- The Astonishing Functional Food: Soy Protein and Soy Constituents
- Soy Protein and Coronary Heart Disease
- Soy and Digestive Tract Health
- Soy Foods in Chronic Renal Disease
- How Can Soy Help Diabetes?
- Soy Protein Enhances Energy, Stamina and Sport Performance
- Soy and Cancers
- Soy and Breast Cancer
- Soy and Menopausal Symptoms
- Soy and Pre-Menstrual Syndromes
- Soy and Bone Health
- Losing Weight Healthily with Soy
- Soy and Urological Cancer
- Soy Lecithin and Human Health
- Clinical Abstracts on Soy
- Soy Clinical Reviews in Reputable Medical Journals: 1995-2002
Soy Protein and Coronary Heart Disease
Reduction of elevated blood LDL-cholesterol levels is given the highest priority in the prevention and treatment of atherosclerosis and CHD (Coronary Heart Disease). Therefore, it is not surprising that much of the research on soybean protein and CHD has centered on soy protein's ability to lower blood levels of LDL-cholesterol in animals and humans. Health professionals are taking a broader view in dealing with hypercholesterolemia as a major risk factor for CHD. Limiting concern to those people with diagnosed hypercholesterolemia may be too narrow an approach to such a widespread problem. It is estimated that 96 million adult Americans-52.1% of the adult population-have blood cholesterol levels of 200 mg/dL or higher, and that about 37.8 million adults-more than 20% of the population-have levels of 240 mg/dL or above.7
CHD is one of the most common and serious forms of cardiovascular disease and refers to diseases of the heart muscle and supporting blood vessels. Scientific evidence demonstrates that diets low in saturated fat and cholesterol may reduce the risk of CHD. Other evidence demonstrates that the addition of soy protein to a diet that is low in saturated fat and cholesterol may also help to reduce the risk of CHD. CHD is a major public health concern in the United States. It accounts for more deaths than any other disease or group of diseases. Early management of risk factors for CHD is a major public health goal that can assist in reducing risk of CHD. High blood total and LDL-cholesterol are major modifiable risk factors in the development of CHD.
High blood total cholesterol and low-density lipoprotein (LDL)-cholesterol levels are associated with increased risk of developing CHD. High CHD rates occur among people with high total cholesterol levels of 240 milligrams per deciliter (mg/dL) (6.21millimole per liter (mmol/L)) or above and LDL-cholesterol levels of 160 mg/dL (4.13 mmol/L) or above. Borderline high risk total cholesterol levels range from 200 to 239 mg/dL (5.17 to 6.18 mmol/L) and 130 to 159 mg/dL (3.36 to 4.11 mmol/L) of LDL-cholesterol. The scientific evidence establishes that diets high in saturated fat and cholesterol are associated with increased levels of blood total and LDL-cholesterol and, thus, with increased risk of CHD. Populations with a low incidence of CHD tend to have relatively low blood total cholesterol and LDL-cholesterol levels. These populations also tend to have dietary patterns that are not only low in total fat, especially saturated fat and cholesterol, but are also relatively high in plant foods that contain dietary fiber and other components.
Based on its review of scientific evidence submitted with comments to the proposed rule, as well as evidence described in the proposed rule, U.S. FDA has concluded that soy protein included in a diet low in saturated fat and cholesterol may reduce the risk of CHD by lowering blood cholesterol levels. This regulation is effective October 26, 1999. In response to the soy protein proposed rule, the agency received approximately 130 submissions, each containing one or more comments, from consumers, consumer organizations, professional organizations, government agencies, industry, trade associations, health care professionals, and research scientists.
In its evaluation of the scientific evidence for a relationship between consumption of soy protein and blood total and LDL-cholesterol levels, the agency found the data suggestive but not sufficient to establish a dose-response for this relationship. However, the agency did find consistent, clinically significant reductions of total and LDL-cholesterol levels in controlled trials that used at least 25 grams (g) of soy protein per day. Therefore, FDA proposed the qualifying criterion for a food to bear the claim as 6.25 g of soy protein per reference amount customarily consumed (RACC) (i.e., 25 g divided by 4 eating occasions per day. FDA concluded that the use of soy protein at the levels necessary to justify a claim is safe and lawful.
