MXPA01005132A - Composition comprising soy protein, dietary fibres and a phytoestrogen compound and use thereof in the prevention and/or treatment of cardiovascular diseases - Google Patents

Abstract

A composition comprising (a) soy protein, (b) a phytoestrogen compound, and (c) dietary fibres. The soy protein (a) is present in an amount of at least 45 weight percent of the total protein content of the composition, said total protein content providing at least 15 percent of the total energy content of the composition. The phytoestrogen compound (b) is preferably a naturally occuring isoflavone and is present in an amount of more than 0.10 weight percent of the soy protein, and the dietary fibres (c) are preferably soybean fibres and are present in an amount of more than 4 weight percent of the total weight of the nutritional composition on a dry basis. The composition is useful in lowering serum cholesterol and LDL-cholesterol and serum triglyceride levels and for increasing the HDL/LDL-cholesterol ratio in serum of a subject suffering from arteriosclerosis and related cardiovascular diseases.

Description

COMPOSITION OF SOY PROTEIN, DIETARY FIBERS AND A COMPOSITE OF PHYTESTROGEN AND USE THEREOF IN THE PREVENTION AND / OR TREATMENT OF CARDIOVASCULAR DISEASES DESCRIPTION OF THE INVENTION The present invention relates to soy protein, phytoestrogens and dietary fibers and compositions thereof suitable for preventing, alleviating and treating cardiovascular diseases. such as arteriosclerosis, hypercholesterolemia, hyperlipidemia, hypertriglyceridemia, hypertension and related cardiovascular diseases. In particular, a composition according to the present invention has improved effects in decreasing levels of total cholesterol in serum and LDL-cholesterol. A composition according to the present invention is also particularly useful in reducing the accumulation of cholesterol in the arterial wall of subjects at high risk of developing cardiovascular disease or already suffering from a cardiovascular disease such as atherosclerosis. A composition according to the present invention is also useful for lowering serum levels of total cholesterol and LDL-cholesterol and / or triglycerides and / or homocysteine and / or increasing serum levels of HDL-cholesterol and / or improving the HDL ratio / LDL in subjects at risk of developing cardiovascular diseases and in subjects already suffering from an arteriosclerotic condition such as atherosclerosis or a related cardiovascular disease. The present invention also relates to the use of these compositions in the manufacture of a medicament for treating a subject suffering from cardiovascular diseases, more particularly arteriosclerosis, hypercholesterolemia, hyperlipidemia, hypertriglyceridemia, hypertension and / or related cardiovascular diseases. The present invention also relates to the use of a composition according to the present invention in the prevention and / or treatment of diseases and disorders and to decrease serum levels of total cholesterol and / or LDL-cholesterol and / or triglycerides and / or serum levels of homocysteine in subjects. In addition, the present invention also provides methods for preventing and / or treating and / or treating prophylactically and / or relieving diseases and disorders by therapy. Lipid metabolism involves biosynthesis and degradation of eg fatty acids, triglycerides and cholesterol. Ingested triglycerides are hydrolyzed in the small intestine and the products of hydrolysis are absorbed by the intestinal mucosa. Due to the relative insolubility of dietary lipids in water, it facilitates the digestion and absorption of lipids by the action of detergent substances such as bile acids secreted from the gallbladder. Bile acids are essential for digestion and absorption of lipids through the intestinal mucosa. The triglycerides and cholesterol synthesized in the liver are transported in the bloodstream to peripheral tissues by transport proteins called lipoproteins. Lipoproteins are tiny vesicles coated by apoproteins, phospholipids and free cholesterol and with an interior consisting of the most hydrophobic lipids, cholesterol esters and triglycerides. Apoproteins and lipoproteins are synthesized primarily in the liver. The lipoproteins are able to perform an apoprotein-mediated binding to a receptor on the surface of a cell in which the complete lipoprotein particle is captured and is further metabolized. Several different lipoprotein families have been characterized and are traditionally classified by their density as determined by centrifugation. A standard lipoprotein classification scheme may include a density increase order, very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL), low density lipoprotein (LDL), and high density lipoprotein (HDL). VLDL contains aximately 60 to 65 percent triglycerides and 5 to 10 percent cholesterol, lecithin and protein. Which are relatively large and function in the transport of triglycerides from the liver to tissue. LDL contains approximately 40 to 50 percent cholesterol and 10 to 15 percent triglycerides, lecithin and protein. They are somewhat smaller than VLDL and also function in the transport of cholesterol from the liver to tissue. HDL contains approximately 75 percent lecithin and protein, while the rest is formed of cholesterol and a small amount of triglycerides. They function in the transport of cholesterol from tissue to the liver and, as such, have the opposite function of LDL. Cholesterol esters can not easily cross cell membranes and are picked up by cells in a receptor-mediated process. Once it binds to the LDL receptor, the LDL particle is internalized by endocytosis, and cholesterol and fatty acids are released and further metabolized. The primary investigations of cholesterol-mediated LDL receptor internalization have generated a better understanding of the relationship between dietary cholesterol, plasma cholesterol levels, and atherosclerosis status. It is believed that white cells that accumulate cholesterol at sites of arterial damage contain a receptor called a purifying receptor. Like the LDL receptor, this purifying receptor acts through the mechanism of endocytosis and mediates the internalization of several extracellular materials. However, the scavenger receptor is non-discriminatory and captures many different types of extracellular materials that include oxidized LDL particles containing cholesterol. In contrast to the LDL receptor, the purifying receptor is not down regulated by a high concentration of cholesterol in the cell. In addition to the lipoproteins mentioned above, the body also contains a type of lipoproteins called chylomicrons. Chylomicrons contain 90 to 95 percent triglycerides and only a small amount of cholesterol, lecithin and protein, and function in the transport of triglycerides from the small intestine to for example the muscles, liver and heart. The metabolism of cholesterol in the human body is very close to the synthesis, transport and degradation of triglycerides. Cholesterol is an essential lipid component in all mammalian cells. This is used to regulate the fluidity of cell membranes and serves as a precursor to certain hormones, vitamin D and bile acids. Cholesterol is synthesized in the liver and transported with blood to peripheral tissues by lipoproteins. The liver has a dual function in the metabolism of cholesterol since it is able to both synthesize cholesterol and convert excess cholesterol into bile acids. It is also capable of excreting cholesterol in the bile.

Bile acids have ampholytic characteristics and contain both hydrophobic and hydrophilic surfaces. This ampholytic character facilitates bile acid-mediated emulsification of lipids in micelles. The formation of micelles allows digestive attacks by water-soluble enzymes and facilitates absorption of lipids through mucosal cells of the intestine. Bile acids are secreted from the liver and stored in the gallbladder before they are passed through the bile duct into the intestine. The biosynthesis of bile acids represents a major metabolic fate of cholesterol and accounts for more than half of approximately 800 mg of cholesterol that is normally metabolized per day in a normal adult. Although bile acids are synthesized in an amount of 400 mg each day, significantly more of this amount is secreted in the intestine. Most of the bile acids that are secreted in the upper small intestine are absorbed in the lower small intestine and recycled to the liver. The process of enterohepatic circulation can be counted by more than 20 to 30 g of bile acids per day. In contrast, the daily elimination of bile acids in feces is counted by only 0.5 g or less. Cholesterol acts on three different levels of regulation of its own synthesis. First, it suppresses the synthesis of endogenous cholesterol by inhibiting HMG-CoA reductase. Second, it activates acyl-Coa: cholesterol acyltransferase (ACAT) which is involved in the synthesis of cholesterol esters and fatty acids linked to acyl-Coa. Third, cholesterol regulates the synthesis of the LDL receptor. Accordingly, a decreased synthesis of LDL receptors will ensure that a cell in which a sufficient amount of cholesterol is already present does not capture cholesterol. Ratatouille can explain why excessive dietary cholesterol generates a rapid rise in blood cholesterol levels. The presence of increased amounts of cholesterol in the blood is known to be positively correlated to arteriosclerosis, a condition commonly attributed to the deposition in the inner lining of an arterial wall of plaque in the form of cholesterol and fats. An arterial condition that commonly occurs is that of atherosclerotic cardiovascular disease. The condition can progress eventually through several stages. A normal structure of an artery is characterized by discrete focal numbers of adhesion monocytes, some intimate foam cells, and some intimal smooth muscle cells, or intimal cell masses in bifurcations. A groove of fat may not occur symptomatically and involve a layer of foam cells. As soon as the arteriosclerosis progresses, the arterial wall will gradually begin to harden due to the deposition of lipids and calcium and proliferation of smooth muscle cells, and the cells may eventually become degenerated. As soon as the wall of an artery thickens, hardens, and loses its elasticity during arteriosclerosis, the blood vessels can develop into twists and turns and become constricted in such a way that the heart works very hard to pump the usual amount of blood through. of the arteries. The condition can progress in a formation of for example fibrous plaque. The fibrous plaque is a slowly reversible condition that can also develop into a complicated lesion. It is likely that cellular degeneration results in a fracture of the arterial wall which in turn leads to the formation of a calcium deposit, formation of platelets and a gradual development of scar tissue that also contributes to cellular degeneration and a substantial elasticity Reduced arterial wall. Atherosclerosis characterized by a restricted flow of blood through a coronary artery can lead to the development of coronary heart disease. A complicated artery injury is often symptomatic, severely reversible and can, in severe cases such as thrombosis, be lethal. A decreased flow of blood through an euthhery can lead to the formation of blood clots and this can eventually lead to thrombosis. If a blood clot forms in a coronary artery, interruption of blood flow can result in the death of part of the heart muscle and cause extremely painful chest pains associated with a heart attack. Arteriosclerotic symptoms depend a lot on the affected arteries and tissues. When arteriosclerosis occurs in the arteries leading to the brain, decreased blood flow and oxygen can cause mental confusion and personality changes. A heart attack can occur if an artery in the brain that has been thinned by a rupture or a blood clot prevents blood from flowing to the brain. This can possibly result in for example partial peirálisis, loss of voice and sometimes of the death. A decrease in blood flow through the coronary arteries results in a shortening of oxygen to the heart muscle and causes chest pain and a painful condition called angina pectoris. Angina pectoris is usually caused by a narrowing or blockage of a coronary artery. An attack of: angina pectoris due to pressure or the result of physical activities that require an increased blood supply to the heart may be caused. Although it is well established that cholesterol, lipids and lipoproteins all contribute to the progression of several atherosclerotic conditions little is known about the causes of arteriosclerosis. Hereditary conditions clearly play a role in some cases and various socio-economic and lifestyle factors such as smoking, hypertension, dietary habits and continuous pressure also contribute to the development of arteriosclerosis. There is no simple cure or medical treatment for arteriosclerosis so far, and doctors usually recommend patients follow a low-fat diet, stop smoking, and exercise regularly. Patients suffering from hypercholesterolemia can be classified into four risk groups: (i) manifest coronary artery disease, (ii) other forms of atherosclerotic vascular disease, (iii) other risk factors for coronary artery disease in the absence of established atherosclerotic cardiovascular disease, and (iv) isolated hypercholesterolemia in the absence of other risk factors. The recommended treatment regimen for risk group iv) is to give general recommendation along with laboratory results for those patients who have a total cholesterol level of 5.0-6.4 mmol / l, without additional follow-up. For patients with cholesterol levels in the range of 6.5-7.9 mmol / l and levels of LDL >; 5.0 mmol / L or an LDL / HDL ratio > 5.0, only a non-pharmacological treatment is offered.

