The medicinal parts are the Soya lecithin extracted from the Soya bean, the Soya oil, and the Soya seed.
Flower and Fruit
The flowers are small, inconspicuous, short pedicled, upright, axillary, and appear in 3 to 8 blossomed clusters. The sepals are campanulate or tubular-campanulate and somewhat bilabiate. The corolla is usually purple, exceeding the calyx only slightly or not at all. The stamens are diadelphous or monodelphous. The style is glabrous. The pod is linear or oblong and constricted between the seeds. The pod is septate and dehiscent. There are 2 to 4 seeds, which are oblong-ovate, white, yellow or black-brown.
Leaves, Stem, and Root
The Soya plant is an erect or twining annual bushy plant. The stem and leaves are thickly villous. The leaves are trifoliate, the leaflets are large, ovate, entire-margined and, particularly on the margins and on the ribs of the lower surface, pubescent.
The Soya plant is indigenous to east Asia but has never been found in the wild. Glycine soja is found in the Amur-Ussuri area, northern China, Taiwan, Korea, and Japan.
Lecithin consists of the phospholipid mixture from Glycine soja seeds and its preparations. Virgin Soybean oil is mixed with 2% water at 60º to 80º C. After the swelling times it is separated by centrifugation and the lecithin paste is evaporated at 100º C in a vacuum until the remaining water content is 0.2 to 0.8%.
Actions & Pharmacology
Phospholipids (45-60%): in particular phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol
Fatty oil (30-35%)
Steroids: Phytosterols (2-5%)
Soy contains high amounts of protein, phytochemicals, and isoflavones, such as genistein and diadzein. In certain hormone-related cancers, the isoflavones in Soy act as antiestrogens and block the uptake of estrogen into tissues such as that of the breast. Soy reduces the effects of androgens on the prostate gland. However, whether Soy is beneficial for breast and prostate cancer remains questionable. Epidemiological studies report a link between Soy consumption and reduction of breast and prostate cancer, but clinical studies are lacking. Soy has a potential use as a protein source to reduce weight loss and diarrhea during chemotherapy based on animal studies.
The FDA has approved health claims that Soy products can lower coronary heart disease by lowering blood cholesterol levels. Germany's Commission E approves of its use for elevated cholesterol as well. Soy may have a beneficial effect on cognitive function, but its role in this capacity needs much more elucidation. Soy protein may improve insulin resistance and glycemic control and may have a use as part of a diabetic regime. Soy is mostly beneficial for use in menopause, but not all clinical trials demonstrate positive results. More studies are needed to further define its role. Soy failed to reduce hot flushes in breast cancer patients. Mild to moderate hypertensive patients supplemented with Soy milk experienced a modest reduction in blood pressure. Soy's role in infant diarrhea is not fully clear. A combination product containing Soy, Dong Quai, and black cohosh improved menstrual migraines dramatically; more study is needed to support this data. Soy has demonstrated small, but significant, effects on bone mineral density in postmenopausal women. Soy protein diets may have advantages over animal protein in renal disease. Several in vitro and in vivo studies reported potential benefits of genistein in the treatment of cystic fibrosis and HIV-1 (Gozlan et al, 1998; Hwang et al, 1997; Illek et al, 1997).
The chemopreventive effects of the isoflavone genistein may be due to its action as an estrogen agonist or antagonist. However, a variety of nonestrogenic mechanisms, including inhibition of protein tyrosine phosphorylation, induction of differentiation, inhibition of DNA topoisomerases, inhibition of specific cell cycle events, induction of apoptosis, inhibition of angiogenesis, and antioxidant activity have been proposed (Tham et al, 1998). In terms of breast cancer, Soy isoflavones are converted in the bowel to antineoplastic agents, which demonstrated cytostatic actions on estrogen receptor-positive and negative human mammary cancer cell lines. The chemopreventive potential of genistein in breast cancer has been demonstrated in numerous in vitro and in vivo studies but few clinical studies are available. Epidemiologic studies have shown an inverse association between hormone-dependent breast cancer incidence and mortality and a Soy-rich Asian diet (Stoll, 1997). In one human study, increased proliferation of breast epithelium was demonstrated. (McMichael-Phillips et al, 1998). High tyrosine kinase activity is associated with tumor tissue. Tyrosine kinase inhibitors (such as genistein) can block the action of growth factors on cells (Wardle, 1998; Helms & Gallaher, 1995).
Genistein was an effective in vitro suppresser of bladder tumor growth and motility, irrespective of epidermal growth factor receptor expression levels. The inhibition of motility was dependent on epidermal growth factor receptor but not p21ras gene expression (Theodurescu et al, 1998; Theodorescu et al, 1998a). The mechanism of the cytotoxic effect of genistein on human prostate cancer cell lines LNCaP, PC3, and DU145 was examined in vitro with non- toxic genistein concentrations ranging between 1.85 to 93 micromoles. An involvement of p53 in growth inhibition of LNCaP, but not PC3 or DU145, by genistein, has been observed (Davies et al, 1998). Genistein induced an antiproliferative effect with a partial G2-M block and apoptosis in human uterine adenocarcinoma cell lines HEC 1A, HEC-1B, AN3Ca, and RL95-2. The antiproliferative effect of genistein was independent of its estrogenic activity but interactions with tyrosine kinase and topoisomerase II were relevant (Muratori et al, 1997).
Soy protein can lower cholesterol in hypercholesterolemic subjects (Morelli et al, 2000). The FDA approved the “health claim” that Soy products (which contain at least 6.25 g of Soy/serving and are low in fat, saturated fat, and cholesterol) can reduce the risk of coronary heart disease by lowering cholesterol. The mechanism by which Soy lowers cholesterol is unknown. The effects are modest (6% to 7%) and 25 g of Soy protein must be consumed a day in order to derive benefit. Examples of estimated Soy protein content are 3 to 10 g/cup of Soy milk and 5 to 13 g of Soy protein/4 ounces of tofu (FDA, 2003; Stone, 2002).