Originally the primary reason for using soy protein in studies comparing the effects of protein from animal and plant sources was the fact that it is the only plant protein equal in quality to animal protein. However, most researchers now use soy protein as the plant protein in studies because of its unique ability to lower blood cholesterol and to favorably affect other biological parameters.
|Protein Source||Mean Blood Cholesterol mg/dL (mmol/l)|
|Whole egg protein||235 (6.1)|
|Wheat gluten||80 (2.1)|
|Soy protein isolates||15 (0.4)|
|Adapted from Hamilton RMG, Carroll KK. Plasma cholesterol levels in rabbits fed low fat, low cholesterol diets. Effects of dietary proteins, carbohydrates and fibre from different sources. Atherosclerosis 1976; 24: 47-62.|
Although not all research studies of soy protein have significantly lowered blood cholesterol, there is compelling evidence from both animal and human studies that, compared to animal protein, soy protein reduces elevated levels of LDL-cholesterol. In 1976 Hamilton and Carroll (8) demonstrated in rabbits fed diets controlled for calories, cholesterol, fat, and nitrogen that isolated soy protein was the least hypercholesterolemic of a dozen animal and plant proteins. Table 1 shows the effect on mean blood cholesterol levels of feeding rabbits two animal and two plant sources of protein for 28 days.
In 1995 Anderson et al. (2) conducted a meta-analysis of 38 clinical studies reported in 29 scientific articles that provided quantitative data showing that consumption of soy protein rather than animal protein significantly decreased blood concentrations of total cholesterol, low-density lipoprotein cholesterol (LDL-cholesterol), and triglycerides in humans. The meta-analysis included 4 studies on children and 34 on adult men and women. Most of the studies used random assignment with cross-over design and similar amounts of total fat and saturated fat in the control and soy-containing diets. In 14 studies, diets were similar to conventional Western diets in fat and cholesterol content; in 18 studies, fat provided <30 percent of energy and <300 milligrams of cholesterol. Weight was maintained or controlled across groups. Twenty of the studies used isolated soy protein, 15 used textured vegetable protein, and 3 used a combination of the two. Soy protein intake in these studies ranged from 17 to 124 grams per day with an average daily intake of 47 grams.
|Index||No of Studies||No of Subjects||Change (mg/dl)||+ 95% CI||% Change|
|Total cholesterol||38||730||-23.2||-32.9 to -13.5||- 9.3|
|LDLcholesterol||31||564||-21.7||-31.7 to -11.2||-12.9|
|HDL-cholesterol||30||551||+1.2||-3.1 to +5.4||+2.4|
|VLDL-cholesterol||20||255||-0.4||-4.6 to +3.9||-2.6|
|Triglycerides||30||628||-13.3||-25.7 to -0.3||-10.5|
|VLDL-cholesterol=very-low-density-lipoprotein cholesterol; CI=confidence interval.
*Net change is expressed as the change during the soy-containing diet minus the change during the control diet.
†To convert values for cholesterol to millimoles per liter, multiply by 0.02586; to convert values for triglycerides to millimoles per liter, multiply by 0.01129.
From Anderson JW, Johnstone BM, Cook-Newell ME. Meta-analysis of the effects of soy protein intake on blood lipids. NEJM 1995;333:276-282.
Table 3 presents changes in blood cholesterol and LDL-cholesterol concentrations according to initial cholesterol concentrations. In the complete regression model, the initial blood cholesterol concentration was the only significant predictor of the change in the blood cholesterol concentration (P<0.001).
|Initial range||127.1 to 197.8||201.2 to 255.4||259.3 to 332.8||>335|
|95% CI||-17.1 to +6.7||-21.8 to +1.7||-37.3 to -7.1||-86.6 to -56.5|
|LDL cholesterol (mg/dl)|
|95% CI||-20.0 to +6.0||-24.3 to +2.9||-35.3 to -1.3||-90.2 to -45.9|
|*Exact ranges are given for cholesterol and total cholesterol concentrations in the quartiles. To convert values for cholesterol to millimoles per liter, multiply by 0.02586. CI denotes confidence interval. Adapted from Anderson JW, Johnstone BM, Cook-Newell ME. Meta-analysis of the effects of soy protein intake on blood lipids. NEJM 1995;333:276-282.|
Although soy protein totally replaced animal protein in some of the studies in the meta-analysis, some studies used partial replacement of animal protein with isolated soy protein10 or the addition of soy protein in the form of soy crispbread to a conventional low-fat diet11. Anderson et al.2 concluded that the daily consumption of 31 to 47 grams of soy protein can significantly decrease blood cholesterol and LDL-cholesterol concentrations.