Treatment with cardiovascular disease drugs may include the use of calcium channel blockers to expand the arteries so that blood can flow more freely, and anticoagulants to prevent blood clots from forming in diseased arteries. Some studies indicate that compounds such as acetylsalicylic acid and sulfinpyrazone, which can reduce and / or inhibit coagulation by reducing platelet reactivity, can also prevent the formation of a thrombus. In advanced cases, surgery that replaces diseased blood vessels with grafts of healthy arteries may be necessary. Several lipid-lowering drugs have also been recommended, as some studies have shown or indicated that even for other healthy patients suffering from mild or moderate hypercholesterolemia, coronary morbidity and mortality are reduced when treated with such drugs that decrease the lipids. The most widely used lipid-lowering drugs in recent years have been statins, such as HMG-CoA reductase inhibitors, bile acid resins, fibrates, nicotinic acid derivatives, and various fish oil concentrates with a high acid content. -3-fat. An increased level of serum triglycerides is now seen as a risk factor for the development of cardiovascular disease. Importantly, recent studies have indicated that serum triglyceride levels currently considered "normal" - 200 mg per deciliter of serum - may indeed be very high. It has been proposed that the "normal" limit for triglycerides should be reduced by as much as 50 percent compared to the limit currently considered to be the "normal" limit (Yahoo New, May 1, 1998). In a group of patients examined more than nearly 20 years, a serum triglyceride level of more than 100 mg per deciliter of serum currently increases the relative risk of contracting a new cardiovascular event by 50 percent and reduces the chance of surviving that event . It is emphasized that until now clinical trials have not examined whether the decrease in triglyceride levels affects the incidence of subsequent cardiovascular events, and research into the effect of serum triglyceride levels on cardiovascular events lag research aimed at establishing the effect of Increased levels of serum cholesterol in the subsequent development of cardiovascular diseases. Adlercreutz (Finnish Medical Society, Ann. Med. 29, 95-120 (1997)) has reviewed the classes of phytoestrogens and isoflavones and has described their influence on a range of cellular activities and metabolic events. It is reported that the ingestion of soy prevents the oxidation of LDL, has not yet been established any antioxidant mechanism. Although isoflavonoids can prevent the development of atherosclerosis, it is a problem to separate the effect of phytoestrogen from the effect of other components in food. It is emphasized that phytoestrogens, particularly in association with soy ingestion, seem to have a great potential to prevent cardiovascular diseases, but since the area is in the early stages of development, an established beneficial effect of soy and isoflavonoids in this regard will have to wait further studies. It is further established that despite the abundant literature in this primary stage of research of dietary phytoestrogens, much work is needed before the use of phytoestrogen can be recommended. However, experimental and epidemiological evidence does not support the observation that these compounds have no effect and that they can form a group of substances with great potential in preventive medicine. It is emphasized that until now, definitive recommendations can not be made regarding the dietary amounts of soy isoflavones necessary for the prevention of disease. No reference is made to a composition comprising a combination of soy protein, a high content of a phytoestrogen compound, and dietary fibers. Anderson (N. Eng. J. Med. 333, 276-282 (1995) analyzes a total of 38 clinical trials and concludes that the consumption of soy protein significantly decreases levels of: cholesterol, LDL-cholesterol and total serum triglycerides. It was found that the ingestion of diets containing soy protein, compared to control diets, is accompanied by a significant reduction in cholesterol, LDL-cholesterol and total triglycerides in serum concentrations, however, the ingestion of soy protein does not affect Significantly, serum HDL-cholesterol concentrations The effect of ingestion of soy protein is dependent on the initial cholesterol concentration.The subjects with normal cholesterol levels do not have significant reductions of 3.3 percent, and also subjects with mild hypercholesterolemia not have significant reductions of 4.4 percent, only subjects with moderate and severe hypercholesterolemia have decreases in ignificatives in cholesterol levels of 7.4 percent and 19.6 percent, respectively. The pattern of changes in LDL-cholesterol concentrations is similar to the pattern of total cholesterol concentrations. Also, changes in serum triglyceride concentrations are significantly related to the initial concentrations of serum triglycerides. Several types of soy proteins are studied, such as isolated soy protein, textured soy protein, or a combination thereof, and it is found that the type of soy protein has no significant effect on the net change in levels of soybean protein. serum cholesterol. The study does not consider a simultaneous uptake of the various types of soy proteins along with dietary fibers. No reference is made to a composition comprising a combination of soy protein, a high content of a phytoestrogen compound, and dietetic fibers. Bakhit (J. Nutr. 124, 213-222 (1993)) studied mild hypercholesterolemic men receiving a basic diet and reports that adding 25 g of soybean protein to low-fat diets, low in cholesterol decreases total concentrations of cholesterol in men with blood lipids! elevated. In subjects who have lower concentrations of; cholesterol (<5.7 mmol / l), this level of ingestion of soy protein does not influence blood lipids, and this suggests that plasma lipids may even be elevated in some subjects after ingestion of soybeans. Other studies have also found that in general, individuals with pre-existing hypercholesterolemia respond to soybean protein, while individuals with normal cholesterol levels do not. Bakhit et al. do not observe an additive effect of concurrent ingestion of soybean protein and soybean fiber. No reference is made to a composition comprising a combination of soy protein, a high content of a phytoestrogen compound, and dietary fibers. Faggioto (Atherosclerosis Reviews 21, 187-194 (1990) establishes that atherosclerosis is an extremely complex disease involving different pathological processes such as inflammation and degeneration.) The onset of atherosclerosis and its progress are very subtle, slow and silent processes, frequently which overlaps with a normal aging process.It is emphasized that although a tremendous amount of accumulated information, it is not possible to fully explain why atherosclerosis is so common in Western civilization, how fat grooves develop in young people , how fatty grooves are converted into fibrous plaques, and what role inflammation plays in, for example, atherosclerosis It is established that even when atherosclerosis becomes symptomatic, the treatment of choice often resorts to surgical procedures, since medical intervention is useless, unless patients undergo therapy of relatively long term and aggressive. No reference is made to a composition comprising a combination of soy protein, a high content of phytoestrogen compound, and dietary fibers. Gooderham (J. Nutr. 126 (8), 2000-20006 (1996)) has suggested that although the complement of soy protein for a typical Western diet may in fact increase plasma concentrations of isoflavones, this may not necessarily be sufficient to count disease risk factors such as high serum levels of cholesterol and triglycerides, and platelet aggregation. Any increase in levels in isoflavone sera after a diet rich in soybean is found to be highly variable among analyzed subjects. It is thought that this is due to for example the synchronization of the consumption of soy protein or the composition of the intestinal flora. The metabolism of isoflavones in the intestine is variable among individuals and remains to be elucidated. It is noted that the levels of isoflavones present in human plasma are probably not sufficient to mediate a significant inhibition of platelet aggregation. It is emphasized that isoflavones in human plasma exist predominantly in the conjugated form of inactive glucuronide, and only a small amount such as about 10 percent exists in the active free forms and conjugated with sulfate. A lack of an effect of isoflavones on total cholesterol levels is reported in a study that is in agreement with others who also discover that soy has little effect in normocholesterolemic individuals, while hypercholesterolemic subjects generally exhibit a decrease in LDL-cholesterol and total in relation to normocholesterolemic subjects. It is emphasized that only a few studies have reported an increased effect on HDL-cholesterol due to the consumption of soy protein and that most studies have shown little or no effect on HDL-colessterol levels. The reported results indicate a similar lack of effect of soy protein in HDL-cholesterol levels in normocholesterolemic subjects. It is emphasized that only isoflavones have been examined separately to determine whether these compounds are responsible for lipid lowering effects associated with ingestion of soy proteins. The administration of purified isoflavoneis to animals has shown variable results in blood lipids. A study conducted in human percolesterolémicos failed to show an effect of isoflavoneis in levels of blood lipids. No reference is made to a composition comprising a combination of soy protein, a high content of a phytoestrogen compound, and dietary fibers. Hendrich (J. Nutr. 124 (9 Suppl.) Has reported that isoflavones may have great beneficial potential for maintaining human health and that isoflavones may be protective of health in potentially available quantities of a human diet containing daily soy foods. The nutritional content of isoflavones is in the range of 0.1 to 1 mg / g in soy foods, various factors such as variety of soybeans, processing fe **, $ and the addition of other ingredients to the food, influence the isoflavone contents of the food. It is established that human intestinal bacteria can destroy the ingested isoflavones to a large extent and that this may be because only 15 to 20 percent of the isoflavones are recovered in intact form from the urine and feces. It is emphasized that much work remains to determine the relationship between the concentration of isoflavones in urine and human plasma and the biological effects of isoflavones. It is noted that although more health-related animal data needed to be obtained, the time is approximated when long-term human feeding trials of purified isoflavones and foods containing isoflavones to examine health-related solutions can be guaranteed. No reference is made to a composition comprising a combination of soy protein, a high content of phytoestrogen compound and dietary fibers. Hunninghake (Am J. Med. 97, 504-508 (1994)) describes an evaluation of hypocholesterolemic effects of a long-term treatment with a mixture of dietary fibers administered twice a day. 59 subjects with hypercholesterolemia who have completed the placebo-controlled study for 15 weeks with dietary fiber for 36 additional weeks with 20 g / day of fiber are treated. There are no significant effects on levels of either triglycerides or HDL. The levels of total cholesterol and LDL-cholesterol and the proportion of HDL / LDL are significantly reduced during treatment. The reductions in average percentage from baseline after 51 weeks of treatment are approximately 5 percent for total cholesterol, 9 percent for LDL-cholesterol and 11 percent for the LDL / HDL ratio. No reference is made to a composition comprising a combination of soy protein, a high content of a phytoestrogen compound and dietary fibers. Knight (Maturitas 22, 167-175 (1995)) provides a synopsis of the literature mainly related to the clinical effects of phytoestrogens in diseases associated with age. A review of literature pertaining to cardiovascular diseases states that the protective effects of phytoestrogens are manifested through changes in lipids, a decrease in LDL-cholesterol and an increase in HDL-cholesterol and vascular effects, with which they are related to both the tone vasomotor and vessel wall conformity. Consumption of soy protein is reported to alter lipid levels and dietary soy protein appears to be anti-atherogenic when compared to several animal proteins. It is concluded that isoflavones represent a large and exciting group of compounds with potential benefits for many diseases. It is emphasized that current evidence justifies the conclusion that phytoestrogens may be among the dietary factors that produce protective effects against heart disease. However, additional clinical studies are required to elucidate its effects more clearly. No reference is made to a composition comprising a combination of soy protein, a high content of a phytoestrogen compound, and dietary fibers. Knight (Obstet, Gynecol. 87, 897-904 (1996)) has reviewed the sources, metabolism, potencies and clinical effects of phytoestrogens in humans. The review suggests that phytoestrogens are among the dietary factors that produce protection against heart disease in vegetarians. Based on epidemiological studies and cell lines, it is emphasized that intervention studies are now an appropriate consideration for evaluating the clinical effects of phytoestrogens due to the potentially important health benefits associated with the consumption of foods containing these compounds. It is concluded that the clinical applications for phytoestrogens are still in their infancy. No reference is made to a composition comprising a combination of soy protein, a high content of a compound of phytoestrogens, and dietary fibers. Packard (Arterioscler, Thromb. Vasc. Biol. 17, 3542-3556 (1997)) has reviewed heterogeneity in lipoprotein classes containing apoB and provides an interpretation of kinetic studies of apoB metabolism in light of structural and functional variations important The review is based on the fact that the lipoprotein classes are composed of a limited number of components with different properties. However, the base seemed to be this heterogeneity and the consequences for illness are not fully understood. The LDL fraction is made up of a small number of subtypes of particles with relatively discrete size and density. Subjects with a preponderance of small-sized LDL have a three-fold increased risk of myocardial infarction regardless of the total LDL concentration present. No reference is made to a composition comprising a combination of soy protein, a high content of phytoestrogen compound, and dietary fibers. Potter (Am. J. Clin. Nutr. 58, 501-506 (1993)) studied the effects of soy protein consumption with and without soy fiber on plasma lipids in mildly hypercholesterolemic men. It is reported that LDL-cholesterol and total concentrations can be significantly decreased in mildly hypercholesterolemic men, as indicated by a 50% replacement of dietary protein with soy protein.

Similar reductions in blood lipids are indicated for isolated soy protein, whether consumed together with soybean cotyledon fiber or cellulose fiber. Plasma triglyceride concentrations are not affected by the various dietary treatments described in the article. The study reveals no effect of cholesterol reduction of the concurrent uptake additive of soybean cotyledon fiber with isolated soy protein, and it is established that it is unknown whether there is an added benefit in the reduction of blood cholesterol concentrations of Increased concurrent uptake of soy protein and fiber in humans. No reference is made to a composition comprising a combination of soy protein, a high content of phytoestrogen compound, and dietary fibers. Reinli (Nutr. Cancer 26, 123-148 (1996)) has reviewed the literature for quantitative data on the levels of known phytoestrogens (daidzein, genistein, coumestrol, formononetin and biochanin A) in food plants. It is reported that daidzein and genistein isoflavones can exist in four related chemical structures, ie, an aglycone structure (daidzein and genistein), a 7-O-glucoside structure (daidzin and genistin), a 6'-O-acetylglucoside structure ( 6'-0-acetyldaidzin and 6"-O-acetylgenistin), and a 6'-0-malonylgucoside structure (6'-O-malonyldaidzin and 6'-O-malonylgenistin).