Effects on Cognitive Function
Memory improved, but not other measures of cognitive function, in postmenopausal women supplemented with Soy isoflavones; larger trials are needed (Kritz- Silverstein et al, 2003). In young healthy adults supplemented with Soy isoflavones, there were improvements in memory and mental flexibility, but not attention and category generation task (File et al, 2001)
Soy contains several isoflavones that degrade to genistein, glycitein, and daidzein. These molecules are structurally related to estradiol (Grauds, 1999). In one study, isoflavones altered estrogen metabolism. Eighteen post menopausal women were given three diets for 93 days each, separated by a 25-day washout period between the diets. The three diets contained Soy protein isolate in concentrations of 0.1 mg/kg/d, 1 mg/kg/d, or 2 mg/kg/d (Xu et al, 2000). Premenopausal women fed a diet containing 60 g of Soy protein/day (equivalent to about 45 mg of isoflavones) had reduced luteinizing and follicle-stimulating hormone levels during their midcycles (Wardle, 1998).
Soy protein contains, in small amounts, several agents that may contribute to its beneficial actions in renal disease. Nicotinamide-N, N-(3-amino-3-carboxypropyl) azetidine-2-carboxylic acid is an angiotensin-converting enzyme inhibitor; phytic acid controls serum phosphate for chronic renal patients and proteinase inhibitors help control inflammatory reactions (Wardle, 1998).
Body Composition/Weight Loss/Lipid profile
Soy protein supplementation was found to have no influence on indicators of body composition but did favorably affect lipid levels. Forty-six postmenopausal women were enrolled in a randomized, placebo-controlled study and assigned to one of four groups: 25 g soy protein (SP); 25 g of soy protein plus resistance exercise (SPE); 25 g of maltodextrine (placebo), or placebo plus resistance exercise (PLE). At baseline and after 16 weeks, body mass index, waist circumference, body fat, muscle mass, and serum lipid levels were measured. To confirm isoflavone absorption, urinary concentrations were determined. After 16 weeks of intervention, both SPE and PLE groups showed a significant increase of 1.3 kg in muscle mass and reduction of waist circumference of -1.4 and -2.1 cm, respectively (p<0.05). Significant decreases in the mean values of total cholesterol and LDL were observed in the users of soy protein alone, indicating the favorable effects of soy protein on lipid profile in postmenopausal women (Maesta et al, 2007).
Forty-three women with body mass index values between 30 and 40 kg/m2 were randomized in intensive dietary interventions using either casein (placebo) or soy shakes. The subjects were instructed to consume three shakes, one prepacked entrée, and five servings of fruit and vegetables daily to achieve an energy intake of 4.5 to 5.0 MJ/d. Weight, body fat, lipid, and glucose measurements were obtained at baseline and at eight and 16 weeks. For both groups combined, subjects lost 8.1% of initial body weight (7.7 kg) at eight weeks and 13.4% (12.7 kg) at 16 weeks. Differences in weight loss and body composition changes between casein and soy treatments were not significant (Anderson et al, 2007).
In another study by the same author and colleagues, a Soy meal replacement (MR) was associated with significant reductions in serum triglycerides at six and 12 weeks. Researchers looked at the effects of a soy-based meal replacement MR on body weight and fat distribution in 90 overweight or obese adults. Participants were randomly assigned to LED (low-energy-diet) providing 1200 kcal/day, with consumption of five soy-based MR or two milk-based MR for the 12-week study. Serum lipoprotein measurements were obtained at baseline, six and 12 weeks. After the end of treatment, participants who used soy MR lost 9.0% of initial body weight, while participants taking milk lost 7.9% of initial body weight. Reductions of serum cholesterol and LDL cholesterol were significantly greater (p<0.015) with soy MR (15% and 17.4%) than with milk MR (7.9 and 7.7%) (Anderson & Hoie, 2005).
Bone Mineral Density
The effects of soy isoflavone supplementation on bone mineral density was investigated in a controlled, parallel-arm, double-blind, trial of 145 adults between the ages of 50 and 80. After 12 months of treatment, soy protein containing isoflavones resulted in a modest benefit in preserving bone mineral density in the spine, but not the hip, in older women (Newton et al, 2006).
Seventy-two patients with a histologically confirmed pre-existing diagnosis of breast cancer were randomized to either soy capsules or placebo during a 12-week period. Quality of life and menopausal symptom scores were assessed at baseline, four, eight, and 12 weeks. Results showed no statistical difference in menopausal symptom scores or quality of life between the two arms of the study (MacGregor et al, 2005).
Dietary intervention with Soy led to significant changes in the regulation of the menstrual cycle of six premenopausal women (21 to 29 years) with regular ovulatory cycles in this controlled study. During the first month of the study, each subject consumed a constant daily diet of non-Soy-containing foods and the first complete menstrual cycle served as a control period. Daily supplementation of 60 g of Soy, containing 45 mg of isoflavones, during the following month, caused a significant increase of follicular phase length (p<0.01), plasma estradiol concentrations during the follicular phase and cholesterol concentrations (9.6%), a significant suppression of midcycle surges of luteinizing and follicle stimulating hormone, and delayed menstruation. These effects may be due to nonsteroidal estrogens of the isoflavone class, which may possess partial estrogen agonistic and antagonistic effects. The authors suggested that a diet rich in dietary estrogens may be protective against breast cancer (Cassidy et al, 1994).