One of the greatest challenges for a physician is the treatment of a child with polygenic or familialhypercholesterolemia (a metabolic disorder caused by a genetic eficiency in LDL-cholesterol receptors). It is estimated that 27 million children age 19 and under-36.5% of all children and adolescents-have blood cholesterol levels of 170 mg/dL and above, a level comparable to 200 mg/dL in adults7. In addition to the direct harm caused by very high cholesterol levels in children, it is believed that the beginnings of adult atherosclerosis can be found in the fatty streaks that develop during childhood. Therefore, elevated blood cholesterol levels in childhood may be a predictor of development of CHD in adult life12. Although dietary modification is the initial treatment for children with hypercholesterolemia, drug therapy is recommended for children over 10 years of age who have severe elevations (LDL-cholesterol >190 mg/dL, or LDL-cholesterol >160 mg/dL and two or more other risk factors)12. Most physicians, however,hesitate to start hypercholesterolemic children on what could become a lifetime of drug therapy,and yet traditional diet therapy often achieves only limited results. The usual 10% drop in total cholesterol achieved with implementation of the "heart-healthy" Step I NCEP diet12 may translate into a decrease of only 30 mg/dL for a child with a total blood cholesterol of 300 mg/dL, a level common in a child heterozygous for familial hypercholesterolemia.13
Gaddi et al.26 achieved an average 21.8% lowering of blood cholesterol in children with familial hypercholesterolemia when soy protein was substituted for animal protein in a low-fat, low-cholesterol diet. In the study of Widhalm et al.14, 23 children with either familial or polygenic hypercholesterolemia lowered their blood cholesterol by 7-8% and LDL-cholesterol by 12-13% by consumption of a conventional low-fat, low-cholesterol diet; however, substitution of soy protein for animal protein in this diet more than doubled the response, resulting in decreases of total cholesterol of 16-18% and of LDL-cholesterol of 22-25%. In hypercholesterolemic children following a standard low-fat, low-cholesterol diet, either the substitution of soy protein for animal protein or the addition of soy protein resulted in greater cholesterol lowering than achieved with diet alone. The cholesterol-lowering effect of soy protein makes diet therapy, which has the benefit of being a non-invasive treatment, a much more potent tool than a low-fat diet alone.
The "What" And "How" Of Cholesterol Lowering
Although there is convincing evidence of soy protein's ability to decrease LDL-cholesterol in hypercholesterolemic individuals, researchers have yet to identify exactly how this reduction is accomplished. To date, research has centered around the study of certain nutritive and non-nutritive components of soy protein and the possible mechanisms by which elevated levels of LDL-cholesterol are reduced. It may very well be that the observed cholesterol-lowering effect of soy protein is the result of not one component or action, but of a number of individual or interrelated factors.
Components of Soy Protein That May Lower Cholesterol
The following nutritive and non-nutritive components of soy proteins have been investigated for cholesterol-lowering activity.
One theory proposed to explain the hypocholesterolemic effect of soy protein is based on the effects of specific amino acids on blood cholesterol levels. Animal studies15-17 indicate that certain amino acids-especially lysine-increase blood cholesterol levels, while arginine counteracts this effect. Therefore, it has been proposed that the ratio of lysine to arginine in the diet is crucial in explaining elevated blood cholesterol levels and the resulting atherosclerosis. This theory is supported by the fact that soy protein provides a more favorable arginine to lysine ratio than casein, the animal protein used in most of these studies. Kritchevsky18 showed that in rabbits a diet in which arginine was added to casein continued to be hypercholesterolemic but reduced atherosclerosis by 25%; however, the addition of lysine to soy protein increased blood cholesterol by ~50% and atherosclerosis by 60%. Some animal studies19-21 have shown that soy protein is more hypocholesterolemic than an identical mixture of its amino acids. This discrepancy suggests that the presence of arginine cannot totally account for the hypocholesterolemic effect of soy protein and that there is another factor or factors involved.