The conjugates (7-0-glucosides, 6 '-O-acetylglucosides, and 6' -O-malonylglucosides) are transformed to aglycones, which are sometimes called free isoflavones, through hydrolysis in the intestinal tract by β-enzymes. glucosidases of intestinal bacteria. Acid hydrolysis in the stomach can also contribute to the formation of free isoflavones. It is not clear how the conjugates easily undergo intestinal hydrolysis and subsequent absorption. It is indicated that the isoflavones are metabolized differently by different animals and humans. No reference is made to a composition comprising a combination of soy protein, a high content of a phytoestrogen compound and dietary fibers. Sniderman (Am. J. Cardiol 79, 64-67 (1997)) presents a risk factor hypothesis with an emphasis on the integral role of LDL in atherogenesis. It is emphasized that a measurement of LDL-cholesterol is an incomplete estimate of the risk attributable to LDL and that other classic risk factors such as hypertension, diabetes and smoking exert their proatherogenic potential quite or exclusively by multiplying the malignant influences of LDL in the arterial wall. It is known that small, dense LDL particles are one of the most common dyslipoproteinemia associated with coronary artery disease. It is reported that elevated levels of lipoprotein (a) are associated with increased coronary risk, but the basis for this is still unclear. No reference is made to a composition comprising a combination of soy protein, a high content of a phytoestrogen compound and dietary fibers. WO 95/10512 relates to a process for producing a vegetable protein serum enriched with isoflavone and describes in a modality a serum having a content of genistein in dry base of about 2.6 to about 8.7 mg / gram and content of daidzein in base dry from about 2.5 to about 6.0 mg / gram. No reference is made to a composition comprising a combination of soy protein, a high content of a phytoestrogen compound, and dietary fibers. WO 95/10529 relates to a process for producing a protein concentrate enriched with isoflavone aglucone and describes in one embodiment a concentrate having in a dry base a genistein content of from about 1.0 to about 2.0 mg / gram and a content of daidzein from about 0.7 to about 1.5 mg / gram. No reference is made to a composition comprising a combination of soy protein, a high content of a phytoestrogen compound, and dietary fibers. WO 95/10530 relates to a process for producing an aqueous extract comprising protein and isoflavones glucone and describes in a modality a vegetable protein isolate having a genistein content in dry base of about 1.5 to about 3.5 mg / gram and a content of daidzein in dry base of about 1.0 to about 3.0 mg / gram. No reference is made to a composition comprising a combination of soy protein, a high content of a phytoestrogen compound and dietary fibers. WO 97/31546 describes data on total replacement programs (for 6 weeks) in weight reduction studies conducted at Karolinska Hospital in Switzerland. It is shown that products comprising isolated soy protein and cotyledon fibers from soybeans reduce serum triglyceride levels by a maximum of 44 percent and cholesterol levels by a maximum of 27 percent for a patient population with an average initial cholesterol content of 5.6 mmol / l. An average value of 6.25 mmol / l is determined for all patients who have serum cholesterol levels above 6 mmol / l, and for this group of patients a reduction in serum cholesterol levels of 33 percent is observed. Since the reported data are part of a weight reduction program, a dietary effect and / or an effect related to weight loss may have contributed to the observed reductions in cholesterol and / or triglycerides. No reference is made to a composition comprising a combination of soy protein, a high content of a phytoestrogen compound and dietetic fibers. WO 97/37547 describes a soy protein product enriched with isoflavone having a protein content greater than 60 percent of the total dry matter, a total dietary fiber content of less than 4 percent of the total dry matter, a sucrose content greater than 10 percent of the total dry matter, total sulfur-containing amino acid content greater than 2.2 percent of the total amino acid content, a stachyose content of less than 1.5 percent by weight of total dry matter , and a total isoflavone content greater than 2.5 mg / gram, equivalent to 0.25 percent. The use of soybean cotyledon fibers is not anticipated and the claimed invention is for use as an ingredient in the production of an edible product 'and not in an arteriosclerosis treatment. Also, the product differs from the composition according to the present invention by comprising total dietary fiber in an amount of less than 4 percent total dry matter, and by containing an unusually low amount of stachyose and a large amount of amino acids that contain sulfur. U.S. Patent 5,320,949 discloses a process for producing a fiber product enriched with isoflavonei aglucone from a vegetable protein material in the form of a coarse slurry and describes in one embodiment a fiber product enriched with aglucone obtainable directly from the process and which has a genistein content of about 1.0 and 2.0 mg / gram and a content of about daidzein of about 0.7 to 1.7 mg / gram. No reference is made to a composition comprising a combination of soy protein, a high content of a phytoestrogen compound, and dietary fibers. No reference is made to a composition comprising soy cotyledon fibers and a phytoestrogen compound. U.S. Patent 5,352,384 describes a fiber product enriched with aglucone having a genistein content of about 1.0 to 2.0 mg / gram and a daidzein content of about 0.7 to 1.7 mg / gram. No reference is made to a composition comprising a combination of soy protein, a high content of a phytoestrogen compound and dietary fibers. European Patents EP 827 698 A2 and EP 827 698 A3 describe a process for producing an extract enriched with isoflavone aglucone from a plant material containing isoflavone and protein conjugates. No reference is made to a composition comprising a combination of soy protein, a high content of a phytoestrogen compound and dietary fibers.

A summary presented at the 38th annual conference of the American Heart Association on Cardiovascular Disease Epidemiology and Prevention held in March 1998 describes a reduction in LDL-cholesterol and total levels in a subject after ingestion of a diet supplemented with 25 grams of protein of soy that contains 4 mg, 25 mg, 42 mg and 58 mg of isoflavones, respectively. A "dose response" effect is reported in such a way that increased amounts of isoflavones are associated with an increased cholesterol reduction. A maximum reduction of LDL-cholesterol serum levels and total of 4 percent and 7 percent, respectively, is reported for the product containing 58 mg of isoflavone. No reference is made to a composition comprising a combination of soy protein, a high content of a phytoestrogen compound and dietary fibers. The present invention provides a nutritional composition having a fixed, high amount of a phytoestrogen compound such as, for example, naturally occurring isoflavones. More particularly, the present invention provides a nutritional composition of extractable soybean ingredients having a fixed, high amount of a phytoestrogen compound such as, for example, naturally occurring isoflavones. More particularly, the present invention relates to a combination comprising a) soy proteins, preferably isolated soy protein, b) a fixed high content of a plant hormone in the form of a phytoestrogen compound, preferably isoflavones found in natural form and c) dietary fibers, preferably soy bean fibers, more preferably soybean bean fibers made from the soybean cotyledon hereinafter referred to as soybean cotyledon fibers. The present invention is useful in the treatment including prophylactically treating cardiovascular diseases such as hypercholesterolemia, hypertriglyceridemia, hyperlipidemia and other cardiovascular diseases such as for example arteriosclerosis. It is an object of the present invention to significantly reduce total serum cholesterol and LDL-cholesterol and triglycerides levels in a mild hypercholesterolemic subject. It is another objective of the present invention to significantly reduce levels of total cholesterol in serum and LDL-cholesterol and triglycerides in a subject suffering from: hypercholesterolemia and / or hyperlipidemia. It is another object of the present invention to make the arterial wall more resistant to the accumulation of lipoproteins. It is a further object of the present invention to provide a composition effective in treating and / or treating prophylactically and / or preventing and / or alleviating an arteriosclerotic condition by reducing the influx of cholesterol and triglycerides in the endothelium of the arterial wall. Still another object of the present invention is to reduce lipid plate formation. A composition according to the present invention can be comprised in a micronutrient as defined hereinafter. The phytoestrogen compounds are naturally occurring plant hormones that show a structural similarity to 17β-estradiol. Phytoestrogens consist of a number of classes including isoflavones, coumestans, lignans and lactones resorcinic acid. The class of isoflavones consists of, among others, genistein, daidzein, equol, glycitein, biochanin A, formononetin and O-desmethylangolesin. The isoflavones genistein and daidzein are found almost exclusively in soybeans. When they are present in the plant the isoflavones are mainly in the form of a glucoside, that is, bound to a sugar molecule. Isoflavones in this form of glucoside can be deconjugated to produce isoflavones in a form called eiglicone, which is the biologically most active form of isoflavones and which is absorbed faster and to a greater degree in the human intestine than isoflavones in the form of glucoside. The in vitro studies have examined the relative estrogenic effect exerted by several phytoestrocjenos that include isoflavones. The resulting potencies compared to estradiol (which have a relative potency of 100), have been reported by Knight (Maturitas 22, 167-175 (1995)) for among others genistein (0.084) and daidzein (0.013). However, the results also show that the estrogen receptor complexes formed by estradiol and isoflavones such as genistein and daidzein are functionally equivalent. The comparative dissociation constant of genistein for the estrogen receptor, as determined in competitive binding assays, is found to be 100 to 10,000 times greater than that of estradiol. The term "naturally occurring" substance as used in the present specification and the appended claims refers to a substance originally isolated from a natural source, such as an animal or a plant, for example a soybean plant, or modified forms of such substance. The naturally occurring substance for use in a composition according to the present invention can be included in a composition according to the present invention as part of the natural source or in any type of extract, isolate or the like thereof, or it may have been isolated from a plant source or synthesized biologically, microbiologically or chemically by any other means. Soy proteins are involved in a * h '' decreased levels of cholesterol and triglycerides, they are easily digestible, and represent a single source of efficient protein to maintain the balance of nitrogen. Soy isoflavones in high intakes also improves this effect. Dietary fibers, such as soybean fibers, especially soybean cotyledon fibers have been shown to reduce serum total cholesterol levels, to normalize gastrointestinal function, and to not influence the absorption of essential minerals. Accordingly, in one aspect the present invention provides a composition comprising (a) a source of soy protein, selected from isolated soy protein, soy protein concentrate, or soybean meal, the source of soy protein providing a amount of soy protein, which is at least 45 weight percent of the total protein content of the composition, the total protein content that provides at least 15 percent of the total energy content of the composition, (b) at least one phytoestrogen compound in an amount of more than 0.16 weight percent of the total protein content of the composition, and (c) dietary fibers in an amount of more than 6.

^ "MküIMillUIMi maMMÉ M I percent by weight of the total weight of the composition on a dry basis. In a more preferred aspect the present invention provides a composition comprising (a) isolated soy protein in an amount of at least 50 percent by weight of the total protein content of the composition, the total protein content it provides at minus 15 percent of the total energy content of the composition, (b) at least one phytoestrogen compound in an amount of more than 0.16 weight percent of the soy protein content of the composition, and (c) soybeans in an amount of more than 6 weight percent of the total weight of the composition on a dry basis. In a more preferred aspect the present invention provides a composition comprising (a) isolated soy protein in an amount of at least 50 percent by weight of the total protein content of the composition, the total protein content it provides at less 15 percent of the total energy content of the composition, (b) at least one phytoestrogen compound in one .. ... J _, amount of more than 0.16 weight percent of the soy protein content of the composition, and (c) soy cotyledon fibers in an amount of more than 6 weight percent of the total weight of the composition on a dry basis. The phytoestrogen compounds are naturally occurring plant substances, which are either structurally or functionally similar to 17β-estradiol or generate estrogenic effects. Phytoestrogens consist of a number of classes that include isoflavones, coumestan, lignan, and resorcinic acid lactones. Examples of isoflavones according to the present invention are genistein, daidzein, equol, glycitein, biochanin A, formononetin and O-demethylangolesin. The phytoestrogen compounds of a composition according to the present invention are preferably isoflavones, more preferably genistein, daidzein, glycitein and / or equol, even more preferably genistein and / or daidzein and even more preferably genestein. Genistein and daidzein are found almost exclusively in soybeans. A preferred composition according to the present invention may therefore comprise a single isoflavone, such as genistein, daidzein, glycitein or equol, or may comprise at least one isoflavone selected from the group consisting of at least genistein, daidzein, glycitein and equol.