A case control study of 18 post menopausal women with breast cancer and 20 healthy women showed that breast cancer subjects had lower urinary Soy isoflavones in a 24-hour urine collection. Significant differences in urinary daidzein levels existed between the two treatment groups. Breast cancer subjects excreted 31 nanomoles/day (nmol/d) and controls excreted 427 nmol/d. Breast cancer patients also showed lower urinary genistein levels (25 nmol/d) compared to control patients (155 nmol/d). Serum testosterone levels were elevated in breast cancer subjects although the difference did not reach statistical significance. Dietary analysis was performed and showed no significant differences in carbohydrate, fat, protein, or fiber consumption between the two groups (Murkies et al, 2000).
Dietary Soy supplementation significantly increased the proliferation rate of breast lobular epithelium and progesterone receptor expression in a randomized, controlled study of 48 women with benign or malignant breast disease. The patients were assigned to continue their normal diet or receive additional 60 g of Soy supplement containing 45 mg of isoflavones. After 14 days, serum concentrations of the phytoestrogens genistein and daidzein increased significantly (p<0.05) in the Soy group. Short-term Soy treatment of premenopausal human breast tissue caused an up-regulation in progesterone receptor expression and an elevation in the number of proliferating epithelial cells. A trend toward increased expression of the proliferation antigen Ki67LI was observed. Radiographic, echographic, cytologic, and histologic examinations were performed for diagnosis. No estrogen antagonistic effects were found (McMichael-Phillips et al, 1998).
Cognitive Function/Mood in Postmenopausal Women
A randomized, double-blind, placebo-controlled crossover study was performed to investigate the effects of Soy isoflavones on mood and cognitive function in 78 postmenopausal women. Investigators administered 60 mg/day isoflavones or placebo for six months. After a wash-out period of one month, the patients who had been treated with phytoestrogens received placebo and vice versa. At the end of each treatment a battery of tests was carried out. The results revealed that of the 17 scores on cognitive performance test and the six for mood assessments, six showed an advantage for the treatment with isoflavones. Of the eight visual analog scales used to indicate mood, seven improved significantly after the treatment with phytoestrogens. This study suggests that isoflavones may have a positive effect on postmenopausal women improving cognitive performance and mood (Casini et al, 2006).
A relatively long-term (12-month), large, double-blind and placebo-controlled trial in which 202 healthy postmenopausal women age 60 to 75 were randomly assigned to a placebo or 25.6 g of soy protein daily (containing 99 mg of isoflavones [52 mg genistein, 41 mg daidzein, and 6 mg glycerin) or total milk protein (as a powder) daily did not find evidence that the Soy protein improved cognitive function, bone mineral density, or plasma lipids when started at age 60 or later. While isoflavones from Soy appear to cause fewer adverse effects than postmenopausal estrogen therapy may, these findings indicate that they don't confer clear positive effects. Cognitive testing results at the final visit were essentially the same as they were at baseline, with assessments for verbal skills, concentration, and visual attention showing no significant inter-group differences or improvements at the final visit. The same was true when women with depression were excluded from the analysis, as this can affect cognition test results). Adherence to the regimen was good. Ultimately, no significant difference was found between the soy protein supplement and placebo groups after a full year (Kreijkamp-Kasper, 2004).
In contrast, postmenopausal women supplemented with Soy isoflavones demonstrated improved verbal memory, but not in other measurements of cognitive function, in a double-blind, randomized, placebo-controlled trial. Postmenopausal women, not on estrogen replacement and in good health, were supplemented with 110 mg of Soy-extracted isoflavones/day (n=27) or an identical placebo (n=26) for 6 months. A trend toward improved cognitive function (visuomotor tracking and attention) was noted in the treatment group as it related to baseline values and between placebo and treatment groups. Significant improvements in category fluency (verbal memory) was noted between treatment and placebo groups (p=0.02) (Kritz- Silverstein et al, 2003).
A short-term supplementation of Soy to young men and women demonstrated significant improvements in memory and mental flexibility in a randomized controlled trial. Student volunteers (15 men, 12 women) were randomized to either receive high-Soy (100 mg total isoflavones/day) or low-Soy diet (0.5 mg total isoflavones/day) for 10 weeks. Significant improvements in short term and long term memory as well as mental flexibility were noted in both men and women who were on the high-Soy diet (p<0.05). Females in the high-Soy diet also significantly improved in letter fluency and planning test. Tests of attention and category generation task did not improve with Soy supplementation (File et al, 2001).
Tofu (a Soy-based product) was associated with reduced cognitive function and organic brain changes in a longitudinal study. Japanese-American men, originally enrolled in the Honolulu Heart Program (HHP) and the Honolulu-Asia Aging Study (HAAS), were assessed for cognitive changes (n=3734) and brain atrophy (neuro-image: n=574; autopsy: n=290) after a review of their dietary habits from 1965 to 1967 and 1971 to 1974. Men with the highest tofu consumption (2 or more servings a week) were more likely to develop cognitive impairment than those with low or no tofu consumption (p<0.05). Low brain weight and enlargement of ventricles were also associated with higher tofu consumption. The authors determined an odds ratio of 1.6 to 2 for having poor cognitive test scores, low brain weight, or ventricular enlargement later in life (White et al, 2000).
Soy protein significantly improved insulin resistance, glycemic control, and serum lipoproteins in women with type 2 diabetes in a randomized, double-blind, placebo-controlled, crossover trial. Postmenopausal women (n=32) with type 2 diabetes were randomized to 30 g of isolated Soy protein (containing 132 mg of isoflavones) or placebo (cellulose) daily for 12 weeks and then crossed over to the opposite treatment for an additional 12 weeks. Isoflavones consisted of genistein (53%), daidzein (37%), and glycitein (10%). Modest yet significant improvements were noted during Soy supplementation for fasting insulin, insulin resistance, glycosylated hemoglobin, total cholesterol, LDL cholesterol, cholesterol/HDL ratio and free thyroxine (p<0.05). No significant changes were noted in HDL cholesterol, triglycerides, weight, blood pressure, creatinine, dehydroepiandrosterone sulfate, androstenedione, or the hypothalamic-pituitary-ovarian axis hormones (Jayagopal et al, 2002).