Tsai et al.22 reported that 10 grams of soy polysaccharide fed to obese individuals with diabetes significantly reduced (P<0.05) the rise of postprandial plasma triglyceride levels. Earlier Tsai et al.23 had shown no significant decrease in blood cholesterol levels in healthy subjects consuming soy polysaccharide. Shorey et al.24 reported that when individuals with mild to moderate hypercholesterolemia ingested soy polysaccharide, total cholesterol was reduced from 5 to 11%, depending on the order of crossover; the 11% decrease was in subjects ingesting soy polysaccharide prior to placebo. Lo et al..25 reported that subjects with primary hyperlipidemia, who were already following the NIH Type II-A diet, achieved an additional 13 mg/dL reduction (P<0.04) in total cholesterol and a 12 mg/dL reduction (P<0.05) in LDL-cholesterol when their diet was supplemented with 25 grams of soy polysaccharide per day. A study conducted in humans by Potter et al.10 showed that the addition of soy fiber to isolated soy protein did not increase its hypocholesterolemic effect. Another study in humans by Bakhit et al.3 indicated that soy fiber has a hypocholesterolemic effect when added to other foods but not when it is fed with soy protein. These results suggest that the hypocholesterolemic effect of soy protein cannot be explained by the soy fiber that may accompany it in the diet.
Phytic acid, which is present in varying amounts in soyfoods, chelates iron, calcium, zinc, and magnesium in the intestinal tract, thereby decreasing the intestinal absorption of these minerals. Diets that are deficient in copper or have a high zinc to copper (Zn/Cu) ratio are associated with hypercholesterolemia27. There is a theory that phytic acid may help lower blood cholesterol levels by chelating zinc and allowing more copper to be absorbed, consequently altering the ratio of zinc to copper. Soy-rich diets provide both phytic acid and copper. Although some animal studies have shown that phytic acid may have a role in lowering cholesterol, they indicate that the mechanism may not be by altering the Zn/Cu ratio28.
Saponins, which are compounds consisting of carbohydrate moieties attached to a steroidal molecule, are associated with protein from soybeans and other plants. Animal studies37 have shown that the addition of saponins from soybeans to the diet decreases blood cholesterol by increasing the excretion of bile. Potter et al.29 found that the addition of soy saponins to a casein-based diet resulted in a lowered blood cholesterol in gerbils; however, when soy saponins were added to a soy protein isolate-based diet, there was no change in blood cholesterol. This finding suggests that the presence of saponins cannot explain the hypocholesterolemic effect of soy protein.
It has been suggested that the Bowman-Birk inhibitor in soy protein may account for its hypocholesterolemic effect. Although all soy protein foods are now heated, which inactivates virtually all of the trypsin inhibitor, it is theorized that the remaining Bowman-Birk inhibitor may increase the secretion of cholecystokinin, which in turn stimulates the gall bladder and increases secretion of bile into the gastrointestinal tract. However, animal studies30 have shown that a diet based on isolated soy protein was hypocholesterolemic while there was no difference in the effect on blood cholesterol levels of two casein-based diets-one with and one without the addition of trypsin inhibitor. This study suggests that trypsin inhibitor is not the hypocholesterolemic component in soy protein.
The major storage proteins in soybeans are two globulins, termed 11S and 7S. Lovati et al.31 conducted in vitro and in vivo studies to investigate the hypothesis that soybean globulins might be involved in the direct up-regulation of liver or peripheral lipoprotein receptors. The results of these studies suggest that soybean globulins, especially the 7S globulin, may stimulate high-affinity LDL-cholesterol receptors in human liver cell cultures. Furthermore, Lovati et al.31 found that animals on a hypercholesterolemic diet who were fed isolated 7S globulin had a significant lowering of blood cholesterol.