A composition according to the present invention may be able to prevent and / or alleviate and / or treat and / or prophylactically treat an arteriosclerotic condition by reducing the accumulation of cholesterol in the arterial wall. This inhibitory effect can be mediated by the binding of naturally occurring isoflavones and / or soy peptides to an estrogen receptor or an estrogen-like receptor present in the endothelium of an artery. Soy peptides are preferably provided by partial hydrolysis of soy protein. Both levels of cholesterol and triglycerides in plasma are usually increased in individuals treated for cardiovascular disease, and these increased levels, unless reduced by treatment, are likely to promote atherosclerosis and / or coronary heart disease (CHD). Beta-2-adrenergic receptors are present in many different types of cells including fat cells and arterial wall cells. The beta-2-adrenergic receptors are involved in the regulation of triglyceride synthesis in fat cells and according to a currently preferred hypothesis, the binding of soy peptides and / or a phytoestrogen compound such as for example an isoflavone which is found in natural form a beta-2 -receptor present in a fat cell or in an arterial wall is effective in reducing for example the synthesis of triglycerides in fat cells and / or the release of triglycerides in the bloodstream and / or reducing the influx of triglycerides in the arterial wall. Soy peptides are preferably provided by partial hydrolysis of soy protein. According to a preferred hypothesis, a composition of the present invention will reduce and / or eliminate one or more of the risk factors for cardiovascular diseases. Accordingly, a composition according to the present invention can be effective in preventing and / or prophylactically treating and / or alleviating and / or treating conditions such as for example hypercholesterolemia, hypertriglyceridemia, hypertension and hyperglycemia. A composition according to the present invention may also be capable of reducing, preventing and / or eliminating fat groove formation and / or fibrous plaque development and / or effective in mediating a regression of one or both arteriosclerotic conditions. According to a preferred hypothesis, a composition according to the present invention will lead to a decrease in serum total cholesterol levels and / or a decrease in serum LDL-cholesterol levels and / or a decrease in serum triglyceride levels and / or effectively increase the HDL_LDL-cholesterol ratio and / or effectively increase serum levels of high density lipoprotein (HDL) and / or generate a decrease in serum levels of low density lipoprotein I LDL). It is desirable to achieve a high HDL / L.DL-cholesterol ratio since this may result in an increased inverse transport of cholesterol and subsequent excretion. Also, it is believed that a composition according to the present invention will affect the metabolism of ApoB lipoprotein which includes the metabolism of a newly discovered class of ApoB comprising lipoprotein particles called small, dense LDL particles. The LDL class of lipoproteins is in fact composed of several components with different properties. The basis for this heterogeneity and the consequences for disease are not fully understood. An increased level of small, dense LDL particles is one of the most common dyslipoproteinemias associated with coronary artery disease, and serum levels of ApoB are often disproportionately high compared to LDL-cholesterol in dyslipoproteinemic patients. The heterogeneity within the lipoprotein classes may be the result of a different lipid content, a different apoprotein composition, an altered protein conformation or a structural variation not yet identified. Subjects with a dense, small LDL preponderemcia have an increased risk of myocardial infarction independent of the total LDL serum concentration. Accordingly, a composition according to the present invention can be effective in decreasing high levels of dense, small LDL. Hypertriglyceridemia is associated with an increase in the coagulation activities of thrombogenic factors such as factor VII and factor X and an increase in the level of tissue plasminogen activator inhibitor PAI-1. The increased concentration of the inhibitor results in a decreased level of plasminogen synthesis and thus a decreased level of plasminogen stimulates lysis of the clot. These changes in coagulation activities contribute to a procoagulant state. According to a currently preferred hypothesis the present invention also provides an effective composition in normalizing homocysteine levels and / or the coagulation activities of at least one thrombogenic factor such as for example factor VII and / or factor X and / or Factor XII, for example, decreasing the increased activity thereof. Also a composition according to the present invention can be effective in promoting a decrease in the level of the tissue plasminogen activator inhibitor., PAI-1, which leads to ^^ iWMüta I ^^ MÉÉÉrirfli a lysis of clot stimulated by increased plasminogen. A composition according to the present invention can also be effective in reducing a platelet aggregation capacity and / or directly or indirectly mediating a reduction in the increased level of lipoprotein (a) associated with a procoagulant state in an arteriosclerotic condition. Accordingly, in one embodiment the present invention provides an effective composition in reducing and / or eliminate risk factors for coronary heart disease (CHD) in obese subjects. Accordingly, a composition according to the present invention may be able to prevent and / or alleviate and / or treat and / or treat prophylactically and / or eliminate hypertriglyceridemia and / or hypercholesterolemia and / or hyperglycemia and / or hypertension and / or effective in mediating an increased proportion of HDL / LDL-cholesterol. A composition according to the present invention can also be effective in treating dyslipidemia such as for example hypertriglyceridemia and / or hypercholesterolemia in connection with increased VLDL, decreased and altered HDL and small dense LDL, and hypertension, all of which are risk factors for atherosclerosis. Accordingly, in one embodiment, a composition of In accordance with the present invention, it may be capable of effectively decreasing and / or eliminating increased serum levels of VLDL, and / or effectively increasing decreased levels in HDL serum, and / or effectively lowering serum LDL levels including low dense serum LDL levels. A composition according to the present invention may be capable of preventing and / or treating and / or treating prophylactically and / or relieving hypertension. A composition according to the present invention can also be effective in suppressing any The effect may otherwise generate an increased change of arterial smooth muscle cells and / or lead to an accumulation of increased cholesterol ester in the arterial wall. In hypercholesterolemia characterized by levels In addition to intracellular cholesterol increases resulting from, for example, increased LDL-cholesterol delivery via the LDL receptor, a composition according to the present invention can be effective in reducing the increased activity of the LDL receptor. A composition according to The present invention may also be capable of alleviating, eliminating? / Or treating any decrease in cholesterol flow mediated by the HDL receptor. Accordingly, a composition according to the invention may be able to reduce and / or eliminate any increased retention of intracellular cholesterol caused by a decrease in pn * ^ ér? n -t * ** «..,. ,. - '- - • - -' - "~ - • - • -" ^ - ^ '"- *'» HDL receptor-mediated flow of cholesterol Modifications to lipoproteins are another risk factor for cardiovascular disease. characterized by glycosylation of protein is associated with arteriosclerosis, and glycosylated lipoproteins such as for example LDL, IDL, VLDL and HDL can be expected to be functionally abnormal.Accordingly, the accumulation of glycosylated LDL in the plasma can be perceived to increase the accumulation of cholesterol ester Also HDL glycosylation can be expected to damage the ability of HDL to bind to the HDL receptor.This damaged link is likely to reduce the level of intracellular cholesterol flow.As a result, glycosylated HDL may well be another factor which potentially contributes to the accumulation of cholesterol in the arterial cell wall A composition according to the present invention may be The aim is to prevent, alleviate, treat, reduce and / or eliminate glycosylation of lipoprotein in the serum of subjects. In addition, a composition according to the present invention can also be effective in preventing modification of lipoprotein caused for example by oxidation, chemical modification such as chemical crosslinking, or modifications caused by an alteration in the lipid composition of the lipoprotein, such as any increase or decrease in the content of triglycerides, cholesterol esters, free cholesterol, and apolipoproteins. Glycosylated lipoproteins have been suggested to be the subject of additional processing leading to. the formation of hyperglycosylated compounds. The glycosylation and hyperglycosylation of proteins including lipoproteins in both pleural and arterial walls may also be expected to be a risk factor for cardiovascular disease including arteriosclerosis. Accordingly, a composition according to the present invention may be able to prevent, treat, reduce, alleviate and / or eliminate the accumulation of hyperglycosylated proteins in both serum and arterial wall cells. By doing this, the composition is actuated to decrease the amount of LDL that leads to being "trapped" in the arterial wall due to the high degree of glycosylation of artery wall proteins. A composition according to the present invention can also be effective in alleviating and / or preventing alterations of the endothelial cell wall by generating an "entrapment" of LDL, and this can be effective in restoring the formation of cells with normal permeability and adhesion parameters. . The glycosylation of lipoproteins, hyperglycosylation, oxidation and / or autoxidative glycosylation, are risk factors for cardiovascular disease such as arteriosclerosis Accordingly, a composition according to the present invention can be effective in eliminating, preventing, alleviating, treating and / or or reduce any incidence of lipoprotein glycosylation, hyperglycosylation, oxidation and / or auto oxidative glycosylation. According to a currently preferred hypothesis, the phytoestrogen compound of a composition according to the present invention is capable of contracting such incidences. The phytoestrogen compound may also be able to prevent, reduce and / or eliminate the formation of for example free radicals that are likely to be involved in such processes, and a composition according to the present invention may be effective in being, promoting and / or facilitate the formation of an effective antioxidant defense system to contract the glycosylation, hyperglycosylation, oxidation and / or autoxidative glycosylation of whey proteins and proteins that include lipoproteins of the arterial cell wall. A composition according to the present invention can effectively act as an antioxidant in the prevention of lipoprotein oxidation and / or glycosylation. By term of autooxidative glycosylation, or glycoxidation, is meant a reaction that leads to an oxidative modification and / or protein crosslinking. An increased production of free radicals and lipid peroxidation can also contribute to the formation of autoxidative glycosylated lipoproteins and this contribution can be effectively prevented and / or eliminated by a composition according to the present invention. According to another currently preferred hypothesis, the binding of a phytoestrogen compound, such as for example an isoflavone, optionally in combination with soy peptides provided preferably by hydrolysis of soy protein, to a receptor in the arterial network, such such as for example the estrogen receptor, or an estrogen-like receptor, is involved in or is effective in controlling the accumulation of lipoproteins in the artery wall, possibly by regulating the permeability of the wall and / or the lipoprotein transport mechanism. between cell membranes. Consequently, the binding of isoflavons such as for example genistein and / or daidzein to a receptor in the arterial wall can reduce the flow of lipoproteins in the arterial wall. The binding of the isoflavone receptor in the arterial wall is particularly effective in controlling, avoid and / or eliminate the formation of fat grooves and / or development of fibrous plaque and / or effective in mediating a regression of one or both of the arteriosclerotic conditions. According to a particularly preferred hypothesis, the binding of isoflavones such as for example genistein and / or daidzein to a receptor in the arterial wall, preferably an estrogen receptor or an estrogen-like receptor, results in increased nitric oxide synthesis in the endothelial cells of the arterial wall. Nitric oxide is known to exert anti arteriosclerotic effects including inhibition of adhesion and aggregation of platelets, and inhibition of smooth muscle cell proliferation. Soy peptides obtained by hydrolysis of soy protein may participate in the binding of isoflavones to an estrogen receptor or to an estrogen-like receptor or the soy peptides may by themselves bind to the receptor and exert an action leading to a synthesis increased nitric oxide. In another currently preferred hypothesis, the establishment of an oxidative potential that promotes lipoprotein oxidation and / or autooxidative glycosylation of lipoprotein occurs concomitantly with, and is most likely caused by, a decrease in cellular antioxidant defense systems. Accordingly, a composition according to the present invention can per e ect act as an antioxidant. This action reduces and / or eliminates the susceptibility of LDL, VLDL, IDL and / or HDL to oxidation. Additionally, a composition according to the present invention can also be effective in reducing an increased susceptibility to endothelial damage and / or to alleviate and / or restore and / or improve an inefficient endothelial cell repair mechanism that leads to endothelial dysfunction. One effect of such action exerted by a composition according to the present invention is to direct development of macrophages away from foam cell formation and to increase the potential for generating arterial smooth muscle cells. In another currently preferred hypothesis, a composition according to the present invention will promote and / or mediate a reduction in arterial wall thickness and will lead to a reduction in the amount of LDL entering the wall. It is believed that an increased thickness of the arterial wall is positively associated with an increased uptake of LDL particles that are likely to either be added or oxidized within the cells of the arterial wall. Also, a composition according to the present invention may be able to reduce, eliminate and / or prevent the formation of increased serum levels of lipoprotein. (a) in a subject. Levels of (a) lipoprotein can be determined primarily in a genetic form, and no current cardiovascular medicine is thought to be effective in lowering serum lipoprotein (a) levels.

BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 shows total cholesterol (mM) levels for the four groups of patients in Example 2 (A: Patients in Group I; B: Patients receiving placebo with the same intake of protein and fibers as Group I, C: Patients in Group I, D: Patients receiving placebo with the same intake of protein and fiber as group II) in each of the 9 visits. CT = total cholesterol. Figure 2 shows the levels of LDL-cholesterol (mM) for the four groups of patients in Example 2 (A: * Patients in Group I; B: Patients receiving placebo with the same intake of protein and fiber as the Group I; C: Patients in Group I; D: Patients receiving placebo with the same ingestion of prptein and fiber as Group II) in each of the 8 visits. LDL-col = LDL-cholesterol. Figure 3 shows HDL-cholesterol (mM) levels for the four groups of patients in Example 2 (A: Patients in Group I; B: Patients receiving placebo with the same intake of protein and fiber as Group I; C: Patients in Group I; D: Patients receiving placebo with the same ingestion of protein and fiber as Group II) in each of the 8 visits. HDL-cdl = HDL-cholesterol. Figure 4 shows the levels of triglycerides (mM) for the four groups of patients in Example 2 (A: Patients in Group I; B: Patients receiving placebo with the same intake of protein and fiber as Group I; : Patients in Group I; D: Patients receiving placebo with the same ingestion of protein and fiber as Group II) in each of the 8 visits. Figure 5 shows the average HDL / LDL-cholesterol ratio for the four groups of patients in Example 2 (A: Patients in Group I; B: Patients receiving placebo with the same intake of protein and fiber as Group I; C: Patients in Group I; D: Patients receiving placebo with the same ingestion of protein and fiber as Group II) in each of the 8 visits. A composition according to the present invention comprises a novel combination of soy protein, preferably isolated soy protein, a phytoestrogen compound, preferably naturally occurring isoflavones and dietary fibers, preferably soybean fibers, more preferably fibers. of soybean cotyledon. The soy protein can be provided by isolated soy protein, soy protein concentrate, soybean meal or the like or any combination thereof. Soy protein isolated is preferred. Isolated soy protein is the main protein fraction of soybeans. This is prepared from high quality, dehusked soybeans, defatted by eliminating a preponderance of the non-protein components resulting in an isolated soy protein fraction that will contain at least 90 percent protein (N x 6.25) in a base free of moisture. The preparation takes place through a series of stages in which the soybean protein portion is separated from the rest of the soybeans. The removal of caydrates results in a product, which is essentially soft in taste and therefore particularly useful in a nutritional composition for humans. Soy protein concentrates are made by removing most of the water-soluble non-protein constituents and defatted soybean oil from the dehulled soybeans. In the present context, a soy protein concentrate will preferably contain at least 65 percent protein in a moisture-free base. Soy protein can also be provided by spya flour, which can be fully grimated soy flour, or defatted, fully fat soy flour comes from whole soybeans., peeled that have been ground into a fine powder and, as the name implies, still contain the fat naturally found in soybeans. The defatted soybean meal comes from whole, dehulled, defatted soybeans that have been ground into a fine powder. The soybean meal is about 50 percent soy protein on a dry weight basis in the present context. The soy protein used in a composition according to the *. present invention should preferably provide all essential amino acids in the amounts required for humans. Preferably, the soy protein must also meet or exceed the pattern of requirement of essential amino acids for children and adults as established by the Food and Agricultural Organization, World Health Organization and United Nations University (FAO / WHO / UNU) . Additionally, the preferred soy protein should be comparable in digestibility to the milk, meat, fish and egg protein. Finally, the preferred soy protein should be effective in maintaining nitrogen balance when consumed at the recommended protein ingestion level. The preferred isolated soy protein products that meet the aforementioned requirements are supplied by Protein Technologies International, Inc. under the trademark SUPRO®. The SUPRO® isolated soy proteins are supplied in many different qualities and SUPRO® XT 12C is a particularly preferred quality. The currently most preferred quality is named SUPR® FXP-H0159. »^ Soy protein is preferably the main or unique protein source in a nutritional composition according to the present invention. However, the portions of the protein source may be provided by other proteins such as for example skim milk, preferably as a powder, and other vegetable or animal proteins including milk proteins. Preferably, at least 45 percent by weight, such as 50 percent by weight, for example at least 60 percent by weight, such as at least 70 percent by weight, for example at least 75 percent by weight, weight, such as at least 80 weight percent, for example at least 85 weight percent, such as at least 90 weight percent, for example at least 95 weight percent, such as minus 98 p >The weight percent of the protein content of the composition is soy protein, and more preferably the substance of the protein is soy protein. In a preferred embodiment of the invention the soy protein is provided by isolated soy protein. In this embodiment, preferably at least 50 percent by weight, for example at least 60 percent by weight, such as at least 70 percent by weight, for example at least 75 percent by weight, such as at least 80 percent by weight, for example at least 85 percent by weight, such as at least 90 percent by weight, for example at least 95 percent by weight, such as at least 98 percent by weight The total protein content weight of the composition is isolated soy protein, and more preferably substantially all of the protein is provided by isolated soy protein. The total protein content of a composition according to the present invention provides at least 15 percent of the total energy content of the composition, for example 18 percent, such as at least 20 percent, for example at least 22 percent, such as at least 25 percent, for example at least 28 percent, such as at least 30 percent, for example at least 32 percent, such as at least 35 percent, for example at least 38 percent, such as at least 40 percent, for example at least 42 percent, such as at least 45 percent, for example at least 48 percent, such as at least 50 percent of the total energy content of the composition, and preferably less than 90 percent of the total energy content of the composition. The phytoestrogen compounds according to the present invention are defined as naturally occurring plant substances, the substances are either structurally or functionally similar to 17β-estradiol or generate estrogenic effects. Phytoestrogens consist of a number of classes that include isoflavones, coumestans, lignans, and resorcinic acid lactones. Examples of isoflavonets according to the present invention are genistein, daidzein, equol, glycitein, biochanin A, formononetin, and O-demethylangolesin. The phytostrophin compounds of a composition according to the present invention are preferably isoflavones, more preferably genistein, daidzein, glycitein and / or equol, even more preferably genistein and / or daidzein and even more preferably genistein. A preferred composition according to the present invention may therefore comprise a simple isoflavone, such as genistein, daidzein, glycitein, or equol, or this may comprise at least one isoflavone selected from the group consisting of at least genistein, daidzein, glycitein and equol. When they are present in the plant the isoflavones are mainly in a form of glucoside, that is, attached to a sugar molecule. This form of glucoside can be deconjugated to produce a form called aglycone, which is the biologically active species. A composition according to the present invention may comprise isoflavones in the form of glucoside and / or aglycone regardless of whether the deconjugation to the aglycone form has taken place biologically, in vitro or by any other means whereby isoflavones are included in a composition according to the present invention or if the aglycone forms are in the native form of the isoflavones. The compound The phytoestrogen is preferably present in an amount of at least about 0.16 percent by weight of the soy protein content, such as at least about 0.18 percent in pe * p., for example at least about 0.20. percent by weight, such as at least about 0.22 percent by weight, for example at least about 0.24 percent by weight, such as at least about 0.25 percent by weight, for example more than about 0.25 percent by weight, such as at least about 0.26 percent by weight, for example at least about 0.28 percent by weight, such as at least about 0.30 weight percent, for example at least about 0.32 weight percent, such as at least about 0.33 weight percent, for example more than about 0.33 weight percent, such as at least about 0.35 percent by weight, for example at least about 0.40 percent by weight, such as at least about 0.45 percent by weight, for example at least about 0.50 percent by weight, such as by at least about 0.55 percent by weight, for example at least about 0.60 percent by weight, such as at least "about 0.65 percent by weight, for example at least about 0.70 weight percent, such as at least about 0.75 weight percent, for example at least about 0.80 weight percent, such as at least about 0.85 weight percent, for example at least about 0.90 weight percent. per cent by weight, such as at least about 1.0 weight percent of the soy protein content, and preferably less than 2.50 weight percent of the soy protein content. At.' past, the downstream processing techniques used in the preparation of soy proteins have included steps that eliminate and / or destroy isoflavones.

The methods are currently available, which provide soy protein products with high, fixed levels of isoflavones found naturally. Isoflavones according to the present invention in glycoside and / or aglycone forms can be included in a composition according to the present invention as a part of such soy protein products and / or by themselves and / or as a part of any . another composition comprising isoflavones. The dietary fibers used in the present invention should. preferably comprising a mixture of insoluble fibers and water soluble fibers also referred to as soluble fibers. Soluble fibers have a diminishing effect on blood cholesterol levels. Exam of dietary fibers comprising soluble fibers are fibers from ap, bananas, oranges, carrots, oats and soybeans. The dietary fibers preferably comprise soluble fibers in an amount of about 5 weight percent, such as about 10 weight percent, for examabout 15 weight percent such as about 20 weight percent, for examabout 25 weight percent. weight, such as about 30 weight percent, for examabout 35 weight percent, such as about 40 weight percent, for examabout 45 weight percent, such as about 10 weight percent, for examabout 55 percent by weight, such as about 60 percent by weight, for examabout 65 percent by weight such as about 70 percent by weight, for examabout 75 percent by weight, such as about 10 percent by weight. percent, by weight, for examabout 85 weight percent, such as about 90 weight percent, for examabout 95 percent by weight, in weight. The dietary fibers used in the present invention are preferably soy bean fibers, more preferably soybean cotyledon fibers. Such fibers are derived from cotyledon of dehusked and defatted soybeans and are comprised of a mixture of soluble and insoluble fibers. The soybean cotyledon fibers are distinctly different from soybean fibers derived from soybean husks as well as other sources of fibers. Soybean cotyledon fibers are soft-flavored, contain no cholesterol, are low in fat and sodium, and have good water binding properties and low caloric content. The soybean cotyledon fibers supplied in a diet modified in fat and low in cholesterol are known to further decrease serum cholesterol levels in a subject suffering from mild to severe hypercholesterolemia. The effect is a decrease in serum levels of total cholesterol including a decrease in LDL-cholesterol. However, HDL-cholesterol and total triglycerides are not significantly affected by soybean cotyledon fibers. Soy bean fibers, in particular soybean cotyledon fibers, are believed to provide a synergistic effect in combination with soy protein and / or with a phytoestrogen compound, such as naturally occurring isoflavones, or to exercise an enhancing effect on the soy protein and / or the phytoestrogen compound, the synergistic or potentiating effect is effective in decreasing serum lipids and cholesterol levels in subjects having normal serum levels as well as elevated serum levels. total cholesterol and total triglycerides. Without wishing to be bound by any specific theory, it is currently believed that both soluble dietary fibers (which function as nutrients) and insoluble dietary fibers (which work as bulking agents), in particular soybean fiber, more particularly soybean cotyledon fibers , provide favorable growth conditions for the microflora in the human intestine, which make the microflora more effective in deconjugating isoflavones in the form of glycoside to the aglycone form. Isoflavones in the aglycone form are absorbed faster and to a greater degree in the human intestine than isoflavones in the form of glucoside, and isoflavones in the form of aglycone are the most biologically active species with respect to decreasing serum levels of lipids and reduce atherosclerosis. In view of the same it can be understood that the administration of a combination of soy proteins, a fixed, high level of isoflavones and a combination of soluble and insoluble fibers is effective in providing increased uptake of isoflavones. The amount of dietary fiber of the total weight of a composition according to the present invention in a dry base is preferably more than 6 weight percent, for example at least 7 weight percent, such as at least 8 weight percent. by weight, for example at least 9 weight percent, "such as at least 10 weight percent, for example at least 11 weight percent, such as at least 12 weight percent, for example at least 13 weight percent, such as at least 14 weight percent, for example at least 15 weight percent, such as at least 16 weight percent, for example at least 17 weight percent by weight, such as at least 18 weight percent, for example at least 19 weight percent, such as t at least 20 weight percent, and * preferably less than 50 weight percent. Preferred amounts of dietary fibers as one percent by weight of the soy protein content should be in the range of about 10 to 100 weight percent,? preferred amounts are in the range of 15 to 90 weight percent, such as 20 to 80 weight percent, for example 25 weight percent, such as 30 weight percent, for example 33 'weight percent , such as 35 weight percent, for example 40 ppr weight percent, such as 50 weight percent, for example 60 weight percent, such as 70 weight percent, for example 75 weight percent. Accordingly, the weight ratio of soy protein to dietary fibers is from about 1.0 to about 10.0 ', preferably more than about 1.0, for example "about 1.24, such as at least about 1.5, for example at least about 1.75. , such as at least about 2.0, for example at least about 2.25, such as at least about 2.5, for example at least about 2.75, such as at least about 3.0 for example at least about 3.25, such as at least about 3.5, for example at least about 3.75, such as at least about 4.0, for example at least about 4.25, such as at least about 4.5, for example at least about 4.75, such as at least less about 5.0, for example at least about 5.5, such as at least about 6-vO, for example at least approximately 7.5. The preferred daily dose of soy bean fibers is from at least 1 g to about 100 g of soy bean fibers, for example from at least 2 to about 75 'g of soy bean fibers, such as from at least about 3 g to about 50 g, for example from at least 4 g to about 40 g, such as from at least 5 to about 30 g, such as from at least 10 g to about 20 g of soy bean fibers .