Infants over 6 months of age had a significantly shorter duration of diarrhea (9.7 hours) while taking a Soy with fiber product than with a Soy-alone product (23.1 hours) (p<0.05). These differences were not statistically significant with the children under 6 months of age. Patients with acute infant diarrhea were given either a Soy or a Soy and Soy fiber diet for 10 days in the rehydration phase of their illness. Acute infant diarrhea was defined as less than 24 months old with acute diarrhea under 3 days of duration and more than 3 watery stools in 24 hours. Three times the usual number of stools/24 hours also qualified. A child was disqualified if there was a pre-existing gastrointestinal illness. The two products used were similar in fat, protein, and carbohydrate composition but Soy fiber (6 g/L) was added to the second formula (Vanderhoof et al, 1997).
Soy-based formula decreased the duration of infant diarrhea when compared to a cow's milk product in this randomized, controlled, double-blind study of infants 2 to 12 months old with diarrhea of less than 1 week. The infants had mild to moderate dehydration from the diarrhea. Seventy-three children were included in the study; 39 of these received a Soy-based formula and 34 received a cow's milk formula after rehydration with an oral or intravenous glucose-electrolyte solution. The duration of diarrhea was shorter in the Soy-based product (4.5 days) than in the cow's milk product (6.6 days) (p=0.03). The number of treatment failures did not differ significantly. The amount of formula eaten and weight gain at 14 days did not differ significantly (Allen et al, 1994).
Hot Flushes, Breast Cancer
No improvement of hot flushes was noted in women with breast cancer supplemented with Soy in a double-blind, placebo-controlled trial. Post menopausal women (mean age approximately 55 years) not on hormone replacement and with a history of breast cancer who were reporting moderate hot flushes were randomized to receive either a Soy beverage (90 mg of isoflavones; n=59) or placebo (rice beverage; n=64) daily for 12 weeks. While both groups reported a reduction in hot flushes and hot flash score, the use of the Soy supplement did not reach significance compared to the placebo group (Van Patten et al, 2002).
A double-blind, placebo-controlled, crossover study of 177 breast cancer survivors 18 years and older found that Soy was no more effective than placebo in the treatment of substantial hot flushes. At baseline, patients averaged 7 hot flushes/day. Seventy percent of patients were on tamoxifen or raloxifene. The women were split into 2 groups; group 1 (n=87) received Soy 600 mg (with 50 mg Soy isoflavones including 40% to 45% genistein, 40% to 45% diadzein, and 10% to 20% glycitein) 3 times daily for 4 weeks and then placebo for 4 weeks. Group 2 (n=88) received placebo for 4 weeks and then Soy for 4 weeks. Response criteria were based on a hot flush patient questionnaire from baseline to 9 weeks. Similar results were demonstrated in hot flush frequency and severity scores in both groups, with a trend toward better results with placebo (Quella et al, 2002).
Replacing high-fat animal protein with soy protein may help improve atherogenic profiles in postmenopausal women. In a randomized, double-blind, placebo-controlled study, 216 postmenopausal women first consumed casein protein-based supplements for four weeks. After a four-week run-in period, participants were randomly assigned to continue the casein placebo or receive soy protein-containing isoflavones for 12 weeks. Results showed total cholesterol, LDL cholesterol, and low-density lipoprotein particle number decreased significantly as compared to placebo at six weeks. Although this decrease continued at 12 weeks in the soy group, the difference from placebo group was attenuated for total cholesterol and low-density lipoprotein particle number (Allen et al, 2007).
To examine the effects on LDL cholesterol and arterial function as the result of dietary supplementation, a randomized, double-blind, placebo-controlled study was performed on 100 hypercholesterolemic but otherwise healthy subjects who were assigned to 24 weeks of daily intake of either Soy supplement, Abalon (30 g Soy protein, 9 g cotyledon fibre and 100 mg isoflavones), or placebo (30 g of casein). No difference in fasting plasma lipid levels or insulin sensitivity was found between treatment groups. Investigators did observe a significant postprandial increase in GIP (glucose-dependent insulinotropic peptide) in the Soy group (p<0.05). They concluded that markers of arterial function were not influenced by soy (Hermansen et al, 2005).
Water-washed Soy protein concentrate had no significant effect on blood lipids in moderately hypercholesterolemic adults compared to a milk-protein based control. This was observed in a randomized, double-blind, controlled clinical trial involving 159 subjects over a period of five weeks (Ma et al, 2005).
Somewhat different results were generated in another 2005 study, in which Soy protein (25 g daily) was determined to be twice as effective as 15 g daily in reducing serum cholesterol levels in 117 men and women with hypercholesterolemia as part of an eight-week, randomized and placebo-controlled trial. Not only did low-density lipoprotein cholesterol levels drop significantly by 5.9% and 1.1%, respectively, but total serum cholesterol and apolipoprotein B levels changed similarly as well. Compared with baseline, levels of high-density lipoprotein cholesterol, homocysteine, triglycerides, folic acid, and vitamin B12 did not alter significantly with either Soy or placebo groups. No serious adverse effects were recorded. The findings suggest that soy protein supplements may offer an uncomplicated method for lowering cardiovascular disease risk (Hoie, 2005).
