has been reported to decrease plasma concentrations of 8-hydroxy-2-deoxy-guanosine (147). Isoflavones also decreased levels of malondialdehyde and increased blood total glutathione (14). In animal models, genistein increased the activities of various antioxidant enzymes such as superoxide dismutase, glutathione reductase, and catalase (176).
  • 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 (177).
  • CalciumCalcium: A combination of soy isoflavones, lactobacilli, calcium, vitamin D3, magnolia bark extract, and magnesium decreased menopausal symptoms and increased well-being in a clinical trial (178). In human research, soy enriched with isoflavones did not have an effect on calcium metabolism (179). A high amount of calcium in the blood has also been suggested as a potential side effect of soy by various secondary sources.
  • Cardiovascular herbs and supplementsCardiovascular herbs and supplements: In human research, consumption of soy containing isoflavones resulted in reduced postocclusion peak flow velocity of the brachial artery (151) and improved endothelium-dependent vasodilation (152). Animal research suggests that soy isoflavonoids reduce the extent of common carotid and internal carotid artery atherosclerosis (153; 154). Red clover isoflavones decreased levels of plasminogen activator inhibitor type 1 in human research (67).
  • Cytochrome P450-metabolized herbs and supplementsCytochrome P450-metabolized herbs and supplements: In vitro, genistein has been reported to be a potent inhibitor of CYP24 (150). Other isoflavones may also inhibit cytochrome P450. The effect of flavanoids in general, including isoflavones, on cytochrome P450 has been reviewed (156). In human research, soy isoflavones did not have an effect on cytochrome P450 3A enzyme induction (157).
  • DiureticsDiuretics: Animal research suggests that the soy isoflavone genistein induced maximal salidiuretic action similar to that of furosemide in rat kidneys (158).
  • FlaxseedFlaxseed: A combination of isoflavones and flax may have additive effects on menopausal symptoms (180; 181).
  • Gastrointestinal herbs and supplementsGastrointestinal herbs and supplements: In postmenopausal women, isoflavones have been reported to alter dominant bacterial communities, including the Clostridium coccoides-Eubacterium rectale cluster, Lactobacillus-Enterococcus group, Faecalibacterium prausnitzii subgroup, and Bifidobacterium genus (167).
  • GinsengGinseng: According to secondary sources, there is a potential for interaction between soy extract and Panax ginseng.
  • Hormonal herbs and supplementsHormonal herbs and supplements: Based on human research, soy and isoflavones may alter levels of various hormones, including progesterone, estrone, estradiol, luteinizing hormone, testosterone, and follicle-stimulating hormone (108; 49; 110; 19; 105; 112). Other changes observed in premenopausal women include decreased 17beta-estradiol, estrone sulfate, estrone, and dehydroepiandrosterone sulfate; increased sex hormone-binding globulin; and altered androstenedione and testosterone levels, dependent on the phase of the menstrual cycle (50; 51; 52; 53), as well as increased urinary 2/16alpha-(OH) estrone ratio and decreased excretion of 4-(OH) estrone (54).
  • HypoglycemicsHypoglycemics: In epidemiological research, women with high genistein intake had lower fasting insulin compared with those that did not consume genistein daily (45). In humans, soy isoflavones lowered blood glucose and insulin levels in some (46), but not all (47), studies.
  • HypotensivesHypotensives: In human research, isoflavone supplementation has been reported to decrease blood pressure in hypertensive patients (55). In human research, consumption of soy, containing isoflavones, did not have an effect on blood pressure, although area-under-the-curve profiles of 24-hour blood pressure measurements were higher after soy vs. gluten (144). Isolated isoflavones increased blood pressure in further human research (56). Thus, isoflavones may have additive or antagonistic effects with hypotensive agents.
  • ImmunomodulatorsImmunomodulators: In postmenopausal women, isoflavones alone and from soy milk increased B cell populations and lowered levels of 8-hydroxy-2-deoxy-guanosine, an oxidative marker of DNA damage (147). The potential for decreased immunity following isoflavone use has been suggested, based on animal models (131). In women, but not men, soy protein high in isoflavones increased levels of interleukin-6 (168).
  • MagnesiumMagnesium: A combination of soy isoflavones, lactobacilli, calcium, vitamin D3, magnolia bark extract, and magnesium decreased menopausal symptoms and increased well-being in a clinical trial (178).
