US 6,203,818 B1Grant
Nutritional supplement for cardiovascular health
Issue Date:2001-03-20
•20 Claims
Abstract
A nutritional supplement for improving cardiovascular health via aiding in preventing, delaying the onset of and/or slowing the progression of atherosclerosis and coronary heart disease, the supplement comprising one or more flavonoids and folic acid or folate; and a method for aiding in preventing, delaying the onset of and/or slowing the progression of atherosclerosis and coronary heart disease are described.
Metadata
Assignee
- Coventry Group, Ltd.
Inventor
- Samuel Russell Vester
Application Information
Application Number:US 09/045,464
Filing Date:1998-03-20
Priority Date:1997-03-20
Art Unit:7
Classifications
IPC:
A61K 3534C07D47500C07D31104
Field of Search:
424569544261549403
Patent Drawings
This patent does not have any drawings.
Description
[0002] This application claims priority from Provisional Application No. 60/041,326 filed Mar. 20, 1997.
Background of the Invention
[0003] This invention relates to a nutritional supplement composition, more particularly, to a nutritional supplement composition that is intended to benefit cardiovascular health via aiding in preventing, delaying the onset of and/or slowing the progression of atherosclerosis and coronary heart disease (CHD), and to a method for aiding in preventing, delaying the onset of and/or slowing the progression of atherosclerosis and CHD by administration of the nutritional supplement composition to an individual.
[0004] According to the 1996 American Heart Association statistical summary, 42% of all deaths in America are from some form of cardiovascular disease. Since cardiovascular disease is the leading cause of death in the United States and many other developed countries, it is not surprising that heart specialists and physicians in general arc frequently asked to provide advice concerning nutritional factors that may aid in preventing, delaying the onset of and/or slowing the progression of atherosclerosis and CHD.
[0005] The use of vitamin and mineral supplements in one's diet is well established. Specifically, vitamin and mineral supplements heretofore devised and used for the purpose of providing daily nutrients are known to consist basically of familiar, predictable and obvious combinations. While many of the known supplements are adequate to fulfil their objectives, few have been specifically composed for improving cardiovascular health via aiding in preventing, delaying the onset of and/or slowing the progression of atherosclerosis and coronary heart disease.
[0006] A number of synthetic drug formulations are available to maintain and benefit cardiovascular health or to treat or prevent atherosclerosis and coronary heart disease. Clofibrate, Gemfibrozil, Questran, Colestipol and HMG CoA reductase inhibitors arc a few examples of synthetic drugs prescribed for decreasing cholesterol and triglyceride levels. All of the above-mentioned drugs have significant potential for side effects which include nausea, hepatic dysfunction, bone marrow suppression, gastrointestinal discomfort, heartburn, diarrhea, constipation, etc.
[0007] Aspirin is known to decrease platelet aggregation, reduce the incidence of transient ischemic attacks, ameliorate a myocardial infarction, and has been used as a prophylactic agent for these purposes. Aspirin, however, is known to have a variety of undesirable side effects. For example, aspirin can contribute to formation of gastric ulcers. At higher doses, patients may experience tinnitus, decreased hearing and vertigo. In addition, patients with hemophilia are particularly susceptible to serious side effects of aspirin.
[0008] Given the above problems, there remains a need for a nutritional supplement that contains naturally occurring ingredients which can by design provide specific nutritional elements that available studies have shown provide potential benefit in preventing, delaying the onset of and/or slowing the progression of atherosclerosis and coronary heart disease. The nutritional supplement of the invention is also expected to provide these benefits without anticipation of untoward side effects.
Summary of the Invention
[0009] The present invention provides a nutritional supplement composition comprising one or more flavonoids and folic acid or folate (i.e., salts or esters of folic acid). More particularly it provides a nutritional supplement formulation containing a prophylactically effective amount of one or more flavonoids and folic acid or folate which is specifically dedicated to aiding in preventing, delaying the onset of and/or slowing the progression of atherosclerosis and CHD. A particularly preferred nutritional supplement composition comprises quercetin and folic acid or folate.