The preferred soybean cotyledon fiber products manufactured by Protein Technologies International, Inc. are sold under the trademark of FIBRIM®. Among the various soy bean fibers produced under the trademark FIBRIM®, FIBRIM® 1020 is particularly preferred because of a particularly pleasant taste and dispersibility for dry mixed beverage applications. FIBRIM® 200P is currently preferred for use in ready-to-prepare liquids. ''. . Two soybean protein and soybean cotyledon fiber compositions are preferred in order to maximize the protein content of soy and isoflavones contained therein ie SUPRO® FXP-H0159 and FRIBRIM® 1020 for dry mixed beverage applications and SUPRO® FXP-H0159 and FIBRIM® 2000 for use in ready-to-prepare liquids. Alternatively, * the present invention provides a composition wherein soy protein is not present and wherein the dietary fibers are soybean cotyledon fibers. This composition comprises soybean cotyledon fibers in an amount of more than 4 weight percent of the total weight of the composition in a dry base, and at least one phytoestrogen compound in an amount of more than 0.10 weight percent of the composition. the cotyledon fibers of soy of the composition > n. The present invention also provides the use of such a composition as a medicament and / or in the manufacture of an effective medicament in preventing and / or treating and / or treating prophylactically and / or relieving and / or eliminating a cardiovascular disease in a subject. The present invention also provides the use of such a composition as a medicament and / or in the manufacture of a medicament effective in preventing and / or treating and / or treating prophylactically and / or relieving, treating alleviating and / or eliminating arteriosclerosis or a disease cardiovascular related in a subject. The present invention also provides the use of such a composition and / or such composition for use in treating arteriosclerosis or a related cardiovascular disease in a subject. When no soy protein is present in the composition, the phytoestrogen compound is preferably present in an amount of at least about 0.12 weight percent of the soybean cotyledon fiber content, such as at least about 0.14 percent by weight in the soybean. weight, for example at least about 0.16 percent by weight, such as at least about 0.18 percent by weight, for example at least about 0.20 percent by weight, such as at least about 0.22 percent by weight, for example at least about 0.24 weight percent, such as at least about 0.25 percent, for example more than about Or-25 weight percent, such as at least about 0.26 weight percent, for example at least about 0.28 weight percent, such as at least about 0.30 weight percent, for example at least about 0.32 percent by weight, such as at least about 0.33 percent by weight, for example more than about 0.33 percent by weight, such as at least about 0.35 percent by weight, for example at least about 0.40 percent by weight , such as at least "about 0.45 percent by weight, for example at least about 0.50 percent by weight, such as at least about 0.55 percent by weight, for example at least about 0.60 percent by weight, such as at least about 0.65 percent by weight, for example at least about 0.70 percent by weight, such as at least about 0.75 percent by weight, for example at least about 0.80 percent by weight, such as at least about 0.85 percent by weight, for example at least about 0.90 percent by weight, such as at least about 1.00 percent by weight, for example at least about 1.25 weight percent, such as at least about 1.50 weight percent, for example at least about 1.75 weight percent, such as at least about 2.00 weight percent, per example at least about 2.50 weight percent, such as at least about 3.00 weight percent, for example at least about 3.5 weight percent. by weight, such as at least about 5.00 weight percent of the soybean cotyledon fiber content of the composition and preferably less than 10.00 weight percent of the soybean cotyledon fiber content of the composition. A composition according to the present invention may optionally comprise a source of carbohydrates, urtá source of fats, flavoring agents, vitamins, minerals, electrolytes, trace elements and other conventional additives. The nutritional composition of the present invention may in one embodiment also comprise one or more flavoring agents such as flavor to cocoa, vanilla, limes, strawberries or soup, such as mushrooms, tomatoes or broths and / or sweeteners such as aspartame as well as other additives such as xanthan gum. When a carbohydrate source is present in a composition according to the present invention, it is preferably present in an amount of less than 30 weight percent ta as less than 25 weight percent of the composition. Preferably, the. amount of carbohydrate amounts to at least 5 percent by weight, more preferably at least 10 percent by weight, and more Preferred by at least 15 percent by weight of the ^^^ e ^^^ sggg ^ «g * gg¡ • * composition. Preferred carbohydrates for use in a composition according to the present invention are dextrose, fructose and / or maltodextrin, or glucous. Skim milk and cocoa reduced in lecithinized fat are other possible sources of carbohydrates. When a source of fats is present in a composition according to the present invention, it is usually present in an amount of 0.5 to 10 weight percent, preferably 1 to 9 weight percent, such as 1.5 to 8 percent by weight, for example from 2 to 7 weight percent, such as from 2.5 to 6 weight percent of the composition. The fat source will preferably comprise polyunsaturated fatty acids and monounsaturated fatty acids and optionally saturated fatty acids as well. Particularly preferred are soy lecithins and α-linolenic acids. The amount of polyunsaturated fatty acids and monbunsaturated fatty acids, including essential fatty acids, may be in the range of 35 to 50, preferably 3-8 to 44, per 100 weight percent of the total amount of the fat source. Essential fatty acids are also called omega-6 and omega-3 fatty acids and include linolic acid and / or linolenic acid (o-linolenic acid). The amount of saturated fatty acids can be from 20 to 30 weight percent, preferably 22 to 26 weight percent, of the total amount of fat.

Vitamins and minerals may optionally be added to a composition according to the present invention in accordance with the limits indicated by health authorities. Preferably, a composition according to the present invention will comprise all the recommended vitamins and minerals. Vitamins will typically include A, Bl, B2, B12, folic acid, niacin, pantothenic acid, bi? Tin, C, D, E, and K. Minerals will typically include iron, zinc, iodine, copper, manganese, chromium, and selenium. Electrolytes, such as sodium, potassium and chlorides, trace elements and other conventional additives can also be added in recommended amounts. A preferred composition can be obtained by mixing: Content Grams per 100 grams ration (%) Isolated soy protein 50.00 18.5 (SUPRO® FXP-H0159) Soy bean fibers 12.50 4.63 (FIBRIM® 1020)., Fructose 22.62 8.37 Reduced fat cocoa 9.30 3.44 lecitinated Soy lecithin 3.55 1.31 Flavors * 1.28 0.47 Xanthan gum 0.50 0.19 Aspartame 0.25 0.09 The composition mentioned above in an amount of preferably about 37 grams corresponds to a serving of a daily diet. The composition has an energy content of approximately 339 kcal (1,437 kJ) per l or grams. * A composition according to the present invention can be used for special dietary use, preferably to lower serum levels of cholesterol and / or triglycerides in hyperlipidemic patients or normocholesterolemic patients suffering from cardiovascular disease. For example, one to three daily meals of ordinary food may be supplemented or replaced by a composition according to the present invention. For the same, significant reductions can be obtained in serum levels of total cholesterol and LDL-cholesterol and triglycerides, as well as an improvement in HDL / LDL-cholesterol ratio. and / or an increase in serum HDL-cholesterol levels. The composition can provide from about 50 to 250 kcal • per serving. The daily dose of a composition according to the present invention can comprise an energy content of 400 to 800, in particular of 450 to 800 kcal / day, which is considered to be a very low calorie diet (DMBC), or this one . it can comprise an energy content of 800 to 1200 kcal '/ day, which is considered to be a low calorie diet (DBC). In another medical embodiment of the present invention, the energy content may correspond to the daily energy requirement of a normal person. The present invention also provides a composition according to the invention in the form of a micronutpente. In this connection a micronutrient is a nutritional complement and / or a pharmacological composition and / or a medicament comprising i) a compound similar to synthetic phytoestrogen capable of binding an estrogen receptor or estrogen-like receptor, and / or ii (a plant extractable compound, which is found naturally in an amount, on a weight basis by weight, in excess of the amount of the compound, when present in a natural host such as a plant cell of which the compound can be extracted or isolated, and optionally iii) soy peptides obtainable from a partial hydrolysis of soy protein. "The naturally occurring plant extractable compound" is preferably but not limited to compounds capable of binding to an estrogen receptor, an estrogen-like receptor, a beta-2-adrenergic receptor, or a receptor that belongs to the beta-2-adrenergic receptor cascade. which are naturally occurring are isolated from plants such as soybeans, they can be selected from the group containing at least phytoestrogens such as soybean phytoestrogens such as soybean isoflavones, soybean protein or soy fragments. the same, for example peptides or amino acid sequences, bean bean fibers, lecithin, linolenic acid, an antioxidant, a saponin, a lignan, a protease inhibitor, a trypsin inhibitor, and a tyrosine kinase inhibitor. Additional constituents of the micronutrient can preferably be selected from a DNA topoisomerase inhibitor, an efe ribosome kinase inhibitor, a growth control factor, such as for example an epidermal growth factor, an alpha transforming growth factor, growth factor derived from platelets, and preferably any growth control factor controllable by a tyrosine kinase activity. The micronutrient may also comprise ormeloxifene and / or levrmeloxifene as described among others by Holm et al. (1997) in Arteriosclerosis, Thrombosis, and Vascular Biology 17 (10), 2264-2272, and in Clinic Investigation 100"(4), 821-828.When the naturally occurring compound is an isoflavone, the isoflavone it may have been deconjugated to the aglycone form either biologically or in vitro prior to incorporation into the micronutrient 5 In a particularly preferred embodiment the present invention provides a composition or a micronutrient according to the present invention in combination with a food ingredient functional comprising a sterol, preferably an ingredient selected from the group consisting of a stanol ester, a tocotrien, a mevinolin, and a phytosterol compound such as, for example, campesterol sitosterol or stigmasterol or a combination thereof. According to a preferred embodiment, a The composition or a micronutrient according to the present invention is for use as a functional food ingredient. A composition or a micronutrient according to the present invention can also be administered as a probe or by intravenous administration, or in tablet form or capsule. The present invention also provides a pharmaceutical preparation comprising the composition or a micronutrient according to the present invention, use of a composition or a micronutrient according to the present invention in therapy and / or diagnostic method performed in the Human or animal body, use of a composition or a -? gft "~ t * x? t¡a * i micronutrient according to the present invention in the manufacture of a medicament and use of a composition or a micronutrient according to the present invention in the manufacture of a medicament for treating a subject suffering from cardiovascular diseases The micronutrient is particularly useful in the prevention and / or treatment and / or prophylactically treatment and / or relief of hypercholesterolemia, hypertriglyceridemia, other hyperlipidemias and arteriosclerosis, atherosclerosis and related cardiovascular diseases. present invention provides a composition according to the present invention for use as a medicament A composition according to the present invention for use as a medicament can be preferably used in preventing and / or treating and / or treating prophylactically and / or alleviating diseases cardiovascular diseases such as for example a disease selects from the group consisting of arteries clerosis, atherosclerosis, arteriolosclerosis, coronary heart disease, angina pectoris, thrombosis, myocardial infarction, and hypertension. Arterioclerosis is a common term for a group of conditions related to the arterial system that leads to an increased arterial wall thickness and a subsequent loss of elasticity. Three major groups of arteriosclerosis frequently referred to as atherosclerosis; 'Mcleckeberg mediasclerosis and arteriolosclerosis. Atherosclerosis is most frequently observed in the aorta and in the main arteries connected to it, in the coronary arteries and arteries of the brain. Monckeberg's mediaclerosis leads to a narrowing of the arteries of the extremities, and arteriolosclerosis is related to a narrowing of the small arteries and arterioles caused mainly by hypertension. The composition according to the present invention is effective in lowering cholesterol levels in normocholesterolemic patients by at least 2%, for example at least 5%, such as at least 8%, for example at least 10%, such as at least 12%, for example at least 14%, such as at least 16%, for example at least 18%, such as at least 20%, for example at least 25%, such as at least minus 30% The composition according to the present invention is effective in lowering triglyceride levels in normocholesterolemic patients by at least 10% such as /. at least 12%, - for example at least 14%, such as at least 16%, for example at least 18%, such as at least 20%, for example at least 25%, such as at least 30% The composition according to the present invention is effective in lowering cholesterol levels in mild hypercholesterolemic patients by at least 3%, for example by at least 5%, such as by at least 8%, for example by at least 10%, such as at least 12%, for example at least 15%, such as at least 20%, for example at least 25%, such as at least 30%, for example at least 35%, such as at least 40%, for example at least 45%. The composition according to the present invention is effective in lowering triglyceride levels in mild hypercholesterolemic patients by at least 15%, such as at least 2%, for example at least 25%, such as at least 30%, for example at least 35%, such as at least 40%, for example at least 45%. The composition according to the present invention is effective in lowering cholesterol levels in severe hypercholesterolemic patients by at least 3%, for example at least 5%, such as at least 8%, for example at least 10%, such as at least 12%, for example at least 15%, such as at least 20% for example at least 25%, such as at least 30% for example at least 35%, such as at least 40% for example at least 45%, such as at least 50% for example at least 55%, such as at least 60%. The composition according to the present invention is effective in lowering triglyceride levels in severe hypercholesterolemic patients by at least% 20, for example at least 25%, such as at least 30%, for example at least 35%, such as at least 40%, for example at least 45%, such as at least 50%, for example at least 55%, such as at least 60%. A composition according to the present invention for use as a medicament may also be effective in reducing the influx of cholesterol and / or triglycerides in the arterial wall and / or reducing the amount of oxidized LDL-cholesterol present in the arterial wall and / or decrease levels in. of cholesterol and / or LDL-cholesterol and / or homocysteine and / or triglycerides and / or increase the proportion of HDL / LDL-cholesterol in serum and / or increase serum levels of HDL-cholesterol. In another embodiment, the present invention provides the use of a composition according to the present invention in the treatment of cardiovascular diseases, eg arteriosclerosis. The use of a composition according to the present invention as a medicament and / or in the manufacture of a medicament for treating a subject suffering from cardiovascular diseases represents another embodiment of the present invention. The use of a composition according to the present invention as a medicament and / or in the manufacture of a medicament for treating a subject suffering from arteriosclerosis still represents another embodiment of the present invention. Such a medication may for example be effective in preventing and / or treating and / or treating prophylactically and / or alleviating for example a cardiovascular disease selected from the group consisting of hypercholesterolemia, hypertriglyceridemia, other hyperlipidemias, arteriosclerosis "; atherosclerosis, arteriolosclerosis, angina pectoris, thrombosis, myocardial damage, and hypertension in a subject, where drugs that are effective in preventing and / or treating and / or treating prophylactically and / or relieving arteriosclerosis and / are more preferred. or atherosclerosis in a subject. The medicament may also be effective in decreasing cholesterol levels and / or LDL-cholesterol levels and / or total triglyceride levels in serum and / or total serum levels of homocysteine in a subject and / or reducing the influx of cholesterol and / or / or triglycerides in the arterial wall and / or reduce the amount of oxidized LDL-cholesterol present in the arterial wall. The medicament may also be effective in increasing the HDL / LDL-cholesterol ratio in a subject's serum and / or increasing HDL-cholesterol levels in a subject. The medicament can also be effective in preventing, reducing or eliminating fat groove formation and &preventing, reducing or eliminating fibrous plaque formation and / or preventing, reducing, or eliminating complicated injury formation. The medication can also be effective in reducing or eliminating the risk of contracting angina and / or reducing or eliminating the risk of a subject contracting a myocardial infarction. The present invention also provides a method for preventing and / or treating and / or treating prophylactically and / or relieving by therapy a cardiovascular disease in the human body, or animal such as an arteriosclerotic condition of a human or animal body, the method comprises the administration of a composition according to the present invention in an amount effective to decrease cholesterol levels and / or serum LDL-cholesterol levels and / or serum triglyceride levels and / or serum homocysteine levels and / or increase the ratio of HDL / LDL-cholesterol in serum and / or HDL / cholesterol levels in serum and / or reduce the influx of cholesterol and / or triglycerides in the arterial wall and / or reduce the amount of oxidized LDL-cholesterol present in the arterial wall and / or preventing, reducing or eliminating fat groove formation and / or preventing, reducing or eliminating fibrous plaque formation and / or preventing, reducing or eliminating complicated and / or reduced injury formation. r or eliminate the risk of contracting angina pectoris and / or reducing or eliminating the risk of a subject contracting a myocardial infarction, and / or alleviating the clinical condition, of patients contracting a myocardial infarction. Cardiovascular disease it is preferably a cardivascular disease selected from the group consisting of hypercholesterolemia, hypertriglyceridemia, other hyperlipidemias, arteriosclerosis, atherosclerosis, arteriolosclerosis, angina pectoris, thrombosis, myocardial infarction and hypertension and most preferred selects arteriosclerosis and atheroclerosis. The treatment period is preferably in the range of 1 to 12 months or more, such as 2 weeks to 9 months, for example 3 weeks to 6 months, such as 4 weeks to 4 months, such as 6 weeks to 3 months. However, the period of treatment will not be limited to these periods and may for example be as long as 12 months, such as for example a long-life treatment in order to prevent cardiovascular diseases. In one embodiment, the present invention provides a pharmaceutical preparation comprising a composition according to the present invention. The pharmaceutical preparation can be prepared in any manner known to the skilled person. In another embodiment, the present invention provides the use of a composition according to the present invention as a nutritional preparation and / or in the manufacture of a nutritional preparation to lower serum cholesterol levels and / or serum LDL-cholesterol levels. / or serum triglyceride levels and / or serum homocysteine levels * and / or to increase the HDL / LDL-cholesterol ratio in serum and / or increase serum HDL-cholesterol levels in a subject. Nutritional preparation can take any form, which is suitable for human or animal consumption. In a preferred embodiment, the composition is a powder mixture, which is suspendable, dispersible or emulsifiable in a liquid for human or animal consumption. The liquid is preferably a liquid containing water such as for example water, coffee, tea or juice. For such purpose, the composition can be packed in a package proposed to cover part of the total nutritional requirement for a defined period of time. The present invention also provides the nutritional preparation in the form of a dietary supplement. The nutritional preparation in one embodiment of the present invention is preferably a functioning food or beverage, ie an easily obtained edible or drinkable substance that is supplemented with a composition according to the present invention to provide a medical or pharmaceutical effect. Accordingly, the present invention provides a composition according to the present invention for use as a functional food ingredient. Functional foods and beverages are preferably selected from the group consisting of "daily products," such as yogurt, and yoghurt ice cream, juice such as orange juice or tomato juice, liquids ready to be prepared for drinking, a dispersible product such as for example margarine or an oil extracted from plants or vegetable, a cereal product, such as a traditional breakfast cereal product, nutritional bars, squash, bread, soups, such as tomato soup, a meat product, such as a hamburger, a substitute product of meat, and a vegetable product. In a further embodiment, a nutritional preparation in accordance with the present invention may be in the form of a liquid ready to be prepared either in a powder form or in the form of a troche, a solid composition such as a nutritional bar. , a fruit bar, a cookie, a cake, a bread or a muffin. In another embodiment, a composition according to the present invention is a liquid nutritional preparation in a liquid containing water, in which the solid ingredients are suspended, dispersed or emulsified in an amount of 10 to 25 weight percent. When the liquid nutritional preparation for drinking is proposed, it will usually comprise a flavoring agent as discussed above. However, the liquid nutritional preparation may also be used for administration by gavage. In another embodiment, the present invention relates to the use of a composition according to the present invention as a partial or total diet for an overweight subject suffering from an arteriosclerotic condition. Overweight subjects often have an increased serum cholesterol level and an increased triglyceride level and are therefore more likely to develop cardiovascular disease. However, the present invention is not limited to treating subjects with an increased risk of contracting arteriosclerosis, i.e. subjects who will likely have increased serum cholesterol and / or triglyceride levels. A composition according to the present invention also has a substantial decreasing effect of serum cholesterol, serum LDL-cholesterol and serum triglycerides in subjects having a more normal lipid profile. The medical use of a composition according to the present invention is not limited to overweight or obese subjects, but can be used for subjects of normal weight who have increased serum levels of cholesterol and / or LDL-cholesterol and / or triglycerides or for subjects with a cardiovascular condition such as "for example arteriosclerosis or a related condition having normal levels in serum of cholesterol and / or LDL-cholesterol and / or triglycerides." Such increased levels in serum of cholesterol and / or LDL-cholesterol and / or triglycerides can be triggered by ingesting a high-fat diet or it can be genetically related.