  • Magnolia bark extractMagnolia bark extract: A combination of soy isoflavones, lactobacilli, calcium, vitamin D3, magnolia bark extract, and magnesium decreased menopausal symptoms and increased well-being in a clinical trial (178).
  • Osteoporosis herbs and supplementsOsteoporosis herbs and supplements: Animal, human, and in vitro research suggests that soy protein, containing isoflavones, may have positive effects on bone density (159; 160; 161; 162; 163; 164). Loss of bone mineral content at the hip over one year was reduced in Taiwanese women supplemented with isolated soy isoflavones; this was significant in women who were at least four years past menopause and had lower body weights or lower calcium intakes (165). In men, soy consumption also increased bone density (97).
  • Neurologic herbs and supplementsNeurologic herbs and supplements: In postmenopausal women, soy isoflavone supplementation was found to improve cognitive performance (87).
  • P-glycoprotein-regulated herbs and supplementsP-glycoprotein-regulated herbs and supplements: The effect of flavanoids, including isoflavones, on ATB binding cassette efflux transporters has been reviewed (170).
  • PhytoestrogensPhytoestrogens: In animal research, genistein bound to the estrogen receptor (48). In human research, consumption of soy, containing isoflavones, decreased estrone and estradiol levels (49). Other changes observed in premenopausal women include decreased 17beta-estradiol, estrone sulfate, estrone, and dehydroepiandrosterone sulfate, dependent on the phase of the menstrual cycle (50; 51; 52; 53; 4), as well as increased urinary 2/16alpha-(OH) estrone ratio and decreased excretion of 4-(OH) estrone (54). In premenopausal women, soy isoflavones affected menstrual cycle length in some, but not all, studies (143; 112), whereas menstruation was interfered with (increased, decreased, irregular) in separate study (50). In human research, soy protein isolate, containing isoflavones, did not have an effect on estrogen-induced endometrial, lipid, or bone changes (182).
  • PhosphatePhosphate: The estrogen-like effects of isoflavones may theoretically affect phosphate levels. Further research is needed before a firm conclusion may be drawn.
  • ProbioticsProbiotics: A combination of soy isoflavones, lactobacilli, calcium, vitamin D3, magnolia bark extract, and magnesium decreased menopausal symptoms and increased well-being in a clinical trial (178). A combination of probiotics and isoflavones did not enhance biologic effects of isoflavones (183; 184). In postmenopausal women, isoflavones have been reported to alter dominant bacterial communities including the Clostridium coccoides-Eubacterium rectale cluster, Lactobacillus-Enterococcus group, Faecalibacterium prausnitzii subgroup, and Bifidobacterium genus (167).
  • ResveratrolResveratrol: Resveratrol and genistein may have additive anticancer effects, based on in vitro research and animal models (185).
  • Thyroid agentsThyroid agents: Soy isoflavones did not have an effect on thyroid hormone levels in postmenopausal women (113); however, in human research, ingestion of soy protein containing isoflavones altered thyroxine, thyroid-stimulating hormone, and triiodothyronine levels in other studies (73; 50; 53). In a review, collective findings suggested that there is little evidence that, in euthyroid, iodine-replete individuals, soy foods or isoflavones adversely affect thyroid function (10). The review also suggested that soy foods may increase the dose of thyroid hormone required by hypothyroid patients. In theory, soy protein foods may increase the risk of developing hypothyroidism in individuals with compromised thyroid function or those whose iodine intake is marginal.
  • Vasodilator herbs and supplementsVasodilator herbs and supplements: In human research, isoflavones have been reported to improve endothelium-dependent vasodilatation without an effect on endothelial-independent arterial diameter or flow (80). In human research, infused dehydroequol, a metabolite of diadzein, had vasodilatory properties in human forearm arteries (173).
  • Vitamin DVitamin D: A combination of soy isoflavones, lactobacilli, calcium, vitamin D3, magnolia bark extract, and magnesium decreased menopausal symptoms and increased well-being in a clinical trial (178).
  • Isoflavones/Food Interactions:

  • CarbohydrateCarbohydrate: In women, metabolism of soy isoflavones to equol (a metabolite of isoflavones) was associated with higher intake of dietary fiber and carbohydrate (186).
