[Soyfoods Symposium 1997 Home Page] Soyfoods Protect From Heart Disease
By Belinda Smith, M.S., R.D. L.D.
Nutrition Research Coordinator/Metabolic Research GroupCoronary heart disease (CHD) is the major cause of death in most developed countries and is rapidly increasing in prevalence in developing countries. In the US, death rates from cardiovascular disease exceed one million annually and the total cost is estimated to exceed $120 billion, the largest disease-related cost to health. While many risk factors, such as cigarette smoking and hypertension, contribute to risk for CHD, lipid abnormalities are the major factors. Low-density lipoproteins (LDL) have a central role in the atherosclerotic process. LDL penetrate the walls of blood vessels where they are oxidized by free radicals and accumulate as a gruel-like material that blocks the blood vessel lumen; this material also can leak into the blood vessel to cause a thrombosis. High-density lipoprotein (HDL) cholesterol has a protective effect and act to prevent LDL oxidation and remove cholesterol that accumulates in the blood vessel wall.
Dietary intervention to reduce heart disease risks includes attention to saturated fat replacement, fiber, and antioxidants, contributions from which soy products provide. Soy protein exerts several cardioprotective effects. First, it decreases LDL-cholesterol levels significantly1. Second, it tends to increase HDL-cholesterol levels1; this is rather unique since most dietary interventions such as oat bran intake or decreased saturated fat intake significantly decrease HDL-cholesterol levels. Third, soy isoflavones have antioxidant properties which protect LDL from oxidation3. Fourth, soy isoflavones have favorable effects on blood vessel function4.
Meta-Analysis
Dr. Anderson teamed up with a dietitian, Maggie Cook Newell, and a statistician, Bryan Johnstone, to do a meta-analysis of soy protein studies. The first step in this review was to exhaustively search the literature to identify all of the clinical studies examining soy protein effects on serum lipid levels. Next they established rigorous criteria for inclusion of the study in the analysis. All acceptable studies had to be conducted as controlled clinical trials which were published in peer-reviewed journals. They next identified important dependent outcome variables (such as serum cholesterol) and independent variables (such as type or amount of soy protein) which might affect the lipid responses. The data was extracted and tabulated from the research reports and entered into the meta-analysis program.
Meta-Analysis Results
Thirty-eight studies including 730 research volunteers were identified. Thirty-four studies included only adults, while four studies included only children. As a soy protein source, 20 used isolated soy protein, 15 used textured soy protein, and three used a combination of isolated and textured soy protein. Soy protein intake averaged 47 grams per day (range 17-124 grams/day) and 15 studies (40%) used ¾31 grams of soy protein daily. In 14 of the studies the test diets resembled a typical Western diet while in 21 studies the diets were low in fat (¾30% of energy) and low in cholesterol (¾200 mg/day). In 19 studies the soy protein and control diets were considered to be comparable with respect to total fat intake, saturated fat intake, cholesterol intake, and weight maintenance.
Soy protein intake was associated with a 9.3% reduction in serum cholesterol, a 12.9% reduction in serum LDL-cholesterol, and a 10.5% reduction in serum triglycerides. All of these decreases were statistically significant. Serum HDL-cholesterol levels increased by 2.4%, a non-significant increase. These findings had a strong consistency because 34 of 38 studies reported that soy protein intake decreased serum cholesterol levels1.
Serum lipid changes were highly correlated with initial levels (P < 0.001). For serum cholesterol, the baseline value accounted for 77% of the variance observed. This indicates that the initial serum cholesterol level is the strongest and most important determinant of the serum cholesterol response to soy protein. The expected reduction in serum LDL-cholesterol for research volunteers was calculated with initial serum cholesterol levels of: normal; mild hypercholesterolemia; moderate hypercholesterolemia; and severe hypercholesterolemia. Those volunteers with normal initial levels had LDL-cholesterol decreases of 7.7% while those with severe hypercholesterolemia had LDL-cholesterol decreases of 24%. This indicates that individuals with more severe hypercholesterolemia are likely to show a greater response to soy protein use.
Most other independent variables or characteristics did not have a significant effect on the serum lipid response to soy protein. Adults and children showed similar responses. The type of diet or matching of diet variables did not have a significant effect. The type of soy protein (isolated versus textured soy protein) did not have a significant effect. Using a special statistical manipulation, they observed that the amount of soy protein had a significant effect. This analysis indicates that the intake of 25 grams of soy protein per day would reduce serum cholesterol by 8.9 mg/dl, 50 grams would reduce it 17.4 mg/dl, and 75 grams of soy protein would reduce serum cholesterol by 26.3 mg/dl. Our study, however, predicted that intake of 17-25 grams of soy protein per day could have a meaningful effect on serum cholesterol levels.