[0010] The present invention also provides a method for aiding in preventing, delaying the onset of and/or slowing the progression of atherosclerosis and CHD which comprises the step of administering the nutritional supplement composition to an individual who is at risk or may be at risk of atherosclerosis and coronary heart disease.
Detailed Description of the Invention
[0011] The present invention provides a composition which is useful as a nutritional supplement to aid in preventing, delaying the onset of and/or slowing the progression of atherosclerosis and coronary heart disease. The composition of the present invention is a combination of one or more flavonoids and folic acid or folate. The combined use of these two supplements is believed to respond to some, if not most, of the common conditions implicated in cardiovascular disease such as platelet aggregation, oxidation of blood lipids in arterial walls, and elevated homocysteine levels. These agents may be combined in an oral dosage with other well known nutritional supplements and/or non-flavonoid antioxidants, e.g., selenium, vitamin E (tocopherol, particularly α-tocopherol, etc.), vitamin C (ascorbic acid) and coenzyme Q10. Dietary fiber supplements may also be used in the composition.
[0012] Flavonoids, also known as “phenylchromones,” are naturally occurring, water-soluble compounds which have antioxidant characteristics. Flavonoids are widely distributed in vascular plants and are found in numerous vegetables, fruits and beverages such as tca and wine (particularly red wine) and, therefore, are a common component of the human diet. The animal kingdom is unable to synthesize the flavone nucleus; flavonoids are therefore strictly exogenous food components of plant origin.
[0013] Flavonoids are conjugated aromatic compounds having the general
[0014] where R1, R2, R3, R4, R5, R6, R7and R8are independently selected from H and OR′ where R′ is H or an alkyl group having about 1 to 10 carbon atoms. As of the mid 1980's more than 4000 chemically unique flavonoids have been identified and this is only a fraction of the total number likely to be present in nature. The most widely occurring flavonoids are flavones and flavonols. While the present invention is open to the use of all flavonoids, flavonols and more particularly, myricetin, (3,5,7,3′,4′,5′,-hexahydroxyflavone), quercetin (3,5,7,3′,4′-pentahydroxyflavone), kaempferol (3,5,7,4′-tetrahydroxyflavone), and flavones apigenin (5,7,4′-trihydroxyflavone) and luteolin (5,7,3′,4′-tetrahydroxyflavone) and glycosides thereof are preferred. The most preferred flavonoid for use in the invention is qucrcetin.
[0015] It is believed that quercetin, which exhibits some of the strongest antioxidant effects of the flavonoids and which has been reported to inhibit oxidation and cytoxicity of low density lipoproteins (LDL), may have beneficial health consequences since oxidized low density lipoproteins are reported to be atherogenic, i.e., they contribute to the buildup of fatty substances in the arterial wall. Lipid peroxidation is caused by free radicals. Free radicals are molecules with at least one unpaired electron, which makes them highly reactive. Free radicals are continually formed in the metabolic processes of the human body but are tightly regulated. Human plasma contains various antioxidants which makes it difficult for such reactions to occur within the plasma. When LDL is within the arterial wall, the situation is different and the plasma antioxidant protection is not available. The reaction that can result in buildup of oxidized lipids in the arterial wall can be stopped or decreased by the presence of an antioxidant such as a flavonoid. Flavonoids appear to act by protecting LDL against oxidation, as they inhibit the generation of lipid peroxides and also may help protect alpha-tocopherol (vitamin E), a major lipophilic antioxidant carried in lipoproteins, from being consumed by oxidation in LDL.
[0016] Epidemiologic studies supporting red wine and black tea as significant sources of flavonoids have led to the inference that consumption of red wine and black tea in some cultures is correlated to reduced risk of CHD. Quercetin is the flavonoid occurring in highest concentration in both red wine and black tea.
[0017] The flavonoid component of the nutritional supplement of the invention may be administered in a daily dose of about 0.1 to 500 mg. and, more likely, about 10 to 50 mg. The most effective amount of flavonoid an individual can consume is not as yet clearly determined.
