Dose responses for varying concentrations of soybean protein were determined in 81 hypercholes-terolemic males (ages 23-74, free-living outpatients, Champaign-Urbana, IL) while being maintained on National Cholesterol Education Program Step-1 diet. (<30% energy from fat, <10% saturated fat, and <300 mg cholesterol). Pertinent baseline data included mild hypercholesterolemia (220-300 mg/dL) and the body mass index range 26.4-27.8. After a three-week lead-in period, subjects were randomly assigned to one of five experimental groups. For six weeks, each group received 50 g/day, which included isolated soy protein (ISP; Supro Plus 675 HG with 1.9 mg total isoflavone aglycone units/g protein, Protein Technologies International, St. Louis, MO) and casein (calcium caseinate, Alanate 391; New Zealand Milk Products, Wellington). The five groups received 50-, 40-, 30-, 20-, and 0 g (control) ISP and 0-, 10-, 20-, 30-, and 50 g casein, respectively. Test proteins were given through baked foods and ready-to-mix beverages, and the consumption of foods was monitored five times per week. Primary outcome measurement was change from baseline for each subject, and there were 15-18 males per group. At six weeks, non-HDL cholesterol was reduced in all groups that received ISP. The reduction in total was significant at six weeks for the groups that 20-, 30-, and 50-g ISP The 40-g ISP reduced total cholesterol 0.053 mmol/L (statistically not significant). At week six, no significant changes were found for concentrations of HDL cholesterol, tria-cylglycerol, apo A-I, or lipoprotein(a) or TC:HDL cholesterol in any group that received ISP. This trial therefore identifies a cholesterol lowering effect with doses as low as 20 g of soy protein/day in this normal-weight, mildly hypercholesterolemic male population.

Another randomized, double-blind, placebo-controlled study from Brazil examined the change in menopausal symptoms and cardiovascular risk factors in 80 postmenopausal women (ages 45-55). These subjects all had to be in menopause at least 12 months, and no subject had been treated with hormonal or lipid lowering therapies within the previous 12 months. Subjects were randomized to either:
1) Isoflavone group (n=40)—Each capsule was 83.3 mg and was composed of soy protein 50.3 mg (60%) and isoflavone 33.3 mg (40%), which consisted of genistein (23.3 mg), daidzein (6.2 mg), and glycetin (3.8 mg).
2) Placebo group (n=40)—Each capsule was 83.3 mg and was composed of purified soy protein 50.3 mg (without any kind of isoflavone) and glucose 33.3 mg.

The 80 women completed the five-month study, which included screening, baseline, and four months of treatment. At the end of the study, menopausal symptoms were assessed; BMI, blood pressure, lipids, hormone levels, and transvaginal sonography were determined; and these data compared to baseline. The Kupperman index was used to evaluate 11 menopausal symptoms: 1) hot flashes (vasomotor), 2) paresthesia, 3) insomnia, 4) nervousness, 5) melancholia, 6) vertigo, 7) weakness, 8) arthralgia/myalgia, 9) headache, 10) palpitation, 11) formication (the sense of feeling ants or insects on the skin). To calculate the index, each symptom is graded (0-3) for no, slight/moderate, or severe complaints. Symptoms are rated as follows: hot flashes (x4) paresthesia (x2), insomnia (x2), nervousness (x2), and all others (xl). Therefore, the highest potential score is 51. The score of hot flashes was based on number of complaints per day: slight (<5), moderate (5-10) or severe (>10).

Evaluations of cardiovascular disease risk indicated that both total and LDL were significantly decreased in the isoflavone group compared with baseline or placebo group. The HDL cholesterol and triglycerides canadian increased in both groups, (control n=40, isoflavone (n=40). Isoflavones decreased total cholesterol (mean ± SEM) by 26.8 ± 5.8 (pO.OOl) and LDL cholesterol by 13.3 ± 4.6 (pO.OOl). HDL cholesterol increased in both groups by 4 ± 1.5 (pO.OOl paired t-test, two-tailed.) were modestly elevated in both control (10.3 ± 6.2) and isoflavone groups (6.5 ± 15). During the four-month treatment period, the menopausal symptoms in the isoflavone group were significantly less than placebo group. The Kupper man menopausal index, decreased approximately 20 points within the isoflavone group, was accompanied by marked improvements in climacteric signs and symptoms.

Phytoestrogens have recently been linked to improved bone health in postmenopausal women in anecdotal, lay press, and agromedical literature. Estrogen consumed in foods of postmenopausal females has long been suggested as playing a role in the decreased osteoporosis in Chinese, Japan, and other Asian countries. Recent reports (Women’s Health Initiative Investigators) in postmenopausal women of serious HRT-induced, adverse side effects from especially the oral estrogen/progesterone combinations have resulted in decreased prescriptions for Prempro (66%) and (33%) during the six months January-June 2003 when compared to January-June 2002.