  • Dietary fiberDietary fiber: High intakes of dietary fiber (40g) resulted in a 55% lower plasma genistein level and a 20% lower urinary genistein level, compared with lower fiber intakes (15g) (187). The intraindividual response of isoflavone bioavailability may be due to differences in intake of protein and dietary fiber, according to results from a clinical trial (188). In women, metabolism of soy isoflavones to equol was associated with higher intake of dietary fiber and carbohydrate (186).
  • Fermented soy productsFermented soy products: Fermentation of soy increased urinary isoflavone recovery in human research (186).
  • FlaxseedFlaxseed: A combination of soy isoflavones and flax may have additive effects on menopausal symptoms (180).
  • FructooligosaccharidesFructooligosaccharides: In animal research, plasma and urinary isoflavones were increased with consumption of fructooligosaccharides (189).
  • IodineIodine: In theory, soy protein foods, containing isoflavones, may increase the risk of developing hypothyroidism in individuals with compromised thyroid function or those whose iodine intake is marginal (73; 50; 53). In a review, collective findings suggested that there is little evidence that, in euthyroid, iodine-replete individuals, soy foods or isoflavones adversely affect thyroid function (10).
  • ProteinProtein: According to results from a clinical trial, isoflavone bioavailability may be dependent on intakes of protein and dietary fiber (188).
  • Soy flourSoy flour: Soy flour may not inhibit absorption or elimination of isoflavones from supplements; however, the bioavailability of daidzein was reduced (190).
  • WheatWheat: 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 (187).
  • Isoflavones/Lab Interactions:

  • 8-hydroxy-2-deoxy-guanosine8-hydroxy-2-deoxy-guanosine: In postmenopausal women, soy milk containing isoflavones, as well as isoflavones alone, lowered levels of 8-hydroxy-2-deoxy-guanosine, an oxidative marker of DNA damage (147).
  • AlbuminAlbumin: In human research, following soy protein consumption, urinary albumin excretion was reported to be negatively correlated with total plasma isoflavones (96).
  • Antioxidant statusAntioxidant status: In human research, isoflavones have been reported to decrease levels of malondialdehyde and increased blood total glutathione (14). In animal models, genistein increased the activities of various antioxidant enzymes such as superoxide dismutase, glutathione reductase, and catalase (176).
  • B cellsB cells: In postmenopausal women, soy milk containing isoflavones, as well as isoflavones alone, increased B cell populations (147).
  • Blood pressureBlood pressure: In human research, isoflavone supplementation has been reported to decrease blood pressure in hypertensive patients (55). Isolated isoflavones increased blood pressure in further human research (56).
  • Body mass indexBody mass index: In epidemiological research, women with high genistein intake had a lower body mass index, compared with those that did not consume genistein daily (45).
  • Bone markersBone markers: In human research, consumption of soy, containing isoflavones, increased the ratio of C-telopeptide to osteocalcin, indicating an uncoupling of the bone resorption and formation process (108). Purified soy isoflavones or soy-containing isoflavones reduced blood or urinary levels of bone turnover markers in some human studies (69; 160). Soy did not affect bone turnover markers in all human studies (59). Red clover isoflavones did not have an effect on bone turnover markers in symptomatic menopausal women (66). In postmenopausal women, total fecal calcium excretion, bone deposition and resorption, and calcium retention were not significantly affected by soy protein containing isoflavones (179).
  • CalciumCalcium: A high amount of calcium in the blood has also been suggested as a potential side effect to soy by various secondary sources.
  • Coagulation panelCoagulation panel: In human research, isoflavones resulted in a decline in platelet thromboxane A2 receptor density (44). Also, red clover is a source of coumarin, which may increase bleeding risk. Red clover isoflavones decreased levels of plasminogen activator inhibitor type 1 in human research (67).
  • C-reactive proteinC-reactive protein: Genistein did not have an effect on C-reactive protein in human research (70). Isoflavones resulted in a nonsignificant reduction in C-reactive protein in human research (191).
  • GhrelinGhrelin: Ghrelin levels were reduced in individuals who produced equol (192).
  • GlucoseGlucose: In humans, isoflavone supplements decreased fasting glucose in women (46).
  • GlutathioneGlutathione: In humans, isoflavones increased blood total glutathione levels (14).