For the purpose of the present invention, subjects who have an initial total serum cholesterol level of 5.7 mmol / L or lower are considered to have a hypocholesterolemic or normal level, while subjects who have a total serum cholesterol level above 5.7 mmoles / l are considered to be hypercholesterolemic. Consequently, when treating normocholesterolemic subjects, it is possible to prevent the development of cardiovascular diseases that originate from serum cholesterol levels below a concentration of 5.7 mmoles / l in subjects particularly sensitive to developing eg arteriosclerosis, or to prevent development Additional cardiovascular disease in patients with previous cardiovascular events. By treating hypercholesterolemic subjects, it is possible to prevent the development of cardiovascular diseases that originate from cholesterol serum levels above a concentration of .5.7 mmol / l in susceptible subjects to develop, for example, arteriosclerosis under such conditions. More particularly, subjects who have a total serum cholesterol level of 5.7 mmol / L to 7.9 mmol / L are considered to be mild hypercholesterolemic. Therefore, by treating these hypercholesterolemic subjects, it is possible to prevent the development of cardiovascular diseases that originate from serum cholesterol levels of 5.7 to 7.9 mmol / l. Subjects who have a total cholesterol level in serum of more than 7.9 mmol / l are considered to be severe hypercholesterolemic. Therefore, by treating these hypercholesterolemic subjects, it is possible to prevent the development of cardiovascular diseases that originate from serum cholesterol levels of more than 7.9 mmol / L. It has also been shown that a composition according to this invention has an enhancing effect for the effect of medications such as for example statins. By combining a composition according to the present invention with for example statins, such as HMG-CoA inhibitors. reductase, bile acid resins, nicotinic acid derivatives, fibrates, oat products, such as oatmeal, rye products and various fish oil concentrates with a high content of 2-fat acids, it is possible to achieve a reduction additional 5 to 15% in levels of total cholesterol and / or LDL-cholesterol and / or triglycerides. The present invention also provides a combination according to the present invention in combination with statin, preferably an inhibitor of HMG-CoA reductase, bile acid resins, fibrates, oat products, rye products, nicotinic acid derivatives and various concentrates of fish oil with a high content of w-3-fatty acids. Example 1 The objective of the present study is to examine whether a product comprising isolated soy protein, soybean fiber fibers, and a high fixed level of isoflavones, is most significantly effective in lowering serum levels of LDL-cholesterol and total cholesterol than the placebo. The study is carried out as a randomized, double-blind, placebo-controlled trial. Fifty-two patients with an average baseline cholesterol level of 7.6 mmol / l complete a six-week treatment. Twenty-four consume a composition according to the invention (Abacor®, Nutri Pharma Asa, Oslo) containing isolated soy protein with high fixed levels of isoflavones, and soybean cotyledon fibers (52 g of soy protein, 230 mg of isoflavones of soybean and 15.5 g of soybean cotyledon fibers, per day). Twenty-eight consume a product with the same intakes of prptein and fiber, based on casein and cellulose (the placebo). • Preparations are given as daily liquid supplements in addition to the patient's regular diets. Both groups are monitored one month after stopping ingestion of the preparations. The average reduction of LDL-cholesterol in the group treated with Abacor® after six weeks is 13.1%, whereas it is "7 ^ 8% (p = 0.014) in the group treated with placebo.The reduction of total cholesterol is greater in the active group compared with that of placebo (8.4% versus 5.1% p = 0.049), without correct for multiple testing High density lipoprotein (HDL) cholesterol shows an increase in both active and placebo groups (6.2% vs. 5.8%). One month after treatments, both groups have returned to pretreatment cholesterol levels The results show that ingestion of a product comprising isolated soy protein with high fixed levels of isoflavones, and sya cotyledon fibers, significantly reduces LDL-cholesterol and serum cholesterol and improves the HDL / LDL-cholesterol ratio. Positive results are achieved in this group of patients after six weeks of treatment Example 2 The objective of the present study is to examine whether a product comprising isolated soy protein, soy bean fibers, and a high level Fixed isoflavones, is significantly more effective in decreasing serum levels of LDL-cholesterol, HDL-cholesterol and total cholesterol than placebo. The study is carried out as a randomized, double-blind, placebo-controlled trial. 160 patients with plasma levels of LDL-cholesterol >; 4 mM, total cholesterol of 5.8 - 7.9 mM and triglycerides < 4.5 mmM complete sixteen weeks of treatment. 80 patients divided into two groups of the same size consume a soy-based product * (Abacor®, Nutri Pharma ASA, Oslo) which contains isolated soy protein with high fixed levels of isoflavones, and soybean cotyledon fibers. Group I (40 patients) received Abacor® I: 18.5 g of soy protein (SUPRO® FXP-H0159), 4.63 g of soy fibers (FIBRIM® 1020), 3.44 g of cocoa reduced in lecitinated fat and 1.31 g of soy lectin on a daily basis; Group II (40 patients) receive Abacor® II; 31 g of soy protein (SUPRO® FXP-H0159), 7.75 g of soy fiber (VlBRIM® 1020), 5.77 g of reduced cocoa in lecitinated fat and 2.2 g of soy lecithin on a daily basis. 80 patients divided into two groups consume a group with the same intakes of protein and fiber, based on casein, whole milk powder and cellulose (the placebo). The preparations are taken as a daily supplement in addition to the regular diets of the patients. The study begins with a standardized dietary program for an average of four months for all study participants (visits 1-4, an average during a four-month course), with extensive education in diet catalog and dietary instructions. After this, study participants receive Abacor® or placebo as described above (visits 4-8, one month between each). Serum levels of total cholesterol are measured (Table I and Figure 1), serum levels of LDL-cholesterol (Table II and Figure 2), serum levels of HDL-cholesterol (Table III and Figure 3), and levels in serum triglycerides (Table IV and Figure 4) in all visits during the entire period. The average HDL / LDL-cholesterol ratio is also calculated (Figure 5). The following designations are used in the following tables: A: Patients in Group IB: Patients receiving placebo with the same intake of protein and fiber as Group II C: Patients in Group II D: Patients receiving placebo with the same intake of protein and fiber as Group II TABLE 1 Total cholesterol (mM) TABLE II TABLE III HDL-Cholesterol (mM) TABLE IV Triglycerides (mM) € -t.