Phytoestrogens are only one group of compounds under the general term phytochemical, or plant chemical; isoflavones, found almost exclusively in soybeans, are one class of phytoestrogen. Phytoestrogens vary greatly in both their estrogenic potency and physiologic effects. Messina et al.32 reported that various in vitro and in vivo assays show genistein exerts an estrogenic effect ranging from approximately 1 x 10-3 to 1 x 10-5 that of diethylstilbestrol or estradiol. Of the three major isoflavones found in soy, genistein has been studied more extensively than daidzein or glycitein. To date, most of the research on isoflavones has been concentrated on their possible role in cancer prevention. Studies of isoflavones and CHD are relatively recent, and it is theorized that the activities of these alcohol-soluble compounds, which may have been inadvertently removed in alcohol extraction during the processing of some soy protein products, may explain some of the inconsistencies in earlier studies of soy protein.Lovati et al.31 showed that animals fed an alcohol extract (soy isoflavones are alcohol soluble) of textured soy protein exhibited lower blood cholesterol levels and increased LDL-cholesterol-receptor activity. Sugano and Koba33 demonstrated that feeding rats the indigestible fraction of soy protein lowered blood cholesterol in the animals by increasing fecal excretion of sterols. However, alcohol extraction of this indigestible fraction, which removed most of the isoflavones, saponins, and other alcohol-soluble compounds, decreased its cholesterol-lowering effect. During a 6-month intervention cross-over study, Anthony et al.34 fed peripubertal rhesus monkeys a moderately atherogenic diet (fat 40% of calories) in which the protein (20% of calories) was soy protein isolate either with the isoflavones genistein and daidzein intact, indicated by (+), or containing only the trace amounts still present after the isoflavones are removed, indicated by (-). When compared to the soy protein(-) diet, the soy protein(+) diet significantly decreased LDL-cholesterol+VLDL-cholesterol by ~30-40% in both males and females and significantly increased HDL-cholesterol in females by ~15%. Ratios of total cholesterol to HDL-cholesterol were lowered ~20% for males and 50% for females. All sex hormones were normal, and at necropsy it was found that the isoflavones had no adverse effects on either male or female reproductive systems. Clarkson et al.35 investigated the result of feeding soy protein isolates with intact isoflavones(+) and with trace amounts of isoflavones(-) to surgically postmenopausal nonhuman primates. The monkeys who received the soy protein isolates with intact isoflavones(+) had significantly lower levels of blood total cholesterol (P<0.01) and LDL-cholesterol+VLDL-cholesterol (P<0.02).
Anthony et al.36 fed moderately atherogenic diets containing casein or soy protein with intact(+) or with trace amounts(-) of isoflavones to male cynomolgus monkeys. Table 6 shows that the level of LDL-cholesterol+VLDL-cholesterol was highest on the casein diet, somewhat lower on the soy protein(-) diet, and significantly lower on the soy protein(+) diet. HDL-cholesterol levels were lowest on the casein diet, significantly higher on the soy protein(-) diet, and highest on the soy protein(+) diet. This group also evaluated the extent of coronary artery atherosclerosis (CAA) by calculating the average of the cross-sectional area of the intimal lesions for three coronary arteries (see Table 6). The prevalence of coronary artery atherosclerosis, which was the proportion of each group with intimal thickness >1/2 the medial thickness, was 73% in the casein group, 64% for the soy protein(-) group, and 45% for the soy protein(+) group. The phytoestrogens did not affect testicular weights.
|Casein||Soy (-)||Soy (+)||Casein vs Soy (-)||Casein vs Soy (+)||Soy (-) vs Soy (+)|
|TC=total blood cholesterol; LDL-C+VLDL-C=LDL-cholesterol plus VLDL-cholesterol; HDL-C=HDL-cholesterol (in mg/dL); CAA
Extent=amount of coronary artery atherosclerosis extent in mm2.
Adapted from Anthony MS, Clarkson TB. Bullock BC. Soy protein versus soy phytoestrogens (isoflavones) in the prevention of coronary artery atherosclerosis of cynomolgus monkeys.
Circulation 1996; 94:abstract, in press. Potter (28) found that the addition of an alcohol extract of isolated soy protein to a casein-based diet reduced LDL-cholesterol levels in rats; however, when the same extract was added to a diet based on soy protein isolates, which naturally contained isoflavones, there was no additional lowering of LDL-cholesterol.
Proposed Mechanisms By Which Soy Protein May Lower Cholesterol
Various mechanisms have been proposed to explain the hypocholesterolemic effect of consuming soy protein.