Meta-Analysis Discussion
This analysis documented that daily intake of soy protein significantly decreases serum cholesterol concentrations in adults and children. The average reduction in serum cholesterol levels was 9.3%. Since every one percent reduction in serum cholesterol decreases estimated risk of heart attack by two to three percent, this serum cholesterol reduction has the potential to reduce risk for CHD by 18-28%.
The specific components and mechanisms responsible for this effect has not been fully established, although several theories have been examined5. Investigators initially focused on the amino acid composition, however more recent research suggests that the soy isoflavones may have an important role in the hypocholestero-lemic effects of soy protein6. Various theories exist regarding the specific actions soy exerts on lipoproteins5. Some studies suggest that alterations in bile acid or cholesterol absorption may cause changes in cholesterol homeostasis. Hormonal changes such as increased thyroid hormone or reduced insulin:glucagon ratios have been suggested to alter cholesterol metabolism. Huff, et al. demonstrated an increased turnover rate of VLDL apoprotein B, without change in VLDL concentration or pool size, in men fed soy protein diets in place of animal protein diets7. Lovati and colleagues report that the LDL-receptor activity of mononuclear cells is eight times greater in hypercholesterolemic subjects receiving soy protein as compared to animal protein8. The soy protein diet dramatically affected LDL degradation.
Monkey Studies
Anthony, Clarkson and colleagues6 have published reports on three studies with monkeys. In these studies, soy protein rich in soy isoflavones favorably affected serum lipid concentrations while soy protein from which the soy isoflavones had been extracted had a minimal impact. These primate studies suggest that soy isoflavones may account for 60-70% of the effects of soy protein.
Other Benefits
Potential benefits of soy protein, independent of cholesterol reduction have been identified and investigated. In vitro studies of vascular cell cultures have shown that the isoflavone genistein inhibits atherosclerotic lesion development by inhibiting cell adhesion, altering growth factor activity and hindering cell proliferation9. It also has been shown to inhibit thrombin formation and platelet activation in vitro4. Peroxidized LDL-cholesterol accelerates platelet aggregation, injures the endothelium of arteries, and is found in high concentrations in patients with atherosclerosis. In vitro studies suggest that genistein and daidzein inhibit LDL-oxidation inside the arterial wall, similar to Vitamin C's action10.
Practical Implications
Emerging research indicates that soy protein intake has a significant favorable effect on serum lipid levels and may reduce risk for atherosclerotic cardiovascular disease1,2,3,4,8,11. The role of soy protein as a protective factor against breast and prostate cancer is under intense investigation3,12. Substituting soy protein for animal protein appears to have protective effects for the kidney, especially for individuals with diabetes13. The role of soy protein in reducing menopausal symptoms is also under investigation12. Finally isoflavone analogues appear to reduce risk for, and have therapeutic value for, persons at risk for osteoporosis12. Based on this evidence we recently proposed these guidelines for soy protein intake published in Dr. Anderson's Antioxidant Book14.
General Prevention
Persons in good general health should have 7 servings of soy protein per week*. This would provide an average of approximately 8-10 grams of soy protein daily with 16-20 mg of soy isoflavones daily. This could be obtained from 8 ounces of soy beverage daily, or two soy muffins daily, or two servings of tofu four times weekly, or four soy burgers weekly, or 1 tablespoon (14g) of isolated soy protein stirred into beverage daily.
Tailored Protection
For persons with diabetes or risk factors for coronary heart disease or persons with strong family histories of heart disease, osteoporosis or diabetes we suggest a goal of 14 servings of soy protein per week*. This would provide an average of approximately 16 to 20 grams of soy protein/d with 32 to 40 mg of soy isoflavones/d.
Disease Reversal
For persons with coronary heart disease or osteoporosis, we recommended a goal of 21 servings of soy protein per week*. This would provide an average of approximately 24 to 30 grams of soy protein daily with 48 to 60 mg of soy isoflavones daily. Isolated soy protein with standardized amounts of isoflavones (1 mg genistein and 2 mg of total isoflavones per gram of protein) are useful for these individuals since they can incorporate most of their daily "quota" of soy protein and isoflavones in a single milkshake.