These results show that the intake of a composition according to the invention in the amounts mentioned above reduces serum levels of total cholesterol with more than 11% for Abacor® I and Abacor® II (Table I and Figure 1). More remarkably, the ingestion of a composition according to the invention reduces serum levels of LDL-cholesterol with 18.2% for Abacor® II after an initial reduction of approximately 5% due to dietary change resulting in a total LDL reduction -cholesterol of approximately 23% with ingestion of a composition according to the invention and a change of diet (Table II and Figure 2). This is among the largest reductions in serum LDL-cholesterol levels observed with food products. Surprisingly, the ingestion of Abacor® I (which has only 60% of the protein content of Abacor® II) reduces serum levels of LDL-cholesterol with 16.0% after the initial reduction, which is very close to the result observed with Abacor ® II. The results further show that serum HDL-cholesterol levels are increased by approximately 10% for Abacor® (Table III and Figure 3), that the serum levels of triglycerides are reduced by more than 10% for abbas Abacor® I and Abacor® II (Table IV and Figure 4), and that the HDL / LDL ratio is improved with approximately 33% for Abacor ® II and approximately 25% for Abacor® i (Figure 5).

Surprisingly, the reduction of cholesterol levels caused by the continuous use of Abacor® does not stop after about a month, as can be expected since the change of cholesterol in the body is 2 to 3 weeks, but cholesterol levels are reduced continuously over a period of four months (see Figures 1 and 2).

Claims (68)

1. CLAIMS 1. A composition characterized in that it comprises: (a) a source of soy protein, selected from isolated soy protein, soy protein concentrate, or soybean meal, the source of soy protein providing a quantity of soy protein , which is at least 45 percent by weight of the total protein content of the composition, the total protein content providing at least 15 percent of the total energy content of the composition; (b) at least one phytoestrogen compound in an amount of more than 0.16 weight percent of the soy protein content of the composition, and (c) dietary fibers in an amount of more than 6 weight percent de-1 total weight of the nutritional composition on a dry basis.
2. 2. A composition according to claim 1, characterized in that the soy protein source is isolated soy protein and the amount of isolated soy protein is at least 50 weight percent of the total protein content.
3. 3. A composition according to claim 2, characterized in that the amount of isolated soy protein is at least 75 weight percent of the total protein content.
4. 4. A composition according to claim 3, characterized in that the amount of isolated soy protein is at least 90 percent by weight of the total protein content.
5. 5. A composition according to claim 4, characterized in that substantially all of the protein is isolated soy protein.
6. 6. A composition according to claim 1, characterized in that the source of soy protein is concentrate of soy protein or soybean meal and the amount of soy protein is at least 50 weight percent of the total protein content. .
7. 7. A composition according to claim 6, characterized in that the amount of soy protein is at least 75 weight percent of the total protein content.
8. 8. A composition according to claim 7, characterized in that the amount of soy protein is at least 90 percent by weight of the total protein content.
9. 9. A composition according to claim because substantially all the protein is protein and soy.
10. 10. A composition according to any of claims 1 to 9, characterized in that the dietary fibers are soy bean fibers.
11. 11. A composition according to claim 10, characterized in that the soy bean fibers are soybean cotyledon fibers.
12. 12. A composition according to any of claims 1 to 11, characterized in that the phytoestrogen compound is present in an amount of at least about 0.20 weight percent of the soy protein content of the composition.
13. 13. A composition according to claim 12, characterized in that the phytoestrogen compound is present in an amount of at least about 0.30 weight percent of the soy protein content of the composition.
14. 14. A * composition according to claim 13, characterized in that the phytoestrogen compound is present in an amount of at least about 0.33 weight percent of the soy protein content of the composition.
15. 15. A composition according to claim 14, characterized in that the phytoestrogen compound is present in an amount of at least about 0.45 weight percent of the soy protein content of the composition.
16. 16. A composition according to claim 15, characterized in that the phytoestrogen compound is present in an amount of at least about 0.75 weight percent of the soy protein content of the composition.
17. 17. A composition according to claim 16, characterized in that the phytoestrogen compound is present in an amount of at least about 1.0 weight percent of the soy protein content of the composition.
18. 18. A composition according to any of claims 1 to 17, characterized in that the phytoestrogen compound is selected from isoflavones.
19. 19. A composition according to claim 18, characterized in that the isoflavones are selected from the group consisting of genistein, daidzein, glycitein and equol.
20. 20. A composition according to claim 19, characterized in that the isoflavones are genistein and / or daidzein.
21. 21. A composition according to claim 20, characterized in that the isoflavone is genistein.
22. 22. A composition according to any of claims 18 to 21, characterized in that some or all of the isoflavones are present in aglycone form.
23. 23. A composition according to any of claims 1 to 22, characterized in that the dietary fibers are present in an amount of at least 7 weight percent of the composition.
24. 24. A composition according to any of claims 1 to 23, characterized in that the weight ratio of soy protein to dietary fiber is at least about 1.0.
25. 25. A composition according to claim 24, characterized in that the weight ratio of soy protein to dietary fiber is at least about 1.5.
26. 26. A composition according to claim 25, characterized in that the weight ratio of soy protein to dietary fiber is at least about 2.0.
27. 27. A composition according to claim 26, characterized in that the weight ratio of soy protein to dietary fiber is at least about 2.5.
28. 28. A composition according to claim 27, characterized in that the weight ratio of soy protein to dietary fiber is at least about 3.0.
29. 29. A composition according to claim 28, characterized in that the weight ratio of soy protein to dietary fiber is at least about 4.0.
30. 30. A composition according to claim 29, characterized in that the weight ratio of soy protein to dietary fiber is at least about 5.0.
31. 31. A composition according to any of claims 1 to 30, characterized in that it is in combination with statins, bile acid resins, derivatives of nicotinic acid, oat products, rye products or concen- , fish oil with a high content of acids? 3 -Greases, or any combination thereof.
32. 32. A composition according to claim 31, characterized in that the statins are selected from the HMG-CoA reductase inhibitors. A composition according to any one of claims 1 to 32, further characterized comprising an additional source of protein and / or an additional source of carbohydrates and / or an additional source of fats. 34. A composition according to claim 33, characterized in that the additional fat source is selected from soy lecithins. 35. A composition according to claim 33, characterized in that the additional source 5 of fats is selected from polyunsaturated and monounsaturated fatty acids. 36. A composition according to any of claims 1 to 35, characterized in that it is in the form of a micronutrient. 37. A composition according to claim 36, characterized in that it additionally comprises a DNA inhibitor, topoisomerase, a ribosome kinase inhibitor, and / or a growth control factor, 38. A composition according to claim 15. 37, characterized in that the growth control factor is a growth control factor controllable by tyrosine kinase activity 39. A composition according to any of claims 34 to 38, further characterized 20 because it comprises ormeloxifene and / or levormeloxifen. 40. A composition according to any of claims 1 to 39, characterized in that it is in combination with a functional food ingredient comprising sterol. • - 25 41. One? composition in accordance with the ^ • m,? »# > < - • SO claim, characterized in that the functional food ingredient comprising a sterol is selected from the group consisting of a stanol ester, a tocotrienol, a mevinolin, and a phytosterol compound, or a combination thereof. 42. A composition according to any of claims 1 to 41, characterized in that it is used as a functional food ingredient. 43. A composition according to claim 42, characterized in that the functional food is selected from the group consisting of daily products, t. juice, ready-to-drink liquids, a dispersible product, a cereal product, nutritional bars, eavesdrops, bread, soups, meat products, meat substitute products, and a vegetable product. 44. A composition according to any of claims 1 to 43, characterized in that it is for special dietary use. 45. A composition according to claim 44, characterized in that it lowers serum levels of: total cholesterol and / or LDL-cholesterol and / or triglycerides in a subject. 46. A combination according to claim 44, characterized in that it decreases serum levels of total cholesterol and / or LDL-cholesterol and / or triglycerides in hyperlipidemic patients or normocholesterolemic patients suffering from cardiovascular disease. 47. A composition according to any of claims 1 to 46, characterized in that it is used as a medicament. 48. A composition according to claim 47, characterized in that it is used to prevent and / or treat and / or prophylactically treat and / or alleviate cardiovascular diseases 49. A composition according to claim 48, characterized in that the use in preventing and / or treating and / or treating prophylactically and / or relieving a cardiovascular disease selected from the group consisting of hypercholesterolemia, hypertriglyceridemia, others, hyperlipidemias, - "arteriosclerosis, atherosclerosis, arteriolosclerosis, coronary heart disease, angina pectoris, thrombosis , myocardial infarction and hypertension. 50. A composition according to claim 47, "characterized in that it is used in decreasing serum levels of homocysteine and / or total cholesterol and / or LDL-cholesterol and / or -triglycerides and / or reducing the influx of cholesterol and / or triglycerides in the arterial wall and / or increase the proportion of HDL / LDL-cholesterol in serum in the arterial wall and / or increase the proportion of HDL / LDL-cholesterol in serum and / or the HDL-cholesterol level in serum of a subject. 51. A pharmaceutical preparation characterized because I understood. a composition according to any one of claims 1 to 50. 52. The use of a composition according to any of claims 1 to 50, characterized by the manufacture of a medicament for treating a subject suffering from cardiovascular diseases. 53. Use in accordance with the claim 52, characterized in that arteriosclerosis is treated in a subject. 54. The "" use according to claim 52 or 53, characterized in that the medicament is effective in preventing and / or treating and / or treating prophylactically and / or relieving a cardiovascular disease selected from the group consisting of hypercholesterolemia, hypertriglyceridemia, other hyperlipidemias, arteriosclerosis, atherosclerosis, arteriolosclerosis, angina pectoris, thrombosis, myocardial infarction and hypertension in a subject. 55. The use according to claim 54, characterized in that the medicine is effective in preventing and / or treating. and / or - treating prophylactically and / or relieving arteriesclerosis in a subject. 56. The use according to claim 54, characterized in that the medicament is effective in preventing and / or treating and / or treating prophylactically and / or relieving atherosclerosis in a subject. 57. The use according to claim 52 or 53, characterized in that the medicament is effective in reducing total serum cholesterol levels and / or serum LDL-cholesterol levels and / or serum triglyceride levels and / or levels in serum. homocysteine serum from a subject and / or increase the proportion of HDL / LDL-cholesterol in serum and / or levels of: HDL-cholesterol in a subject's serum. 58. The use according to claim 52 or 53, characterized in that the medicament is effective in reducing the influx of cholesterol and / or triglycerides in the arterial wall of a subject. 59. Use in accordance with the claim 52 or 53, characterized in that the medicament is effective in preventing, reducing or eliminating fat groove formation and / or reducing the amount of oxidized LDL-cholesterol present in the arterial wall and / or .. «'preventing, reducing or eliminating formation of fibrous plaque and / or 'prevent, reduce or eliminate complicated formation of injury., 60. The use according to claim 52 or 53, characterized in that the medicament is effective in reducing or eliminating the risk of a person contracting angina of chest and / or reduce or eliminate the risk of a subject contracting a myocardial infarction. 61. The use of a composition according to any of claims 1 to 50, characterized by the manufacture of a nutritional preparation for decreasing total serum cholesterol levels and / or serum LDL-cholesterol levels and / or triglyceride levels. in serum and / or serum homocysteine levels and / or to increase the HDL / LDL-cholesterol ratio and / or HDL-cholesterol levels in a subject's serum. 62. Use in accordance with the claim 61, characterized in that the nutritional preparation is in the form of a dietary supplement. 63. The use of a composition according to any of claims 1 to 50, characterized in that it is a partial or total diet for an overweight subject suffering from an arteriosclerotic condition. 64. A method for preventing and / or treating and / or treating prophylactically and / or relieving by therapy a cardiovascular disease in a human or animal body, the method characterized in that it comprises administering to the human or animal body a composition in accordance with any of claims 1 to 50 in an amount effective to decrease serum cholesterol levels and / or serum LDL-cholesterol levels and / or serum triglyceride levels and / or serum homocysteine levels and / or increase the proportion of HDL / LDL-cholesterol in serum and / or serum HDL-cholesterol levels and / or reducing the influx of cholesterol and / or triglycerides in the arterial wall and / or preventing, reducing or eliminating fat groove formation and / or prevention, reduction or elimination of fibrous plaque formation and / or preventing, reducing or eliminating complicated lesion formation and / or reducing or eliminating a subject's risk of contracting angina and / or reducing or eliminating the risk of a sujet or of contracting a myocardial infarction. 65. A method in accordance with the claim 64, characterized in that cardiovascular disease is an arteriosclerotic condition of the human or animal body. 66. A method according to claim 64, characterized in that cardiovascular diseases are selected from the group consisting of hypercholesterolemia, hypertriglyceridemia, other hyperlipidemias, arteriosclerosis, atherosclerosis, arteriolosclerosis, angina pectoris, thrombosis, myocardial infarction, and hypertension. 67. A method according to claim 66, characterized in that the cardiovascular disease is arteriosclerosis. 68. A method according to claim 66, characterized in that the. cardiovascular disease is atherosclerosis.