An earlier, randomized, crossover study found that plasma and urinary isoflavone levels markedly increased with regular consumption of whole Soybean extracts in adults (23 men and 10 post-menopausal women). However, no overall differences in plasma lipids, blood pressure, or arterial compliance were identified as compared to the group consuming a control (dairy) diet. The whole Soybean contained not only Soy protein with isoflavones but polyunsaturated fat and soluble fiber that might further enhance cardiovascular benefits. The soy intervention component involved consumption of four servings daily (250 ml per serving) of either or both Soy milk or yogurt as part of the normal diet. After five weeks, the group switched to a dairy diet (or vice versa) that included four servings daily (250 ml per serving) of either or both low-fat dairy milk or yogurt. The 23 volunteers who completed the crossover trial were mildly hypercholesterolemic (total plasma cholesterol >5.5 mmol/l and (or) mildly hypertensive (blood pressure >140/90 mm Hg) but not taking medication for either at study start. The authors assert that this may have been the first assessment of the power of whole Soybean to affect vessel function. All participants appeared to comply with the diet instructions. Of note is that a later analysis of the data indicated that participants who were equol-positive had significant improvements in plasma lipids; equol is a metabolite of daidzein produced by digestion of bacteria in the gut, and the ability to produce it may be linked to certain health benefits. More research on the potential role of equol in lowering lipid levels are merited (Meyer, 2004).
Soy isoflavones decreased lipid levels in a randomized, double-blind, placebo-controlled study of 80 healthy women aged 45 to 55 years. Subjects received isoflavones 100 mg (including genistein 69.9 mg, daidzein 18.6 mg, and glycitein 11.4 mg) (n=40) or placebo (n=40) daily for 5 months. Total cholesterol (TC) and LDL cholesterol decreased significantly in the isoflavone group (TC=199; LDL=120) compared to placebo (TC=227; LDL=139) and baseline (TC=226; LDL=134) (p<0.001). No side effects were observed (Han et al, 2002).
Total cholesterol did not change but HDL (“good”) cholesterol increased and non-HDL cholesterol decreased in this study of 66 hypercholesterolemic, post-menopausal women who were studied in a 6-month, double-blind study. All subjects had a normalization period for 2 weeks, then received National Cholesterol Education Program (NCEP) Step 1 diet with either protein from casein and nonfat dry milk (control group), protein from Soy containing moderate 1.39 mg/g of protein) amounts of isoflavones (MI group), or a Soy protein group with high (2.25 mg/g) amounts of isoflavones (HI) group. Non-HDL cholesteral was reduced in both groups compared to the controls (p<0.05) but total cholesterol was not changed. HDL cholesterol increased in both Soy groups (p less than 0.05). The total cholesterol to HDL cholesterol ratio was also decreased compared to the control (p<0.05) (Baum et al, 1998).
A Soy protein diet reduced LDL cholesterol, and the LDL to HDL ratio in one study of 26 men. The reductions were independent of age, weight, and pretreatment lipid concentrations. Thirteen men with hypercholesterolemia and 13 normocholesterolemic patients (20 to 50 years) were randomly given either an NCEP Step 1 diet with animal protein or the NCEP diet with Soy protein for 5 weeks. Either animal or Soy protein represented 75% or more of the total protein in the diet. After a 10 to 15 week washout period, subjects were crossed over to the other study diet (Wong et al, 1998).
Twice-weekly topical administration of a purified Soy phosphatidylcholine in ethanol solution with butylated hydroxytoluene 0.01% to 20 men and 20 women with serum cholesterol greater than 250 mg/dL produced a 25% reduction in serum cholesterol (p<0.01) and a 23% reduction LDL cholesterol (p<0.01). The trial was 8 weeks long (Hsia et al, 1995).
Dietary isoflavonoid phytoestrogen supplementation did not alter serum lipid and lipoprotein (a) concentrations in a randomized, double-blind, placebo-controlled study of 59 healthy volunteers with average serum cholesterol concentrations (Hodgson et al, 1998).
Oral daily administration of 60 g of a Soy protein isolate beverage powder for 28 days had no beneficial effects on plasma cholesterol and platelet aggregation in a randomized, controlled study of 20 healthy male subjects. Although genistein (907 nmol/L) and daidzein (498 nmol/L) plasma levels in the Soy group were higher than plasma levels obtained with traditional Japanese diets, no significant differences in collagen or 9,11-dideoxy-11-alpha,9-alpha-epoxymethanoprostaglandin F2- alpha (U46619)-induced platelet aggregation were observed in both groups. Plasma total cholesterol and HDL-cholesterol concentrations and plasma phospholipid polyunsaturated fatty acid composition showed no differences between Soy protein and casein supplementation (Gooderham et al, 1996).
An average drop in total cholesterol of 21.8% was found in 16 children with familial hypercholesterolemia who were given a Soy diet for 8 weeks. The children were first stabilized on a control, low lipid and cholesterol diet, then given the Soy protein diet with similar low lipids. Slight changes were noted in triglyceridemia and in HDL cholesterol concentration (Gaddi et al, 1987).
Soy formula diets fed to infants through the first 6 months of life resulted in lower total serum cholesterol and serum triglycerides (p<0.05) than in whey-based diets. Infants were divided into 5 groups: human milk (HM)(n=29), Soy formula (SF)(n=25), whey-based low-degree hydrolysate (Why)(n=15), casein-based high-degree hydrolysate (Chy)(n=13), and Soy plus collagen-based high-degree hydrolysate (SHy) (n=10). The mean total cholesterol level was lowest in the SHy group (3.0 mmol/L), followed by the SF and HM groups (3.3 mmol/L), the Chy group (3.4 mmol/L), and then the Why group (3.8 mmol/L). The similar order for triglycerides was 0.9 mmol/L for Soy, 1.2 mmol/L for HM and Why, and 1.6 for the Chy and Shy groups (Giovannini et al, 1994).
To examine the effects of dietary Soy/isoflavones on 24-hour blood pressure profiles and arterial function, a six-month, double-blind, placebo-controlled, crossover trial was performed. Forty-one hypertensive subjects received either Soy cereal (40 g Soy protein, 118 isoflavones) or gluten placebo cereal for three months. Soy dietary supplementation had no effect on arterial function, ambulatory blood pressure parameters, or central blood pressure (Teede et al, 2006).