  • HormonesHormones: In human research, consumption of soy decreased estrone and estradiol levels (49; 109). In postmenopausal women, levels of luteinizing hormone decreased once soy treatment was discontinued (110). Soy isoflavones did not have an effect on hormone levels in women; however, dehydroepiandrosterone sulfate concentrations were lower in older men (111). In females consuming increased levels of soy protein containing isoflavones, midcycle peaks of luteinizing hormone and follicle-stimulating hormone were suppressed (112). Other changes observed in premenopausal women include decreased 17beta-estradiol, estrone sulfate, estrone, and dehydroepiandrosterone sulfate; increased sex hormone-binding globulin; and altered androstenedione and testosterone levels, dependent on the phase of the menstrual cycle (50; 51; 52; 53), as well as increased urinary 2/16alpha-(OH) estrone ratio and decreased excretion of 4-(OH) estrone (54).
  • InsulinInsulin: Use of isoflavone supplements in women decreased fasting insulin (46). In epidemiological research, women with high genistein intake had lower fasting insulin compared with those that did not consume genistein daily (45).
  • Insulin-like growth factor-1 (IGF-1)Insulin-like growth factor-1 (IGF-1): Soy isoflavone supplementation did not have an effect on insulin-like growth factor levels in various human studies (100; 193; 194; 195; 196).
  • Intestinal floraIntestinal flora: In postmenopausal women, isoflavones have been reported to alter dominant bacterial communities including the Clostridium coccoides-Eubacterium rectale cluster, Lactobacillus-Enterococcus group, Faecalibacterium prausnitzii subgroup, and Bifidobacterium genus (167).
  • IsoflavonesIsoflavones: In human research, consumption of soy isoflavones increased levels of isoflavones in the blood, urine, and nipple aspirate (46; 151; 47; 99; 58; 144; 59; 69; 14; 148; 197; 184; 198; 199; 200; 201). Urinary isoflavones may be used as a marker of soy exposure over time (198; 199; 202; 200; 203; 204; 144; 205).
  • Lipid panelLipid panel: In human research, purified isoflavones did not have a reducing effect on plasma lipids in some studies (47; 61; 98), although increases in HDL (and HDL3) cholesterol and apolipoprotein A-1 have been noted (99; 90; 70; 100; 101; 4), as have reductions in total cholesterol (65), triglycerides (66; 67; 68), and LDL cholesterol (69; 70; 71; 72; 4), and changes in LDL size to be less atherogenic (72), in other studies.
  • MalondialdehydeMalondialdehyde: In humans, isoflavones decreased levels of malondialdehyde (14).
  • Peptide YY (PYY)Peptide YY (PYY): In humans, isoflavone supplementation increased levels of PYY in serum (192).
  • PhosphatePhosphate: The estrogen-like effects of isoflavones may theoretically affect phosphate levels. Further research is needed before a firm conclusion may be drawn.
  • Plasminogen activator inhibitor type 1Plasminogen activator inhibitor type 1: In human research, red clover isoflavones decreased levels of plasminogen activator inhibitor type 1 (67).
  • Platelet thromboxane A2 receptor densityPlatelet thromboxane A2 receptor density: In human research, isoflavones resulted in a decline in platelet thromboxane A2 receptor density (44).
  • ProgesteroneProgesterone: In human research, consumption of soy, containing isoflavones, increased plasma progesterone levels in females (108).
  • ProstacyclinProstacyclin: In human research, prostacyclin production increased in postmenopausal women supplemented with isoflavones (206).
  • Prostate-specific antigen (PSA)Prostate-specific antigen (PSA): Soy isoflavones reduced levels of prostate-specific antigen in prostate cancer patients (106) and healthy men (207; 208), but not in elderly men with elevated PSA (209).
  • TestosteroneTestosterone: Dietary consumption of soy flour reduced levels of testosterone in males (19), and red clover isoflavones increased plasma testosterone in postmenopausal females (105). Testosterone levels were altered in premenopausal women, dependent on the phase of the menstrual cycle. In prostate cancer patients, soy isoflavones reduced levels of testosterone (106). In human research, serum dehydroepiandrosterone was decreased by 31.7% following supplementation with soy isoflavones (107).
  • Thyroid function testsThyroid function tests: Soy isoflavones did not have an effect on thyroid hormone levels in postmenopausal women (113). In human research, ingestion of soy protein containing isoflavones increased thyroxine, thyroid-stimulating hormone, and triiodothyronine after 3-6 months (73). However, the changes were not considered to be clinically significant by the author. Thyroid hormones were also affected in separate research, increasing or decreasing, depending on phase of the menstrual cycle (50; 53).