A large study (n=650) of Hong Kong southern Chinese females has correlated soy food intake using food frequency tertiles and documents these effects on bone health. There were nine major sources of soy foods evaluated by low, medium, and high daily intake. Bone mineral density (BMD) was measured at lumbar spine (L2-4), femoral neck, trochanter, Ward’s triangle, and total hip using dual-energy x-ray absorptiometry in 293 premenopausal and 357 postmenopausal women. BMD measurements of the three groups of phytoestrogen intakes were evaluated after controlling for age, weight, height, and years since menopause, smoking, alcohol, calcium intake, and previous hormonal replacement therapy (only 4.5% within postmenopausal women group had previous HRT). Their data indicate that postmenopausal females consuming higher daily intake of soy foods had increases in bone mineral density at three characteristics locations: Lumbar spines 2-4, total hip, and femoral head (Ward’s triangle). Ward’s triangle, an area of radiolucency between primary trabecular patterns within the femoral neck, is a particularly prone to osteoporosis in menopausal women. Though soybean foods appear to increase BMD within these three anatomic areas in postmenopausal Chinese women, there were no detectable effects in premenopausal women presumably because there was still enough circulating endogenous estrogen. Evidence exists that soybean sources of estrogen in postmenopausal women induce positive effects in bone physiology. This results in a decreased loss of bone because soybean foods slow the resorption of bone. Women with the highest intake of isoflavones had significantly lower levels of serum PTH, osteocalcin, and urinary NTx excretion when compared to the low isoflavone intake group.

Two Canadian studies involving unique populations of hyperlipidemic Caucasians reported the effects of soy foods on elevated serum lipoproteins. The first involves 41 subjects, whose mean age was 62 and mean BMI=25.3. No subject had clinical or biochemical evidences of diabetes, liver, or renal disease. All subjects had elevated LDL cholesterol (>4.1 mmol/L). The three phases included: 1) Control phase—low fat dairy, egg substitution, low fat cheeses, and protein foods of the NCHEP Step-II diet (<7% energy from saturated fats and <200 mg/d of dietary cholesterol) 2) Low isoflavone phase, and 3) High isoflavone phase. The major isoflavones were genistein, daidzein, and glycetin, and the approximate amounts obtained in the low phase were 10 mg/d and 73 mg/d in the high phase. Sources of soy protein and isoflavones were soy milk (low fat 0.1% fat), soy hot dogs, breakfast links, cold cuts, and tofu burgers and nuggets made from soybeans. Their results indicated that there was over 96% compliance to the diets in all three phases. There was no significant difference in blood lipid responses between the low- and high-phase isoflavone groups, but both exhibited significantly more effects than the control phase. More specifically, there were significant decreases in total cholesterol (7%) and LDL (7.1%). Both soy isoflavone phases decreased the oxidized LDL levels and homocysteine levels (6%). The high isoflavone group experienced a 8% decrease in SBP in men but not women. A follow-up outpatient (three-month) study from the same Toronto center has been completed in 46 subjects. The randomized, clinical trial was designed to compare low-fat foods and lovastatin 20 mg/day in hyperlipidemic Caucasians. There were 25 males and 21 postmenopausal women and only one black female. The mean age was 59 (range 36-85 years), mean body mass index (BMI) was 27.6 ± 0.5 (range 20.5-35.5). Mean LDL cholesterol was >158 mg/dL or >4.1 mmol/L. No subject had a history of heart disease, diabetes, renal or liver disease, and no subject was receiving lipid-lowering agents. (Twenty-one subjects had been treated with oral statins, but all had discontinued these medications two weeks prior to study and five subjects received antihypertensive medications throughout the study.) There was only one cigarette smoker. All subjects received the NCHEP Step-II diet for one month prior to study entry. Subjects were randomized to either: 1) a diet very low in saturated fat, based on milled wholewheat cereals and low-fat dairy foods (n=16; control) 2) same diet plus lovastatin, 20 mg/d (n=14), or 3) diet high in plant sterols (dietary portfolio) derived from enriched margarines (1.0 g/1,000 kcal), soy protein (21.4 g/1,000 kcal), viscous fibers (9.8 g/1,000 kcal), and almonds (14 g/1,000 kcal; n=16). The control, statin, and dietary portfolio groups had mean (SE) decreases in LDL cholesterol of 8.0 ± 2.1% (PO.002), 30.9 ± 3.6% (PO.OOl), and 28.6 ± 3.2% (PO.OOl), respectively. The reductions in C-reactive protein were 10 ± 8.6% (control), 33.3 ± 8.3% (statin group) and 28.2 ± 10.8% (dietary portfolio). Hence, there was no significant difference in efficacy between the statin group and dietary portfolio group, yet both diets were superior to the control diet. Both Canadian studies confirm soybean foods, often-reported serum-cholesterol-lowering effects, even within in this unique Caucasian population (no biochemical or clinical indicators of diabetes, liver or renal disease). Preventive primary care must now mandate that soy foods, which are known to lower the bad LDL cholesterol, become a primary intervention for elevated before our polypharmacy approach.