By contrast, a cookie containing 40 g of Soybean protein resulted in a reduction in blood pressure in a randomized, double-blind controlled trial in three communities in China. The study involved 302 adults (35 to 64 years old) with high-normal or mildly elevated untreated systolic blood pressure of 130 to 159 mm Hg and diastolic pressure of 80 to 99 mm Hg or both. The participants were randomized to consume the Soybean protein cookies or a control cookie (a complex carbohydrate) daily for 12 weeks. Blood pressure was measured at baseline, six weeks, and 12 weeks. At this final reading, the time in which the Soybean cookies was consumed were linked to reduced diastolic and systolic blood pressure values by approximately 3 to 4 mm Hg more than the time that the carbohydrate cookies were consumed. Most participants ate the cookies in place of their usual breakfasts (He, 2005).
In a similar finding, supplemental Soy milk demonstrated a modest but significant reduction in blood pressure in a placebo-controlled, randomized trial. Patients with mild to moderate essential hypertension (n=40; 25 male, 15 female) were randomly assigned to receive 500 mL of Soy milk (containing 63 mg daidzein, 80 mg genistein), or 500 mL cow's milk twice daily for 3 months, following a 4-week washout period (without any medications, including antihypertensives). The Soy group significantly (p<0.001) reduced systolic blood pressure by 18.4 mm/Hg (± 10.7), diastolic blood pressure by 15.9 mm/Hg (± 9.8), and mean blood pressure by 16.7 mm/Hg (± 9.0) compared to 1.4 mm/Hg (± 7.2), 3.7 mm/Hg (± 5.0), 3.0 mm/Hg (± 4.6), respectively, for cow's milk. Reductions in blood pressure were associated with urinary genistein excretion but not daidzein (Rivas et al, 2002).
Menopausal Symptoms/Hot Flushes
A systematic review and meta-analysis of nonhormonal therapies for menopausal hot flushes found mixed results for the ability of Soy isoflavone extracts to lessen this common symptom. In fact, results for Soy isoflavone extracts were contradictory overall—even among the largest and highest quality trials, the authors concluded. The weak estrogenic and anti-estrogenic activities and ability to bind to estrogen receptors of isoflavones from Soy (and red clover) could potentially mediate hot flushes triggered by estrogen deficiency in menopause, but this action also could cause adverse effects. Evidence as a whole, the authors conclude, does not support recommending Soy in any form (flour, powder, in foods) for relieving hot flushes and is not an optimal choice for most women (Nelson 2006).
A systematic review of 10 clinical trials involving monotherapy of Soy or Soy isoflavones for perimenopausal symptoms, with focus on hot flushes, demonstrated equivocal results. Four of the randomized trials had beneficial effects, while six did not. Authors reported a dosing range of the studies of 34 to 134.5 mg a day of Soy isoflavones. Of the 6 that did not demonstrate beneficial effects, one of them demonstrated a positive trend that did not reach significance. Adverse events were insignificant, with no serious side effects other than mild gastrointestinal complaints (Huntley and Ernst, 2004).
Soy isoflavones decreased menopausal symptoms in a randomized, double-blind, placebo-controlled study of 80 healthy women 45 to 55 years. Subjects received isoflavones 100 mg (including genistein 69.9 mg, daidzein 18.6 mg, glycitein 11.4 mg) (n=40), or placebo (n=40) daily for five months. Subjects taking isoflavones experienced a significant decrease in menopausal symptoms measured using the Kupperman index compared with placebo and baseline (24.9 with isoflavones, 41.6 with placebo, and 44.6 at baseline) (p<0.01). The Kupperman index rates hot flushes, paresthesia, insomnia, nervousness, melancholia, vertigo, weakness, arthralgia or myalgia, headache, palpitations, and formication. No side effects were observed (Han et al, 2002).
Soy isoflavone extract reduced the frequency of hot flushes in postmenopausal women in a double-blind, placebo-controlled trial. Postmenopausal women, who not on hormone replacement therapy who requested treatment for hot flushes and with no menstrual period for at least 6 months, were randomized to receive four, 325 mg PhytoSoya® (for a total of 70 mg isoflavones/day; n=38) or placebo (cellulose; n=34) for 16 weeks. The authors claimed a mean reduction in hot flush frequency using last observation carried forward for the intention to treat analysis (p=0.0103; -3.6 (95% confidence interval - 6.2; -.9), but significance was not reached using 16-week observed data (Drapier-Faure, et al, 2002).
Soy had no effect on menopausal symptoms in a double-blind, placebo-controlled, trial. Women (42 to 62 years), not on hormone replacement, were randomized to receive either isoflavone-rich Soy protein (80.4 milligrams a day of aglycone components; n=24), isoflavone-poor Soy protein (4.4 milligrams a day of aglycone components; n=24) or whey protein control (n=21) for 24 weeks. No significant changes were noted for those women taking Soy for reductions in hot flushes or night sweat frequency, duration, or severity. All symptoms in all groups improved with time, suggesting a placebo effect or time as a factor in improvement (Germain et al, 2001).
Hot flushes were reduced in frequency and severity in postmenopausal women treated with a Soy isoflavone extract containing 50 mg of genistein and daidzein/day in a double-blind, randomized, placebo-controlled study. Subjects were randomized to receive the Soy extract treatment (n=89) or placebo (n=86) daily for 12 weeks. The Soy group experienced a significant decrease in hot flash severity (p=0.01) in comparison to the placebo group (Upmalis et al, 2000). An earlier double-blind, placebo-controlled, parallel, multicenter, randomized study of post menopausal women also showed a reduction in hot flushes (Albertazzi et al, 1998).