[0018] Folic acid is a B complex vitamin. It is water-soluble and occurs naturally in green plants, fresh fruit, and yeast. Folic acid along with vitamins B12(cyanocobalamin) and B6, plays a key part in homocysteine metabolism. Medical studies have demonstrated that there is a statistically significant positive correlation between total plasma homocysteine levels and the incidence of atherosclerosis and coronary heart disease. Men whose homocysteine levels arc known to be significantly elevated are more likely to suffer myocardial infarction. Also, it has been demonstrated that inadequate folic acid or folate intake is the main determinate of the homocysteine-related increase in carotid artery thickening, another significant manifestation of atherosclerotic disease. The mechanism by which elevated blood homocysteine causes accelerated atherosclerosis has not been clearly established. U.S. population dietary surveys have demonstrated that up to 40 percent of the population may not consume enough folic acid to prevent elevated blood homocysteine levels. Folic acid or folate supplements in the range of 0.4 to 2 mg. per day are usually sufficient to reduce or normalize high homocysteine levels. The folic acid or folate of the nutritional supplement may be administered in a daily dose of about 0.1 to 10 mg. and, more typically, about 0.4 to 1 mg.
[0019] In addition to the flavonoids and folic acid or folate, the supplement of the invention may also contain Vitamin B12and Vitamin B6. Vitamins B12and B6belong to the vitamin B complex group. These closely related vitamins are found in rice, bran, yeast, wheat germ, etc. Each member of the vitamin B complex group is a distinctly different substance with different functions. No one B vitamin can fully replace any other. Vitamin B12is a preferred component of the nutritional supplement of the invention as it provides a safeguard for patients with a vitamin B 12deficiency or pernicious anemia. Vitamin B6 can also be present.
[0020] Other well known nutritional supplements such as non-flavonoid antioxidants, e.g., selenium, vitamin E (α-tocopherol, etc.), vitamin C (ascorbic acid), coenzyme Q10, niacin and beta-carotene may be effectively used in the nutritional supplement of this invention.
[0021] Other additives may be incorporated in the nutritional supplement of the present invention. Such additives include minerals, e.g., boron, etc. and trace metals such as zinc, magnesium, manganese, chromium, molybdenum, copper, iron, calcium, and potassium; and other micronutrients such as thiamine, riboflavin, niacin, pantothenic acid, pyridoxine, choline, biotin, inositol, para-aminobenzoic acid, vitamin D, vitamin K, vitamin A, etc. In another embodiment of the invention a dietary fiber supplement such as oat bran or other natural fiber source may also be added to the composition.
[0022] Typically the nutritional supplement will further include a pharmaceutically acceptable carrier such as lactose, glucose, sucrose, corn starch, potato starch, cellulose acetate, ethyl cellulose, etc. Diluents and other additives such as one or more phannaceutically acceptable binding agents, fillers, supports, thickening agents, taste-improving agents, coloring agents, preservatives, stabilizers, regulators, emulsifiers or mixtures thereof may be used depending on the form of the composition employed.
[0023] In addition to providing the aforementioned compositions, the invention also includes a method for orally administering the composition in dosages effective to aid in preventing, delaying the onset of and/or slowing the progression of atherosclerosis and coronary heart disease and, more particularly, to a method for orally administering the aforesaid composition to an individual who is at risk of or may be at risk of atherosclerosis and coronary heart disease. The supplement is preferably administered orally but may be administered parenterally. Suitable forms for the nutritional supplement composition for oral or parenteral administration include tablets, capsules, lozenges, syrips, granules, solutions and suspensions which contain unit doses of the supplement for administration once or several times a day. The nutritional supplement composition of the invention will typically be administered orally as a tablet or a capsule. Tablets, gel tabs, capsules, liquid and sustained release formulations can be formulated and prepared according to manufacturing techniques well known in the pharmaceutical industry and in a variety of dosage forms.
[0024] Having described the invention in detail, it will be apparent that numerous modifications and variations are possible.
Claims
What is claimed is:
1. A nutritional supplement useful in aiding in preventing, delaying the onset of and/or slowing the progression of atherosclerosis comprising quercetin and folic acid or folate wherein said quercetin is present in the supplement in an amount which provides a daily dosage of about 0.1 to 500 mg and folic acid or folate is present in the supplement in an amount to provide a daily dosage of about 0.1 to 10 mg.