Stimulation of Bile Acid Excretion
Some studies (38), primarily in animals, have shown that, compared to casein, soy protein increases fecal excretion of bile acids, possibly by releasing a bile acid-binding peptide fragment during digestion. This action causes cholesterol to be removed from the body, resulting in increased liver synthesis of cholesterol for enhanced synthesis of bile acids and in greater LDL-cholesterol-receptor activity28. Potter28 stated that studies in animals that compared the direct effects on liver metabolism of soy protein, casein, and amino acid mixtures corresponding to these two proteins suggest that the hypocholesterolemic effect may be due to some other factor in soy protein, and not soy protein per se. Therefore, it was suggested that although consumption of soy protein may result in lowered blood cholesterol through enhanced bile acid secretion in certain species, any hypocholesterolemic effects of corresponding amino acid mixtures might be via another mechanism.
Changes in Liver Metabolism of Cholesterol. Several studies in animals21, 39 have noted various effects on liver metabolism of cholesterol of feeding soy protein compared to casein. Soy protein significantly decreased blood total and LDL-cholesterol, increased HMG CoA (3-hydroxy-3- methylglutaryl co-enzyme A) reductase inhibitory activity, increased the removal of LDL-cholesterol and VLDL-cholesterol, increased apolipoprotein B and E receptor activities, and decreased cholesterol 7ÿ-hydroxylase activity. However, feeding an amino acid mixture corresponding to soy protein did not achieve the same effect as the intact proteins. These results suggest that a factor in soy protein other than its constituent amino acids may be at least partly responsible for these changes in the liver metabolism of cholesterol and the resulting hypocholesterolemic effect. It is likely that the mechanism by which soy protein lowers blood cholesterol may be a combination of factors working in concert. Using a rabbit model, Beynen40 demonstrated a feasible explanation for soy protein's hypocholesterolemic effects.
When compared to casein, soy protein reduces the absorption of cholesterol in the intestinal tract and may reduce the reabsorption of bile acids. This leads to the observed increase in fecal excretion of neutral steroids and bile acids, which, in turn, causes the liver to convert more cholesterol into bile acids, thereby depleting its cholesterol pool. The liver responds by increasing the number of LDL-cholesterol receptors, causing a fall in blood cholesterol, and by enhancing de novo synthesis of cholesterol to prevent a deficiency. The extra cholesterol taken up by the liver via the LDL-cholesterol receptors can be used to produce bile acids, which may be excreted. The resulting enhanced cholesterol turnover resolves into a new steady state-a balance between increased cholesterol synthesis in the liver and increased fecal excretion of bile acids-in which blood cholesterol is low and the number of LDL-cholesterol receptors is high.
It is an accepted fact that estrogen reduces risk for CHD41. Estrogen decreases LDL-cholesterol, increases HDL-cholesterol, and improves vasomotor tone and vessel wall compliance. Hormone replacement therapy (HRT) and ischaemic heart disease show an overall relative risk ratio for estrogen use of 0.56, which means that the risk of ischaemic heart disease for women taking HRT is 44% less than that for women not taking HRT41. Soy isoflavones, which are proposed to be tissue specific34, may act as an estrogen-like compound and produce similar effects to estrogen. In some studies42-43, altered hormone concentrations have been observed in animals consuming soy. One theory42-43 is that the hypocholesterolemic effect of soy protein results from its ability to increase blood thyroxine levels; the theory is based on the fact that feeding soy protein isolate increases plasma thyroxine in animals and that raising thyroxine levels decreases plasma cholesterol. In animals consumption of soy protein results in metabolic changes affecting blood cholesterol that are similar to those of hyperthyroidism, i.e., increases in LDL-cholesterol-receptor activity, HMG CoA reductase activity, and bile acid excretion and decreases in total and LDL-cholesterol15; however, Balmir et al.43 found that elevated thyroxine levels did not correspond to changes in blood lipids in rats and hamsters. These findings are not confirmed in humans. Although the component of soy protein responsible for these hormonal changes has not been identified, it is suggested that the lower ratio of lysine to arginine may decrease secretion of insulin and increase secretion of glucagon. A high ratio of insulin to glucagon is thought to increase risk for CHD because it stimulates lipogenesis28. Sugano et al.45 found that rats fed plant protein instead of animal protein had higher blood levels of glucagon and lower levels of insulin. Sanchez and Hubbard15 postulated a relationship between blood levels of cholesterol and free amino acids in man. They found that lysine and branched-chain amino acids are associated with higher levels of blood cholesterol and arginine and glycine with lower levels. When they fed soy protein or casein to hypercholesterolemic and to normocholesterolemic subjects, the soy protein resulted in increased blood levels of arginine and glycine both in hypercholesterolemic and in normocholesterolemic subjects and in a low insulin/glucagon ratio in hypercholesterolemic subjects. These data support the hypothesis that dietary and plasma amino acids may regulate the control of cholesterol via insulin and glucagon.