A combination Soy, Donq quai, and Black Cohosh supplement successfully reduced migraine frequency in a double-blind, randomized, placebo-controlled trial. Following a 4-week placebo run-in period, patients were randomized to receive either a phytoestrogen supplement (n =20) containing: 75 mg Soy extract (40% isoflavones), 50 mg Dong Quai extract (standardized to 1% ligustilide), and 25 mg Black Cohosh (standardized to 8% triterpenes) or an identical looking placebo (n=18) twice daily for 24 weeks. Significant reductions in the primary outcome measure of mean number of menstrual migraine attacks (weeks 9 to 24) was observed in the supplemented group compared to placebo (4.7 (95% confidence interval 1.59 to 7.81) vs 10.3 (6.12 to 14.48); p<0.01). Secondary outcomes including frequency of any migraine attack (weeks 20 to 24), mean headache severity score (weeks 20 to 24), self-medicated triptans doses (weeks 20 to 24), and doses of analgesics (weeks 20 to 24) were all significantly reduced compared to placebo (p less than 0.01) (Burke et al, 2002).
Soy had a mildly beneficial effect on bone mineral content in women in a randomized, double-blind, placebo-controlled trial. Post menopausal Chinese women (48 to 62 years) were randomly assigned to receive either a 0.5 g Soy extract (40 mg isoflavones) (n=68), a 1 g Soy extract (80 mg isoflavones) (n=68), or placebo (n=67) daily for 1 year. Isoflavones consisted of daidzein (46.4%), glycetein (38.8%), and genistein (14.7%). All women also took calcium 500 mg/day and vitamin D 125 international units/day for a year. No statistically significant difference in bone mineral density (BMD) was noted. Positive changes to bone mineral content (BMC) were noted at the trochanter in subjects in the high-dose group compared to placebo and mid-dose groups (p<0.05) (Chen et al, 2003).
Soy protein exerted a beneficial effect on serum and urinary biomarkers of bone metabolism in women in a double-blind, parallel design study. Forty-two postmenopausal women (mean age 62.4 years) were randomly assigned to receive either 40 g Soy protein (n=20) or 40 g milk-based protein (n = 22) daily for 3 months. Soy protein had the greatest effects on women who were not on hormone replacement therapy. In this sub-roup, a significant decrease in urinary deoxypyridinoline (Dpd) excretion (p =0.0041) and a substantial increase in serum IGF-I (p= 0.0001) were noted compared to baseline, while corresponding changes were not noted in those on milk-based protein (Arjmandi et al, 2003).
A randomized trial of 187 healthy postmenopausal women demonstrated that a diet rich in Soy is not as effective as hormone replacement therapy (HRT) on the main biomarkers of bone turnover, but the Soy diet did stimulate osteoblastic activity. The women were divided into 3 groups and were followed for 6 months; diet intervention group (average 47 mg/day of isoflavones) (n=53), HRT group (n=53, type and dose not specified), and control group (n=58). The biomarkers of bone turnover measured were osteocalcin, N-telopeptide-C, hydroxyproline, and cortical and trabecular bone mineral density. A significant decrease in bone turnover was demonstrated only in the HRT group (p<0.05). Osteocalcin levels significantly increased in the Soy diet group (5.45; CI=0.36 to 10.5; p<0.05). Bone mineral density decreased significantly only in the control group (-.03; CI=-.06 to .001, p<0.05). Fifty-five percent of subjects in the Soy-rich diet group did not complete the study due to dislike of Soy and difficulty finding and cooking Soy foods (Chiechi et al, 2002).
Treatment with Soy protein decreased bone loss from the lumbar spine in postmenopausal women in a randomized, double-blind trial (Alekel et al, 2000). Limited increases in bone density and mineralization occurred in 66 hypercholesterolemic, postmenopausal women who were given 40 g/day of moderate to high isoflavone containing Soy protein in a 6-month, double-blind, parallel-group study (Potter et al, 1998).
Six months of treatment with 40 g of Soy protein/day (containing 90 mg of isoflavone) produced increased lumbar spine mineral content and density. A dose with 56 mg of isoflavones did not have this effect (Finkel, 1998).
The incidence of prostate cancer is much lower in Asian than Western men, suggesting a possible link to environmental factors such as diet. This population-based prospective examination in 43,509 men from Japan aged 45 to 74 years old looked at the intake of Soy isoflavones in the diet and the incidence of prostate cancer over time. The participants filled out a validated questionnaire that included questions about 147 food items at various times from 1995 through 2004. While consumption of Soy food, miso soup, genistein and and daidzein were not associated with the incidence of total prostate cancer, consumption did decrease the risk of localized prostate cancer. Notably, in men over age 60, consumption of isoflavones and Soy foods were linked to a dose-dependent decrease in the risk of localized cancer. Also, men with the highest intake of isoflavones (specifically, as genistin equal to or greater than 32.8 mg/d) had a decreased risk of prostate cancer compared with those with the lowest intake (as genistein less than 13.2 mg/d). This inverse association between isoflavone and localized prostate cancer in Japan may be the first prospective study to show this association, Notably, however, the isoflavone intake did also tend to be associated with an increased risk of advanced prostate cancer. More research in the form of clinical trials is needed to clarify these effects (Kurahashi, 2007).
In earlier research, Soy had no effect of serum prostate specific antigen (PSA) in a series of randomized, crossover trials. Healthy men (n=46) with various baseline PSA levels were recruited for studies on the effects of Soy on blood lipids. Pooled analysis from four studies showed treatment phases that lasted from 3 to 4 weeks, with average Soy protein consumption of 44 g (116 mg isoflavones) daily. Although Soy consumption was significant enough to reduce serum cholesterol and oxidized low-density lipoprotein concentration, no effect on PSA values were seen (Jenkins et al, 2003).
Treatment with isolated Soy protein (ISP) beverages in 34 elderly men (>55 years) with elevated PSA (> 4 nanogram/milliliter) had no effect on either PSA or p105 (pro-oncogene) in a randomized, double-blind, crossover study (Urban et al, 2001).