2. The supplement of claim 1 wherein said supplement additionally contains a flavonoid selected from the group consisting of myricetin, kaempferol, luteolin and apigenin.
3. The supplement of claim 1 wherein said quercetin is present in an amount to provide a daily dosage of about 10 to 50 mg and said folic acid or folate is present in an amount to provide a daily dosage of about 0.4 to 1.0 mg.
4. The supplement of claim 1 wherein the supplement additionally contains another nutrient selected from the group consisting of vitamin B12, vitamin B6, non-flavonoid antioxidants, minerals and trace metals.
5. The supplement of claim 1 wherein said supplement additionally contains a antioxidant selected from the group consisting of selenium, vitamin E, vitamin C, niacin, beta-carotene, coenzyme Q10, or combinations thereof.
6. The supplement of claim 1 wherein said supplement additionally contains zinc, copper, magnesium, manganese, chromium, molybdenum, iron, calcium, or combinations thereof.
7. The supplement of claim 1 wherein said supplement further includes one or more pharmaceutically acceptable binding agents, fillers, supports, thickening agents, taste-improving agents, coloring agents, preservatives, stabilizers, regulators, emulsifiers, or mixtures thereof.
8. A method for aiding in preventing, delaying the onset of and/or slowing the progression of atherosclerosis and coronary heart disease in a person comprising the step of administering to said person a nutritional supplement including quercetin and folic acid or folate wherein said supplement is administered in an amount which provides a daily dosage of quercetin of about 0.1 to 500 mg and a daily dosage of folic acid or folate of about 0.1 to 10 mg.
9. The method of claim 8 wherein said quercetin is present in an amount to provide a daily dosage of about 10 to 50 mg and said folic acid or folate is present in an amount to provide a daily dosage of about 0.4 to 1.0 mg.
10. The method of claim 8 wherein said supplement additionally contains other nutrients selected from the group consisting of vitamin B12, vitamin B6, non-flavonoid antioxidants, minerals and trace metals.
11. The method of claim 8 wherein said supplement additionally contains anon-flavonoid antioxidants selected from the group consisting of selenium, vitamin E, vitamin C, niacin, beta-carotene, coenzyme Q10, or combinations thereof.
12. The method of claim 11 wherein said supplement additionally contains a non-flavonoid minerals and trace metals selected from the group consisting of zinc, copper, magnesium, manganese, chromium, molybdenum, iron, calcium, or combinations thereof.
13. The method of claim 8 wherein said supplement further includes one or more pharmaceutically acceptable binding agents, fillers, supports, thickening agents, taste-improving agents, coloring agents, preservatives, stabilizers, regulators, emulsifiers, or mixtures thereof.
14. The method of claim 8 wherein said nutritional supplement is administered orally as a tablet, capsule, liquid, or powder one or several times a day, or said nutritional supplement is administered parenterally.
15. A nutritional supplement comprising quercetin, folic acid or folate, and a dietary fiber supplement wherein said quercetin is present in an amount which provides a daily dosage of about 0.1 to 500 mg and said folic acid or folate is present in an amount which provides a daily dosage of about 0.1 to 10 mg.
16. A method for aiding in preventing, delaying the onset of and/or slowing the progression of atherosclerosis and coronary heart disease in a person comprising the step of administering to said person a nutritional supplement including quercetin, folic acid or folate, and a dietary fiber supplement wherein said quercetin is present in an amount which provides a daily dosage of about 0.1 to 500 mg and said folic acid or folate is present in an amount which provides a daily dosage of about 0.1to 10 mg.
17. The supplement of claim 1 wherein the supplement additionally contains Vitamin C or Vitamin E.
18. The supplement of claim 17 wherein the supplement additionally contains coenzyme Q10.
19. The method of claim 8 wherein said supplement additionally contains Vitamin C or Vitamin E.
20. The method of claim 19 wherein said supplement additionally contains coenzyme Q10.
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