Regulation of LDL-Cholesterol Receptors
One mechanism proposed to explain soy protein's ability to reduce blood LDL-cholesterol levels is an increase in LDL-cholesterol-receptors, resulting in increased LDL-cholesterol removal from blood. Carroll and Kurowska45 reviewed studies showing that in animals a cholesterol-free casein diet down-regulated LDL-cholesterol receptors in hepatocytes, thereby increasing blood LDL-cholesterol levels, and stimulated the synthesis of apolipoprotein B, the primary apolipoprotein in LDL-cholesterol. Lovati et al46 found that hypercholesterolemic mice fed an alcohol extract of soy protein exhibited a "remarkable increase of the number of high-affinity lipoprotein receptors." Lovati et al.47 conducted a study in humans in which patients with severe Type II hyperlipoproteinemia consumed a diet containing 26% fat and 20% protein in which the protein came either from soy textured vegetable protein or from animal sources. In this study, the soy protein diet reduced total cholesterol by 15.9% and LDL-cholesterol by 16.4% compared to the animal protein diet or to baseline. However, the soy protein diet increased degradation of LDL-cholesterol by up-regulation of the LDL-cholesterol receptors on mononuclear cells 16-fold compared to baseline and 8-fold compared to the standard low-fat diet with animal protein. These results suggest that some as yet unidentified factor in soy protein regulates the expression of lipoprotein receptors in peripheral cells. This appeared to be especially true when LDL-cholesterol-receptor activity had been greatly suppressed, either by hypercholesterolemia or by a high-cholesterol diet. Sirtori and his associates have studied the effects of soy protein in more than 1,000 individuals during the last 20 years. They concluded that soy protein up-regulates depressed LDL-cholesterol receptors48.
Who Should Be Consuming Soy Protein?
Of course, it would be of health benefit for most people to substitute soy protein for some of the animal protein they typically eat. However, there are certain groups that are conspicuous by the specific advantages soy protein offers them.
People with Hypercholesterolemia
Soy protein is like every other weapon in the arsenal against hypercholesterolemia and coronary heart disease in that people exhibit individual variation in their response to its use. However, there is convincing evidence supporting the hypocholesterolemic effect of as little as 25 grams of soy protein per day as part of a low-fat diet (3). This is especially important in the dietary treatment of patients with Type IIa hyperlipoproteinemia, who may show a minimal response to the standard cholesterol-lowering diet. Substitution of foods manufactured with soy protein isolates containing isoflavones for part of the animal protein in a low-fat diet makes that diet more likely to effect a significant reduction in total and LDL-cholesterol. And the greatest reduction will be in the more hypercholesterolemic individuals. The incorporation of soy protein as a basic part of the cholesterol-lowering diet should increase the diet's effectiveness and may either decrease the need for medication or, in some cases, make it unnecessary.
- Chen J., Campbell T.C., Li J., Peto R. Diet, Lifestyle and Mortality in China. A Study of the Characteristics of 65 Chinese Counties. Oxford University Press, (Oxford, UK), Cornell University Press, (Ithaca, NY), People's Medical Publishing House, (Beijing PRC), 894 pp. 1991. The findings of this study strongly indicate that a substantial change in American dietary patterns from animal-based foods to plant-based foods must occur for there to be a substantial change in incidence patterns of chronic, degenerative diseases such as cancer and coronary heart disease.
- Anderson J.W., Johnstone B.M., Cook-Newell M.E. "Meta-Analysis of the Effects of Soy Protein Intake on Serum Lipids." New England Journal of Medicine, 333:276-282, August 3, 1995. "Conclusions: We found that the consumption of soy protein rather than animal protein significantly decreased serum concentrations of total cholesterol, LDL cholesterol, and triglycerides."