Sources of Soy Protein
Textured soy protein or textured vegetable protein (TVP) is an excellent source of soy protein and isoflavones. Soy beverages have variable amounts of soy protein but optimal products provide about 8 grams of soy protein per serving. Soy flour can be used in baking a variety of breads, muffins and cookies. Tofu is an excellent source of soy protein but is more difficult to incorporate into a typical American diet than other soy protein sources. Soy protein concentrates available in some soy burgers and other products have lower concentrations of soy isoflavones because of the alcohol extraction process; the effects of soy protein concentrate products which are low in soy isoflavones on serum lipid concentrations are not well defined. Isolated soy protein products provide about 2 mg of isoflavones per gram of protein and may be the most reliable source of isoflavones from food products.
Conclusions
Soy protein and its isoflavones provide many health benefits. Careful studies indicate that regular intake of soy protein is associated with favorable changes in serum lipoprotein concentrations. Our meta-analysis1 noted that soy protein intake was accompanied by a significant 9.3% reduction in serum cholesterol concentrations, a significant 12.9% reduction in LDL-cholesterol levels, a significant 10% reduction in serum triglycerides and a 2.4% increase in serum HDL-cholesterol values.
Emerging research indicates that soy protein intake may reduce risk for atherosclerotic cardiovascular disease by favorable alterations in serum lipoprotein concentrations, by the antioxidant action and favorable effects on the health of vascular endothelium mediated by soy isoflavones.
*These recommendations outlined in our book written for the general public14 are provisional and are based on the best scientific information available at the time of writing (August 1996). Recommendations for use of soy protein for persons with breast or prostate cancer, or family histories of breast cancer, are controversial and are not included here.
REFERENCES
1Anderson JW, Johnstone BM, Cook-Newell ME. Meta-analysis of effects of soy protein intake on serum lipids in humans. N Engl J Med 1995; 333:276-282
2Kanazawa T, Osanai T, Zhang XS, Uemura T, Yin XZ, Onedera K, et al. Protective effects of soy protein on the peroxidizability of lipoproteins in cerebral vascular diseases. J Nutr 1995; 125:639S-646S.
3Wei H, Bowen R, Cai Q, Barnes S, Wang Y. Antioxidant and antipromotional effects of the soybean isoflavone genistein. Proc Soc Exper Biol Med 1995; 208:124-130.
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5Potter SM. Overview of proposed mechanisms for the hypocholesterolemic effect of soy. J Nutr 1995; 125:606S-611S.
6Anthony MS, Clarkson TB, Hughes CL, Morgan TM, Burke GL. Soybean isoflavones improve cardiovascular risk factors without affecting the reproductive system of peripubertal rhesus monkeys. J Nutr 1996; 126:43-50.
7Huff MW, Giovannetti PM, Wolfe BM. Turnover of very low-density lipoprotein-apoprotein B is increased by substitution of soybean protein for meat and dairy protein in the diets of hypercholesterolemic men. Am J Clin Nutr 1984; 39:888-897.
8Lovati MR, Manzoni C, Canavesi A, Sirtori M, Vaccarino V, Marchi M, et al. Soybean protein diet increases low density lipoprotein receptor activity in mononuclear cells from hypercholesterolemic patients. J Clin Invest 1987; 80:1498-1502.
9Raines EW, Ross R. Biology of atherosclerotic plaque formation: possible role of growth factors in lesion development and the potential impact of soy. J Nutr 1995; 125:624S-630S.
10Hodgson J, Croft K, Puddey I, Mori T, Beilin L. Soybean isoflavonaids and their metabolic products inhibit in vitro lipoproteinoxidation in serum. J. Nutr Biochem 1996; 7:664-669.
11Sirtori C, Lovati M, Manzoni C, Monetti M, Pazzuccone F, Gatti E. Soy and cholesterol reduction: clinical experience. J Nutr 1995; 125:598S-605S.
12Messina M. Modern applications for an ancient bean; soybeans and the prevention and treatment of chronic disease. J Nutr 1995; 125:567S-569S.
13Anderson JW, Breecher MM. Dr. Anderson's Antioxidant, Antiaging Health Program. (Chapter 7. The Joys of Soy). New York: Carroll & Graf. 1996.
14Anderson JW, Blake JE, Turner J, Smith BM. Soy protein effects on renal functions and proteinuria for individuals with non-insulin-dependent diabetes mellitus. Am J Clin Nutr 1997; In press.
15Wang H, Murphy PA. Isoflavone content in commercial soybean foods. J Agric Food Chem 1994; 42:1666-1673.
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