Quality of Life, Postmenopausal
No particular or marked overall benefit of one-year supplementation with Soy protein containing isoflavones on quality of life was observed in 202 postmenopausal women (age 60 to 75) in this double-blind, randomized and placebo-controlled trial. The daily Soy protein supplement was a powder that contained 25.6 g Soy protein with 52 mg genistein, 41 mg daidzein, and 6 mg glycein. The placebo was milk protein. A questionnaire was used to assess changes in quality of life such as health status, depression, and life satisfaction (Kok. 2005).
A Soy-based, low-protein, vegetarian diet was well tolerated, maintained renal function, and improved some nutritional aspects in patients with chronic renal failure. Patients were more compliant with recommended caloric, protein, and phosphate intakes on the Soy diet versus the animal protein diet (p<0.05). These results translate to higher caloric diets, which were lower in protein and phosphate that are essential for patients with chronic renal failure. Nine patients with chronic renal failure (glomerular filtration rate (GFR) of 15 to 50 mL/minute/1.73 m2) completed testing in a randomized, crossover trial of 2 different diets. Both diets were low protein; one contained Soy and the other contained animal-based protein. The GFR was the same at 6 months and remained the same throughout the study in both groups. Nutritional status (body mass, midarm circumference, lean body mass, percent body fat) remained the same over the one year of the study. The Soy group had a higher calorie intake, a lower protein intake, and a lower protein intake/kg than either prediet baseline or the animal protein diet (p<0.05). The Soy diet also lowered blood urea nitrogen, urine urea nitrogen, protein catabolic rate, 24-hour urine creatinine, and phosphate more than the animal protein diet (Soroka et al, 1998).
Indications & Usage
Approved by Commission E:
- Raised levels of cholesterol
Soybean is used for less severe forms of hypercholesterolemia when dietary measures are required. Soybean is also used for liver and gallbladder complaints, anemia, poor concentration, cerebral and nerve conditions, and general debility.
Soybean is used for hyperhidrosis, night sweats, confusion, and joint pain.
There are no known contraindications to the use of Soy.
Precautions & Adverse Reactions
Minor side effects may include occasional gastrointestinal effects, such as stomach pain, loose stool and diarrhea.
Lower circulating estrogen levels and longer menstrual cycles have been reported with Soy-rich diets. Vomiting has been reported, as has contact dermatitis. Gastrointestinal symptoms and atopic dermatitis may occur with the use of Soy formulas but anaphylaxis is extremely rare. A meta analysis of 17 studies on allergy to Soy formulas was represented by 27% history- based studies, 4% challenged test based studies, and about 3% skin prick tests (Cantani & Lucenti, 1997).
A meta analysis of 14 trials determined that there is a link between the consumption of fermented Soy foods and risk of stomach cancer in Asian populations. The inverse relationship between stomach cancer and non-fermented Soy foods was also present. The authors of the analysis state that none of the studies have taken into account such confounders as salt, N-nitroso compounds, and additional plant foods that might be eaten in conjunction with non-fermented Soy foods and, therefore, makes these conclusions suspect (Wu et al, 2000).
Central Nervous System Effects
A prospective cohort study of 3,734 Japanese-American men found that those who consumed higher amounts of tofu in middle life were significantly more likely to demonstrate poor cognitive test performance, enlargement of ventricles, and low brain weight. The investigators hypothesized that the result may be due to the ability of some Soy isoflavones to inhibit tyrosine kinase, an enzyme that is involved with neuronal plasticity (White et al, 2000).
Lower estrogen levels and longer menstrual cycles have been reported with Soy-rich diets (Cassidy et al, 1994).
Dietary Soy consumption was associated with greater than a twofold increased risk of bladder cancer in the Singapore Chinese Health Study of 63,257 Chinese men and women (Sun et al, 2002).
An epidemiologic study suggests that early Soy formula feeding may be associated with autoimmune thyroid disorders later in life (Fort et al, 1990). In a review article, this hypothesis was supported by animal and in vitro studies that suggested genistein may stimulate immune function by antigen formation through covalent binding of genistein to thyroid peroxidase (TPO) (Doerge & Chang, 2002; Doerge & Sheehan, 2002). Soy-containing formulas were associated with goiter and hypothyroidism in infants in the 1960s until the addition of iodine to formulas. The relationship between Soy and goiter is well known in animals and appears to be related to iodine deficiency (Doerge & Sheehan, 2002).
Concurrent use of soy and levothyroxine may result in decreased effectiveness of levothyroxine. Clinical Management: Soy administered either as a supplement or as a dietary component may impair absorption of levothyroxine. It is thought that this effect would be minimized if administration times were separated by two hours or more, but no data exists to verify this assumption. Patients should be advised to avoid the combination. Thyroid function tests should be monitored in patients who elect to use soy with levothyroxine. Levothyroxine dose requirements may increase. Serum thyroxine and thyrotropin levels should be obtained within 6 weeks of soy discontinuation to determine if levothyroxine dose requirements have decreased.
Concurrent use of soy and warfarin may result in reduced warfarin effectiveness. Clinical Management: Monitor the INR closely whenever initiating or discontinuing soy milk or other soy foods or supplements in a patient taking warfarin. One case report described a decreased INR in a patient taking warfarin after starting Soy milk (Cambria-Kiely, 2002).
Concurrent use of soy and iron may result in reduced iron absorption. Clinical Management: Soy administered either as a supplement or as a dietary component may impair absorption of iron. It is thought that this effect would be minimized if administration times were separated by two hours or more, but no data exists to verify this assumption. Patients should be advised to avoid the combination.
Other Possible Risks
Concurrent use of soy and tamoxifen may result in decreased tamoxifen effectiveness. Clinical Management: Avoid concomitant use of soy and tamoxifen.
Mode of Administration
Preparations for oral administration.
The average dose is 3.5 g of phospholipids (phosphatidylcholine).
Soybean preparations must be protected from light and tightly sealed.