- Bakhit, R.M., Klein B.P., Essex-Sorlie D, Ham J.O., Erdman J.W. Jr., Potter S.M. "Intake of 25 g of Soybean Protein with or without Soybean Fibers Alters Plasma Lipids in Men with Elevated Cholesterol Concentrations." J Nutr 1994;124:213-222.
- National Heart, Lung and Blood Institute, 1992; American Heart Association, 1998.
- Lipid Research Clinics Program. The Lipid Research Clinics Coronary Primary Prevention Trial Results. II. The relationship of reduction in incidence of coronary heart disease to cholesterol lowering. JAMA 1984; 251: 365-74.
- Descovich G.C. et al. "Multicentre Study of Soybean Protein Diet for Outpatient Hyper-Cholesterolaemic Patients." Lancet1980;2:709-12.
- American Heart Association. Heart and Stroke Facts: 1996 Statistical Supplement.Dallas (TX): American Heart Association, 1995.
- Hamilton RMG, Carroll KK. Plasma cholesterol levels in rabbits fed low fat, low cholesterol diets. Effects of dietary proteins, carbohydrates and fibre from different sources. Atherosclerosis 1976;24:47-62.
- Carroll KK. Review of clinical studies on cholesterol-lowering response to soy protein. J Am Diet Assoc 1991;91:820-827.
- Potter SM, Bakhit RM, Essex-Sorlie DL, et al. Depression of plasma cholesterol in men by consumption of baked products containing soy protein. Am J Clin Nutr 1993;58:501-506.
- Kolb S, Sailer D. Soybean protein crispbread as additional dietetic measure in hypercholesterolaemia. Nutr Rep Int 1984;30:719-724.
- National Cholesterol Education Program. Report of the Expert Panel on Blood Cholesterol Levels in Children and Adolescents. Bethesda (MD): National Institutes of Health, National Heart, Lung, and Blood Institute; 1991 Sept. NIH Publication No.:91-2732.
- Williams C, personal communication.
- Widhalm K, Brazda G, Schneider B, Kohl S. Effect of soy protein diet versus standard low fat, low cholesterol diet on lipid and lipoprotein levels in children with familial or polygenic hypercholesterolemia. J Pediatr 1993;123 (1):30-34.
- Sanchez A, Hubbard RW. Plasma amino acids and the insulin/glucagon ratio as an explanation for the dietary protein modulation of atherosclerosis. Med Hypoth1991; 35:324-329.
- Kurowska EM, Carroll KK. Effect of high levels of selected dietary essential amino acids on hypercholesterolemia and down-regulation of hepatic LDL receptors in rabbits. Biochimica et Biophysica Acta 1992;1126:185-191.
- Kurowska EM, Carroll KK. Hypercholesterolemic responses in rabbits to selected groups of dietary essential amino acids. J Nutr 1994;124:364-370.
- Kritchevsky D. Dietary protein and experimental atherosclerosis. Ann NY Acad Sci1993;676:180-187.
- Huff MW, Carroll KK. Effects of dietary proteins and amino acid mixtures on plasma cholesterol levels in rabbits. J Nutr 1980;110:1676-1685.
- Carroll KK. Dietary protein and cardiovascular disease. In: Basan NG, Paoletti R, Iacono JM, eds. Current Topics in Nutrition and Disease, Vol. 5, New Trends in Nutrition, Lipid Research, and Cardiovascular Diseases. New York: Alan R. Liss, Inc, 1981, 167-177.
- Tasker TE, Potter SM. Effects of dietary protein source on plasma lipids, HMG CoA reductase activity, and hepatic glutathione levels in gerbils. J Nutr Biochem 1993;4:458-462.
- Tsai AC, Vinik AI, Lasichak A, Lo GS. Effects of soy polysaccharide on postprandial plasma glucose, insulin, glucagon, pancreatic polypeptide, somatostatin, and triglyceride in obese diabetic patients. Am J Clin Nutr 1987;45:596-601.
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- DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Food Labeling: Health Claims; Soy Protein and Coronary Heart Disease Federal Register: October 26, 1999 (Volume 64, Number 206)], United States of America